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FRANCESCA MONARI

Docente a contratto
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto
Tutor di tirocinio
Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze sede Policlinico

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Pubblicazioni

2022 - First-trimester prediction model for placental vascular disorders: an observational prospective study [Articolo su rivista]
Monari, Francesca; Spano' Bascio, Ludovica; Banchelli, Federico; Neri, Isabella; Bertucci, Emma; Ferrari, Francesca; Menichini, Daniela; D'Amico, Roberto; Facchinetti, Fabio
abstract

This study aims to develop a multivariable predictive model for the risk of placental vascular complications (PVC), by using biochemical, biophysical, anamnestic and clinical maternal features available at the first trimester. PVC include gestational hypertension, preeclampsia, placenta abruption, intrauterine growth restriction (IUGR), and stillbirth. Prospective study that included all singleton pregnancies attending the first-trimester aneuploidy screening (11 +0–12 +6 weeks) at Obstetrics Unit of the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. In a total of 503 women included in the analysis, 40 patients were in the PVC group. The final prediction model for PVC included the following independent variables: pre-pregnancy BMI ≥ 30 (OR = 2.65, 95% CI = 1.04; 6.75, p = 0.0415), increasing values of mean arterial pressure (OR = 1.06, 95% CI = 1.02; 1.10, p = 0.0008), PAPP-A < 2.40465 U/L (OR = 0.43, 95% CI = 0.19; 0.96, p = 0.0388) and decreasing values of PlGf (MoM) (OR = 0.28, 95% CI = 0.10; 0.79, p = 0.0153). The area under the ROC curve was 79.4% indicating a satisfactory predictive accuracy. The best predictive cut-off for this score was equal to − 2.562, which corresponds to a 7.2 % probability of having PVC. By using such a cut-off, the risk of PVC can be predicted in our sample with sensitivity equal to 82,4 % and specificity equal to 69,9 %. This model for early prediction of PVC is a promising tool to early identify women at greater risk for placenta vascular complications.

2022 - Screening for Low-Tract Genital Infections in Women with Threatened Preterm Labor: Which Role? [Articolo su rivista]
Sileo, Filomena Giulia; Inversetti, Annalisa; Bonati, Francesca; Celora, Gabriella; Donno, Valeria; Giuliani, Giulia Andrea; Pellegrini, Rosamaria; Monari, Francesca; Locatelli, Anna; Facchinetti, Fabio
abstract

The aim of this study was to evaluate the possible relationship between cultural specimens and preterm birth in women admitted for threatened preterm labor. Preterm birth is the leading cause of neonatal mortality and antenatal hospitalization; several risk factors including intrauterine infections have been identified, but its real causes remain poorly understood.

2021 - A first trimester prediction model for large for gestational age infants: a preliminary study [Articolo su rivista]
Monari, F.; Menichini, D.; Spano' Bascio, L.; Grandi, G.; Banchelli, F.; Neri, I.; D'Amico, R.; Facchinetti, F.
abstract

Background: Large for gestational age infants (LGA) have increased risk of adverse short-term perinatal outcomes. This study aims to develop a multivariable prediction model for the risk of giving birth to a LGA baby, by using biochemical, biophysical, anamnestic, and clinical maternal characteristics available at first trimester. Methods: Prospective study that included all singleton pregnancies attending the first trimester aneuploidy screening at the Obstetric Unit of the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. Results: A total of 503 consecutive women were included in the analysis. The final prediction model for LGA, included multiparity (OR = 2.8, 95% CI: 1.6–4.9, p = 0.001), pre-pregnancy BMI (OR = 1.08, 95% CI: 1.03–1.14, p = 0.002) and PAPP-A MoM (OR = 1.43, 95% CI: 1.08–1.90, p = 0.013). The area under the ROC curve was 70.5%, indicating a satisfactory predictive accuracy. The best predictive cut-off for this score was equal to − 1.378, which corresponds to a 20.1% probability of having a LGA infant. By using such a cut-off, the risk of LGA can be predicted in our sample with sensitivity of 55.2% and specificity of 79.0%. Conclusion: At first trimester, a model including multiparity, pre-pregnancy BMI and PAPP-A satisfactorily predicted the risk of giving birth to a LGA infant. This promising tool, once applied early in pregnancy, would identify women deserving targeted interventions. Trial registration: ClinicalTrials.gov NCT04838431, 09/04/2021.

2020 - The Burden of Placental Histopathology in Stillbirths Associated With Maternal Obesity [Articolo su rivista]
Avagliano, L.; Monari, F.; Po', G.; Salerno, C.; Mascherpa, M.; Maiorana, A.; Facchinetti, F.; Bulfamante, G. P.
abstract

OBJECTIVES: Obesity is an increasing health problem that has become a common medical disorder among women of childbearing age, representing worldwide a risk factor for stillbirth. The aim of the study is to evaluate the association between placental histopathologic findings and obesity in stillbirth. METHODS: Placentas were analyzed according to the Amsterdam consensus statement. Histologic findings in stillbirth from obese and lean mothers were analyzed and compared with those observed in liveborn controls. RESULTS: Stillbirth in obese mothers displayed placental pathology in all gestational ages, mostly at term of pregnancy. The most observed placental lesions were those consistent with maternal vascular malperfusion of the placental bed. Decidual arteriopathy and placental infarcts appeared specifically associated with maternal obesity. Moreover, obese women with stillbirth showed the highest cumulative number of placental lesions. CONCLUSIONS: Considering the significant association between stillbirth, maternal obesity, and placental histopathologic findings, health care providers should be aware about the importance of placental examination in obese women, especially in stillborn cases. The high prevalence of lesions consistent with vascular malperfusion of the placental bed suggests that stillbirth prevention strategies in obese women should rely on the development of tools to study and improve decidual artery functioning early in pregnancy.

2019 - A regional audit system for stillbirth: A way to better understand the phenomenon [Articolo su rivista]
Po, G.; Monari, F.; Zanni, F.; Grandi, G.; Lupi, C.; Facchinetti, F.; Mancini, L.; Lugli, L.; Lanzoni, C.; Sgarbi, L.; Chiossi, C.; Ricchieri, F.; Roberta, C.; Contiero, R.; Garani, G.; Pedriali, M.; Rossi, S.; Fini, S.; Di Bartolo, M.; Radi, D.; Vancini, A.; Donati, A.; Guadalupi, E.; Righetti, F.; Salerno, A.; Cocchi, G.; Morandi, R.; Gabrielli, L.; Graziano, C.; Seri, M.; Caprara, G.; Mario, S. N. C.; Fantuz, F.; Ferlini, F.; Righi, E.; Silvestrini, D.; Foschi, F.; Fieni, S.; Frusca, T.; Ferretti, A.; Galli, L.; Magnani, C.; Silini, E.; Balduzzi, L.; Bellini, M.; Rodolfi, A. M.; Sgarabotto, M. P.; Fragni, G.; Comitini, G.; Bonasoni, M. P.; Fioroni, L.; Rozzi, C.; Tuzio, A.; Vito, I.; Mammoliti, P.; De Ambrosi, E.; Ricci, M.; Bandini, A.; Belosi, C.; Muratori, C.; Zago, S.; Turci, A.; Vitarelli, M.
abstract

Background: Implementation of high-quality national audits for perinatal mortality are needed to improve the registration of all perinatal deaths and the identification of the causes of death. This study aims to evaluate the implementation of a Regional Audit System for Stillbirth in Emilia-Romagna Region, Italy. Methods: For each stillbirth (≥ 22 weeks of gestation, ≥ 500 g) occurred between January 1, 2014 to December 1, 2016 (n = 332), the same diagnostic workup was performed and a clinical record with data about mother and stillborn was completed. Every case was discussed in a multidisciplinary local audit to assess both the cause of death (ReCoDe classification) and the quality of care. Data were reviewed by the Regional Audit Group. Stillbirth rates, causes of death and the quality of care were established for each case. Results: Total stillbirth rate was 3.09 per 1000 births (332/107,528). Late stillbirth rate was 2.3 per 1000 (251/107,087). Sixteen stillbirths were not registered by the Regional Birth Register. The most prevalent cause of death was placental disorder (33.3%), followed by fetal (17.6%), cord (14.2%) and maternal disorders (7.6%). Unexplained cases were 14%. Compared to local audits, the regional group attributed different causes of death in 17% of cases. At multivariate analysis, infections were associated with early stillbirths (OR 3.38, CI95% 1.62-7.03) and intrapartum cases (OR 6.64, CI95% 2.61-17.02). Placental disorders were related to growth restriction (OR 1.89, CI95% 1.06-3.36) and were more frequent before term (OR 1.86, CI95% 1.11-3.15). Stillbirths judged possibly/probably preventable with a different management (10.9%) occurred more frequently in non-Italian women and were mainly related to maternal disorders (OR 6.64, CI95% 2.61-17.02). Conclusions: Regional Audit System for Stillbirth improves the registration of stillbirth and allows to define the causes of death. Moreover, sub-optimal care was recognized, allowing to identify populations which could benefit from preventive measures.

2019 - Iatrogenic late preterm birth: when is it recommended? A Delphi survey promoted by the Italian Society of Perinatal Medicine [Articolo su rivista]
Monari, F.; Parazzini, F.; Cetin, I.; Ballarini, M.; Facchinetti, F.
abstract

Background: The rate of iatrogenic Late Preterm (LP) Birth varies in different settings. This is due to the lack of strong evidence/guidelines on the management of the different maternal, fetal and placental complications affecting pregnancy in the LP window. Steroid prophylaxis is also under discussion. Aim: To build recommendations about the management of main medical complications (pregestational diabetes, placenta previa, preeclampsia, cholestasis, p-PROM, intrauterine growth restriction -IUGR-) occurring in the LP period to reduce clinical heterogeneity. Methods: A group of Italian Perinatal experts were identified by Scientific Societies. A Delphi consensus methodology was used to reach agreement on different clinical sceneries. Two rounds of consultation by using a purpose built on-line survey and a third open panel discussion were performed. Results: The panel of 50 experts reached agreement for the vast majority of clinical sceneries (Placenta Previa, Preeclampsia, Diabetes, Cholestasis). Overall, there was agreement to be conservative at 34 weeks and in favor of delivery at 36 weeks. The management of p-PROM and mostly of IUGR were characterized by a minor degree of consensus. Corticosteroids were found necessary at the 34th week and unnecessary at the 36th week. Conclusions: Besides providing some guidance on clinical indications for LP iatrogenic delivery, these results represent a stimulus for designing future trials investigating the grey areas in this field.

2017 - Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome: the PREGNANTS study [Articolo su rivista]
Saccone, Gabriele; Berghella, Vincenzo; Maruotti, Giuseppe Maria; Ghi, Tullio; Rizzo, Giuseppe; Simonazzi, Giuliana; Rizzo, Nicola; Facchinetti, Fabio; Dall'Asta, Andrea; Visentin, Silvia; Sarno, Laura; Xodo, Serena; Bernabini, Dalila; Monari, Francesca; Roman, Amanda; Eke, Ahizechukwu Chigoziem; Hoxha, Ariela; Ruffatti, Amelia; Schuit, Ewoud; Martinelli, Pasquale
abstract

Antiphospholipid syndrome is an autoimmune, hypercoagulable state that is caused by antiphospholipid antibodies. Anticardiolipin antibodies, anti-β2 glycoprotein-I, and lupus anticoagulant are the main autoantibodies found in antiphospholipid syndrome. Despite the amassed body of clinical knowledge, the risk of obstetric complications that are associated with specific antibody profile has not been well-established.

2016 - Adverse perinatal outcome in subsequent pregnancy after stillbirth by placental vascular disorders [Articolo su rivista]
Monari, Francesca; Pedrielli, Giulia; Vergani, Patrizia; Pozzi, Elisa; Mecacci, Federico; Serena, Caterina; Neri, Isabella; Facchinetti, Fabio
abstract

Objective: To evaluate outcome in the pregnancy following a stillbirth (SB) by a placental vascular disorders. Study Design: A prospective, observational, multicenter study was conducted in woman with a history of stillbirth (> 22 weeks) between 2005 and June 2013, in 3 Italian University Hospitals. Causes of SB were previously identified after extensive investigations. Pregnant women were enrolled within the first trimester. The main outcome was "adverse neonatal outcome", including perinatal death, fetal growth restriction, early preterm birth <33+6 weeks, hypoxicischemic encephalopathy, intracranial hemorrhage or respiratory distress. Results: Out of 364 index pregnancies, 320 women (87.9%) had a subsequent pregnancy during the study period. Forty-seven had an early pregnancy loss. Out of 273 babies, 67 (24.5%) had an adverse perinatal outcome, including 1 SB and 1 early neonatal death (3.7/1000). Women who had a SB related to placental vascular disorders (39.6%), were at higher risk of an adverse neonatal outcome compared with women whose SB was unexplained or resulted from other causes (Adj. OR = 2.1, 95%CI: 1.2-3.8). Moreover, also obesity independently predicts an adverse perinatal outcome (Adj OR = 2.1, 95%CI: 1.1-4.3). Conclusion: When previous SB is related to placental vascular disorders there is a high risk for adverse neonatal outcomes in the subsequent pregnancy. Maternal obesity is an additional risk factor.

2013 - Fetal bacterial infections in antepartum stillbirth: a case series [Articolo su rivista]
Monari, Francesca; Gabrielli, L; Gargano, Giuseppe; Annessi, Eleonora; Ferrari, Francesca; Rivasi, Francesco; Facchinetti, Fabio
abstract

OBJECTIVES: This study aims to assess the frequency of fetal bacterial infections in stillbirth (SB) and to evaluate the best samples for the diagnosis of infection-related SB. STUDY DESIGN: Consecutive cases of antepartum SB were enrolled. Vaginal and placental swabs, as well as heart blood cultures and surface swabs from the neonate, were collected. Histological examinations were performed by the same examiner. Immunohistochemistry for leukocyte common antigen was performed in the placenta and fetus. Each case was discussed in a multidisciplinary audit. RESULTS: One hundred and nine cases were enrolled. Fetal blood cultures were positive in 20/95 cases (21%). Significant histological findings in the placenta/cord and in at least one fetal organ were observed in 8 cases of them (4 Group B Streptococcus GBS, 2 Listeria monocytogenes, 1 Coagulase negative Staphylococcus, 1 Pseudomonas aeruginosa). Neither tissue damage nor inflammatory infiltrate was found in the 12 remnant cases. Funisitis while not histological chorioamnionitis was associated with microbiological findings. Positive findings in maternal/placental/fetal swabs occurred in 18-32% of cases with both negative fetal blood cultures and histopathological findings. With the exception of GBS, no other bacteria agent could be detected by any of the swabs. CONCLUSIONS: Eight cases (8.4%) fulfilled both microbiological and histology criteria allowing the diagnosis of SB-related fetal infection demonstrating that search for infections is essential in SB evaluation. Fetal blood culture, placenta swab for GBS and search for histological funisitis are mandatory actions within the SB work-up in order to guide pathology examination and reach clinical conclusions.

2012 - RELATION BETWEEN MATERNAL THROMBOPHILIA AND STILLBIRTH ACCORDING TO CAUSES/ASSOCIATED CONDITIONS OF DEATH [Articolo su rivista]
Monari, Francesca; Alberico, S; Avagliano, L; Cetin, I; Cozzolino, S; Gargano, G; Marozio, L; Mecacci, F; Neri, Isabella; Tranquilli, Al; Venturini, P; Facchinetti, Fabio
abstract

OBJECTIVE: To investigate maternal thrombophilia in cases of Stillbirth (SB), also an uncertain topic because most case series were not characterised for cause/associated conditions of death. STUDY DESIGN: In a consecutive, prospective, multicentre design, maternal DNA was obtained in 171 cases of antenatal SB and 326 controls (uneventful pregnancy at term, 1:2 ratio). Diagnostic work-up of SB included obstetric history, neonatologist inspection, placenta histology, autopsy, microbiology/chromosome evaluations. Results audited in each centre were classified by two of us by using CoDAC. Cases were subdivided into explained SB where a cause of death was identified and although no defined cause was detected in the remnants, 64 cases found conditions associated with placenta-vascular disorders (including preeclampsia, growth restriction and placenta abruption - PVD). In the remnant 79 cases, no cause of death or associated condition was found. Antithrombin activity, Factor V Leiden, G20210A Prothrombin mutation (FII mutation) and acquired thrombophilia were analysed. RESULTS: Overall, the presence of a thrombophilic defect was significantly more prevalent in mothers with SBs compared to controls. In particular, SB mothers showed an increased risk of carrying Factor II mutation (OR=3.2, 95\% CI: 1.3-8.3, p=0.01), namely in unexplained cases. Such mutation was significantly associated also with previous SB (OR=8.9, 95\%CI 1.2-70.5). At multiple logistic regression, Factor II mutation was the only significantly associated variable with SB (adj OR=3.8, 95\% CI: 1.3-13.5). CONCLUSION: These data suggest that Factor II mutation is the only condition specifically associated with unexplained SB and could represents a risk of recurrence. PVD-associated condition is unrelated to thrombophilia.

2011 - Stillbirth: issues and new insights [Articolo su rivista]
Facchinetti, Fabio; Ferrari, Francesca; Monari, Francesca; Neri, Isabella
abstract

Disparities in stillbirth (SB) are mainly related to socioeconomic factors. Developing countries have a SB rate five-times higher than that of developed countries, one-third of which occur intrapartum. Instead, in developed countries the access to antenatal care became the first preventive intervention for SB. In this article, we summarize strategies for SB prevention in the developing and developed world. Moreover, we report a critical evaluation of the six most used classification systems, highlighting the best performer. Similarly, we summarize the necessary diagnostic examinations for an appropriate classification of SB. Some of the new lines of investigation are reported here. However, any new finding on the cause of SB has to acknowledge a model of interpretation that takes into account a triad; the fetus and its characteristics, the uterine environment and the circumstances of death.

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 - Management of subsequent pregnancy after antepartum stillbirth. A review. [Articolo su rivista]
Monari, Francesca; Facchinetti, Fabio
abstract

In literature, there is a paucity of information about the management of the subsequent pregnancy after stillbirth (SB). we undertook a systematic review of the literature focusing on the evidence for antenatal interventions with the potential to prevent SB and we try to summarise the management of the pregnancy subsequent to a SB. The diverse interventions and their efficacy will be reported according to the possible causes and/or conditions associated to the previous SB. Few of the studies reported SB as an outcome and the evidence was frequently conflicting. Several interventions showed clear evidence of impact on SB, including the scrupulous control of blood sugar by using multiple doses of insulin, frequent antenatal foetal monitoring and timing of delivery in diabetic women; the prophylaxis with low dose of aspirin in high-risk women; or serial sonograms for foetal growth, Doppler studies and antepartum foetal testing in women with previous growth restricted foetus. Other interventions instead reduced know risk factors for SB but failed to show statistically significant impact on SB rate. Overall, early access to care, at least three ultrasounds examinations, screening for the main pregnancy-related disorders and timely delivery are the milestone of appropriate antenatal care in women with previous SB.

2009 - Computerized Evaluation of Fetal Heart Rate during Tocolytic Treatment: Comparison between Atosiban and Ritodrine. [Articolo su rivista]
Neri, Isabella; Monari, Francesca; Herbert, Valensise; Barbara, Vasapollo; Facchinetti, Fabio; Volpe, Annibale
abstract

We compared the effects of ritodrine and atosiban treatments on fetal cardiovascular behavior by computerized nonstress test (c-NST) analysis. Women diagnosed with preterm labor were randomized to receive either atosiban or ritodrine. A c-NST was performed at least 12 hours after the last corticosteroid administration. Differences in fetal cardiovascular behavior were evident when treatment was given before 30 weeks' gestation. Ritodrine induced higher fetal heart rates, lower long-term variation values, and lower low:high-frequency ratios compared with atosiban. Atosiban induced higher gestational ages at delivery and higher birth weights than ritodrine. The mean Apgar scores were similar for atosiban and ritodrine groups at 1 and 5 minutes. No 5-minute Apgar score was &lt; 7. With respect with atosiban, ritodrine treatment induces tachycardia and a lower variability of fetal heart rate. Such changes could be erroneously interpreted as signal of fetal distress, namely at lower gestational age.

2008 - Obstetricians' and midwives' attitudes toward cesarean section [Articolo su rivista]
Monari, Francesca; Di Mario, S; Facchinetti, Fabio; Basevi, V.
abstract

BACKGROUND: The cesarean section rate has increased worldwide over the past 20 years; in Italy, it is now more than 35 percent. Although clinical factors are important, the attitudes of health practitioners toward cesarean section need further investigation to correctly identify facilitators and barriers to changes. The objective of this study was to explore the attitudes toward cesarean section of midwives and obstetricians who worked in the same geographical area. METHODS: Face-to-face structured interviews using an adaptation of the Survey of Clinicians' Views on Caesarean Section, an anonymous questionnaire with 35 open and closed answers on practitioners' views on cesarean section, were conducted. The questionnaire was given to the entire group of midwives and obstetricians working in Modena, a northern Italian district. RESULTS: Of 262 eligible practitioners, 248 were interviewed (response rate 94.6%). The midwives' attitudes toward cesarean section differed from those of the obstetricians. Sixty-five percent of midwives considered the rates of cesarean section in their hospitals to be too high compared with 34 percent of obstetricians (p < 0.001). Midwives were also less inclined to believe that cesarean section provides benefits to the mother (p = 0.02) or that it is indicated by previous cesarean delivery (p < 0.001). No differences were observed between male and female obstetricians. CONCLUSIONS: In this survey, the attitudes toward cesarean section were correlated more with professional role than with gender. This information can help policy makers to shape interventions aimed at providing better care for pregnant and childbearing women.