Treatment with valacyclovir during pregnancy for prevention of congenital cytomegalovirus infection: a real-life multicenter Italian observational study.

BACKGROUND: Valacyclovir is the only treatment demonstrated to be effective for the prevention of vertical transmission of cytomegalovirus within a clinical randomized, placebo-controlled trial and has been reimbursed by the Italian National Health System since December 2020. OBJECTIVE: This study reported the results of a real-life Italian multicenter observational study on cytomegalovirus infection in pregnancy evaluating the effect of the introduction of valacyclovir in the clinical practice for the prevention of vertical transmission of cytomegalovirus. STUDY DESIGN: The outcomes of women who received valacyclovir treatment and their fetuses or newborns were compared with those of a retrospective cohort observed between 2010 and 2020 who did not receive the antiviral treatment. The inclusion criterion was the diagnosis of cytomegalovirus primary infection occurring in the periconceptional period or up to 24 weeks of gestation. The primary outcome was the transmission by the time of amniocentesis. The secondary outcomes were termination of pregnancy, transmission at birth, symptomatic infection at birth, and a composite outcome (termination of pregnancy or transmission at birth). RESULTS: A total of 447 pregnant women from 10 centers were enrolled, 205 women treated with valacyclovir (called the valacyclovir group, including 1 twin pregnancy) and 242 women not treated with valacyclovir (called the no-valacyclovir group, including 2 twin pregnancies). Valacyclovir treatment was significantly associated with a reduction of the diagnosis of congenital cytomegalovirus infection by the time of amniocentesis (weighted odds ratio, 0.39; 90% confidence interval, 0.22-0.68; P=.005; relative reduction of 61%), termination of pregnancy (weighted odds ratio, 0.36; 90% confidence interval, 0.17-0.75; P=.0021; relative reduction of 64%), symptomatic congenital cytomegalovirus infection at birth (weighted odds ratio, 0.17; 90% confidence interval, 0.06-0.49; P=.006; relative reduction of 83%). The treatment had no significant effect on the rate of diagnosis of congenital cytomegalovirus infection at birth (weighted odds ratio, 0.85; 90% confidence interval, 0.57-1.26; P=.500), but the composite outcome (termination of pregnancy or diagnosis of congenital cytomegalovirus infection at birth) occurred more frequently in the no-valacyclovir group (weighted odds ratio, 0.62; 90% confidence interval, 0.44-0.88; P=.024). Of note, the only symptomatic newborns with congenital cytomegalovirus infection in the valacyclovir group (n=3) were among those with positive amniocentesis. Moreover, 19 women (9.3%) reported an adverse reaction to valacyclovir treatment, classified as mild in 17 cases and moderate in 2 cases. Lastly, 4 women (1.9%) presented renal toxicity with a slight increase in creatinine level, which was reversible after treatment suspension. CONCLUSION: Our real-life data confirm that valacyclovir significantly reduces the rate of congenital cytomegalovirus diagnosis at the time of amniocentesis with a good tolerability profile and show that the treatment is associated with a reduction of termination of pregnancy and symptomatic congenital cytomegalovirus infection at birth.

Neurodevelopmental outcomes of very preterm infants born following early foetal growth restriction with absent end-diastolic umbilical flow.

This study aims to assess the impact of time of onset and features of early foetal growth restriction (FGR) with absent end-diastolic flow (AEDF) on pregnancy outcomes and on preterm infants' clinical and neurodevelopmental outcomes up to 2 years corrected age. This is a retrospective, cohort study led at a level IV Obstetric and Neonatal Unit in Bologna, Italy. Pregnant women were eligible if having singleton pregnancies, with no major foetal anomaly detected, and diagnosed with early FGR + AEDF (defined as FGR + AEDF detected before 32 weeks gestation). Early FGR + AEDF was further classified according to time of onset and specific features into very early and persistent (VEP, FGR + AEDF first detected at 20-24 weeks gestation and persistent at the following scans), very early but transient (VET, FGR + AEDF detected at 20-24 weeks gestation and progressively improving at the following scans) and later (LA, FGR + AEDF detected between 25 and 32 weeks gestation). Pregnancy and neonatal outcomes and infant follow-up data were collected and compared among groups. Neurodevelopment was assessed using the revised Griffiths Mental Developmental Scales (GMDS-R) 0-2 years. A regression analysis was performed to identify early predictors of preterm infants' neurodevelopmental impairment. Fifty-two pregnant women with an antenatal diagnosis of early FGR + AEDF were included in the study (16 VEP, 14 VET, 22 LA). Four intrauterine foetal deaths occurred, all in the VEP group (p = 0.010). Compared to LA infants, VEP infants were born with lower gestational age and lower birth weight, had lower arterial cord blood pH and were at higher risk for intraventricular haemorrhage and periventricular leukomalacia (p < 0.05 for all comparisons). At 12 months, VEP infants had worse GMDS-R scores, both in the general quotient (mean [SD] 91.8 [12.4] vs 104.6 [8.7] in LA) and in the performance domain (mean [SD] 93.3 [15.4] vs 108.8 [8.8] in LA). This latter difference persisted at 24 months (mean [SD] 68.3 [17.0] vs 92.9 [17.7] in LA). In multivariate analysis, at 12 months corrected age, PVL was found to be an independent predictor of impaired general quotient, while the features and timing of antenatal Doppler alterations predicted worse scores in the performance domain.   Conclusion: Timing of onset and features of early FGR + AEDF might impact differently on neonatal clinical and neurodevelopmental outcomes. Shared awareness of the importance of FGR + AEDF features between obstetricians and neonatologists may offer valuable tools for antenatal counselling and for tailoring pregnancy management and neonatal follow-up in light of specific antenatal and neonatal risk factors. What is Known: • Foetal growth restriction (FGR), together with antenatal umbilical Doppler abnormalities, is known to affect maternal and neonatal outcomes. • Infants born preterm and growth-restricted face the highest risk for neurodevelopmental impairment, especially when FGR occurs early during pregnancy (early FGR, before 32 weeks gestation). What is New: • The timing of onset and features of FGR and antenatal umbilical Doppler abnormalities impact differently on maternal and neonatal outcomes; when FGR and Doppler abnormalities occur very early, at the limit of neonatal viability, and persist until delivery, infants face the highest risk for neurodevelopmental impairment. • Shared knowledge between obstetricians and neonatologists about timing of onset and features of FGR would provide a valuable tool for informed antenatal counselling in high-risk pregnancies.

Analysis and distribution of per- and polyfluoroalkyl substances in decidua and villi placenta explants.

Placenta mediates the transfer of nutrients, oxygen and drugs from mother to fetus. It is constituted by two cellular layers separated by the intervillous space: the outer is in direct contact with maternal blood (decidua placenta), and the inner (villi) directly in contact with the fetus. Environmental contaminants, such as per- and polyfluoroalkyl substances (PFAS) also demonstrated the ability to cross the tissue multiple layers, posing at risk the health of the fetus. The aim of the present study was to analyse the PFAS amount in decidua and villi placenta explants and to study differences in their distribution among the two side of this organ. The determination of 23 PFAS was carried out by liquid chromatography coupled to high-resolution accurate mass spectrometry (LC-HRAM). Our research included women who delivered at term between 2021 and 2022. Our data indicated that all samples contained at least one PFAS, demonstrating the ubiquitarian presence of these compounds in our population. A high occurrence of PFOS, PFOA and PFHxS, followed by PFHxA, PFBS and PFUnA was found. The fluorotelomer 6:2 FTS was also present in more than 40% of samples and this represent the first data on placenta explants. Mean and median PFAS values for decidual explants were 0.5 ng/g and 0.4 ng/g (SD 0.3), while for villi explants mean and median values were 0.6 ng/g and 0.4 ng/g (SD 0.4). A different pattern of accumulation was observed between villi and decidual explants for PFOS, PFOA and PFUnA (villi > decidua) and PFHxA, PFHxS, PFBS and 6:2 FTS (decidua > villi). Even if the mechanism of this selectively accumuation is not yet understood, molecular degree of ionization and its lipophilicity could at least in part explain this difference. This study expands the limited data describing PFAS levels in the placenta and pose attention on PFAS exposure during pregnancy.

Utility of Doppler-Ultrasound and Liver Elastography in the Evaluation of Patients with Suspected Pregnancy-Related Liver Disease.

Grayscale abdomen ultrasound (US) is routinely performed in pregnant women with suspected pregnancy-related liver dysfunction, but its diagnostic yield is very low. We aimed to investigate the association between Doppler-US findings, liver stiffness measurement (LSM) and different causes of pregnancy-related liver dysfunction. This is a prospective cohort study of pregnant women referred to our tertiary center for any suspected gastrointestinal disease between 2017 and 2019 and undergoing Doppler-US and liver elastography. Patients with previous liver disease were excluded from the analysis. For group comparisons of categorical and continuous variables, the chi-square test or Mann-Whitney test, and the McNemar test were used, as appropriate. A total of 112 patients were included in the final analysis, of whom 41 (36.6%) presented with suspected liver disease: 23 intrahepatic cholestasis of pregnancy (ICP), six with gestational hypertensive disorders and 12 cases with undetermined causes of elevated liver enzymes. Values of LSM were higher and significantly associated with a diagnosis of gestational hypertensive disorder (AUROC = 0.815). No significant differences at Doppler-US or LSM were found between ICP patients and controls. Patients with undetermined causes of hypertransaminasemia showed higher hepatic and splenic resistive indexes than controls, suggesting splanchnic congestion. The evaluation of Doppler-US and liver elastography is clinically useful in patients with suspected liver dysfunction during pregnancy. Liver stiffness represents a promising non-invasive tool for the assessment of patients with gestational hypertensive disorders.

Hazard and cumulative incidence of umbilical cord metabolic acidemia at birth in fetuses experiencing the second stage of labor and pathologic intrapartum fetal heart rate requiring expedited delivery.

PURPOSE: The aim of the study was to determine the cause-specific hazard (CSH) and the cumulative incidence function (CIF) for umbilical cord metabolic acidemia at birth (MA; pH < 7.0 and/or BE [Formula: see text] - 12 mmol/L) at delivery in patients experiencing the 2nd stage of labor (2STG), stratified for both FIGO-2015 pathologic intrapartum cardiotocography requiring expedited delivery (CTG_RED) and duration of 2nd stage of labor. METHODS: 3459 pregnancies experiencing the 2nd stage of labor and delivering at the Division of Obstetrics and Prenatal Medicine, IRCCS Sant'Orsola-Malpighi Hospital, Bologna (Italy), were identified between 2018 and 2019. Survival analysis was used to assess CSH and CIF for MA, stratified for FIGO-2015 pathologic CTG and relevant covariates. RESULTS: FIGO-2015 pathological CTG with expedited operative delivery or urgent cesarean section within 10 or 20 min from diagnosis, respectively occurred in 282/3459 (8.20%). The rate of MA at delivery was 3.32% (115/3459). The spline of CSH for MA showed a direct correlation with the duration of 2STG always presenting higher values and greater slope in the presence of pathologic CTG, with plateau between 60 and 120 min and rapid increase after 120 min. The CIF at 180 min in the 2STG was 2.67% for nonpathological and 10.63% for pathological CTG_RED. Nulliparity, pathological CTG, and meconium-stained amniotic fluid resulted significant predictors of MA in our multivariable model. CONCLUSION: The risk for MA increases moderately across the 2STG with nonpathological CTG and quadruples with pathological CTG_RED. Adjustment for other predictors of MA including meconium-stained amniotic fluid and nulliparity reveals a significant hazard increase for MA associated with pathologic CTG_RED.

The cumulative incidence of neonatal metabolic acidemia after terminal bradycardia in the 2nd stage of labor: a survival-based model.

PURPOSE: The aim of the study was to estimate by a survival analysis model the hazard function (HF) for neonatal metabolic acidemia (MA) throughout the 2nd stage of labor (2STG) at the time of occurrence of a terminal bradycardia ≥ 10 min requiring expedited delivery, and the cumulative incidence function (CIF) for MA according with the duration of bradycardia stratified in 10-12 min and > 12 min. METHODS: Singleton pregnancies experiencing terminal fetal bradycardia requiring expedited delivery in the 2STG at 38 + 0-41 + 3 weeks and delivering in the year 2019, were identified. The presence of MA (pH < 7 and/or BE ≤ - 12 mmol/L) was determined based on the acid-base status in the umbilical artery cord blood. Survival analysis was used to assess the hazard function (HF) and the cumulative incidence function (CIF) for MA occurring after terminal fetal bradycardia, at the 2STG. RESULTS: Out of a non-consecutive population of 12,331 pregnancies, there were 52 cases that fit the inclusion criteria. Twenty-four (46.2%) of those develop MA. Abnormal quantitative pH values and the HF for MA correlated with the duration of 2STG at the time of bradycardia onset, but not with bradycardia duration. After 60 min of duration of 2STG, the HF (or instantaneous rate of failure) increased dramatically (from 1.2 to 20 about at 120 min). At paired duration of 2STG, a higher CIF was observed for the terminal bradycardia > 12 min. CONCLUSION: Forty-six percent of term fetuses with terminal bradycardia had MA at birth. Despite the low sensitivity and a non-significant association with quantitative pH values, the duration of terminal bradycardia in the 2STG is associated with a higher CIF for MA.

Increased nuchal translucency can be ascertained using transverse planes.

BACKGROUND: The detection of increased nuchal translucency is crucial for the assessment risk of aneuploidies and other fetal anomalies. OBJECTIVE: This study aimed to investigate the ability of a transverse view of the fetal head to detect increased fetal nuchal translucency at 11 to 13 weeks of gestation. STUDY DESIGN: This was a prospective study enrolling a nonconsecutive series of women who attended our outpatient clinic from January 2020 to April 2021 for combined screening and were examined by operators certified by the Fetal Medicine Foundation. In each patient, nuchal translucency measurements were obtained both from a median sagittal view and from a transverse view. A second sonologist blinded to the results of the first examination obtained another measurement to assess intermethod and interobsever reproducibility. RESULTS: A total of 1023 women were enrolled. An excellent correlation was found between sagittal and transverse nuchal translucency measurements, with a mean difference of 0.01 mm (95% confidence interval, -0.01 to 0.02). No systematic difference was found between the 2 techniques. The inter-rater reliability (intraclass correlation coefficient, 0.957; 95% confidence interval, 0.892-0.983) and intrarater reliability (intraclass correlation coefficient, 0.976; 95% confidence interval, 0.941-0.990) of axial measurements were almost perfect. Transverse measurements of 3.0 mm identified all cases with sagittal measurements of ≥3.0 with a specificity of 99.7%; transverse measurements of >3.2 mm identified all cases with sagittal measurements of 3.5 mm with a specificity of 99.7%. The time required to obtain transverse nuchal translucency measurements was considerably shorter than for sagittal measurements, particularly when the fetus had an unfavorable position. CONCLUSION: When the sonogram is performed by an expert sonologist, the difference in nuchal translucency measurement obtained with a transverse or sagittal plane is minimal. Increased nuchal translucency can be reliably identified by using transverse views, and in some cases, this may technically be advantageous.

Second trimester uterine arteries pulsatility index is a function of placental pathology and provides insights on stillbirth aetiology: A multicenter matched case-control study.

INTRODUCTION: The aim of this study was to investigate the relationships between maternal vascular malperfusions (MVM) and second trimester uterine arteries pulsatility index (UtA-PI) in cases of stillbirth (SB), compared to live-birth (LB) matched controls. METHODS: This was a multicentre, observational, matched case-control study performed at five referral maternity centres over a 4-year period including SB and LB control pregnancies at high-risk for preeclampsia (PE) and/or fetal growth restriction (FGR), matched and stratified for UtA-PI MoM quartiles values of the SB cases. Logistic regression was used to assess the rates of each MVM finding, within each increasing MoM quartile subcategory in SB and matched LB controls. RESULTS: 82 SB and 82 LB matched high-risk pregnancies were included. Placental hypoplasia, placental infarction, retroplacental hematoma, distal villous hypoplasia and accelerated villous maturation showed a significant correlation with UtA-PI. At univariable analysis, placental infarction and distal villous hypoplasia were more highly associated with the increasing quartile uterine Doppler measurements (odds ratio 2.24 and 2.23, respectively). Logistic regressions showed a significant positive and independent association between rates of retroplacental hematoma or distal villous hypoplasia and stillbirth within corresponding UtA-PI MoM quartiles (odds ratio 5.21 and 2.28, respectively). DISCUSSION: We are providing evidence for characterization of two major etiological stillbirth categories, characterized by a positive or absent association with UtA-PI impairment and specific histopathological placental MVM lesions. Our results support a strict third trimester follow-up of cases with increased second trimester UtA-PI, in order to improve the reproductive chances of these pregnant patients.

Abnormal Circulating Maternal miRNA Expression Is Associated with a Low (<4%) Cell-Free DNA Fetal Fraction.

The present pilot study investigates whether an abnormal miRNA profile in NIPT plasma samples can explain the finding of a low cell-free DNA (cfDNA) fetal fraction (cfDNAff) in euploid fetuses and non-obese women. Twelve women who underwent neoBona® NIPT with a normal fetal karyotype were studied. Six with a cfDNAff < 4% were matched with a control group with normal levels of cfDNAff > 4%. Samples were processed using the nanostring nCounter® platform with a panel of 800 miRNAs. Four of the maternal miRNAs, miR-579, miR-612, miR-3144 and miR-6721, had a significant abnormal expression in patients. A data filtering analysis showed that miR-579, miR-612, miR-3144 and miR-6721 targeted 169, 1, 48 and 136 placenta-specific genes, respectively. miR-579, miR-3144 and miR-6721 shared placenta-specific targeted genes involved in trophoblast invasion and migration pathways (IGF2R, PTCD2, SATB2, PLAC8). Moreover, the miRNA target genes encoded proteins localized in the placenta and involved in the pathogenesis of pre-eclampsia, including chorion-specific transcription factor GCMa, PRG2, Lin-28 Homolog B and IGFBP1. In conclusion, aberrant maternal miRNA expression in circulating plasma could be a source of dysregulating trophoblast invasion and migration and could represent a novel cause of a low cfDNAff in the sera of pregnant women at the time of NIPT analysis.

Fetal Biometry: A Method for Comparing Local Curve Populations with Those from Major Reference Standards.

OBJECTIVES: This study aimed to present a statistical method for assessing potential differences between fetal growth standard curves and local curve population. METHODS: This was an observational repeated measures longitudinal study. We used a simulation model to generate random distribution of the international population from the IG-21st for fetal AC using the original equations of means and standard deviations (SD) obtained by the fractional polynomial method. A general linear model (GLM) allowed us to calculate new equations originating from simulated intergrowth-21st data (SIM_IG21st) and to compare them, by visual inspection of the estimated coefficients and their 95% CI, with the original published. We used further GLMs for evaluating the goodness of fitting of our local curve and comparing the relative equations of means and SD with those of SIM_IG21st. Finally, the impact of percentile differences between the 2 curves was quantified. RESULTS: SIM_IG21st data yielded very similar coefficients than those of IG-21st reference to such an extent that means and SD and percentiles of interest were identical to the original. The comparison between SIM_IG21st curve and local curves showed a nonsignificant intercept and a slight difference of the 2 slopes (GA and GA3) for the equations of the mean. As a result, the local curve resulted in greater AC values. A difference in the intercept but not in the slopes (GA2, GA3, and GA3 * lnGA) was instead reported for the equations of the SD. In the percentile comparison, the local curve resulted in an overestimation of the 3rd and the 10th percentile that corresponded to the 4th and 12th percentiles of SIM_IG21st, respectively. CONCLUSION: This statistical method allows sonographers to assess potential differences between standard curves and local curve population, enabling a more proper identification of abnormal growth trajectories.

Prenatal Noninvasive Trio-WES in a Case of Pregnancy-Related Liver Disorder.

Liver disease in pregnancy may present as an acute condition related to the gestational period, characterized by pruritus, jaundice, and abnormal liver function. The disease may be misdiagnosed with other liver diseases, some of which may have consequences for fetal health. It is therefore advisable to implement rapid diagnostic strategies to provide information for the management of pregnancy in these conditions. We report the case of a healthy woman with a twin pregnancy from homologous in vitro fertilization (IVF), who in the third trimester presented jaundice and malaise. Biochemical investigations and liver hyperechogenicity raised the suspicion of acute fatty liver disease of pregnancy (AFLP). Non-invasive prenatal whole-exome sequencing (WES) in the trio identified the Phe305Ile heterozygous variant in the ATP8B1 gene. Considering the twin pregnancy, the percentage of the variant versus the wild allele was of 31%, suggesting heterozygosity present in the mother alone. This analysis showed that the mother was affected by benign recurrent intrahepatic cholestasis of pregnancy (ICP1: # 147480) and indicated the opportunity to anticipate childbirth to avoid worsening of the mother's health. WES after the birth of the twins confirmed the molecular data.

Prenatal Screening for Developmental Displacement of the Hip: The BUDDHA (Pre-Birth Ultrasound for Developmental Displacement of the Hip Assessment) Study.

BACKGROUND: developmental dysplasia of the hip has an incidence of 3-5 out of 1000 children. Currently, only postnatal screening is available. OBJECTIVE: to test the feasibility of a method based on Graf technique application at antenatal ultrasound in assessing the normal development of the hip in unselected term fetuses. METHODS: a prospective cohort study in a single university tertiary hospital from January 2017 to January 2020. Single uncomplicated term pregnancies (37-40 weeks) attending our center for routine ultrasound were consecutively recruited for the purpose of the study. A 3D volume acquisition was launched on the coxofemoral joint of the fetus by a single expert operator, and offline analysis was then performed in the multiplanar mode by two operators (blinded to each other analysis) in order to measure the alpha and beta angles according to our modified Graf technique. Intra- and inter-observer variations were calculated. Reference charts for normal values of both angles were produced. Postnatal ultrasound was then performed to measure the Graf angles in newborns, confirming a normal development of the hip. RESULTS: in the study period, 433 uncomplicated term pregnancies underwent 3D ultrasound for the assessment of the fetal hip. One case was subsequently excluded because of confirmed postnatal diagnosis of developmental dysplasia of the hip. The measurement of our modified Graf angles was feasible at prenatal ultrasound with a good reproducibility. The inter-rater and intra-rater reliability of both angles was substantial. Reference charts for normal values of both angles were produced. CONCLUSIONS: the evaluation of the coxofemoral joint in fetuses at term of gestation has never been attempted before. The Graf technique application, currently employed at postnatal ultrasound, may also be adapted to prenatal ultrasound with a substantial reproducibility. However, there was no evidence of a linear relationship between prenatal and postnatal alpha angles and beta angles. Further research is needed to establish if developmental dysplasia of the hip could be diagnosed antenatally.

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

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.

Brain death in pregnancy: a systematic review focusing on perinatal outcomes.

OBJECTIVE: Brain death (BD) during pregnancy might justify in select cases maternal somatic support to obtain fetal viability and maximize perinatal outcome. This study is a systematic review of the literature on cases of brain death in pregnancy with attempt to prolong pregnancy to assess perinatal outcomes. DATA SOURCES: We performed a systematic review of the literature using Ovid MEDLINE, Scopus, PubMed (including Cochrane database), and CINHAIL from inception to April 2020. STUDY ELIGIBILITY CRITERIA: Relevant articles describing any case report of maternal brain death were identified from the aforementioned databases without any time, language, or study limitations. Studies were deemed eligible for inclusion if they described at least 1 case of maternal brain death. METHODS: Only cases of brain death in pregnancy with maternal somatic support aimed at maximizing perinatal outcome were included. Maternal management strategy, diagnosis, clinical course, fetal monitoring, delivery, and fetal and neonatal outcome data were collected. Mean, range, standard deviation, and percentage calculations were used as applicable. RESULTS: After exclusion, 35 cases of brain death in pregnancy were analyzed. The mean gestational age at diagnosis of brain death was at 20.2±5.3 weeks, and most cases (68%) were associated with maternal intracranial hemorrhage, subarachnoid hemorrhage, and hematoma. The most common maternal complications during the study were infections (69%) (eg, pneumonia, urinary tract infection, sepsis), circulatory instability (63%), diabetes insipidus (56%), thermal variability (41%), and panhypopituitarism (34%). The most common indications for delivery were maternal cardiocirculatory instability (38%) and nonreassuring fetal testing (35%). The mean gestational age at delivery was 27.2±4.7 weeks and differed depending on the gestational age at diagnosis of brain death. Most deliveries (89%) were via cesarean delivery. There were 8 cases (23%) of intrauterine fetal demise in the second trimester of pregnancy (14-25 weeks), and 27 neonates (77%) were born alive. Of the 35 cases of brain in pregnancy, 8 neonates (23%) were described as "healthy" at birth, 15 neonates (43%) had normal longer-term follow-up (>1 month to 8 years; mean, 20.3 months), 2 neonates (6%) had neurologic sequelae (born at 23 and 24 weeks of gestation), and 2 neonates (6%) died (born at 25 and 27 weeks of gestation). Mean birth weight was 1,229 grams, and small for gestational age was present in 17% of neonates. The rate of live birth differed by gestational age at diagnosis of brain death: 50% at <14 weeks, 54.5% at 14 to 19 6/7 weeks, 91.7% at 20 to 23 6/7 weeks, 100% at 24 to 27 6/7 weeks, and 100% at 28 to 31 6/7 weeks. CONCLUSION: In 35 cases of brain death in pregnancy at a mean gestation age of 20 weeks, maternal somatic support aimed at maximizing perinatal outcome lasted for about 7 weeks, with 77% of neonates being born alive and 85% of these infants having a normal outcome at 20 months of life. The data of this study will be helpful in counseling families and practitioners faced with such rare and complex cases.

Quantification of Posterior Risk Related to Intrapartum FIGO 2015 Criteria for Cardiotocography in the Second Stage of Labor.

INTRODUCTION: Intrapartum cardiotocography (CTG) was used for several decades to detect a stressed fetus so that delivery can be expedited to prevent birth asphyxia. The main aim of the study was to calculate the risk of neonatal acidemia (pH ≤ 7.10) according to duration of the 2nd stage of labor and occurrence of the International Federation of Gynecology and Obstetrics (FIGO) 2015 CTG classification parameters. MATERIALS AND METHODS: This was a retrospective case-control study on 552 pregnancies receiving continuous CTG monitoring in labor and immediate hemogasanalysis at birth. Cases with umbilical artery (UA) pH ≤ 7.10 and controls with UA pH ≥ 7.10 were matched for parity and gestational age at delivery, with ratio 1:5. Logistic regression analysis, adjusted for the expected risk in the general population, was used to calculate the baseline risk of UA pH ≤ 7.10 in the absence of any CTG pathological feature and those associated with pathological CTG patterns occurring in the 2nd stage according to FIGO 2015. RESULTS: Seventy-three cases and 387 controls reached 2nd stage and were included in the analysis. For those reaching 2nd stage, the mean adjusted risk of acidemia associated with nonpathological CTG was 1.6%. Stratification of risk according to duration of the 2nd stage yielded risks of neonatal acidemia of 1.23, 2.08, 5.81, and 15.22% at 30, 60, 120, and 180 min, respectively. Bradycardia >10 min was associated with risk of neonatal acidemia of 9.9 and 15.8% for 2nd-stage durations of 30 and 60 min, respectively. Risks associated with 1 prolonged deceleration >5 min were 6.80, 11.08, 27.0, and 51.0% at 30, 60, 120, and 180 min, respectively. Repetitive late or prolonged decelerations >30 min were associated with risk of neonatal acidemia of 2.43, 4.14, 11.17, and 26.45% at 30, 60, 120, and 180 min, respectively. CONCLUSION: The risk of neonatal acidemia is directly proportional to duration of the 2nd stage, irrespective of the presence of CTG abnormalities, increasing 12-fold (1.2-15.3%) from 30 to 180 min. Occurrence of FIGO 2015 pathological CTG patterns showed a decreasing impact from bradycardia >10 min to decelerations >5 min, recurrent later or prolonged decelerations >30 min, and nonpathological CTG.

Obstetric anal sphincter injuries: strategies for prevention, diagnosis, and management.

Obstetric anal sphincter injuries (OASIS) are one of the most common causes of anal incontinence (AI) in women of reproductive age and can have a significant impact on quality of life. However, many women do not report symptoms to their physicians because of embarrassment and shame. Therefore, prevention and diagnosis of the tear is essential. Diagnostic strategies have evolved considerably in recent years, with an increase in prevalence of OASIS as a consequence. The use of 3D endoanal (3D-EAUS) and 4D transperineal ultrasound (4D-TPUS), in addition to standard clinical examination have enhanced the detection of OASIS. Once identified, adequate repair by a skilled practitioner and optimal postpartum management should be ensured in order to reduce the risk of anal incontinence. This review presents the available evidence on strategies for prevention, diagnosis, and management of OASIS.