Publications by authors named "Marco Liberati"

85 Publications

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 06 15:1-9. 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

Outcomes of second stage cesarean section following the use of a fetal head elevation device: A systematic review and meta-analysis.

Eur J Obstet Gynecol Reprod Biol 2021 Jul 1;262:1-6. Epub 2021 May 1.

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

Objectives: To explore maternal and perinatal outcomes of women undergoing full dilatation cesarean section (CS) who had compared to those who did not have application of fetal head elevation device (FHED).

Material And Methods: Pubmed, Embase, Cinahl, Clinical Trial.Gov and Google Scholar databases were searched. Inclusion criteria were studies exploring maternal and perinatal outcomes in women having compared to those not having FHED at full dilatation CS. The outcomes explored were: hysterotomy to delivery time (sec), mean estimated blood loss (ml), blood loss > 1000 mL, need for blood transfusion, uterine incision extension, operative complications, need for re-operation, urinary retention, hospital re-admission, length of in hospital stay, Apgar score < 3 at 1 min, Apgar score < 7 at 5 min, neonatal arterial Ph, arterial pH < 7.1, admission to neonatal intensive care unit (NICU), neonatal sepsis, need for neonatal endotracheal intubation, neonatal death. Random effect head-to-head meta-analyses combining summary mean difference (MD), and odd ratio (OR) were used to analyze the data.

Results: Ten studies (1326 women) were included. The mean time from hysterotomy to delivery was lower in women having compared to those not having FHED (MD: -52.26 s, 95 % CI -55.2 to -34.94, p < 0.001). Women who had FHED had also a lower mean estimated blood loss (MD: -130.82 mL, 95 % CI -130.1 to -381.0; p < 0.001) and a shorter stay in the hospital (MD: -0.884 h, 95 % CI -1.07 to -0.70; p < 0.001) compared to controls. Pregnant women having FHED at full dilatation CS had a lower risk of uterine incision extension (OR: 0.50, 95 % CI 0.3 to 0.9; p = 0.02), need for blood transfusion (OR: 0.39, 95 % CI 0.2 to 0.7; p = 0.04) and operative complications (OR: 0.44, 95 % CI 0.2 to 0.9; p = 0.03) compared to controls, while there was no difference in the other maternal outcomes between the two groups. When exploring perinatal outcome, women who received FHED had higher mean arterial pH values (MD: 0.617, 95 % CI 0.43 to 0.88; p < 0.001) and a lower risk of neonatal sepsis (OR: 0.10, 95 % CI 0.01 to 0.99; p = 0.05) and admission to NICU (OR: 0.63, 95 % CI 0.5 to 0.9; p = 0.008) compared to controls.

Conclusion: Application of FHED at full dilatation CS seems to be associated with improvement in some maternal and neonatal outcomes.
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http://dx.doi.org/10.1016/j.ejogrb.2021.04.043DOI Listing
July 2021

Induction of labor in late-FGR.

Minerva Obstet Gynecol 2021 May 5. Epub 2021 May 5.

Centre 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
May 2021

Ovarian hyperstimulation syndrome and adverse pregnancy outcome: a systematic review and meta-analysis.

Minerva Obstet Gynecol 2021 May 5. Epub 2021 May 5.

Fetal Medicine Unit, Department of Medical and Surgical Sciences, Department of Obstetrics and Gynecology, University of Foggia, Foggia, Italy -

Purpose Of The Article: To investigate the association between ovarian hyperstimulation syndrome (OHSS) and adverse pregnancy outcome.

Material And Methods: Medline, Embase and Cochrane databases were searched. The primary outcome was a composite score of adverse maternal outcome including either preterm birth (PTB), gestational diabetes mellitus (GDM), pre-eclampsia (PE) or pregnancy induced hypertension, intra-hepatic cholestasis of pregnancy, thromboembolic events or need for caesarean section (CS). Secondary outcomes were a composite score of adverse fetal outcome including either miscarriage, low birthweight, fetal anomalies or intra-uterine fetal death (IUD) and the individual components of both primary and secondary outcomes.

Results: 13 studies (3303 ART pregnancies with and 89720 without OHSS) were included. The risk of composite adverse maternal outcome (RR: 8.8, 95% CI 8.1-9.5) was higher in women with compared to those without OHSS. The association between OHSS and adverse pregnancy outcome was mainly due to the higher risk of PTB (RR: 11.4, 95% CI 10.5-12.4), while there was no difference in the risk of others primary outcome. Likewise, the risk of composite fetal outcome was higher in pregnancies with a prior OHSS (RR: 1.5, 95% CI 1.1-2.0). The strength of association between OHSS and composite adverse maternal outcome persisted when considering singleton pregnancies or those with severe disease.

Conclusions: Pregnancies complicated by OHSS are at high risk of adverse pregnancy outcome, especially PTB.
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http://dx.doi.org/10.23736/S2724-606X.21.04806-5DOI Listing
May 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

Childbirth Care among SARS-CoV-2 Positive Women in Italy.

Int J Environ Res Public Health 2021 04 16;18(8). Epub 2021 Apr 16.

Servizio Assistenza Territoriale, Direzione Generale Cura Della Persona, Salute e Welfare, Emilia-Romagna Region, 40127 Bologna, Italy.

The new coronavirus emergency spread to Italy when little was known about the infection's impact on mothers and newborns. This study aims to describe the extent to which clinical practice has protected childbirth physiology and preserved the mother-child bond during the first wave of the pandemic in Italy. A national population-based prospective cohort study was performed enrolling women with confirmed SARS-CoV-2 infection admitted for childbirth to any Italian hospital from 25 February to 31 July 2020. All cases were prospectively notified, and information on peripartum care (mother-newborn separation, skin-to-skin contact, breastfeeding, and rooming-in) and maternal and perinatal outcomes were collected in a structured form and entered in a web-based secure system. The paper describes a cohort of 525 SARS-CoV-2 positive women who gave birth. At hospital admission, 44.8% of the cohort was asymptomatic. At delivery, 51.9% of the mothers had a birth support person in the delivery room; the average caesarean section rate of 33.7% remained stable compared to the national figure. On average, 39.0% of mothers were separated from their newborns at birth, 26.6% practised skin-to-skin, 72.1% roomed in with their babies, and 79.6% of the infants received their mother's milk. The infants separated and not separated from their SARS-CoV-2 positive mothers both had good outcomes. At the beginning of the pandemic, childbirth raised awareness and concern due to limited available evidence and led to "better safe than sorry" care choices. An improvement of the peripartum care indicators was observed over time.
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http://dx.doi.org/10.3390/ijerph18084244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074190PMC
April 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

Fat mass and obesity-associated (FTO) gene epigenetic modifications in gestational diabetes: new insights and possible pathophysiological connections.

Acta Diabetol 2021 Aug 20;58(8):997-1007. Epub 2021 Mar 20.

Department of Medicine and Aging, School of Medicine and Health Sciences, "G. D'Annunzio" University, Chieti-Pescara, Via dei Vestini, 66100, Chieti, Italy.

Aims: Gestational diabetes mellitus (GDM) can lead to short- and long-term complications for the child. Epigenetic alterations could contribute to explaining the metabolic disturbances associated with foetal programming. Although the role of the FTO gene remains unclear, it affects metabolic phenotypes probably mediated by epigenetic mechanisms. The aim of this study was to assess whether placental DNA epigenetic modifications at FTO promoter-associated cysteine-phosphate-guanine (CpG) sites are correlated with GDM. A secondary aim was to evaluate the association between the placental FTO DNA methylation and the maternal metabolic traits in women with and without GDM.

Methods: Socio-demographic characteristics, clinical parameters at the third trimester of pregnancy, Mediterranean diet adherence, and physical activity were assessed in 33 GDM women and 27 controls. Clinical information about the newborns was registered at birth. The FTO rs9939609 (T > A) was genotyped.

Results: No association between FTO DNA methylation and GDM was found. DNA methylation on the maternal side at the CpG1 was associated with maternal smoking in GDM (p = 0.034), and DNA methylation at the CpG3 was correlated with smoking or former smoking in controls (p = 0.023). A higher level of TGs was correlated with higher foetal placental DNA methylation at the CpG2 (p = 0.036) in GDM. An inverse association between HDL-C and maternal placental DNA methylation at the CpG3 in controls (p = 0.045) was found. An association between FTO rs9939609 and neonatal birthweight (p = 0.033) was detected.

Conclusions: In the awareness that the obesity pathophysiology is complex, the study adds a piece to this intricate mosaic.
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http://dx.doi.org/10.1007/s00592-020-01668-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272710PMC
August 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

Outcome of fetal Vein Galen aneurysmal malformations: a systematic review and meta-analysis.

J Matern Fetal Neonatal Med 2021 Jan 28:1-6. Epub 2021 Jan 28.

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

Objectives: To report the outcome of fetuses with a prenatal diagnosis of Vein of Galen (VOG) malformation.

Methods: PubMed and Embase databases were searched. Random effect meta-analysis of proportions was used to analyze the data. The outcomes explored were prenatal ultrasound findings, mortality, preterm birth (PTB), abnormal neurological outcome, associated findings detected at post-natal brain imaging, need for anticonvulsant therapy, and the rate of children free from neurological impairment. Random effect meta-analysis of proportions were used to analyze the data.

Results: Eleven studies (226 fetuses with a prenatal diagnosis of VOG malformation) were included. All cases were detected during the third trimester of pregnancy. Ventriculomegaly was detected in 31.8% (95% CI 27.6-47.7), cardiomegaly or other ultrasound signs of cardiac compromise in 23.1% (95% CI 14.9-32.5) and hydrops in 7.3% (95% CI 2.8-13.6) of cases. The incidence of IUD, NND, and PND was 1.5% (95% CI 0.2-4.3), 23.8% (95% CI 16.9-31.4), and 24.5% (95% CI 17.6-32.2), respectively, while 12.6% (95% CI 6.0-21.2) of pregnancies were complicated by PTB. Abnormal neurodevelopmental outcome was observed in 36.7% (95% CI 27.9-39.7) of cases, while 60.5% (95% CI 17.0-82.0) of children had abnormal findings on post-natal imaging and only 29.7% (95% CI 23.3-36.5) were free from neurological impairment after birth, although there was a wide heterogeneity in the time at follow-up between the included studies.

Conclusion: VOG malformation diagnoses during fetal life is associated with a high incidence of brain damage, cardiac compromise, and abnormal neurodevelopmental outcome after birth.
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http://dx.doi.org/10.1080/14767058.2021.1878494DOI Listing
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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http://dx.doi.org/10.1016/j.ejogrb.2020.11.036DOI Listing
March 2021

Role of ante-partum ultrasound in predicting vaginal birth after cesarean section: A prospective cohort study.

Eur J Obstet Gynecol Reprod Biol 2021 Jan 21;256:385-390. Epub 2020 Nov 21.

Department of Obstetric-Section and Gynecology, University of Chieti, Chieti, Italy.

Introduction: Vaginal birth after caesarean delivery is associated with better outcomes compared to repeat caesarean section. Accurate antenatal risk stratification of women undergoing a trial of labor after caesarean section is crucial in order to maximize perinatal and maternal outcomes. The primary aim of this study was to explore the role of antepartum ultrasound in predicting the probability of vaginal birth in women attempting trial of labor; the secondary aim was to build a multiparametric prediction model including pregnancy and ultrasound characteristics able to predict vaginal birth and compare its diagnostic performance with previously developed models based exclusively upon clinical and pregnancy characteristics.

Methods: Prospective study of consecutive singleton pregnancies scheduled for trial of labor undergoing a dedicated antepartum ultrasound assessment at 36-38 weeks of gestation. Head circumference, estimated fetal weight cervical length, sub-pubic angle were recorded before the onset of labour. The obstetricians and midwives attending the delivery suite were blinded to the ultrasound findings. Multivariate logistic regression and area under the curve analyses were used to explore the strength of association and test the diagnostic accuracy of different maternal and ultrasound characteristics in predicting vaginal birth. Comparison with previously reported clinical models developed by the Maternal-Fetal Medicine Unit Network (Grobman's models) was performed using De Long analysis.

Results: A total of 161women who underwent trial of labor were included in the study. Among them 114 (70.8 %) women had successful vaginal birth. At multivariable logistic regression analysis maternal height (adjusted odds ratio (aOR):1.24;9 5% Confidence Interval (CI)1.17-1.33), previous C-section for arrest labor (aOR:0.77; 95 %CI0.66-0.93), cervical dilation at admission (aOR:1.35 ; 95 %CI1.12-1.74), fetal head circumference (aOR:0.77 ; 5%CI0.43-0.89), subpubic angle (aOR:1.39 95 %CI1.11-1.99) and cervical length (aOR:0.82 95 % CI0.54-0.98) were independently associated with VBAC. A model integrating these variables had an area under curve of 0.839(95 % CI 0.710-0.727) for the prediction of vaginal birth, significantly higher than those achieved with intake (0.694; 95 %CI0.549-0.815; p = 0.01) and admission (0.732: 95 % CI 0.590-0.84; p = 0.04) models reported by Grobman.

Conclusion: Antepartum prediction of vaginal birth after a caesarean section is feasible. Fetal head circumference, subpubic angle and cervical length are independently associated and predictive of vaginal birth. Adding these variables to a multiparametric model including maternal parameters improves the diagnostic accuracy of vaginal birth compared to those based only on maternal characteristic.
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http://dx.doi.org/10.1016/j.ejogrb.2020.11.056DOI Listing
January 2021

Role of Extracellular Vesicles in Epithelial Ovarian Cancer: A Systematic Review.

Int J Mol Sci 2020 Nov 19;21(22). Epub 2020 Nov 19.

Department of Medical, Gynecologic and Obstetric Unit, University of Sassari, 07100 Sassari, Italy.

Extracellular vesicles (EVs) are a heterogeneous group of cell-derived submicron vesicles released under physiological or pathological conditions. EVs mediate the cellular crosstalk, thus contributing to defining the tumor microenvironment, including in epithelial ovarian cancer (EOC). The available literature investigating the role of EVs in EOC has been reviewed following PRISMA guidelines, focusing on the role of EVs in early disease diagnosis, metastatic spread, and the development of chemoresistance in EOC. Data were identified from searches of Medline, Current Contents, PubMed, and from references in relevant articles from 2010 to 1 April 2020. The research yielded 194 results. Of these, a total of 36 papers, 9 reviews, and 27 original types of research were retained and analyzed. The literature findings demonstrate that a panel of EV-derived circulating miRNAs may be useful for early diagnosis of EOC. Furthermore, it appears clear that EVs are involved in mediating two crucial processes for metastatic and chemoresistance development: the epithelial-mesenchymal transition, and tumor escape from the immune system response. Further studies, more focused on in vivo evidence, are urgently needed to clarify the role of EV assessment in the clinical management of EOC patients.
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http://dx.doi.org/10.3390/ijms21228762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699467PMC
November 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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http://dx.doi.org/10.1515/jpm-2020-0355DOI Listing
November 2020

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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http://dx.doi.org/10.1016/j.ejogrb.2020.07.032DOI Listing
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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http://dx.doi.org/10.1016/j.ejogrb.2020.07.020DOI Listing
September 2020

Neonatal Morbidity of Monoamniotic Twin Pregnancies: A Systematic Review and Meta-analysis.

Am J Perinatol 2020 Jul 28. Epub 2020 Jul 28.

Department of Obstetrics and Gynecology, Fetal Medicine and Cardiology Unit, University of Foggia, Foggia, Italy.

Objective:  This study was aimed to report the incidence of neonatal morbidity in monochorionic monoamniotic (MCMA) twin pregnancies according to gestational age at birth and type of management adopted (inpatient or outpatient).

Study Design:  Medline and Embase databases were searched. Inclusion criteria were nonanomalous MCMA twins. The primary outcome was a composite score of neonatal morbidity, defined as the occurrence of at least one of the following outcomes: respiratory morbidity, overall neurological morbidity, severe neurological morbidity, and infectious morbidity, necrotizing enterocolitis at different gestational age windows (24-30, 31-32, 33-34, and 35-36 weeks). Secondary outcomes were the individual components of the primary outcome and admission to neonatal intensive care unit (NICU). Subanalysis according to the type of surveillance strategy (inpatient compared with outpatient) was also performed. Random effect meta-analyses were used to analyze the data.

Results:  A total of 14 studies including 685 MCMA twin pregnancies without fetal anomalies were included. At 24 to 30, 31 to 32, 33 to 34, and 35 to 36 weeks of gestation, the rate of composite morbidity was 75.4, 65.5, 37.6, and 18.5%, respectively, the rate of respiratory morbidity was 74.2, 59.1, 35.5, and 12.2%, respectively, while overall neurological morbidity occurred in 15.3, 10.2, 4.3, and 0% of the cases, respectively. Infectious morbidity complicated 13, 4.2, 3.1, and 0% of newborns while 92.1, 81.6, 58.7, and 0% of cases required admission to NICU. Morbidity in pregnancies delivered between 35 and 36 weeks of gestation was affected by the very small sample size of cases included. When comparing the occurrence of overall morbidity according to the type of management (inpatient or outpatient), there was no difference between the two surveillance strategies ( = 0.114).

Conclusion:  MCMA pregnancies are at high risk of composite neonatal morbidity, mainly respiratory morbidity that gradually decreases with increasing gestational age at delivery with a significant reduction for pregnancies delivered between 33 and 34 weeks. We found no difference in the occurrence of neonatal morbidity between pregnancies managed as inpatient or outpatient.

Key Points: · MCMA pregnancies are at high risk of composite neonatal morbidity, mainly respiratory morbidity.. · Neonatal morbidity gradually decreases with increasing GA at delivery, mostly between 33 and 34 weeks.. · There is no difference in the occurrence of neonatal morbidity between in- or outpatient management..
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http://dx.doi.org/10.1055/s-0040-1714420DOI Listing
July 2020

Role of prenatal magnetic resonance imaging in fetuses with isolated agenesis of corpus callosum in the era of fetal neurosonography: A systematic review and meta-analysis.

Acta Obstet Gynecol Scand 2021 01 24;100(1):7-16. Epub 2020 Aug 24.

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

Introduction: Corpus callosum agenesis (ACC) is frequently diagnosed during fetal life; its prognosis depends also on additional anomalies. The additional value of fetal magnetic resonance imaging (MRI) in fetuses with "isolated" complete (cACC) and partial (pACC) agenesis of the corpus callosum on ultrasound is still debated.

Material And Methods: We performed a systematic literature review and meta-analysis including fetuses with a prenatal diagnosis of cACC and pACC without associated structural anomalies on ultrasound, undergoing fetal MRI. The primary outcome was the rate of additional anomalies detected at fetal MRI. Further analyses assessed the effect of type of ultrasound assessment (neurosonography vs standard axial assessment), gestational age at fetal MRI and rate of postnatally detected brain anomalies. Random-effect meta-analyses of proportions were used to analyze the data.

Results: Fourteen studies (798 fetuses) were included. In cases with isolated cACC, 10.9% (95% CI 4.1-20.6) and 4.3% (95% CI 1.4-8.8) additional anomalies were detected by fetal MRI and postnatally, respectively. Stratifying according to the type of ultrasound assessment, the rate of associated anomalies detected only on fetal MRI was 5.7% (95% CI 0.5-16.0) with dedicated neurosonography and 18.5% (95% CI 7.8-32.4) with a standard axial assessment. In fetuses with isolated pACC, 13.4% (95% CI 4.0-27.0) and 16.2% (95% CI 5.9-30.3) additional anomalies were detected by fetal MRI or postnatally, respectively. Stratifying according to the type of ultrasound assessment, the rate of associated anomalies detected only on fetal MRI was 11.4% (95% CI 2.7-25.0) when dedicated neurosonography was performed. Cortical and posterior fossa anomalies represented the most common anomalies missed at ultrasound with both cACC and pACC. Due to the very small number of included cases, stratification according to early (<24 weeks of gestation) and late (>24 weeks) fetal MRI could not be done for either cACC or pACC.

Conclusions: The rate of associated anomalies detected exclusively at fetal MRI in isolated ACC undergoing neurosonography is lower than previously reported. Cortical and posterior fossa anomalies are among the most common anomalies detected exclusively at MRI, thus confirming the crucial role of fetal MRI in determining the prognosis of these fetuses. However, some anomalies still go undetected prenatally and this should be stressed during parental counseling.
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http://dx.doi.org/10.1111/aogs.13958DOI Listing
January 2021

Abdominal pregnancy: Things to keep in mind!

Eur J Obstet Gynecol Reprod Biol 2020 Sep 26;252:628-629. Epub 2020 Jun 26.

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

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http://dx.doi.org/10.1016/j.ejogrb.2020.06.050DOI Listing
September 2020

Reproductive outcome after cesarean scar pregnancy: A systematic review and meta-analysis.

Acta Obstet Gynecol Scand 2020 10 19;99(10):1278-1289. Epub 2020 Jun 19.

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

Introduction: To evaluate subsequent reproductive among women with a prior cesarean scar pregnancy (CSP).

Material And Methods: MEDLINE, Embase and ClinicalTrials.gov databases were searched. Inclusion criteria were women with a prior CSP, defined as the gestational sac or trophoblast within the dehiscence/niche of the previous cesarean section scar or implanted on top of it. The primary outcome was the recurrence of CSP; secondary outcomes were the chance of achieving a pregnancy after CSP, miscarriage, preterm birth, uterine rupture and the occurrence of placenta accreta spectrum disorders. Subgroup analysis according to the management of CSP (surgical vs non-surgical) was also performed. Random effect meta-analyses of proportions were used to analyze the data.

Results: Forty-four studies (3598 women with CSP) were included. CSP recurred in 17.6% of women. Miscarriage, preterm birth and placenta accreta spectrum disorders complicated 19.1% (65/341), 10.3% (25/243) and 4.0% of pregnancies, and 67.0% were uncomplicated. When stratifying the analysis according to the type of management, CSP recurred in 21% of women undergoing surgical and in 15.2% of those undergoing non-surgical management. Placenta accreta spectrum disorders complicated 4.0% and 12.0% of cases, respectively.

Conclusions: Women with a prior CSP are at high risk of recurrence, miscarriage, preterm birth and placenta accreta spectrum. There is still insufficient evidence to elucidate whether the type of management adopted (surgical vs non-surgical) can impact reproductive outcome after CSP. Further large, prospective studies sharing an objective protocol of prenatal management and long-term follow up are needed to establish the optimal management of CSP and to elucidate whether it may affect its risk of recurrence and pregnancy outcome in subsequent gestations.
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http://dx.doi.org/10.1111/aogs.13918DOI Listing
October 2020

Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic review and meta-analysis.

Am J Obstet Gynecol MFM 2020 05 25;2(2):100107. Epub 2020 Mar 25.

Departments of Obstetrics and Gynecology and Medical and Surgical Sciences, University of Foggia, Foggia, Italy.

Objective: The aim of this systematic review was to report pregnancy and perinatal outcomes of coronavirus spectrum infections, and particularly coronavirus 2019 (COVID-19) disease because of severe acute respiratory syndrome-coronavirus-2 infection during pregnancy.

Data Sources: Medline, Embase, Cinahl, and Clinicaltrials.gov databases were searched electronically utilizing combinations of word variants for coronavirus or severe acute respiratory syndrome or SARS or Middle East respiratory syndrome or MERS or COVID-19 and pregnancy. The search and selection criteria were restricted to English language.

Study Eligibility Criteria: Inclusion criteria were hospitalized pregnant women with a confirmed coronavirus related-illness, defined as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), or COVID-19.

Study Appraisal And Synthesis Methods: We used meta-analyses of proportions to combine data and reported pooled proportions, so that a pooled proportion may not coincide with the actual raw proportion in the results. The pregnancy outcomes observed included miscarriage, preterm birth, preeclampsia, preterm prelabor rupture of membranes, fetal growth restriction, and mode of delivery. The perinatal outcomes observed were fetal distress, Apgar score <7 at 5 minutes, neonatal asphyxia, admission to a neonatal intensive care unit, perinatal death, and evidence of vertical transmission.

Results: Nineteen studies including 79 hospitalized women were eligible for this systematic review: 41 pregnancies (51.9%) affected by COVID-19, 12 (15.2%) by MERS, and 26 (32.9%) by SARS. An overt diagnosis of pneumonia was made in 91.8%, and the most common symptoms were fever (82.6%), cough (57.1%), and dyspnea (27.0%). For all coronavirus infections, the pooled proportion of miscarriage was 64.7% (8/12; 95% confidence interval, 37.9-87.3), although reported only for women affected by SARS in two studies with no control group; the pooled proportion of preterm birth <37 weeks was 24.3% (14/56; 95% confidence interval, 12.5-38.6); premature prelabor rupture of membranes occurred in 20.7% (6/34; 95% confidence interval, 9.5-34.9), preeclampsia in 16.2% (2/19; 95% confidence interval, 4.2-34.1), and fetal growth restriction in 11.7% (2/29; 95% confidence interval, 3.2-24.4), although reported only for women affected by SARS; 84% (50/58) were delivered by cesarean; the pooled proportion of perinatal death was 11.1% (5/60; 95% confidence interval, 84.8-19.6), and 57.2% of newborns (3/12; 95% confidence interval, 3.6-99.8) were admitted to the neonatal intensive care unit. When focusing on COVID-19, the most common adverse pregnancy outcome was preterm birth <37 weeks, occurring in 41.1% of cases (14/32; 95% confidence interval, 25.6-57.6), while the pooled proportion of perinatal death was 7.0% (2/41; 95% confidence interval, 1.4-16.3). None of the 41 newborns assessed showed clinical signs of vertical transmission.

Conclusion: In hospitalized mothers infected with coronavirus infections, including COVID-19, >90% of whom also had pneumonia, preterm birth is the most common adverse pregnancy outcome. COVID-19 infection was associated with higher rate (and pooled proportions) of preterm birth, preeclampsia, cesarean, and perinatal death. There have been no published cases of clinical evidence of vertical transmission. Evidence is accumulating rapidly, so these data may need to be updated soon. The findings from this study can guide and enhance prenatal counseling of women with COVID-19 infection occurring during pregnancy, although they should be interpreted with caution in view of the very small number of included cases.
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http://dx.doi.org/10.1016/j.ajogmf.2020.100107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104131PMC
May 2020

Extracellular Vesicles in Feto-Maternal Crosstalk and Pregnancy Disorders.

Int J Mol Sci 2020 Mar 19;21(6). Epub 2020 Mar 19.

Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy.

Extracellular vesicles (EVs) actively participate in inter-cellular crosstalk and have progressively emerged as key players of organized communities of cells within multicellular organisms in health and disease. For these reasons, EVs are attracting the attention of many investigators across different biomedical fields. In this scenario, the possibility to study specific placental-derived EVs in the maternal peripheral blood may open novel perspectives in the development of new early biomarkers for major obstetric pathological conditions. Here we reviewed the involvement of EVs in feto-maternal crosstalk mechanisms, both in physiological and pathological conditions (preeclampsia, fetal growth restriction, preterm labor, gestational diabetes mellitus), also underlining the usefulness of EV characterization in maternal-fetal medicine.
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http://dx.doi.org/10.3390/ijms21062120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139847PMC
March 2020

Pre- and postnatal brain hemodynamics in pregnancies at term: correlation with Doppler ultrasound, birthweight, and adverse perinatal outcome.

J Matern Fetal Neonatal Med 2020 Mar 9:1-7. Epub 2020 Mar 9.

Department of Medical and Surgical Sciences, Institute of Obstetrics and Gynecology, University of Foggia, Foggia, Italy.

To elucidate the correlation between pre- and postnatal cerebral Doppler in pregnancies close to term and to explore whether they are associated with perinatal outcome. Prospective study on singleton pregnancies at 36-37 weeks of gestation. The primary outcome was a composite score of perinatal morbidity, while secondary outcomes were adverse intra-partum outcome and abnormal acid-base status. All pregnancies underwent ultrasound assessment of umbilical artery (UA), middle cerebral artery (MCA), uterine arteries (UtAs) pulsatility index (PI), and cerebroplacental ratio (CPR). At birth, neonatal MCA PI was measured 72 h from delivery and correlated with prenatal Doppler, primary and secondary outcomes. Fisher's test and multivariate logistic regression analysis were used to analyze the data. One hundred and sixty-six fetuses with both pre- and postnatal Doppler assessment of the MCA were included in the study. The risk of composite perinatal morbidity was higher in fetuses (OR: 5.7, 95% CI 2.2-14.6) and newborns (OR: 4.1, 95% CI 1.8-9.6) with fetal MCA PI < 10th centile. Likewise, the incidence of abnormal acid-base status was higher both in fetuses (20 versus 4.2%,  = .026) and newborns (17.1 versus 3.2%,  = .001) with a low MCA PI before and at birth, respectively. At logistic regression analysis, fetal and neonatal MCAPI were independently associated with composite perinatal morbidity and abnormal acid-base status, but not with adverse intra-partum outcome. In small for gestational age (SGA) fetuses, the incidence of composite perinatal morbidity was higher in fetuses and new-borns presenting compared to those not presenting with an MCA PI < 10th centile (61.5 versus 20%,  = .003 and 52.6% versus 7.1%,  = .008, respectively), while such association was lost when considering non-SGA fetuses. A low MCA PI is associated with adverse perinatal outcome in pregnancies at term and tends to persist after birth.
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http://dx.doi.org/10.1080/14767058.2020.1731456DOI Listing
March 2020

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 2020 08 15;223(2):189-203. Epub 2020 Feb 15.

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

Objective: The aim of this systematic review and meta-analysis of randomized controlled trials was to evaluate the effect of delayed versus immediate pushing in the second stage of labor on mode of delivery and other outcomes in women with neuraxial analgesia.

Data Sources: The research was conducted using MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID, and the Cochrane Library as electronic databases, from the inception of each database to August 2019. No restrictions for language or geographic location were applied.

Study Eligibility Criteria: Selection criteria included only randomized controlled trials in pregnant women randomized to either delayed or immediate pushing during the second stage of labor.

Study Appraisal And Synthesis Methods: The primary outcome was mode of delivery. The summary measures were reported as relative risk or as mean difference with 95% confidence intervals using the random effects model of DerSimonian and Laird. An I (Higgins I) value of greater than 0% was used to identify heterogeneity.

Results: Twelve randomized controlled trials, including 5445 women with neuraxial analgesia randomized to delayed versus immediate pushing during the second stage of labor, were included in the meta-analysis. Of the 5445 women included in the meta-analysis, 2754 were randomized to the delayed pushing group and 2691 to the immediate pushing group. No significant difference between delayed and immediate pushing was found for spontaneous vaginal delivery (80.9% versus 78.3%; relative risk, 1.05; 95% confidence interval, 1.00-1.10; 12 randomized controlled trials, 5540 women), operative vaginal delivery (12.8% versus 14.6%; relative risk, 0.89; 95% confidence interval, 0.75-1.08; 11 randomized controlled trials, 5395 women), and cesarean delivery (6.9% versus 7.9%; relative risk, 0.89; 95% confidence interval, 0.73-1.07; 11 randomized controlled trials; 5395 women). Women randomized to the delayed pushing group had a significantly shorter length of active pushing (mean difference, -27.54 minutes; 95% confidence interval, -43.04 to -12.04; 7 randomized controlled trials, 4737 women) at the expense of a significantly longer overall duration of the second stage of labor (mean difference, 46.17 minutes; 95% confidence interval, 32.63-59.71; 8 studies; 4890 women). The incidence of chorioamnionitis (9.1% versus 6.6%; relative risk, 1.37, 95% confidence interval, 1.04-1.81; 1 randomized controlled trial, 2404 women) and low umbilical cord pH (2.7% versus 1.3%; relative risk, 2.00; 95% confidence interval, 1.30-3.07; 5 randomized controlled trials, 4549 women) were significantly higher in the delayed pushing group.

Conclusion: In women with spontaneous or induced labor at term with neuraxial analgesia, delayed pushing in the second stage does not affect the mode of delivery, although it reduces the time of active pushing at the expense of a longer second stage. This prolongation of labor was associated with a higher incidence of chorioamnionitis and low umbilical cord pH. Based on these findings, delayed pushing cannot be routinely advocated for the management of the second stage.
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http://dx.doi.org/10.1016/j.ajog.2020.02.002DOI Listing
August 2020

Prenatal risk factors for urgent atrial septostomy at birth in fetuses with transposition of the great arteries: a systematic review and meta-analysis.

J Matern Fetal Neonatal Med 2020 Feb 10:1-9. Epub 2020 Feb 10.

Department of Obstetrics and Gynaecology, Ospedali Riuniti, University of Foggia, Foggia, Italy.

To explore the role of fetal echocardiography in predicting the risk of urgent balloon atrial septostomy (BAS) at birth in fetuses diagnosed with transposition of the great arteries (TGA). Medline, Embase, and Cochrane databases were searched. The primary aim was to explore the differences in prenatal echocardiographic parameters among fetuses diagnosed with TGA that required urgent BAS within 24 h of birth due to life-threatening cyanosis compared to those who did not require such procedure. Random-effect meta-analyses were used to compute the data. Six studies (292 fetuses) were included. Restrictive appearance of the FO was present in 64.5% (95% CI = 39.8-85.7) of fetuses with TGA requiring BAS at birth compared to 7.9% (95% CI = 2.1-16.8) not requiring such procedure (OR = 71.1; 95% CI = 8.3-608.5,  < .0001). Hypermobile appearance of the atrial septum was present in 39.1% (95% CI = 26.4-56.5) of fetuses requiring BAS at birth compared to 9.8% (95% CI = 1.4-24.3) of those which did (OR 3.6; 95% CI = 1.4-9.0,  = .05). There was no difference in the prevalence of redundant ( = .374) or fixed ( = .051) atrial septum, bidirectional flow in the DA ( = .26) or an abnormal size of the DA ( = .06) in fetuses requiring urgent BAS at birth compared to those which did not. Mean (±SD) size of the right atrium was smaller in the fetuses with TGA undergoing urgent BAS at birth (23.4 ± 6.7) compared to those which did not (29.2 ± 6.2,  = .01). The mean (±SD) ratio between the FO and the aortic valve diameters (1.01 ± 0.41 versus 1.41 ± 0.43,  = .009) and the mean (±SD) ratio between the FO diameter and the septal length (0.36 ± 0.13 versus 0.51 ± 0.14,  = .001) were significantly smaller in fetuses requiring compared to those not undergoing urgent BAS at birth. The diagnostic accuracy of each independent ultrasound marker of the need for urgent BAS showed an overall good specificity but a low sensitivity. Fetal echocardiography prior to birth can stratify the risk of BAS in fetuses with TGA. Further studies are needed to validate these findings and build individualized multiparametric predictive models in order to more accurately identify those fetuses with TGA at a higher risk of urgent BAS after birth.
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http://dx.doi.org/10.1080/14767058.2020.1725883DOI Listing
February 2020

Diagnostic Accuracy of Doppler Ultrasound in Predicting Perinatal Outcome in Appropriate for Gestational Age Fetuses: A Prospective Study.

Ultraschall Med 2020 Feb 10. Epub 2020 Feb 10.

Department of Clinical Medicine, Faculty of Health Sciences, University-Hospital of Northern Norway, UiT Norges arktiske universitet Alta, Norway.

Objective:  To elucidate the role of Doppler ultrasound in predicting perinatal outcome in appropriate for gestational age (AGA) fetuses at term.

Material And Methods:  Prospective study carried out in a dedicated research ultrasound clinic. The inclusion criterion was AGA fetuses, defined as those with an estimated fetal weight between the 10 and 90 percentile, at 36 + 0-37 + 6 weeks of gestation. The primary outcome was a composite score of adverse perinatal outcome including either adverse intrapartum events or abnormal acid-base status at birth. Secondary outcomes were the individual components of the primary outcome. The Doppler parameters explored were umbilical artery (UA) PI, middle cerebral artery (MCA) PI, uterine arteries (UtA) PI and cerebroplacental ratio (CPR). Attending clinicians were blinded to Doppler findings. Logistic regression and ROC curve analyses were used to analyze the data.

Results:  553 AGA fetuses were included. There was no difference in mean UA PI (p = 0.486), MCA PI (p = 0.621), CPR (p = 0.832) and UtA PI (p = 0.611) between pregnancies complicated by composite perinatal morbidity compared to those not complicated by composite perinatal morbidity. In pregnancies complicated by adverse intrapartum outcome, the mean MCA PI (1.47 ± 0.4 vs 1.61 ± 0.4, p = 0.0039) was lower compared to the control group, while there was no difference in UA PI (p = 0.758), CPR (p = 0.108), and UtA PI (p = 0.177). Finally, there was no difference in any of the Doppler parameters explored between AGA fetuses with abnormal acid-base status at birth compared to those without abnormal acid-base status at birth. In the logistic regression analysis, UA PI, MCA PI, CPR, UtA PI, EFW and AC percentiles were not independently associated with composite adverse outcome, adverse intrapartum outcome or abnormal acid-base status at birth in non-SGA fetuses. The diagnostic performance of all of these Doppler parameters for predicting composite adverse outcome, adverse intrapartum outcome and abnormal acid-base status was poor.

Conclusion:  Cerebroplacental and maternal Doppler is not associated with or predictive of adverse pregnancy outcome in AGA fetuses close to term.
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http://dx.doi.org/10.1055/a-1072-5161DOI Listing
February 2020

Outcome of fetal echogenic bowel: A systematic review and meta-analysis.

Prenat Diagn 2021 Mar 21;41(4):391-399. Epub 2021 Feb 21.

Department of Obstetrics and Gynecology, University of Foggia, Foggia, Italy.

The main aim of this systematic review was to explore the outcome of fetuses with isolated echogenic bowel (EB) on antenatal ultrasound. Inclusion criteria were singleton pregnancies with isolated EB no associated major structural anomalies at the time of diagnosis. The outcomes observed were: chromosomal anomalies, cystic fibrosis (CF), associated structural anomalies detected only at follow-up scans and at birth, regression during pregnancy, congenital infections, intra-uterine (IUD), neonatal (NND) and perinatal (PND) death. Twenty-five studies (12 971 fetuses) were included. Chromosomal anomalies occurred in 3.3% of the fetuses, mainly Trisomy 21 and aneuploidies involving the sex chromosomes. Cystic fibrosis occurred in 2.2%. Congenital infections affected 2.2%, mainly congenital Cytomegalovirus (CMV) infection. The majority of fetuses with EB experienced regression or disappearance of the EB at follow-up scans. Associated anomalies were detected at a follow-up scan in 1.8%. Associated anomalies were detected at birth and missed at ultrasound in 2.1% of cases. IUD occurred in 3.2% of cases while the corresponding figures for NND and PND were 0.4% and 3.1%. Fetuses with EB are at increased risk of adverse perinatal outcome, highlighting the need for a thorough antenatal management and postnatal follow-up. Assessment during pregnancy and after birth should be performed in order to look for signs of fetal aneuploidy, congenital infections and associated structural anomalies.
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http://dx.doi.org/10.1002/pd.5638DOI Listing
March 2021

Prenatal imaging features and postnatal outcomes of isolated fetal duplex renal collecting system: A systematic review and meta-analysis.

Prenat Diagn 2020 03 28;40(4):424-431. Epub 2020 Jan 28.

Department of Medical and Surgical Sciences, Institute of Obstetrics and Gynecology, University of Foggia, Foggia, Italy.

Objectives: To perform a systematic review of studies reporting the outcome of fetuses with a prenatal diagnosis of isolated duplex collecting system (DCS).

Methods: Inclusion criteria were studies reporting the outcome of fetuses with a prenatal diagnosis of isolated DCS, defined as DCS not associated with other major structural anomalies at the time of diagnosis. The outcomes observed were: imaging features of DCS on prenatal ultrasound, associated anomalies detected exclusively at prenatal follow-up ultrasound and at birth, abnormal karyotype, symptoms at birth (including vesicoureteral reflux [VUR] and urinary tract infections [UTI]), need for and type of surgical approach, complications after surgery, and accuracy of prenatal ultrasound in correctly identifying this anomaly.

Results: Eleven studies (284 fetuses with a prenatal diagnosis of DCS) were included. On ultrasound, DCS was associated with ureterocele in 70.7% and with megaureter in 36.6% of cases. Worsening of pelvic/ureteric dilatation was reported to occur in 41.3% of fetuses. At birth, 4.3% of fetuses affected by DCS showed associated renal anomalies. After birth, VUR and UTI presented in 51.3% and 21.7% of children respectively, while 33.6% required surgery. Prenatal diagnosis of DCS was confirmed in 90.9% of included cases.

Conclusion: DCS diagnosed prenatally is associated with a generally good outcome. Prenatal ultrasound has a good diagnostic accuracy, while detailed postnatal assessment is required in order to identify associated renal anomalies.
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http://dx.doi.org/10.1002/pd.5622DOI Listing
March 2020

Diagnostic accuracy of Doppler ultrasound in predicting perinatal outcome in pregnancies at term: A prospective longitudinal study.

Acta Obstet Gynecol Scand 2020 01 9;99(1):42-47. Epub 2019 Oct 9.

Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy.

Introduction: To explore the strength of association and the diagnostic accuracy of umbilical (UA), middle cerebral (MCA), uterine arteries pulsatility index (PI) and the cerebroplacental ratio in predicting an adverse outcome when applied to singleton pregnancies at term.

Material And Methods: Prospective study carried out in a dedicated research ultrasound clinic. Attended clinicians were blinded to Doppler findings. Inclusion criteria were consecutive singleton pregnancies between 36 and 37  weeks of gestation. The primary outcome was a composite score of adverse perinatal outcome. Logistic regression and ROC curve analyses were used to analyze the data.

Results: In all, 600 consecutive singleton pregnancies from 36 weeks of gestation were included in the study. Mean MCA PI (1.1 ± 0.2 vs 1.5 ± 0.4, P < 0.001) and cerebroplacental ratio (1.4 ± 0.4 vs 1.9 ± 0.6, P < 0.001) were lower, whereas uterine arteries PI (0.8 ±0.2 vs 0.7 ±0.3, P = 0.001) was higher in pregnancies experiencing than in those not experiencing composite adverse outcome. Conversely, there was no difference in either UA PI (P = 0.399) or estimated fetal weight centile (P = 0.712) between the two groups, but AC centile was lower in fetuses experiencing composite adverse outcome (45.4 vs 53.2, P = 0.040). At logistic regression analysis, MCA PI (odds ratio [OR] 0.1, 95% CI 0.01-.2, P = 0.001), uterine arteries PI (OR 1.4, 95% CI 1.2-1.6, P = 0.001), abdominal circumference centile (OR 1.12, 95% CI 1.1-1.4, P = 0.001) and gestational age at birth (OR 1.6, 95% CI 1.2-2.1, P = 0.004) were independently associated with composite adverse outcome. Despite this, the diagnostic accuracy of Doppler in predicting adverse pregnancy outcome at term was poor.

Conclusions: MCA PI and cerebroplacental ratio are associated with adverse perinatal outcome at term. However, their predictive accuracy for perinatal compromise is poor, and thus their use as standalone screening test for adverse perinatal outcome in singleton pregnancies at term is not supported.
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http://dx.doi.org/10.1111/aogs.13705DOI Listing
January 2020
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