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FRANCESCA MISELLI

Dottorando
Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze

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Pubblicazioni

2025 - Outcome prediction for late-onset sepsis after premature birth [Articolo su rivista]
Miselli, Francesca; Costantini, Riccardo Cuoghi; Maugeri, Melissa; Deonette, Elisa; Mazzotti, Sofia; Bedetti, Luca; Lugli, Licia; Rossi, Katia; Roversi, Mariafederica; Berardi, Alberto
abstract

Background: Our aim was to develop a quantitative model for immediately estimating the risk of death and/or brain injury in late-onset sepsis (LOS) in preterm infants, based on objective and measurable data available at the time sepsis is first suspected (i.e., time of blood culture collection). Methods: Retrospective study on neonates ≤36 weeks’ gestation with a positive blood and/or cerebrospinal fluid culture after 72 hours from birth. Results: Among 3217 preterm live births, 94 cases were included (median gestational age 26.5 weeks’ IQR 25.0;28.0), of whom 26 (27.7%) had poor outcomes (17 death; 9 brain injuries). Infants with poor outcomes showed lower postnatal age (11.5 vs 12.5 days, p < 0.001), lower mean blood pressure (30.5 vs 43 mmHg, p < 0.001) and higher lactate levels (4.4 vs 1.5 mmol/l, p < 0.001). Our multivariable model showed good discrimination and calibration (c statistic=0.8618, Hosmer-Lemeshow p = 0.8532), stratifying the population into 3 groups: low-risk (sensitivity 97%, specificity 52%), middle-risk, and high-risk (sensitivity 77%, specificity 80%). Conclusion: This predictive model performs well as a practical and easy-to-use tool to help clinicians early identify the sickest neonates who may benefit from timely and aggressive support (e.g., central line, haemodynamic assessment) and close monitoring (e.g., 1:1 nursing assignment, frequent reassessments). Impact: We lack data to early identify the severity of neonatal late-onset sepsis in preterm infants. Delay in treatment contributes to poor prognosis. We developed a model for early prediction of poor outcomes (mortality and brain injuries). The model utilizes immediately available and measurable data at the time sepsis is first suspected. This can help clinicians in tailoring management based on individual risks.

2024 - Can a Shorter Dwell Time Reduce Infective Complications Associated with the Use of Umbilical Catheters? [Articolo su rivista]
Buttera, M.; Corso, L.; Casadei, L.; Valenza, C.; Sforza, F.; Candia, F.; Miselli, F.; Baraldi, C.; Lugli, L.; Berardi, A.; Iughetti, L.
abstract

Background: Umbilical venous catheters (UVCs) are the standard of care in neonatal intensive care units (NICUs) to administer fluids, parenteral nutrition and medications, although complications may occur, including central line-associated blood stream infections (CLABSIs). However, the dwell time to reduce CLABSI risk remains an open issue. Methods: We performed a single-center retrospective study of newborns hospitalized in the Modena NICU with at least one UVC inserted over a 6-year period (period 1: January 2011-December 2013; period 2: January 2019-December 2021). We selected a non-consecutive 6-year period to emphasize the differences in UVC management practices that have occurred over time in our NICU. The UVC dwell time and catheter-related complications during the first 4 weeks of life were examined. Results: The UVC dwell time was shorter in period 2 (median 4 days vs. 5 days, p < 0.00001). Between the two periods, the incidence of CLABSIs remained unchanged (p = 0.5425). However, in period 2, there was an increased need for peripherally inserted central catheters (PICCs) after UVC removal, with a rise in PICC infections after UVC removal (p = 0.0239). Conclusions: In our NICU, shortening UVC dwell time from 5 to 4 days did not decrease the UVC-related complications. Instead, the earlier removal of UVCs led to a higher number of PICCs inserted, possibly increasing the overall infectious risk.

2024 - Correction: Enteral and Parenteral Treatment with Caffeine for Preterm Infants in the Delivery Room: A Randomised Trial (Pediatric Drugs, (2023), 25, 1, (79-86), 10.1007/s40272-022-00541-y) [Articolo su rivista]
Dani, C.; Cecchi, A.; Ciarcià, M.; Miselli, F.; Luzzati, M.; Remaschi, G.; Bona, M. D.; la Marca, G.; Boni, L.
abstract

2024 - Cranial ultrasound in preterm infants ≤ 32 weeks gestation—novel insights from the use of very high-frequency (18-5 MHz) transducers: a case series [Articolo su rivista]
Miselli, F.; Guidotti, I.; Di Martino, M.; Bedetti, L.; Minotti, C.; Spaggiari, E.; Malmusi, G.; Lugli, L.; Corso, L.; Berardi, A.
abstract

The quality of cranial ultrasound has improved over time, with advancing technology leading to higher resolution, faster image processing, digital display, and back-up. However, some brain lesions may remain difficult to characterize: since higher frequencies result in greater spatial resolution, the use of additional transducers may overcome some of these limitations. The very high-frequency transducers (18-5 MHz) are currently employed for small parts and lung ultrasound. Here we report the first case series comparing the very high-frequency probes (18-5 MHz) with standard micro-convex probes (8-5 MHz) for cranial ultrasound in preterm infants. In this case series, we compared cranial ultrasound images obtained with a micro-convex transducer (8-5 MHz) and those obtained with a very high-frequency (18-5 MHz) linear array transducer in 13 preterm infants ≤ 32 weeks gestation (9 with cerebral abnormalities and 4 with normal findings). Ultrasound examinations using the very high-frequency linear transducer and the standard medium-frequency micro-convex transducer were performed simultaneously. We also compared ultrasound findings with brain MRI images obtained at term corrected age. Ultrasound images obtained with the very high-frequency (18-5 MHz) transducer showed high quality and accuracy. Notably, despite their higher frequency and expected limited penetration capacity, brain size is small enough in preterm infants, so that brain structures are close to the transducer, allowing for complete evaluation. Conclusion: We propose the routine use of very high-frequency linear probes as a complementary scanning modality for cranial ultrasound in preterm infants ≤ 32 weeks gestation. (Table presented.)

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 - Identifying skull fractures after head trauma in infants with ultrasonography: is that possible? [Articolo su rivista]
Filice, R.; Miselli, F.; Guidotti, I.; Lugli, L.; Palazzi, G.; Berardi, A.; Iughetti, L.
abstract

Management of pediatric head trauma requires a delicate balance between accuracy and safety, with a dual emphasis on prompt diagnosis while minimizing radiation exposure. Ultrasonography (US) shows promise in this regard. A case study involving a 10-month-old infant with acute right parietal swelling revealed the utility of US in detecting a corresponding hypoechoic lesion, along with an underlying suspected fracture line of the vault and subdural hematoma. Subsequent CT confirmed the fracture, while MRI confirmed the subdural hematoma. At one-month follow-up, MRI demonstrated hematoma reabsorption, while US revealed a bone callus in its advanced phase. Although US is not yet standard practice for pediatric head trauma, its ability to detect fractures in infants suggests its potential role: when a fracture is evident on US, it may serve as an indication to perform neuroimaging. Potentially, adoption of US could contribute to mitigation of children’s exposure to ionizing radiation.

2024 - LATE-ONSET GROUP B STREPTOCOCCAL INFECTIONS: WHAT DO PAEDIATRICIANS NEED TO KNOW? [Articolo su rivista]
Riccipetitoni, L.; Miselli, F.; Buttera, M.; Bondi, C.; Mazzotti, S.; Baraldi, N.; Bedetti, L.; Lugli, L.; Berardi, A.
abstract

2024 - Measurement of lung oxygenation by near‐infrared spectroscopy in preterm infants with bronchopulmonary dysplasia [Articolo su rivista]
Dani, Carlo; Miselli, Francesca; Zini, Tommaso; Scarponi, Davide; Luzzati, Michele; Sarcina, Davide; Fusco, Monica; Dianori, Francesco; Berardi, Alberto
abstract

IntroductionIt has recently been reported that it is possible to monitor lung oxygenation (rSO2L) by near-infrared spectroscopy (NIRS) in preterm infants with respiratory distress syndrome (RDS). Thus, our aim was to assess the possibility of monitoring rSO2L in infants with evolving and established bronchopulmonary dysplasia (BPD) and to evaluate if rSO2L correlates with BPD severity and other oxygenation indices.MethodsWe studied 40 preterm infants with gestational age <= 30 weeks at risk for BPD. Patients were continuously studied for 2 h by NIRS at 28 +/- 7 days of life and 36 weeks +/- 7 days of postmenstrual age.ResultsrSO2L was similar at the first and second NIRS recordings (71.8 +/- 7.2 vs. 71.4 +/- 4.2%) in the overall population, but it was higher in infants with mild than in those with moderate-to-severe BPD at both the first (73.3 +/- 3.1 vs. 71.2 +/- 3.2%, p = .042) and second (72.3 +/- 2.8 vs. 70.5 +/- 2.8, p = .049) NIRS recording. A rSO2L cutoff value of 71.6% in the first recording was associated with a risk for moderate-to-severe BPD with a sensitivity of 66% and a specificity of 60%. Linear regression analysis demonstrated a significant positive relationship between rSO2L and SpO2/FiO2 ratio (p = .013) and a/APO2 (p = .004).ConclusionsMonitoring of rSO2L by NIRS in preterm infants with evolving and established BPD is feasible and safe. rSO2L was found to be higher in infants with mild BPD, and predicts the risk for developing moderate-to-severe BPD and correlates with other indices of oxygenation.

2024 - Nasal intermittent positive pressure ventilation during less invasive surfactant administration in preterm infants: An open-label randomized controlled study [Articolo su rivista]
Dani, C.; Napolitano, M.; Barone, C.; Manna, A.; Nigro, G.; Scarpelli, G.; Bonanno, E.; Gatto, S.; Cavigioli, F.; Forcellini, C.; Petoello, E.; Beghini, R.; Ciarcia, M.; Fusco, M.; Mosca, F.; Lavizzari, A.; Gitto, E.; Barbuscia, L.; Betta, P.; Mattia, C.; Corvaglia, L.; Vedovato, S.; Vento, G.; Maffei, G.; Falsaperla, R.; Lago, P.; Boni, L.; Lista, G.; Luzzati, M.; Miselli, F.; Foderini, M. V.; Balestriere, L.; Riccardi, D.; Roseto, V.; Rotta, I.; Picone, V.; Molisso, A.; Pirozzi, E.; Faiella, A.; Orsini, B.; Toro, F. M.; Castoldi, F.; Mercadante, D.; Amatruda, M.; Marseglia, L. M.; Aceti, A.; Capretti, M. G.; Grison, A.; Bottoni, A.; Fusco, P.; Tana, M.; Rinaldi, M.; Liberatore, P.; Fracchiolia, A.; Cimino, C.; Vendramin, S.
abstract

Introduction: Approximately half of very preterm infants with respiratory distress syndrome (RDS) fail treatment with nasal continuous positive airway pressure (NCPAP) and need mechanical ventilation (MV). Objectives: Our aim with this study was to evaluate if nasal intermittent positive pressure ventilation (NIPPV) during less invasive surfactant treatment (LISA) can improve respiratory outcome compared with NCPAP. Materials and Methods: We carried out an open-label randomized controlled trial at tertiary neonatal intensive care units in which infants with RDS born at 25+0−31+6 weeks of gestation between December 1, 2020 and October 31, 2022 were supported with NCPAP before and after surfactant administration and received NIPPV or NCPAP during LISA. The primary endpoint was the need for a second dose of surfactant or MV in the first 72 h of life. Other endpoints were need and duration of invasive and noninvasive respiratory supports, changes in SpO2/FiO2 ratio after LISA, and adverse effect rate. Results: We enrolled 101 infants in the NIPPV group and 99 in the NCPAP group. The unadjusted odds ratio for the composite primary outcome was 0.873 (95% confidence interval: 0.456–1.671; p =.681). We found that the SpO2/FiO2 ratio was transiently higher in the LISA plus NIPPV than in the LISA plus NCPAP group, while adverse effects of LISA had similar occurrence in the two arms. Conclusions: The application of NIPPV or NCPAP during LISA in very preterm infants supported with NCPAP before and after surfactant administration had similar effects on the short-term respiratory outcome and are both safe. Our study does not support the use of NIPPV during LISA.

2024 - Neonatal Sequential Organ Failure Assessment Score Predicts Respiratory Outcomes in Preterm Newborns with Late-Onset Sepsis: A Retrospective Study [Articolo su rivista]
Poggi, Chiara; Sarcina, Davide; Miselli, Francesca; Ciarcià, Martina; Dani, Carlo
abstract

Introduction: Neonatal sequential organ failure assessment (nSOFA) score predicts mortality in preterm newborns. The aim of the study was to assess whether nSOFA score could predict respiratory outcomes in preterm infants with late-onset sepsis (LOS). Methods: This retrospective, observational, single-center study enrolled infants with gestational age <32 weeks born between January 2016 and June 2023 who experienced an episode of LOS during NICU stay. The primary outcome was death or bronchopulmonary dysplasia (BPD); secondary outcomes were BPD, death or mechanical ventilation (MV) on day 5 after the onset of LOS, and MV on day 5 after the onset of LOS. The nSOFA score was assessed at the onset of LOS and after 6 +/- 1, 12 +/- 3, and 24 +/- 3 h. Results: Neonatal SOFA score was significantly higher in patients who developed each outcome versus those who did not at all timings. Maximal nSOFA score during the first 24 h after onset of LOS was an independent predictive factor for death or BPD (p = 0.007), BPD (p = 0.009), and death or MV on day 5 (p = 0.009), areas under the curve (AUC) were 0.740 (95% CI: 0.656-0.828), 0.700 (95% CI: 0.602-0.800), and 0.800 (95% CI: 0.710-0.889), respectively. Maximal nSOFA score also predicted moderate to severe BPD (p = 0.019) and death or moderate to severe BPD (p < 0.001). Maximal nSOFA >= 4 was associated with odds ratio (OR) of 7.37 (95% CI: 2.42-22.44) for death or BPD, 4.86 (95% CI: 1.54-15.28) for BPD, and 7.99 (95% CI: 3.47-18.36) for death or MV on day 5. AUC of the predicting model was 0.895 (95% CI: 0.801-0.928) for BPD, 0.897 (95% CI: 0.830-0.939) for death or BPD, 0.904 (95% CI: 0.851-0.956) for MV on day 5, 0.923 (95% CI: 0.892-0.973) for death or MV on day 5. Conclusion: Maximal nSOFA score during the first 24 h after the onset of LOS predicts respiratory outcomes and allows identification of patients who may crucially benefit from lung-protective measures.

2024 - Neurodevelopmental Outcome after Culture-Proven or So-Called Culture-Negative Sepsis in Preterm Infants [Articolo su rivista]
Bedetti, Luca; Corso, Lucia; Miselli, Francesca; Guidotti, Isotta; Toffoli, Carlotta; Miglio, Rossella; Roversi, Maria Federica; Muttini, Elisa Della Casa; Pugliese, Marisa; Bertoncelli, Natascia; Zini, Tommaso; Mazzotti, Sofia; Lugli, Licia; Lucaccioni, Laura; Berardi, Alberto
abstract

(1) Background: Prematurity is a serious condition associated with long-term neurological disability. This study aimed to compare the neurodevelopmental outcomes of preterm neonates with or without sepsis. (2) Methods: This single-center retrospective case-control study included infants with birth weight < 1500 g and/or gestational age <= 30 weeks. Short-term outcomes, brain MRI findings, and severe functional disability (SFD) at age 24 months were compared between infants with culture-proven or culture-negative sepsis or without sepsis. A chi-squared test or Mann-Whitney U test was used to compare the clinical and instrumental characteristics and the outcomes between cases and controls. (3) Results: Infants with sepsis (all sepsis n = 76; of which culture-proven n = 33 and culture-negative n = 43) were matched with infants without sepsis (n = 76). Compared with infants without sepsis, both all sepsis and culture-proven sepsis were associated with SFD. In multivariate logistic regression analysis, SFD was associated with intraventricular hemorrhage (OR 4.7, CI 1.7-13.1, p = 0.002) and all sepsis (OR 3.68, CI 1.2-11.2, p = 0.021). (4) Conclusions: All sepsis and culture-proven sepsis were associated with SFD. Compared with infants without sepsis, culture-negative sepsis was not associated with an increased risk of SFD. Given the association between poor outcomes and culture-proven sepsis, its prevention in the neonatal intensive care unit is a priority.

2024 - Neurodevelopmental Outcome and Neuroimaging of Very Low Birth Weight Infants from an Italian NICU Adopting the Family-Centered Care Model [Articolo su rivista]
Lugli, Licia; Pugliese, Marisa; Bertoncelli, Natascia; Bedetti, Luca; Agnini, Cristina; Guidotti, Isotta; Roversi, Maria Federica; Della Casa, Elisa Muttini; Cavalleri, Francesca; Todeschini, Alessandra; Di Caprio, Antonella; Zini, Tommaso; Corso, Lucia; Miselli, Francesca; Ferrari, Fabrizio; Berardi, Alberto
abstract

Background: Improvements in perinatal care have substantially decreased mortality rates among preterm infants, yet their neurodevelopmental outcomes and quality of life persist as a pertinent public health concern. Family-centered care has emerged as a holistic philosophy that promotes effective alliances among patients, families, and healthcare providers to improve the quality of care. Aims: This longitudinal prospective study aims to evaluate the neurodevelopmental outcomes and brain MRI findings in a cohort of preterm newborns admitted to a neonatal intensive care unit (NICU) adopting a family-centered care model. Methods: Very low birth weight (VLBW) infants admitted to the NICU of Modena between 2015 and 2020 were enrolled. Infants who underwent conventional brain magnetic resonance imaging (MRI) at term-equivalent age were included. Neurodevelopmental follow-up was performed until the age of 24 months by a multidisciplinary team using the Amiel-Tison neurological assessment and the Griffiths Mental Developmental Scales (GMDS-R). Neurodevelopmental outcomes were classified as major sequelae (cerebral palsy, DQ ≤ 70, severe sensory impairment), minor sequelae (minor neurological signs such as clumsiness or DQ between 71 and 85), and normal outcomes (no neurological signs and DQ > 85). Risk factors for severe outcomes were assessed. Results: In total, 49 of the 356 infants (13.8%) died before hospital discharge, and 2 were excluded because of congenital disorders. Of the remaining 305 infants, 222 (72.8%) completed the 24 month follow-up and were included in the study. Neurodevelopmental outcomes were classified as normal (n = 173, 77.9%), minor (n = 34, 15.3%), and major sequelae (n = 15, 6.8%). Among 221 infants undergoing brain MRI, 76 (34.4%) had major lesions (intraventricular hemorrhage, hemorrhagic parenchymal infarction, periventricular leukomalacia, and large cerebellar hemorrhage). In the multivariate regression model, the retinopathy of prematurity (OR 1.8; p value 0.016) and periventricular–intraventricular hemorrhage (OR 5.6; p value < 0.004) were associated with major sequelae. Conclusions: We reported low rates of severe neurodevelopmental outcomes in VLBW infants born in an Italian NICU with FCC. Identifying the risk factors for severe outcomes can assist in tailoring and optimizing early interventions on an individual basis, both within the NICU and after discharge.

2024 - Neurodevelopmental outcome of neonatal seizures: A longitudinal study [Articolo su rivista]
Lugli, L.; Bariola, M. C.; Guidotti, I.; Pugliese, M.; Roversi, M. F.; Bedetti, L.; Della Casa Muttini, E.; Miselli, F.; Ori, L.; Lucaccioni, L.; Bertoncelli, N.; Rossi, K.; Crestani, S.; Bergonzini, P.; Iughetti, L.; Ferrari, F.; Berardi, A.
abstract

Introduction: Neonatal seizures (NS) are the most common neurological emergency in the neonatal period. The International League Against Epilepsy (ILAE) proposed a new classification of NS based on semiology and highlighted the correlation between semiology and aetiology. However, neurodevelopmental outcomes have not been comprehensively evaluated based on this new classification. Aims: To evaluate neurodevelopmental outcomes and potential risk factors for severe outcomes in NS. Methods: Patients with video electroencephalogram confirmed NS were evaluated. Seizure aetiology, cerebral magnetic resonance imaging (MRI) data, background electroencephalograms data, general movements, and neurodevelopmental outcomes were analysed. Severe outcomes were one of the following: death, cerebral palsy, Griffiths developmental quotient <70, epilepsy, deafness, or blindness. Results: A total of 74 neonates were evaluated: 62 (83.8 %) with acute provoked NS (primarily hypoxic-ischaemic encephalopathy), and 12 (16.2 %) with neonatal-onset epilepsies (self-limited neonatal epilepsy, developmental and epileptic encephalopathy, cerebral malformations). Of these, 32 (43.2 %) had electrographic seizures, while 42 (56.7 %) had electroclinical seizures – 38 (90.5 %) were motor (42.1 % clonic) and 4 (9.5 %) were non-motor phenomena. Severe outcomes occurred in 33 of the 74 (44.6 %) participants. In multivariate analysis, neonatal-onset epilepsies (odds ratio [OR]: 1.3; 95 % confidence interval [CI]: 1.1–1.6), status epilepticus (OR: 5.4; 95 % CI: 1.5–19.9), and abnormal general movements (OR: 3.4; 95 % CI: 1.9–7.6) were associated with severe outcomes. Conclusions: At present, hypoxic-ischaemic encephalopathy remains the most frequent aetiology of NS. The prognosis of neonatal-onset epilepsies was worse than that of acute provoked NS, and status epilepticus was the most predictive factor for adverse outcomes.

2024 - Patent ductus arteriosus (also non-hemodynamically significant) correlates with poor outcomes in very low birth weight infants. A multicenter cohort study [Articolo su rivista]
Chesi, E.; Rossi, K.; Ancora, G.; Baraldi, C.; Corradi, M.; Di Dio, F.; Di Fazzio, G.; Galletti, S.; Mescoli, G.; Papa, I.; Solinas, A.; Braglia, L.; Di Caprio, A.; Cuoghi Costantini, R.; Miselli, F.; Berardi, A.; Gargano, G.
abstract

Objectives To standardize the diagnosis of patent ductus arteriosus (PDA) and report its association with adverse neonatal outcomes in very low birth weight infants (VLBW, birth weight < 1500 g). Study design A multicenter prospective observational study was conducted in Emilia Romagna from March 2018 to October 2019. The association between ultrasound grading of PDA and adverse neonatal outcomes was evaluated after correction for gestational age. A diagnosis of hemodynamically significant PDA (hsPDA) was established when the PDA diameter was ≥ 1.6 mm at the pulmonary end with growing or pulsatile flow pattern, and at least 2 of 3 indexes of pulmonary overcirculation and/or systemic hypoperfusion were present. Results 218 VLBW infants were included. Among infants treated for PDA closure in the first postnatal week, up to 40% did not have hsPDA on ultrasound, but experienced clinical worsening. The risk of death was 15 times higher among neonates with non-hemodynamically significant PDA (non-hsPDA) compared to neonates with no PDA. In contrast, the risk of death was similar between neonates with hsPDA and neonates with no PDA. The occurrence of BPD was 6-fold higher among neonates with hsPDA, with no apparent beneficial role of early treatment for PDA closure. The risk of IVH (grade ≥ 3) and ROP (grade ≥ 3) increased by 8.7-fold and 18-fold, respectively, when both systemic hypoperfusion and pulmonary overcirculation were present in hsPDA. Conclusions The increased risk of mortality in neonates with non-hsPDA underscores the potential inadequacy of criteria for defining hsPDA within the first 3 postnatal days (as they may be adversely affected by other clinically severe factors, i.e. persistent pulmonary hypertension and mechanical ventilation). Parameters such as length, diameter, and morphology may serve as more suitable ultrasound indicators during this period, to be combined with clinical data for individualized management. Additionally, BPD, IVH (grade ≥ 3) and ROP (grade ≥ 3) are associated with hsPDA. The existence of an optimal timeframe for closing PDA to minimize these adverse neonatal outcomes remains uncertain.

2024 - Sustaining the Continued Effectiveness of an Antimicrobial Stewardship Program in Preterm Infants [Articolo su rivista]
Zini, Tommaso; Miselli, Francesca; D'Esposito, Chiara; Fidanza, Lucia; Cuoghi Costantini, Riccardo; Corso, Lucia; Mazzotti, Sofia; Rossi, Cecilia; Spaggiari, Eugenio; Rossi, Katia; Lugli, Licia; Bedetti, Luca; Berardi, Alberto
abstract

Background: There are wide variations in antibiotic use in neonatal intensive care units (NICUs). Limited data are available on antimicrobial stewardship (AS) programs and long-term maintenance of AS interventions in preterm very-low-birth-weight (VLBW) infants. Methods: We extended a single-centre observational study carried out in an Italian NICU. Three periods were compared: I. "baseline" (2011-2012), II. "intervention" (2016-2017), and III. "maintenance" (2020-2021). Intensive training of medical and nursing staff on AS occurred between periods I and II. AS protocols and algorithms were maintained and implemented between periods II and III. Results: There were 111, 119, and 100 VLBW infants in periods I, II, and III, respectively. In the "intervention period", there was a reduction in antibiotic use, reported as days of antibiotic therapy per 1000 patient days (215 vs. 302, p < 0.01). In the "maintenance period", the number of culture-proven sepsis increased. Nevertheless, antibiotic exposure of uninfected VLBW infants was lower, while no sepsis-related deaths occurred. Our restriction was mostly directed at shortening antibiotic regimens with a policy of 48 h rule-out sepsis (median days of early empiric antibiotics: 6 vs. 3 vs. 2 in periods I, II, and III, respectively, p < 0.001). Moreover, antibiotics administered for so-called culture-negative sepsis were reduced (22% vs. 11% vs. 6%, p = 0.002), especially in infants with a birth weight between 1000 and 1499 g. Conclusions: AS is feasible in preterm VLBW infants, and antibiotic use can be safely reduced. AS interventions, namely, the shortening of antibiotic courses in uninfected infants, can be sustained over time with periodic clinical audits and daily discussion of antimicrobial therapies among staff members.

2024 - The Motor Optimality Score—Revised Improves Early Detection of Unilateral Cerebral Palsy in Infants with Perinatal Cerebral Stroke [Articolo su rivista]
Bertoncelli, N.; Corso, L.; Bedetti, L.; Della Casa, E. M.; Roversi, M. F.; Toni, G.; Pugliese, M.; Guidotti, I.; Miselli, F.; Lucaccioni, L.; Rossi, C.; Berardi, A.; Lugli, L.
abstract

Background: Neonatal cerebral stroke includes a range of focal and multifocal ischemic and hemorrhagic brain lesions, occurring in about one of 3000 live births. More than 50% of children with neonatal stroke develop adverse outcomes, mainly unilateral cerebral palsy. Asymmetries in segmental movements at three months have been proven to be an early sign of CP in infants with unilateral brain damage. Recognition of additional early signs could enhance prognostic assessment and enable an early and targeted intervention. Aim: The aim of the study was to assess early signs of CP in infants with arterial cerebral stroke through the General Movements Assessment and the Motor Optimality Score—Revised (MOS-R). Method: Twenty-four infants born at term (12 females and 12 males) diagnosed with ACS, and 24 healthy infants (16 females and 8 males) were assessed. The GMs (fidgety movements) and MOS-R were assessed from videos recorded at 11–14 weeks of post-term age. Cognitive and motor outcomes were assessed at 24 months using the Griffiths III developmental quotient and Amiel-Tison neurological examination. The gross motor function classification system expanded and revised (GMFCS-E&R) was adopted to categorize CP. Results: Among infants with ACS, 21 (87.5%) developed unilateral CP. Most of them showed non-disabling CP (14 had GMFCS-E&R grade 1 [66.6%], 6 grade 2 [28.6%], and 1 grade 5 [4.8%]). Fidgety movements (FMs) were absent in 17 (70.8%), sporadic in 4 (16.7%) infants, and normal in 3 (12.5%). Segmental movement asymmetry was found in 22/24 (91.7%). According to the MOS-R, motor items (kicking, mouth movements), postural patterns (midline centered head, finger posture variability), and movement character (monotonous and stiff) were statistically different among infants with ACS and healthy infants. The MOS-R median global score was lower in the group with ACS compared to the control group (6 vs 26; p < 0.01). FMs, segmental movement asymmetry, and MOS-R global score were significantly correlated with abnormal outcome. MOS-R global scores less than or equal to 13 had 100% specificity and sensitivity in predicting GMFCS-E&R grade ≥ 2 CP in infants with ACS. Conclusions: The rate of CP was high among infants with ACS, but in most cases it showed low GMFCS-E&R grades. The study highlighted a significant correlation between MOS-R, together with absent FMs and unilateral CP in infants with ACS. Moreover, the MOS-R showed high sensitivity and specificity in the prediction of CP. Combined assessment of FMs and MOS-R could help to better identify infants at high risk of developing UCP in a population of infants with ACS. Early identification of precocious signs of unilateral CP is fundamental to providing an early individualized intervention.

2024 - The key role of public health in renovating Italian biomedical doctoral programs [Articolo su rivista]
Palandri, Lucia; Urbano, Teresa; Pezzuoli, Carla; Miselli, Francesca; Caraffi, Riccardo; Filippini, Tommaso; Bargellini, Annalisa; Righi, Elena; Mazzi, Davide; Vigezzi, Giacomo Pietro; Odone, Anna; Marmiroli, Sandra; Boriani, Giuseppe; Vinceti, Marco
abstract

Background: A key renovation of doctoral programs is currently ongoing in Italy. Public health and its competencies may play a pivotal role in high-level training to scientific research, including interdisciplinary and methodological abilities. Methods: As a case study, we used the ongoing renovation of the Clinical and Experimental Medicine doctoral program at the University of Modena and Reggio Emilia. We focused on how the program is designed to meet national requirements as well as students' needs, thus improving educational standards for scientific research in the biomedical field, and on the specific contribution of public health and epidemiology in such an effort. Results: The renovation process of doctoral programs in Italy, with specific reference to the biomedical field, focuses on epidemiologic-statistical methodology, ethics, language and communication skills, and open science from an interdisciplinary and international perspective. In the specific context of the doctoral program assessed in the study and from a broader perspective, public health appears to play a key role, taking advantage of most recent methodological advancements, and contributing to the renovation of the learning process and its systematic quality monitoring. Conclusions: From a comparative assessment of this case study and Italian legislation, the key role of public health has emerged in the renovation process of doctoral programs in the biomedical field.

2024 - Timing and adequacy of intrapartum antibiotic prophylaxis: new insights for future guidelines [Articolo su rivista]
Miselli, F.; Lugli, L.; Bedetti, L.; Mazzotti, S.; Buttera, M.; Berardi, A.
abstract

2024 - Ultrasound-Guided Centrally Inserted Central Catheter (CICC) Placement in Newborns: A Safe Clinical Training Program in a Neonatal Intensive Care Unit [Articolo su rivista]
Zini, Tommaso; Corso, Lucia; Mazzi, Cinzia; Baraldi, Cecilia; Nieddu, Elisa; Rinaldi, Laura; Miselli, Francesca; Bedetti, Luca; Spaggiari, Eugenio; Rossi, Katia; Berardi, Alberto; Lugli, Licia; On Behalf Of The Cvc Study Group, Null
abstract

Background: Centrally inserted central catheters (CICCs) are increasingly used in neonatal care. CICCs have garnered attention and adoption owing to their advantageous features. Therefore, achieving clinical competence in ultrasound-guided CICC insertion in term and preterm infants is of paramount importance for neonatologists. A safe clinical training program should include theoretical teaching and clinical practice, simulation and supervised CICC insertions. Methods: We planned a training program for neonatologists for ultrasound-guided CICCs placement at our level III neonatal intensive care unit (NICU) in Modena, Italy. In this single-centre prospective observational study, we present the preliminary results of a 12-month training period. Two paediatric anaesthesiologists participated as trainers, and a multidisciplinary team was established for continuing education, consisting of neonatologists, nurses, and anaesthesiologists. We detail the features of our training program and present the modalities of CICC placement in newborns. Results: The success rate of procedures was 100%. In 80.5% of cases, the insertion was obtained at the first ultrasound-guided venipuncture. No procedure-related complications occurred in neonates (median gestational age 36 weeks, IQR 26-40; median birth weight 1200 g, IQR 622-2930). Three of the six neonatologists (50%) who participated in the clinical training program have achieved good clinical competence. One of them has acquired the necessary skills to in turn supervise other colleagues. Conclusions: Our ongoing clinical training program was safe and effective. Conducting the program within the NICU contributes to the implementation of medical and nursing skills of the entire staff.

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 - 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 - Effect of fortification on the osmolality of human milk [Articolo su rivista]
Elia, S.; Ciarcia, M.; Cini, N.; Luceri, F.; Mattei, M. L.; Miselli, F.; Perugi, S.; Fanelli, A.; Dani, C.
abstract

Background: It is known that human milk fortifiers (HMF) increases osmolality of human milk (HM) but some aspects of fortification have not been deeply investigated. Our aim was to evaluate the effect of fortification on the osmolality of donor human milk (DHM) and mother’s own milk (MOM) over 72 h of storage using two commercial fortifiers and medium-chain triglycerides (MCT) supplementation. Methods: Pasteurized DHM and unpasteurized preterm MOM were fortified with 4% PreNAN FM85, 4% PreNAN FM85 plus 2% MCT, or 4% Aptamil BMF. Osmolality was measured in unfortified DHM and MOM and, moreover, just after fortification (T0), and after 6 (T6), 24 (T24) and 72 h (T72) to determine the effect of mixing and storage. Results: Unfortified DHM and MOM did not show changes of osmolality. Fortification increased osmolality of DHM and MOM without changes during the study period, except for Aptamil BMF which increased osmolality of MOM. The addition of MCT to fortified human milk (FHM) did not affect its osmolality. Conclusions: Changes of osmolality in the 72 h following fortification of both DHM and MOM did not exceed the safety values supporting the theoretically possibility of preparing 72 h volumes of FHM. Supplementation with MCT of FHM does not change osmolality suggesting that increasing energy intake in preterm infants via this approach is safe.

2023 - Enteral and Parenteral Treatment with Caffeine for Preterm Infants in the Delivery Room: A Randomised Trial [Articolo su rivista]
Dani, C.; Cecchi, A.; Ciarcia, M.; Miselli, F.; Luzzati, M.; Remaschi, G.; Bona, M. D.; la Marca, G.; Boni, L.
abstract

Background: Early treatment with caffeine in the delivery room (DR) has been proposed to decrease the need for mechanical ventilation (MV) by limiting episodes of apnoea and improving respiratory mechanics in preterm infants. Our aim was to verify the hypothesis that intravenous or enteral administration of caffeine can be performed in the preterm infant in the DR. Methods: Infants with 25±0–29±6 weeks of gestational age were enrolled and randomised to receive 20 mg/kg of caffeine citrate intravenously, via the umbilical vein, or enterally, through an orogastric tube, within 10 min of birth. Caffeine blood level was measured at 60 ± 15 min after administration and 60 ± 15 min before the next dose (5 mg/kg). The primary endpoint was evaluation of the success rate of intravenous and enteral administration of caffeine in the DR. Results: Nineteen patients were treated with intravenous caffeine and 19 with enteral caffeine. In all patients the procedure was successfully performed. Peak blood level of caffeine 60 ± 15 min after administration in the DR was found to be below the therapeutic range (5 µg/mL) in 25 % of samples and above the therapeutic range in 3%. Blood level of caffeine 60 ± 15 min before administration of the second dose was found to be below the therapeutic range in 18% of samples. Conclusions: Intravenous and enteral administration of caffeine can be performed in the DR without interfering with infants’ postnatal assistance. Some patients did not reach the therapeutic range, raising the question of which dose is the most effective to prevent MV. Clinical Trial Registration: ClinicalTrials.gov identifier NCT04044976; EudraCT number 2018-003626-91.

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 - 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 - Noninvasive Monitoring Strategies for Bronchopulmonary Dysplasia or Post-Prematurity Respiratory Disease: Current Challenges and Future Prospects [Articolo su rivista]
Zini, Tommaso; Miselli, Francesca; Berardi, Alberto
abstract

Definitions of bronchopulmonary dysplasia (BPD) or post-prematurity respiratory disease (PPRD) aim to stratify the risk of mortality and morbidity, with an emphasis on long-term respiratory outcomes. There is no univocal classification of BPD due to its complex multifactorial nature and the substantial heterogeneity of clinical presentation. Currently, there is no definitive treatment available for extremely premature very-low-birth-weight infants with BPD, and challenges in finding targeted preventive therapies persist. However, innovative stem cell-based postnatal therapies targeting BPD-free survival are emerging, which are likely to be offered in the first few days of life to high-risk premature infants. Hence, we need easy-to-use noninvasive tools for a standardized, precise, and reliable BPD assessment at a very early stage, to support clinical decision-making and to predict the response to treatment. In this non-systematic review, we present an overview of strategies for monitoring preterm infants with early and evolving BPD-PPRD, and we make some remarks on future prospects, with a focus on near-infrared spectroscopy (NIRS).

2023 - Prognostic accuracy of Neonatal SOFA score versus SIRS criteria in preterm infants with late-onset sepsis [Articolo su rivista]
Poggi, C.; Ciarcia, M.; Miselli, F.; Dani, C.
abstract

Neonatal SOFA score was reported as an accurate predictor of mortality while the prognostic accuracy of SIRS criteria is unknown. The aim was to compare neonatal SOFA and SIRS criteria for the prediction of late onset sepsis-related mortality in preterm newborns. Newborns ≤ 32 weeks with late onset sepsis were retrospectively studied. Neonatal SOFA and SIRS criteria were calculated at onset of sepsis (T0), and after 6 ± 1 (T1), 12 ± 3 (T2) and 24 ± 3 h (T3). Outcome was death during antibiotic treatment for late onset sepsis. We studied 112 newborns with gestational age 26.9 ± 2.3 weeks; 11% met the study outcome. Neonatal SOFA was significantly higher in non-survivors vs. survivors at all time intervals; SIRS criteria were significantly higher in non-survivors vs. survivors at T1, T2 and T3. Neonatal SOFA increased over time in non-survivors (p = 0.003). At T0, the area under receiver operating characteristics curve was significantly higher for neonatal SOFA score than SIRS criteria (0.950 vs. 0.569; p = 0.0002), and the best calculated cut-off for T0 neonatal SOFA score was 4. In multivariate analysis T0 and T1 neonatal SOFA were predictors of late onset sepsis-related mortality (p = 0.048 and p < 0.001). Conclusion: Neonatal SOFA score showed greater discriminatory capacity for mortality than SIRS criteria and might be helpful to plan management for patients at higher risk of death. What is Known: • Neonatal SOFA score may be an accurate prognostic tool. • No prognostic score has been fully standardized for septic newborns in NICU. What is New: • Neonatal SOFA score outperformed SIRS criteria for the prediction of prognosis in preterm infants with late onset sepsis. • Neonatal SOFA score assessed at onset of sepsis and 6 hrs later is a predictor of mortality.

2023 - Splenomegaly in Kawasaki Disease: A Pitfall in Diagnosis [Articolo su rivista]
Miselli, F.; Mastrolia, M. V.; Simonini, G.; Trapani, S.; Calabri, G. B.
abstract

Among the 365 children diagnosed as having Kawasaki disease (KD), only 5 children (1.4%) presented with splenomegaly: 2 complicated by macrophage activation syndrome and 3 ultimately received a diagnosis of alternative systemic illness. Splenomegaly is atypical in KD and a potential marker of an underling complication, namely macrophage activation syndrome, or diagnosis other than KD.

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 - 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 - Effect of selective gastric residual monitoring on enteral intake in preterm infants [Articolo su rivista]
Elia, S.; Ciarcia, M.; Miselli, F.; Bertini, G.; Dani, C.
abstract

Objective: Prefeed gastric residuals (GRs) monitoring has been correlated with an increased time to reach full feeds and longer parenteral nutrition without beneficial effect on necrotizing enterocolitis (NEC) occurrence. We aimed to assess effects of a new local protocol to provide for the selective evaluation of GRs excluding their routine monitoring. Methods: We carried out a retrospective study based on a “before and after” design in a cohort of infants born at 23+0–31+6 weeks of gestation. The primary outcome was the age at full enteral feeding (150 mL/kg/d). Secondary outcomes included age at regaining of birth weight, and evaluation of Z-scores of weight, length, and head circumference at discharge. Results: We studied 49 infants in the selective GR group and 59 in the routine GR group. Age at full (150 mL/kg) enteral feeding (17.8 ± 10.1 vs. 22.9 ± 10.5 days, P = 0.017) and regaining of birth weight (11.1 ± 3.0 vs. 12.5 ± 3.5 days, P = 0.039) were lower while the Z-scores of weight at discharge (-1.10 ± 0.83 vs. -1.60 ± 1.45, P = 0.040) were higher in infants in the selective GR group in comparison with infants in the routine GR group. Conclusions: Selective monitoring of GRs decreased age at full enteral feeding and at regaining of birth weight and induced better Z-scores of weight at discharge in comparison with routine GR monitoring in a cohort of extremely preterm infants without increasing the incidence of NEC. Omitting prefeed GRs monitoring in clinical practice seems reasonable.

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 - 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 - Is recombinant tissue plasminogen activator treatment a safe choice in very and extremely preterm infants with intracardiac thrombosis? [Articolo su rivista]
Ciarcia, M.; Corsini, I.; Miselli, F.; Luzzati, M.; Coviello, C.; Leonardi, V.; Pratesi, S.; Dani, C.
abstract

2022 - Measurement of lung oxygenation by near-infrared spectroscopy in preterm infants with respiratory distress syndrome: A proof-of-concept study [Articolo su rivista]
Dani, C.; Ciarcia, M.; Miselli, F.; Luzzati, M.; Petrolini, C.; Corsini, I.; Simone, P.
abstract

Introduction: Noninvasive markers more accurate than FiO2 would be useful to assess the severity of RDS and guide its treatment. Our aim was to assess for the first time the possibility of continuously monitoring lung oxygenation (rSO2L) by near-infrared spectroscopy (NIRS) and to evaluate whether rSO2L correlates with other oxygenation indices and RDS severity. Methods: We carried out this proof-of-concept study on 20 preterm infants with RDS requiring noninvasive respiratory support. Patients were continuously studied for 24 h by NIRS and rSO2L was correlated with SpO2/FiO2 ratio, a/APO2, and O.I. Results: The overall value of rSO2L was 80.1 ± 6.2%, without significant differences between the right and left hemithorax (80.2 ± 6.7 vs. 80.0 ± 5.7%; p = 0.869). Mean values of total, right, and left rSO2L did not significantly change during the 24-h study period. Linear regression analysis demonstrated a significant positive relationship between total rSO2L and SpO2/FiO2 ratio (p < 0.001) and a/APO2 (p = 0.040), and a negative relationship between total rSO2L and O.I. (r = −0.309; p = 0.022). Conclusions: Continuous monitoring of rSO2L by NIRS in preterm infants with RDS is feasible and safe. The correlation of rSO2L with other indices of oxygenation and RDS severity supports the accuracy and reliability of this measurement.

2022 - Mediterranean Diet in Developmental Age: A Narrative Review of Current Evidences and Research Gaps [Articolo su rivista]
Farella, I.; Miselli, F.; Campanozzi, A.; Grosso, F. M.; Laforgia, N.; Baldassarre, M. E.
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Numerous studies in recent decades have shown that Mediterranean diet (MD) can reduce the risk of developing obesity in pediatric patients. The current narrative review summarizes recent evidence regarding the impact of MD across the different stages of child development, starting from fetal development, analyzing breastfeeding and weaning, through childhood up to adolescence, highlighting the gaps in knowledge for each age group. A literature search covering evidence published between 1 January 2000 and 1 March 2022 and concerning children only was conducted using multiple keywords and standardized terminology in PubMed database. A lack of scientific evidence about MD adherence concerns the age group undergoing weaning, thus between 6 months and one year of life. In the other age groups, adherence to MD and its beneficial effects in terms of obesity prevention has been extensively investigated, however, there are still few studies that correlate this dietary style with the incidence of non-communicable diseases. Furthermore, research on multi-intervention strategy should be implemented, especially regarding the role of education of children and families in taking up this healthy dietary style.

2022 - Platelet Count and Volume and Pharmacological Closure with Paracetamol of Ductus Arteriosus in Preterm Infants [Articolo su rivista]
Dani, C.; Ciarcia, M.; Miselli, F.; Luzzati, M.; Coviello, C.; Paladini, A.; Bottoni, A.; D'Andrea, V.; Vento, G.
abstract

Background: Low platelet count might promote resistance to pharmacological closure with indomethacin and ibuprofen of a hemodynamically significant patent ductus arteriosus (hsPDA). However, no studies have investigated if this occurs with paracetamol. Methods: We retrospectively assessed the correlation between platelet count, mean platelet volume (MPV), and plateletcrit (PCT), as well as the effectiveness of paracetamol in closing hsPDA in infants born at 23+0 –31+6 weeks of gestation who were treated with 15 mg/kg/6 h of i.v. paracetamol for 3 days. Results: We studied 79 infants: 37 (47%) Had closure after a course of paracetamol and 42 (53%) did not. Platelet count and PCT did not correlate with paracetamol success or failure in closing hsPDA, while MPV was lower at birth (10.7 ± 1.4 vs. 9.5 ± 1.1; p < 0.001) and prior to starting therapy (11.7 ± 1.9 vs. 11.0 ± 1.6; p = 0.079) in refractory infants. Regression analysis confirmed that the low MVP measured prior to starting the treatment increased the risk of hsPDA paracetamol closure failure (OR 1.664, 95% CI 1.153–2.401). Conclusions: The greater MPV correlated positively with the effectiveness of paracetamol in closing hsPDA, while platelet count and PCT did not influence closure rates. Additional studies are needed to confirm our results.

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.
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2022 - Splanchnic oxygenation during phototherapy in preterm infants with hyperbilirubinemia [Articolo su rivista]
Dani, C.; Ciarcia, M.; Miselli, F.; Luzzati, M.; Petrolini, C.; Corsini, I.; Pratesi, S.
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Background: It has been reported that preterm infants can develop feeding intolerance during phototherapy (PT) and that PT can affect mesenteric perfusion in these patients. Aims: Our aim was to assess if PT can decrease regional splanchnic oxygenation (rSO2S) measured by near infrared spectroscopy (NIRS). Study design: We prospectively studied infants with gestational age of 25–34 weeks with hyperbilirubinemia requiring PT. Splanchnic regional oxygenation (rSO2S), oxygen extraction fraction (FOES), and cerebrosplanchnic oxygenation ratio (CSOR) were recorded before, during, and after PT discontinuation. Results: During PT rSO2S and CSOR significantly decreased and this effect lasted for some hours after its interruption. FOES contemporary increased, although this effect was not statistically significant. Conclusions: PT treatment decreases splanchnic oxygenation in preterm infants likely due to peripheral vasodilation which triggers a redistribution of blood flow. These results can help explain the association between PT and the development of feeding intolerance in preterm infants.

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 - The management of late preterm infants: effects of rooming-in assistance versus direct admission to neonatal care units [Articolo su rivista]
Dani, C.; Ciarcia, M.; Miselli, F.; Luzzati, M.; Coviello, C.; Azzarelli, F.; Ferrara, M.; Lori, I.; Pezzati, M.
abstract

Late preterm infants (LPIs) represent a significant percentage of all neonates (6–8%), but there are limited published data on their postnatal management. Our aim was to compare the frequency of neonatal intensive care unit (NICU) admission and the breastfeeding rate of LPIs born at 35+0–36+6 weeks of gestation who were cared for by initial rooming in strategy rather than directly admitted to the special care unit (SCU) and, eventually, to the NICU. We carried out a retrospective study in the perinatal centers of Careggi University Hospital (CUH) and San Giovanni di Dio Hospital in Florence, Italy, where the first and second strategies were applied, respectively. Main outcomes were LPIs admission rate at SCU/NICU and breastfeeding rate at discharge. We studied 190 LPIs born at SGDH and 240 born at CUH. The admission rate in SCU (81 vs. 43%; P < 0.001) and NICU (20 vs. 10%; P = 0.008) was higher in SGDH than in CUH, as was the exclusive breastfeeding rate (36 vs. 22%; P < 0.001). However, infants who were assisted in rooming-in at CUH and infants with similar clinical characteristics at SGDH had similar mixed (60 vs. 69%) and exclusive (35 vs. 31%) breastfeeding rates. Conclusion: Postnatal assistance of LPIs in rooming-in, eventually followed by admission in SCU/NICU based on their clinical conditions, allowed to safely halve their hospitalization. The assistance of infants in rooming-in did not negatively affect their breastfeeding rate. These results support the possibility of assisting LPIs in rooming-in.What is Known:• Late preterm infants represent a significant percentage of all neonates.• Early rooming-in and breastfeeding is recommended for late preterm infants.What is New:• Postnatal assistance of late preterm infants in rooming-in, followed when necessary by admission in neonatal units based on clinical conditions, allowed to safely avoid about half the number of hospitalizations in comparison with direct admission in neonatal units.• This strategy did not affect breastfeeding rate. Infants who were admitted to SCU/NICU after initial rooming-in had worst breastfeeding rate.

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 - Coronary Involvement in Cardiac Neonatal Lupus [Articolo su rivista]
Miselli, F.; Capponi, G.; Greco, M.; Azzarelli, A.; Calabri, G. B.
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2021 - Neonatal heart failure and noncompaction/dilated cardiomyopathy from mucopolysaccharidosis. First description in literature [Articolo su rivista]
Miselli, F.; Brambilla, A.; Calabri, G. B.; Favilli, S.; Sanvito, M. C.; Ragni, L.; Torcetta, F.; Rossi, K.; Donati, M. A.; Procopio, E.
abstract

Mucopolysaccharidosis are genetic disorders due to deficiency of lysosomal enzymes, resulting in abnormal glycosaminoglycans accumulation in several tissues. Heart involvement tends to be progressive and worsens with age. We describe the first case of mucopolysaccharidosis type I presenting with noncompaction/dilated-mixed cardiomyopathy and heart failure within neonatal period, which responded successfully to specific metabolic treatment. Cardiac function recovered after enzyme replacement therapy and hematopoietic stem cell transplantation, adding to the existing knowledge of the disease.

2019 - Methicillin-resistant Staphylococcus aureus eradication in cystic fibrosis patients: A randomized multicenter study [Articolo su rivista]
Dolce, Daniela; Neri, Stella; Grisotto, Laura; Campana, Silvia; Ravenni, Novella; Miselli, Francesca; Camera, Erica; Zavataro, Lucia; Braggion, Cesare; Fiscarelli, Ersilia V.; Lucidi, Vincenzina; Cariani, Lisa; Girelli, Daniela; Faelli, Nadia; Colombo, Carla; Lucanto, Cristina; Lombardo, Mariangela; Magazzu, Giuseppe; Tosco, Antonella; Raia, Valeria; Manara, Serena; Pasolli, Edoardo; Armanini, Federica; Segata, Nicola; Biggeri, Annibale; Taccetti, Giovanni
abstract