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Alberto BERARDI

Professore Associato
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto

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Pubblicazioni

2024 - Fentanyl analgesia in asphyxiated newborns treated with therapeutic hypothermia [Articolo su rivista]
Lugli, L.; Spada, C.; Garetti, E.; Guidotti, I.; Roversi, M. F.; Della Casa, E.; Bedetti, L.; Lucaccioni, L.; Pugliese, M.; Ferrari, F.; Iughetti, L.; Lago, P.; Berardi, A.
abstract

Introduction: Therapeutic hypothermia is the standard care for asphyxiated newborns. Discomfort and pain during treatment are common and may affect therapeutic efficacy of hypothermia. Opioid analgosedation is commonly used in the clinical setting, but its effects in the cooled newborns is poorly investigated. Objective: The aim of this study was to assess the safety of fentanyl analgosedation during therapeutic hypothermia, by evaluating severe adverse effects and possible correlation with the neurodevelopmental outcome. Methods: We analyzed asphyxiated newborns treated with hypothermia receiving fentanyl intravenous infusion (years 2013–2018). Severe neurodevelopmental outcome was defined as cerebral palsy or Griffith’s developmental quotient <70 or major sensorineural deficit. Severe brain lesions were defined as cortical or/and basal ganglia extensive involvement. Results: Fentanyl cumulative dose was variable (61.7 ± 18.5 µg/kg; range 34.3–120.3 µg/kg) among 45 enrolled patients. Respiratory depression was recorded in 13.3% cases of 30 spontaneously breathing patients. Severe brain lesions and severe neurodevelopmental disability were found in 24.4 and 11.1% of all included cases, respectively. Higher cumulative fentanyl dose was not associated with poor outcome. Conclusions: Fentanyl treatment during therapeutic hypothermia does not negatively affect the neurodevelopmental outcome, thus on the contrary, it may contribute to ameliorate neuroprotection in the asphyxiated cooled newborns.

2024 - Fetal hepatic calcification in severe KAT6A (Arboleda-Tham) syndrome [Articolo su rivista]
Di Caprio, A.; Rossi, C.; Bertucci, E.; Bedetti, L.; Bertoncelli, N.; Miselli, F.; Corso, L.; Bondi, C.; Iughetti, L.; Berardi, A.; Lugli, L.
abstract

: Arboleda-Tham syndrome (ARTHS, MIM 616268) is a rare genetic disease, due to a pathogenic variant of Lysine (K) Acetyltransferase 6A (KAT6A) with autosomal dominant inheritance. Firstly described in 2015, ARTHS is one of the more common causes of undiagnosed syndromic intellectual disability. Due to extreme phenotypic variability, ARTHS clinical diagnosis is challenging, mostly at early stage of the disease. Moreover, because of the wide and unspecific spectrum of ARTHS, identification of the syndrome during prenatal life rarely occurs. Therefore, reported cases of KAT6A syndrome have been identified primarily through clinical or research exome sequencing in a gene-centric approach. In order to expands the genotypic and phenotypic spectrum of ARTHS, we describe prenatal and postnatal findings in a patient with a novel frameshift KAT6A pathogenic variant, displaying a severe phenotype with previously unreported clinical features.

2024 - Subtle impairment of neurodevelopment in infants with late fetal growth restriction [Articolo su rivista]
Lucaccioni, L.; Boncompagni, A.; Pugliese, M.; Talucci, G.; Della Casa, E.; Bertoncelli, N.; Coscia, A.; Bedetti, L.; Berardi, A.; Iughetti, L.; Ferrari, F.
abstract

Introduction: Children with late fetal growth restriction (FGR) are at high risk of being born small for gestational age (SGA). These categories of newborns are at increased risk for neurodevelopment impairment. The general movements assessment, in particular at fidgety age, has been used to predict neurological dysfunctions. This study aimed to evaluate growth recovery, presence of fidgety movements at 3 months, and neurodevelopmental outcome at 2 years of age in term late FGR infants and adequate for gestational age (AGA) controls. Methods: Prospective clinical evaluation. At 3 months auxological parameters (AP) and neurological examination were evaluated while at 24 months neurodevelopment outcome by Griffiths Mental Development Scales (GMDS-R) was evaluated. Results: 38 late FGR and 20 AGA controls completed the study. Despite a significant catch up, at 3 months 13% of late FGR presented at least one auxological parameter <3° percentile. Moreover, 23.7% of late FGR infants did not show fidgety movements compared to 100% AGA controls (p <.001). Cranial circumference at birth resulted a positive predictive factor for FMs (p =.039). At 2 years of age, a difference statistically significant between late FGR and AGA was detected in GMDS-R. Conclusion: Independently from growth recovery, fidgety movements resulted less expressed in late FGR infants, and at 2 years of age the neurodevelopmental assessment revealed differences in each domain of evaluation between late FGR and AGA infants, although within normal ranges.

2023 - Antibiotic Prophylaxis for the Prevention of Urinary Tract Infections in Children: Guideline and Recommendations from the Emilia-Romagna Pediatric Urinary Tract Infections (UTI-Ped-ER) Study Group [Articolo su rivista]
Autore, Giovanni; Bernardi, Luca; Ghidini, Filippo; La Scola, Claudio; Berardi, Alberto; Biasucci, Giacomo; Marchetti, Federico; Pasini, Andrea; Capra, Maria Elena; Castellini, Claudia; Cioni, Vera; Cantatore, Sante; Cella, Andrea; Cusenza, Francesca; De Fanti, Alessandro; Della Casa Muttini, Elisa; Di Costanzo, Margherita; Dozza, Alessandra; Gatti, Claudia; Malaventura, Cristina; Pierantoni, Luca; Parente, Giovanni; Pelusi, Gabriella; Perrone, Serafina; Serra, Laura; Torcetta, Francesco; Valletta, Enrico; Vergine, Gianluca; Antodaro, Francesco; Bergomi, Andrea; Chiarlolanza, Jennifer; Leoni, Laura; Mazzini, Franco; Sacchetti, Roberto; Suppiej, Agnese; Iughetti, Lorenzo; Pession, Andrea; Lima, Mario; Esposito, Susanna
abstract

2023 - Antimicrobial Resistance Pattern and Empirical Antibiotic Treatments in Neonatal Sepsis: A Retrospective, Single-Center, 12-Year Study [Articolo su rivista]
Minotti, C.; Di Caprio, A.; Facchini, L.; Bedetti, L.; Miselli, F.; Rossi, C.; Della Casa Muttini, E.; Lugli, L.; Luppi, L.; Ferrari, F.; Berardi, A.
abstract

Neonatal sepsis is an important cause of morbidity and mortality in neonatal intensive care units (NICUs). Continuous evaluation of antimicrobial resistance (AMR) profiles is advised to implement antimicrobial stewardship (AMS) programs and establish effective empiric antibiotic protocols. AMS may reduce AMR in NICUs and improve sepsis outcomes. In this retrospective observational study, we report data on culture-positive neonatal sepsis, assessing differences after the implementation of an AMS program (2011–2016 vs. 2017–2022). A total of 215 positive bacterial cultures from 169 infants were retrieved, with 79 early-onset (36.7%) and 136 late-onset (63.3%) sepsis episodes. Frequent causative agents for early-onset sepsis were S. agalactiae and E. coli, all susceptible to empiric treatment. Late-onset sepsis was mainly caused by Enterobacterales and S. aureus. Aminoglycosides, cefotaxime, and piperacillin-tazobactam resistance among Enterobacterales was substantially low; S. aureus was mostly susceptible to oxacillin and vancomycin. There were no differences in mortality and multidrug-resistant pathogens rates between the two study periods. There were five episodes of fungal late-onset sepsis, mostly due to C. albicans, of which one was fatal. The microbial distribution pattern and AMR profiles overlapped with other European studies. Because susceptibility patterns are rapidly changing worldwide, with the emerging threat of Methicillin-resistant S. aureus and extended-spectrum beta-lactamases producers, infection prevention and control practices and AMS strategies require continuous optimization to limit selection pressure and AMR escalation.

2023 - Assessing risks of leaving the umbilical cord uncut: A case–control study [Articolo su rivista]
Bedetti, L.; Zinani, I.; Lugli, L.; Iughetti, L.; Facchinetti, F.; Berardi, A.
abstract

2023 - COVID-19 restrictions and hygiene measures reduce the rates of respiratory infections and wheezing among preterm infants [Articolo su rivista]
Scarponi, D.; Bedetti, L.; Zini, T.; Di Martino, M.; Cingolani, G. M.; Spaggiari, E.; Rossi, K.; Miselli, F.; Lugli, L.; Bergamini, B. M.; Iughetti, L.; Berardi, A.
abstract

Background and aim: During the 2020 and 2021 Italian COVID-19 pandemic social restrictions and strict hygiene measures were recommended to limit the spread of SARS-CoV-2. We aimed to assess whether rates of respiratory infections and wheezing in preterm infants have changed during the pandemic. Methods: Single center, retrospective study. Preterm infants in the first 6 months of life discharged home prior to (Period 1, January 2017 - December 2019) or during the pandemic (Period 2, January 2020 - March 2021) were compared. Rates of respiratory infection and wheezing in preterm infants with or without bronchopulmonary dysplasia (BDP) were assessed. Results: During period 2 premature infants had lower rates of respiratory infections (36 out of 55 in Period 1 vs 11 out of 28 in Period 2, P=0.023) and wheezing (20 out of 55 in Period 1 vs 1 out of 28 in Period 2, P=0.001). This difference remained significant when infants with BPD (all grades) were analyzed separately (respiratory infections 26 out of 40 in Period 1 vs 7 out of 24 in Period 2, P=0.005; wheezing 16 out of 40 in Period 1 vs 1 out of 24 in Period 2, P=0.001). In contrast, respiratory infections and wheezing in preterm infants without BPD did not change after pandemic. Conclusions: Episodes of respiratory infections and wheezing among preterm infants were reduced during pandemic. We highlight the importance of proper family education for preventing respiratory tract infections in preterm infants with BPD, beyond the extraordinary conditions of the COVID-19 pandemic.

2023 - Continuous Fentanyl Infusion in Newborns with Hypoxic–Ischemic Encephalopathy Treated with Therapeutic Hypothermia: Background, Aims, and Study Protocol for Time-Concentration Profiles [Articolo su rivista]
Lugli, L.; Garetti, E.; Goffredo, B. M.; Candia, F.; Crestani, S.; Spada, C.; Guidotti, I.; Bedetti, L.; Miselli, F.; Della Casa, E. M.; Roversi, M. F.; Simeoli, R.; Cairoli, S.; Merazzi, D.; Lago, P.; Iughetti, L.; Berardi, A.
abstract

Therapeutic hypothermia (TH) is the standard of care for newborns with moderate to severe hypoxic–ischemic encephalopathy (HIE). Discomfort and pain during treatment are common and may affect the therapeutic efficacy of TH. Opioid sedation and analgesia (SA) are generally used in clinical practice, and fentanyl is one of the most frequently administered drugs. However, although fentanyl’s pharmacokinetics (PKs) may be altered by hypothermic treatment, the PK behavior of this opioid drug in cooled newborns with HIE has been poorly investigated. The aim of this phase 1 study protocol (Trial ID: FentanylTH; EUDRACT number: 2020-000836-23) is to evaluate the fentanyl time-concentration profiles of full-term newborns with HIE who have been treated with TH. Newborns undergoing TH receive a standard fentanyl regimen (2 mcg/Kg of fentanyl as a loading dose, followed by a continuous infusion—1 mcg/kg/h—during the 72 h of TH and subsequent rewarming). Fentanyl plasma concentrations before bolus administration, at the end of the loading dose, and 24-48-72-96 h after infusion are measured. The median, maximum, and minimum plasma concentrations, together with drug clearance, are determined. This study will explore the fentanyl time-concentration profiles of cooled, full-term newborns with HIE, thereby helping to optimize the fentanyl SA dosing regimen during TH.

2023 - Early Skin-to-Skin Contact in Preterm Infants: Is It Safe? An Italian Experience [Articolo su rivista]
Bedetti, L.; Lugli, L.; Bertoncelli, N.; Spaggiari, E.; Garetti, E.; Lucaccioni, L.; Cipolli, F.; Berardi, A.
abstract

Background: Skin-to-skin contact (SSC) is one of the four components of kangaroo care (KC) and is also a valued alternative to incubators in low-income countries. SSC has also become a standard of care in high-income countries because of its short- and long-term benefits and its positive effect on infant growth and neurodevelopmental outcome. However, barriers in the implementation of SSC, especially with preterm infants, are common in NICUs because parents and health care professionals can perceive it as potentially risky for the clinical stability of preterm infants. Previous studies have assessed safety before and during SSC by monitoring vital parameters during short-time intervals. Aims: To demonstrate the safety of early SSC in preterm infants during at least 90 min intervals. Design: Prospective observational monocentric study. Methods: Preterm infants born between June 2018 and June 2020 with a gestational age of ≤33 weeks and a birth weight of <2000 g were monitored while performing an SSC session during the first three weeks of life. Infants with necrotizing enterocolitis, sepsis, and congenital malformations on mechanical ventilation or with more than five apneas in the hour before SSC were excluded. Continuous oxygen saturation (SaO2), heart rate (HR), and respiratory rate (RR) were registered during an SSC session and in the hour before. The minimum duration of an SSC session was 90 min. Information regarding postmenstrual age (PMA), body weight, respiratory support, presence of a central venous catheter and the onset of sepsis within 72 h after a session was collected. Two physicians, blinded to infant conditions and the period of analysis (before or during SSC), evaluated desaturation episodes (SaO2 < 85%, >15 s), bradycardia (HR < 100, >15 s) and apneas (pause in breathing > 20 s associated with desaturation and/or bradycardia). A Wilcoxon rank sum test was used for the statistical analysis. Results: In total, 83 episodes of SSC were analyzed for a total of 38 infants. The mean gestational age at birth was 29 weeks (range 23–33 weeks). Median PMA, days of life, and body weight at SSC were 31 weeks (range 25–34 weeks), 10 days (range 1–20 days), and 1131 g (range 631–2206 g), respectively. We found that 77% of infants were on respiratory support and 47% of them had a central venous catheter (umbilical or peripherally inserted central catheter) during SSC. The total duration of desaturation, bradycardia, and the number of apneas were not statistically different during the SSC session and the hour before. No catheter dislocation or ruptures were reported. Conclusions: These findings highlighted the safety of early SSC in preterm infants and the possibility of performing it in an intensive care setting in the first weeks of life. In addition, these findings should reassure health care professionals offering this practice as a standard of care. SSC plays a key role in the care of preterm infants due to its short- and long-term positive benefits, and it deserves to be increasingly offered to infants and their parents.

2023 - Exposure to prolonged rupture of membranes at term increases the risk for ventilatory support in uninfected neonates [Articolo su rivista]
Tramontano, Anna Luna; Menichini, Daniela; Lazzarin, Sara; Sponzilli, Alessandra; Zinani, Isotta; Facchinetti, Fabio; Berardi, Alberto
abstract

Background: The effects of prolonged rupture of membranes (ROM) on perinatal outcomes are still unclear and the management of those women remains controversial. This study aims to evaluate how the exposure of pregnant women to a prolonged ROM affects maternal and neonatal outcomes. Methods: This retrospective cohort study included singleton pregnant women at term delivering between January 2019, and March 2020 in a tertiary hospital. All relevant sociodemographic, pregnancy, and perinatal variables (maternal age, pre-pregnancy BMI, labor, and delivery outcomes) were collected anonymously. Data were compared between the "ROM < 24 hours" and "ROM ≥24 hours" study groups. Results: A total of 2689 dyads were included in the study and divided according to their ROM-delivery time: ROM <24 hours, (2369 women, 88.1%), and ROM ≥ 24 hours (320 women, 11.9%). Maternal baseline characteristics were comparable except for the rate of nulliparous women, which was significantly higher among patients with ROM ≥ 24 hours. No significant differences were found regarding infectious neonatal outcomes. However, mechanical ventilation and CPAP were more common among neonates born after ROM ≥ 24 h. The greater likelihood of neonatal respiratory distress was also confirmed among infants born to GBS-negative women with ROM ≥ 24 hours (15 out of 267 neonates, 5.6% vs 52 out of 1529 with ROM < 24 hours, 3.4%, p=0.04). Conclusions: According to the actual expectant policy, prolonged ROM is associated with an increased risk of respiratory support, in non-infected neonates. Further investigations are required to explain such an association.

2023 - Healthy preterm newborns: Altered innate immunity and impaired monocyte function [Articolo su rivista]
De Biasi, Sara; Neroni, Anita; Nasi, Milena; Lo Tartaro, Domenico; Borella, Rebecca; Gibellini, Lara; Lucaccioni, Laura; Bertucci, Emma; Lugli, Licia; Miselli, Francesca; Bedetti, Luca; Neri, Isabella; Ferrari, Fabrizio; Facchinetti, Fabio; Berardi, Alberto; Cossarizza, Andrea
abstract

: Birth prior to 37 completed weeks of gestation is referred to as preterm (PT). Premature newborns are at increased risk of developing infections as neonatal immunity is a developing structure. Monocytes, which are key players after birth, activate inflammasomes. Investigations into the identification of innate immune profiles in premature compared to full-term infants are limited. Our research includes the investigation of monocytes and NK cells, gene expression, and plasma cytokine levels to investigate any potential differences among a cohort of 68 healthy PT and full-term infants. According to high-dimensional flow cytometry, PT infants have higher proportions of CD56+/- CD16+ NK cells and immature monocytes, and lower proportions of classical monocytes. Gene expression revealed lower proportions of inflammasome activation after in vitro monocyte stimulation and the quantification of plasma cytokine levels expressed higher concentrations of alarmin S100A8. Our findings suggest that PT newborns have altered innate immunity and monocyte functional impairment, and pro-inflammatory plasmatic profile. This may explain PT infants' increased susceptibility to infectious disease and should pave the way for novel therapeutic strategies and clinical interventions.

2023 - Infectious Risks Related to Umbilical Venous Catheter Dwell Time and Its Replacement in Newborns: A Narrative Review of Current Evidence [Articolo su rivista]
Corso, L.; Buttera, M.; Candia, F.; Sforza, F.; Rossi, K.; Lugli, L.; Miselli, F.; Bedetti, L.; Baraldi, C.; Lucaccioni, L.; Iughetti, L.; Berardi, A.
abstract

The use of umbilical venous catheters (UVCs) has become the standard of care in the neonatal intensive care unit (NICU) to administer fluids, medications and parenteral nutrition. However, it is well known that UVCs can lead to some serious complications, both mechanical and infective, including CLABSI (Central Line-Associated Bloodstream Infections). Most authors recommend removing UVC within a maximum of 14 days from its placement. However, the last Infusion Therapy Standards of Practice (INS) guidelines recommends limiting the UVC dwell time to 7 to 10 days, to reduce risks of infectious and thrombotic complications. These guidelines also suggest as an infection prevention strategy to remove UVC after 4 days, followed by the insertion of a PICC if a central line is still needed. Nevertheless, the maximum UVC dwell time to reduce the risk of CLABSI is still controversial, as well as the time of its replacement with a PICC. In this study we reviewed a total of 177 articles, found by using the PubMed database with the following search strings: “UVC AND neonates”, “(neonate* OR newborn*) AND (UVC OR central catheter*) AND (infection*)”. We also analyze the INS guidelines to provide the reader an updated overview on this topic. The purpose of this review is to give updated information on CVCs infectious risks by examining the literature in this field. These data could help clinicians in deciding the best time to remove or to replace the UVC with a PICC, to reduce CLABSIs risk. Despite the lack of strong evidence, the risk of CLABSI seems to be minimized when UVC is removed/replaced within 7 days from insertion and this indication is emerging from more recent and larger studies.

2023 - Late-Onset Sepsis Mortality among Preterm Infants: Beyond Time to First Antibiotics [Articolo su rivista]
Miselli, F.; Crestani, S.; Maugeri, M.; Passini, E.; Spaggiari, V.; Deonette, E.; Cosic, B.; Rossi, K.; Roversi, M. F.; Bedetti, L.; Lugli, L.; Costantini, R. C.; Berardi, A.
abstract

Objective: To investigate the impact of timing, in vitro activity and appropriateness of empirical antimicrobials on the outcome of late-onset sepsis among preterm very low birth weight infants that are at high risk of developing meningitis. Study design: This retrospective study included 83 LOS episodes in 73 very low birth weight infants born at ≤32 weeks’ gestation with positive blood and/or cerebrospinal fluid culture or polymerase chain reaction at >72 h of age. To define the appropriateness of empirical antimicrobials we considered both their in vitro activity and their ideal delivery through the blood-brain barrier when meningitis was confirmed or not ruled out through a lumbar puncture. The primary outcome was sepsis-related mortality. The secondary outcome was the development of brain lesions. Timing, in vitro activity and appropriateness of empirical antimicrobials, were compared between fatal and non-fatal episodes. Uni- and multi-variable analyses were carried out for the primary outcome. Results: Time to antibiotics and in vitro activity of empirical antimicrobials were similar between fatal and non-fatal cases. By contrast, empirical antimicrobials were appropriate in a lower proportion of fatal episodes of late-onset sepsis (4/17, 24%) compared to non-fatal episodes (39/66, 59%). After adjusting for Gram-negative vs. Gram-positive pathogen and for other supportive measures (time to volume administration), inappropriate empirical antimicrobials remained associated with mortality (aOR, 10.3; 95% CI, 1.4–76.8, p = 0.023), while timing to first antibiotics was not (aOR 0.9; 95% CI, 0.7–1.2, p = 0.408; AUC = 0.88). The association between appropriate antimicrobials and brain sequelae was also significant (p = 0.024). Conclusions: The risk of sepsis-related mortality and brain sequelae in preterm very low birth weight infants is significantly associated with the appropriateness (rather than the timing and the in vitro activity) of empirical antimicrobials. Until meningitis is ruled out through lumbar puncture, septic very low birth weight infants at high risk of mortality should receive empiric antimicrobials with high delivery through the blood-brain barrier.

2023 - Less is more: Antibiotics at the beginning of life [Articolo su rivista]
Stocker, M.; Klingenberg, C.; Naver, L.; Nordberg, V.; Berardi, A.; el Helou, S.; Fusch, G.; Bliss, J. M.; Lehnick, D.; Dimopoulou, V.; Guerina, N.; Seliga-Siwecka, J.; Maton, P.; Lagae, D.; Mari, J.; Janota, J.; Agyeman, P. K. A.; Pfister, R.; Latorre, G.; Maffei, G.; Laforgia, N.; Mozes, E.; Stordal, K.; Strunk, T.; Giannoni, E.
abstract

Antibiotic exposure at the beginning of life can lead to increased antimicrobial resistance and perturbations of the developing microbiome. Early-life microbiome disruption increases the risks of developing chronic diseases later in life. Fear of missing evolving neonatal sepsis is the key driver for antibiotic overtreatment early in life. Bias (a systemic deviation towards overtreatment) and noise (a random scatter) affect the decision-making process. In this perspective, we advocate for a factual approach quantifying the burden of treatment in relation to the burden of disease balancing antimicrobial stewardship and effective sepsis management.

2023 - Lumbar Puncture and Meningitis in Infants with Proven Early- or Late-Onset Sepsis: An Italian Prospective Multicenter Observational Study [Articolo su rivista]
Bedetti, Luca; Miselli, Francesca; Minotti, Chiara; Latorre, Giuseppe; Loprieno, Sabrina; Foglianese, Alessandra; Laforgia, Nicola; Perrone, Barbara; Ciccia, Matilde; Capretti, Maria Grazia; Giugno, Chiara; Rizzo, Vittoria; Merazzi, Daniele; Fanaro, Silvia; Taurino, Lucia; Pulvirenti, Rita Maria; Orlandini, Silvia; Auriti, Cinzia; Haass, Cristina; Ligi, Laura; Vellani, Giulia; Tzialla, Chryssoula; Tuoni, Cristina; Santori, Daniele; China, Mariachiara; Baroni, Lorenza; Nider, Silvia; Visintini, Federica; Decembrino, Lidia; Nicolini, Giangiacomo; Creti, Roberta; Pellacani, Elena; Dondi, Arianna; Lanari, Marcello; Benenati, Belinda; Biasucci, Giacomo; Gambini, Lucia; Lugli, Licia; Berardi, Alberto
abstract

2023 - Lung UltrasouNd Guided surfactant therapy in preterm infants: an international multicenter randomized control trial (LUNG study) [Articolo su rivista]
Corsini, I.; Rodriguez-Fanjul, J.; Raimondi, F.; Boni, L.; Berardi, A.; Aldecoa-Bilbao, V.; Alonso-Ojembarrena, A.; Ancora, G.; Aversa, S.; Beghini, R.; Meseguer, N. B.; Capasso, L.; Chesi, F.; Ciarcia, M.; Concheiro, A.; Corvaglia, L.; Ficial, B.; Filippi, L.; Carballal, J. F.; Fusco, M.; Gatto, S.; Ginovart, G.; Gregorio-Hernandez, R.; Lista, G.; Sanchez-Luna, M.; Martini, S.; Massenzi, L.; Miselli, F.; Mercadante, D.; Mosca, F.; Palacio, M. T.; Perri, A.; Piano, F.; Prieto, M. P.; Fernandez, L. R.; Risso, F. M.; Savoia, M.; Staffler, A.; Vento, G.; Dani, C.
abstract

Background: The management of respiratory distress syndrome (RDS) in premature newborns is based on different types of non-invasive respiratory support and on surfactant replacement therapy (SRT) to avoid mechanical ventilation as it may eventually result in lung damage. European guidelines currently recommend SRT only when the fraction of inspired oxygen (FiO2) exceeds 0.30. The literature describes that early SRT decreases the risk of bronchopulmonary dysplasia (BPD) and mortality. Lung ultrasound score (LUS) in preterm infants affected by RDS has proven to be able to predict the need for SRT and different single-center studies have shown that LUS may increase the proportion of infants that received early SRT. Therefore, the aim of this study is to determine if the use of LUS as a decision tool for SRT in preterm infants affected by RDS allows for the reduction of the incidence of BPD or death in the study group. Methods/design: In this study, 668 spontaneously-breathing preterm infants, born at 25+0 to 29+6 weeks’ gestation, in nasal continuous positive airway pressure (nCPAP) will be randomized to receive SRT only when the FiO2 cut-off exceeds 0.3 (control group) or if the LUS score is higher than 8 or the FiO2 requirements exceed 0.3 (study group) (334 infants per arm). The primary outcome will be the difference in proportion of infants with BPD or death in the study group managed compared to the control group. Discussion: Based on previous published studies, it seems that LUS may decrease the time to administer surfactant therapy. It is known that early surfactant administration decreases BPD and mortality. Therefore, there is rationale for hypothesizing a reduction in BPD or death in the group of patients in which the decision to administer exogenous surfactant is based on lung ultrasound scores. Trial registration: ClinicalTrials.gov identifier NCT05198375 . Registered on 20 January 2022.

2023 - Monitoring of Auditory Function in Newborns of Women Infected by SARS-CoV-2 during Pregnancy [Articolo su rivista]
Apa, E.; Presutti, M. T.; Rossi, C.; Roversi, M. F.; Neri, S.; Gargano, G.; Bianchin, G.; Polizzi, V.; Caragli, V.; Monzani, D.; Berardi, A.; Palma, S.; Genovese, E.
abstract

Background: Gestational SARS-CoV-2 infection can impact maternal and neonatal health. The virus has also been reported to cause newborn sensorineural hearing loss, but its consequences for the auditory system are not fully understood. Objective: The aim of this study was to evaluate the impact of maternal SARS-CoV-2 infection during pregnancy on newborn’ hearing function during the first year of life. Methods: An observational study was conducted from 1 November 2020 to 30 November 2021 at University Modena Hospital. All newborns whose mother had been infected by SARS-CoV-2 during pregnancy were enrolled and underwent audiological evaluation at birth and at 1 year of age. Results: A total of 119 neonates were born from mothers infected by SARS-CoV-2 during pregnancy. At birth, five newborns (4.2%) presented an increased threshold of ABR (Auditory Brainstem Evoked Response), but the results were confirmed only in 1.6% of cases, when repeated 1 month later, while the ABR thresholds in all other children returned to normal limits. At the 1-year follow-up, no cases of moderate or severe hearing loss were observed, while concomitant disorders of the middle ear were frequently observed. Conclusions: Maternal SARS-CoV-2 infection, regardless of the trimester in which it was contracted, appears not to induce moderate or severe hearing loss in infants. It is important to clarify the possible effect of the virus on late-onset hearing loss and future research is needed.

2023 - Timing of Symptoms of Early-Onset Sepsis after Intrapartum Antibiotic Prophylaxis: Can It Inform the Neonatal Management? [Articolo su rivista]
Berardi, A.; Trevisani, V.; Di Caprio, A.; Caccamo, P.; Latorre, G.; Loprieno, S.; Foglianese, A.; Laforgia, N.; Perrone, B.; Nicolini, G.; Ciccia, M.; Capretti, M. G.; Giugno, C.; Rizzo, V.; Merazzi, D.; Fanaro, S.; Taurino, L.; Pulvirenti, R. M.; Orlandini, S.; Auriti, C.; Haass, C.; Ligi, L.; Vellani, G.; Tzialla, C.; Tuoni, C.; Santori, D.; Baroni, L.; China, M.; Bua, J.; Visintini, F.; Decembrino, L.; Creti, R.; Miselli, F.; Bedetti, L.; Lugli, L.
abstract

The effectiveness of “inadequate” intrapartum antibiotic prophylaxis (IAP administered < 4 h prior to delivery) in preventing early-onset sepsis (EOS) is debated. Italian prospective surveillance cohort data (2003–2022) were used to study the type and duration of IAP according to the timing of symptoms onset of group B streptococcus (GBS) and E. coli culture-confirmed EOS cases. IAP was defined “active” when the pathogen yielded in cultures was susceptible. We identified 263 EOS cases (GBS = 191; E. coli = 72). Among GBS EOS, 25% had received IAP (always active when beta-lactams were administered). Most IAP-exposed neonates with GBS were symptomatic at birth (67%) or remained asymptomatic (25%), regardless of IAP duration. Among E. coli EOS, 60% were IAP-exposed. However, IAP was active in only 8% of cases, and these newborns remained asymptomatic or presented with symptoms prior to 6 h of life. In contrast, most newborns exposed to an “inactive” IAP (52%) developed symptoms from 1 to >48 h of life. The key element to define IAP “adequate” seems the pathogen’s antimicrobial susceptibility rather than its duration. Newborns exposed to an active antimicrobial (as frequently occurs with GBS infections), who remain asymptomatic in the first 6 h of life, are likely uninfected. Because E. coli isolates are often unsusceptible to beta-lactam antibiotics, IAP-exposed neonates frequently develop symptoms of EOS after birth, up to 48 h of life and beyond.

2022 - Analysis of Antibiotic Exposure and Early-Onset Neonatal Sepsis in Europe, North America, and Australia [Articolo su rivista]
Giannoni, Eric; Dimopoulou, Varvara; Klingenberg, Claus; Navér, Lars; Nordberg, Viveka; Berardi, Alberto; El Helou, Salhab; Fusch, Gerhard; Bliss, Joseph M; Lehnick, Dirk; Guerina, Nicholas; Seliga-Siwecka, Joanna; Maton, Pierre; Lagae, Donatienne; Mari, Judit; Janota, Jan; Agyeman, Philipp K A; Pfister, Riccardo; Latorre, Giuseppe; Maffei, Gianfranco; Laforgia, Nicola; Mózes, Eniko; Størdal, Ketil; Strunk, Tobias; Stocker, Martin
abstract

Importance: Appropriate use of antibiotics is life-saving in neonatal early-onset sepsis (EOS), but overuse of antibiotics is associated with antimicrobial resistance and long-term adverse outcomes. Large international studies quantifying early-life antibiotic exposure along with EOS incidence are needed to provide a basis for future interventions aimed at safely reducing neonatal antibiotic exposure. Objective: To compare early postnatal exposure to antibiotics, incidence of EOS, and mortality among different networks in high-income countries. Design, setting, and participants: This is a retrospective, cross-sectional study of late-preterm and full-term neonates born between January 1, 2014, and December 31, 2018, in 13 hospital-based or population-based networks from 11 countries in Europe and North America and Australia. The study included all infants born alive at a gestational age greater than or equal to 34 weeks in the participating networks. Data were analyzed from October 2021 to March 2022. Exposures: Exposure to antibiotics started in the first postnatal week. Main outcomes and measures: The main outcomes were the proportion of late-preterm and full-term neonates receiving intravenous antibiotics, the duration of antibiotic treatment, the incidence of culture-proven EOS, and all-cause and EOS-associated mortality. Results: A total of 757 979 late-preterm and full-term neonates were born in the participating networks during the study period; 21 703 neonates (2.86%; 95% CI, 2.83%-2.90%), including 12 886 boys (59.4%) with a median (IQR) gestational age of 39 (36-40) weeks and median (IQR) birth weight of 3250 (2750-3750) g, received intravenous antibiotics during the first postnatal week. The proportion of neonates started on antibiotics ranged from 1.18% to 12.45% among networks. The median (IQR) duration of treatment was 9 (7-14) days for neonates with EOS and 4 (3-6) days for those without EOS. This led to an antibiotic exposure of 135 days per 1000 live births (range across networks, 54-491 days per 1000 live births). The incidence of EOS was 0.49 cases per 1000 live births (range, 0.18-1.45 cases per 1000 live births). EOS-associated mortality was 3.20% (12 of 375 neonates; range, 0.00%-12.00%). For each case of EOS, 58 neonates were started on antibiotics and 273 antibiotic days were administered. Conclusions and relevance: The findings of this study suggest that antibiotic exposure during the first postnatal week is disproportionate compared with the burden of EOS and that there are wide (up to 9-fold) variations internationally. This study defined a set of indicators reporting on both dimensions to facilitate benchmarking and future interventions aimed at safely reducing antibiotic exposure in early life.

2022 - Antibiotic Exposure, Common Morbidities and Main Intestinal Microbial Groups in Very Preterm Neonates: A Pilot Study [Articolo su rivista]
Bozzi Cionci, N.; Lucaccioni, L.; Pietrella, E.; Ficara, M.; Spada, C.; Torelli, P.; Bedetti, L.; Lugli, L.; Di Gioia, D.; Berardi, A.
abstract

Prematurity exposes newborns to increased risks of infections and it is associated with critical morbidities. Preterm infants often require antibiotic therapies that can affect the correct establishment of gut microbiota. The aim of this study was to investigate targeted intestinal bacteria in preterm neonates with common morbidities and receiving antibiotic treatments of variable duration. Stool samples were collected after birth, at 15, 30 and 90 days of life. qPCR quantification of selected microbial groups (Bifidobacterium spp., Bacteroides fragilis group, Enterobacteriaceae, Clostridium cluster I and total bacteria) was performed and correlation between their levels, the duration of antibiotic treatment and different clinical conditions was studied. An increasing trend over time was observed for all microbial groups, especially for Bifdobacterium spp. Prolonged exposure to antibiotics in the first weeks of life affected Clostridium and B. fragilis levels, but these changes no longer persisted at 90 days of life. Variations of bacterial counts were associated with the length of hospital stay, feeding and mechanical ventilation. Late-onset sepsis and patent ductus arteriosus reduced the counts of Bifidobacterium, whereas B. fragilis was influenced by compromised respiratory conditions. This study can be a start point for the identification of microbial biomarkers associated with some common morbidities and tailored strategies for a healthy microbial development.

2022 - Autosomal recessive cutis laxa type IIIA: Report of a patient with severe phenotype and review of the literature [Articolo su rivista]
Lugli, Licia; Cavalleri, Francesca; Bertucci, Emma; Fischer-Zirnsak, Björn; Cinelli, Giulia; Trevisani, Viola; Rossi, Cecilia; Riva, Marika; Iughetti, Lorenzo; Berardi, Alberto
abstract

Autosomal recessive cutis laxa type IIIA is a very rare genetic condition, caused by pathogenic variants in ALDH18A1, encoding delta-1-pyrroline-5-carboxylate synthase (P5CS). This enzyme catalyzes the reduction of glutamic acid to delta1-pyrroline-5-carboxylate, playing a key role in the de novo biosynthesis of proline, ornithine, and arginine. Autosomal recessive cutis laxa type IIIA is characterized by abundant and wrinkled skin, skeletal anomalies, cataract or corneal clouding and neuro-developmental disorders of variable degree. We report on a patient with autosomal recessive cutis laxa type IIIA, due to a homozygous missense c.1273C > T; p. (Arg425Cys) pathogenic variant in ALDH18A1. The patient presented a severe phenotype with serious urological involvement, peculiar cerebro-vascular abnormalities and neurodevelopmental compromise. This description contributes to better characterize the phenotypic spectrum associated with ALDH18A1 pathogenic variants, confirming the systemic involvement as a typical feature of autosomal recessive cutis laxa type IIIA.

2022 - Can Fraction of Inspired Oxygen Predict Extubation Failure in Preterm Infants? [Articolo su rivista]
Spaggiari, E.; Amato, M.; Ricca, O. A.; Zini, L. C.; Bianchedi, I.; Lugli, L.; Boncompagni, A.; Guidotti, I.; Rossi, C.; Bedetti, L.; Iughetti, L.; Berardi, A.
abstract

Background: Prolonged mechanical ventilation in preterm infants may cause complications. We aimed to analyze the variables affecting extubation outcomes in preterm infants at high risk of extubation failure. Methods: This was a single-center, observational, retrospective study. Extubation failure was defined as survival with the need for reintubation within 72 h. Successfully extubated neonates (group 1) were compared to those with failed extubation (group 2). Multivariate logistic regression analysis evaluated factors that predicted extubation outcomes. Results: Eighty infants with a birth weight under 1000 g and/or gestational age (GA) under 28 weeks were included. Extubation failure occurred in 29 (36.2%) and success in 51 (63.8%) neonates. Most failures (75.9%) occurred within 24 h. Pre-extubation inspired oxygen fraction (FiO2) of 27% had a sensitivity of 58.6% and specificity of 64.7% for extubation failure. Post-extubation FiO2 of 32% had a sensitivity of 65.5% and specificity of 62.8% for failure. Prolonged membrane rupture (PROM) and high GA were associated with extubation success in multivariate logistic regression analysis. Conclusions: High GA and PROM were associated with extubation success. Pre-and post-extubation FiO2 values were not significantly predictive of extubation failure. Further studies should evaluate if overall assessment, including ventilatory parameters and clinical factors, can predict extubation success in neonates.

2022 - Challenges in the growth and development of newborns with extra-uterine growth restriction [Articolo su rivista]
Lucaccioni, L.; Iughetti, L.; Berardi, A.; Predieri, B.
abstract

Introduction: Extra-uterine growth restriction (EUGR) is a condition caused by the failure of very preterm infants to reach their potential growth during the NICU hospital stay. Despite enormous improvements in nutritional support and strategies, the growth pattern of preterm infants is still far from the one expected. Areas covered: This review focuses on what EUGR is, highlighting controversial aspects of this topic. EUGR is still missing a univocal definition, and the international debate is also open on what is the best growth chart to use. Moreover, professionals in NICU may not be trained on how to perform anthropometric measurements, increasing the risk of over- or underestimation, especially for length assessment. EUGR has recently been described as one of the main comorbidities in NICU, influencing growth, metabolism, and neurodevelopment later in life. Expert opinion: There is still much to investigate about what the best growth pattern in the NICU should be. What is known so far is that the majority of preterm neonates develop EUGR, and this leads to several short- and long-term consequences. It is imperative that neonatologists and pediatric endocrinologists work together, to modulate growth in the NICU.

2022 - Correspondence on “Disorder of sex development associated with a novel homozygous nonsense mutation in COG6 expands the phenotypic spectrum of COG6-CDG” [Articolo su rivista]
Lugli, L.; Pollazzon, M.; Bigoni, S.; Caraffi, S. G.; Ferlini, A.; Ferri, L.; Morrone, A.; Calabrese, O.; Iughetti, L.; Garavelli, L.; Berardi, A.
abstract

2022 - Early-onset meningitis with delayed presentation: Is there a role for prevention? [Articolo su rivista]
Miselli, F.; Lugli, L.; Bedetti, L.; Zinani, I.; Berardi, A.
abstract

2022 - Enteroviral Infections in the First Three Months of Life [Articolo su rivista]
Sandoni, M.; Ciardo, L.; Tamburini, C.; Boncompagni, A.; Rossi, C.; Guidotti, I.; Garetti, E.; Lugli, L.; Iughetti, L.; Berardi, A.
abstract

Enteroviruses (EVs) are an important source of infection in the paediatric age, with most cases concerning the neonatal age and early infancy. Molecular epidemiology is crucial to understand the circulation of main serotypes in a specific area and period due to their extreme epidemiological variability. The diagnosis of EVs infection currently relies on the detection of EVs RNA in biological samples (usually cerebrospinal fluid and plasma, but also throat swabs and feces) through a poly-merase chain reaction assay. Although EVs infections usually have a benign course, they sometimes become life threatening, especially when symptoms develop in the first few days of life. Mortality is primarily associated with myocarditis, acute hepatitis, and multi-organ failure. Neurodevelopmental sequelae have been reported following severe infections with central nervous system involvement. Unfortunately, at present, the treatment of EVs infections is mainly supportive. The use of specific antiviral agents in severe neonatal infections has been reported in single cases or studies includ-ing few neonates. Therefore, further studies are needed to confirm the efficacy of these drugs in clinical practice.

2022 - Escherichia coli Is Overtaking Group B Streptococcus in Early-Onset Neonatal Sepsis [Articolo su rivista]
Miselli, F.; Cuoghi Costantini, R.; Creti, R.; Sforza, F.; Fanaro, S.; Ciccia, M.; Piccinini, G.; Rizzo, V.; Pasini, L.; Biasucci, G.; Pagano, R.; Capretti, M.; China, M.; Gambini, L.; Pulvirenti, R. M.; Dondi, A.; Lanari, M.; Pedna, M.; Ambretti, S.; Lugli, L.; Bedetti, L.; Berardi, A.
abstract

The widespread use of intrapartum antibiotic prophylaxis (IAP) to prevent group B streptococcus (GBS) early-onset sepsis (EOS) is changing the epidemiology of EOS. Italian prospective area-based surveillance data (from 1 January 2016 to 31 December 2020) were used, from which we identified 64 cases of culture-proven EOS (E. coli, n = 39; GBS, n = 25) among 159,898 live births (annual incidence rates of 0.24 and 0.16 per 1000, respectively). Approximately 10% of E. coli isolates were resistant to both gentamicin and ampicillin. Five neonates died; among them, four were born very pre-term (E. coli, n = 3; GBS, n = 1) and one was born full-term (E. coli, n = 1). After adjustment for gestational age, IAP-exposed neonates had ≥95% lower risk of death, as compared to IAP-unexposed neonates, both in the whole cohort (OR 0.04, 95% CI 0.00–0.70; p = 0.03) and in the E. coli EOS cohort (OR 0.05, 95% CI 0.00–0.88; p = 0.04). In multi-variable logistic regression analysis, IAP was inversely associated with severe disease (OR = 0.12, 95% CI 0.02–0.76; p = 0.03). E. coli is now the leading pathogen in neonatal EOS, and its incidence is close to that of GBS in full-term neonates. IAP reduces the risk of severe disease and death. Importantly, approximately 10% of E. coli isolates causing EOS were found to be resistant to typical first-line antibiotics.

2022 - Foot-to-Foot Contact Among Initial Goal-Directed Movements Supports the Prognostic Value of Fidgety Movements in HIE-Cooled Infants [Articolo su rivista]
Ferrari, F.; Bedetti, L.; Bertoncelli, N.; Roversi, M. F.; Della Casa, E.; Guidotti, I.; Ori, L.; D'Amico, R.; Valeri, L.; Lugli, L.; Lucaccioni, L.; Berardi, A.
abstract

Background: Few studies conducted to date have observed general movements in infants affected by hypoxic–ischemic encephalopathy (HIE) who underwent therapeutic hypothermia. We investigated whether foot-to-foot contact (FF) could support the predictive value of fidgety movements (FMs) in infants affected by HIE and treated with brain cooling. Methods: Spontaneous motility was video recorded for 3–5 min at 12 weeks post-term age in 58 full-term newborn infants affected by perinatal asphyxia who were cooled due to moderate to severe HIE. FF and FMs were blindly scored by three independent observers. At 24 months, each patient underwent a neurological examination by Amiel-Tison and Grenier. Results: At 24 months, 47 infants had developed typically at neurological examination, eight had developed mild motor impairment, and three developed cerebral palsy (CP). At 12 weeks, 34 (58.6%) infants had shown normal FMs, four of whom developed mild motor impairment. Twenty-four infants (41.4%) exhibited abnormal or no FMs, four of whom developed mild motor impairment and three developed CP. FF was present in 20 infants (34.5%), two of whom developed mild motor impairment. FF was absent in 38 infants (65.5%), six of whom developed mild motor impairment and three developed CP. Both FMs and FF, considered separately, were 100% sensitive for predicting CP at 24 months, but only 61 and 36%, respectively, were specific. Summing the two patterns together, the specificity increases to 73%, considering only CP as an abnormal outcome, and increases to 74% when considering CP plus mild motor impairment. Unexpectedly, fidgety movements were absent in 24 infants with typical motor outcomes, 17 of whom showed a typical motor outcome. Conclusions: FF is already part of motor repertoire at 12 weeks and allows a comparison of spontaneous non-voluntary movements (FMs) to pre-voluntary movements (FF). FF supports FMs for both sensitivity and specificity. A second video recording at 16–18 weeks, when pedipulation is present in healthy infants, is suggested: it may better define the presence or absence of goal-directed motility.

2022 - Group B Streptococcus Late-onset Neonatal Disease: An Update in Management and Prevention [Articolo su rivista]
Miselli, F.; Creti, R.; Lugli, L.; Berardi, A.
abstract

2022 - Laboratory breakpoints for assessing high level gentamicin resistance in Streptococcus agalactiae: it is the time for a consensus [Articolo su rivista]
Creti, R.; Imperi, M.; Berardi, A.; Angeletti, S.; Gherardi, G.
abstract

2022 - Maternal Singing but Not Speech Enhances Vagal Activity in Preterm Infants during Hospitalization: Preliminary Results [Articolo su rivista]
Filippa, M.; Nardelli, M.; Della Casa, E.; Berardi, A.; Picciolini, O.; Meloni, S.; Lunardi, C.; Cecchi, A.; Sansavini, A.; Corvaglia, L.; Scilingo, E. P.; Ferrari, F.
abstract

Background: Early parental interventions in the Neonatal Intensive Care Units (NICUs) have beneficial effects on preterm infants’ short and long-term outcomes. The aim of this study was to investigate the effects of Early Vocal Contact (EVC)—singing and speaking—on preterm infants’ vagal activity and autonomic nervous system (ANS) maturation. Methods: In this multi-center randomized clinical trial, twenty-four stable preterm infants, born at 25–32 weeks gestational age, were randomized to either the EVC group or control group, where mothers did not interact with the babies but observed their behavior. Heart Rate Variability (HRV) was acquired before intervention (pre-condition), during vocal contact, and after it (post condition). Results: No significant effect of the vocal contact, singing and speaking, was found in HRV when the intervention group was compared to the control group. However, a significant difference between the singing and the pre and post conditions, respectively, preceding and following the singing intervention, was found in the Low and High Frequency power nu, and in the low/high frequency features (p = 0.037). By contrast, no significant effect of the speaking was found. Conclusions: Maternal singing, but not speaking, enhances preterm infants’ vagal activity in the short-term, thus improving the ANS stability. Future analyses will investigate the effect of enhanced vagal activity on short and long-term developmental outcomes of preterm infants in the NICU.

2022 - Monitoring of Communication Precursors in Extremely Low Birth Weight (ELBW) Newborns by Video Analysis Method: Preliminary Results [Articolo su rivista]
Sundas, L.; Palma, S.; Pugliese, M.; Roversi, M. F.; Apa, E.; Berardi, A.; Genovese, E.; Monzani, D.
abstract

Background: The survival of extremely low birth weight infants (ELBW) has increased worldwide. Even in the absence of major disabilities, ELBW infants show difficulty in simple language functions. It is relevant to assess early abilities, which are the base of early linguistic skills, in order to implement customized intervention programs in ELBW infants. Aims: To evaluate communication precursors of language development in ELBW infants at 12 and 24 months of correct age (C.A). To investigate the correlation of linguistic and communicative prerequisites with mental development outcome at 24 months CA. Method: 52 ELBW neonates (mean gestational age 26.6 weeks, mean birth weight was 775 g) who were admitted to the neonatal intensive care unit of the University Hospital of Modena, were enrolled. Data were collected from archived audio-video recordings of neurodevelopmental follow-up visits. Video analysis of communicative and linguistic developmental was performed at 12 and 24 months CA. Neurodevelopmental outcome was evaluated with Mental Developmental Scales (GMDS-R). Results: The video-analysis showed that infants at 12 months CA used predominantly eye contacts and gestural turns, while vocal turns were scant. At 24 months CA, a significant change in eye contacts, vocal turns, gestural turns, and utterances (p < 0.001) occurred. The total number of utterances (p = 0.036) and eye contacts (p = 0.045) were significantly correlated to the Development Quotient (DQ) of Hearing and Language scale. Moreover, a significant correlation was found with the Personal-Social scale vocal turns (p = 0.009) and the total number of utterances (p = 0,02). Finally, the Global Quotient of the GMDS-R was related to the Vocal Turns (p = 0.034) and the total number of Utterances (p = 0.013). Conclusions: ELBW infants at 12 months CA use predominantly eye contacts and gestural turns to communicate with adults. At 24 months CA, the child’s communicative intention evolves from gestural to verbal communication. The latter is characterized by an increase in both vocal turns and the number of utterances produced during interaction. The video analysis we implement appears to be a sensitive tool for early assessment of communication and language development and to refine early intervention.

2022 - Multiple thrombosis of the cerebral venous sinuses, neonatal seizures, and minor parenchymal lesions: a case report and a review of the literature [Articolo su rivista]
Bedetti, L.; Poluzzi, S.; Guidotti, I.; Lucaccioni, L.; Rota, C.; Cavalleri, F.; Pugliese, M.; Iughetti, L.; Lugli, L.; Berardi, A.
abstract

Background: Cerebral sinovenous thrombosis (CSVT) is a rare disease with potential catastrophic consequences. However, neonatal brain damage after venous injury and long-term neurologic outcomes have been poorly investigated. Some found an association between site and number of sinus occlusions, severity of lesions, clinical presentation and the neurodevelopmental outcome. Case presentation: We describe the case of a term newborn girl with multiple CSVT who presented with clonic seizures and who received early treatment with heparin. MRI scans showed a progressive recanalization of deep venous system, and only minor cerebral lesions were present at 3 months of life. Neurocognitive outcome was normal at 12 months of life. Conclusions: This case demonstrates that multiple CSVT presenting with severe seizures does not necessarily underlie major cerebral lesions or lead to severely abnormal neurodevelopmental outcome.

2022 - Neonatal seizures treatment based on conventional multichannel EEG monitoring: an overview of therapeutic options [Articolo su rivista]
Guidotti, Isotta; Lugli, Licia; Ori, Luca; Roversi, Maria Federica; Casa Muttini, Elisa Della; Bedetti, Luca; Pugliese, Marisa; Cavalleri, Francesca; Stefanelli, Francesca; Ferrari, Fabrizio; Berardi, Alberto
abstract

Introduction: Seizures are the main neurological emergency during the neonatal period and are mostly acute and focal. The prognosis mainly depends on the underlying etiology. Conventional multichannel video-electroencephalographic (cEEG) monitoring is the gold standard for diagnosis, but treatment remains a challenge. Areas covered: : This review, based on PubMed search over the last 4 decades, focuses on the current treatment options for neonatal seizures based on cEEG monitoring. There is still no consensus on seizure therapy, owing to poor scientific evidence. Traditionally, the first-line treatments are phenobarbital and phenytoin, followed by midazolam and lidocaine, but their efficacy is limited. Therefore, current evidence strongly suggests the use of alternative antiseizure medications. Randomized controlled trials of new drugs are ongoing. Expert opinion: : Therapy for neonatal seizures should be prompt and tailored, based on semeiology, mirror of the underlying cause, and cEEG features. Further research should focus on antiseizure medications that directly act on the etiopathogenetic mechanism responsible for seizures and are therefore more effective in seizure control.

2022 - Neonatal septic shock, a focus on first line interventions [Articolo su rivista]
Spaggiari, Valentina; Passini, Erica; Crestani, Sara; Roversi, Maria Federica; Bedetti, Luca; Rossi, Katia; Lucaccioni, Laura; Baraldi, Cecilia; Della Casa Muttini, Elisa; Lugli, Licia; Iughetti, Lorenzo; Berardi, Alberto
abstract

Septic shock is a main cause of morbidity and mortality in neonates. Septic shock evolves from compensated to uncompensated through 3 distinct phases. Prompt diagnosis is challenging, since neonatal septic shock may overlap with the physiological changes occurring at birth. The outcome of septic shock depends on a prompt recognition of symptoms and a strict adherence to cardiopulmonary resuscitation guidelines. Fluid administration plays a major role in the initial management of septic shock. If there is no response to volume filling, inotropes must be infused within one hour of onset (dopamine, dobutamine, adrenaline). Life-threatening infections require immediate and aggressive empiric use of antimicrobials. In the pediatric age, delay in antibiotic initiation for treating septic shock is associated with poor outcome and increased risk of mortality. There is a gap regarding first line interventions in neonatal septic shock. This review addresses initial interventions in the treatment of neonatal septic shock and discusses currently available evidences., These interventions may allow to improve the outcome if they are promptly carried out.

2022 - Omenn Syndrome due to RAG1 Mutation Presenting With Nonimmune Hydrops Fetalis in Two Siblings [Articolo su rivista]
Valeri, L.; Lugli, L.; Iughetti, L.; Soresina, A.; Giliani, S.; Porta, F.; Berardi, A.
abstract

Omenn syndrome (OS) is a rare variant of severe combined immunodeficiency characterized by susceptibility to severe opportunistic infections and peculiar manifestations, such as protein-losing erythroderma, alopecia, hepatosplenomegaly, lymphadenopathies, and severe diarrhea. The typical form of the disease is caused by hypomorphic mutation of the recombination-activating genes (RAG1 and RAG2), which are critical in initiating the molecular processes leading to lymphocyte and immunoglobulin receptor formation. Affected patients lack B cells, whereas autoreactive oligoclonal T cells infiltrate the skin, gut, spleen, and liver. In the absence of hematopoietic stem cell transplantation, patients with OS usually succumb early in life because of opportunistic infections. The incidence of OS is estimated to be <1 per 1 000 000; however, the actual frequency is difficult to ascertain. We report 2 siblings affected by OS due to a homozygous frameshift mutation (NM_000448.3:c.519delT, p.E174Sfs*26) in the RAG1 gene presenting with nonimmune hydrops fetalis (NIHF). To the best of our knowledge, this is the first reported association between OS and NIHF. NIHF specifically refers to the presence of ≥2 abnormal fluid collections in the fetus, without red blood cell alloimmunization. A broad spectrum of pathologies is associated with NIHF; however, in ∼20% of the cases, the primary cause remains unclear. Understanding the etiology of NIHF is essential for guiding clinical management, determining prognosis, and informing parents regarding recurrence risk. Our case contributes to expanding the spectrum of OS presentation and highlights the importance of a complete immunologic and genetic workup in otherwise unexplained cases of NIHF.

2022 - Polygraphic EEG Can Identify Asphyxiated Infants for Therapeutic Hypothermia and Predict Neurodevelopmental Outcomes [Articolo su rivista]
Lugli, L.; Guidotti, I.; Pugliese, M.; Roversi, M. F.; Bedetti, L.; Della Casa Muttini, E.; Cavalleri, F.; Todeschini, A.; Genovese, M.; Ori, L.; Amato, M.; Miselli, F.; Lucaccioni, L.; Bertoncelli, N.; Candia, F.; Maura, T.; Iughetti, L.; Ferrari, F.; Berardi, A.
abstract

Background: Neonatal encephalopathy due to perinatal asphyxia is one of the leading causes of neonatal death and morbidity worldwide. The neurodevelopmental outcomes of asphyxiated neonates have considerably improved after therapeutic hypothermia (TH). The current challenge is to identify all newborns with encephalopathy at risk of cerebral lesions and subsequent disability within 6 h of life and who may be within the window period for treatment with TH. This study evaluated the neurodevelopmental outcomes in surviving asphyxiated neonates who did and did not receive TH, based on clinical and polygraphic electroencephalographic (p-EEG) criteria. Methods: The study included 139 asphyxiated newborns divided into two groups: 82 who received TH and 57 who were not cooled. TH was administered to asphyxiated newborns (gestational age ≥ 35 weeks, birth weight ≥ 1800 g) with encephalopathy of any grade and moderate-to-severe p-EEG abnormalities or seizures. Neurodevelopmental outcomes between the groups at 24 months of life and the risk factors for severe outcomes were assessed. Results: Severe neurodevelopmental impairment occurred in 10 (7.2%) out of the 139 enrolled neonates. Nine out of the 82 cooled neonates (11.0%) had severe neurodevelopmental impairment. All but one neonate (98.2%) who did not receive TH had normal outcomes. The multivariate logistic regression analysis showed that abnormal p-EEG patterns (OR: 27.6; IC: 2.8–267.6) and general movements (OR: 3.2; IC: 1.0–10.0) were significantly associated with severe neurodevelopmental impairment (area under ROC curve: 92.7%). Conclusion: The combination of clinical and p-EEG evaluations in hypoxic–ischemic encephalopathy contributed to a more accurate selection of patients treated with therapeutic hypothermia. When administered to infants with moderate to severe p-EEG abnormalities, TH prevents approximately 90% of severe neurodevelopmental impairment after any grade of hypoxic–ischemic encephalopathy.

2022 - Should we give antibiotics to neonates with mild non-progressive symptoms? A comparison of serial clinical observation and the neonatal sepsis risk calculator [Articolo su rivista]
Berardi, A.; Zinani, I.; Bedetti, L.; Vaccina, E.; Toschi, A.; Toni, G.; Lecis, M.; Leone, F.; Monari, F.; Cozzolino, M.; Zini, T.; Boncompagni, A.; Iughetti, L.; Miselli, F.; Lugli, L.
abstract

2022 - Sudden Unexpected Postnatal Collapse and Therapeutic Hypothermia: What’s Going On? [Articolo su rivista]
Bedetti, L.; Lugli, L.; Garetti, E.; Guidotti, I.; Roversi, M. F.; Della Casa, E.; Miselli, F.; Bariola, M. C.; Di Caprio, A.; Pugliese, M.; Ferrari, F.; Berardi, A.
abstract

Sudden unexpected postnatal collapse (SUPC) is a rare event, potentially associated with catastrophic consequences. Since the beginning of the 2000s, therapeutic hypothermia (TH) has been proposed as a treatment for asphyxiated neonates after SUPC. However, only a few studies have reported the outcome of SUPC after TH. The current study presents the long-term neurodevelopmental outcome of four cases of SUPC treated with TH in a single Italian center. Furthermore, we reviewed the previous literature concerning 49 cases of SUPC treated with TH. Among 53 total cases (of whom four occurred in our center), 15 (28.3%) died before discharge from the NICU. A neurodevelopmental follow-up was available only for 21 (55.3%) out of the 38 surviving cases, and seven infants developed neurodevelopmental sequelae. TH should be considered in neonates with asphyxia after SUPC. However, SUPC is a rare event, and there is a lack of comparative clinical data to establish the risk/benefit of TH after SUPC with different degrees of asphyxia. Analysis of large cohorts of newborns with SUPC, whether treated with TH or untreated, are needed in order to better identify infants who should undergo TH.

2022 - Townes-Brocks syndrome with craniosynostosis in two siblings [Articolo su rivista]
Lugli, L.; Rossi, C.; Ceccarelli, P. L.; Calabrese, O.; Bedetti, L.; Miselli, F.; Bianchini, M. A.; Iughetti, L.; Berardi, A.
abstract

This report describes a novel truncating c.709C > T p.(Gln237*) SALL1 variant in two siblings exhibiting sagittal craniosynostosis as a unique feature of Townes-Brocks syndrome (TBS, OMIM #107480). TBS is a rare autosomal dominant syndrome with variable phenotypes, including anorectal, renal, limb, and ear abnormalities, which results from heterozygous variants in the SALL1 gene, predominantly located in the 802 bp “hot spot region” within exon 2. Recent studies have suggested that aberrations in primary cilia and sonic hedgehog signalling contribute to the TBS phenotypes. The presence of the novel c.709C > T p.(Gln237*) SALL1 variant was confirmed in both the siblings and their father, whereas no mutations currently associated with craniosynostosis were detected. We hypothesise that the truncating c.709C > T p.(Gln237*) SALL1 variant, which occurs outside the “hot spot region” and inside the glutamine-rich domain coding region, could interfere with ciliary signalling and mechanotransduction, contributing to premature fusion of calvarial sutures. This report broadens the genetic and phenotypic spectrum of TBS and provides the first clinical evidence of craniosynostosis as a novel feature of the syndrome.

2022 - Transmission of Group B Streptococcus in late-onset neonatal disease: a narrative review of current evidence [Articolo su rivista]
Miselli, F.; Frabboni, I.; Di Martino, M.; Zinani, I.; Buttera, M.; Insalaco, A.; Stefanelli, F.; Lugli, L.; Berardi, A.
abstract

Group B streptococcus (GBS) late-onset disease (LOD, occurring from 7 through 89 days of life) is an important cause of sepsis and meningitis in infants. The pathogenesis and modes of transmission of LOD to neonates are yet to be elucidated. Established risk factors for the incidence of LOD include maternal GBS colonisation, young maternal age, preterm birth, HIV exposure and African ethnicity. The mucosal colonisation by GBS may be acquired perinatally or in the postpartum period from maternal or other sources. Growing evidence has demonstrated the predominant role of maternal sources in the transmission of LOD. Intrapartum antibiotic prophylaxis (IAP) to prevent early-onset disease reduces neonatal GBS colonisation during delivery; however, a significant proportion of IAP-exposed neonates born to GBS-carrier mothers acquire the pathogen at mucosal sites in the first weeks of life. GBS-infected breast milk, with or without presence of mastitis, is considered a potential vehicle for transmitting GBS. Furthermore, horizontal transmission is possible from nosocomial and other community sources. Although unfrequently reported, nosocomial transmission of GBS in the neonatal intensive care unit is probably less rare than is usually believed. GBS disease can sometime recur and is usually caused by the same GBS serotype that caused the primary infection. This review aims to discuss the dynamics of transmission of GBS in the neonatal LOD.

2021 - Antibiotic use in very low birth weight neonates after an antimicrobial stewardship program [Articolo su rivista]
Berardi, A.; Zinani, I.; Rossi, C.; Spaggiari, E.; D'Amico, V.; Toni, G.; Bedetti, L.; Lucaccioni, L.; Iughetti, L.; Lugli, L.
abstract

There is insufficient data regarding antimicrobial stewardship (AS) and outcomes of very low birth weight (VLBW) neonates after AS programs. This observational, retrospective study addressed AS and outcomes of VLBW neonates admitted to an Italian level-three center. Two periods were compared: (i) baseline, before AS (January 2011-December 2012) and (ii) intervention, after AS (January 2016-December 2017). Between these two periods, procedures were put in place to inform medical and nursing staff regarding AS. There were 111 and 119 VLBW neonates in the baseline (6744 live births) and in the intervention period (5902 live births), respectively. The number of infants exposed to antibiotics (70%) during the hospital stay did not change, but the total days of therapy (DOT, median 12 vs. 5) and DOT/1000 patient days (302 vs. 215) decreased in the intervention period (p < 0.01), as well as the median duration of first antibiotic treatment (144 vs. 48 h, p < 0.01). A re-analysis of single cases of culture-proven or culture-negative sepsis failed to demonstrate any association between deaths and a delay or insufficient antibiotic use in the intervention period. In conclusion, AS is feasible in preterm VLBW neonates and antibiotic use can be safely reduced.

2021 - Brain cooling reduces the risk of post-neonatal epilepsy in newborns affected by moderate to severe hypoxic-ischemic encephalopathy [Articolo su rivista]
Lugli, Licia; Balestri, Eleonora; Berardi, Alberto; Guidotti, Isotta; Cavalleri, Francesca; Todeschini, Alessandra; Pugliese, Marisa; Muttini Della Casa, Elisa; Lucaccioni, Laura; Ferrari, Fabrizio
abstract

Neonatal hypoxic-ischemic encephalopathy is still a significant cause of neonatal death and neurodevelopmental disabilities, such as cerebral palsy, mental delay, and epilepsy. After the introduction of therapeutic hypothermia, the prognosis of hypoxic-ischemic encephalopathy has improved, with reduction of death and disabilities. However, few studies evaluated whether hypothermia affects rate and severity of post-neonatal epilepsy. We evaluated rates, characteristics and prognostic markers of post-neonatal epilepsy in infants with moderate to severe hypoxic-ischemic encephalopathy treated or not with therapeutic hypothermia.

2021 - Brief comments on three existing approaches for managing neonates at risk of early-onset sepsis [Articolo su rivista]
Vaccina, E.; Luglio, A.; Ceccoli, M.; Lecis, M.; Leone, F.; Zini, T.; Toni, G.; Lugli, L.; Lucaccioni, L.; Iughetti, L.; Berardi, A.
abstract

Background: Growing concerns regarding the adverse effects of antibiotics during the first days of life and the marked reduction in the incidence of early-onset sepsis (EOS) are changing the clinical practice for managing neonates at risk of EOS. Strategies avoiding unnecessary antibiotics while promoting mother-infant bonding and breastfeeding deserve to be considered. Main body: We compare strategies for managing newborns at risk of EOS recommended by the American Academy of Pediatrics, which are among the most followed recommendations worldwide. Currently three different approaches are suggested in asymptomatic full-term or late preterm neonates: i) the conventional management, based on standard perinatal risk factors for EOS alone, ii) the neonatal sepsis calculator, a multivariate risk assessment based on individualized, quantitative risk estimates (relying on maternal risk factors for EOS) combined with physical examination findings at birth and in the following hours and iii) an approach entirely based on newborn clinical condition (serial clinical observation) during the first 48 h of life. We discuss advantages and limitations of these approaches, by analyzing studies supporting each strategy. Approximately 40% of infants who develop EOS cannot be identified on the basis of maternal RFs or laboratory tests, therefore close monitoring of the asymptomatic but at-risk infant remains crucial. A key question is to know what proportion of babies with mild, unspecific symptoms at birth can be managed safely without giving antibiotics. Conclusions: Both neonatal sepsis calculator and serial clinical observation may miss cases of EOS, and clinical vigilance for all neonates is essential There is a need to assess which symptoms at birth are more predictive of EOS, and therefore require immediate interventions, or symptoms that can be carefully reevaluated without necessarily treat immediately the neonate with antibiotics. Studies comparing strategies for managing neonates are recommended.

2021 - Caution advised regarding lung recruitment before surfactant – Authors’ reply [Articolo su rivista]
Vento, G.; Ventura, M. L.; Pastorino, R.; van Kaam, A. H.; Carnielli, V.; Cools, F.; Dani, C.; Mosca, F.; Polglase, G.; Tagliabue, P.; Boni, L.; Cota, F.; Tana, M.; Tirone, C.; Aurilia, C.; Lio, A.; Cost, S.; D'Andrea, V.; Lucente, M.; Nigro, G.; Giordano, L.; Roma, V.; Villani, P.; Fusco, F. P.; Fasolato, V.; Colnaghi, M. R.; Matassa, P. G.; Vendettuoli, V.; Poggi, C.; Del Vecchi, A.; Petrillo, F.; Betta, P.; Mattia, C.; Garani, G.; Solinas, A.; Gitto, E.; Salvo, V.; Gargano, G.; Balestri, E.; Sandri, F.; Mescoli, G.; Martinelli, S.; Ilardi, L.; Ciarmoli, E.; Di Fabio, S.; Maranella, E.; Grassia, C.; Ausanio, G.; Rossi, V.; Motta, A.; Tina, L. G.; Maiolo, K.; Nobile, S.; Messner, H.; Staffler, A.; Ferrero, F.; Stasi, I.; Pieragostini, L.; Mondello, I.; Haass, C.; Consigli, C.; Vedovato, S.; Grison, A.; Maffei, G.; Presta, G.; Perniola, R.; Vitaliti, M.; Re, M. P.; De Curtis, M.; Cardilli, V.; Lago, P.; Tormena, F.; Orfeo, L.; Gizzi, C.; Massenzi, L.; Gazzolo, D.; Strozzi, M. C. M.; Bottino, R.; Pontiggia, F.; Berardi, A.; Guidotti, I.; Cacace, C.; Meli, V.; Quartulli, L.; Scorrano, A.; Casati, A.; Grappone, L.; Pillow, J. J.
abstract

2021 - Disorder of sex development associated with a novel homozygous nonsense mutation in COG6 expands the phenotypic spectrum of COG6-CDG [Articolo su rivista]
Lugli, L.; Bariola, M. C.; Ferri, L.; Lucaccioni, L.; Bertucci, E.; Cattini, U.; Torcetta, F.; Morrone, A.; Iughetti, L.; Berardi, A.
abstract

Congenital disorders of glycosylation (CDG) are an expanding group of metabolic disorders that result from abnormal protein glycosylation. A special subgroup of CDG type II comprises defects in the Conserved Oligomeric Golgi Complex (COG). In order to further delineate the genotypic and phenotypic spectrum of COG complex defect, we describe a novel variant of COG6 gene found in homozygosity in a Moroccan patient with severe presentation of COG6-CDG (OMIM #614576). We compared the phenotype of our patient with other previously reported COG6-CDG cases. Common features in COG6-CDG are facial dysmorphism, growth retardation, microcephaly, developmental disability, liver or gastrointestinal disease, recurrent infections, hypohidrosis/hyperthermia. In addition to these phenotypic features, our patient exhibited a disorder of sexual differentiation, which has rarely been reported in COG6-CDG. We hypothesize that the severe COG6 gene mutation interferes with glycosylation of a disintegrin and metalloprotease family members, inhibiting the correct gonadal distal tip cells migration, fundamental for the genitalia morphogenesis. This report broadens the genetic and phenotypic spectrum of COG6-CDG and provides further supportive evidence that COG6-CDG can present as a disorder of sexual differentiation.

2021 - Heart failure caused by VGAM: a lesson for diagnosis and treatment from a case and literature review [Articolo su rivista]
Spada, C.; Pietrella, E.; Caramaschi, E.; Bergonzini, P.; Berardi, A.; Lucaccioni, L.; Iughetti, L.
abstract

We describe the case of a neonate with signs of heart failure. Echocardiography showed a structural normal heart shape with left ventricular dysfunction. At 2 months of age, a vein of Galen arteriovenous malformation was diagnosed through a brain magnetic resonance imaging. Embolization therapy was accomplished and a clinical and neurological follow-up was started. This clinical case highlights how important it is considering an intracranial cause in the differential diagnosis of neonatal congestive heart failure (CHF). We performed a narrative minireview of the literature about treatments and outcome of this malformation in association to CHF, to point out how complex the diagnosis of vein of Galen aneurysmal malformation (VGAM) may be and how an early diagnosis is important for its management.

2021 - Homozygous n.64C>T mutation in mitochondrial RNA-processing endoribonuclease gene causes cartilage hair hypoplasia syndrome in two siblings [Articolo su rivista]
Lugli, L.; Ciancia, S.; Bertucci, E.; Lucaccioni, L.; Calabrese, O.; Madeo, S.; Berardi, A.; Iughetti, L.
abstract

Cartilage hair hypoplasia syndrome (OMIM # 250250) is a rare autosomal recessive metaphyseal dysplasia, characterized by disproportionate short stature, hair hypoplasia and variable extra-skeletal manifestations, including immunodeficiency, anemia, intestinal diseases and predisposition to cancers. Cartilage hair hypoplasia syndrome has a broad phenotype and it is caused by homozygous or compound heterozygous mutation in the mitochondrial RNA-processing endoribonuclease on chromosome 9p13. Although it is well known as a primordial dwarfism, descriptions of the prenatal growth are missing. To add further details to the knowledge of the phenotypic spectrum of the disease, we report on two siblings with cartilage hair hypoplasia syndrome, presenting n.64C > T homozygous mutation in the mitochondrial RNA-processing endoribonuclease gene. We describe the prenatal and postnatal growth pattern of the two affected patients, showing severe pre- and post-natal growth deficiency.

2021 - Invasive group b streptococcal disease in neonates and infants, Italy, years 2015-2019 [Articolo su rivista]
Creti, R.; Imperi, M.; Berardi, A.; Lindh, E.; Alfarone, G.; Pataracchia, M.; Recchia, S.
abstract

Invasive infections by group B streptococci (iGBS) are the leading cause of sepsis and meningitis in the first three months of life worldwide. The clinical and microbiological characteristics of neonatal and infant iGBS in Italy during the years 2015-2019 were investigated. Voluntary-based surveillance reported 191 cases (67 early-onset (EOD) and 124 late-onset disease (LOD)) and 89 bacterial isolates were received. The main clinical manifestations were sepsis (59.2%) followed by meningitis (21.5%), bacteremia (12.0%) and septic shock (6.3%). Hospitalized preterm babies accounted for one third of iGBS and constituted the most fragile population in terms of mortality (8.2%) and brain damage (16.4%). GBS serotype III was predominant in EOD (56%) and caused almost all LOD (95%). The rate of resistance to clindamycin reached 28.8%. Most of clindamycin-resistant GBS strains (76%) were serotype III-ST17 and possessed the genetic markers of the emerging multidrug resistant (MDR) CC-17 sub-clone. Our data revealed that iGBS is changing since it is increasingly reported as a healthcare-associated infection (22.6%), mainly caused by MDR-CC17. Continuous monitoring of the clinical and microbiological characteristics of iGBS remains of primary importance and it represents, at present, the most effective tool to support prevention strategies and the research on the developing GBS vaccine.

2021 - Long term outcomes of infants born by mothers with thyroid dysfunction during pregnancy [Articolo su rivista]
Lucaccioni, L.; Ficara, M.; Cenciarelli, V.; Berardi, A.; Predieri, B.; Iughetti, L.
abstract

According to Barker’s hypothesis, sub-optimal conditions during gestation might affect the pre-disposition for diseases in adulthood. Alteration in endocrine functions during pregnancy, such us thyroid function or glucose metabolism, are not exempt. It is well known that subclinical hypothyroidism and thy-roperoxidase antibodies-positive euthyroidism during early pregnancy are associated with increased risk of gestational diabetes mellitus and both conditions influence pregnancy outcome and newborn development and metabolism at short and long terms. Fetal production of thyroid hormones starts from the 12th week of gestational age. The transplacental passage of maternal thyroxine (T4) is therefore essential for the fetal neu-rological development, especially during the first half of pregnancy. If this passage is interrupted, such as in premature birth, neonates are more susceptible to develop impaired thyroid function, because of physiological immaturity of their hypothalamic-pituitary-thyroid axis, acute illnesses and stressful events (sepsis, invasive procedures, drugs). The aim of this review is to investigate the short and long term effects of maternal dysthy-roidisms on term and preterm newborns, with particular attention to the metabolic and thyroid consequences. Metabolic syndrome, higher body mass index and greater waist circumference, seem to be more prevalent in children of TPO-Ab-positive mothers. Maternal hypothyroidism may be associated with higher risk of gestational diabetes and adverse birth outcomes, such as preeclampsia, preterm delivery, fetal death and low birth weight offspring. In adulthood, preterm (< 37 weeks of gestational age) or low birth weight (<2.500 g) newborns seem to be more susceptible to develop gestational diabetes, preeclampsia, type 2 diabetes mellitus and behavioral alterations. (www.actabiomedica.it).

2021 - Lung recruitment before surfactant administration in extremely preterm neonates with respiratory distress syndrome (IN-REC-SUR-E): a randomised, unblinded, controlled trial [Articolo su rivista]
Vento, G.; Ventura, M. L.; Pastorino, R.; van Kaam, A. H.; Carnielli, V.; Cools, F.; Dani, C.; Mosca, F.; Polglase, G.; Tagliabue, P.; Boni, L.; Cota, F.; Tana, M.; Tirone, C.; Aurilia, C.; Lio, A.; Costa, S.; D'Andrea, V.; Lucente, M.; Nigro, G.; Giordano, L.; Roma, V.; Villani, P. E.; Fusco, F. P.; Fasolato, V.; Colnaghi, M. R.; Matassa, P. G.; Vendettuoli, V.; Poggi, C.; Del Vecchio, A.; Petrillo, F.; Betta, P.; Mattia, C.; Garani, G.; Solinas, A.; Gitto, E.; Salvo, V.; Gargano, G.; Balestri, E.; Sandri, F.; Mescoli, G.; Martinelli, S.; Ilardi, L.; Ciarmoli, E.; Di Fabio, S.; Maranella, E.; Grassia, C.; Ausanio, G.; Rossi, V.; Motta, A.; Tina, L. G.; Maiolo, K.; Nobile, S.; Messner, H.; Staffler, A.; Ferrero, F.; Stasi, I.; Pieragostini, L.; Mondello, I.; Haass, C.; Consigli, C.; Vedovato, S.; Grison, A.; Maffei, G.; Presta, G.; Perniola, R.; Vitaliti, M.; Re, M. P.; De Curtis, M.; Cardilli, V.; Lago, P.; Tormena, F.; Orfeo, L.; Gizzi, C.; Massenzi, L.; Gazzolo, D.; Strozzi, M. C. M.; Bottino, R.; Pontiggia, F.; Berardi, A.; Guidotti, I.; Cacace, C.; Meli, V.; Quartulli, L.; Scorrano, A.; Casati, A.; Grappone, L.; Pillow, J. J.
abstract

Background: The importance of lung recruitment before surfactant administration has been shown in animal studies. Well designed trials in preterm infants are absent. We aimed to examine whether the application of a recruitment manoeuvre just before surfactant administration, followed by rapid extubation (intubate-recruit-surfactant-extubate [IN-REC-SUR-E]), decreased the need for mechanical ventilation during the first 72 h of life compared with no recruitment manoeuvre (ie, intubate-surfactant-extubate [IN-SUR-E]). Methods: We did a randomised, unblinded, controlled trial in 35 tertiary neonatal intensive care units in Italy. Spontaneously breathing extremely preterm neonates (24 + 0 to 27 + 6 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 h of life were randomly assigned (1:1) with a minimisation algorithm to IN-REC-SUR-E or IN-SUR-E using an interactive web-based electronic system, stratified by clinical site and gestational age. The primary outcome was the need for mechanical ventilation in the first 72 h of life. Analyses were done in intention-to-treat and per-protocol populations, with a log-binomial regression model correcting for stratification factors to estimate adjusted relative risk (RR). This study is registered with ClinicalTrials.gov, NCT02482766. Findings: Of 556 infants assessed for eligibility, 218 infants were recruited from Nov 12, 2015, to Sept 23, 2018, and included in the intention-to-treat analysis. The requirement for mechanical ventilation during the first 72 h of life was reduced in the IN-REC-SUR-E group (43 [40%] of 107) compared with the IN-SUR-E group (60 [54%] of 111; adjusted RR 0·75, 95% CI 0·57–0·98; p=0·037), with a number needed to treat of 7·2 (95% CI 3·7–135·0). The addition of the recruitment manoeuvre did not adversely affect the safety outcomes of in-hospital mortality (19 [19%] of 101 in the IN-REC-SUR-E group vs 37 [33%] of 111 in the IN-SUR-E group), pneumothorax (four [4%] of 101 vs seven [6%] of 111), or grade 3 or worse intraventricular haemorrhage (12 [12%] of 101 vs 17 [15%] of 111). Interpretation: A lung recruitment manoeuvre just before surfactant administration improved the efficacy of surfactant treatment in extremely preterm neonates compared with the standard IN-SUR-E technique, without increasing the risk of adverse neonatal outcomes. The reduced need for mechanical ventilation during the first 72 h of life might facilitate implementation of a non-invasive respiratory support strategy. Funding: None.

2021 - Maternal carriage in late-onset group b streptococcus disease, Italy [Articolo su rivista]
Berardi, A.; Spada, C.; Creti, R.; Auriti, C.; Gambini, L.; Rizzo, V.; Capretti, M.; Laforgia, N.; Papa, I.; Tarocco, A.; Lanzoni, A.; Biasucci, G.; Piccinini, G.; Nardella, G.; Latorre, G.; Merazzi, D.; Travan, L.; Reggiani, M. L. B.; Baroni, L.; Ciccia, M.; Lucaccioni, L.; Iughetti, L.; Lugli, L.
abstract

We retrospectively investigated mother-to-infant transmission of group B Streptococcus (GBS) in 98 cases of lateonset disease reported during 2007-2018 by a network in Italy. Mothers with full assessment of vaginal/rectal carriage tested at prenatal screening (APS) and at time of late onset (ATLO) were included. Thirty-three mothers (33.7%) were never GBS colonized; 65 (66.3%) were vaginal/rectal colonized, of which 36 (36.7%) were persistently colonized. Mothers with vaginal/rectal colonization ATLO had high rates of GBS bacteriuria (33.9%) and positive breast milk culture (27.5%). GBS strains from mother- infant pairs were serotype III and possessed the surface protein antigen Rib. All but 1 strain belonged to clonal complex 17. GBS strains from 4 mother-infant pairs were indistinguishable through pulsed-fi eld gel electrophoresis. At least two thirds of late-onset cases are transmitted from mothers, who often have vaginal/rectal carriage, positive breast milk culture, or GBS bacteriuria, which suggests heavy maternal colonization.

2021 - Minipuberty: Looking Back to Understand Moving Forward [Articolo su rivista]
Lucaccioni, L.; Trevisani, V.; Boncompagni, A.; Marrozzini, L.; Berardi, A.; Iughetti, L.
abstract

Hypothalamic-pituitary-gonadal (HPG) axis activation occurs three times in life: the first is during fetal life, and has a crucial role in sex determination, the second time is during the first postnatal months of life, and the third is with the onset of puberty. These windows of activation recall the three windows of the “Developmental Origin of Health and Disease” (DOHaD) paradigm and may play a substantial role in several aspects of human development, such as growth, behavior, and neurodevelopment. From the second trimester of pregnancy there is a peak in gonadotropin levels, followed by a decrease toward term and complete suppression at birth. This is due to the negative feedback of placental estrogens. Studies have shown that in this prenatal HPG axis activation, gonadotropin levels display a sex-related pattern which plays a crucial role in sex differentiation of internal and external genitalia. Soon after birth, there is a new increase in LH, FSH, and sex hormone concentrations, both in males and females, due to HPG re-activation. This postnatal activation is known as “minipuberty.” The HPG axis activity in infancy demonstrates a pulsatile pattern with hormone levels similar to those of true puberty. We review the studies on the changes of these hormones in infancy and their influence on several aspects of future development, from linear growth to fertility and neurobehavior.

2021 - Neuroprem 2: An Italian Study of Neurodevelopmental Outcomes of Very Low Birth Weight Infants [Articolo su rivista]
Lugli, L.; Bedetti, L.; Guidotti, I.; Pugliese, M.; Picciolini, O.; Roversi, M. F.; DellaCasa Muttini, E.; Lucaccioni, L.; Bertoncelli, N.; Ancora, G.; Gargano, G.; Mosca, F.; Sandri, F.; Corvaglia, L. T.; Solinas, A.; Perrone, S.; Stella, M.; Iughetti, L.; Berardi, A.; Ferrari, F.
abstract

Background: Despite the increased survival of preterm newborns worldwide, the risk of neurodevelopmental disabilities remains high. Analyzing the outcomes of the preterm population can identify risk factors and enable specific early interventions. Aims: Neuroprem is a prospective cohort study of very low birth weight (VLBW) infants that aims to evaluate the neurodevelopmental outcomes and risk factors for severe functional disability at 2 years of corrected age. Methods: Nine Italian neonatal intensive care units participated in the network. The Griffiths Mental Developmental Scales (GMDS-R) or the Bayley Scales of Infant and Toddler Development (BSDI III) and a neuro-functional evaluation (according to the International Classification of Disability and Health and Neuro-Functional Assessment, or NFA ICF-CY) were administered to VLBW infants at 24 months of corrected age. The primary outcome measure was severe functional disability, defined as cerebral palsy, bilateral blindness, deafness, an NFA ICF-CY of >2, a BSDI III cognitive composite score of <2 SD, or a GMDS-R global quotient score of <2 SD. Perinatal risk factors for severe functional disability were assessed through multivariate logistic regression analysis. Results: Among 502 VLBW survivors who completed the 24-month follow-up, 48 (9.6%) presented severe functional disability, of whom 27 had cerebral palsy (5.4%). Rates of severe functional disability and cerebral palsy were higher in neonates with a lower gestational age (p < 0.001). Overall, 147 infants (29.3%) were referred to neuromotor intervention. In the multivariate regression model, gestational age at birth OR 0.79; 95% CI 0.67–0.90; p = 0.001) and periventricular-intraventricular hemorrhage (OR 2.51; 95% CI 1.19–5.26; p = 0.015) were significantly associated with severe functional disability. Conclusion: Neuroprem 2 provides updated information on the neurodevelopmental outcomes of VLBW infants in a large Italian cohort. The overall rate of neurodevelopmental disabilities was quite lower than reported in the previous literature. These data indicate the need for structured follow-up programs from a national neonatal network perspective.

2021 - Newborn hearing screening programme based on an integrated hospital and community care system. Results of the first 4 years of activity [Articolo su rivista]
Palma, S.; Roversi, M. F.; Alberici, M. P.; Negri, M.; Chiossi, C.; Berardi, A.; Genovese, E.
abstract

Since January 2012, babies born in the province of Modena, Italy, have routinely undergone hearing testing as part of a two-stage screening programme. Newborn hearing screening (NHS) has been based on an integrated hospital and community care system and this study aims to assess screening coverage, referral rates, the prevalence, type and extent of hearing loss several years into the programme. Data were collected from January 1, 2012 to December 31, 2015. Coverage was over 99% in all five facilities of the province. The ratio of “fails of the screening” to the total number of infants tested varied over the period from 1.2% to 0.9% in the third level facility, and from 0.8% to 0.4% in the other four. Although hearing loss was mainly associated with dysmorphicsyndromic diseases or a family history of hearing loss, some 23% of cases were identified with no known risk factors. We highlight the importance of the NHSP and the need for strong support from healthcare administrators to ensure high coverage. This is especially true since although the prevalence of hearing loss was higher among infants with audiological risk factors, several cases of hearing loss were found in newborns with no known risk factors.

2021 - Occhio all’asimmetria toracica alla nascita... e se fosse la sindrome di Poland?. [Articolo su rivista]
Di Caprio, A; Bedetti, L; Madeo, Sf; Lucaccioni, L; Roversi, F; Iughetti, L; Berardi, A.
abstract

Poland syndrome is a rare congenital disorder characterized by agenesis of the pectoralis major muscle. It is usually unilateral and right-sided and can be associated with several thoracic and upper limb defects. Early diagnosis and timely therapeutic approaches play an important role, improving the quality of life of patients and their families. This case report aims to show the benefits of early diagnosis, especially for follow-up management.

2021 - Pneumococcal septic shock after neonatal respiratory syncytial virus bronchiolitis: A case report and literature review [Articolo su rivista]
Di Caprio, A.; Coccolini, E.; Zagni, P.; Vaccina, E.; Lucaccioni, L.; Lugli, L.; Iughetti, L.; Berardi, A.
abstract

Background: Bronchiolitis is a common cause of hospitalisation of infants less than a year old, with most infants recovering without complications. Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis. Antimicrobial stewardship programmes do not recommend antibiotics for viral infections in neonates unless documented evidence of secondary bacterial infection is present. Case report: We present the case of a 7-day-old infant admitted to hospital with chest retractions and fever. The baby was hospitalised, empirical antibiotic therapy was administered, and non-invasive ventilation was started. When the viral aetiology was identified and clinical conditions improved, antibiotics were discontinued. However, after 48 hours, the newborn’s condition worsened because of pneumococcal septic shock. Intravenous fluids, catecholamine support, and wide-spectrum antibiotics were administered. Non-invasive ventilation was re-started and continued until the full recovery. Conclusions: There is increasing evidence that RSV and S. pneumoniae co-infect and interact with each other, thus increasing respiratory diseases’ severity. We provide a brief overview of the main international guidelines for managing bronchiolitis. Guidelines suggest avoidance of antibiotics use when the diagnosis of viral bronchiolitis is confirmed. We discuss the uncertainties regarding antibiotic use, especially in younger infants, who are more exposed to risks of bacterial superinfection. (www.actabiomedica.it).

2021 - Pregnant woman infected by Coronavirus disease (COVID-19) and calcifications of the fetal bowel and gallbladder [Articolo su rivista]
Sileo, Fg; Tramontano, Al; Leone, C; Meacci, M; Gennari, W; Ternelli, G; La Marca, A; Lugli, L; Berardi, A; Facchinetti, F; Bertucci, E
abstract

COVID-19 was declared to be a pandemic due to the rapid increase of cases around the world, including the number of pregnant women. Data about vertical transmission of COVID-19 are still limited and controversial: in most cases, although a positive mother, the virus could not be isolated in amniotic fluid, cord blood, breast milk or neonatal throat swab in these patients. No data have been published about possible intrauterine sonographic signs of infection. A pregnant woman was diagnosed with SARS-CoV-2 at 35 t5 weeks of gestation and managed conservatively at home. At transabdominal ultrasound at 38+3 weeks, fetal bowel and gallbladder calcifications were noted. CMV and other infectious agents were ruled out an iterative caesarean section was performed at 38+5 weeks without complications. Placenta resulted negative for SARS-CoV-2; the umbilical cord blood sample was IgG positive and IgM negative as per maternal infection. The baby developed respiratory distress syndrome requiring endotracheal surfactant administration and nasal-CPAP for one day but nasopharyngeal swabs at birth and after 48 hours were SARS-CoV-2 negative. Neonatal abdominal ultrasound showed normal liver, acalculous gallbladder with mild parietal thickening. The baby was discharged in good conditions. Although gallbladder calcifications and echogenic bowel are highly suspicious of viral infection and were thought to be due to the vertical transmission of SARS-CoV-2, these findings were not corroborated by the results of our diagnostic tests; these sonographic findings might represent a false positive of fetal infection in mother affected by COVID-19 since vertical transmission appears to be rare.

2021 - SEPTIC SHOCK in the FIRST THREE MONTHS of LIFE [Articolo su rivista]
Crestani, S.; Passini, E.; Spaggiari, V.; Toffoli, C.; Boncompagni, A.; Bedetti, L.; Spaggiari, E.; Lucaccioni, L.; Lugli, L.; Roversi, F.; Rossi, K.; Iughetti, L.; Berardi, A.
abstract

Shock is a generalized tissue hypoperfusion that leads to severe cellular distress and complicates some cases of paediatric and neonatal sepsis. Although a reduction in associated sepsis mortality has been observed in the last decades, it remains one of the most important causes of death or long-term neurodevelopmental disabilities in children. Prompt recognition of this condition is therefore essential to improve survival and long-term outcome. The paediatrician and the neonatologist must therefore be able to promptly recognize the signs and symptoms of sepsis and septic shock to set up an adequate treatment according to the most recent international guidelines. This article provides epidemiological data from Italian and international studies, describes the pathophysiology and clinical manifestations of sepsis and septic shock, as well as the therapeutic indications according to very recent recommendations.

2021 - Safety and Success of Lumbar Puncture in Young Infants: A Prospective Observational Study [Articolo su rivista]
Bedetti, L.; Lugli, L.; Marrozzini, L.; Baraldi, A.; Leone, F.; Baroni, L.; Lucaccioni, L.; Rossi, C.; Roversi, M. F.; D'Amico, R.; Iughetti, L.; Berardi, A.
abstract

Objective: This study aims to evaluate safety and success rates of lumbar puncture (LP) and to identify factors associated with adverse events or failure of LP in infants. Methods: This two-center prospective observational study investigated infants younger than 90 days of age who underwent LP. Need for resuscitation oxygen desaturation (SpO2 < 90%), bradycardia and intraventricular hemorrhage were considered adverse events. LP failed if cerebrospinal spinal fluid was not collected or had traces of blood. Logistic regression analysis was used to evaluate whether corrected gestational age (GA), body weight at LP, position, and any respiratory support during LP affected SpO2 desaturation or failure of LP. Results: Among 204 LPs, 134 were performed in full-term and 70 in pre-term born infants. SpO2 desaturations occurred during 45 (22.4%) LPs. At multivariate analysis, lower GA at LP (p < 0.001), non-invasive respiratory support (p 0.007) and mechanical ventilation (p 0.004) were associated with SpO2 desaturations. Transient, self-resolving bradycardia occurred in 7 (3.4%) infants. Two infants had intraventricular hemorrhage detected within 72 h of LP. No further adverse events were registered. Failure of LP occurred in 38.2% of cases and was not associated with any of the factors evaluated. Conclusions: LP was safe in most infants. Body weight or GA at LP did not affect LP failure. These data are useful to clinicians, providing information on the safety of the procedure.

2021 - The discharge of children with medical complexity: an 11-year study in an italian neonatal intensive care unit [Articolo su rivista]
Lugli, L.; Garetti, E.; Rossi, K.; Torcetta, F.; Cuomo, G.; Lucaccioni, L.; Pugliese, M.; Bertoncelli, N.; Rossi, C.; Riva, M.; Iughetti, L.; Ferrari, F.; Berardi, A.
abstract

Background - In the last few years care for children with severe chronic conditions is a topic of increasing interest. Children with chronic illness often require a high complexity of care and a high level of coordination among health services. Objective - The primary aim of this study is the assessment of children with chronic disease and high complexity of care (children with medical complexity), discharged from the Neonatal Intensive Care Unit (NICU) of Modena University-Hospital. The secondary aim is to assess the outcome of these patients. Methods - Patients with chronic diseases and high complexity of care (children with medical complexity), aged 0-6 months, and admitted to the NICU of Modena in the years 2009-2019 were recruited. Results - 59 subjects were included, of which 15 (25.4%) were born preterm, 11 (18.6%) suffered from hypoxic-ischemic encephalopathy, 33 (56%) had genetic diseases or malformations. All patients were discharged home, except for one patient who was discharged to hospice. The average hospital length of stay was 116.0 ± 63.4 days. Follow-up visits showed that 25 cases (42.4%) remained unchanged, 18 (30.5%) improved and 16 (27.1%) died. Conclusion - This study allows an assessment of patients with early diagnosis of chronic disease with high complexity of care, showing that some of these patients could be eligible for palliative care. The management of children with medical complexity requires diagnostic-therapeutic programmes that focus on them and their families and connect hospital and territorial health services.

2021 - The ontogeny of limbs movements towards midline in healthy infants born at term [Articolo su rivista]
Lucaccioni, Laura; Bertoncelli, Natascia; Comini, Martina; Martignoni, Laura; Coscia, Alessandra; Lugli, Licia; Righi, Elena; Iughetti, Lorenzo; Berardi, Alberto; Ferrari, Fabrizio
abstract

Background: Movements towards midline are part of the age-adequate motor repertoire of infants. They develop contemporaneously to general movements, changing from occasional simple contact to proper midline motor patterns. Aim: The aim of this study is to describe the ontogeny of movements towards midline in full term healthy infants. Study design:Parents were asked to record their infant every second week, from term age to 22 weeks post-term. Subjects:25 healthy full-term infants. Result: Three main epochs of development were detected: in the first one, between birth and 4 weeks post-term, movements towards midline were occasional, apparently due to the dominant flexed posture of elbow and knees and the adducted posture of shoulders and hips. In the second epoch, from 4 to 8 weeks, the limbs movements towards midline markedly decreased. In the third one, after 8 weeks, movements towards midline increased again in frequency, first appearing in lower limbs then in upper limbs, first solely as contact and thereafter as manipulation. A temporal overlapping with the occurrence of intermittent or continual fidgety movements was detected. Conclusions: Movements towards midline progressively change, through a defined timeline, in full term healthy infants. The increased knowledge about the normal age-adequate motor repertoire can help physicians in clinical assessment of high risk infants.

2021 - Understanding factors in group b streptococcus late-onset disease [Articolo su rivista]
Berardi, A.; Trevisani, V.; Di Caprio, A.; Bua, J.; China, M.; Perrone, B.; Pagano, R.; Lucaccioni, L.; Fanaro, S.; Iughetti, L.; Lugli, L.; Creti, R.
abstract

Group B streptococcus (GBS) infection remains a leading cause of sepsis, pneumonia, and meningitis in infants. Rates of GBS early onset disease have declined following the widcespread use of intrapartum antibiotic prophylaxis; hence, late-onset infections (LOGBS) are currently a common presentation of neonatal GBS dicsease. The pathogenesis, mode of transmission, and risk factors associated with LOGBS are unclear, which interfere with effective prevention efforts. GBS may be transmitted from the mother to the infant at the time of delivery or during the postpartum period via contaminated breast milk, or as nosocomial or community-acquired infection. Maternal GBS colonization, pre-maturity, young maternal age, HIV exposure, and ethnicity (Black) are identified as risk factors for LOGBS disease; however, further studies are necessary to confirm additional risk factors, if any, for the implementation of effective prevention strategies. This narrative review discusses current and previous studies that have reported LOGBS. Few well-designed studies have described this condition; therefore, reliable assessment of maternal GBS colonization, breastfeeding, and twin delivery as risk factors for LOGBS remains limited.

2021 - Unexpected hearing improvement after treatment with valganciclovir in a child with congenital cytomegalovirus infection [Articolo su rivista]
Palma, Silvia; Mazzoni, Laura; Roversi, Maria Federica; Botti, Cecilia; Monzani, Daniele; Berardi, Alberto; Genovese, Elisabetta
abstract

A 32-week preterm-born male with symptomatic congenital cytomegalovirus infection was treated with valganciclovir. He was also affected by congenital severe bilateral hearing loss and, unexpectedly, a normalization of the hearing threshold was reached at one year of age. The improvement of hearing level in relationship with both the late development of the auditory system and the administration of antiviral therapy is discussed. This case also highlights the importance of early diagnosis of congenital cytomegalovirus associated with close follow-up.

2021 - What happens when the newborn hearing screening program is integrated with congenital Cytomegalovirus infection screening? Preliminary results in a tertiary hospital [Articolo su rivista]
Palma, S.; Botti, C.; Roversi, M. F.; Bettini, M.; Pietrosemoli, P.; Berardi, A.; Genovese, E.
abstract

Objective: Early diagnosis of congenital Cytomegalovirus (cCMV) infection related hearing loss has increased since the spread of newborn hearing screening (NHS) programs worldwide. However, since most newborns affected are asymptomatic at birth but may develop hearing loss later, some of them may elude the NHS. The aim of this study was to compare the results in two cohorts of children, in one of which all newborns who failed the NHS were tested for cCMV. Methods: We retrospectively compared the results of early diagnosis of cCMV-related hearing loss between two groups of patients at a high-volume centre. Group 1 included the first 3 years of activity without a targeted cCMV screening and was composed of children born between 2012 and 2014. Group 2 included neonates born between 2015 and 2017: in this group, those who failed the NHS underwent urine CMV analysis within 14 days. Results: There were 17,229 live births during the study period, 20 were diagnosed with cCMV infection, with a global prevalence of 1.1:1000. 72 neonates (0.42%) with hearing loss were identified, 7% of which were diagnosed with cCMV infection, 3/34 (8.8%) in group 1 and 2/38 (5.3%) in group 2 (p =.66). One newborn in group 2 was identified through the protocol. The percentage of patients affected by cCMV-related hearing loss diagnosed during the NHS showed non-significant differences in the two groups. Conclusion: Our results suggest that the suspicion index of cCMV infection in a tertiary hospital is currently high and neonatologists are able to identify most symptomatic cases which have higher risk of developing hearing loss. Coupling the cCMV screening and the NHS program is worthwhile as it allows early recognition of asymptomatic cases with hearing loss and subsequent immediate administration of antiviral therapy.

2020 - An Uninfected Preterm Newborn Inadvertently Fed SARS-CoV-2-Positive Breast Milk [Articolo su rivista]
Lugli, Licia; Bedetti, Luca; Lucaccioni, Laura; Gennari, William; Leone, Chiara; Ancora, Gina; Berardi, Alberto
abstract

2020 - Changes of intestinal microbiota in early life [Articolo su rivista]
Ficara, Monica; Pietrella, Elisa; Spada, Caterina; Casa Muttini Elisa, Della; Lucaccioni, Laura; Iughetti, Lorenzo; Berardi, Alberto
abstract

There is increasing evidence that the intestinal microbiota plays a pivotal role in the maturation of the immune system and in the prevention of diseases occurring during the neonatal period, childhood and adulthood. A number of nonphysiological conditions during the perinatal period (ie caesarean section, prolonged hospitalization, formula feeding, low gestational age) may negatively affect the normal development of the microbiota, leading to decreased amounts of lactobacilli and bifidobacteria and increased amounts of Clostridia . In addition, perinatal antibiotics can cause intestinal dysbiosis that has been associated with short- and long-term diseases. For example, prolonged early empiric antibiotics increase the risk of necrotizing enterocolitis and late-onset sepsis in preterm neonates, whereas the administration of intrapartum antibiotic prophylaxis has been associated with inflammatory bowel diseases, obesity and atopic conditions, such as eczema and wheezing. Promoting breastfeeding, reducing the length of hospital stay, and reducing unnecessary antibiotic therapies are useful strategies to counterbalance unintended effects of these conditions.

2020 - Different audiologic outcomes in twins with congenital cytomegalovirus infection [Articolo su rivista]
Botti, C.; Palma, S.; Roversi, M. F.; Monzani, D.; Berardi, A.; Genovese, E.
abstract

Congenital cytomegalovirus (cCMV) infection is a major cause of hearing loss in children. A few cases of cCMV twin pregnancies are reported in the literature. Twins can react differently to maternal infection, but hearing loss is rarely evaluated. Two couples of twins with cCMV infection and different audiologic outcomes are reported. The first couple of twins was composed by two male twins, both affected by cCMV infection. The first born had normal hearing function, and the second born had sensorineural hearing loss (SNHL). In the second couple, a male and a female twin, only the male twin was affected by cCMV infection, and both had normal hearing function. In this case series, an interesting finding was the association between the presence of viral DNA in liquor and hearing loss in one newborn. Further research is needed to better understand the pathophysiology of SNHL caused by cCMV infection.

2020 - Efficacy and safety of exogenous surfactant therapy in patients under 12 months of age invasively ventilated for severe bronchiolitis (SURFABRON): protocol for a multicentre, randomised, double-blind, controlled, non-profit trial [Articolo su rivista]
Biban, P.; Conti, G.; Wolfler, A. M.; Carlassara, S.; Gitto, E.; Rulli, I.; Moscatelli, A.; Micalizzi, C.; Savron, F.; Sagredini, R.; Genoni, G.; Binotti, M.; Caramelli, F.; Fae, M.; Pettenazzo, A.; Stritoni, V.; D'Amato, L.; Zito Marinosci, G.; Calderini, E.; Scalia Catenacci, S.; Berardi, A.; Torcetta, F.; Bonanomi, E.; Bonacina, D.; Ivani, G.; Santuz, P.
abstract

INTRODUCTION: Some evidence indicates that exogenous surfactant therapy may be effective in infants with acute viral bronchiolitis, even though more confirmatory data are needed. To date, no large multicentre trials have evaluated the effectiveness and safety of exogenous surfactant in severe cases of bronchiolitis requiring invasive mechanical ventilation (IMV). METHODS AND ANALYSIS: This is a multicentre randomised, placebo-controlled, double-blind study, performed in 19 Italian paediatric intensive care units (PICUs). Eligible participants are infants under the age of 12 months hospitalised in a PICU, suffering from severe acute hypoxaemic bronchiolitis, requiring IMV. We adopted a more restrictive definition of bronchiolitis, including only infants below 12 months of age, to maintain the population as much homogeneous as possible. The primary outcome is to evaluate whether exogenous surfactant therapy (Curosurf, Chiesi Pharmaceuticals, Italy) is effective compared with placebo (air) in reducing the duration of IMV in the first 14 days of hospitalisation, in infants suffering from acute hypoxaemic viral bronchiolitis. Secondary outcomes are duration of non-invasive mechanical ventilation in the post-extubation phase, number of cases requiring new intubation after previous extubation within 14 days from randomisation, PICU and hospital length of stay (LOS), duration of oxygen dependency, effects on oxygenation and ventilatory parameters during invasive mechanical respiratory support, need for repeating treatment within 24 hours of first treatment, use of other interventions (eg, high-frequency oscillatory ventilation, nitric oxide, extracorporeal membrane oxygenation), mortality within the first 14 days of PICU stay and before hospital discharge, side effects and serious adverse events. ETHICS AND DISSEMINATION: The trial design and protocol have received approval by the Italian National Agency for Drugs (AIFA) and by the Regional Ethical Committee of Verona University Hospital (1494CESC). Findings will be disseminated through publication in peer-reviewed journals, conference/meeting presentations and media. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, issue date 22 May 2019. NCT03959384.

2020 - Endocrine-disrupting chemicals and their effects during female puberty: A review of current evidence [Articolo su rivista]
Lucaccioni, L.; Trevisani, V.; Marrozzini, L.; Bertoncelli, N.; Predieri, B.; Lugli, L.; Berardi, A.; Iughetti, L.
abstract

Puberty is the process of physical changes between childhood and adulthood during which adolescents reach sexual maturity and become capable of reproduction. It is considered one of the main temporal windows of susceptibility for the influence of the endocrine-disrupting chemicals (EDCs). EDCs may act as single chemical agents or as chemical mixtures; they can be pubertal influencers, accelerating and anticipating the processing of maturation of secondary sexual characteristics. Moreover, recent studies have started to point out how exposure to EDCs during puberty may predispose to breast cancer later in life. In fact, the estrogen-mimicking endocrine disruptors (EEDs) may influence breast tissue development during puberty in two main ways: the first is the action on the proliferation of the breast stromal cells, the second concerns epigenetic mechanisms. The aim of this mini-review was to better highlight what is new and what is not completely known regarding the role of EDCs during puberty.

2020 - Intrapartum beta-lactam antibiotics for preventing group B streptococcal early-onset disease: can we abandon the concept of ‘inadequate’ intrapartum antibiotic prophylaxis? [Articolo su rivista]
Berardi, A.; Spada, C.; Vaccina, E.; Boncompagni, A.; Bedetti, L.; Lucaccioni, L.
abstract

Introduction: Neonatal sepsis remains a serious and potentially fatal illness. Intrapartum antibiotic prophylaxis (IAP) prevents group B streptococcal (GBS) early-onset sepsis. The optimal duration of IAP (adequate IAP) to reduce vertical transmission of GBS has been debated. Understanding the mechanism of action of IAP may help in minimizing neonatal evaluation and unnecessary antibiotic use. Areas covered: In recent years, several studies on pharmacokinetics and clinical use of IAP have been published. Although penicillin and ampicillin are the most preferred antibiotics, the clinical efficacy of non-beta-lactam antibiotics, including clindamycin and vancomycin, used in cases of penicillin anaphylaxis-associated allergy, remains debatable. This is a narrative review of the literature regarding the impact of ‘inadequate’ IAP on the clinical management of women and newborns. Expert opinion: Recent evidence suggests that ‘inadequate’ IAP with beta-lactams is more effective in preventing vertical transmission of GBS than previously thought. Newborns exposed to intrapartum beta-lactams and who are asymptomatic at birth are likely uninfected, irrespective of IAP duration before delivery. Hence, we may abandon the concept of ‘inadequate’ IAP with beta-lactams in early-onset GBS sepsis, relying primarily on clinical signs observed at birth for managing IAP-exposed neonates.

2020 - Neuroprem: The Neuro-developmental outcome of very low birth weight infants in an Italian region [Articolo su rivista]
Lugli, L.; Pugliese, M.; Plessi, C.; Berardi, A.; Guidotti, I.; Ancora, G.; Grandi, S.; Gargano, G.; Braibanti, S.; Sandri, F.; Soffritti, S.; Ballardini, E.; Arena, V.; Stella, M.; Perrone, S.; Moretti, S.; Rizzo, V.; Ferrari, F.
abstract

Introduction: The survival of preterm babies has increased worldwide, but the risk of neuro-developmental disabilities remains high, which is of concern to both the public and professionals. The early identification of children at risk of neuro-developmental disabilities may increase access to intervention, potentially influencing the outcome. Aims: Neuroprem is an area-based prospective cohort study on the neuro-developmental outcome of very low birth weight (VLBW) infants that aims to define severe functional disability at 2 years of age. Methods: Surviving VLBW infants from an Italian network of 7 neonatal intensive care units (NICUs) were assessed for 24 months through the Griffiths Mental Developmental Scales (GMDS-R) or the Bayley Scales of Infant and Toddler Development (BSDI III) and neuro-functional evaluation according to the International Classification of Disability and Health (ICF-CY). The primary outcome measure was severe functional disability at 2 years of age, defined as cerebral palsy, a BSDI III cognitive composite score < 2 standard deviation (SD) or a GMDS-R global quotients score < 2 SD, bilateral blindness or deafness. Results: Among 211 surviving VLBW infants, 153 completed follow-up at 24 months (72.5%). Thirteen patients (8.5%) developed a severe functional disability, of whom 7 presented with cerebral palsy (overall rate of 4.5%). Patients with cerebral palsy were all classified with ICF-CY scores of 3 or 4. BSDI III composite scores and GMDS-R subscales were significantly correlated with ICF-CY scores (p < 0.01). Conclusion: Neuroprem represents an Italian network of NICUs aiming to work together to ensure preterm neuro-developmental assessment. This study updates information on VLBW outcomes in an Italian region, showing a rate of cerebral palsy and major developmental disabilities in line with or even lower than those of similar international studies. Therefore, Neuroprem provides encouraging data on VLBW neurological outcomes and supports the implementation of a preterm follow-up programme from a national network perspective.

2020 - Overwhelming sepsis in a neonate affected by Zellweger syndrome due to a compound heterozygosis in PEX 6 gene: a case report [Articolo su rivista]
Lucaccioni, L.; Righi, B.; Cingolani, G. M.; Lugli, L.; Della Casa, E.; Torcetta, F.; Iughetti, L.; Berardi, A.
abstract

Background: Peroxisome biogenesis disorders (PBDs) are a group of metabolic diseases caused by dysfunction of peroxisomes. Different forms of PBDs are described; the most severe one is the Zellweger syndrome (ZS). We report on an unusual presentation of Zellweger syndrome manifesting in a newborn with severe and fulminant sepsis, causing death during the neonatal period. Case presentation: A term male Caucasian neonate presented at birth with hypotonia and poor feeding associated with dysmorphic craniofacial features and skeletal abnormalities. Blood tests showed progressive leukopenia; ultrasounds revealed cerebral and renal abnormalities. He died on the fourth day of life because of an irreversible Gram-negative sepsis. Post-mortem tests on blood and urine samples showed biochemical alterations suggestive of ZS confirmed by genetic test. Conclusions: ZS is an early and severe forms of PBDs. Peroxisomes are known to be involved in lipid metabolism, but recent studies suggest their fundamental role in modulating immune response and inflammation. In case of clinical suspicion of ZS it is important to focus the attention on the prevention and management of infections that can rapidly progress to death.

2020 - Risk factors for group B streptococcus early-onset disease: an Italian, area-based, case-control study [Articolo su rivista]
Berardi, Alberto; Spada, Caterina; Creti, Roberta; Ambretti, Simone; Chiarabini, Rossana; Barozzi, Agostino; Pagano, Rossella; Sarti, Mario; Pedna, Maria Federica; Fornaciari, Sara; Azzalli, Milena; Dodi, Icilio; Bacchi Reggiani, Maria Letizia; Lanzoni, Angela; Vaccina, Eleonora; Iughetti, Lorenzo; Lucaccioni, Laura
abstract

Purpose: Intrapartum antibiotic prophylaxis (IAP) prevents group B streptococcus (GBS) early-onset disease (EOD). No European study evaluates the relative impact of risk factors (RFs) for EOD after a screening-based strategy and widespread IAP use We aimed to evaluate the risks of EOD in an Italian region where a screening-based strategy for preventing EOD was implemented. Materials and methods: Cases of EOD born at or above 35 weeks' gestation were reviewed and matched with controls. Results: There were 109 cases of EOD among 532,154 live births. Most cases had negative GBS prenatal screening (56/91, 61.5%) and were unexposed to IAP (86/109, 78.9%). At multivariate analysis, GBS bacteriuria (OR = 6.99), positive prenatal screening (OR = 13.7) and maternal intrapartum fever (OR = 188.3) were associated with an increased risk of EOD, whereas intrapartum beta-lactam antibiotics were associated with a decreased risk of EOD (≥4 h: OR = 0.008; <4 h: OR = 0.04). Neonates born to nonfebrile, GBS positive pregnant women, receiving beta-lactam antibiotics had very low probability of EOD, particularly if IAP was adequate. Conclusions: GBS positive prenatal screening, GBS bacteriuria and intrapartum fever are associated with EOD. Intrapartum beta-lactam antibiotics reduce the probability of EOD in neonates born to nonfebrile mothers.

2020 - Serial clinical observation for management of newborns at risk of early-onset sepsis [Articolo su rivista]
Berardi, Alberto; Bedetti, Luca; Spada, Caterina; Lucaccioni, Laura; Frymoyer, Adam
abstract

Current management approaches for asymptomatic neonates at risk of early onset sepsis remain controversial. Strategies based entirely on clinical observation (SCO, serial clinical observation) have gained consensus.

2020 - The Italian arm of the PREPARE study: an international project to evaluate and license a maternal vaccine against group B streptococcus [Articolo su rivista]
Berardi, Alberto; Cassetti, Tiziana; Creti, Roberta; Vocale, Caterina; Ambretti, Simone; Sarti, Mario; Facchinetti, Fabio; Cose, Stephen; Heath, Paul; Le Doare, Kirsty
abstract

BACKGROUND: Group B streptococcus (GBS) is a leading cause of sepsis, pneumonia and meningitis in infants, with long term neurodevelopmental sequelae. GBS may be associated with poor pregnancy outcomes, including spontaneous abortion, stillbirth and preterm birth. Intrapartum antibiotic prophylaxis (IAP) is currently the only way to prevent early-onset disease (presenting at 0 to 6days of life), although it has no impact on the disease presenting over 6days of life and its implementation is challenging in resource poor countries. A maternal vaccine against GBS could reduce all GBS manifestations as well as improve pregnancy outcomes, even in low-income countries.MAIN BODY: The term "PREPARE" designates an international project aimed at developing a maternal vaccination platform to test vaccines against neonatal GBS infections by maternal immunization. It is a non-profit, multi-center, interventional and experimental study (promoted by the St George University of London. [UK]) with the aim of developing a maternal vaccination platform, determining pregnancy outcomes, and defining the extent of GBS infections in children and mothers in Africa. PREPARE also aims to estimate the protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa and to conduct two trials on candidate GBS vaccines. PREPARE consists of 6 work packages. In four European countries (Italy, UK, Netherlands, France) the recruitment of cases and controls will start in 2020 and will end in 2022. The Italian PREPARE network includes 41 centers. The Italian network aims to collect: GBS isolates from infants with invasive disease, maternal and neonatal sera (cases); cord sera and GBS strains from colonized mothers whose infants do not develop GBS infection (controls).SHORT CONCLUSION: PREPARE will contribute information on protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa. The vaccine that will be tested by the PREPARE study could be an effective strategy to prevent GBS disease.

2019 - Clinical characterization of neonatal and pediatric enteroviral infections: an Italian single center study [Articolo su rivista]
Berardi, Alberto; Sandoni, Marcello; Toffoli, Carlotta; Boncompagni, Alessandra; Gennari, William; Bergamini, Maria Barbara; Lucaccioni, Laura; Iughetti, Lorenzo
abstract

Enteroviruses (EVs) are an important cause of illness, especially in neonates and young infants. Clinical and laboratory findings at different ages, brain imaging, and outcomes have been inadequately investigated.

2019 - Epidemiology and complications of late-onset sepsis: An Italian area-based study [Articolo su rivista]
Berardi, A.; Sforza, F.; Baroni, L.; Spada, C.; Ambretti, S.; Biasucci, G.; Bolognesi, S.; Capretti, M.; Carretto, E.; Ciccia, M.; Lanari, M.; Pedna, M. F.; Rizzo, V.; Venturelli, C.; Tzialla, C.; Lucaccioni, L.; Reggiani, M. L. B.
abstract

Background Most studies regarding late-onset sepsis (LOS) address selected populations (i.e., neonates with low birth weight or extremely preterm neonates). Studying all age groups is more suitable to assess the burden of single pathogens and their clinical relevance. Methods This is a retrospective regional study involving paediatric departments and NICUs in Emilia-Romagna (Italy). Regional laboratory databases were searched from 2009 to 2012. Records of infants (aged 4 to 90 days) with a positive blood or cerebrospinal fluid (CSF) culture were retrospectively reviewed and analysed according to acquisition mode (whether hospital- or community-acquired). Results During the study period, there were 146,682 live births (LBs), with 296 patients experiencing 331 episodes of LOS (incidence rate: 2.3/1000 LBs). Brain lesions upon discharge from the hospital were found in 12.3% (40/296) of cases, with death occurring in 7.1% (23/296; 0.14/ 1000 LBs). With respect to full-term neonates, extremely preterm or extremely low birth weight neonates had very high risk of LOS and related mortality (> 100- and > 800-fold higher respectively). Hospital-acquired LOS (n = 209) was significantly associated with very low birth weight, extremely preterm birth, pneumonia, mechanical ventilation, and death (p< 0.01). At multivariate logistic regression analysis, catecholamine support (OR = 3.2), central venous line before LOS (OR = 14.9), and meningitis (OR = 44.7) were associated with brain lesions or death in hospital-acquired LOS (area under the ROC curve 0.81, H-L p = 0.41). Commonly identified pathogens included coagulase-negative staphylococci (CoNS n = 71, 21.4%), Escherichia coli (n = 50, 15.1%), Staphylococcus aureus (n = 41, 12.4%) and Enterobacteriaceae (n = 41, 12.4%). Group B streptococcus was the predominant cause of meningitis (16 of 38 cases, 42%). Most pathogens were sensitive to first line antibiotics. Conclusions This study provides the first Italian data regarding late-onset sepsis (LOS) in all gestational age groups. Compared to full-term neonates, very high rates of LOS and mortality occurred in neonates with a lower birth weight and gestational age. Group B streptococcus was the leading cause of meningitis. Excluding CoNS, the predominant pathogens were Escherichia coli and Staphylococcus aureus. Neonates with hospital-acquired LOS had a worse outcome. Antibiotic associations, recommended for empirical treatment of hospital- or community-acquired LOS, were adequate.

2019 - Extra Uterine Growth Restriction (EUGR) in very low birth weight infants: Growth recovery and neurodevelopment by the corrected age of 2 years old [Abstract in Rivista]
Lucaccioni, Laura; Arrigoni, Marta; Elisa Della Casa, ; Natascia, Bertoncelli; Predieri, Barbara; Berardi, Alberto; Pugliese, Marisa; Ferrari, Fabrizio; Iughetti, Lorenzo
abstract

Background: Extra Uterine Growth Restriction (EUGR) represents a serious comorbidity in infants born very low birth weight (VLBW). In fact, failure in postnatal growth and malnutrition at vulnerable ages can interfere with growth recovery and neurodevelopment at older ages. Hypothesis: Aim of the study was to assess whether and how the postnatal early growth patterns of VLBW may affect later growth, spontaneous motility at three months of corrected age (CA) and neurodevelopment at 2 years CA. Study Design: Retrospective single-centre study of 547 infants (255M) born VLBW between 2005 and 2015. Each participant underwent: a) anthropometric assessments of weight (W), length (L) and head circumference (HC) at birth, at discharge from the NICU and at 2 years CA; b) Evaluation of Fidgety movements (F) at three months CA; c) Neurodevelopmental assessment at 2 years CA through the Griffith Mental Development Scales. Results: From the overall population, growth percentiles at discharge were significantly lower than at birth (L p<0.01; W p<0.01; HC p< 0.01). Longitudinal data showed a significant growth restriction between birth (AGA for W:73%; AGA for L:73.2%) and discharge (AGA for W:36%; AGA for L:31.2%). Gestational age, duration of hospitalisation, bronchopulmonary dysplasia and intra ventricular haemorrhage were found to be predictive factors for EUGR at discharge. At 2 years CA, SGA at discharge but not at birth, showed significantly lower stature compared to the AGA ones (p:0.04). Significant correlation was found between F and L (p:0.04; r:0.12) and HC (p<0.02; r:0.2) at discharge, but not at birth. Moreover, a significant difference was found between F and locomotor outcome at two years CA (p<0.01). W and L at discharge, but not at birth, were significantly related to worse locomotor outcome at two years of CA (respectively, p:0.03, r:0.14; p:0.01, r:0.18). In particular, who was found SGA at discharge, both for W and/or L, had the worse motor outcome compared to the AGA ones (respectively, p:0.04 and p:0.01). Conclusions: VLBW growth measurements at discharge, but not at birth, are related to poorer growth and neurodevelopment at later ages, especially in children who become SGA. Lower scores in locomotor assessment at two years CA have been observed in infants with anomalies of F, suggesting how spontaneous motility could predict later neurodevelopmental outcomes. Our findings highlight the necessity of a close clinical follow-up of growth patterns during preterm hospitalization aiming to decrease the incidence of EUGR.

2019 - Further Delineation of Pyridoxine-Responsive Pyridoxine Phosphate Oxidase Deficiency Epilepsy: Report of a New Case and Review of the Literature With Genotype-Phenotype Correlation [Articolo su rivista]
Lugli, L.; Bariola, M. C.; Ori, L.; Lucaccioni, L.; Berardi, A.; Ferrari, F.
abstract

In recent years, the clinical spectrum of pyridoxine phosphate oxidase (PNPO) deficiency has broadened. There are a growing number of patients with a transient or lasting response to pyridoxine in addition to cases that respond more traditionally to pyridoxal-phosphate. However, among pyridoxine-responsive patients with PNPO gene mutation, there are only a few reports on electroencephalogram (EEG) ictal/interictal patterns, and data regarding the outcomes are inconsistent. We describe a case of neonatal onset epilepsy with missense mutation c(674G>A) p(R225 H) in PNPO gene and pyridoxine responsiveness. Comparing this patient with 24 cases of previously described pyridoxine-responsive pyridoxine phosphate oxidase deficiency epilepsy, we found that patients carrying the missense mutation c(674G>A) p(R225 H) of the PNPO gene might have a more severe epileptic phenotype, possibly because of their lower residual PNPO activity. Indeed, pyridoxine-responsive pyridoxine phosphate oxidase deficiency epilepsy remains a challenge, with neurodevelopmental disabilities occurring in about half of the cases.

2019 - Group B Streptococcus early-onset disease and observation of well-appearing newborns [Articolo su rivista]
Berardi, A.; Spada, Concetta; Reggiani, M. L. B.; Creti, R.; Baroni, L.; Capretti, M. G.; Ciccia, M.; Fiorini, V.; Gambini, L.; Gargano, G.; Papa, I.; Piccinini, G.; Rizzo, V.; Sandri, F.; Lucaccioni, L.
abstract

Background International guidelines lack a substantial consensus regarding management of asymptomatic full-term and late preterm neonates at risk for early-onset disease (EOS). Large cohorts of newborns are suitable to increase the understanding of the safety and efficacy of a given strategy. Methods This is a prospective, area-based, cohort study involving regional birth facilities of Emilia-Romagna (Italy). We compared cases of EOS (at or above 35 weeks’ gestation) registered in 2003–2009 (baseline period: 266,646 LBs) and in 2010–2016, after introduction of a new strategy (serial physical examinations, SPEs) for managing asymptomatic neonates at risk for EOS (intervention period: 265,508 LBs). Results There were 108 cases of EOS (baseline period, n = 60; intervention period, n = 48). Twenty-two (20.4%) remained asymptomatic through the first 72 hours of life, whereas 86 (79.6%) developed symptoms, in most cases (52/86, 60.5%) at birth or within 6 hours. The median age at presentation was significantly earlier in the intrapartum antibiotic prophylaxis (IAP)exposed than in the IAP-unexposed neonates (0 hours, IQR 0.0000–0.0000 vs 6 hours, IQR 0.0000–15.0000, p<0.001). High number of neonates (n = 531) asymptomatic at birth, exposed to intrapartum fever, should be treated empirically for each newborn who subsequently develops sepsis. IAP exposed neonates increased (12% vs 33%, p = 0.01), age at presentation decreased (median 6 vs 1 hours, p = 0.01), whereas meningitis, mechanical ventilation and mortality did not change in baseline vs intervention period. After implementing the SPEs, no cases had adverse outcomes due to the strategy, and no cases developed severe disease after 6 hours of life. Conclusions Infants with EOS exposed to IAP developed symptoms at birth in almost all cases, and those who appeared well at birth had a very low chance of having EOS. The risk of EOS in neonates (asymptomatic at birth) exposed to intrapartum fever was low. Although definite conclusions on causation are lacking, our data support SPEs of asymptomatic newborns at risk for EOS. SPEs seems a safe and effective alternative to laboratory screening and empirical antibiotic therapy.

2019 - Hearing loss in children with congenital cytomegalovirus infection: An 11-year retrospective study based on laboratory database of a tertiary paediatric hospital [Articolo su rivista]
Palma, S.; Roversi, M. F.; Bettini, M.; Mazzoni, S.; Pietrosemoli, P.; Lucaccioni, L.; Berardi, A.; Genovese, E.
abstract

Congenital cytomegalovirus infection is considered the main cause of infantile non-genetic neurosensory hearing loss. Although this correlation was described more than 50 years ago, the natural history of internal ear involvement has not yet been fully defined. Hearing loss is the most frequent sequela and is seen in a variable percentage up to 30%; the hearing threshold is characterised by fluctuations or progressive deterioration. The purpose of this study was to evaluate the prevalence of hearing loss in cases of congenital CMV infection from Modena county, starting from the database of the microbiology and virology reference laboratory. All children undergoing urine testing for suspected CMV infection or viral DNA testing on Guthrie Card in the period between January 2004 and December 2014 were enrolled in the study. Family paediatricians were contacted and asked about clinical information on the possible presence at birth or subsequent occurrence of hearing loss, excluding cases where this was not possible. The results showed an annual prevalence of congenital cytomegalovirus infection among suspected cases that was stable over time despite the progressive increase in subjects tested. The prevalence of hearing loss was in line with the literature, whereas in long-term follow-up cases of moderate, medium-to-severe hearing loss with late onset were not detected. The introduction of newborn hearing screening in the county has allowed early diagnosis of hearing loss at birth as non-TEOAE-born births underwent a urine virus test. Moreover, despite all the limitations of the study, we can conclude that European epidemiological studies are needed to better define the relationship between congenital CMV infection and internal ear disease as the impact of environmental and genetic factors is still not entirely clarified.

2019 - Hospital clusters of invasive Group B Streptococcal disease: A systematic review [Articolo su rivista]
Collin, S. M.; Lamb, P.; Jauneikaite, E.; Le Doare, K.; Creti, R.; Berardi, A.; Heath, P. T.; Sriskandan, S.; Lamagni, T.
abstract

Objectives: To characterize outbreaks of invasive Group B Streptococcal (iGBS) disease in hospitals. Methods: Systematic review using electronic databases to identify studies describing iGBS outbreaks/clusters or cross-infection/acquisition in healthcare settings where ‘cluster’ was defined as ≥2 linked cases. PROSPERO CRD42018096297. Results: Twenty-five references were included describing 30 hospital clusters (26 neonatal, 4 adult) in 11 countries from 1966 to 2019. Cross-infection between unrelated neonates was reported in 19 clusters involving an early-onset (<7 days of life; n = 3), late-onset (7–90 days; n = 13) index case or colonized infant (n = 3) followed by one or more late-onset cases (median serial interval 9 days (IQR 3–17, range 0–50 days, n = 45)); linkage was determined by phage typing in 3 clusters, PFGE/MLST/PCR in 8, WGS in 4, non-molecular methods in 4. Postulated routes of transmission in neonatal clusters were via clinical personnel and equipment, particularly during periods of crowding and high patient-to-nurse ratio. Of 4 adult clusters, one was attributed to droplet spread between respiratory cases, one to handling of haemodialysis catheters and two unspecified. Conclusions: Long intervals between cases were identified in most of the clusters, a characteristic which potentially hinders detection of GBS hospital outbreaks without enhanced surveillance supported by genomics.

2019 - Linfangioma cistico neonatale: descrizione di un caso clinico [Articolo su rivista]
Bonvicini, Federico; Baraldi, Alessandro; Lugli, Licia; Torcetta, Francesco; Rossi, Katia; Berardi, Alberto; Iughetti, Lorenzo
abstract

Il linfangioma cistico è una rara malformazione linfatica benigna a prevalente insorgenza nelle regioni cervico-facciale e ascellare. Le forme viscerali sono rare, mentre cute e mucose sono mag- giormente colpite. La diagnosi prenatale ecografica è possibile, tuttavia la maggior parte insorge a fine gestazione. In epoca pos - tnatale, in caso di masse atipiche, può essere necessario, oltre alla stadiazione in RM, procedere all’analisi citologica per escludere lesioni di natura maligna. L’ escissione chirurgica non è esente da complicanze procedurali e sovente risulta incompleta portando a recidive locali. In casi selezionati è possibile considerare laser- terapia, scleroterapia e la terapia farmacologica [1]. Le principali complicanze sono infezioni, emorragie, idrotorace e/o chiloto- race.

2019 - Motor and Postural Patterns Concomitant with General Movements Are Associated with Cerebral Palsy at Term and Fidgety Age in Preterm Infants [Articolo su rivista]
Ferrari, Fabrizio; Plessi, Carlotta; Lucaccioni, Laura; Bertoncelli, Natascia; Bedetti, Luca; Ori, Luca; Berardi, Alberto; Della Casa, Elisa; Iughetti, Lorenzo; D'Amico, Roberto
abstract

General movements (GMs) in combination with neurological examination and magnetic resonance imaging at term age can accurately determine the risk of cerebral palsy. The present study aimed to assess whether 11 motor and postural patterns concomitant with GMs were associated with cerebral palsy. Video recordings performed after birth in 79 preterm infants were reviewed retrospectively. Thirty-seven infants developed cerebral palsy at 2 years corrected age and the remaining 42 showed typical development. GMs were assessed from preterm to fidgety age and GM trajectories were defined. The 11 motor and postural patterns were evaluated at each age and longitudinally, alone and in combination with GM trajectories. A logistic regression model was used to assess the association between GMs, concomitant motor and postural patterns, and cerebral palsy. We confirmed that high-risk GM trajectories were associated with cerebral palsy (odds ratio = 44.40, 95% confidence interval = 11.74-167.85). An association between concomitant motor and postural patterns and cerebral palsy was found for some of the patterns at term age and for all of them at fidgety age. Therefore, at term age, concomitant motor and postural patterns can support GMs for the early diagnosis of cerebral palsy.

2019 - Observation on the newborn at risk of early-onset sepsis: The approach of the Emilia-Romagna Region (Italy) [Osservazione nel neonato a rischio di sepsi precoce: L'Approccio della Regione Emilia-Romagna] [Articolo su rivista]
Berardi, A.; Spada, C.; Ciccia, M.; Capretti, M.; Brusa, G.; Sandri, F.; Balestri, E.; Rocca, L.; Gambini, L.; Azzalli, M.; Rizzo, V.; Piccinini, G.; Vaccina, E.; Lucaccioni, L.
abstract

L’approccio al neonato a rischio di infezione batterica precoce è un problema emergente e in continua evoluzione. In passato l’approccio era basato principalmente sull’esecuzione di test di laboratorio, che sono risultati però scarsamente predittivi e causa di ripetuti prelievi di sangue e antibiotico-terapie ingiustificate, con alterazioni del nascente microbiota intestinale e possibili effetti a lungo termine. La medicalizzazione di neonati asintomatici interferisce inoltre con l’allattamento al seno. Recenti esperienze in Friuli Venezia Giulia ed Emilia-Romagna suggeriscono come sia utile un approccio meno invasivo, basato essenzialmente sull’osservazione clinica attenta e ripetuta a orari standard di neonati asintomatici a termine o lievemente pretermine, indipendentemente dal loro grado di rischio. Tale approccio è utile a una diagnosi tempestiva, non separa le madri dai loro piccoli e conseguentemente non interferisce con lo sviluppo del nascente microbiota intestinale né con l’allattamento al seno.

2019 - Perché fare il trial con Piridossina nelle convulsioni neonatali refrattarie: un caso di epilessia PNPO responsiva alla Piridossina [Articolo su rivista]
Bariola, Maria Carolina; Russo, Giovanna; Iughetti, Lorenzo; Berardi, Alberto; Ferrari, Fabrizio; Lugli, Licia
abstract

L’epilessia piridossino dipendente (PDE) e l’epilessia piridossal/fosfato dipendente (PNPO) sono difficilmente distinguibili da un punto di vista clinico: si caratterizzano per spasmi mioclonici (talora a esordio prenatale), associati a irritabilità, insonnia e startles.

2019 - Pitfalls in the diagnosis of meningitis in neonates and young infants: the role of lumbar puncture [Articolo su rivista]
Bedetti, Luca; Marrozzini, Lucia; Baraldi, Alessandro; Spezia, Elisabetta; Iughetti, Lorenzo; Lucaccioni, Laura; Berardi, Alberto
abstract

Meningitis occurs frequently in neonates and can lead to a number of acute, severe complications and long-term disabilities. An early diagnosis of neonatal meningitis is essential to reduce mortality and to improve outcomes. Initial clinical signs of meningitis are often subtle and frequently overlap with those of sepsis, and current haematologic tests do not distinguish sepsis from meningitis. Thus, lumbar puncture remains the gold standard for the diagnosis of meningitis in infants, and this procedure is recommended in clinical guidelines. Nevertheless, in clinical practice, lumbar puncture is frequently deferred or omitted due to concerns regarding hypothetical adverse events or limited experience of the performer. Future studies should assess whether a combination of clinical findings and select haematological tests at disease onset can identify those neonates with the highest risk of meningitis who should undergo lumbar puncture. Furthermore, clinicians should be convinced that the actual benefits of an early diagnosis of meningitis far outweigh the hypothetical risks associated with lumbar puncture.

2019 - Severe metabolic alkalosis due to diuretic treatment in a patient with distal renal tubular acidosis: a rare association. [Articolo su rivista]
Lucaccioni, Laura; Coccolini, Elena; Dozza, Alessandra; Cantatore, Sante Lucio; Berardi, Alberto; Predieri, Barbara; Iughetti, Lorenzo
abstract

Introduction: Distal renal tubular acidosis is a rare genetic disease, characterised by deficit in renal tubular transport. Clinical features are metabolic acidosis with hypercloraemia and hypokalemia, and inability in urine acidification. Hypercalciuria may also be present, often treated with the use of a diuretic therapy with thiazides. Case Presentation: We present a severe disease onset in a neonate with consanguineous parents, both autosomal-recessive for an ATP6VOA4 gene mutation, and a nevertheless severe episode of metabolic alkalosis, occurred in the same patient after few months, during the diuretic therapy. Conclusion: Biochemical results lead us to hypothesize a susceptibility to the treatment that need further investigations.

2019 - Strategies for preventing early-onset sepsis and for managing neonates at-risk: wide variability across six Western countries [Articolo su rivista]
Berardi, Alberto; Rossi, Cecilia; Spada, Caterina; Vellani, Giulia; Guidotti, Isotta; Lanzoni, Angela; Azzalli, Milena; Papa, Irene; Giugno, Chiara; Lucaccioni, Laura
abstract

Group B streptococcus (GBS) early-onset sepsis (EOS) has declined after widespread intrapartum antibiotic prophylaxis. However, strategies for preventing EOS may differ across countries. The analysis of their strategies allows to compare the effectiveness of prevention in different countries and suggests opportunities for improvement.

2019 - The oral communications presented by post graduate students in pediatrics at the Conference: From Tabiano to Parma [Relazione in Atti di Convegno]
Bariola, M. C.; Russo, G.; Iughetti, L.; Berardi, A.; Ferrari, F.; Lugli, L.; Giulia, L. A.; Euro, C.; Monica, S.; Rita, G. M.; Giuseppe, M.
abstract

2019 - Un neonato a termine ipotonico: pensa anche alla sindrome di Prader-Willi [Articolo su rivista]
Bariola, Maria Carolina; Vaccina, E.; Lugli, L.; Berardi, A.; Lucaccioni, L.; Iughetti, L.; F. Ferrari.,
abstract

The paper describes the case of a term newborn infant, born by elective caesarean section with no prenatal and perinatal risk factors. He presented with an unexpected cardiorespiratory depression at birth, severe hypotonia, feeding problems and peculiar dysmorphism: micrognathia with chubby cheeks, small hands and right cryptorchidism. In the suspect of Prader-Willi syndrome, DNA methylation test confirmed the diagnostic hypothesis. The simultaneous presence of neonatal hypotonia, poor suck and peculiar dysmorphism should suggest Prader-Willi syndrome and thus the performance of the DNA methylation test to confirm the diagnosis for a timely and adequate therapeutic work-up.

2019 - Unusual meningitis caused by non-typhoid Salmonella in an italian infant: a case report. [Articolo su rivista]
Ficara, Monica; Cenciarelli, Valentina; Montanari, Lisa; Righi, Beatrice; Fontjin, Simone; Cingolani, Greta Miriam; Predieri, Barbara; Berardi, Alberto; Lucaccioni, Laura; Iughetti, Lorenzo
abstract

Background: Non-typhoid Salmonella (NTS) is an important cause of bacterial meningitis in newborn and infants in developing countries, but rarely in industrialized ones. We describe an unusual presentation of bacterial meningitis in an infant, focusing on his diagnostic and therapeutic management. Case report: An Italian two-month old male presented high fever and diarrhea with blood, associated with irritability. Inflammatory markers were high, cerebrospinal fluid analysis was compatible with bacterial meningitides but microbiological investigations were negative. Salmonella enteritidis was isolated from blood. Cerebral ultrasound and MRI showed periencephalic collection of purulent material. Specific antibiotic therapy with cefotaxime was initiated with improvement of clinical conditions and blood tests. Brain MRI follow up improved progressively. Conclusions: Most of pediatric patients with NTS infection develop self-limited gastroenteritis, but in 3-8% of the cases complications such as bacteremia and meningitis may occur, especially in weak patients. Cerebral imaging can be useful to identify neurological findings. Although there is no standardized treatment for this condition, specific antibiotic therapy for at least four weeks is recommended. Neuroimaging follow up is required due to high risk of relapse.

2019 - Worse global intellectual and worse neuropsychological functioning in preterm-born children at preschool age: a meta-analysis [Articolo su rivista]
Arpi, Elena; D'Amico, Roberto; Lucaccioni, Laura; Bedetti, Luca; Berardi, Alberto; Ferrari, Fabrizio
abstract

Preterm births (<32 weeks of gestational age) are associated with cognitive problems that are difficult to diagnose in infancy but potentially detectable at preschool age. This review aimed to evaluate the extent to which total intelligence quotient (IQ) and neuropsychological functions at ages three to five years differ between children born at <32 weeks gestational age or <1,500 g birth weight and children born at term. The secondary aim was to determine if cognitive performance differs between extremely preterm (EPT)/extremely low birth weight (ELBW) children and very preterm (VPT) or very low birth weight (VLBW) children.

2018 - Are postnatal ampicillin levels actually related to the duration of intrapartum antibiotic prophylaxis prior to delivery? A pharmacokinetic study in 120 neonates [Articolo su rivista]
Berardi, Alberto; Pietrangiolillo, Zaira; Bacchi Reggiani, Maria Letizia; Bianco, Valentina; Gallesi, Daniela; Rossi, Katia; Facchinetti, Fabio; Ferrari, Fabrizio
abstract

To assess ampicillin levels according to the duration of intrapartum antibiotic prophylaxis (IAP).

2018 - Brain-derived neurotrophic factor and epilepsy: a systematic review [Articolo su rivista]
Iughetti, L; Lucaccioni, L; Fugetto, F; Predieri, B; Berardi, A; Ferrari, F.
abstract

Several in vitro, ex vivo and in vivo studies imply brain-derived neurotrophic factor (BDNF) in the pathophysiology of epilepsy. Aim of our work is to report the most important findings regarding BDNF and its potential role in epilepsy. We targeted those publications addressing both in vitro and in vivo evidences of relationship between BDNF and epilepsy. Basic researches, randomized trials, cohort studies, and reviews were contemplated to give a breadth of clinical data. Medline, CENTRAL, and Science Direct were searched till August 2017 using keywords agreed by the authors. Together with a defined role in developmental and mature brain, BDNF has excitatory effects in neuronal cultures and animal brain slices. Furthermore, both BDNF and its conjugated receptor (i.e. Tropomyosin receptor kinase B or TrkB) are increased in animal models and humans with epilepsy, particularly in the temporal and hippocampal areas. Acute injection of BDNF in brain of mice induces seizures, which are almost or totally abolished blocking its transcription and pathway. Chronic infusion of BDNF is conversely associated with a decreased neuronal excitability, probably via several mechanism including an increase in central levels of neuropeptide Y (NPY), altered conductance of chloride, and downregulation of TrkB. While genetic studies are inconclusive, serum BDNF is more frequently higher in patients with epilepsy and appears to be correlated to severity of disease. Current evidences suggest that inhibiting BDNF-TrkB signaling and reinforcing the NPY system could represent a potential therapeutic strategy for epilepsy, especially for temporal lobe epilepsy.

2018 - Group B streptococcus late-onset disease,contaminated breast milk and mothers persistently GBS negative: Report of 3cases [Articolo su rivista]
Nicolini, Giangiacomo; Borellini, Martina; Loizzo, Vitaliana; Creti, Roberta; Memo, Luigi; Berardi, Alberto
abstract

Background: Human milk is fundamental for its nutritional properties and to protect newborns, but it is not sterile and can sometime transmit bacteria. Few anecdotal cases suggest that breast milk could be a possible source of group B Streptococcus (GBS) late onset disease, although the pathogenesis is not entirely understood. Case presentation: We report 3 cases of GBS late onset disease in full-term newborns. Fresh breast milk cultures yielded GBS, but mothers of neonates had no signs of mastitis and remained persistently GBS negative at rectovaginal site. Conclusions: Breast milk containing group B Streptococcus can be a risk factor for late onset disease. The persistent negative maternal GBS status supports the assumption that newborns, colonised in the throat, could be the initial source of GBS, while the mammary gland could act as a GBS replication site. It is unclear whether a low bacterial load may represent only contamination rather than true milk infection.

2018 - I.S.Mu.L.T. hyaluronic acid injections in musculoskeletal disorders guidelines [Articolo su rivista]
Frizziero, A.; Oliva, F. V. F.; Berardi, A.; Ceccarelli, F.; Costantino, C.; Faldini, C.; Foti, C.; Masiero, S.; Porcellini, G.; Vulpiani, M. C.; Abatangelo, G.; Mahmoud, A.; Buonocore, D.; Buda, R.; Dossena, M.; Frizziero, L.; Galletti, S.; Via, A. G.; Merolla, G.; Migliore, A.; Nicoletti, S.; Padolino, A.; Terreni, M.; Valent, A.; Vannini, F.; Verri, M.; Vetrano, M.; Bacciu, S.; Bossa, M.; Calderazzi, F.; Carolla, A.; Finotti, P.; Gasparre, G.; Natali, S.; Pellicciari, L.; Piccirilli, E.; Pintus, E.; Romiti, D.; Vertuccio, A.; Maffulli, N.
abstract

Intra-articular and peri-articular hyaluronic acid (HA) injections are widely used to treat several musculoskeletal pathologies. Although clinical outcomes are often positive for different conditions, an holistic consensus on this topic is still lacking. Our work is divided in two main sessions: in the first section we analyzed the preclinical bases for HA treatment in musculoskeletal pathologies, while in the second part we discussed the evidence on the use of HA injections in each district of musculoskeletal system. The aim of this work is to provide to the physician a feasible guideline rapidly to consult in the clinical practice. Level of evidence: Ia.

2018 - LA MENINGITE NEL NEONATO E NEL PICCOLO LATTANTE [Articolo su rivista]
Bedetti, L.; Baraldi, A.; Leone, Federica; Marrozzini, L.; Iughetti, L.; Lucaccioni, L.; Berardi, A.
abstract

Bacterial meningitis may cause long term disabilities or death, particularly at younger ages. Early diagnosis and prompt antibiotic therapy are essential for improving outcome. The diagnosis of meningitis in newborns and young infants is a challenge because symptoms and signs are frequently vague and non-specific, in particular at the onset of the disease. Cerebrospinal fluid culture and analysis remain nowadays the gold standard for diagnosis. Clinicians often defer lumbar puncture because of concerns of complications, although data concerning the risks of lumbar puncture at younger ages are poorly defined. Perhaps a combination of laboratory markers and selected clinical symptoms at the onset of meningitis would identify neonates with higher risk of meningitis who should necessarily undergo lumbar puncture. Currently, clinicians should be aware that the advantage of an early diagnosis of meningitis through lumbar puncture overcomes the risks related to the procedure.

2018 - Male or Female? What about disorders of sex development [Articolo su rivista]
Lucaccioni, L; Boncompagni, A; Pietrella, E; Ceccarelli, Pl; Ferrari, F; Berardi, A; Iughetti, L.
abstract

After the first trimester of pregnancy future parents are commonly asked if their child will be male or female. Such a question creates many expectations and implies the true determination of the baby's identity. Indeed, since the earliest stages of pregnancy knowing the gender of unborn babies creates expectations in their families, which grow with the approach of childbirth. Babies born with atypical genitalia, which consequently makes impossible to address whether they are really the same as they had been imagined, create considerable difficulties in their parents, who see their believes undermined. The evaluation of infants' genitalia, taken for granted when referring to genitalia phenotypically in the standard and often not reported for brevity in the first clinical examination after birth, becomes fundamental in case of atypia. In order to be able to take best care of such children, it is necessary to know how the hypothalamus-pituitary-gonad axis and the consequent genital development work and to understand, whenever possible, what the problem was to be able to build the best plan to support families and patients.

2018 - Neonates at Risk of Early-Onset Sepsis: Which Is the Best Approach? [Articolo su rivista]
Berardi, Alberto; Spada, Caterina; Capretti, Maria Grazia; Ciccia, Matilde; Pulvirenti, Maria Rita; Vezzosi, Martina; Sandri, Fabrizio
abstract

No abstract

2018 - Palivizumab nella profilassi stagionale delle infezioni da virus respiratorio sinciziale [Articolo su rivista]
Alessandroni, R; Ancora, G; Berardi, A; Casadio, L; Di Dio, F; Faldella, G; Garani, G; Gargano, G; Lanzoni, A; Marchetti, F; Raimondi, L; Sandri, F; Stella, M; Vandini, S; Marata, A; Giroldini, R.
abstract

nessun abstract

2018 - Persistent intestinal bleeding due to severe CMV-related thrombocytopenia in a preterm newborn [Articolo su rivista]
Berardi, Alberto; Spaggiari, Eugenio; Cattelani, Chiara; Roversi, MARIA FEDERICA; Pecorari, Monica; Lazzarotto, Tiziana; Ferrari, Fabrizio
abstract

The optimal threshold for neonatal platelet transfusions in sick newborns is still uncertain. We report a congenital cytomegalovirus (CMV) infection in a premature neonate with severe thrombocytopenia who subsequently presented with necrotizing enterocolitis and intestinal bleeding. The baby recovered after platelet transfusions were discontinued and the therapy was switched from intravenous ganciclovir to oral valganciclovir. We discuss both measures, speculating on the key role of platelet transfusions.

2018 - Secondary prevention of early-onset sepsis: A less invasive Italian approach for managing neonates at risk [Articolo su rivista]
Berardi, Alberto; Tzialla, Chryssoula; Travan, Laura; Bua, Jenny; Santori, Daniele; Azzalli, Milena; Spada, Caterina; Lucaccioni, Laura
abstract

Strategies to prevent early-onset sepsis (EOS) have led to a substantial decline in many countries. However, one of the most controversial topics in neonatology is the management of asymptomatic full-term and late preterm neonates at risk for EOS, and guidelines lack substantial consensus regarding this issue. A strategy for managing neonates, entirely based on serial physical examinations, has been developed in two Italian regions. This strategy seems safe, while reducing laboratory tests and unnecessary antibiotics. In the current commentary we provide area-based data concerning the prevention of EOS in 2 northern Italian regions, and we detail the results of their strategy for managing healthy-appearing newborns at risk for EOS.

2018 - Two Overlapping Clusters of Group B Streptococcus Late-onset Disease in a Neonatal Intensive Care Unit [Articolo su rivista]
Berardi, Alberto; Guidotti, Isotta; Creti, Roberta; Alfarone, Giovanna; Grottola, Antonella; Venturelli, Claudia; Fregni Serpini, Giulia; Della Casa, Elisa; Vecchi, Elena; Boncompagni, Alessandra; Toffoli, Carlotta; Ferrari, Fabrizio
abstract

OBJECTIVES: Current predominant routes of group B Streptococcus (GBS) transmission in preterm neonates admitted to neonatal intensive care unit (NICU) are poorly defined. We report 2 overlapping clusters of GBS late-onset disease (LOD) from June to September 2015 in an Italian NICU.METHODS: During the outbreak, possible sources of transmission (equipment, feeding bottles and breast pumps) were swabbed. Specimens from throat and rectum were collected on a weekly basis from all neonates admitted to NICU. Colonized or infected neonates had cohorting. Bacterial isolates were characterized by serologic and molecular typing methods.RESULTS: GBS was isolated in 2 full-term and 7 preterm neonates. Strains belonged to serotype III, with 3 different sequence types (ST17, ST182 and ST19). Full-term neonates were colonized with GBS strains unrelated to the clusters (ST182 and ST19). Two distinct ST17 strains caused 2 clusters in preterm neonates: a first cluster with 1 case of LOD and a second, larger cluster with 6 LOD in 5 neonates (one of them had recurrence). ST17 strains were isolated from vaginorectal and milk samples of 2 mothers. Two preterm neonates had no evidence of colonization for weeks, until they presented with LOD.CONCLUSIONS: Molecular analyses identified the presence of multiclonal GBS strains and 2 clusters of 7 cases of GBS-LOD. The dynamics of transmission of GBS within the NICU were complex. Breast milk was suspected to be one of the possible sources. In a research setting, the screening of GBS carrier mothers who deliver very preterm could contribute to the tracking of GBS transmission.

2017 - An area-based study on intrapartum antibiotic prophylaxis for preventing group B streptococcus early-onset disease: advances and limitations. [Articolo su rivista]
Berardi, Alberto; Rossi, Cecilia; Bacchi Reggiani, Maria Letizia; Bastelli, Annalisa; Capretti, Maria Grazia; Chiossi, Claudio; Fiorini, Valentina; Gambini, Lucia; Gavioli, Sara; Lanari, Marcello; Memo, Luigi; Papa, Irene; Pini, Luana; Rizzo, Maria Vittoria; Zucchini, Andrea; Facchinetti, Fabio; Ferrari, Fabrizio
abstract

The prevalence of maternal group-B-streptococcus (GBS) colonization and risk factors (RFs) for neonatal early-onset disease (EOD) in Europe are poorly defined. Large-scale information concerning adherence to recommendations for preventing GBS-EOD are lacking.

2017 - Antimicrobial stewardship in newborns and young infants: Why and how to do it [Articolo su rivista]
Berardi, Alberto; Ficara, Monica; Pietrella, Elisa; Boncompagni, Alessandra; Toffoli, Carlotta; Anastasia, Bianchini; Elisa Della Casa, ; Spada, Caterina; Spaggiari, Eugenio; Matilde, Ciccia; Giancarlo, Gargano; Rizzo, Giovanna Valeria; Milena, Azzalli; Giacomo, Biasucci; Gambini, L.; Serenella, Bolognesi; Giancarlo, Piccinini; Ferrari, Fabrizio
abstract

Le resistenze antibiotiche stanno aumentando in tutto il mondo per l’abuso di terapie in sanità umana e veterinaria. Si prevede che entro pochi decenni i germi multiresistenti diverranno la prima causa assoluta di morte. Nel neonato l’abuso di terapie antibiotiche è dovuto alla potenziale gravità della sepsi neonatale, alla scarsa specificità dei suoi sintomi e alla mancanza di test diagnostici accurati e predittivi. Per prevenire l’emergenza di resistenze occorre un uso accorto degli antibiotici, protocolli strutturati e una serie di misure aggiuntive condivise da tutto il personale. Il presente documento sintetizza le recenti indicazioni prodotte in Emilia-Romagna dopo revisione della letteratura.

2017 - Gestational group B streptococcal infection in two twin pregnancies [Articolo su rivista]
Ciccia, Matilde; Salerno, Angela; Mascio, Alberto Di; Berardi, Alberto; Chakrokh, Roksana; Sandri, Fabrizio
abstract

Twin pregnancies represent an interesting pattern in which selective infection of one gestational sac over the other can occur. Despite the ubiquity of Group B streptococcus (GBS), only a few cases documenting twin gestational GBS infections have been reported. We describe two cases of gestational GBS infection in twin pregnancies (a monochorionic/diamniotic pregnancy and a dichorionic/diamniotic pregnancy) both resulting in the death of one twin.

2017 - Lotus Birth Associated With Idiopathic Neonatal Hepatitis [Articolo su rivista]
Tricarico, Antonella; Bianco, Valentina; Iughetti, Lorenzo; Ferrari, Fabrizio; Berardi, Alberto
abstract

In the present case, the infant presented with a complication of LB. There was a close temporal relationship between LB and the onset of clinical symptoms. The baby had persistent jaundice associated with a severe increase in aspartate and alanine aminotransferases without evidence of cholestasis. Recovery occurred spontaneously after the first months of life. Hepatobiliary, hematological, metabolic, endocrine, and genetic disorders were ruled out.

2017 - Neonatal group B streptococcus infections: Prevention strategies, clinical and microbiologic characteristics in 7 years of surveillance [Articolo su rivista]
Creti, Roberta; Imperi, Monica; Berardi, Alberto; Pataracchia, Marco; Recchia, Simona; Alfarone, Giovanna; Baldassarri, Lucilla
abstract

Background: The characteristics of group B streptococcus (GBS) neonatal disease in a period of 7 years are reported. Methods: The estimation of the neonatal GBS disease risk and prevention strategies adopted at delivery in absence of national guidelines was evaluated by the analysis of 3501 questionnaires. Notification of 194 neonatal GBS infections was recorded. In addition, 115 strains from neonatal earlyonset disease (EOD) and late-onset disease, respectively, plus 320 strains from pregnant women were analyzed by molecular typing methods and for antibiotic resistance. Results: Preterm deliveries, precipitous labor and GBS negatively screened mothers were the prominent causes for an inadequate or lack of intrapartum antibiotic prophylaxis and EOD occurrence. The superimposable serotype distribution of GBS strains from EOD and from antenatal screening confirmed the vertical transmission from mother to neonate as the cause of disease. On the contrary, late-onset disease was almost exclusively caused by the internationally diffused clonal complex 17. Erythromycin resistance was detected in 17% of strains. Resistance to clindamycin was 15.3 %. Conclusions: The administration of intrapartum antibiotic prophylaxis to negatively GBS screened women in presence of risk factors was a deviation from the recommendations issued by the Centers for Disease Control and Prevention, and it should deserve further consideration. Routine surveillance and molecular typing of circulating clones are essential for the effective management of the neonatal GBS disease.

2017 - Neonatal pyknocytosis in a preterm dizygotic twin [Articolo su rivista]
Berardi, Alberto; Balestri, Eleonora; Bonacorsi, Goretta; Chiossi, Claudio; Palazzi, Giovanni; Spaggiari, Eugenio; Ferrari, Fabrizio
abstract

Infantile pyknocytosis (IP) is a rare, self-limited neonatal haemolytic anaemia that may require multiple blood transfusions. Only a little more than 50 cases have been reported in the medical literature, and the great majority of them concerns term infants. The etiology of IP is not well understood; most likely it results from a transient extra-corpuscular factor, whose nature is unknown, transmitted from mother to child or, alternatively, from a deficiency of an anti-oxidative agent. We report the case of two preterm twins, one of which suffered from IP and developed severe anaemia at age 2 wk, while the other was unaffected. Although no specific agent was identified as the cause of anaemia and IP, we speculate that the transmission of an agent from mother to child was unlikely, as only twin one suffered from IP. Smelly greenish diarrhoea occurred just before the presentation of IP, suggesting that the same agent led to both the diarrhoea and the oxidative injury. Because IP may remain underdiagnosed, it should be considered in cases of early unexplained severe hemolytic anemia.

2017 - Strategies for preventing group B streptococcal infections in newborns: A nation-wide survey of Italian policies [Articolo su rivista]
Tzialla, Chryssoula; Berardi, Alberto; Farina, Claudio; Clerici, Pierangelo; Borghesi, Alessandro; Viora, Elsa; Scollo, Paolo; Stronati, Mauro
abstract

Background: There are no Italian data regarding the strategies for preventing neonatal group B streptococcal (GBS) infection. We conducted a national survey in order to explore obstetrical, neonatal and microbiological practices for the GBS prevention. Methods: Three distinct questionnaires were sent to obstetricians, neonatologists and microbiologists. Questionnaires included data on prenatal GBS screening, maternal risk factors, intrapartum antibiotic prophylaxis, microbiological information concerning specimen processing and GBS antimicrobial susceptibility. Results: All respondent obstetrical units used the culture-based screening approach to identify women who should receive intrapartum antibiotic prophylaxis, and more than half of the microbiological laboratories (58%) reported using specimen processing consistent with CDC guidelines. Most neonatal units (89 out of 107, 82%) reported using protocols for preventing GBS early-onset sepsis consistent with CDC guidelines. Conclusions: The screening-based strategy is largely prevalent in Italy, and most protocols for preventing GBS early-onset sepsis are consistent with CDC guidelines. However, we found discrepancies in practices among centers that may reflect the lack of Italian guidelines issued by public health organizations.

2016 - Congenital Glioblastoma multiforme and eruptive disseminated Spitz nevi [Articolo su rivista]
Mandel, Victor Desmond; Persechino, Flavia; Berardi, Alberto; Ponti, Giovanni; Ciardo, Silvana; Rossi, Cecilia; Pellacani, Giovanni; Farnetani, Francesca
abstract

Background: Glioblastoma multiforme (GBM) is the deadliest malignant primary brain tumor in adults. GBM develops primarily in the cerebral hemispheres but can develop in other parts of the central nervous system. Its congenital variant is a very rare disease with few cases described in literature. Case presentation: We describe the case of a patient with congenital GBM who developed eruptive disseminated Spitz nevi (EDSN) after chemotherapy. Few cases of EDSN have been described in literature and this rare clinical variant, which occurs predominantly in adults, is characterized by multiple Spitz nevi in the trunk, buttocks, elbows and knees. There is no satisfactory treatment for EDSN and the best therapeutic choice is considered the clinical observation of melanocytic lesions. Conclusion: We recommend a close follow-up of these patients with clinical observation, dermoscopy and reflectance confocal microscopy (RCM). However, we suggest a surgical excision of the lesions suspected of being malignant.

2016 - Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: Study protocol for a randomized controlled trial [Articolo su rivista]
Vento, Giovanni; Pastorino, Roberta; Boni, Luca; Cota, Francesco; Carnielli, Virgilio; Cools, Filip; Dani, Carlo; Mosca, Fabio; Pillow, Jane; Polglase, Graeme; Tagliabue, Paolo; van Kaam, Anton H.; Ventura, Maria Luisa; Tana, Milena; Tirone, Chiara; Aurilia, Claudia; Lio, Alessandra; Ricci, Cinzia; Gambacorta, Alessandro; Consigli, Chiara; D'Onofrio, Danila; Gizzi, Camilla; Massenzi, Luca; Cardilli, Viviana; Casati, Alessandra; Bottino, Roberto; Pontiggia, Federica; Ciarmoli, Elena; Martinelli, Stefano; Ilardi, Laura; Colnaghi, Mariarosa; Matassa, Piero Giuseppe; Vendettuoli, Valentina; Villani, Paolo; Fusco, Francesca; Gazzolo, Diego; Ricotti, Alberto; Ferrero, Federica; Stasi, Ilaria; Magaldi, Rosario; Maffei, Gianfranco; Presta, Giuseppe; Perniola, Roberto; Messina, Francesco; Montesano, Giovanna; Poggi, Chiara; Giordano, Lucio; Roma, Enza; Grassia, Carolina; Ausanio, Gaetano; Sandri, Fabrizio; Mescoli, Giovanna; Giura, Francesco; Garani, Giampaolo; Solinas, Agostina; Lucente, Maria; Nigro, Gabriella; Del Vecchio, Antonello; Petrillo, Flavia; Orfeo, Luigi; Grappone, Lidia; Quartulli, Lorenzo; Scorrano, Antonio; Messner, Hubert; Staffler, Alex; Gargano, Giancarlo; Balestri, Eleonora; Nobile, Stefano; Cacace, Caterina; Meli, Valerio; Dallaglio, Sara; Pasqua, Betta; Mattia, Loretta; Gitto, Eloisa; Vitaliti, Marcello; Re, Maria Paola; Vedovato, Stefania; Grison, Alessandra; Berardi, Alberto; Torcetta, Francesco; Guidotti, Isotta; di Fabio, Sandra; Maranella, Eugenia; Mondello, Isabella; Visentin, Stefano; Tormena, Francesca
abstract

Background: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria. Methods/design: In this study, 206 spontaneously breathing infants born at 24+0-27+6 weeks' gestation and failing nCPAP during the first 24 h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3 days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30 min after surfactant administration or when they meet the nCPAP failure criteria after extubation. Discussion: From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge. Trial registration: ClinicalTrials.gov identifier: NCT02482766. Registered on 1 June 2015.

2016 - Group B streptococcal maternal vaccination, the goal is near [Articolo su rivista]
Berardi, Alberto; Ferrari, Fabrizio
abstract

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2016 - Hypothermia reduces seizure burden and improves neurological outcome in severe hypoxic–ischemic encephalopathy: an observational study [Articolo su rivista]
Guidotti, Isotta; Lugli, Licia; Guerra, Maria Pina; Ori, Luca; Gallo, Claudio; Cavalleri, Francesca; Ranzi, Andrea; Frassoldati, Rossella; Berardi, Alberto; Ferrari, Fabrizio
abstract

Aim: To evaluate the antiepileptic effect of hypothermia and its association with neurological outcome in infants with moderate and severe hypoxic–ischemic encephalopathy (HIE). Method: We compared polygraphic electroencephalography monitoring and outcome data in 39 cooled and 33 non-cooled term newborn infants, born between January 2005 and March 2013, and hospitalized because of signs of asphyxia and moderate to severe HIE. Results: Cooled newborn infants had fewer seizures (14/39 vs 20/33 p=0.036) and status epilepticus (7/39 vs 13/33, p=0.043), a lower mean duration of seizures (18mins vs 133mins, p=0.026), fewer administered antiepileptic drugs (median 0 vs 1, p=0.045), and more commonly a good outcome at 24 months (normal/mild motor impairment in 32/39 vs 16/33, p=0.003). Seizure burden (accumulated duration of seizures over a defined period) in cooled patients with both moderate (0.0 vs 0.1; p=0.045) and severe HIE (0.3 vs 4.9; p=0.018) was lower than in non-cooled patients. Compared with non-cooled patients, a good outcome was more common in cooled newborn infants with severe HIE (p=0.003). Interpretation: Hypothermia has an antiepileptic effect in both moderate and severe neonatal HIE. The lower seizure burden in cooled newborn infants with severe HIE is more commonly associated with normal outcome at 24 months.

2016 - Pathogenesis of Streptococcus in Humans [Capitolo/Saggio]
Creti, R; Gherardi, G; Berardi, A; Baldassarri, L
abstract

no abstract

2016 - Serial physical examinations, a simple and reliable tool for managing neonates at risk for early-onset sepsis [Articolo su rivista]
Berardi, Alberto; Buffagni, Anna Maria; Rossi, Cecilia; Vaccina, Eleonora; Cattelani, Chiara; Gambini, Lucia; Baccilieri, Federica; Varioli, Francesca; Ferrari, Fabrizio
abstract

To investigate whether serial physical examinations (SPEs) are a safe tool for managing neonates at risk for early-onset sepsis (EOS).

2016 - The burden of early-onset sepsis in Emilia-Romagna (Italy): a 4-year, population-based study [Articolo su rivista]
Berardi, Alberto; Baroni, Lorenza; Bacchi Reggiani, Maria Letizia; Ambretti, Simone; Biasucci, Giacomo; Bolognesi, Serenella; Capretti, Maria Grazia; Carretto, Edoardo; Ciccia, Matilde; Fiorini, Valentina; Fortini, Cinzia; Gargano, Giancarlo; Pedna, Maria Federica; Rizzo, Vittoria; Creti, Roberta; Ferrari, Fabrizio; Memo, L.; Nicolini, G.; Campanile, A.; Tridapalli, E.; Ciccia, M.; Bastelli, A.; Sandri, F.; Ambretti, S.; Capretti, M. G.; Gentili, A.; Ragni, L.; Albarelli, A.; Piscina, A.; Borghi, A.; Simoni, A.; Fiorini, V.; Grande, E. D.; Polese, A.; Biasini, A.; China, M. C.; Rizzo, V.; Zucchini, A.; Malaguti, L.; Contiero, R.; Fortini, C.; Garani, G.; Rossi, M. R.; Nasi, S.; Bacchini, P.; Baldassarri, P.; Pulvirenti, R. M.; Vaienti, F.; Venturoli, V.; Bidetti, M. L.; Colla, R.; Toniato, M.; Carlo, C. D.; Lanari, M.; Serra, L.; Silvestrini, D.; Facchinetti, F.; Ferrari, F.; Lugli, L.; Venturelli, C.; Sarti, M.; Volta, A.; Dodi, I.; Gambini, L.; Guidi, B.; Bertelli, M.; Biasucci, G.; Chiarabini, R.; Padrini, D.; Piepoli, M.; Riboni, S.; Rubbi, P.; Pedna, M. F.; Sambri, V.; Perrone, A.; Preti, P.; Marchetti, F.; Piccinini, G. C.; Amarri, S.; Carretto, E.; Gargano, G.; Pedori, S.; Riva, M.; Rossi, C.; Zuelli, C.; Bolognesi, S.; Papa, I.; Vergine, G.; Viola, L.; Chiossi, C.; Pagano, R.; Zanacca, C.; Palmieri, R.
abstract

Objective: To provide the first Italian data on pathogens causing early-onset sepsis (EOS) and their antimicrobial susceptibility, after the successfully prevention of Group B streptococcus (GBS) EOS. Methods: Retrospective area-based cohort study from Emilia-Romagna (Italy). Cases of EOS registered (from 2009 to 2012) in all gestational age neonates were reviewed. Results: Live births (LB) numbered 146 682. Ninety neonates had EOS and 12 died (incidence rates of 0.61 and 0.08/1000 LB, respectively). EOS and mortality were the highest among neonates with a birth weight <1000 g (20.37/1000 LB and 8.49/1000 LB, respectively). The most common pathogens were GBS (n = 27, 0.18/1000 LB) and Escherichia coli (n = 19, 0.13/1000 LB). Most infants affected by E. coli EOS were born preterm (n = 13), had complications (n = 4) or died (n = 7). Among 90 isolates tested, only 3 were resistant to both first line empirical antibiotics. Multivariate logistic regression analysis showed that low gestational age, caesarean section and low platelet count at presentation were significantly associated with death or brain lesions (area under ROC curve = 0.939, H-L = 0.944, sensitivity 76.0%, specificity 90.7%). Conclusions: GBS slightly exceeds E. coli as a cause of EOS. However, E. coli is the prominent cause of death, complications and in most cases affects preterm neonates. Empirical antimicrobial therapy of EOS seems appropriate.

2016 - The ontogeny of fidgety movements from 4 to 20 weeks post-term age in healthy full-term infants [Articolo su rivista]
Ferrari, Fabrizio; Frassoldati, Rossella; Berardi, Alberto; Di Palma, Francesca; Ori, Luca; Lucaccioni, Laura; Bertoncelli, Natascia; Einspieler, Christa
abstract

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2016 - Un caso di forma eruttiva di nevi di Spitz [Poster]
Mandel, Victor Desmond; Persechino, Flavia; Berardi, Alberto; Ciardo, Silvana; Pellacani, Giovanni; Farnetani, Francesca
abstract

Si presenta il caso di un paziente che aveva avuto un glioblastoma multiforme congenito, per il quale era stato sottoposto ad un intervento chirurgico ed a cicli di chemioterapia. All’età di 16 mesi il paziente giungeva alla nostra attenzione per la comparsa di numerosi nevi. I nevi erano principalmente localizzati al tronco, apparivano di differente colore e morfologia ed avevano una dimensione variabile tra 2 mm e 21 mm. All’esame dermoscopico molti di questi nevi presentavano un pattern starburst, globulare o multicomponente con asimmetriche aree ipopigmentate e bordi irregolari. Tali caratteristiche dermatoscopiche deponevano per nevi di Spitz. Tale diagnosi veniva confermata utilizzando il microscopio confocale. Considerando il numero di nevi di Spitz osservati veniva posta diagnosi di forma eruttiva di nevi di Spitz e veniva deciso di eseguire un rigoroso follow-up di tali lesioni invece di eseguire più escissioni chirurgiche. Ciononostante, durante il follow-up, nel sospetto di essere maligna, veniva asportata una di queste lesioni, che all’esame istologico risultava essere un nevo di Spitz. Attualmente il paziente ha 3 anni di età e durante il follow-up è stata notata la comparsa di altri nevi di Spitz, ma nessun nevo di Spitz è cambiato nel tempo.

2015 - Fatal pneumonia following maternal HSV-1 viraemia in late pregnancy [Articolo su rivista]
Berardi, Alberto; Gallo, Claudio; Lugli, Licia; Guidotti, Isotta; Gargano, Giancarlo; Maccio, Livia; Pietrosemoli, Paola; Ferrari, Fabrizio
abstract

Neonatal Herpes simplex virus (HSV) pneumonia without apparent accompanying disseminated infection is a rare condition. We describe a case of neonatal pneumonia following maternal HSV type 1 viraemia in late pregnancy. A review of the literature shows that cases of HSV presenting as pneumonia in the first week of life are the most severe form of neonatal HSV.

2015 - Genomic analysis reveals the molecular basis for capsule loss in the group B Streptococcus population [Articolo su rivista]
Rosini, Roberto; Campisi, Edmondo; De Chiara, Matteo; Tettelin, Hervé; Rinaudo, Daniela; Toniolo, Chiara; Metruccio, Matteo; Guidotti, Silvia; Skov Sørensen, Uffe B.; Kilian, Mogens; Ramirez, Mario; Janulczyk, Robert; Donati, Claudio; Grandi, Guido; Margarit, Immaculada; Melin, P.; Decheva, A.; Petrunov, B.; Kriz, P.; Berner, R.; Hufnagel, M.; Kunze, M.; Creti, R.; Baldassarri, L.; Berardi, A.; Orefici, G.; Granger, J. R.; De La Rosa Fraile, M.; Afshar, B.; Efstratiou, A.; Maione, D.; Telford, J. L.
abstract

The human and bovine bacterial pathogen Streptococcus agalactiae (Group B Streptococcus, GBS) expresses a thick polysaccharide capsule that constitutes a major virulence factor and vaccine target. GBS can be classified into ten distinct serotypes differing in the chemical composition of their capsular polysaccharide. However, non-typeable strains that do not react with anti-capsular sera are frequently isolated from colonized and infected humans and cattle. To gain a comprehensive insight into the molecular basis for the loss of capsule expression in GBS, a collection of well-characterized non-typeable strains was investigated by genome sequencing. Genome based phylogenetic analysis extended to a wide population of sequenced strains confirmed the recently observed high clonality among GBS lineages mainly containing human strains, and revealed a much higher degree of diversity in the bovine population. Remarkably, non-typeable strains were equally distributed in all lineages. A number of distinct mutations in the cps operon were identified that were apparently responsible for inactivation of capsule synthesis. The most frequent genetic alterations were point mutations leading to stop codons in the cps genes, and the main target was found to be cpsE encoding the portal glycosyl trasferase of capsule biosynthesis. Complementation of strains carrying missense mutations in cpsE with a wild-type gene restored capsule expression allowing the identification of amino acid residues essential for enzyme activity.

2015 - Group B streptococcal infections in the newborn infant and the potential value of maternal vaccination [Articolo su rivista]
Berardi, Alberto; Cattelani, Chiara; Creti, Roberta; Berner, Reinhard; Pietrangiolillo, Zaira; Margarit, Immaculada; Maione, Domenico; Ferrari, Fabrizio
abstract

Group B Streptococcus (GBS) is a leading cause of neonatal bacterial infections in developed countries. Early-onset disease (EOD) occurs at day 0-6 and late-onset disease occurs at day 7-89. Currently, the prevention of EOD relies upon intrapartum antibiotic prophylaxis (IAP) given to women who are GBS positive at prenatal screening or women with risk factors for EOD. Although successfully implemented, IAP has not fully eradicated EOD, and incidence rates of late-onset disease remain unchanged. Furthermore, antibiotic resistance may result from widespread antibiotic use. New prophylactic strategies are therefore of critical importance. A vaccine active against GBS, administered during pregnancy and combined with targeted IAP, could overcome these problems and reduce the mortality and morbidity associated with invasive diseases.

2015 - Intrapartum GBS screening and antibiotic prophylaxis: A European consensus conference [Articolo su rivista]
Di Renzo, G. C.; Melin, P.; Berardi, A.; Blennow, M.; Carbonell-Estrany, X.; Donzelli, G. P.; Hakansson, S.; Hod, M.; Hughes, R.; Kurtzer, M.; Poyart, C.; Shinwell, E.; Stray-Pedersen, B.; Wielgos, M.; El Helali, N.
abstract

Group B streptococcus (GBS) remains worldwide a leading cause of severe neonatal disease. Since the end of the 1990s, various strategies for prevention of the early onset neonatal disease have been implemented and have evolved. When a universal antenatal GBS screening-based strategy is used to identify women who are given an intrapartum antimicrobial prophylaxis, a substantial reduction of incidence up to 80% has been reported in the USA as in other countries including European countries. However recommendations are still a matter of debate due to challenges and controversies on how best to identify candidates for prophylaxis and to drawbacks of intrapartum administration of antibiotics. In Europe, some countries recommend either antenatal GBS screening or risk-based strategies, or any combination, and others do not have national or any other kind of guidelines for prevention of GBS perinatal disease. Furthermore, accurate population-based data of incidence of GBS neonatal disease are not available in some countries and hamper good effectiveness evaluation of prevention strategies. To facilitate a consensus towards European guidelines for the management of pregnant women in labor and during pregnancy for the prevention of GBS perinatal disease, a conference was organized in 2013 with a group of experts in neonatology, gynecology-obstetrics and clinical microbiology coming from European representative countries. The group reviewed available data, identified areas where results were suboptimal, where revised procedures and new technologies could improve current practices for prevention of perinatal GBS disease. The key decision issued after the conference is to recommend intrapartum antimicrobial prophylaxis based on a universal intrapartum GBS screening strategy using a rapid real time testing.

2015 - Intrapartum antibiotic prophylaxis for Group B Streptococcus and risks of unnecessary antibiotics [Articolo su rivista]
Berardi, Alberto; Ferrari, Fabrizio; Facchinetti, Fabio
abstract

We much appreciated the Clinical Opinion by Turrentine1 regarding intrapartum antibiotic prophylaxis (IAP) for the prevention of neonatal group B Streptococcus (GBS) early-onset sepsis. The author raises concerns about cases of inadequate duration (<4 hours) of IAP before delivery. Indeed, as much as 25-40% of GBS-colonized women will not receive the 4 hours of IAP that are recommended by guidelines. To optimize fetal exposure, Turrentine recommends strategies such as (1) to postpone artificial rupture of membranes (or administration of oxytocin) until 4 hours IAP is completed and (2) to start IAP before the initiation of uterotonic agents in women who are admitted for induction of labor. Although the first step is feasible, a woman with a Bishop score <5 may be exposed to several antibiotic doses until delivery. The minimum duration of IAP for the prevention of early-onset GBS sepsis remains uncertain, because existing data are conflicting. There is evidence that bactericidal levels of β-lactam antibiotics in fetal blood are achieved as early as 3 minutes and that levels that exceed 10- to 179-fold of the minimal inhibitory concentration for GBS persist for up to 2 hours. Although neonatal colonization (NC) is only a proxy marker of infection, the study of NC gives useful information regarding the effects of IAP within the amniotic fluid. We demonstrated that intravenous ampicillin that is given <2 hours before delivery is very effective in reducing NC.2 More recently, we evaluated NC in a larger prospective cohort study. Almost 40% of 44 neonates without IAP exposure get colonized at 24-48 hours of birth, whereas rates of NC were low (between 9.3% and 0) in the 458 neonates who were exposed to IAP.3 Interestingly, rates of NC did not vary significantly in the range of <1–12 h before delivery (score test for trend of odds; P = .13). No cases of NC were found after 12 hours of IAP. Both studies provide strong evidence of a rapid action of ampicillin within the amniotic fluid, although they do not provide firm evidence regarding the time necessary to ensure the effectiveness. Although the labor process is capricious, delivery is largely a slow, rather than a fast, event (unfortunately for women and their caregivers!). Therefore, we raise concerns regarding intrapartum management strategies that perhaps allow some neonatal benefit, while exposing a greater number of women to unnecessary antibiotics, which is a probable harmful consequence to public health.4

2015 - Safety of physical examination alone for managing well-appearing neonates ≥35 weeks gestation at risk for early-onset sepsis [Articolo su rivista]
Berardi, Alberto; Fornaciari, Sara; Rossi, Cecilia; Patianna, Viviana; Bacchi Reggiani, Maria Letizia; Ferrari, Filippo; Neri, Isabella; Ferrari, Fabrizio
abstract

Objective: The published data to support recommendations for prevention and management of well-appearing at-risk newborns (WAARNs) for early-onset sepsis (EOS) are limited.Methods: Retrospective cohort study comparing two different strategies for managing WAARNs (≥35 weeks gestation) during a 6-year period (Period 1, from 2005 to 2007; Period 2, from 2009 to 2011). WAARNs were defined as healthy-appearing neonates evaluated because of risk factors for EOS. Laboratory evaluation plus simplified physical examination (Period 1) was compared with physical examination alone (PEA, Period 2). The use of antibiotics, the length of stay, the timeliness of diagnosis and the risk of falling ill immediately after hospital discharge in both periods were also compared.Results: WAARNs receiving empirical antibiotics were 14/500 (Period 1) and 3/500 (Period 2, p = 0.01). Median length of stay was 4 (Period 1) and 3 days (Period 2, p = 0.04). Symptoms of EOS were earlier than laboratory evaluation results in 42/44 neonates. Severe disease was diagnosed within 6 h of life in all neonates. No WAARNs presented with EOS following hospital discharge.Conclusions: WAARNs managed through PEA received less unnecessary antibiotics and had a shorter length of stay. They had no increased risk of severe complications or increased risk of becoming ill following hospital discharge.

2014 - Acidic pH strongly enhances in vitro biofilm formation by a subset of hypervirulent ST-17 Streptococcus agalactiae strains [Articolo su rivista]
D'Urzo, Nunzia; Martinelli, Manuele; Pezzicoli, Alfredo; De Cesare, Virginia; Pinto, Vittoria; Margarit, Immaculada; Telford, John Laird; Maione, Domenico; Melin, P.; Decheva, A.; Petrunov, B.; Kriz, P.; Berner, R.; Büchele, A.; Hufnagel, M.; Kunze, M.; Creti, R.; Badassari, L.; Berardi, A.; Orefici, G.; Granger, J. R.; De La Rosa Fraile, M.; Afshar, B.; Efstratiou, A.
abstract

Streptococcus agalactiae, also known as group B Streptococcus (GBS), is a primary colonizer of the anogenital mucosa of up to 40% of healthy women and an important cause of invasive neonatal infections worldwide. Among the 10 known capsular serotypes, GBS type III accounts for 30 to 76% of the cases of neonatal meningitis. In recent years, the ability of GBS to form biofilm attracted attention for its possible role in fitness and virulence. Here, a new in vitro biofilm formation protocol was developed to guarantee more stringent conditions, to better discriminate between strong-, low-, and non-biofilm-forming strains, and to facilitate interpretation of data. This protocol was used to screen the biofilm-forming abilities of 366 GBS clinical isolates from pregnant women and from neonatal infections of different serotypes in relation to medium composition and pH. The results identified a subset of isolates of serotypes III and V that formed strong biofilms under acidic conditions. Importantly, the best biofilm formers belonged to serotype III hypervirulent clone ST-17. Moreover, the abilities of proteinase K to strongly inhibit biofilm formation and to disaggregate mature biofilms suggested that proteins play an essential role in promoting GBS biofilm initiation and contribute to biofilm structural stability. © 2014, American Society for Microbiology.

2014 - Factors associated with intrapartum transmission of group B Streptococcus [Articolo su rivista]
Berardi, Alberto; Rossi, Cecilia; Guidotti, Isotta; Vellani, Giulia; Lugli, Licia; Bacchi Reggiani, Maria Letizia; Ferrari, Filippo; Facchinetti, Fabio; Ferrari, Fabrizio
abstract

Data regarding the minimum duration of intrapartum antibiotic prophylaxis (IAP) required for preventing group B Streptococcus (GBS) early-onset sepsis are conflicting. Understanding factors that influence neonatal colonization (NC) might help us understand factors associated with failure of prophylaxis.

2014 - Group B streptococci in milk and neonatal colonisation [Articolo su rivista]
Berardi, Alberto; Rossi, Cecilia; Guidotti, Isotta; Zucchini, Andrea; De Carlo, Luigi; Ferrari, Fabrizio
abstract

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2014 - Infezione neonatale da herpes simplex virus. Medico e Bambino [Articolo su rivista]
Spezia, Elisabetta; Guidotti, I; Fornaciari, S; Rossi, C; Ferrarif, ; Berardi, A
abstract

non specificato

2014 - Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline [Articolo su rivista]
Da Cunha, Violette; Davies, Mark R.; Douarre, Pierre-Emmanuel; Rosinski-Chupin, Isabelle; Margarit, Immaculada; Spinali, Sebastien; Perkins, Tim; Lechat, Pierre; Dmytruk, Nicolas; Sauvage, Elisabeth; Ma, Laurence; Romi, Benedetta; Tichit, Magali; Lopez-Sanchez, Maria-José; Descorps-Declere, Stéphane; Souche, Erika; Buchrieser, Carmen; Trieu-Cuot, Patrick; Moszer, Ivan; Clermont, Dominique; Maione, Domenico; Bouchier, Christiane; Mcmillan, David J.; Parkhill, Julian; Telford, John L.; Dougan, Gordan; Walker, Mark J.; Holden, Matthew T. G.; Poyart, Claire; Glaser, Philippe; Melin, Pierette; Decheva, Antoaneta; Petrunov, Bogdan; Kriz, Paula; Berner, Reinhard; Buchele, Anna; Hufnagel, Markus; Kunze, Mirjam; Creti, Roberta; Baldassarri, Lucilla; Orefici, Graziella; Berardi, Alberto; Granger, Javier Rodriguez; Fraile, Manuel De La Rosa; Afshar, Baharak; Efstratiou, Androulla
abstract

Streptococcus agalactiae (Group B Streptococcus, GBS) is a commensal of the digestive and genitourinary tracts of humans that emerged as the leading cause of bacterial neonatal infections in Europe and North America during the 1960s. Due to the lack of epidemiological and genomic data, the reasons for this emergence are unknown. Here we show by comparative genome analysis and phylogenetic reconstruction of 229 isolates that the rise of human GBS infections corresponds to the selection and worldwide dissemination of only a few clones. The parallel expansion of the clones is preceded by the insertion of integrative and conjugative elements conferring tetracycline resistance (TcR). Thus, we propose that the use of tetracycline from 1948 onwards led in humans to the complete replacement of a diverse GBS population by only few TcR clones particularly well adapted to their host, causing the observed emergence of GBS diseases in neonates. © 2014 Macmillan Publishers Limited. All rights reserved.

2013 - Characteristics of neonatal GBS disease during a multicentre study (2007-2010) and in the year 2012 [Articolo su rivista]
Creti, R; Berardi, A; Baldassarri, L; Imperi, M; Pataracchia, M; Alfarone, G; Recchia, S
abstract

iNTRODUCTION: The characteristics of Group B Streptococcal (GBS) early onset (EOD) and late onset (LOD) neonatal infections in Italy were analyzed. Two periods were considered, a first 3-years period (2007-2010), when notification of GBS infections was enforced under the auspices of the Italian Ministry of Health, and a second 1 year period (2012) when reporting on neonatal GBS disease continued on voluntary basis. METHODS: A standardized form was used to collect data on cases of neonatal GBS disease. They included both maternal and neonatal data. RESULTS AND DISCUSSION: The two surveys underlined that preterm deliveries, precipitous labor and negatively GBS screened mothers are common causes of EOD occurrence, possibly explained by inadequate, or lack of, intrapartum antibiotic prophylaxis. Nevertheless, measures for reducing prevention failures and EOD incidence by an higher adherence to prevention strategies, as the Centre for Disease Control recommendations, are still possible and should be encouraged.

2013 - Group B Streptococcal colonization in 160 mother-baby pairs: A prospective cohort study [Articolo su rivista]
Berardi, Alberto; Rossi, Cecilia; Creti, Roberta; China, Mariachiara; Gherardi, Giovanni; Venturelli, Claudia; Rumpianesi, Fabio; Ferrari, Fabrizio
abstract

Methods. aEuro integral In prospective, cohort study, 167 infants born to 167 GBS culture-positive mothers without additional risk factors were enrolled. Cultures were collected both, at 10--24 h after birth (admission) and at discharge. Results. aEuro integral Among 137 infants born to mothers who received inadequate prophylaxis, 5 (3.6%%, C.I. == 0.5--6.8) were colonized (>= a parts per thousand yen1 sites) at admission, at discharge, or both, at admission and discharge. Eighty-two women received prophylaxis < 2 h before delivery and two infants (2.4%%) were colonized at discharge. Eighteen (60.0%%, C.I. == 42.5--77.5) of 30 infants who were not exposed to prophylaxis were colonized at admission or both, at admission and discharge. Colonization was significantly more frequent among infants born to untreated mothers with respect to infants born to women who received inadequate prophylaxis (either < 2 or < 4 h). Conclusions. aEuro integral In this selected group, inadequate prophylaxis significantly interrupted vertical colonization. This effect was evident even if prophylaxis started < 2 h before delivery.

2013 - Group B streptococcus late-onset disease and milk transmission [Articolo su rivista]
Berardi, Alberto; Rossi, Cecilia; Guidotti, Isotta; Vagnarelli, Federica; Ferrari, Fabrizio
abstract

.

2013 - Group b streptococcus late-onset disease: 2003-2010 [Articolo su rivista]
Berardi, Alberto; Rossi, Cecilia; Lugli, Licia; Creti, Roberta; Reggiani, Maria Letizia Bacchi; Lanari, Marcello; Memo, Luigi; Pedna, Maria Federica; Venturelli, Claudia; Perrone, Enrica; Ciccia, Matilde; Tridapalli, Elisabetta; Piepoli, Marina; Contiero, Raffaella; Ferrari, Fabrizio
abstract

BACKGROUND: There is insufficient population-based data on group B streptococcus (GBS) late-onset disease (LOD). Risk factors and routes of GBS transmission are poorly understood. METHODS: A prospective, cohort study was conducted to collect incidence data on LOD and evaluate GBS infections over an 8-year period (2003-2010). Starting from January 2007, maternal rectovaginal and breast milk cultures were routinely collected on confirmation of the LOD diagnosis to assess maternal GBS culture status. RESULTS: The incidence rate of LOD was 0.32 per 1000 live births (1.4 and 0.24 per 1000 live births for preterm and term newborns, respectively). The registered cases of LOD (n = 100) were classified as sepsis (n = 57), meningitis (n = 36), or focal infection (n = 7). Thirty neonates were preterm (2 had recurrent infection); 68 were term. Four infants died (3 early preterm, 1 term). At the time the LOD diagnosis was confirmed, 3 (6%) of 53 mothers had GBS mastitis, and 30 (64%) of 47 carried GBS at the rectovaginal site. Early (7-30 days) LOD presentation was associated with neonatal brain lesions or death (odds ratio: 0.96 [95% confidence interval: 0.93-0.99]). Intrapartum antibiotic exposure was significantly associated with mild (12 of 22) rather than severe (11 of 45; P = .03) LOD. CONCLUSIONS: Preterm neonates had the highest rates of LOD and mortality. Most mothers carried GBS at the time of the LOD diagnosis, whereas 6% had mastitis. Intrapartum antibiotics were associated both with delayed presentation of symptoms and milder LOD. Pediatrics 2013;131:e361-e368

2013 - Impact of perinatal practices for early-onset group b streptococcal disease prevention [Articolo su rivista]
Berardi, Alberto; Lugli, Licia; Rossi, Cecilia; Guidotti, Isotta; Lanari, Marcello; Creti, Roberta; Perrone, Enrica; Biasini, Augusto; Sandri, Fabrizio; Volta, Alessandro; China, Mariachiara; Sabatini, Laura; Baldassarri, Lucilla; Vagnarelli, Federica; Ferrari, Fabrizio
abstract

Background:Prevention of residual cases of neonatal group B streptococcus (GBS) early-onset disease (EOGBS) has become a goal in the past decade. This study is aimed at evaluating changes in the incidence of EOGBS over a 9-year period after the implementation of a screening-based approach and comparing 2 different protocols for managing healthy-appearing at-risk newborns (ARNs). Methods:A screening-based strategy was introduced in Emilia-Romagna (Italy) in 2003. A prospective, cohort study was conducted from 2003 to 2011; culture-proven EOGBS cases were analyzed in 2 periods: period 1 (2003 to 2008) and period 2 (2009 to 2011). ARNs (>35 weeks’ gestation) were managed according to 2 different protocols: laboratory testing plus observation (period 1) was replaced with expectant observation alone (period 2). Results:Ninety-one EOGBS cases were observed (incidence rate: 0.26/1000 live births). The incidence in full-term babies declined from 0.30 (period 1) to 0.14/1000 live births (period 2, P = 0.04). Recto-vaginal screening cultures in full-term mothers increased significantly from 10/45 (period 1) to 10/14 (period 2, P = 0.002). EOGBS was diagnosed earlier in ARNs than in not-at-risk newborns (mean age 5.5 versus 14.5 hours, P = 0.007). There were no differences in age at diagnosis irrespective of whether ARNs were managed with laboratory testing plus observation (mean 3.5 hours, period 1) or with expectant observation alone (mean 2.4 hours, period 2). Conclusions:When screening cultures were handled according to standard protocols, cases of EOGBS in full-term newborns simultaneously decreased. ARNs were diagnosed in a timely manner through both strategies. The clinical yield of laboratory testing was negligible. © 2013 Lippincott Williams & Wilkins, Inc.

2013 - La gestione del nato a rischio di infezione precoce [Articolo su rivista]
Berardi, A; Guidotti, I; Vellani, G; Rossi, C; Lugli, L; Creti, R; Fornaciari, S; Patianna, V; Ferrari, F
abstract

The management of neonates at risk of early-onset sepsis is a challenge. In the last years, the approach has been based on laboratory tests that have been proven to be low predictive. Recent Italian data suggest that a less invasive approach, based on careful physical examination, may replace testing. Starting from 2009 in Emilia Romagna (Italy) asymptomatic neonates at risk of early-onset sepsis do not undergo sepsis workup. Clinicians and nurses in turn fill in and sign a standardized form (detailing general wellbeing, skin colour including perfusion, and the presence of respiratory signs) at close intervals. At-risk neonates are diagnosed in a timely manner through this strategy.

2012 - Congenital syphilis in Italy: A multicentre study [Articolo su rivista]
Tridapalli, E.; Capretti, M. G.; Reggiani, M. L. B.; Stronati, M.; Faldella, G.; Auriti, C.; Balata, A.; Barera, G.; Bennato, E.; Berardi, A.; Bolognesi, S.; Bonomi, A.; Boulos, F.; Brambilla, C.; Branchi, M.; Cabiati, G.; Caddia, V.; Calzetti, G.; Campanile, A.; Cataldo, P.; Cavagna, R.; Chiarolini, A.; Ciccia, M.; Ciccotti, R.; Ciofalo, A.; Contiero, R.; Corona, G.; Corso, G.; Costa, L.; Coviello, C.; Cristofori, G.; Crivellaro, C.; Cucchi, G.; Danese, G.; Da Riol, R.; Decembrino, L.; Delogu, A.; Del Vecchio, A.; Da Riol, R.; De Sanctis, L.; Di Chiara, G.; Di Comite, A.; Di Grande, E. C.; D'Onofrio, A. M.; Faccia, P.; Ferrari, D.; Fortunati, P.; Gabriella, T. L.; Galimberti, D.; Garzia, P.; Giorgino, M.; Gragnani, S.; Gurrido, R.; Lacaita, G.; Leone, G.; Lipari, A.; Lorenzini, C.; Lo Sciotto, P.; Malagutti, L.; Maschio, F.; Matteucci, L.; Migliozzi, L.; Mileti, F.; Murgia, M. R.; Navone, M.; Nosari, N.; Notarmuzi, M. L.; Pagliani, L.; Paino, D.; Papa, I.; Papili, F.; Parisi, G.; Perocchi, F.; Perona, A.; Pirrami, R.; Pitassi, I.; Priore, ; Raponi, S.; Rizzo, V.; Robieux, I.; Rossi, A.; Ruffini, E.; Russo, R.; Salvi, G.; Serra, L.; Sferlazzo, S.; Solimano, T.; Spadaro, V.; Stramare, D.; Stroppiana, P.; Tarquini, E.; Taurino, L.; Tedoldi, S.; Tessariol, D.; Travaglio, M. D.; Vagnarelli, F.; Valente, A.; Valentini, P.; Volta, A.; Zaffaroni, M.
abstract

Objective: To study the prevalence of congenital syphilis and its risk factors in Italy. Study design: Prospective study from 1 July 2006 to 30 June 2007. Data on mother-child pairs were collected for every syphilis seropositive mother. Results: Maternal syphilis seroprevalence at delivery was 0.17%. 207 infants were born to 203 syphilis seropositive mothers. In 25 newborns it was possible to diagnose congenital syphilis (20/100 000 live births). Maternal risk factors included age <20 years, no antenatal care and no adequate treatment. The infected babies were more often preterm or weighed <2000 g at birth. Discussion: Many syphilis seropositive mothers were foreign born but the risk of an infected newborn was not higher in foreign-born than in Italian seropositive women. The significant factors were lack of antenatal screening and inadequate maternal treatment. Conclusion: Syphilis is a re-emerging infection in Italy. Prevention strategies should include antenatal serological tests for all pregnant women and treatment for infected mothers.

2012 - Prevention of group B streptococcal neonatal disease revisited. the DEVANI European project [Articolo su rivista]
Rodriguez-Granger, J.; Alvargonzalez, J. C.; Berardi, A.; Berner, R.; Kunze, M.; Hufnagel, M.; Melin, P.; Decheva, A.; Orefici, G.; Poyart, C.; Telford, J.; Efstratiou, A.; Killian, M.; Krizova, P.; Baldassarri, L.; Spellerberg, B.; Puertas, A.; Rosa-Fraile, M.
abstract

The purpose of this paper was to present the current knowledge on the prevention of group B streptococcus (GBS) neonatal infections and the status of prevention policies in European countries and to present the DEVANI pan- European program, launched in 2008. The aim of this program was to assess the GBS neonatal infection burden in Europe, to design a new vaccine to immunize neonates against GBS infections, to improve the laboratory performance for the diagnosis of GBS colonization and infection, and to improve the methods for the typing of GBS strains. The current guidelines for GBS prevention in different countries were ascertained and a picture of the burden before and after the instauration of prevention policies has been drawn. After the issue of the Centers for Disease Control and Prevention (CDC) guidelines, many European countries have adopted universal screening for the GBS colonization of pregnant women and intrapartum prophylaxis to colonized mothers. Nevertheless, some European countries continue advocating the risk factor approach to GBS prevention. Most European countries have implemented policies to prevent GBS neonatal infections and the burden of the disease has decreased during the last several years. Nevertheless, further steps are necessary in order to develop new strategies of prevention, to improve microbiological techniques to detect GBS colonization and infection, and to coordinate the prevention policies in the EU. © Springer-Verlag 2012.

2011 - Efficacy of intrapartum chemoprophylaxis less than 4 hours duration. [Articolo su rivista]
Berardi, A.; Rossi, C.; Biasini, A.; Minniti, S.; Venturelli, C.; Ferrari, Fabrizio; Facchinetti, Fabio
abstract

Objective. Current guidelines for prevention of group B streptococcus (GBS) early-onset infection recommend to administer antibiotic during labor at least 4 h prior to delivery (adequate prophylaxis). We aimed to determine if neonatal GBS colonization may be significantly decreased in case of inadequate (<4 h) duration of ampicillin prophylaxis.Methods. In prospective, cohort study, 167 infants born to 167 GBS culture-positive mothers without additional risk factors were enrolled. Cultures were collected both, at 10–24 h after birth (admission) and at discharge.Results. Among 137 infants born to mothers who received inadequate prophylaxis, 5 (3.6%, C.I. = 0.5–6.8) were colonized (≥1 sites) at admission, at discharge, or both, at admission and discharge. Eighty-two women received prophylaxis <2 h before delivery and two infants (2.4%) were colonized at discharge.Eighteen (60.0%, C.I. = 42.5–77.5) of 30 infants who were not exposed to prophylaxis were colonized at admission or both, at admission and discharge.Colonization was significantly more frequent among infants born to untreated mothers with respect to infants born to women who received inadequate prophylaxis (either <2 or <4 h).Conclusions. In this selected group, inadequate prophylaxis significantly interrupted vertical colonization. This effect was evident even if prophylaxis started <2 h before delivery.

2011 - General movements in full-term infants with perinatal asphyxia are related to Basal Ganglia and thalamic lesions. [Articolo su rivista]
Ferrari, Fabrizio; Todeschini, A; Guidotti, I; Martinez Biarge, M; Roversi, Mf; Berardi, A; Ranzi, A; Cowan, Fm; Rutherford, Ma
abstract

OBJECTIVE: To correlate the site and severity of brain lesions seen on magnetic resonance imaging (MRI) with the quality of general movements in term infants with hypoxic-ischemic encephalopathy (HIE) and compare the prognostic value of general movements and MRI for motor outcome.STUDY DESIGN: Early brain MRI scans in 34 term infants with HIE not treated with hypothermia were reviewed and scored for site of injury and lesion pattern by an experienced neuroradiologist. General movement quality and trajectories at 1 and 3 postnatal months were evaluated. Motor outcome was assessed at 24 months.RESULTS: MRI scores for the basal ganglia and thalami, posterior limb of the internal capsule, white matter, and cortex and lesion patterns were correlated with 1-month and 3-month general movements and general movement trajectories; central gray matter scores were correlated most strongly with cramped-synchronized general movements and abnormal motor outcome. MRI scores were 100% sensitive and 72.2% specific for motor outcome, and cramped-synchronized general movements were 100% specific and 68.7% sensitive for motor outcome.CONCLUSIONS: In term infants with HIE, the site and severity of brain lesions seen on early MRI are highly correlated with general movements. Central gray matter damage leads to cramped-synchronized general movements and poor motor outcome. Early MRI scans and general movements are complementary tools for predicting motor outcome.

2011 - Intrapartum antibiotic prophylaxis failure and group-B streptococcus early-onset disease [Articolo su rivista]
Berardi, Alberto; Lugli, Licia; Rossi, Cecilia; China, Mariachiara; Chiossi, Claudio; Gambini, Lucia; Guidi, Battista; Pedna, Maria Federica; Piepoli, Marina; Simoni, Angela; Ferrari, Fabrizio
abstract

Objectives. To determine factors influencing intrapartum antibiotic prophylaxis (IAP) failure in the prevention of group B streptococcus (GBS) early-onset disease (EOD).Methods. GBS EOD case is defined as isolation of GBS from a normally sterile body site (e.g. blood or cerebrospinal fluid) in infants aged ≤7 days. During a consecutive 93-month period, GBS EOD cases and care data were reviewed.Results. Seventy-nine GBS EOD cases were registered; 67 infants were born to women who received no i.v. antibiotics during labor. The 12 EOD cases exposed to IAP were more likely to be associated with emergency caesarean section (p = 0.0015), maternal obstetric risk factors (ORFs) (p = 0.0061), particularly intrapartum fever (p = 0.0002), and to present with signs of illness at birth (p = 0.0015). Correct dosages, agents, and timing were registered in three cases only; of which two were associated with intrapartum fever.Conclusions. ORFs, emergency caesarean section, and signs of illness at birth are significantly associated with GBS EOD in infants exposed to IAP. This study also suggests that recommended IAP agents, dosages, and timing are infrequently associated with EOD. Strict protocol adherence is recommended in all cases.

2011 - Invasive neonatal GBS infections from an area-based surveillance study in Italy [Articolo su rivista]
Imperi, M.; Gherardi, G.; Berardi, A.; Baldassarri, L.; Pataracchia, M.; Dicuonzo, G.; Orefici, G.; Creti, R.
abstract

During an area-based study, 75 group B streptococcus (GBS) strains isolated both from early-onset disease (EOD, 37 strains) and from late-onset disease (LOD, 38 strains) were analysed for serotype, pulsed field gel electrophoresis (PFGE) and multilocus sequence typing profiles, protein markers and antibiotic resistance. Serotype III, possessing the rib gene, was the most frequent (54 strains, 72%) and responsible for 89.5% and 54% of LOD and EOD, respectively. Forty-six serotype III strains belonged to the same PFGE type and clonal complex 17, already described as an over-represented clone in neonatal invasive GBS infections. Other serotypes were Ia (9.3%), II (6.7%), Ib (5.3%), V (5.3%) and IV (1.3%). Seventeen PFGE groups were identified comprising strains with related sequence types; conversely, strains displaying the same sequence type could belong to different PFGE groups. When both neonate and maternal strains from vaginorectal swabs and/or milk were available (eight cases), they were indistinguishable. Resistance to erythromycin (12%) was associated with a constitutive resistance to clindamycin in five cases (four carrying the erm(B) gene and one both the erm(B) and mef(E) genes) and with an inducible clindamycin resistance in two cases (one possessing the erm(A) gene, the other the erm(T) gene). Two isolates displayed the M phenotype (mef(E) gene). All strains but five were resistant to tetracycline, mostly mediated by the tet(M) gene (97.1%). The study underlined the importance of an active surveillance system for the elucidation of a GBS population structure causing neonatal infections and allowed the detection of rare antibiotic resistance determinants [erm(T)]. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

2011 - La rete di sorveglianza delle infezioni da streptococco beta-emolitico di gruppo B in Emilia Romagna [Relazione in Atti di Convegno]
Berardi, A; Lugli, L; Rossi, C; Fornaciari, S; China, M; Creti, R; Baldassarri, L; Venturelli, C; Pedna, Mf; Ciccia, M; Di Carlo, C; Pedori, S; Serra, L; Sabatini, L; ., Rossi MR; Ferrari, F; Bidetti, M; Ferrari, F
abstract

NESSUN ABSTRACT

2011 - Neonatal herpes simplex virus. [Articolo su rivista]
Berardi, A.; Lugli, L.; Rossi, C.; Maria, C. L.; Guidotti, Isotta; Gallo, C.; Ferrari, Fabrizio
abstract

Herpes simplex virus is an important cause of neonatal infection, which can lead to death or long-term disabilities. Rarely in utero, the transmission frequently occurs during delivery. The disease may be disseminated, localized to the central nervous system, or involving skin, eye and/or mouth. Mortality rates markedly decreased with high-dose antiviral treatment. Diagnosis of neonatal infection is based on viral isolation from ulcerated vesicles or by scarifying mucocutaneous lesions. Recently polymerase chain reaction plays a central role for both viral detection (skin, mucosal, cerebrospinal fluid samples) and response to therapy. Vertical transmission may be decreased by prophylactic antiviral treatment.

2011 - Severe acquired cytomegalovirus infection in a full-term, formula-fed infant: Case Report [Articolo su rivista]
Berardi, Alberto; Rossi, Cecilia; Fiorini, Valentina; Rivi, Cristina; Vagnarelli, Federica; Guaraldi, Nicola; Pietrosemoli, Paola; Lazzarotto, Tiziana; Ferrari, Fabrizio
abstract

Background: Cases of cytomegalovirus colitis are exceptionally reported in immuno-competent infant. The pathogenesis is uncertain but breast-feeding is considered as a main source of postnatal infection.Case Presentation: Here we report a full-term, formula-fed infant who developed a severe cytomegalovirus anaemia and colitis when aged 2 months.Conclusion: Even if the molecular identity between the cytomegalovirus-isolate of the infant and the maternal virus could not be demonstrated, we confirmed through laboratory investigation that cytomegalovirus infection was acquired postnatally. However, the source of cytomegalovirus infection remained unclear. Alternative modes of cytomegalovirus transmission are discussed. © 2011 Berardi et al; licensee BioMed Central Ltd.

2011 - Universal antenatal screening for group B streptococcus in Emilia-Romagna [Articolo su rivista]
Berardi, A.; Fazzio, G. D.; Gavioli, Sara; Di Grande, E.; Groppi, A.; Papa, I.; Piccinini, G.; Simoni, A.; Tridapalli, E.; Volta, A.; Facchinetti, Fabio; Ferrari, Fabrizio
abstract

Background: Group B streptococcus (GBS) is a leading cause of severe infections in newborns. Intrapartum antibiotic chemoprophylaxis (IAP) reduces the rate of early-onset disease. The aim of this study is to determine the degree of clinicians’ compliance with the suggested protocol for GBS prevention in Emilia-Romagna (Italy). Methods: Characteristics of each delivery were prospectively recorded in the period between October 2005 to December 2005. Standardized pro-forma were used to collect data. Results: Among 5118 babies, 7.2% (369) were preterm and 92.3% were born at term (4749). Antenatal screening was performed in 86.6% of women who delivered at term, of which 18.1% were GBS culture-positive. Information regarding culture site was available in 93.2% of women screened and recto-vaginal cultures were documented in 42.7%. IAP was administered to 28.7% of 3937 women at term who had either spontaneous delivery or emergency caesarean section. In this cohort, 15.9% were diagnosed GBS culture-positive, of which 92.6% received IAP. Prophylaxis was also administered to 8.4% (331) of women for no apparent reason. Compared with tertiary level hospitals, women delivering in primary/secondary hospitals were more likely to be both GBS screened (P < 0.0001; OR 3.04; CI 2.33–3.97) and to receive prophylaxis ≥4 hours before delivery (P = 0.0025; OR 1.57; CI 1.17–2.12). Conclusions: GBS screening was performed in >85% of women and >90% of culture-positive women received prophylaxis. However, there is a need to educate clinicians about protocol adherence, as most cultures were suboptimal and cases of unnecessary IAP were administered. The screening was more effective in hospitals with fewer deliveries.

2010 - Group B Streptococcus early-onset disease in Emilia-romagna: review after introduction of a screening-based approach. [Articolo su rivista]
Berardi, A; Lugli, L; Baronciani, D; Rossi, C; Ciccia, M; Creti, R; Gambini, L; Mariani, S; Papa, I; Tridapalli, E; Vagnarelli, F; Ferrari, Fabrizio; GBS Prevention Working Group of Emilia, Romagna
abstract

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of neonatal bacterial infections. Early-onset infections have decreased in recent years but, despite considerable efforts poured into prevention, cases continue to occur.OBJECTIVES: To analyze trends and identify determining factors for the persistence of the GBS infections. To evaluate the impact of antenatal screening and intrapartum chemoprophylaxis on the clinical presentation of the infection.METHODS: A prospective cohort, population-based study has been ongoing in Emilia-Romagna (Italy) since 2003. Invasive GBS infections, observed between 2003 and 2008 in infants aged < 7 days were analyzed.RESULTS: Among 214,120 live births, 61 early-infections were observed. Fourteen infants (23.0%) were born preterm. Among 47 infants who were delivered at term, 28 were born to mothers who had no risk factors and 7 were born to mothers who had none other than GBS colonization. Forty-one women at term had been screened prenatally; among them, only 10 were documented as GBS culture-positive.Disease severity was highest in infants at lower gestational ages, but most meningitis cases were observed in term infants born to mothers who were GBS culture-negative at screening.Nine newborns had culture-proven infection despite having received intrapartum antibiotics. They were born to mothers with > or =1 obstetrical risk factors and 5 mothers had been treated during labor with macrolides.CONCLUSION: Most infections presented in infants whose mothers had been screened as GBS culture-negative. Missed opportunities for prevention contributed more than prophylaxis failures to the early-onset disease burden.

2010 - L-arginine supplementation in women with chronic hypertension: impact on blood pressure and maternal and neonatal complications. [Articolo su rivista]
Neri, Isabella; Monari, Francesca; Sgarbi, L.; Berardi, A.; Masellis, G.; Facchinetti, Fabio
abstract

To evaluate L-arginine (L-Arg) supplementation in pregnant women with chronic hypertension and its effects on blood pressure (BP) and maternal and neonatal complications.We enrolled 80 women affected by mild chronic hypertension referred to the High Risk Clinic of the Mother-Infant Department of the University of Modena and Reggio Emilia. Each woman after obtaining oral consent was randomized to receive oral L-Arg versus placebo and thereafter submitted to 24-h ambulatory BP monitoring. The primary outcome was BP change after 10-12 weeks of treatment. Secondary outcomes were as follows: percentage of women on antihypertensive treatment at delivery, maternal, and fetal outcome.The BP changes after 10-12 weeks of treatment did not differ between groups. A lower percentage of women received antihypertensive drugs in the L-Arg group than the placebo group. The incidence of superimposed preeclampsia indicated delivery before the 34th weeks and certain neonatal complications tended to be higher in the placebo group.L-Arg supplementation in pregnant women with mild chronic hypertension does not significantly affect overall BP but is associated with less need for antihypertensive medications and a trend toward fewer maternal and neonatal complications. The results of the study were limited by the small sample size and by the exclusion of women with severe chronic hypertension. In our policy, these patients needed many hypertensive drugs and were normally managed by the cardiologist. Nevertheless, considering the promising results on maternal and fetal outcome, we believe that further studies should be performed to confirm such data and to clarify the role of L-Arg as a protective supplement in high-risk pregnancy.

2010 - Neonatal bacterial meningitis. [Articolo su rivista]
Berardi, A; Lugli, L; Rossi, C; China, Mc; Vellani, G; Contiero, R; Calanca, F; Camerlo, F; Casula, F; Di Carlo, C; Rossi, Mr; Chiarabini, R; Ferrari, M; Minniti, S; Venturelli, C; Silvestrini, D; Dodi, I; Zucchini, A; Ferrari, Fabrizio; Infezioni da Streptococco B., Della Regione Emilia Romagna
abstract

Neonatal bacterial meningitis (NM) continues to be a serious disease with an unchanging rate of adverse outcome of 20-60%, despite a worldwide decline in mortality. The 3 major pathogens in developed countries are: Group B streptococcus, gram negative rods and Lysteria monocytogenes. Signs and symptoms of NM may be subtle, unspecific, vague, atypical or absent. In order to exclude NM, all infants with proven or suspected sepsis should undergo lumbar puncture. Positive culture of cerebrospinal fluid may be the only way to diagnose NM and to identify the pathogen, as CSF parameters Smay be normal at early stages and NM may occur frequently (up to 30% of cases) in the absence of bacteraemia. When NM is suspected, treatment must be aggressive, as the goal is to achieve bactericidal concentration of antibiotics and to sterilize CSF as soon as possible. Antibiotics should be administered intravenously, at the highest clinically validated doses. Empiric antibiotic treatment should include agents active against all main pathogens; currently the recommended empiric treatment of NM is ampicillin, plus an aminoglycoside and a third-generation cephalosporn. Therapy should be reassessed after cultures and antibiotic susceptibility is available. Prevention of neonatal sepsis, early recognition of infants at risk, prompt treatment and future adjunctive therapies will improve prognosis. Finally, we present the first preliminary Italian data on GBS meningitis. Data are obtained from an area-based study conducted In Emilia-Romagna during 2003 to 2009.

2010 - The network of surveillance of infections streptococcal B in Emilia-Romagna: Prevention of early infections [La rete di sorveglianza delle infezioni da Streptococco B nella Regione Emilia-Romagna: Prevenzione delle infezioni precoci] [Articolo su rivista]
Berardi, A.; Lugli, L.; Rossi, C.; Bidetti, M. L.; Calanca, F.; Casula, F.; China, M.; Chiossi, C.; Fazio, G. D.; Galuppi, E.; Gavioli, S.; Pedna, M. F.; Piepoli, M.; Ricci, L.; Sarti, M.; Simoni, A.; Ferrari, M.; Ferrari, Fabrizio
abstract

Prospective area based study of group B Streptococcus infections Background Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis in newborns Intrapartum administration of antibiotics to GBS colonized mothers reduces the rate of early-onset disease. Objectives To promote a common prevention strategy in an Italian region, to analyze clinical findings, trends of disease incidence and factors which determine the persistence of the disease. Methods Prospective, area-based study, during a 6 years period; all delivery units and regional laboratories involved in the study. Results A screening-based strategy was adopted by centres. The incidence of earlyonset disease was low with respect to European countries; most of residual cases were associated with the culture detection failure of organisms at 35-37 weeks of gestation. Meningitis was much more common among infants with late-onset disease. Both, early- and late-onset infections had no significant variations of disease incidence during the 6 years study period. Conclusions Prevention strategies reduced the rate and the severity of early-infections. Most residual cases were due to the culture detection failure of organisms at antenatal screening; additional efforts are therefore required to implement the strategy.

2009 - "Nest" improves movements of preterm infants ( Review ) [Il "nido" migliora il movimento del neonato pretermine] [Articolo su rivista]
Ferrari, Fabrizio; Bertoncelli, N.; Roversi, M. F.; Lugli, L.; Pugliese, M.; Berardi, A.; Gallo, C.
abstract

Fragile and unstable preterm infants are exposed in the Neonatal Intensive Care Unit (NICU) to a non-optimal physiological environment and to invasive procedures and handling, which may induce pain and stress. One of the major aims of Individualized Developmental Care is to promote age-adequate postures, thereby reducing the distressing conditions of extrauterine life of preterm infants which may have negative effects on the immature brain. The "nest", adopted by most Italian NICUs, aims at stabilising body posture and promoting movements towards the body, thus facilitating rest periods and sleep.

2009 - Diagnostica clinica ed EEG di sofferenza cerebrale nel nato a termine [Capitolo/Saggio]
Ferrari, Fabrizio; Lugli, L; Pugliese, M; Berardi, A; Ori, L; Bertoncelli, N; Gallo, C; Roversi, Mf
abstract

NO ABSTRACT

2009 - Infezione da Herpes simplex [Capitolo/Saggio]
Berardi, A; Saccani, Ilenia; Bonetti, A; Crisafi, Antonella
abstract

no abstract

2009 - Infezione da Streptococco beta-emolitico di gruppo B [Capitolo/Saggio]
Berardi, A; Rossi, C; China, Mc; Lugli, L
abstract

no abstract

2009 - Preventing bacterial infections with pilus-based vaccines: The group B streptococcus paradigm [Articolo su rivista]
Margarit, Immaculada; Rinaudo, Cira Daniela; Galeotti, Cesira L.; Maione, Domenico; Ghezzo, Claudia; Buttazzoni, Elena; Rosini, Roberto; Runci, Ylenia; Mora, Marirosa; Buccato, Scilla; Pagani, Massimiliano; Tresoldi, Eleonora; Berardi, Alberto; Creti, Roberta; Baker, Carol J.; Telford, John L.; Grandi, Guido
abstract

We recently described the presence of 3 pilus variants in the human pathogen group B streptococcus (GBS; also known as Streptococcus agalactiae), each encoded by a distinct pathogenicity island, as well as the ability of pilus components to elicit protection in mice against homologous challenge. To determine whether a vaccine containing a combination of proteins from the 3 pilus types could provide broad protection, we analyzed pili distribution and conservation in 289 clinical isolates. We found that pilus sequences in each island are conserved, all strains carried at least 1 of the 3 islands, and a combination of the 3 pilus components conferred protection against all tested GBS challenge strains. These data are the first to indicate that a vaccine exclusively constituted by pilus components can be effective in preventing infections caused by GBS, and they pave the way for the use of a similar approach against other pathogenic streptococci. © 2008 by the Infectious Diseases Society of America. All rights reserved.

2008 - Group B Streptococcus and preventive strategies in Europe [Articolo su rivista]
Berardi, A; Lugli, L; Rossi, C; Morini, Ms; Vagnarelli, F; Ferrari, Fabrizio
abstract

NO ABSTRACT

2007 - Group B streptococcal infections in a northern region of Italy. [Articolo su rivista]
Berardi, A; Lugli, L; Baronciani, D; Creti, R; Rossi, K; Ciccia, M; Gambini, L; Mariani, S; Papa, I; Serra, L; Tridapalli, E; Ferrari, Fabrizio; GBS Prevention Working Group of Emilia, Romagna
abstract

BACKGROUND:Group B streptococcus is a leading cause of neonatal bacterial infections. Despite adoption of preventive strategies, cases of infection continue to occur and there is concern that widespread antimicrobial prophylaxis might delay rather than prevent disease onset, increasing the rates of late-onset diseases.OBJECTIVES:The purpose of this study was to determine the incidence and clinical features of early- and late-onset group B streptococcus disease in a northern region of Italy where a screening-based approach had been proposed.METHODS:A population-based study was prospectively conducted in Emilia-Romagna, Italy. Infections that occurred during 2003-2005 in infants aged <3 months were analyzed.RESULTS:Among 112,933 live births, 56 cases of invasive disease (30 early- and 26 late-onset disease) were observed, giving an annual group B streptococcus disease incidence of 0.50 per 1000 live births. Eleven infants with early-onset disease showed no signs of illness or were mildly ill, whereas 19 had moderate-to-severe symptoms, and culture-proven meningitis was found in 2. Risk factors were detected in 12 women. Twenty-two mothers had antenatal screening; 5 were group B streptococcus colonized, but 17 were culture-negative. Prophylaxis was administered in 3 women. Three infants with late-onset diseases were mildly ill, whereas 23 had moderate-to-severe symptoms. Risk factors were found in 7 mothers. Late-onset diseases were clinically more severe than early-onset diseases; meningitis was diagnosed in 12 infants, and 4 of 26 died.CONCLUSIONS:The incidence of early-onset disease was low. Some early infections were still observed because of negative screening results or missed opportunity for prevention. Late-onset diseases accounted for most meningitis cases and deaths. Strict adherence to protocols and adoption of optimal culture methods would further improve prevention of early-onset disease, but the aim of future strategies should be the prevention of all invasive diseases.

2007 - Group B streptococcus: early- and late-onset infections [Articolo su rivista]
Berardi, A; Tzialla, C; Riva, M; Cerbo, R M; Creti, R
abstract

Group B streptococcus has emerged as a prominent neonatal pathogen in developed countries since the late 1960s. The incidence of disease remained fairly constant until the 1990 s, when prevention efforts increased. American consensus guidelines were endorsed in the mid 1990 s; since then a decrease in disease incidence has been reported in the United States. This review summarizes the main issues regarding the prevention of neonatal infection and presents aspects of group B streptococcal disease with the first population data recently obtained in a northern region of Italy.

2007 - Le infezioni da Streptococco B in Italia: un problema importante per la salute della donna e del bambino [Articolo su rivista]
Baldassarri, L; Creti, ; Berardi, A; Orefici, G
abstract

NO ABSTRACT

2007 - Le infezioni da Streptococco beta emolitico di gruppo B: l’esperienza dell’Emilia-Romagna. [Articolo su rivista]
Berardi, A; Lugli, L; Benaglia, G.; Cassani, C.; Chiossi, C; Cipolloni, P; Falcioni, F; Gentili, A; Mantovani, A; Paltrinieri, G; Piccinini, L; Rossi M., R; Rubbi, P; Simoni, A; Somenzi, P.
abstract

NESSUN ABSTRACT

2007 - Le infezioni da streptococco B in Emilia-Romagna: un problema sempre più pediatrico [Articolo su rivista]
Berardi, A; Lugli, L; Pagano, Rossella; Biasini, A; Calanca, Fabrizio; Dodi, I; Galuppi, E; Morini, Ms; Moro, Ml; Sarti, M; Silvestrini, Deborah; Solari, E; Somenzi, P; Tridapalli, E; Rivi, C; Riva, M; Vagnarelli, F; Ferrari, F.
abstract

Introduction: Group B streptococcus (GBS) is still a leading cause of neonatal sepsis and meningitis. It can result in death or long-term disabilities, including mental retardation and hearing or vision loss. Even if the adoption of preventive strategies significantly decreased the rate of early-onset infections, cases of GBS infection continue to occur. Methods: We determined incidence and clinical features of disease in Emilia-Romagna, a Northern region of Italy where GBS preventive strategies have been implemented. Results: The total number of live births was 12,933. Early-onset infections (EOD) were 30 (2 infants died), whereas late-onset diseases (LOD) were 26 (4 infants died), with the latter accounting for most meningitis and deaths. Risk factors were found in 12 and 7 infants with EOD and LOD respectively. 2 women. Twenty-one term mothers had antenatal screening: four were GBS colonized but 17 were culture negative. Conclusion: The incidence of EOD found in Emilia-Romagna is one of the lowest in Europe. Several early infections were still observed because of negative screening results. LODs accounted for most meningitis cases and deaths.

2007 - L’infezione da Streptococco beta emolitico di gruppo B in eta’ pediatrica. [Articolo su rivista]
Berardi, A; Lugli, L; Bottura, C; Chierici, R; Colla, R; Di Grande, E; Groppi, Alessandra; Guidi, B; Montini, G; Mordini, B; Ricci, L; Testa, G; Toniato, M; Venturelli, C; Visani, MARIA STEFANIA; Volta, A.
abstract

NO ABSTRACT

2006 - ABSENCE OF NEONATAL STREPTOCOCCAL COLONIZATION AFTER PLANNED CESAREAN SECTION [Articolo su rivista]
Berardi, A; Rossi, K; Pizzi, C; Baronciani, D; Venturelli, C; Ferrari, Fabrizio; Facchinetti, Fabio
abstract

no abstract

2006 - Apnee neonatali: aspetti neurologici [Articolo su rivista]
Ferrari, Fabrizio; Lugli, L; Guerra, Mp; Berardi, A; Roversi, Mf; Ori, L; Todeschini, A; Cavalleri, F.
abstract

No abstract avaible

2006 - Cerebellar Haemorrage in Preterm Infants: Ultrasound Study [Articolo su rivista]
Berardi, A; Lugli, L; Roversi, Mf; Galloc, ; Pugleise, M; Todeschini, A; Cavalleri, F; Mavilla, L; Ferrari, Fabrizio
abstract

No abstract

2006 - IL NEONATO IPOTONICO [Relazione in Atti di Convegno]
Ferrari, Fabrizio; Lugli, L; Roversi, Mf; Berardi, A; Pugliese, M; Todeschini, A; Cavalleri, F.
abstract

NO ABSTRACT

2006 - Kernicterus associated with hereditary spherocytosis and UGT1A1 promoter polymorphism. [Articolo su rivista]
Berardi, A; Lugli, L; Ferrari, Fabrizio; Gargano, G; D'Apolito, M; Marrone, A; Iolascon, A.
abstract

INTRODUCTION: An apparent re-emergence of kernicterus has been recently reported, with some cases occurring in otherwise healthy breastfed newborn.METHODS: We describe a case of kernicterus in a term Caucasian newborn.RESULTS: An exceptional polymorphism of UGT1A1 gene promoter co-existed with asymptomatic inherited spherocytosis, due to erythroid anion exchange (band-3) deficiency. Both concurred to the development of severe neonatal hyperbilirubinaemia.CONCLUSION: As some cases of kernikterus remain unresolved, haemolytic diseases and bilirubin metabolism disorders should be carefully investigated in unexplained severe neonatal hyperbilirubinaemia.

2006 - LA PROFILASSI DELL'INFEZIONE NEONATALE PRECOCE DA SGB: UN APPROCCIO RAGIONATO [Articolo su rivista]
Ferrari, Fabrizio; Berardi, A; Rossi, K; Bussetti, C; Mordini, B; Cattani, S; Gargano, G; Pancaldi, Me; Roversi, Mf
abstract

N/A

2006 - Reccomendation for GBS Prevention by The Italian Society of Perinatal Medicine [Articolo su rivista]
Berardi, A; Lugli, L; Rossi, K; Della Casa Muttini, E; Gallo, C; Gargano, G; Tridapalli, E; Stella, M; Ferrari, Fabrizio; Emilia Romagan GBS Prevention Working, Group
abstract

No abstract avaible

2006 - Septic shock in children [Lo shock settico in età pediatrica] [Articolo su rivista]
Berardi, A; Mariowi, I; Pagano, R; Scirpoli, F; Lugli, L; Garehi, E; Roversi, Mf; Ferrari, Fabrizio
abstract

Septic shock is still a leading cause of mortality and morbidity in children. Even if predominant in the first year of life, it can occur at all ages. Early intervention, including ABC of resuscitation, early and aggressive administration of i.v. fluids, and empirical antibiotic therapy changed its prognosis in the last years. Further improvement of septic shock outcome could be obtained in the next future by therapies that can directly modulate inflammatory responses. To increase survival, we underline the need of an early diagnosis, possibly before hospital admission.

2005 - Emorragia cerebellare isolata nel pretermine: il ruolo dell'ecografia cerebrale attraverso la fontanella mastoidea [Articolo su rivista]
Lugli, L; Mariotti, I; Berardi, A; Gallo, C; Garetti, E; Guerra, Mp; Della Casa, E; Roversi, Mf; Gargano, G; Ferrari, Fabrizio
abstract

No abstract

2005 - GBS prevention policies in a North Italian Area [Articolo su rivista]
Berardi, A; Lugli, L; Rossi, K; Della Casa Muttini, E; Gallo, C; Gargano, G; Tridapalli, E; Stella, M; Ferrari, Fabrizio; Emilia Romagan GBS Prevention Working, Group
abstract

No abstract avaible

2005 - L'INFEZIONE DA STREPTOCOCCO DI GRUPPO B IN EMILIA ROMAGNA [Articolo su rivista]
Berardi, A; Lugli, L; Rossi, K; Tridapalli, E; Stella, M; Biasini, A; Ciccia, M; Della Casa, P; Lombardi, M; Paltrinieri, Al; Papa, L; Silvestrini, D; Ferrari, Fabrizio; Gruppo Regionale per la Profilassi dell'Infezione da Streptococco, B.
abstract

NO ABSTRACT AVAIBLE

2005 - Neonatal Group B streptococcal infection in a North Italian area [Articolo su rivista]
Berardi, A; Lugli, L; Rossi, K; Tridapalli, E; Roversi, Mf; Facchinetti, Fabio; Ferrari, Fabrizio; Emilia Romagan GBS Prevention Working, Group
abstract

Background Group B streptococcus (GBS) is the leading cause of early-onset infections (EOI) in the developed world. Few data are available in Europe about incidence and clinical findings of neonatal disease. We reviewed cases occurred in the last 2 years in Emilia-Romagna (an area with about 4 500 000 million people).Methods Neonatal, pediatric departments and laboratories fulfilled a chart for any case of disease observed during 2003 and 2004. GBS was recovered in blood or cerebrospinal fluid (CSF). Prenatal screening, risk factors, intrapartum chemoprophylaxis (IAP) and clinical findings were analysed.Results: We observed 21 EOI and 13 late onset (LOI). Incidence was 0.56 and 0.38/1.000 live birth in 2003 and 2004 respectively. Mortality was 12,5% (1 EOI and 3 LOI). Among 21 EOI, 7 were bacteraemia, 12 sepsis and 2 meningitis. CSF was not collected in 8/14 symptomatic infants. Six mothers were vaginally colonized; 13/21 were negative and 2 unscreened; 5/21 had one or more risk factors. Only 2 (suspected chorioamnionitis) received a complete IAP, while 19/21 were untreated. Among 13 LOI, 3/13 mothers were colonized and 5/13 had 1 or more risk factors. LOI were: 5 sepsis, 7 meningitis and 1 focal infection. CSF was not collected in 5/13.Conclusion: Incidence of GBS infection was similar to that currently reported in US. Most EOI (90.5%) had no prophylaxis. Risk factors were detected in 23.8 % of EOI (GBS bacteriuria was not routinely screened). Meningitis was diagnosed in 33.3 % symptomatic infants, but CSF analysis was not performed in 48.1% cases. More efforts are needed to improve prophylaxis strategies.

2005 - Ohtahara Syndrome and Arthrogryposis [Articolo su rivista]
Guerra, Mp; Lugli, L; Berardi, A; Roversi, Mf; Ferrari, P; Pellicano, Fa; Ferrari, Fabrizio
abstract

No abstrct

2004 - Impact of Chronic Lung Disease on Very Low Birth Weight infants: a collaborative study of the Italian Group of Neonatal Pneumology [Articolo su rivista]
Cavazza, A; Tagliabue, P; Fedeli, T; Forziati, V; De, Vita; Auriemma, A; Teani, M; Villani, P; De Toni, A; Demaria, F; Berardi, A; Bernardo, I; Biasini, A; Pellegatta, R; Merazzi, D; Regazzoni, M; Macabruni, M; Licursi, E; Scarpelli, G; Dani, C; Donzelli, G; Cioni, Mi; Rinaldi, G; Bonacci, W; Morandi, F; Perotti, G; Bottura, C; Barberis, I; Cordaro, S; Carrera, G; Cella, D; Bianchi, C; Introvini, P; Lisata, G; Bonati, M; Campi, R; Carpentieri, M; Scarcella, A; Santantonio, A; Gancia, P; Strano, F; Cassata, N; Magnani, C; Costato, C; Pelti, M; Finocchi, M; Sorrentino, E; Zecca, E; Romagnoli, C; Bagnoli, F; Savant Levette, P; Martano, C; Visentin, S; Battajon, N
abstract

Objective. To evaluate the incidence and risk factors for chronic lung disease in a population of very low birth weight infants. Methods. In a prospective multicentric trial all very low birth weight infants (< 1500 g) accepted in 36 Italian Neonatal Intensive care units were studied from February 89 to January 99. For each patient were recorded maternal history, perinatal events, respiratory disease, infections, patent ductus arteriosus, retinopathy of prematurity, intraventricular haemorrhage and final outcome. Logistic regression analysis was performed in a multivariate assessment of risk factors for chronic lung disease. Results. In the study were included 1634 patients: 1387 infants survived beyond 36 weeks and 6.9% of them still oxygen dependent. The incidence of chronic lung disease was higher among babies with a gestational age of < 28 weeks and weight ² 1000 g. The multivariate analysis showed that low birth weight, respiratory distress syndrome, persistent ductus arteriosus and sepsis were the main risk factors. Conclusions. In our study the incidence of chronic lung disease was relatively low

2004 - L’infezione neonatale da Herpes simplex virus [Capitolo/Saggio]
Berardi, A; Della Casa, E; Lugli, L; Rossi, K; Pancaldi, Me; Cattani, S; Ferrari, F; Avanzini, A
abstract

no abstract

2004 - Maternal anaphylaxis and fetal brain damage after intrapartum chemoprophylaxis. [Articolo su rivista]
Berardi, A; Rossi, K; Cavalleri, F; Simoni, A; Aguzzoli, L; Masellis, G; Ferrari, Fabrizio
abstract

We report a case of maternal anaphylaxis following intrapartum chemoprophylaxis. The term fetus developed severe brain damage as a consequence of intrapartum asphyxia. The lesions resulted from maternal hypotension following anaphylaxis. We discuss the feto-maternal risks and the controversial treatment of such a condition. The increasing number of penicillin-treated parturients will result in further cases of maternal anaphylaxis than previously found.

2004 - Prevention of group B streptococcal infection in a North-Italian area [Articolo su rivista]
Berardi, A; Lugli, L; Rossi, K; Tridapalli, E; Facchinetti, Fabio
abstract

No abstract available

2004 - Strategie preventive dell'ifezione neonatale da Streptococco di gruppo B [Monografia/Trattato scientifico]
Berardi, A; Rossi, K; Bussetti, C; Cattani, S; Gallo, C; Gargano, G; Della Casa, E; Pancaldi, Me; Roversi, Mf; Venturelli, C; Ferrari, Fabrizio
abstract

No abstract

2004 - [Prophylaxis of group B streptococcal infections in the birth centers of Emilia Romagna]. [Articolo su rivista]
Berardi, A; Rossi, K; Lugli, L; Tridapalli, E; Ferrari, Fabrizio
abstract

OBJECTIVES:In the last decade several guidelines for prevention of neonatal group B streptococcal invasive disease have been published, mainly based on administration of intrapartum antibiotics. The spread of such recommendations yielded a reduction of the early-onset disease. The aim of the study was to investigate the practices for prophylaxis of neonatal infection in our region during the 2000 and to standardize them according to the new available evidence.METHODS:We conducted a multicenter study in Emilia Romagna, sending by mail a detailed questionnaire to the 28 birth centers of our region.RESULTS:Fifteen centers answered to the questionnaire. The practices were often differing from the recommendations of scientific societies. The most sensitive methods to identify colonized women were not widely used. Colonized infants were frequently treated with antibiotics and discharged later from the nursery. The incidence of neonatal invasive diseases was low, but most centers did not regularly collect a blood culture before antibiotic treatment is started.CONCLUSIONS:Repeated meetings among centers promoted the diffusion of information, the implementation of a shared protocol and the spread of the practices. The results of such meetings will be evalued in the next months.

2002 - CONVULSIONI NEONATALI DA ASFISSIA PERINATALE: QUALE TERAPIA? [Articolo su rivista]
Ferrari, Fabrizio; Roversi, Mf; Guerra, Mp; Pugliese, M; Bertoncelli, N; Berardi, A; Gargano, G; Cattani, S; Biagioni, O.
abstract

No abstract

2002 - DIFFUSION-WEIGHTED MRI OF MAPLE SYRUP URINE DISEASE ENCEPHALOPATHY [Articolo su rivista]
Cavalleri, F; Berardi, A; Burlina, Ab; Ferrari, F; Mavilla, L
abstract

DIFFUSION-WEIGHTED MRI OF MAPLE SYRUP URINE DISEASE ENCEPHALOPATHY

2002 - HERPES SIMPLEX: PREVENZIONE E TRATTAMENTO [Articolo su rivista]
Ferrari, Fabrizio; Berardi, A; Rossi, K; DELLA CASA MUTTINI, E; Pancaldi, Me; Gargano, G; Roversi, Mf; Boselli, F.
abstract

No abstract

2002 - INFEZIONE PERINATALE DA STREPTOCOCCO DI GRUPPO B [Relazione in Atti di Convegno]
Ferrari, Fabrizio; Berardi, A; Rossi, K; Bussetti, C; Madeo, S; Mordini, B; Cattani, S; DELLA CASA MUTTINI, E; Garetti, E; Geti, M; Pancaldi, Me; Piccinini, L; Venturelli, C.
abstract

No abstract

2002 - Prophylaxis of neonatal group B streptococcal infection[La profilassi dell'infezione neonatale da streptococco di gruppo B] [Articolo su rivista]
Berardi, A.; Rossi, K.; Bussetti, C.; Ferrari, Fabrizio
abstract

Group B Streptococcus is the leading cause of vertically transmitted neonatal bacterial infections. The consequence of early and late-onset infections can be fatal diseases or severe neurological sequelae, when central nervous system is involved. Many efforts have been made on prevention, but the infection is not totally controlled. Bacteriological screening of all mothers between the 35th and the 37th week oF gestation otgestation, followed by maternal intrapartum chemoprophylaxis (by penicillin or ampicillin) of colonised women represents today the most effective strategy to prevent the disease.

2002 - The mastoid view: a different approach to the ultrasound exploration of neonatal brain. [Articolo su rivista]
Berardi, A
abstract

Objectives. We aimed to determine whether imaging through the mastoid fontanelle improves the accuracy of the standard sonographic examination, and evaluate for how long this approach is feasible after the first month of life. Methods. Therefore, for 4 months, we performed a prospective study of 32 neonates admitted to our neonatal intensive care and of 33 outpatients evaluated during follow-up visits. Results. We describe a cranial ultrasound scan approach that allows, by mastoid view, a detailed exploration of the posterior fossa structures and midbrain. Conclusions. We describe several pathological findings detected with this approach and discuss some limitations of the technique.

2001 - Intraventricular hemorrhage in full term newborns. A case report with a review of the literature [Articolo su rivista]
Berardi, A; Guidi, B; Cattani, S; Cavalleri, F; Gargano, G; Pastorelli, S; Rota, C; Roversi, Mf; Ferrari, F.; Cavazzuti, Gb
abstract

We report the case of a full term newborn with intraventricular hemorrhage and non-specific clinical findings. Cranial ultrasound scan, performed during the first days of life, allowed us to detect the hemorrhage and its evolution; a subsequent MRI allowed us to locate the site of the hematoma and to exclude the presence of deep venous thrombosis and parenchymal lesions. A review of the most frequent causes and sites of intraventricular hemorrhage in full term newborn infants is reported.

2000 - SEPSIS CAUSED BY CORYNEBACTERIUM XEROSIS IN NEONATOLOGY: REPORT OF A CLINICAL CASE [Articolo su rivista]
Ferrari, Fabrizio; Cattani, S; Venturelli, C; Berardi, A; Bussetti, C; DE CARIS, V; Casolari, C; Piccinini, L; Pastorelli, S; DELLA CASA MUTTINI, E; Gallo, C; Rumpianesi, F.
abstract

The pathogenicity of the nondiphtheria corynebacteria, most commonly known as coryneform bacteria in humans has been recognized in the last two decades. Corynebacterium xerosis is part of the normal flora of the skin, nasopharynx, conjunctives and it has recently been isolated from vaginal swabs. During the last few years, there has been an increased number of case reports claiming an association of C. xerosis with diseases, like septicemia, endocarditis, pleuropneumonia, peritonitis, osteomyelitis, septic arthritis, mediastinitis, meningitis, ventriculitis specially in immunocompromised patients or surgical patients. Infections due to C. xerosis have been reported rarely in newborn. We report a case of sepsis due to C. xerosis in a newborn without evident immunodeficiency. Our case further support the recognition of C. xerosis as a human pathogen and reinforces the fact that it should not be routinely considered as a contaminant.

2000 - STATO DI MALE CONVULSIVO IN UN LATTANTE DISMORFICO [Relazione in Atti di Convegno]
Ferrari, Fabrizio; DELLA CASA MUTTINI, E; Milioli, S; Berardi, A; Sturloni, N; Cattani, S; Gargano, G; Roversi, Mf; Spattini, A; Ferrari, P.
abstract

No abstract

2000 - Sepsis caused by Corynebacterium xerosis in neonatology: A case report [Articolo su rivista]
Cattani, S.; Buffett, C.; Piccinini, L.; Gallo, C.; Venturelli, C.; De Caris, V.; Pastorelli, S.; Rumpianesi, F.; Berardi, A.; Casolari, C.; Della, E.; Muttini, C.; Ferrari, F.
abstract

The pathogenicity of the nondiphtheria corynebacteria, most commonly known as coryneform bacteria in humans has been recognized in the last two decades. Corynebacterium xerosis is part of the normal flora of the skin, nasopharynx, conjunctives and it has recently been isolated from vaginal swabs. During the last few years, there has been an increased number of case reports claiming an association of C. xerosis with diseases, like septicemia, endocarditis, pleuropneumonia, peritonitis, osteomyelitis, septic arthritis, mediastinitis, meningitis, ventriculitis specially in immunocompromised patients or surgical patients. Infections due to C. xerosis have been reported rarely in newborn. We report a case of sepsis due to C. xerosis in a newborn without evident immunodeficiency. Our case further support the recognition of C. xerosis as a human pathogen and reinforces the fact that it should not be routinely considered as a contaminant.

1999 - Accogliere il neonato patologico o prematuro: conciliare le ragioni dell'amore e dell'istituzione ospedaliera [Capitolo/Saggio]
Ferrari, Fabrizio; Cattani, S; Roversi, Mf; Gargano, G; Biagioni, O; Berardi, A.
abstract

no abstract

1999 - Anemia fetale da incopatibilità ABO con complicanze neurologiche post-natali [Relazione in Atti di Convegno]
Cattani, S; Berardi, A; Mordini, B; Baldini, A; De Palma, M; Biagioni, O; De caris, V; Gargano, G; Guidi, B; Rota, C; Roversi, Mf; Ferrari, Fabrizio
abstract

No abstract

1999 - Diagnostica clinica e per immagini [Articolo su rivista]
Ferrari, Fabrizio; Roversi, Mf; Berardi, A; Tavani, F; Cavazzuti, Gb
abstract

No abstract

1999 - Immunodeficienza combinata da deficit di espressione delle molecole di HLA di classe II: difficoltà diagnostiche in una rara affezione [Articolo su rivista]
Berardi, A; Roncaglia, R; Roversi, Mf; Gargano, G; Biagioni, O; Cattani, S; Mordini, B; Ferrari, Fabrizio
abstract

No abstract

1999 - La "care" del neonato prematuro in terpaia intensiva [Articolo su rivista]
Ferrari, Fabrizio; Roversi, Mf; Biagioni, O; Berardi, A; Gargano, G; Cattani, S; Cavazzuti, Gb
abstract

No abstract avaible

1997 - Patogenesi e clinica del danno neurologico nel neonato SGA [Relazione in Atti di Convegno]
Ferrari, Fabrizio; Gargano, G; Berardi, A; Roversi, Mf; Mazza, V; Cavazzuti, Gb
abstract

No abstract

1997 - Sopravvivenza e qualità della vita nei neonati ELBW [Relazione in Atti di Convegno]
Ferrari, Fabrizio; Roversi, Mf; Gargano, G; Gallo, C; Berardi, A; Biagioni, O.
abstract

No abstract

1994 - Trasfusione in utero da gemello a gemello e miocardiopatia ipertrofica compensatoria [Relazione in Atti di Convegno]
Berardi, A; Biagioni, O; Capriotti, T; Bosi, Mp; Barbani, Mt; Gargano, Gc; Roversi, Mf; Vagnarelli, F; Mazza, V; Ferrari, Fabrizio
abstract

No abstract

1993 - Meningiti batteriche neonatali: analisi della casisitica di dodici anni [Relazione in Atti di Convegno]
Guarino, I; Barbani, Mt; Gargano, G; Berardi, A; Capriotti, T; Bosi, Mp; Giustardi, A; Piccinini, L; Ferrari, Fabrizio
abstract

NO ABSTRACT