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A primary goal of obstetrical practice is the optimization of maternal and perinatal health. This goal translates into a seemingly simple assessment with regard to considerations of the timing of delivery: delivery should occur when the benefits are greater than those of continued pregnancy. In the absence of an indication for cesarean delivery, planned delivery is initiated with induction of labor. When medical or obstetrical complications exist, they may guide recommendations regarding the timing of delivery. In the absence of these complications, gestational age also has been used to guide delivery timing, given its association with both maternal and perinatal adverse outcomes. If there is no medical indication, delivery before 39 weeks has been discouraged, given its association with greater chances of adverse perinatal outcomes. Conversely, it has been recommended that delivery occur by 42 weeks of gestation, given the perinatal risks that accrue in the post-term period. Historically, a 39-week induction of labor, particularly for individuals with no previous birth, has not been routinely offered in the absence of medical or obstetrical indications. That approach was based on numerous observational studies that demonstrated an increased risk of cesarean delivery and other adverse outcomes among individuals who underwent labor induction compared to those in spontaneous labor. However, from a management and person-centered-choice perspective, the relevant comparison is between those undergoing planned labor induction at a given time vs those planning to continue pregnancy beyond that time. When individuals have been compared using that rubric—either in observational studies or randomized trials that have been performed in a wide variety of locations and populations— there has not been evidence that induction increases adverse perinatal or maternal outcomes. Conversely, even when the only indication for delivery is the achievement of a full-term gestational age, evidence suggests that multiple different outcomes, including cesarean delivery, hypertensive disorders of pregnancy, neonatal respiratory impairment, and perinatal mortality, are less likely when induction is performed. This information underscores the importance of making the preferences of pregnant individuals for different birth processes and outcomes central to the approach to delivery timing. [ABSTRACT FROM AUTHOR]

This study aimed to estimate the perinatal mortality associated with prenatally diagnosed vasa previa and to determine what proportion of those perinatal deaths are directly attributable to vasa previa. The following databases have been searched from January 1, 1987, to January 1, 2023: PubMed, Scopus, Web of Science, and Embase. Our study included all studies (cohort studies and case series or reports) that had patients in which a prenatal diagnosis of vasa previa was made. Case series or reports were excluded from the meta-analysis. All cases in which prenatal diagnosis was not made were excluded from the study. The programming language software R (version 4.2.2) was used to conduct the meta-analysis. The data were logit transformed and pooled using the fixed effects model. The between-study heterogeneity was reported by I 2 . The publication bias was evaluated using a funnel plot and the Peters regression test. The Newcastle-Ottawa scale was used to assess the risk of bias. Overall, 113 studies with a cumulative sample size of 1297 pregnant individuals were included. This study included 25 cohort studies with 1167 pregnancies and 88 case series or reports with 130 pregnancies. Moreover, 13 perinatal deaths occurred among these pregnancies, consisting of 2 stillbirths and 11 neonatal deaths. Among the cohort studies, the overall perinatal mortality was 0.94% (95% confidence interval, 0.52–1.70; I 2 =0.0%). The pooled perinatal mortality attributed to vasa previa was 0.51% (95% confidence interval, 0.23–1.14; I 2 =0.0%). Stillbirth and neonatal death were reported in 0.20% (95% confidence interval, 0.05–0.80; I 2 =0.0%) and 0.77% (95% confidence interval, 0.40–1.48; I 2 =0.0%) of pregnancies, respectively. Perinatal death is uncommon after a prenatal diagnosis of vasa previa. Approximately half of the cases of perinatal mortality are not directly attributable to vasa previa. This information will help in guiding physicians in counseling and will provide reassurance to pregnant individuals with a prenatal diagnosis of vasa previa. [ABSTRACT FROM AUTHOR]

Objective: This systematic review and meta-analysis investigated whether the use of low-dose aspirin during pregnancy by women with chronic hypertension reduces the odds of superimposed preeclampsia and poor perinatal outcomes.Data Sources: In September 2021, the following sources were searched: Embase, MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and EU Clinical Trials Register. Only human studies were included, with no time or language restrictions.Study Eligibility Criteria: Cohort, case-control, and randomized controlled studies reporting women with chronic hypertension pregnant with a singleton were included. Eligible studies compared low-dose aspirin use during pregnancy with a control arm.Methods: Risk of bias was assessed using the RoB 2 and ROBINS-I tools. A meta-analysis was performed using a random-effects model, estimating odds ratios and 95% confidence and prediction intervals, and the quality of data was assessed with the GRADE approach. Heterogeneity was investigated in regard to study methodology, timing of commencement of aspirin, and the outcome of preterm preeclampsia.Results: Nine studies (3 retrospective cohort studies and 6 randomized trials) including 2150 women with chronic hypertension were included. Low-dose aspirin prophylaxis did not significantly reduce the odds of superimposed preeclampsia in the randomized controlled trials (odds ratio, 0.83; 95% confidence interval, 0.55-1.25; prediction interval, 0.27-2.56; low-quality evidence) or observational studies (odds ratio, 1.21; 95% confidence interval, 0.78-1.87; prediction interval, 0.07-20.80; very low-quality evidence). Low-dose aspirin also did not reduce the odds of preterm preeclampsia (odds ratio, 1.17; 95% confidence interval, 0.74-1.86), and early aspirin initiation had no significant impact. There was no significant effect on small-for-gestational-age neonates or perinatal mortality; however, there was a significant reduction in preterm birth (odds ratio, 0.63; 95% confidence interval, 0.45-0.89; moderate-quality evidence). The quality of the evidence is limited by heterogeneity and risk of bias.Conclusion: This meta-analysis was unable to demonstrate a significant change in the odds of superimposed preeclampsia, small-for-gestational-age infants, or perinatal mortality with the use of low-dose aspirin in women with chronic hypertension. However, significant reduction in preterm birth justifies the continued use of aspirin prophylaxis. This work was prospectively registered on the International Prospective Register of Systematic Reviews (registration number CRD42021285921). [ABSTRACT FROM AUTHOR]

This study aimed to systematically assess perinatal outcomes of pregnancies complicated by maternal cardiomyopathy. PubMed, Ovid Embase, Ovid MEDLINE, the Cochrane Library, and ClinicalTrials.gov were systematically searched from inception to August 25, 2022. Observational cohort, case-control, and case-cohort studies in human populations were included if they reported predefined perinatal outcomes in pregnant women with cardiomyopathy (any subtype) and an appropriate control population (either pregnant women with no known cardiac disease or pregnant women with noncardiomyopathy cardiac disease). Of note, 2 reviewers independently assessed the articles for eligibility and risk of bias, and conflicts were resolved by a third reviewer. Data were extracted and synthesized according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology guidelines. Here, 13 studies (representing 2,291,024 pregnancies) were eligible for inclusion. Perinatal death was more likely in neonates born to women with cardiomyopathy than in (1) neonates born to women with no cardiac disease (stillbirth: odds ratio, 20.82; 95% confidence interval, 6.68–64.95; I 2 = not available; P <.00001; neonatal mortality: odds ratio, 6.75; 95% confidence interval, 3.54–12.89; I 2 =0%; P <.00001) and (2) neonates born to women with other forms of cardiac disease (stillbirth: odds ratio, 3.75; 95% confidence interval, 1.86–7.59; I 2 =0%; P =.0002; neonatal mortality: odds ratio, 2.42; 95% confidence interval, 1.39–4.21; I 2 =0%; P =.002). Pregnancies affected by maternal cardiomyopathy were significantly more likely to result in preterm birth (odds ratio, 2.21; 95% confidence interval, 1.31–3.73; I 2 =77%; P =.003) and small-for-gestational-age neonates (odds ratio, 2.97; 95% confidence interval, 2.38–3.70; I 2 =47%; P <.00001), both major causes of short- and long-term morbidities, than pregnancies affected by other forms of cardiac disease. There was an increased likelihood of adverse perinatal outcomes in pregnancies affected by maternal cardiomyopathy compared with both pregnancies affected by noncardiomyopathy cardiac disease and pregnancies without cardiac disease. Women with cardiomyopathy who plan to get pregnant should receive detailed counseling regarding these risks and have their pregnancies managed by experienced multidisciplinary teams that can provide close fetal monitoring and neonatology expertise. [ABSTRACT FROM AUTHOR]

Stillbirth is a recognized complication of COVID-19 in pregnant women that has recently been demonstrated to be caused by SARS-CoV-2 infection of the placenta. Multiple global studies have found that the placental pathology present in cases of stillbirth consists of a combination of concurrent destructive findings that include increased fibrin deposition that typically reaches the level of massive perivillous fibrin deposition, chronic histiocytic intervillositis, and trophoblast necrosis. These 3 pathologic lesions, collectively termed SARS-CoV-2 placentitis, can cause severe and diffuse placental parenchymal destruction that can affect >75% of the placenta, effectively rendering it incapable of performing its function of oxygenating the fetus and leading to stillbirth and neonatal death via malperfusion and placental insufficiency. Placental infection and destruction can occur in the absence of demonstrable fetal infection. Development of SARS-CoV-2 placentitis is a complex process that may have both an infectious and immunologic basis. An important observation is that in all reported cases of SARS-CoV-2 placentitis causing stillbirth and neonatal death, the mothers were unvaccinated. SARS-CoV-2 placentitis is likely the result of an episode of SARS-CoV-2 viremia at some time during the pregnancy. This article discusses clinical and pathologic aspects of the relationship between maternal COVID-19 vaccination, SARS-CoV-2 placentitis, and perinatal death. [ABSTRACT FROM AUTHOR]

No fetal growth standard is currently endorsed for universal use in the United States. Newer standards improve upon the methodologic limitations of older studies; however, before adopting into practice, it is important to know how recent standards perform at identifying fetal undergrowth or overgrowth and at predicting subsequent neonatal morbidity or mortality in US populations. To compare classification of estimated fetal weight that is <5th or 10th percentile or >90th percentile by 6 population-based fetal growth standards and the ability of these standards to predict a composite of neonatal morbidity and mortality. We used data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be cohort, which recruited nulliparous women in the first trimester at 8 US clinical centers (2010–2014). Estimated fetal weight was obtained from ultrasounds at 16 to 21 and 22 to 29 weeks of gestation (N=9534 women). We calculated rates of fetal growth restriction (estimated fetal weight <5th and 10th percentiles; fetal growth restriction<5 and fetal growth restriction<10) and estimated fetal weight >90th percentile (estimated fetal weight>90) from 3 large prospective fetal growth cohorts with similar rigorous methodologies: INTERGROWTH-21, World Health Organization-sex-specific and combined, Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific and unified, and the historic Hadlock reference. To determine whether differential classification of fetal growth restriction or estimated fetal weight >90 among standards was clinically meaningful, we then compared area under the curve and sensitivity of each standard to predict small for gestational age or large for gestational age at birth, composite perinatal morbidity and mortality alone, and small for gestational age or large for gestational age with composite perinatal morbidity and mortality. The standards classified different proportions of fetal growth restriction and estimated fetal weight>90 for ultrasounds at 16 to 21 (visit 2) and 22 to 29 (visit 3) weeks of gestation. At visit 2, the Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific, World Health Organization sex-specific and World Health Organization-combined identified similar rates of fetal growth restriction<10 (8.4%–8.5%) with the other 2 having lower rates, whereas Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific identified the highest rate of fetal growth restriction<5 (5.0%) compared with the other references. At visit 3, World Health Organization sex-specific classified 9.2% of fetuses as fetal growth restriction<10, whereas the other 5 classified a lower proportion as follows: World Health Organization-combined (8.4%), Eunice Kennedy Shriver National Institute of Child Health and Human Development race-ethnic-specific (7.7%), INTERGROWTH (6.2%), Hadlock (6.1%), and Eunice Kennedy Shriver National Institute of Child Health and Human Development unified (5.1%). INTERGROWTH classified the highest (21.3%) as estimated fetal weight>90 whereas Hadlock classified the lowest (8.3%). When predicting composite perinatal morbidity and mortality in the setting of early-onset fetal growth restriction, World Health Organization had the highest area under the curve of 0.53 (95% confidence interval, 0.51–0.53) for fetal growth restriction<10 at 22 to 29 weeks of gestation, but the areas under the curve were similar among standards (0.52). Sensitivity was generally low across standards (22.7%–29.1%). When predicting small for gestational age birthweight with composite neonatal morbidity or mortality, for fetal growth restriction<10 at 22 to 29 weeks of gestation, World Health Organization sex-specific had the highest area under the curve (0.64; 95% confidence interval, 0.60–0.67) and INTERGROWTH had the lowest (area under the curve=0.58; 95% confidence interval 0.55–0.62), though all standards had low sensitivity (7.0%–9.6%). Despite classifying different proportions of fetuses as fetal growth restriction or estimated fetal weight>90, all standards performed similarly in predicting perinatal morbidity and mortality. Classification of different percentages of fetuses as fetal growth restriction or estimated fetal weight>90 among references may have clinical implications in the management of pregnancies, such as increased antenatal monitoring for fetal growth restriction or cesarean delivery for suspected large for gestational age. Our findings highlight the importance of knowing how standards perform in local populations, but more research is needed to determine if any standard performs better at identifying the risk of morbidity or mortality. [ABSTRACT FROM AUTHOR]

One of the hallmarks of twin pregnancies is the slower rate of fetal growth when compared with singleton pregnancies during the third trimester. The mechanisms underlying this phenomenon and whether it represents pathology or benign physiological adaptation are currently unclear. One important implication of these questions relates to the type growth charts that should be used by care providers to monitor growth of twin fetuses. If the slower growth represents pathology (ie, intrauterine growth restriction caused uteroplacental insufficiency), it would be preferable to use a singleton growth chart to identify a small twin fetus that is at risk for perinatal mortality and morbidity. If, however, the relative smallness of twins is the result of benign adaptive mechanisms, it is likely preferable to use a twin-based charts to avoid overdiagnosis of intrauterine growth restriction in twin pregnancies. In the current review, we addressed this question by describing the differences in fetal growth between twin and singleton pregnancies, reviewing the current knowledge regarding the mechanisms responsible for slower fetal growth in twins, summarizing available empirical evidence on the diagnostic accuracy of the 2 types of charts for intrauterine growth restriction in twin pregnancies, and addressing the question of whether uncomplicated dichorionic twins are at an increased risk for fetal death when compared with singleton fetuses. We identified a growing body of evidence that shows that the use of twin charts can reduce the proportion of twin fetuses identified with suspected intrauterine growth restriction by up to 8-fold and can lead to a diagnosis of intrauterine growth restriction that is more strongly associated with adverse perinatal outcomes and hypertensive disorders than a diagnosis of intrauterine growth restriction based on a singleton-based chart without compromising the detection of twin fetuses at risk for adverse outcomes caused by uteroplacental insufficiency. We further found that small for gestational age twins are less likely to experience adverse perinatal outcomes or to have evidence of uteroplacental insufficiency than small for gestational age singletons and that recent data question the longstanding view that uncomplicated dichorionic twins are at an increased risk for fetal death caused by placental insufficiency. Overall, it seems that, based on existing evidence, the of use twin charts is reasonable and may be preferred over the use of singleton charts when monitoring the growth of twin fetuses. Still, it is important to note that the available data have considerable limitations and are primarily derived from observational studies. Therefore, adequately-powered trials are likely needed to confirm the benefit of twin charts before their use is adopted by professional societies. [ABSTRACT FROM AUTHOR]

Preterm birth is a leading cause of perinatal morbidity and mortality. Antenatal corticosteroid administration before preterm birth reduces the risks of perinatal death, respiratory morbidity, necrotizing enterocolitis, and intraventricular hemorrhage and reduces the costs of perinatal care. Antenatal corticosteroids are optimally effective when administered within 7 days before preterm birth. However, only 20% to 40% of early preterm infants receive antenatal corticosteroids within 7 days before birth, in part because it is difficult to predict the precise timing of preterm birth. Until 2020, The Joint Commission had a Perinatal Care quality metric measuring the rate of antenatal corticosteroid administration at any time before early preterm birth. This metric incentivized providers to use antenatal corticosteroids liberally. The Joint Commission retired the metric in 2020 after the rate reached more than 97% in The Joint Commission-accredited hospitals. However, the metric did not evaluate whether the timing of antenatal corticosteroid administration was optimal, that is, within 7 days of birth. A 2016 multistakeholder Cooperative Workshop recommended the development of a new quality metric to assess the rate of optimally timed antenatal corticosteroids among early preterm births. In this statement, we outline proposed specifications for such a metric and discuss potential uses, advantages, limitations, and barriers. Furthermore, we propose a balancing metric that tracks the percentage of patients treated with antenatal corticosteroids who ultimately give birth at term. We suggest that the use of these new metrics may incentivize more conservative antenatal corticosteroid timing, which could, in turn, lead to meaningfully improved outcomes for preterm neonates. [ABSTRACT FROM AUTHOR]

In randomized trials, 1 primary outcome is typically chosen to evaluate the consequences of an intervention, whereas other important outcomes are relegated to secondary outcomes. This issue is amplified for many obstetrical trials in which an intervention may have consequences for both the pregnant person and the child. In contrast, desirability of outcome ranking, a paradigm shift for the design and analysis of clinical trials based on patient-centric evaluation, allows multiple outcomes—including from >1 individual—to be considered concurrently. This study aimed to describe desirability of outcome ranking methodology tailored to obstetrical trials and to apply the methodology to maternal–perinatal paired (dyadic) outcomes in which both individuals may be affected by an intervention but may experience discordant outcomes (eg, an obstetrical intervention may improve perinatal but worsen maternal outcomes). This secondary analysis applies the desirability of outcome ranking methodology to data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network ARRIVE trial. The original analysis found no substantial difference in the primary (perinatal composite) outcome, but a decreased risk of the secondary outcome of cesarean delivery with elective induction at 39 weeks. In the present desirability-of-outcome-ranking analysis, dyadic outcomes ranging from spontaneous vaginal delivery without severe neonatal complication (most desirable) to cesarean delivery with perinatal death (least desirable) were classified into 8 categories ranked by overall desirability by experienced investigators. Distributions of the desirability of outcome ranking were compared by estimating the probability of having a more desirable dyadic outcome with elective induction at 39 weeks of gestation than with expectant management. To account for various perspectives on these outcomes, a complementary analysis, called the partial credit strategy, was used to grade outcomes on a 100-point scale and estimate the difference in overall treatment scores between groups using a t test. All 6096 participants from the trial were included. The probability of a better dyadic outcome for a randomly selected patient who was randomized to elective induction was 53% (95% confidence interval, 51–54), implying that elective induction led to a better overall outcome for the dyad when taking multiple outcomes into account concurrently. Furthermore, the desirability-of-outcome-ranking probability of averting cesarean delivery with elective induction was 52% (95% confidence interval, 51–53), which was not at the expense of an operative vaginal delivery or a poorer outcome for the perinate (ie, survival with a severe neonatal complication or perinatal death). Randomization to elective induction was also advantageous in most of the partial credit score scenarios. Desirability-of-outcome-ranking methodology is a useful tool for obstetrical trials because it provides a concurrent view of the effect of an intervention on multiple dyadic outcomes, potentially allowing for better translation of data for decision-making and person-centered care. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Fetal death because of miscarriage, unexpected intrauterine fetal demise, or termination of pregnancy is a traumatic event for any family. Despite advances in prenatal imaging and genetic diagnosis, conventional autopsy remains the gold standard because it can provide additional information not available during fetal life in up to 40% of cases and this by itself may change the recurrence risk and hence future counseling for parents. However, conventional autopsy is negatively affected by procedures involving long reporting times because the fetal brain is prone to the effect of autolysis, which may result in suboptimal examinations, particularly of the central nervous system. More importantly, fewer than 50%-60% of parents consent to invasive autopsy, mainly owing to the concerns about body disfigurement. Consequently, this has led to the development of noninvasive perinatal virtual autopsy using imaging techniques. Because a significant component of conventional autopsy involves the anatomic examination of organs, imaging techniques such as magnetic resonance imaging, ultrasound, and computed tomography are possible alternatives. With a parental acceptance rate of nearly 100%, imaging techniques as part of postmortem examination have become widely used in recent years in some countries. Postmortem magnetic resonance imaging using 1.5-Tesla magnets is the most studied technique and offers an overall diagnostic accuracy of 77%-94%. It is probably the best choice as a virtual autopsy technique for fetuses >20 weeks' gestation. However, for fetuses <20 weeks' gestation, its performance is poor. The use of higher magnetic resonance imaging magnetic fields such as 3-Tesla may slightly improve performance. Of note, in cases of fetal maceration, magnetic resonance imaging may offer diagnoses in a proportion of brain lesions wherein conventional autopsy fails. Postmortem ultrasound examination using a high-frequency probe offers overall sensitivity and specificity of 67%-77% and 74%-90%, respectively, with the advantage of easy access and affordability. The main difference between postmortem ultrasound and magnetic resonance imaging relates to their respective abilities to obtain images of sufficient quality for a confident diagnosis. The nondiagnostic rate using postmortem ultrasound ranges from 17% to 30%, depending on the organ examined, whereas the nondiagnostic rate using postmortem magnetic resonance imaging in most situations is far less than 10%. For fetuses ≤20 weeks' gestation, microfocus computed tomography achieves close to 100% agreement with autopsy and is likely to be the technique of the future in this subgroup. The lack of histology has always been listed as 1 limitation of all postmortem imaging techniques. Image-guided needle tissue biopsy coupled with any postmortem imaging can overcome this limitation. In addition to describing the diagnostic accuracy and limitations of each imaging technology, we propose a novel, stepwise diagnostic approach and describe the possible application of these techniques in clinical practice as an alternative or an adjunct or for triage to select cases that would specifically benefit from invasive examination, with the aim of reducing parental distress and pathologist workload. The widespread use of postmortem fetal imaging is inevitable, meaning that hurdles such as specialized training and dedicated financing must be overcome to improve access to these newer, well-validated techniques. [ABSTRACT FROM AUTHOR]

Objective Data: Chronic hypertension is associated with adverse perinatal outcomes, although the optimal treatment is unclear. The aim of this network metaanalysis was to simultaneously compare the efficacy and safety of antihypertensive agents in pregnant women with chronic hypertension.Study: Medline, Scopus, CENTRAL, Web of Science, Clinicaltrials.gov, and Google Scholar databases were searched systematically from inception to December 15, 2019. Both randomized controlled trials and cohort studies were held eligible if they reported the effects of antihypertensive agents on perinatal outcomes among women with chronic hypertension.Study Appraisal and Synthesis Methods: The primary outcomes were preeclampsia and small-for-gestational-age risk. A frequentist network metaanalytic random-effects model was fitted. The main analysis was based on randomized controlled trials. The credibility of evidence was assessed by taking into account within-study bias, across-studies bias, indirectness, imprecision, heterogeneity, and incoherence.Results: Twenty-two studies (14 randomized controlled trials and 8 cohorts) were included, comprising 4464 women. Pooling of randomized controlled trials indicated that no agent significantly affected the incidence of preeclampsia. Atenolol was associated with significantly higher risk of small-for-gestational age compared with placebo (odds ratio, 26.00; 95% confidence interval, 2.61-259.29) and is ranked as the worst treatment (P-score=.98). The incidence of severe hypertension was significantly lower when nifedipine (odds ratio, 0.27; 95% confidence interval, 0.14-0.55), methyldopa (odds ratio, 0.31; 95% confidence interval, 0.17-0.56), ketanserin (odds ratio, 0.29; 95% confidence interval, 0.09-0.90), and pindolol (odds ratio, 0.17; 95% confidence interval, 0.05-0.55) were administered compared with no drug intake. The highest probability scores were calculated for furosemide (P-score=.86), amlodipine (P-score=.82), and placebo (P-score=.82). The use of nifedipine and methyldopa were associated with significantly lower placental abruption rates (odds ratio, 0.29 [95% confidence interval, 0.15-0.58] and 0.23 [95% confidence interval, 0.11-0.46], respectively). No significant differences were estimated for cesarean delivery, perinatal death, preterm birth, and gestational age at delivery.Conclusion: Atenolol was associated with a significantly increased risk for small-for-gestational-age infants. The incidence of severe hypertension was significantly lower when nifedipine and methyldopa were administered, although preeclampsia risk was similar among antihypertensive agents. Future large-scale trials should provide guidance about the choice of antihypertensive treatment and the goal blood pressure during pregnancy. [ABSTRACT FROM AUTHOR]

Chronic hypertension and associated cardiovascular disease are among the leading causes of maternal and perinatal morbidity and death in the United States. Chronic hypertension in pregnancy is associated with a host of adverse outcomes that include preeclampsia, cesarean delivery, cerebrovascular accidents, fetal growth restriction, preterm birth, and maternal and perinatal death. There are several key issues related to the diagnosis and management of chronic hypertension in pregnancy where data are limited and further research is needed. These challenges and recent guidelines for the management of chronic hypertension are reviewed. Well-timed pregnancies are of utmost importance to reduce the risks of chronic hypertension; long-acting reversible contraceptive options are preferred. Research to determine optimal blood pressure thresholds for diagnosis and treatment to optimize short- and long-term maternal and perinatal outcomes should be prioritized along with interventions to reduce extant racial and ethnic disparities. [ABSTRACT FROM AUTHOR]

Vasa previa is an obstetrical condition in which fetal vessels located near the cervix traverse the fetal membranes unprotected by underlying placenta. Type I vasa previa arises directly from a velamentous cord root, whereas types II and III arise from an accessory lobe or a distal lobe of the same placenta, respectively. Fetoscopic laser ablation for types II and III vasa previa is a novel therapeutic option with benefits that include surgical resolution of the vasa previa, avoidance of prolonged hospitalization, and opportunity for a term vaginal delivery. The potential risks of fetoscopy can be mitigated by delaying laser surgery until a gestational age of 31 to 33 weeks, immediately before anticipated hospitalized surveillance. This study aimed to assess feasibility and outcomes of types II and III vasa previa patients treated via fetoscopic laser ablation in the third trimester. This is a retrospective study of singleton pregnancies with types II and III vasa previa treated with fetoscopic laser ablation at a gestational age ≥31 weeks at a single center between 2006 and 2022. Pregnancy and newborn outcomes were assessed. Continuous variables are expressed as mean±standard deviation. Of 84 patients referred for vasa previa, 57 did not undergo laser ablation: 19 either had no or resolved vasa previa, 25 had type I vasa previa (laser-contraindicated), and 13 had type II or III vasa previa but declined laser treatment. Of the remaining 27 patients who underwent laser ablation, 7 were excluded (laser performed at <31 weeks and/or twins), leaving 20 study patients. The mean gestational age at fetoscopic laser ablation was 32.0±0.6 weeks, and total operative time was 62.1±19.6 minutes. There were no perioperative complications. All patients had successful occlusion of the vasa previa vessels (1 required a second procedure). All patients were subsequently managed as outpatients. The mean gestational age at delivery was 37.2±1.8 weeks, the mean birthweight was 2795±465 g, and 70% delivered vaginally. Neonatal intensive care unit admission occurred in 3 cases: 1 for respiratory distress syndrome and 2 for hyperbilirubinemia requiring phototherapy. There were no cases of neonatal transfusion, intraventricular hemorrhage, sepsis, patent ductus arteriosus, or death. Laser ablation for types II and III vasa previa at 31 to 33 gestational weeks was technically achievable and resulted in favorable outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

Sustained fetal tachyarrhythmia can evolve into a life-threatening condition in 40% of cases when hydrops develops, with a 27% risk of perinatal death. Several antiarrhythmic drugs can be given solely or in combination to the mother to achieve therapeutic transplacental concentrations. Therapeutic failure could lead to progressive cardiac insufficiency and restrict therapeutic options to either elective delivery or direct fetal administration of antiarrhythmic drugs, which may increase the risk of death. We report for the first time successful fetal transesophageal pacing to treat a hydropic fetus with drug-resistant tachyarrhythmia. [ABSTRACT FROM AUTHOR]

Mothers who are obese carry heavier fetuses and have lower rates of small for gestational age (<10th birthweight centile) infants. However, their infants may be growth-restricted (with an increased risk of stillbirth) at a higher birthweight centile compared with infants from healthy-weight women. This study aimed to quantify the birthweight centile at which the risk of stillbirth in infants born to obese women equaled that of <10th-centile infants born to healthy-weight women, and clarify the relationship between maternal body mass index, infant size, and stillbirth. We conducted a retrospective cohort study on all infants born in Victoria, Australia, from 2009 to 2019 (754,946 cases for analysis). We applied uncustomized birthweight centiles to all infants, and stratified the maternal cohort by body mass index (<20 kg/m2, 20–25 kg/m2, 25–30 kg/m2, 30–35 kg/m2, 35–40 kg/m2, ≥40 kg/m2). For each body mass index category, we assessed proportions of infants born <10th centile and <3rd centile, stillbirth rates among infants of all sizes, and small for gestational age infants. We calculated the stillbirth rate (per 1000) and relative risk (risk of stillbirth if born <10th centile vs >10th centile) for healthy-weight women (body mass index, 20–25 kg/m2). We then determined the birthweight centile for infants born to mothers within other body mass index categories that equaled that rate or risk. Stillbirth rates increased with increasing maternal body mass index. Infants classified as small for gestational age (<10th centile) from mothers with high body mass index had a higher risk of stillbirth (relative risk, 3.15; 95% confidence interval, 2.22–4.47; for mothers with body mass index ≥40 kg/m2 vs healthy-weight mothers [body mass index, 20–25 kg/m2]). The stillbirth rate (stillborn infants per 1000 births) among <10th-centile infants born to healthy-weight mothers was 7.5 per 1000. The same stillbirth rate was observed at higher birthweight centiles for infants of women with higher body mass index (<18th centile for those with a body mass index of 25–30 kg/m2, <25th centile for body mass index of 30–35 kg/m2, <31st centile for body mass index of 35–40 kg/m2, <41st centile for body mass index of ≥40 kg/m2). The relative risk of stillbirth among small for gestational age infants of healthy-weight mothers was 5.46 (95% confidence interval, 4.65–6.40). The birthweight centile with a comparable relative risk of stillbirth increased with increasing body mass index (<16th centile for women with body mass index of 25–30 kg/m2, <19th centile for body mass index of 30–35 kg/m2, <28th centile for body mass index of 35–40 kg/m2, <30th centile for body mass index ≥40 kg/m2). Obesity affects the relationship between infant size and perinatal mortality. The stillbirth risk observed in <10th-centile infants from healthy-weight mothers occurs at higher birthweight centiles with overweight or obese mothers. Clinicians should be aware that the same infant risk exists at a higher birthweight centile for women with higher body mass index. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) is associated with an increased risk of perinatal morbidity and mortality and has lifetime implications for the risk of chronic medical conditions. Antenatal diagnosis of FGR remains poor, with the majority of cases remaining undiagnosed. Although several factors contribute to the underdiagnosis of FGR, the error in ultrasound estimation of fetal weight (EFW) generally is not considered in clinical practice. In this commentary, we suggest that the intrinsic, or systematic, error in ultrasound EFW is a significant factor contributing to the underestimation of fetuses predicted to have FGR and should be incorporated into screening and surveillance recommendations. To illustrate this point, we present an analytic model of published data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies characterizing and quantifying the impact of the systematic error in ultrasound EFW on the underdiagnosis of FGR. Independent of the centile at which the risk of adverse outcome related to FGR begins, whether the 10th, 5th or 3rd percentile, our analysis suggests the need to modify to the current paradigm for identifying and responding to fetuses estimated to be at risk. [ABSTRACT FROM AUTHOR]

Perinatal depression is associated with a high risk of morbidity and mortality and may have long-term consequences on child development. The US Preventive Services Task Force has recently recognized the importance of identifying and treating women with depression in the perinatal period. However, screening and accessing appropriate treatment come with logistical challenges. In many areas, there may not be sufficient access to psychiatric care, and, until these resources develop, the burden may inadvertently fall on obstetricians. As a result, understanding the risks of perinatal depression in comparison with the risks of treatment is important. Many studies of selective serotonin reuptake inhibitors in pregnancy fail to control for underlying depressive illness, which can lead to misinterpretation of selective serotonin reuptake inhibitor risk by clinicians. This review discusses the risks and benefits of selective serotonin reuptake inhibitor treatment in pregnancy within the context of perinatal depression. Whereas selective serotonin reuptake inhibitors may be associated with certain risks, the absolute risks are low and may be outweighed by the risks of untreated depression for many women and their offspring. [ABSTRACT FROM AUTHOR]

A Randomized Trial of Induction Versus Expectant Management (ARRIVE) was conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network from March 2014 to August 2017.This large multicenter, unmasked, randomized controlled trial was performed to test the hypothesis that elective IOL at 39 weeks of gestation, compared with expectant management among low-risk nulliparous women, reduces the risk of a composite outcome of perinatal death or severe neonatal morbidity. Nulliparous women with reliable dating and no obstetric or medical complications were eligible, regardless of favorability of cervical examination. The purpose of this document is to review the findings of the recent randomized trial and to provide guidance for implementation of the study findings. [ABSTRACT FROM AUTHOR]

Background: Preterm birth is the major cause of perinatal mortality in the United States. In the past, pregnant women have been recommended to not exercise because of presumed risks of preterm birth. Physical activity has been theoretically related to preterm birth because it increases the release of catecholamines, especially norepinephrine, which might stimulate myometrial activity. Conversely, exercise may reduce the risk of preterm birth by other mechanisms such as decreased oxidative stress or improved placenta vascularization. Therefore, the safety of exercise regarding preterm birth and its effects on gestational age at delivery remain controversial.Objective: The objective of the study was to evaluate the effects of exercise during pregnancy on the risk of preterm birth.Data Sources: MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID, and Cochrane Library were searched from the inception of each database to April 2016.Study Design: Selection criteria included only randomized clinical trials of pregnant women randomized before 23 weeks to an aerobic exercise regimen or not. Types of participants included women of normal weight with uncomplicated, singleton pregnancies without any obstetric contraindication to physical activity. The summary measures were reported as relative risk or as mean difference with 95% confidence intervals. The primary outcome was the incidence of preterm birth <37 weeks.Tabulation, Integration, and Results: Of the 2059 women included in the meta-analysis, 1022 (49.6%) were randomized to the exercise group and 1037 (50.4%) to the control group. Aerobic exercise lasted about 35-90 minutes 3-4 times per week. Women who were randomized to aerobic exercise had a similar incidence of preterm birth of <37 weeks (4.5% vs 4.4%; relative risk, 1.01, 95% confidence interval, 0.68-1.50) and a similar mean gestational age at delivery (mean difference, 0.05 week, 95% confidence interval, -0.07 to 0.17) compared with controls. Women in the exercise group had a significantly higher incidence of vaginal delivery (73.6% vs 67.5%; relative risk, 1.09, 95% confidence interval, 1.04-1.15) and a significantly lower incidence of cesarean delivery (17.9% vs 22%; relative risk, 0.82, 95% confidence interval, 0.69-0.97) compared with controls. The incidence of operative vaginal delivery (12.9% vs 16.5%; relative risk, 0.78, 95% confidence interval, 0.61-1.01) was similar in both groups. Women in the exercise group had a significantly lower incidence of gestational diabetes mellitus (2.9% vs 5.6%; relative risk, 0.51, 95% confidence interval, 0.31-0.82) and a significantly lower incidence of hypertensive disorders (1.0% vs 5.6%; relative risk, 0.21, 95% confidence interval, 0.09-0.45) compared with controls. No differences in low birthweight (5.2% vs 4.7%; relative risk, 1.11, 95% confidence interval, 0.72-1.73) and mean birthweight (mean difference, -10.46 g, 95% confidence interval, -47.10 to 26.21) between the exercise group and controls were found.Conclusion: Aerobic exercise for 35-90 minutes 3-4 times per week during pregnancy can be safely performed by normal-weight women with singleton, uncomplicated gestations because this is not associated with an increased risk of preterm birth or with a reduction in mean gestational age at delivery. Exercise was associated with a significantly higher incidence of vaginal delivery and a significantly lower incidence of cesarean delivery, with a significantly lower incidence of gestational diabetes mellitus and hypertensive disorders and therefore should be encouraged. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia (PE) affects 2-3% of all pregnancies and is a major cause of maternal and perinatal morbidity and mortality. We have proposed a 2-stage strategy for the identification of pregnancies at high risk of developing PE. The objective of the first stage, at 11-13 weeks' gestation, is a reduction in the prevalence of the disease through pharmacological intervention in the high-risk group. The objective of the second stage, during the second and/or third trimesters, is to improve perinatal outcome through close monitoring of the high-risk group for earlier diagnosis of the clinical signs of the disease and selection of the appropriate, time, place, and method of delivery.Objective: The objective of the study was to examine the performance of screening for PE by a combination of maternal factors with early third-trimester biomarkers.Study Design: This was a cohort study and data were derived from consecutive women with singleton pregnancies attending for their routine hospital visit at 30-34 weeks' gestation in 3 maternity hospitals in England between March 2011 and December 2014. In the first phase of the study, only uterine artery pulsatility index (UTPI) was measured and then measurement of mean arterial pressure (MAP) was added, and in the final phase, the serum concentration of placental growth factor (PLGF) was measured and then soluble fms-like tyrosine kinase-1 (SFLT) was added. We had data on UTPI, MAP, PLGF, and SFLT from 30,935, 29,042, 10,123, and 8,264 pregnancies, respectively. The Bayes theorem was used to combine the a priori risk from maternal factors with various combinations of biomarker multiple of the median values. Ten-fold cross-validation was used to estimate the performance of screening for PE requiring delivery at < 37 weeks' gestation (preterm-PE) and those delivering at ≥ 37 weeks (term-PE). The empirical performance was compared with model predictions.Results: In pregnancies that developed PE, the values of MAP, UTPI, and SFLT were increased and PLGF was decreased. For all biomarkers the deviation from normal was greater for preterm-PE than term-PE, and therefore, the performance of screening was inversely related to the gestational age at which delivery become necessary for maternal and/or fetal indications. Combined screening by maternal factors, MAP, UTPI, PLGF, and SFLT predicted 98% (95% confidence interval, 88-100%) of preterm-PE and 49% (95% confidence interval, 42-57%) of term-PE, at a false-positive rate of 5%. These empirical detection rates are compatible with the respective model-based rates of 98% and 54%, but the latter were optimistically biased.Conclusion: Combination of maternal factors and biomarkers in the early third trimester could predict nearly all cases of preterm-PE and half of those with term-PE, at 5% false-positive rate. [ABSTRACT FROM AUTHOR]

The aim of this metaanalysis was to evaluate the risk of the development of obstetric complications in women with celiac disease. We searched electronic databases from their inception until February 2015. We included all cohort studies that reported the incidence of obstetric complications in women with celiac disease compared with women without celiac disease (ie, control group). Studies without a control group and case-control studies were excluded. The primary outcome was defined a priori and was the incidence of a composite of obstetric complications that included intrauterine growth restriction, small for gestational age, low birthweight, preeclampsia and preterm birth. Secondary outcomes included the incidence of preterm birth, intrauterine growth restriction, stillbirth, preeclampsia, small for gestational age, and low birthweight. The review was registered with PROSPERO (CRD42015017263) before data extraction. All authors were contacted to obtain the original databases and perform individual participant data metaanalysis. Primary and secondary outcomes were assessed in the aggregate data analysis and in the individual participant data metaanalysis. We included 10 cohort studies (4,844,555 women) in this metaanalysis. Four authors provided the entire databases for the individual participant data analysis. Because none of the included studies stratified data for the primary outcome (ie, composite outcome), the assessment of this outcome for the aggregate analysis was not feasible. Aggregate data analysis showed that, compared with women in the control group, women with celiac disease (both treated and untreated) had a significantly higher risk of the development of preterm birth (adjusted odds ratio, 1.35; 95% confidence interval, 1.09-1.66), intrauterine growth restriction (odds ratio, 2.48; 95% confidence interval, 1.32-4.67), stillbirth (odds ratio, 4.84; 95% confidence interval, 1.08-21.75), low birthweight (odds ratio, 1.63; 95% confidence interval, 1.06-2.51), and small for gestational age (odds ratio, 4.52; 95% confidence interval, 1.02-20.08); no statistically significant difference was found in the incidence of preeclampsia (odds ratio, 2.45; 95% confidence interval, 0.90-6.70). The risk of preterm birth was still significantly higher both in the subgroup analysis of only women with diagnosed and treated celiac disease (odds ratio, 1.26; 95% confidence interval, 1.06-1.48) and in the subgroup analysis of only women with undiagnosed and untreated celiac disease (odds ratio, 2.50; 95% confidence interval; 1.06-5.87). Women with diagnosed and treated celiac disease had a significantly lower risk of the development of preterm birth, compared with undiagnosed and untreated celiac disease (odds ratio, 0.80; 95% confidence interval, 0.64-0.99). The individual participant data metaanalysis showed that women with celiac disease had a significantly higher risk of composite obstetric complications compared with control subjects (odds ratio, 1.51; 95% confidence interval, 1.17-1.94). Our individual participant data concurs with the aggregate analysis for all the secondary outcomes. In summary, women with celiac disease had a significantly higher risk of the development of obstetric complications that included preterm birth, intrauterine growth restriction, stillbirth, low birthweight, and small for gestational age. Since the treatment with gluten-free diet leads to a significant decrease of preterm delivery, physicians should warn these women about the importance of a strict diet to improve obstetric outcomes. Future studies calculating cost-effectiveness of screening for celiac disease during pregnancy, which could be easily performed, economically and noninvasively, are needed. In addition, further studies are required to determine whether women with adverse pregnancy outcomes should be screened for celiac disease, particularly in countries where the prevalence is high. [ABSTRACT FROM AUTHOR]

Background: Spontaneous preterm birth (SPB) is the leading cause of perinatal morbidity and mortality. In twins, the rate of preterm birth is higher than in singletons; interventions to prevent preterm birth are needed in this high-risk population.Objective: We sought to test whether a cervical pessary reduces the preterm birth rate in twin pregnancies with sonographic short cervix.Study Design: A prospective, open-label, multicenter, randomized clinical trial was conducted in 5 hospitals in Spain. The ethics committees of all participating hospitals approved the protocol. The trial was registered as ClinicalTrials.gov, number NCT01242410. Eligible women were scanned in Spain. The primary outcome was SPB <34 weeks of gestation. Neonatal morbidity and mortality were also evaluated.Results: Cervical length was measured in 2287 women; 137 pregnant women with a sonographic cervical length ≤25 mm (of 154 detected with a short cervix) were randomly assigned to receive a cervical pessary or expectant management (1:1 ratio). SPB <34 weeks of gestation was significantly less frequent in the pessary group than in the expectant management group (11/68 [16.2%] vs 26/66 [39.4%]; relative risk, 0.41; 95% confidence interval, 0.22-0.76). Pessary use was associated with a significant reduction in the rate of birthweight <2500 g (P = .01). No significant differences were observed in composite neonatal morbidity outcome (8/136 [5.9%] vs 12/130 [9.1%]; relative risk, 0.64; 95% confidence interval, 0.27-1.50) or neonatal mortality (none) between the groups. No serious adverse effects associated with the use of a cervical pessary were observed.Conclusion: The insertion of a cervical pessary was associated with a significant reduction in the SPB rate. We propose the use of a cervical pessary for preventing preterm birth in twin pregnancies of mothers with a short cervix. [ABSTRACT FROM AUTHOR]

With the legalization of recreational marijuana in many states, we anticipate more women will be using and self-reporting marijuana use in pregnancy. Marijuana is the most common illicit drug used in pregnancy, with a prevalence of use ranging from 3% to 30% in various populations. Marijuana freely crosses the placenta and is found in breast milk. It may have adverse effects on both perinatal outcomes and fetal neurodevelopment. Specifically, marijuana may be associated with fetal growth restriction, stillbirth, and preterm birth. However, data are far from uniform regarding adverse perinatal outcomes. Existing studies are plagued by confounding by tobacco and other drug exposures as well as sociodemographic factors. In addition, there is a lack of quantification of marijuana exposure by the trimester of use and a lack of corroboration of maternal self-report with biological sampling, which contributes to the heterogeneity of study results. There is an emerging body of evidence indicating that marijuana may cause problems with neurological development, resulting in hyperactivity, poor cognitive function, and changes in dopaminergic receptors. In addition, contemporary marijuana products have higher quantities of delta-9-tetrahydrocannabinol than in the 1980s when much of the marijuana research was completed. The effects on the pregnancy and fetus may therefore be different than those previously seen. Further research is needed to provide evidence-based counseling of women regarding the anticipated outcomes of marijuana use in pregnancy. In the meantime, women should be advised not to use marijuana in pregnancy or while lactating. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholestasis of pregnancy is associated with adverse pregnancy outcomes, including sudden fetal cardiac arrhythmias, resulting in stillbirth. This association has been correlated with the total bile acid levels, which are a marker for disease severity. Studies are yet to determine if intrahepatic cholestasis of pregnancy severity is also associated with increased rates of other adverse neonatal outcomes.Objective: This study aimed to determine whether pregnancies complicated by intrahepatic cholestasis of pregnancy show a bile acid severity-based relationship with other adverse obstetrical outcomes beyond stillbirth alone.Study Design: This was a retrospective cohort study of singleton, nonanomalous gestations complicated by intrahepatic cholestasis of pregnancy at the Elmhurst Hospital Center from 2005 to 2019. Severity was defined by the peak total bile acid levels (μmol/L): mild (10-19), low moderate (20-39), high moderate (40-99), and severe (>100). We examined the rates of spontaneous preterm labor, fetal growth restriction, preterm prelabor rupture of membranes, iatrogenic preterm birth, meconium-stained amniotic fluid, cesarean delivery for nonreassuring fetal heart tracing, umbilical artery pH, neonatal intensive care unit admission, and neonatal birthweight. The chi-square, Fisher exact, Student t, Mann-Whitney, and multivariate regression tests were used to determine the association of intrahepatic cholestasis of pregnancy severity and adverse neonatal outcomes. In all analyses, mild severity was used as the base comparator. A P value of <.05 and 95% confidence interval not crossing 1.00 indicated statistical significance.Results: Of the 1202 pregnancies complicated by intrahepatic cholestasis of pregnancy, 306 (25.5%) were mild, 449 were low moderate (37.4%), 327 were high moderate (27.2%), and 120 were severe (10.0%). After adjusting for confounders, progressive intrahepatic cholestasis of pregnancy severity was associated with an increased risk of spontaneous preterm labor (low moderate adjusted odds ratio, 1.60; 95% confidence interval, 0.76-3.38; high moderate adjusted odds ratio, 3.49; 95% confidence interval, 1.69-7.22; severe adjusted odds ratio, 6.58; 95% confidence interval, 2.97-14.55), iatrogenic preterm birth (low moderate adjusted odds ratio, 1.54; 95% confidence interval, 0.95-2.52; high moderate adjusted odds ratio, 3.11; 95% confidence interval, 1.91-5.06; severe adjusted odds ratio, 4.94; 95% confidence interval, 2.81-8.71), and meconium-stained amniotic fluid (low moderate adjusted odds ratio, 1.33; 95% confidence interval, 0.75-2.36; high moderate adjusted odds ratio, 2.63; 95% confidence interval, 1.48-4.65; severe adjusted odds ratio, 3.91; 95% confidence interval, 1.98-7.69). There was no significant association between intrahepatic cholestasis of pregnancy severity and other adverse outcomes.Conclusion: The findings suggest that intrahepatic cholestasis of pregnancy disease severity is associated with an increased risk of spontaneous preterm labor, iatrogenic preterm birth, and meconium-stained amniotic fluid. These findings provide valuable insight toward patient anticipatory counseling. [ABSTRACT FROM AUTHOR]

Background: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be was established to investigate the underlying causes and pathophysiological pathways associated with adverse pregnancy outcomes in nulliparous gravidas.Objective: This study aimed to study placental physiology and identify novel biomarkers concerning adverse pregnancy outcomes, including preterm birth (medically indicated and spontaneous), preeclampsia, small-for-gestational-age neonates, and stillbirth. We measured levels of placental proteins in the maternal circulation in the first 2 trimesters of pregnancy.Study Design: Maternal serum samples were collected at 2 study visits (6-13 weeks and 16-21 weeks), and levels of 9 analytes were measured. The analytes we measured were vascular endothelial growth factor, placental growth factor, endoglin, soluble fms-like tyrosine kinase-1, A disintegrin and metalloproteinase domain-containing protein 12, pregnancy-associated plasma protein A, free beta-human chorionic gonadotropin, inhibin A, and alpha-fetoprotein. The primary outcome was preterm birth between 20 0/7 and 36 6/7 weeks of gestation. The secondary outcomes were spontaneous preterm births, medically indicated preterm births, preeclampsia, small-for-gestational-age neonates, and stillbirth.Results: A total of 10,038 eligible gravidas were enrolled in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort, from which a nested case-control study was performed comparing 800 cases with preterm birth (466 spontaneous preterm births, 330 medically indicated preterm births, and 4 unclassified preterm births), 568 with preeclampsia, 406 with small-for-gestational-age birth, and 49 with stillbirth with 911 controls who delivered at term without complications. Although levels of each analyte generally differed between cases and controls at 1 or 2 visits, the odds ratios revealed a <2-fold difference between cases and controls in all comparisons. Receiver operating characteristic curves, generated to determine the relationship between analyte levels and preterm birth and the other adverse pregnancy outcomes, resulted in areas under the receiver operating characteristic curves that were relatively low (range, 0.50-0.64) for each analyte. Logistic regression modeling demonstrated that areas under the receiver operating characteristic curves for predicting adverse pregnancy outcomes were greater using baseline clinical characteristics and combinations of analytes than baseline characteristics alone, but areas under the receiver operating characteristic curves remained relatively low for each outcome (range, 0.65-0.78).Conclusion: We have found significant associations between maternal serum levels of analytes evaluated early in pregnancy and subsequent adverse pregnancy outcomes in nulliparous gravidas. However, the test characteristics for these analytes do not support their use as clinical biomarkers to predict adverse pregnancy outcomes, either alone or in combination with maternal clinical characteristics. [ABSTRACT FROM AUTHOR]

Objective: Pregnancy hypertension is a leading cause of maternal and perinatal mortality and morbidity. Between 34+0 and 36+6 weeks gestation, it is uncertain whether planned delivery could reduce maternal complications without serious neonatal consequences. In this individual participant data meta-analysis, we aimed to compare planned delivery to expectant management, focusing specifically on women with preeclampsia.Data Sources: We performed an electronic database search using a prespecified search strategy, including trials published between January 1, 2000 and December 18, 2021. We sought individual participant-level data from all eligible trials.Study Eligibility Criteria: We included women with singleton or multifetal pregnancies with preeclampsia from 34 weeks gestation onward.Methods: The primary maternal outcome was a composite of maternal mortality or morbidity. The primary perinatal outcome was a composite of perinatal mortality or morbidity. We analyzed all the available data for each prespecified outcome on an intention-to-treat basis. For primary individual patient data analyses, we used a 1-stage fixed effects model.Results: We included 1790 participants from 6 trials in our analysis. Planned delivery from 34 weeks gestation onward significantly reduced the risk of maternal morbidity (2.6% vs 4.4%; adjusted risk ratio, 0.59; 95% confidence interval, 0.36-0.98) compared with expectant management. The primary composite perinatal outcome was increased by planned delivery (20.9% vs 17.1%; adjusted risk ratio, 1.22; 95% confidence interval, 1.01-1.47), driven by short-term neonatal respiratory morbidity. However, infants in the expectant management group were more likely to be born small for gestational age (7.8% vs 10.6%; risk ratio, 0.74; 95% confidence interval, 0.55-0.99).Conclusion: Planned early delivery in women with late preterm preeclampsia provides clear maternal benefits and may reduce the risk of the infant being born small for gestational age, with a possible increase in short-term neonatal respiratory morbidity. The potential benefits and risks of prolonging a pregnancy complicated by preeclampsia should be discussed with women as part of a shared decision-making process. [ABSTRACT FROM AUTHOR]

Background: A definition of preeclampsia that incorporates the assessment of maternal, fetal, and uteroplacental status would optimize the identification of pregnancies at risk of complications at term gestational age. This definition would include "carrying forward" angiogenic test results from 35 to 36 weeks of gestation to term gestational age. Would this approach still be useful if testing is performed earlier or at a routine midgestation scan and the result is used to inform the diagnosis of preeclampsia that developed thereafter?Objective: This study aimed to evaluate whether fetoplacental assessment at a 19- to 23-week scan could be "carried forward" to contribute to the classification of preeclampsia and improve the detection of women and fetuses at risk of adverse outcomes associated with hypertension.Study Design: In this prospective cohort study of singleton pregnancies at 2 maternity hospitals in England (October 2011 to March 2020), women attending a routine hospital visit at 19 to 23 weeks of gestation underwent an assessment that included history, ultrasonographic estimated fetal weight, Doppler measurements of the pulsatility index in uterine arteries, and serum placental growth factor. Preeclampsia was defined according to various definitions: (1) traditional, based on new-onset proteinuria at ≥20 weeks of gestation; (2) 2013 American College of Obstetricians and Gynecologists; (3) 2018 International Society for the Study of Hypertension in Pregnancy maternal factor; (4) 2018 International Society for the Study of Hypertension in Pregnancy maternal-fetal factor (death or growth restriction), based on ultrasound scans at the 19 0/7 to 23 6/7 week of gestation (an estimated fetal weight of <3rd percentile or estimated fetal weight between the 3rd and 10th percentiles with a uterine artery pulsatility index of >95th percentile); and (5) 2021 International Society for the Study of Hypertension in Pregnancy maternal-fetal factor plus placental growth factor (with abnormal placental growth factor defined as an estimated fetal weight of <5th percentile for gestational age). The detection rates for outcomes of interest (ie, severe maternal hypertension, major maternal morbidity, perinatal mortality or major neonatal morbidity, neonatal intensive care unit admission ≥48 hours, and birthweight of <3rd percentile) ascertained by health record review were compared using the chi-square test. A P value of <.05 was considered statistically significant.Results: Among 40,241 singleton pregnancies, preeclampsia incidence varied by definition, from lows of 2.6% (traditional) and 3.0% (American College of Obstetricians and Gynecologists) to a high of 3.8% (International Society for the Study of Hypertension in Pregnancy maternal-fetal factor plus placental growth factor). The International Society for the Study of Hypertension in Pregnancy maternal-fetal factor plus placental growth factor definition (vs the traditional) best identified women who developed adverse outcomes: severe hypertension (detection rate: 70.6% vs 52.8%; P<.001), major maternal morbidity (detection rate: 100% vs 87.5%; P=.027), perinatal mortality or major morbidity (detection rate: 84.6% vs 69.5%; P=.004), neonatal intensive care unit admission ≥48 hours (detection rate: 76.6% vs 63.2%;, P=.0002), and birthweight of <3rd percentile (detection rate: 81.3% vs 61.9%; P<.0001]. The detection rates improved, going from the American College of Obstetricians and Gynecologists definition to the International Society for the Study of Hypertension in Pregnancy maternal-fetal factor plus placental growth factor definition, for severe hypertension (11.4%; P=.003), perinatal mortality or major morbidity (10.6%; P=.03), neonatal intensive care unit admission ≥48 hours (8.6%; P=.01), and birthweight of <3rd percentile (16.2%; P<.001). However, going from the International Society for the Study of Hypertension in Pregnancy maternal-fetal factor definition to the International Society for the Study of Hypertension in Pregnancy maternal-fetal factor plus placental growth factor definition, the detection of fetuses with a birthweight of <3rd percentile improved by 7.0% (P=.01), but no other improvement was seen for severe hypertension (1.7%; P=.33), major maternal morbidity (0%), perinatal mortality or major morbidity (4.0%; P=.20), and neonatal intensive care unit admission ≥48 hours (3.2%; P=.17).Conclusion: The criteria for uteroplacental dysfunction (including placental growth factor) from the 19- to 23-week assessment can be used in the assessment of women who are later suspected of having PE, to best identify pregnancies at risk of adverse outcomes. [ABSTRACT FROM AUTHOR]

Objective: The ideal time for birth in pregnancies diagnosed with vasa previa remains unclear. We conducted a systematic review aiming to identify the gestational age at delivery that best balances the risks for prematurity with that of pregnancy prolongation in cases with prenatally diagnosed vasa previa.Data Sources: Ovid MEDLINE, PubMed, CINAHL, Embase, Scopus, and Web of Science were searched from inception to January 2022.Study Eligibility Criteria: The intervention analyzed was delivery at various gestational ages in pregnancies prenatally diagnosed with vasa previa. Cohort studies, case series, and case reports were included in the qualitative synthesis. When summary figures could not be obtained directly from the studies for the quantitative synthesis, authors were contacted and asked to provide a breakdown of perinatal outcomes by gestational age at birth.Methods: Study appraisal was completed using the National Institutes of Health quality assessment tool for the respective study types. Statistical analysis was performed using a random-effects meta-analysis of proportions.Results: The search identified 3435 studies of which 1264 were duplicates. After screening 2171 titles and abstracts, 140 studies proceeded to the full-text screen. A total of 37 studies were included for analysis, 14 of which were included in a quantitative synthesis. Among 490 neonates, there were 2 perinatal deaths (0.4%), both of which were neonatal deaths before 32 weeks' gestation. In general, the rate of neonatal complications decreased steadily from <32 weeks' gestation (4.6% rate of perinatal death, 91.2% respiratory distress, 11.4% 5-minute Apgar score <7, 23.3% neonatal blood transfusion, 100% neonatal intensive care unit admission, and 100% low birthweight) to 36 weeks' gestation (0% perinatal death, 5.3% respiratory distress, 0% 5-minute Apgar score <7, 2.9% neonatal blood transfusion, 29.2% neonatal intensive care unit admission, and 30.9% low birthweight). Complications then increased slightly at 37 weeks' gestation before decreasing again at 38 weeks' gestation.Conclusion: Prolonging pregnancies until 36 weeks' gestation seems to be safe and beneficial in otherwise uncomplicated pregnancies with antenatally diagnosed vasa previa. [ABSTRACT FROM AUTHOR]

Background: Several studies have assessed preoperative and operative factors associated with fetal demise after laser for TTTS, yet these findings are not completely conclusive.Objective: This study aimed to identify risk factors for single fetal demise (recipient and donor twins) after fetoscopic laser photocoagulation for twin-to-twin transfusion syndrome.Study Design: We searched PubMed, Scopus, and Web of Science systematically from the inception of the database to June 2020. We conducted a systemic review on studies investigating risk factors for fetal demise (donor and/or recipient) after fetoscopic laser photocoagulation in monochorionic pregnancies complicated with twin-to-twin transfusion syndrome. Initially, we investigated the cohort of women with twin-to-twin transfusion syndrome that underwent fetoscopic laser photocoagulation at our 2 high-volume fetal centers between 2012 and 2020 to identify risk factors for donor demise and recipient demise. Furthermore, we conducted a systematic review of the literature to better characterize these factors. Among studies that met the entry criteria, multiple preoperative and operative factors were tabulated. The random-effect model was used to pool the standardized mean differences or odds ratios and corresponding 95% confidence intervals. Heterogeneity was assessed using the I2 value.Results: A total of 514 pregnancies with twin-to-twin transfusion syndrome managed with fetoscopic laser photocoagulation were included in the final analysis. Following the logistic regression, factors that remained significant for donor demise were selective fetal growth restriction (odds ratio, 1.9; 95% confidence interval, 1.3-2.8; P=.001) and umbilical artery blood flow with absent or reversed end-diastolic velocity of the donor (odds ratio, 2.06; 95% confidence interval, 1.2-3.4; P=.004). A significant factor associated with recipient demise was absent or reversed a-wave in the ductus venosus of the recipient (odds ratio, 1.74; 95% confidence interval, 1.07-3.13; P=.04). Data from 23 studies and our current cohort were included. A total of 4892 pregnancies with twin-to-twin transfusion syndrome managed with fetoscopic laser photocoagulation were analyzed for risk factors for donor demise, and 4594 pregnancies with twin-to-twin transfusion syndrome were analyzed for recipient demise. Among studies, the overall incidence rates ranged from 10.9% to 35.8% for donor demise and 7.3% to 24.5% for recipient demise. Significant risk factors for donor demise were intertwin estimated fetal weight discordance of >25% (odds ratio, 1.86; 95% confidence interval, 1.44-2.4; I2, 0.0%), selective fetal growth restriction (odds ratio, 1.78; 95% confidence interval, 1.4-2.27; I2, 0.0%), twin-to-twin transfusion syndrome stage III (odds ratio, 2.18; 95% confidence interval, 1.53-3.12; I2, 0.0%), umbilical artery blood flow with absent or reversed end-diastolic velocity of the donor (odds ratio, 2.31; 95% confidence interval, 1.9-2.8; I2, 23.7%), absent or reversed a-wave in the ductus venosus of the donor (odds ratio, 1.83; 95% confidence interval, 1.45-2.3; I2, 0.0%), and presence of arterioarterial anastomoses (odds ratio, 2.81; 95% confidence interval, 1.35-5.85; I2, 90.7%). Sequential selective coagulation was protective against donor demise (odds ratio, 0.31; 95% confidence interval, 0.16-0.58; I2, 0.0%). Significant risk factors for recipient demise were twin-to-twin transfusion syndrome stage IV (odds ratio, 2.18; 95% confidence interval, 1.01-4.6; I2, 16.5%), umbilical artery blood flow with absent or reversed end-diastolic velocity of the recipient (odds ratio, 2.68; 95% confidence interval, 1.91-3.74; I2, 0.0%), absent or reversed a-wave in the ductus venosus of the recipient (odds ratio, 2.37; 95% confidence interval, 1.55-3.64; I2, 60.2%), and middle cerebral artery peak systolic velocity of >1.5 multiple of the median (odds ratio, 3.06; 95% confidence interval, 1.36-6.88; I2, 0.0%).Conclusion: Abnormal blood flow patterns represented by abnormal Doppler studies and low fetal weight were associated with single fetal demise in women with twin-to-twin transfusion syndrome undergoing laser therapy. Although sequential selective coagulation was protective against donor demise, the presence of arterioarterial anastomoses was considerably associated with donor demise. This meta-analysis extensively investigated the association of a wide range of preoperative and operative factors with fetal demise. These findings may be important inpatient counseling, in further understanding the disease, and perhaps in improving surgical techniques. [ABSTRACT FROM AUTHOR]

Objective Second-born twins on average weigh less than first-born twins and have been reported at an elevated risk of perinatal mortality. Whether the risk differences depend on their relative birth size is unknown. The present study aimed to evaluate the association of birth order with perinatal mortality by birth order-specific weight difference in twin pregnancies. Study Design In a retrospective cohort study of 258,800 twin pregnancies without reported congenital anomalies using the US matched multiple birth data 1995-2000 (the available largest multiple birth dataset), conditional logistic regression was applied to estimate the odds ratio (OR) of perinatal death adjusted for fetus-specific characteristics (sex, presentation, and birthweight for gestational age). Results Comparing second vs first twins, the risks of perinatal death were similar if they had similar birthweights (within 5%) and were increasingly higher if second twins weighed progressively less (adjusted ORs were 1.37, 1.90, and 3.94 if weighed 5.0-14.9%, 15.0-24.9%, and ≥25.0% less, respectively), and progressively lower if they weighed increasingly more (adjusted ORs were 0.67, 0.63, and 0.36 if weighed 5.0-14.9%, 15.0-24.9%, and ≥25.0% more, respectively) (all P < .001). The perinatal mortality rates were not significantly different in cesarean deliveries or preterm (<37 weeks) vaginal deliveries but were significantly higher in second twins in term vaginal deliveries (3.1 vs 1.8 per 1000; adjusted OR, 2.15; P < .001). Conclusion Perinatal mortality risk differences in second vs first twins depend on their relative birth size. Vaginal delivery at term is associated with a substantially greater risk of perinatal mortality in second twins. [ABSTRACT FROM AUTHOR]

Background: Neurologic injury in the surviving twin is a risk after single fetal demise in a monochorionic pregnancy.Objective: This study aimed to describe fetal magnetic resonance neuroimaging findings in pregnancies complicated by single fetal demise after laser photocoagulation for twin-twin transfusion syndrome.Study Design: This was a single-center retrospective analysis of a cohort of prospectively collected patients in a monochorionic twin registry who had fetoscopic laser photocoagulation for twin-twin transfusion syndrome with single fetal demise at follow-up. Magnetic resonance neuroimaging was offered 3 to 4 weeks after the demise to assess for potential neurologic sequelae. Magnetic resonance images were interpreted by 2 board-certified neuroradiologists and classified as normal, mildly abnormal, or severely abnormal. The groups were compared on the basis of recipient vs donor demise using the Fisher exact test and Mann-Whitney U test. Multivariate logistic regression was performed to determine risk factors for abnormal magnetic resonance neuroimaging.Results: In 378 laser photocoagulation procedures, 64 cases (16.9%) of single demise were identified (36 in the donor group and 28 in the recipient group). Of note, 6 patients had rupture of membranes with nonviable delivery (3 from each group). Moreover, 40 patients (69%) underwent magnetic resonance imaging. Of those patients, 12 (30%) had abnormal findings: 10 (83%) were associated with mild changes, and 2 (17%) were associated with severe findings. Abnormal magnetic resonance neuroimaging was seen in 3 of 22 patients (14%) after donor demise and 9 of 18 patients (50%) after recipient demise (P=.02). Logistic regression revealed that recipient vs donor demise was an independent risk factor for abnormal magnetic resonance imaging. In addition, 2 pregnancies with severe magnetic resonance imaging findings had complicated courses.Conclusion: Mildly abnormal magnetic resonance neuroimaging findings were common after laser photocoagulation for twin-twin transfusion syndrome complicated by single fetal demise and were more common in cases of recipient demise than donor demise. Severe magnetic resonance neuroimaging findings in this series were limited to patients with complicated peri- or postoperative courses. [ABSTRACT FROM AUTHOR]

Objective: To assess perinatal outcomes of first pregnancy after remission from gestational trophoblastic neoplasia and the impact of the time between the end of chemotherapy and the subsequent pregnancy.Data Sources: The Medical Subject Headings related to perinatal outcomes, chemotherapy, and gestational trophoblastic neoplasia were used alone or in combination to retrieve relevant articles. We searched all references registered until April, 2019 in Embase, LILACS, MEDLINE, the Cochrane Central Register of Controlled Trials, and Web of Science.Study Eligibility Criteria: We included any observational or interventional studies that evaluated perinatal outcomes of first pregnancy after chemotherapy for gestational trophoblastic neoplasia. Animal studies, narrative reviews, expert opinions, and previous treatments with potential risks for future perinatal outcomes which may introduce confounding bias were excluded.Study Appraisal and Synthesis Methods: Two reviewers independently screened all identified references for eligibility and data extraction. Methodological quality and bias of included studies were assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies from the National Institutes of Health. For the meta-analysis, the measures of association were calculated using bivariate random-effects models. Statistical heterogeneity was evaluated with I2 statistics and explored through sensitivity analysis. Publication bias was assessed by visual inspection of the funnel plot or Egger's test, according to the number of articles included. For all analyses, a P value of <.05 indicated statistical significance. This study was registered on PROSPERO (CRD42018116513).Results: A total of 763 studies were identified after literature search and 23 original studies were included in the systematic review and in the meta-analysis. The combined data from the subgroup meta-analysis (outcome vs time after chemotherapy) showed an incidence of spontaneous abortion of 15.28% (95% confidence interval, 12.37-18.74; I2=73%), 3.30% of malformation (95% confidence interval, 2.27-4.79; I2=31%), 6.19% of prematurity (95% confidence interval, 5.03-7.59; I2=0), and 1.73% of stillbirth (95% confidence interval, 1.17-2.55; I2=0%). These results were not influenced by the time between the end of chemotherapy and the subsequent pregnancy in most of the studied outcomes, including malformation (P=.14, I2=31%), prematurity (P=.46, I2=0), and stillbirth (P=.66, I2=0). However, there was a higher occurrence of spontaneous abortion (P<.01, I2=73%) in pregnancies that occurred ≤6 months after chemotherapy.Conclusion: Chemotherapy for gestational trophoblastic neoplasia does not appear to increase the chance of unfavorable perinatal outcomes, except for the higher occurrence of spontaneous abortion in pregnancies occurring ≤6 months after chemotherapy. [ABSTRACT FROM AUTHOR]

The rate of twin pregnancies in the United States has stabilized at 32 per 1000 births in 2006. Aside from determining chorionicity, first-trimester screening and second-trimester ultrasound scanning should ascertain whether there are structural or chromosomal abnormalities. Compared with singleton births, genetic amniocentesis–related loss at <24 weeks of gestation for twin births is higher (0.9% vs 2.9%, respectively). Selective termination for an anomalous fetus is an option, although the pregnancy loss rate is 7% at experienced centers. For singleton and twin births for African American and white women, approximately 50% of preterm births are indicated; approximately one-third of these births are spontaneous, and 10% of the births occur after preterm premature rupture of membranes. From 1989-2000, the rate of preterm twin births increased, for African American and white women alike, although the perinatal mortality rate has actually decreased. As with singleton births, tocolytics should be used judiciously and only for a limited time (<48 hours) in twin births. Administration of antenatal corticosteroids is an evidence-based recommendation. [ABSTRACT FROM AUTHOR]

We sought to review emerging data on the use of progesterone to prevent preterm birth (PTB). Using the terms “preterm or premature” and “progesterone” we queried the PubMed database, restricting our search to January 1, 2000, forward and selected randomized clinical trials (RCTs) and metaanalyses of RCTs that evaluated the use of progesterone for the prevention of PTB. We reviewed 238 abstracts and supplemented our review by a bibliographic search of selected reports. We focused on the pharmacologic aspects of progesterone and risk factor-specific outcomes. We identified a total of 17 relevant reports: 8 individual RCTs, 6 metaanalyses, and 3 national guidelines. Individual trials and metaanalyses support that synthetic intramuscular 17-alpha-hydroxyprogesterone effectively reduces the incidence of recurrent PTB in women with a history of spontaneous PTB. One trial found that vaginally administered natural progesterone reduced the risk of early PTB in women with a foreshortened cervix. The data are suggestive but inconclusive about: (1) the benefits of progesterone in the setting of arrested preterm labor; and (2) whether progesterone lowers perinatal morbidity or mortality. In some women, progesterone reduces the risk of PTB. Further study is required to identify appropriate candidates and optimal formulations. [Copyright &y& Elsevier]

Background: The main reason to avoid trial of labor after cesarean delivery is the possibility of uterine rupture. Identifying women at risk is thus an important aim, for it would enable women at low risk to proceed with a secure planned vaginal birth.Objective: To evaluate the impact of proposing mode of delivery based on the ultrasound measurement of the lower uterine segment thickness on a composite outcome of maternal-fetal mortality and morbidity, compared with usual management, among pregnant women with a previous cesarean delivery.Study Design: This multicenter, randomized, controlled, parallel-group, unmasked trial was conducted at 8 referral university hospitals with a neonatal intensive care unit and enrolled 2948 women at 36 weeks 0 days to 38 weeks 6 days of gestation with 1 previous low transverse cesarean delivery and no contraindication to trial of labor. Women in the study group had their lower uterine segment thickness measured by ultrasound. Those with measurements >3.5 mm, were encouraged to choose a planned vaginal delivery, and those with measurements ≤3.5 mm, were encouraged to choose a planned repeat cesarean delivery. This measurement was not taken in the control group; their mode of delivery was decided according to standard management. The primary outcome was a composite criterion comprising maternal mortality, uterine rupture, uterine dehiscence, hysterectomy, thromboembolic disease, transfusion, endometritis, perinatal death, or neonatal encephalopathy. Prespecified secondary outcomes were repeat cesarean deliveries, elective or after trial of labor.Results: The study group included 1472 women, and the control group included 1476 women. These groups were similar at baseline. The primary outcome occurred in 3.4% of the study group and 4.3% of the control group (relative risk, 0.78; 95% confidence interval, 0.54-1.13: risk difference, -1.0%; 95% confidence interval, -2.4 to 0.5). The uterine rupture rate in the study group was 0.4% and in the control group 0.9% (relative risk, 0.43; 95% confidence interval, 0.15-1.19). The planned cesarean delivery rate was 16.4% in the study group and 13.7% in the control group (relative risk, 1.21; 95% confidence interval, 1.00-1.47), whereas the rates of cesarean delivery during labor were 25.1% and 25.0% (relative risk, 1.01; 95% confidence interval, 0.89-1.14) in the study and control groups, respectively.Conclusion: Ultrasound measurements of lower uterine segment thickness did not result in a statistically significant lower frequency of maternal and perinatal adverse outcomes than standard management. However, because this study was underpowered, further research should be encouraged. [ABSTRACT FROM AUTHOR]