Publications by authors named "Daniele Di Mascio"

59 Publications

Risk of neural tube defects according to maternal body mass index: a systematic review and meta-analysis.

J Matern Fetal Neonatal Med 2021 Jul 5:1-10. Epub 2021 Jul 5.

Department of Maternal and Child Health and Urologynecological Sciences, Sapienza University of Rome, Umberto I Hospital, Rome, Italy.

Introduction: The aim of our systematic review and meta-analysis was to evaluate the risk of neural tube defects (NTDs) according to the pre-pregnancy body mass index.

Materials And Methods: Electronic databases were searched (MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID, and Cochrane Library). Selection criteria included prospective and retrospective cohort studies reporting the prevalence of fetal NTDs in obese, overweight, and underweight pregnant women. Odds ratios (ORs) comparing risk among these subsets of pregnancies with normal weight mothers were determined with 95% confidence intervals (CI). The evaluated outcome was the association between maternal underweight, overweight, and obesity and the risk of NTDs.

Results: We included ten studies published between 2000 and 2017, including underweight, overweight, and obese pregnant women with fetal NTD (cases) and pregnant women with recommended BMI with fetal NTD (controls). Compared with normal BMI women, obese mothers were at significantly higher risk of fetal NTDs (0.53 0.33%; OR 1.62 95% CI 1.32-1.99,  < .0001), while no difference for the risk of NTDs was found when comparing overweight (0.34 0.32%; OR 1.09 95% CI 0.92-1.3,  = .3) and underweight (0.65 0.24%; OR 1.34 95% CI 0.73-2.47,  = .34) with normal weight pregnant women.

Discussion: Obese pregnant women are at significantly higher risk NTDs, while no significant difference has been found in overweight and underweight pregnant women. Key message Obese pregnant women are at significantly higher risk of NTDs, such as spina bifida compared with normal weight women. No difference was found when comparing overweight and underweight with normal weight women.
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http://dx.doi.org/10.1080/14767058.2021.1946789DOI Listing
July 2021

Reply to Delayed versus immediate pushing in the second stage of labor in women with neuraxial analgesia: a systematic review and meta-analysis of randomized controlled trials.

Am J Obstet Gynecol 2021 Jun 23. Epub 2021 Jun 23.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College, Thomas Jefferson University, 834 Chestnut St., Philadelphia, PA 19107. Electronic address:

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http://dx.doi.org/10.1016/j.ajog.2021.06.073DOI Listing
June 2021

Induction within or after 12 hours of ≥36 weeks' prelabor rupture of membranes: a systematic review and meta-analysis.

Am J Obstet Gynecol MFM 2021 Jun 18;3(5):100425. Epub 2021 Jun 18.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA. Electronic address:

Objective: This study aimed to evaluate the incidence of chorioamnionitis in women with singleton gestations with ≥36 weeks' prelabor rupture of membranes induced with oxytocin within or after 12 hours of prelabor rupture of membranes.

Data Sources: The search was conducted using MEDLINE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID, and Cochrane Library as electronic databases from their inception to May 2020.

Study Eligibility Criteria: Randomized controlled trials of women with singleton cephalic gestations and prelabor rupture of membranes at ≥36 weeks comparing induction of labor with oxytocin either ≤12 hours after prelabor rupture of membranes or >12 hours after prelabor rupture of membranes (expectant management group).

Study Appraisal And Synthesis Methods: The risk of bias in each included study was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. All analyses were done using an intention-to-treat approach, evaluating women according to the treatment group to which they were randomly allocated in the original trials. The primary outcome was the incidence of chorioamnionitis.

Results: After exclusions, 9 randomized controlled trials including 3759 women were analyzed. Women with singleton cephalic gestations and prelabor rupture of membranes at ≥36 weeks who have induction of labor ≤12 hours after prelabor rupture of membranes have shorter time between prelabor rupture of membranes and delivery (-12.68 hours; 95% confidence interval, -16.15 to -9.21) and higher chance of delivering within 24 hours of prelabor rupture of membranes (91% vs 46%; relative risk, 1.93; 95% confidence interval, 1.59-2.35). Cesarean and operative vaginal deliveries were not significantly different between the groups. Induction of labor ≤12 hours after prelabor rupture of membranes was also associated with significantly fewer incidences of chorioamnionitis (5.3% vs 9.9%; relative risk, 0.62; 95% confidence interval, 0.40-0.97), endometritis (2.4% vs 4.2%; relative risk, 0.59; 95% confidence interval, 0.40-0.87), neonatal sepsis (6.1% vs 11.8%; relative risk, 0.46; 95% confidence interval, 0.27-0.79), and admission to neonatal intensive care unit (6.4% vs 12.0%; relative risk, 0.54; 95% confidence interval, 0.43-0.69) compared with women managed expectantly, usually at >24 hours. The subgroup analysis of 3323 women with induction of labor at ≤6 hours showed similar results, including similar significant reductions in chorioamnionitis, endometritis, neonatal sepsis, and admission to neonatal intensive care unit.

Conclusion: Women with symptoms of prelabor rupture of membranes at ≥36 weeks should be evaluated promptly, and if prelabor rupture of membranes is confirmed, they should have induction of labor within 12 hours and perhaps even within 6 hours since the first symptom of prelabor rupture of membranes. This management is associated with significantly less morbidity, especially in terms of infections, for both the mother and the baby, with no evidence of any harm.
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http://dx.doi.org/10.1016/j.ajogmf.2021.100425DOI Listing
June 2021

Comparison between Cerebroplacental Ratio and Umbilicocerebral Ratio in Predicting Adverse Perinatal Outcome in Pregnancies Complicated by Late Fetal Growth Restriction: A Multicenter, Retrospective Study.

Fetal Diagn Ther 2021 15;48(6):448-456. Epub 2021 Jun 15.

Center for High Risk Pregnancy and Fetal Care, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy.

Introduction: The role of cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) to predict adverse intrapartum and perinatal outcomes in pregnancies complicated by late fetal growth restriction (FGR) remains controversial.

Methods: This was a multicenter, retrospective cohort study involving 5 referral centers in Italy and Spain, including singleton pregnancies complicated by late FGR, as defined by Delphi consensus criteria, with a scan 1 week prior to delivery. The primary objective was to compare the diagnostic accuracy of the CPR and UCR for the prediction of a composite adverse outcome, defined as the presence of either an adverse intrapartum outcome (need for operative delivery/cesarean section for suspected fetal distress) or an adverse perinatal outcome (intrauterine death, Apgar score <7 at 5 min, arterial pH <7.1, base excess of >-11 mEq/mL, or neonatal intensive care unit admission).

Results: Median CPR absolute values (1.11 vs. 1.22, p = 0.018) and centiles (3 vs. 4, p = 0.028) were lower in pregnancies with a composite adverse outcome than in those without it. Median UCR absolute values (0.89 vs. 0.82, p = 0.018) and centiles (97 vs. 96, p = 0.028) were higher. However, the area under the curve, 95% confidence interval for predicting the composite adverse outcome showed a poor predictive value: 0.580 (0.512-0.646) for the raw absolute values of CPR and UCR, and 0.575 (0.507-0.642) for CPR and UCR centiles adjusted for gestational age. The use of dichotomized values (CPR <1, UCR >1 or CPR <5th centile, UCR >95th centile) did not improve the diagnostic accuracy.

Conclusion: The CPR and UCR measured in the week prior delivery are of low predictive value to assess adverse intrapartum and perinatal outcomes in pregnancies with late FGR.
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http://dx.doi.org/10.1159/000516443DOI Listing
June 2021

Diagnostic performance of cerebroplacental and umbilicocerebral ratio in appropriate for gestational age and late growth restricted fetuses attempting vaginal delivery: a multicenter, retrospective study.

J Matern Fetal Neonatal Med 2021 Jun 8:1-7. Epub 2021 Jun 8.

Fetal Medicine Unit, Maternal and Child Health and Development Network, Department of Obstetrics and Gynecology, University Hospital 12 de Octubre, Complutense University of Madrid, Madrid, Spain.

Background: Cerebroplacental Doppler studies have been advocated to predict the risk of adverse perinatal outcome (APO) irrespective of fetal weight.

Objective: To report the diagnostic performance of cerebroplacental (CPR) and umbilicocerebral (UCR) ratios in predicting APO in appropriate for gestational age (AGA) fetuses and in those affected by late fetal growth restriction (FGR) attempting vaginal delivery.

Study Design: Multicenter, retrospective, nested case-control study between 1 January 2017 and January 2020 involving five referral centers in Italy and Spain. Singleton gestations with a scan between 36 and 40 weeks and within two weeks of attempting vaginal delivery were included. Fetal arterial Doppler and biometry were collected. The AGA group was defined as fetuses with an estimated fetal weight and abdominal circumference >10th and <90th percentile, while the late FGR group was defined by Delphi consensus criteria. The primary outcome was the prediction of a composite of perinatal adverse outcomes including either intrauterine death, Apgar score at 5 min <7, abnormal acid-base status (umbilical artery pH < 7.1 or base excess of more than -11) and neonatal intensive care unit (NICU) admission. Area under the curve (AUC) analysis was performed.

Results: 646 pregnancies (317 in the AGA group and 329 in the late FGR group) were included. APO were present in 12.6% AGA and 24.3% late FGR pregnancies, with an odds ratio of 2.22 (95% CI 1.46-3.37). The performance of CPR and UCR for predicting APO was poor in both AGA [AUC: 0.44 (0.39-0.51)] and late FGR fetuses [AUC: 0.56 (0.49-0.61)].

Conclusions: CPR and UCR on their own are poor prognostic predictors of APO irrespective of fetal weight.
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http://dx.doi.org/10.1080/14767058.2021.1926977DOI Listing
June 2021

The efficacy of abdominal binders in reducing postoperative pain and distress after cesarean delivery: A meta-analysis of randomized controlled trials.

Eur J Obstet Gynecol Reprod Biol 2021 Jul 9;262:73-79. Epub 2021 May 9.

Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Policlinico Umberto I, Rome, Italy.

Objective: To evaluate the efficacy of abdominal binders in reducing postoperative pain, patient distress and surgical postoperative sequelae after cesarean delivery (CD).

Methods: A comprehensive search in electronic databases (MEDLINE, EMBASE, and Cochrane Central) was performed up to February 2021. Selection criteria included randomized clinical trials investigating the application or not of abdominal binder after CD. The primary outcome was postoperative pain, measured using the visual analog scale (VAS) pain score. Secondary outcomes were divided into short- and long-term postoperative outcomes, including patient distress, need for additional pain medications, time to mobilization, return to normal daily activities, surgical site infection, fascial dehiscence or incisional hernia, and rectus abdominis diastasis. The summary measures were reported as mean difference with 95 % confidence intervals (CI) using the random effects model of DerSimonian and Laird. An I (Higgins I) value of greater than 0% was used to identify heterogeneity.

Results: Four RCTs involving 601 women were included for meta-analysis: 310 (51.6 %) were randomized to the abdominal binder and 291 (48.4 %) to no abdominal binder group. There was no statistically significant difference between the two groups for VAS score either at 24 h (MD -0.97, 95 % CI -2.23 to 0.30; p = 0.13) and at 48 h (MD -0.30, 95 % CI -0.71 to 0.11; p = 0.15). Conversely, there was a significant reduction in postoperative distress (SDS) both at 24 h (MD -2.23, 95 % CI -3.77 to -0.70; p = 0.004) and 48 h (MD -2.37, 95 % CI -3.86 to -0.87; p = 0.002).

Conclusion: The present meta-analysis shows that the use of abdominal binders after CD significantly reduces patient distress.
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http://dx.doi.org/10.1016/j.ejogrb.2021.05.014DOI Listing
July 2021

Induction of labor in late FGR.

Minerva Obstet Gynecol 2021 Aug 5;73(4):490-493. Epub 2021 May 5.

Center for Fetal Care and High-Risk Pregnancy, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy -

Late-onset FGR is a peculiar condition characterized by the inability for the fetus to reach its growth potential diagnosed from 32 weeks of gestation. Placental insufficiency is among the leading causes of late FGR and is commonly due to a primary maternal cardiovascular non-adaptation potentially leading to fetal decompensation during labor especially once exposed to uterine hyperstimulation. Abnormalities that usually characterize late FGR include reduced fetal growth, decreased Amniotic Fluid Index, and loss of fetal heart rate variability at CTG. Fetal hemodynamics study by Doppler ultrasound significantly improved management of pregnancies affected by fetal growth restriction. A major issue when dealing with pregnancies complicated by late FGR is how to induce these women. Induction of labor (IOL) can be essentially accomplished by pharmacological and non-pharmacological agents. Recent studies suggested that the pregnancies complicated by late FGR should undergo a tailored approach for IOL in view of the higher risk of fetal decompensation following uterine hyperstimulation. The present review aims to provide an up to date on the different types of IOL which can guide clinical management.
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http://dx.doi.org/10.23736/S2724-606X.21.04820-XDOI Listing
August 2021

Role of progesterone, cerclage and pessary in preventing preterm birth in twin pregnancies: A systematic review and network meta-analysis.

Eur J Obstet Gynecol Reprod Biol 2021 Jun 24;261:166-177. Epub 2021 Apr 24.

Fetal Medicine Unit, Saint George's University of London, London, United Kingdom; Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, United Kingdom.

Objective: To determine the role of progesterone, pessary and cervical cerclage in reducing the risk of (preterm birth) PTB in twin pregnancies and compare these interventions using pairwise and network meta-analysis.

Study Design: Medline, Embase, CINAHL and Cochrane databases were explored. The inclusion criteria were studies in which twin pregnancies were randomized to an intervention for the prevention of PTB (any type of progesterone, cervical cerclage, cervical pessary, or any combination of these) or to a control group (e.g. placebo or treatment as usual). Interventions of interest were either progesterone [vaginal or oral natural progesterone or intramuscular 17a-hydroxyprogesterone caproate (17-OHPC)], cerclage (McDonald or Shirodkar), or cervical pessary. The primary outcome was PTB < 34 weeks of gestation. Both primary and secondary outcomes were explored in an unselected population of twin pregnancies and in women at higher risk of PTB (defined as those with cervical length <25 mm). Random-effect head-to-head and a multiple-treatment meta-analyses were used to analyze the data and results expressed as risk ratios.

Results: 26 studies were included in the meta-analysis. When considering an unselected population of twin pregnancies, vaginal progesterone, intra-muscular17-OHPC or pessary did not reduce the risk of PTB < 34 weeks of gestation (all p > 0.05). When stratifying the analysis for spontaneous PTB, neither pessary, vaginal or intramuscular 17-OHPC were associated with a significant reduction in the risk of PTB compared to controls (all p > 0.05), while there was no study on cerclage which explored this outcome in an unselected population of twin pregnancies. When considering twin pregnancies with short cervical length (≤25 mm), there was no contribution of either pessary, vaginal progesterone, intra-muscular 17-OHPC or cerclage in reducing the risk of overall PTB < 34 weeks of gestation.

Conclusions: Cervical pessary, progesterone and cerclage do not show a significant effect in reducing the rate of PTB or perinatal morbidity in twins, either when these interventions are applied to an unselected population of twins or in pregnancies with a short cervix.
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http://dx.doi.org/10.1016/j.ejogrb.2021.04.023DOI Listing
June 2021

Fetoscopic laser ablation in twin-to-twin transfusion syndrome: tips for counselling.

Minerva Obstet Gynecol 2021 Apr;73(2):247-252

Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Rome, Italy.

Twin-to-twin transfusion syndrome (TTTS) is a serious complication that affects approximately 10-15% of monochorionic twin pregnancies. The most important role for the development of this condition is the presence of an unbalanced flow through the inter-twin vascular anastomoses. Depending on the number, type and direction of the connecting vessels, blood can be transfused disproportionately from one twin (the donor) to the other twin (the recipient). The diagnosis is defined prenatally by ultrasound and involves of two main criteria: the presence of a monochorionic diamniotic (MCDA) pregnancy; and the presence of oligohydramnios in the donor's sac- deep vertical pocket (DVP) 2 cm - and polyhydramnios in the recipient's sac- DVP>8 cm. Once diagnosed, TTTS is usually graded by using the Quintero staging system, that is composed by five stages, from oligohydramnios in the donor and polyhydramnios in the recipient twin to fetal demise in one or both twins. Photocoagulation of the anastomotic vessels, usually followed by equatorial dichorionization, it has currently become the most common fetoscopic operation today and is considered as the gold standard for stage II-IV TTTS. pPROM, chorioamniotic separation and iatrogenic preterm birth are among the most common complications of fetoscopic laser ablation, and the mean gestational age at delivery after laser procedure is about 31 weeks.
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http://dx.doi.org/10.23736/S2724-606X.20.04714-0DOI Listing
April 2021

Maternal and neonatal outcomes of pregnancies complicated by late fetal growth restriction undergoing induction of labor with dinoprostone compared with cervical balloon: A retrospective, international study.

Acta Obstet Gynecol Scand 2021 07 1;100(7):1313-1321. Epub 2021 Apr 1.

Center for High-Risk Pregnancy and Fetal Care, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy.

Introduction: The aim of this study was to compare vaginal dinoprostone and mechanical methods for induction of labor (IOL) in pregnancies complicated by late fetal growth restriction.

Material And Methods: Multicenter, retrospective, cohort study involving six referral centers in Italy and Spain. Inclusion criteria were pregnancies complicated by late fetal growth restriction as defined by Delphi consensus criteria. The primary outcome was the occurrence of uterine tachysystole; secondary outcomes were either cesarean delivery or operative vaginal delivery for non-reassuring fetal status, a composite score of adverse neonatal outcome and admission to neonatal intensive care unit (NICU). Univariate and multivariate logistic regression analysis was used to analyze the data.

Results: A total of 571 pregnancies complicated by late fetal growth restriction undergoing IOL (391 with dinoprostone and 180 with mechanical methods) were included in the analysis. The incidence of uterine tachysystole (19.2% vs. 5.6%; p = 0.001) was higher in women undergoing IOL with dinoprostone than in those undergoing IOL with mechanical methods. Similarly, the incidence of cesarean delivery or operative delivery for non-reassuring fetal status (25.6% vs. 17.2%; p = 0.027), composite adverse neonatal outcome (26.1% vs. 16.7%; p = 0.013) and NICU admission (16.9% vs. 5.6%; p < 0.001) was higher in women undergoing IOL with dinoprostone than in those undergoing IOL with mechanical methods. At logistic regression analysis, IOL with mechanical methods was associated with a significantly lower risk of uterine tachysystole (odds ratio 0.26, 95% confidence interval 0.13-0.54; p < 0.001).

Conclusions: In pregnancies complicated by late fetal growth restriction, IOL with mechanical methods is associated with a lower risk of uterine tachysystole, cesarean delivery or operative delivery for non-reassuring fetal status, and adverse neonatal outcome compared with pharmacological methods.
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http://dx.doi.org/10.1111/aogs.14135DOI Listing
July 2021

Pregnant women's perspectives on severe acute respiratory syndrome coronavirus 2 vaccine.

Am J Obstet Gynecol MFM 2021 Mar 23;3(4):100352. Epub 2021 Mar 23.

Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy (Drs Carbone, Sirico, Di Girolamo, Saccone, Donadono, Cuomo, Gabrielli, Migliorini, and Prof Maruotti).

Background: Since coronavirus disease 2019 vaccines have been distributed, a debate has raised on whether pregnant women should get the vaccine. No available data exist so far regarding the safety, efficacy, and toxicology of these vaccines when administered during pregnancy. Most of the Obstetrics and Gynecology societies suggested that pregnant could agree to be vaccinated, after a thorough counseling of risks and benefits with their gynecologists, thus leading to an autonomous decision.

Objective: This study aimed to evaluate the attitude to coronavirus disease 2019 vaccination in pregnant and breastfeeding women in Italy.

Study Design: A survey was made at the University of Naples Federico II and the Ospedale Cristo Re, Tor Vergata University of Rome, on pregnant and breastfeeding women asking their perspectives on the available vaccines after reading the recommendations issued by our national Obstetrics, Gynecology, and Neonatology societies. The questionnaire included 12 items finalized to evaluate general features of the women and 6 items specifically correlated to their attitudes toward the severe acute respiratory syndrome coronavirus 2 vaccination. Chi-square or Fisher's exact tests were used to compare group differences of categorical variables and Wilcoxon signed rank or Mann-Whitney U test for continuous variables. The study was approved by the institutional review boards of the University of Naples Federico II (ref. no. 409/2020) and the Ospedale Cristo Re, Tor Vergata University of Rome (ref. #Ost4-2020).

Results: Most of the included women did not agree to eventually receive severe acute respiratory syndrome coronavirus 2 vaccine during pregnancy (40 [28.2%] vs 102 [71.8%]). Being pregnant was considered a determinant factor to refuse the vaccine prophylaxis (99 [69.7%] vs 43 [30.3%]; chi-square test=24.187; P<.001), even if a very large percentage declared to be generally in favor of vaccines (128 [90.1%] vs 14 [9.9%]; chi-square test=6.091; P=.014) and most of them confirmed they received or would receive other recommended vaccines during pregnancy (75 [52.8%] vs 67 [47.2%]; chi-square test=10.996; P=.001).

Conclusion: Urgent data are needed on the safety, efficacy, and toxicology of severe acute respiratory syndrome coronavirus 2 vaccines during pregnancy to modify this trend and to help obstetricians during the counseling. Furthermore, pregnant women should be included in future vaccine development trials to not incur again in such uncertainty.
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http://dx.doi.org/10.1016/j.ajogmf.2021.100352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985679PMC
March 2021

Maternal outcomes of cesarean delivery performed at early gestational ages: a systematic review and meta-analysis.

Am J Obstet Gynecol MFM 2021 Mar 22;3(4):100360. Epub 2021 Mar 22.

Center for High-Risk Pregnancy and Fetal Care, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy. Electronic address:

Objective: This study aimed to report maternal outcomes of preterm (<34 weeks of gestation) cesarean delivery.

Data Sources: Medline, Embase, and ClinicalTrials.gov databases were searched electronically on September 1, 2020, utilizing combinations of the relevant medical subject heading terms, key words, and word variants for "cesarean delivery" and "outcome."

Study Eligibility Criteria: We included only studies reporting maternal outcomes of cesarean delivery performed at <34 weeks of gestation.

Study Appraisal And Synthesis Methods: The primary outcome was a composite score of maternal surgical morbidity including maternal death, severe intrasurgical or postpartum hemorrhage, hysterectomy, need for blood transfusion, and damage to adjacent organs. Secondary outcomes were individual components of the primary outcome, need for reoperation, postsurgical infection, thromboembolism, and hysterectomy. We also performed 2 subgroup analyses considering cesarean delivery performed at <28 and <26 weeks of gestation. Meta-analyses of proportions using random effects model were used to combine data.

Results: A total of 15 studies involving 8378 women undergoing cesarean delivery at <34 weeks of gestation were included in the systematic review. Composite adverse maternal outcome was reported in 16.2% of women (95% confidence interval, 15.4-17.0) undergoing a cesarean delivery before 34 weeks of gestation. Hemorrhage, either intra- or postoperative, was observed in 6.9% of cases (95% confidence interval, 6.4-7.5), whereas 6.3% (95% confidence interval, 4.2-8.7) required blood transfusion. Damage to adjacent organs complicated the primary surgery in 2.0% of women (95% confidence interval, 0.1-6.4), whereas 1.2% (95% confidence interval, 0.3-3.4) required a reoperation after cesarean delivery. Maternal death occurred in 0.1% (95% confidence interval, 0.0-1.4). In women undergoing cesarean delivery at <28 weeks of gestation, composite adverse maternal outcome complicated 22.9% of cases (95% confidence interval, 16.7-33.8) and 14.0% (95% confidence interval, 5.8-24.9) experienced hemorrhage whereas 7.7% (95% confidence interval, 4.4-11.8) required blood transfusion. Finally, when considering women undergoing cesarean delivery at <26 weeks of gestation, composite adverse maternal outcome was reported in 24.8% (95% confidence interval, 10.1-43.4), whereas the corresponding figures for hemorrhage and need for blood transfusion were 9.2% (95% confidence interval, 1.7-21.6) and 6.1% (95% confidence interval, 0.3-10.0), respectively.

Conclusion: Early cesarean delivery is affected by a high rate of maternal intra- and postoperative complications. The findings from systematic review can help clinicians in counseling parents when cesarean delivery is required in an early gestational age.
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http://dx.doi.org/10.1016/j.ajogmf.2021.100360DOI Listing
March 2021

Adverse Pregnancy Outcomes Among Individuals With and Without Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Systematic Review and Meta-analysis.

Obstet Gynecol 2021 04;137(4):585-596

Department of Obstetrics, Gynecology, and Reproductive Sciences, McGovern Medical School, the University of Texas Health Science Center at Houston, Houston, Texas; the Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Rome, Italy; the Department of Obstetrics and Gynecology, NYU Langone Health, NYU Winthrop Hospital, NYU Long Island School of Medicine, Mineola, New York; and the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.

Objective: To compare the risk of intrauterine fetal death (20 weeks of gestation or later) and neonatal death among individuals who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared with those who tested negative for SARS-CoV-2 on admission for delivery.

Data Sources: MEDLINE, Ovid, EMBASE, Cumulative Index to Nursing and Allied Health, and Cochrane Library were searched from their inception until July 17, 2020. Hand search for additional articles continued through September 24, 2020. ClinicalTrials.gov was searched on October 21, 2020.

Methods Of Study Selection: The inclusion criteria were publications that compared at least 20 cases of both pregnant patients who tested positive for SARS-CoV-2 on admission to labor and delivery and those who tested negative. Exclusion criteria were publications with fewer than 20 individuals in either category or those lacking data on primary outcomes. A systematic search of the selected databases was performed, with co-primary outcomes being rates of intrauterine fetal death and neonatal death. Secondary outcomes included rates of maternal and neonatal adverse outcomes.

Tabulation, Integration, And Results: Of the 941 articles and completed trials identified, six studies met criteria. Our analysis included 728 deliveries to patients who tested positive for SARS-CoV-2 and 3,836 contemporaneous deliveries to patients who tested negative. Intrauterine fetal death occurred in 8 of 728 (1.1%) patients who tested positive and 44 of 3,836 (1.1%) who tested negative (P=.60). Neonatal death occurred in 0 of 432 (0.0%) patients who tested positive and 5 of 2,400 (0.2%) who tested negative (P=.90). Preterm birth occurred in 95 of 714 (13.3%) patients who tested positive and 446 of 3,759 (11.9%) who tested negative (P=.31). Maternal death occurred in 3 of 559 (0.5%) patients who tested positive and 8 of 3,155 (0.3%) who tested negative (P=.23).

Conclusion: The incidences of intrauterine fetal death and neonatal death were similar among individuals who tested positive compared with negative for SARS-CoV-2 when admitted to labor and delivery. Other immediate outcomes of the newborns were also similar among those born to individuals who tested positive compared with negative for SARS-CoV-2.

Systematic Review Registration: PROSPERO, CRD42020203475.
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http://dx.doi.org/10.1097/AOG.0000000000004320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984633PMC
April 2021

Maternal and perinatal outcomes in high compared to low risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection (phase 2): the World Association of Perinatal Medicine working group on coronavirus disease 2019.

Am J Obstet Gynecol MFM 2021 02 20;3(4):100329. Epub 2021 Feb 20.

Department of Obstetrics and Gynecology, Centre for High-Risk Pregnancy and Fetal Care, University of Chieti, Chieti, Italy (Dr Liberati, Dr Sebastiano, Dr Oronzi, Dr Cerra, and Dr Buca).

Background: It has still to be ascertained whether severe acute respiratory syndrome coronavirus 2 infection in pregnancy is associated with worse maternal and fetal outcomes compared to low risk gestations.

Objective: This study aimed to evaluate maternal and perinatal outcomes in high- and low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection.

Study Design: This was a multinational retrospective cohort study involving women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection from 76 centers from 25 countries in Europe, the United States, South America, Asia, and Australia from April 4, 2020, to October 28, 2020. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit, use of mechanical ventilation, or death. The secondary outcome was a composite measure of adverse perinatal outcome, including miscarriage, fetal loss, neonatal and perinatal death, and admission to the neonatal intensive care unit. All outcomes were assessed in high- and low-risk pregnancies. Pregnancies were considered high risk in case of either preexisting chronic medical conditions in pregnancy or obstetrical disorders occurring in pregnancy. The Fisher exact test and logistic regression analysis were used to analyze the data.

Results: A total of 887 singleton pregnancies who tested positive for severe acute respiratory syndrome coronavirus 2 infection using reverse transcription-polymerase chain reaction of nasal and pharyngeal swab specimens were included in the study. The risk of composite adverse maternal outcomes was higher in high-risk pregnancies than in low-risk pregnancies (odds ratio, 1.52; 95% confidence interval, 1.03-2.24; P=.035). In addition, women carrying high-risk pregnancies were at higher risk of hospital admission (odds ratio, 1.48; 95% confidence interval, 1.07-2.04; P=.002), presence of severe respiratory symptoms (odds ratio, 2.13; 95% confidence interval, 0.41-3.21; P=.001), admission to the intensive care unit (odds ratio, 2.63; 95% confidence interval, 1.42-4.88), and invasive mechanical ventilation (odds ratio, 2.65; 95% confidence interval, 1.19-5.94; P=.002). When exploring perinatal outcomes, high-risk pregnancies were at high risk of adverse perinatal outcomes (odds ratio, 1.78; 95% confidence interval, 0.15-2.72; P=.009). However, such association was mainly because of the higher incidence of miscarriage in high-risk pregnancies compared with that in low-risk pregnancies (5.3% vs 1.6%, P=.008); furthermore, there was no difference in other explored outcomes between the 2 study groups. At logistic regression analysis, maternal age (odds ratio, 1.12; 95% confidence interval, 1.02-1.22; P=.023) and high-risk pregnancy (odds ratio, 4.21; 95% confidence interval, 3.90-5.11; P<.001) were independently associated with adverse maternal outcomes.

Conclusion: High-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection were at higher risk of adverse maternal outcomes than low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection.
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http://dx.doi.org/10.1016/j.ajogmf.2021.100329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896113PMC
February 2021

Coronavirus disease 2019 vaccine in pregnant women: not so far! The importance of counseling and the need for evidence-based data.

Am J Obstet Gynecol MFM 2021 05 1;3(3):100324. Epub 2021 Feb 1.

Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Rome, Italy.

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http://dx.doi.org/10.1016/j.ajogmf.2021.100324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129723PMC
May 2021

Stepwise implementation of vaginal cleansing and azithromycin at cesarean: a quality improvement study.

J Matern Fetal Neonatal Med 2021 Feb 1:1-8. Epub 2021 Feb 1.

Division of Neonatology, Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

Objective: We aimed to decrease our surgical site infection (SSI) rate by 30% by sequential implementation of vaginal cleansing and azithromycin for women who underwent a cesarean delivery (CD) after having labored or experienced rupture of membranes.

Methods: This is a quality improvement project that assessed the stepwise implementation of two interventions within three time periods: (1) 12 months prior to implementation of either intervention; (2) 14 months of vaginal cleansing as infection prophylaxis; (3) 16 months of vaginal cleansing and azithromycin as infection prophylaxis. The primary outcome measure was the SSI as defined by the Center for Disease Control and Prevention and analyzed by control charts. The process measures were compliance rates of vaginal cleansing and azithromycin. Significance was detected by rules for determining a special cause variation. This study followed the SQUIRE 2.0 guidelines for reporting on quality improvement.

Results: There were 1033 patients included from the three study periods. The total rate of SSI decreased from 22.8% to 15.2% after implementing vaginal cleansing. Special cause variation was detected with an 8-point shift starting 4 months after implementation of vaginal cleansing. This decrease was sustained during the following 26 months. Adding azithromycin did not significantly lower the SSI rate further. When examined separately, deep SSI ( = .009) and endometritis ( = .001) significantly decreased in the post-intervention periods. Pre-operative vaginal cleansing compliance rose to 74%, and then further increased to 85% 1 year after implementation. Azithromycin compliance rose to 75%. Total length of postpartum stay decreased over the study periods from 3.5 ± 1.4 days to 3.2 ± 0.8 days ( = .001).

Conclusion: In this quality improvement study, implementation of vaginal cleansing decreased the SSI rate by 33%, from 22.8% to 15.2%. The addition of azithromycin did not result in any additional change in SSI rate.
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February 2021

Ultrasound evaluation of the uterus in the uncomplicated postpartum period: a systematic review.

Am J Obstet Gynecol MFM 2021 05 23;3(3):100318. Epub 2021 Jan 23.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA (Dr Bellussi and Dr Berghella). Electronic address:

Objective: The aim of this systematic review and meta-analysis was to define the means and the upper limits of normal for endometrial thickness and uterine measurements in uncomplicated pregnancies at different postpartum periods.

Data Sources: A search was conducted in the Medline, Embase, Cinahl, and Clinicaltrials.gov databases up to January 30, 2020.

Study Eligibility Criteria: We included studies reporting sonographic parameters of the uterus in the normal postpartum period.

Methods: The continuous variables were expressed as means with standard deviations. The upper limits of normal were defined as the 95th percentile. Clinically significant differences in the uterine measurements between subgroups were defined as ≥2 cm; significant differences in the uterine volume were defined as >10%. The primary outcome was the endometrial thickness; others sonographic parameters that were analyzed were the uterine anteroposterior diameter, longitudinal diameter, width, and volume.

Results: A total of 5260 articles were identified. Of these, 80 were assessed for their eligibility for inclusion and 32 studies were included in this systematic review. These studies included 3106 women (55% multiparas and 82% with vaginal deliveries) who underwent transabdominal and/or transvaginal ultrasound from the first postpartum day to a maximum of 6 weeks postpartum. The upper limit of normal (95th percentile) for the endometrial thickness was 25 mm by 7 days postpartum and this continued to decrease (18 mm at 14 days, 12 mm at 4 weeks, and 9 mm at 6 weeks) in a similar manner for all the women regardless of parity or mode of delivery. All the other uterine measurements also gradually decreased during the puerperium for all the women regardless of parity or mode of delivery.

Conclusion: These upper limits of normal for the postpartum endometrium and uterine measurements in uncomplicated pregnancies provide clinical guidance for the sonographic evaluation of women with complicated postpartum courses.
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May 2021

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

J Perinat Med 2020 Dec 2;49(1):111-115. Epub 2020 Dec 2.

Department of Obstetrics and Gynaecology, Fetal Medicine Unit, Maternal and Child Health and Development Network, University Hospital 12 de Octubre, Complutense University of Madrid, Madrid, Spain.

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http://dx.doi.org/10.1515/jpm-2020-0539DOI Listing
December 2020

Psychopathology associated with coronavirus disease 2019 among pregnant women.

Am J Obstet Gynecol MFM 2021 01 4;3(1):100290. Epub 2020 Dec 4.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College, Thomas Jefferson University, 833 Chestnut, Philadelphia, PA 19107. Electronic address:

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http://dx.doi.org/10.1016/j.ajogmf.2020.100290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833641PMC
January 2021

Outcome of cesarean scar pregnancy according to gestational age at diagnosis: A systematic review and meta-analysis.

Eur J Obstet Gynecol Reprod Biol 2021 Mar 12;258:53-59. Epub 2020 Nov 12.

Center for Fetal Care and High-Risk Pregnancy, Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy. Electronic address:

Objective: The association between the most severe types of placenta accreta spectrum disorders and caesarean scar pregnancy (CSP) poses the question of whether early diagnosis may impact the clinical outcome of these anomalies. The aim of this study is to report the outcome of cesarean scar pregnancy (CSP) diagnosed in the early (≤9 weeks) versus late (>9 weeks) first trimester of pregnancy.

Study Design: Medline, Embase and Clinicaltrail.gov databases were searched. Studies including cases of CSP with an early (≤9 weeks of gestation) compared to a late (>9 weeks) first trimester diagnosis of CSP, followed by immediate treatment, were included in this systematic review. The primary outcome was a composite measure of severe maternal morbidity including either severe first trimester bleeding, need for blood transfusion, uterine rupture or emergency hysterectomy. The secondary outcomes were the individual components of the primary outcome. Random-effect meta-analyses were used to combine data.

Results: Thirty-six studies (724 women with CSP) were included. Overall, composite adverse outcome complicated 5.9 % (95 % CI 3.5-9.0) of CSP diagnosed ≤9 weeks and 32.4 % (95 % CI 15.7-51.8) of those diagnosed >9 weeks. Massive hemorrhage occurred in 4.3 % (95 % CI 2.3-7.0) of women with early and in 28.0 % (95 % CI 14.1-44.5) of those with late first trimester diagnosis of CSP, while the corresponding figures for the need for blood transfusion were 1.5 % (95 % CI 0.6-2.8) and 15.8 % (95 % CI 5.5-30.2) respectively. Uterine rupture occurred in 2.5 % (95 % CI 1.2-4.1) of women with a prenatal diagnosis of CSP ≤ 9 weeks and in 7.5 % (95 % CI 2.5-14.9) of those with CSP > 9 weeks, while an emergency intervention involving hysterectomy was required in 3.7 % (95 % CI 2.2-5.4) and 16.3 % (95 % CI5.9-30.6) respectively. When computing the risk, early diagnosis of CSP was associated with a significantly lower risk of composite adverse outcome, (OR: 0.14; 95 % CI 0.1-0.4 p < 0.001).

Conclusions: Early first trimester diagnosis of CSP is associated with a significantly lower risk of maternal complications, thus supporting a policy of universal screening for these anomalies in women with a prior cesarean delivery although the cost-effectiveness of such policy should be tested in future studies.
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March 2021

Evidence-based labor management: before labor (Part 1).

Am J Obstet Gynecol MFM 2020 02 20;2(1):100080. Epub 2019 Dec 20.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA; Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Italy.

In preparation for labor and delivery, there is high-quality evidence for providers to recommend perineal massage with oil for 5-10 minutes daily starting at 34 weeks until labor; ≥1 daily sets of repeated voluntary contractions of the pelvic floor muscles, performed at least several days of the week starting at approximately 30-32 weeks gestation; no x-ray pelvimetry; sweeping of membranes weekly starting at 37-38 weeks gestation; for women with a risk factor for abnormal outcome plans should be made to deliver in a hospital setting; for low-risk women, alongside birth center birth is associated with maternal benefits and higher satisfaction, compared with hospital birth; midwife-led care for low-risk women; continuous support by a professional such as doula, midwife, or nurse during labor; and training of birth attendants in low- and middle-income countries.
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February 2020

Pregnant women's knowledge and behaviour to prevent cytomegalovirus infection: an observational study.

J Perinat Med 2021 Mar 23;49(3):327-332. Epub 2020 Oct 23.

Department of Maternal and Child Health and Urological Sciences, Umberto I Hospital, Sapienza University of Rome, Rome, Italy.

Objectives: Congenital cytomegalovirus (cCMV) infection can negatively affect pregnancy outcomes, but may be prevented by simple precautions. Literature suggests that gynaecologists do not always adequately inform about preventive behaviour and most pregnant women have a low-level knowledge regarding cCMV infection. The aim of this study is to evaluate knowledge and risk behaviours related to cCMV infection in an unselected group of pregnant women.

Methods: An institutional based cross-sectional study was conducted in three Maternal and Fetal Divisions in Rome between November and February 2019 on 296 pregnant women, their knowledge on cCMV was measured using six cytomegalovirus (CMV) related questions.

Results: Out of the 296 respondents, 59.1% had heard, read or seen information about cCMV infection. Regarding the way of transmission, 96/296 (32.4%) correctly recognize children as a potential source of the infection but only 25/296 (8.44%) knew all prevention practices, 28/296 (9.5%) of women reported that they have never performed cCMV test during pregnancy.

Conclusions: The results of this survey show that knowledge on cCMV infection among pregnant women is poor. This highlights the need to improve counselling on all preventive practices for cCMV infection during perinatal care consultation.
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March 2021

Perinatal mortality and morbidity of SARS-COV-2 infection during pregnancy in European countries: Findings from an international study.

Eur J Obstet Gynecol Reprod Biol 2021 Jan 10;256:505-507. Epub 2020 Oct 10.

Center for High Risk Pregnancy and Fetal Care, Department of Obstetrics and Gynecology, University of Chieti, Italy. Electronic address:

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547591PMC
January 2021

Obstetrical and perinatal outcomes in fetuses with early versus late sonographic diagnosis of short femur length: A single-center, prospective, cohort study.

Eur J Obstet Gynecol Reprod Biol 2020 Nov 17;254:170-174. Epub 2020 Sep 17.

Department of Maternal and Child Health and Urological Sciences, Sapienza University of Rome, Italy.

Objectives: The aim of this study was to evaluate obstetrical and perinatal outcomes in fetuses with short femur length diagnosed before or after 24 weeks of gestation.

Study Design: This was a prospective cohort study on singleton pregnancies with a diagnosis of fetal femur < 5 centile. Included patients were divided into two groups: patients with a first diagnosis of femur length < 5th percentile at 14-24 weeks (group A) and those with the first diagnosis made at > 24 weeks (group B).

Results: 147 patients were included for the analysis. Group A and group B included 66 (44.9%) and 81 (55.1%) cases. Abnormal fetal karyotype and skeletal dysplasia rates were significantly higher (27.3% vs 3.7%,P < 0.001 and 19.7% vs 3.7%, P = 0.002) in group A. Women in group B had a higher incidence of small for gestational age and intrauterine growth restriction (7.6% vs 24.7%, P = 0.007 and 19.7% vs 44.4%, P = 0.002). There was a significant higher incidence of live births in group B (34.9% vs 97.5%, P < 0.001), while the rate of termination of pregnancy was increased in group A (56.1% vs 1.2%, P < 0.001). No significant difference was found in perinatal outcomes of live births, when comparing group A and B.

Conclusions: The incidence of abnormal karyotype and skeletal dysplasia is higher when short femur length diagnosed earlier in gestation, while the incidence of small for gestational age, intrauterine growth restriction and the rate of live births are significantly increased when short femur length is diagnosed later during pregnancy.
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November 2020

Diagnostic accuracy of prenatal ultrasound in identifying the level of the lesion in fetuses with open spina bifida: A systematic review and meta-analysis.

Acta Obstet Gynecol Scand 2021 02 11;100(2):210-219. Epub 2020 Oct 11.

Center for Fetal Care and High-risk Pregnancy, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy.

Introduction: The role of prenatal ultrasound in correctly identifying the level of the lesion in fetuses with open spina bifida has yet to be determined. The primary aim of this systematic review was to report the diagnostic accuracy of ultrasound in determining the level of the lesion in fetuses with open spina bifida. The secondary aim was to elucidate whether prenatal magnetic resonance imaging (MRI) improves the diagnostic performance of prenatal imaging in correctly identifying the level of the lesion.

Material And Methods: Inclusion criteria were studies reporting the agreement between ultrasound, MRI and postnatal or postmortem assessment of fetuses with spina bifida. Agreement was defined as: complete (when the upper level of the lesion detected prenatally was the same recorded at postnatal or postmortem evaluation), within one (when the upper level of the lesion recorded prenatally was within one vertebral body higher or lower than that reported postnatally) and within two vertebral bodies (when the upper level of the lesion recorded prenatally was within two vertebral bodies higher or lower than that reported postnatally or postmortem evaluation). Meta-analyses of proportions were used to combine data.

Results: Fourteen studies (655 fetuses) were included. Ultrasound was able to identify the correct level of the lesion in 40.9% (95% confidence interval [CI] 26.9-55.6) of cases. The upper level of the lesion recorded on ultrasound was within one vertebral body in 76.2% (95% CI 65.0-85.9) of cases and within two segments in 92.4% (95% CI 84.3-97.7). Fetal MRI detected the exact level of the lesion in 42.5% (95% CI 35.9-45.2) of cases; the level of the lesion recorded on MRI was higher in 26.4% (95% CI 20.0-33.3) of cases and lower in 32.4% (95% CI 25.5-39.7) than that confirmed postnatally. The upper level of the lesion recorded on MRI was within one vertebral body in 76.2% (95% CI 65.9-85.2) of cases and within two segments in 94.2% (95% CI 90.2-97.2).

Conclusions: Both ultrasound and MRI have a moderate diagnostic accuracy in identify the upper level of the lesion in fetuses with open spina bifida.
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February 2021

In Reply.

Obstet Gynecol 2020 10;136(4):849-850

Department of Obstetrics, Gynecology, and Reproductive Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas.

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October 2020

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

J Perinat Med 2020 11;48(9):950-958

Department of Obstetrics and Gynaecology, Ospedale di San Leonardo, Castellammare di Stabia, Italy.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.
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November 2020

Reply.

Am J Obstet Gynecol 2021 01 17;224(1):128-129. Epub 2020 Sep 17.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College of Thomas Jefferson University, 833 Chestnut, Philadelphia, PA 19107. Electronic address:

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January 2021

Comparison between cerebroplacental ratio and umbilicocerebral ratio in predicting adverse perinatal outcome at term.

Eur J Obstet Gynecol Reprod Biol 2020 Sep 24;252:439-443. Epub 2020 Jul 24.

Centre for High Risk Pregnancy and Fetal Care, Department of Obstetrics and Gynecology, University of Chieti, Italy. Electronic address:

Objective: Cerebroplacental ratio (CPR) has been associated with adverse perinatal outcome irrespective of fetal weight. More recently, it has been proposed that the ratio between umbilical and middle cerebral artery pulsatility index, the umbilicocerebral ratio (UCR) had a higher diagnostic accuracy compared to CPR in predicting adverse outcome. The aim of the study was to compare the diagnostic accuracy of CPR and UCR in predicting adverse perinatal outcome in the third trimester of pregnancy.

Study Design: Secondary analysis of prospective study carried out in a dedicated research ultrasound clinic in a single tertiary referral center over a one-year period. Inclusion criteria were consecutive singleton pregnancies between 36 + 0 and 37 + 6 weeks of gestation. Exclusion criteria were multiple gestations, pregnancies affected by structural or chromosomal anomalies, maternal medical complications or drugs intake and abnormal Doppler waveform in the UA, defined as PI>95th or absent/end diastolic flow. All women were pre-screened at 28-32 weeks of gestation in order to rule out signs of early fetal growth restriction. The primary outcome was to compare the diagnostic performance of CPR and UCR in detecting the presence of fetuses affected by a composite adverse outcome.

Results: Mean CPR (1.35 ± 0.39 vs 1.85 ± 0.58, p < 0.001) was significantly lower while mean UCR (0.78 ± 0.25 vs 0.58 ± 0.20, p = 0.001) was significantly higher in pregnancies experiencing compared to those not experiencing composite adverse outcome. There was no difference between CPR and UCR in predicting adverse perinatal outcome in the third trimester of pregnancy and both showed a very low diagnostic accuracy. CPR had an AUC of 0.51 (95 % CI 0.43-0.58) while UCR had an AUC of 0.51 (95 % CI 0.43-0.58) in predicting composite adverse outcome. Likewise, there was no difference in the diagnostic accuracy of CRP (AUC: 0.600, 95 % CI 0.36-0.83) and UCR (AUC: 0.589, 95 % CI 0.35-0.83) when considering only SGA fetuses.

Conclusions: A low CPR and a high UCR are significantly associated with adverse perinatal outcome in singleton pregnancies at term. There was no difference between CPR and UCR in predicting perinatal outcome. Despite this, the diagnostic accuracy of both these parameters is too poor to advocate for their use as a screening tool of perinatal impairment at term, unless specific indications, such as SGA or FGR, have been identified.
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September 2020

Adverse intrapartum outcome in pregnancies complicated by small for gestational age and late fetal growth restriction undergoing induction of labor with Dinoprostone, Misoprostol or mechanical methods: A systematic review and meta-analysis.

Eur J Obstet Gynecol Reprod Biol 2020 Sep 18;252:455-467. Epub 2020 Jul 18.

Department of Obstetrics and Gynecology, Department of Medical and Surgical Sciences, University of Foggia, Italy. Electronic address:

Objective: To investigate the outcome of pregnancies with small baby, including both small for gestational age (SGA) and late fetal growth restriction (FGR) fetuses, undergoing induction of labor (IOL) with Dinoprostone, Misoprostol or mechanical methods.

Study Design: Medline, Embase and Cochrane databases were searched. Inclusion criteria were non-anomalous singleton pregnancies complicated by the presence of a small fetus, defined as a fetus with estimated fetal weight (EFW) or abdominal circumference (AC) <10th centile undergoing IOL from 34 weeks of gestation with vaginal Dinoprostone, vaginal misoprostol, or mechanical methods (including either Foley or Cook balloon catheters). The primary outcome was a composite measure of adverse intrapartum outcome. Secondary outcomes were the individual components of the primary outcome, perinatal mortality and morbidity. All the explored outcomes were reported in three different sub-groups of pregnancies complicated by a small fetus including: all small fetuses (defined as those with an EFW and/or AC <10th centile irrespective of fetal Doppler status), late FGR fetuses (defined as those with EFW and/or AC <3rd centile or AC/EFW <10th centile associated with abnormal cerebroplacental Dopplers) and SGA fetuses (defined as those with EFW and/or AC <10th but >3rd centile with normal cerebroplacental Dopplers). Quality assessment of each included study was performed using the Risk of Bias in Non-randomized Studies-of Interventions tool (ROBINS-I), while the GRADE methodology was used to assess the quality of the body of retrieved evidence. Meta-analyses of proportions and individual data random-effect logistic regression were used to analyze the data.

Results: 12 studies (1711 pregnancies) were included. In the overall population of small fetuses, composite adverse intra-partum outcome occurred in 21.2 % (95 % CI 10.0-34.9) of pregnancies induced with Dinoprostone, 18.0 % (95 % CI 6.9-32.5) of those with Misoprostol and 11.6 % (95 % CI 5.5-19.3) of those undergoing IOL with mechanical methods. Cesarean section (CS) for non-reassuring fetal status (NRFS) was required in 18.1 % (95 % CI 9.9-28.3) of pregnancies induced with Dinoprostone, 9.4 % (95 % CI 1.4-22.0) of those with Misoprostol and 8.1 % (95 % CI 5.0-11.6) of those undergoing mechanical induction. Likewise, uterine tachysystole, was recorded on CTG in 13.8 % (95 % CI 6.9-22.3) of cases induced with Dinoprostone, 7.5 % (95 % CI 2.1-15.4) of those with Misoprostol and 3.8 % (95 % CI 0-4.4) of those induced with mechanical methods. Composite adverse perinatal outcome following delivery complicated 2.9 % (95 % CI 0.5-6.7) newborns after IOL with Dinoprostone, 0.6 % (95 % CI 0-2.5) with Misoprostol and 0.7 % (95 % CI 0-7.1) with mechanical methods. In pregnancies complicated by late FGR, adverse intrapartum outcome occurred in 25.3 % (95 % CI 18.8-32.5) of women undergoing IOL with Dinoprostone, compared to 7.4 % (95 % CI 3.9-11.7) of those with mechanical methods, while CS for NRFS was performed in 23.8 % (95 % CI 17.3-30.9) and 6.2 % (95 % CI 2.8-10.5) of the cases, respectively. Finally, in SGA fetuses, composite adverse intrapartum outcome complicated 8.4 % (95 % CI 4.6-13.0) of pregnancies induced with Dinoprostone, 18.6 % (95 % CI 13.1-25.2) of those with Misoprostol and 8.7 (95 % CI 2.5-17.5) of those undergoing mechanical IOL, while CS for NRF was performed in 8.4 % (95 % CI 4.6-13.0) of women induced with Dinoprostone, 18.6 % (95 % CI 13.1-25.2) of those with Misoprostol and 8.7 % (95 % CI 2.5-17.5) of those undergoing mechanical induction. Overall, the quality of the included studies was low and was downgraded due to considerable clinical and statistical heterogeneity.

Conclusions: There is limited evidence on the optimal type of IOL in pregnancies with small fetuses. Mechanical methods seem to be associated with a lower occurrence of adverse intrapartum outcomes, but a direct comparison between different techniques could not be performed.
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September 2020
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