Search

A healthy pregnancy depends on complex interrelated biological adaptations involving placentation, maternal immune responses, and hormonal homeostasis. Recent advances in high-throughput technologies have provided access to multiomics biological data that, combined with clinical and social data, can provide a deeper understanding of normal and abnormal pregnancies. Integration of these heterogeneous datasets using state-of-the-art machine-learning methods can enable the prediction of short- and long-term health trajectories for a mother and offspring and the development of treatments to prevent or minimize complications. We review advanced machine-learning methods that could: provide deeper biological insights into a pregnancy not yet unveiled by current methodologies; clarify the etiologies and heterogeneity of pathologies that affect a pregnancy; and suggest the best approaches to address disparities in outcomes affecting vulnerable populations.

Prenatal ultrasound (US) has been shown to overestimate the incidence of suspected fetal growth restriction (FGR) in gastroschisis cases. This is largely because of altered sonographic abdominal circumference (AC) measurements when comparing gastroschisis cases with population nomograms. Individualized Growth Assessment (IGA) evaluates fetal growth using serial US measurements that allow consideration of the growth potential for a given case. Our goal was to assess the utility of IGA for distinguishing normal and pathological fetal growth in gastroschisis cases.Pregnancies with prenatally diagnosed fetal gastroschisis were managed and delivered at a single academic medical center. US fetal biometry including head circumference (HC), abdominal circumference (AC), and femur diaphysis length (FDL), and neonatal measurements including birthweight and HC were collected and analyzed for 32 consecutive fetal gastroschisis cases with at least two 2nd and two 3rd trimester measurements. Second trimester growth velocities were compared to a group of 118 non-anomalous fetuses with normal neonatal growth outcomes. Gastroschisis cases were classified into groups based on fetal growth pathology score (FGPS9) patterns. Agreement between IGA (FGPS9) and serial conventional estimated fetal weight (EFW) measurements for determining growth pathology was evaluated. Neonatal size outcomes were compared between conventional birthweight classifications for determining small for gestational age (SGA) and IGA Growth Potential Realization Index (GPRI) for weight and head circumference measurements.Fetal growth pathology score (FGPS9) measurements identified three in-utero growth patterns: no growth pathology, growth restriction and recovery, and progressive growth restriction. In the no growth pathology group (We present the first study using IGA to evaluate normal and pathological fetal growth in prenatally diagnosed gastroschisis cases. IGA was able to delineate two 3rd trimester growth pathology patterns - one with persistent growth restriction and another with in-utero growth recovery. Further validation of these initial findings with larger cohorts is warranted.

Introduction: In fetuses with hypoplastic left-heart syndrome (HLHS), maternal hyperoxygenation (MHO) may aid risk stratification. We hypothesized that pulmonary vein (Pvein) velocity time integral (VTI) change with MHO would more reliably identify neonates who undergo emergent atrial septoplasty (EAS) than changes in pulmonary arterial pulsatility index (PA PI). Methods: Fetuses with HLHS who underwent MHO testing at our institution between 2014 and 2019 were identified. Data were reviewed in a blinded, retrospective manner. Pvein VTI ratio (prograde:retrograde) was calculated. The primary outcome was neonatal EAS. Results: Twenty-seven HLHS fetuses underwent MHO, and 5 (19%) underwent EAS. Without MHO, a Pvein VTI ratio Discussion/Conclusion: Addition of MHO appears to improve the diagnostic ability of the Pvein VTI ratio to identify HLHS fetuses who undergo EAS. The Pvein VTI ratio change may more accurately identify fetuses who undergo EAS than change in PA PI and has less interobserver variability.

Purpose of review Congenital diaphragmatic hernia (CDH) is a structural birth defect that results in significant neonatal morbidity and mortality. CDH occurs in 2-4 per 10 000 pregnancies, and despite meaningful advances in neonatal intensive care, the mortality rate in infants with isolated CDH is still 25-30%. In this review, we will present data on the molecular underpinnings of pathological lung development in CDH, prenatal diagnosis, and prognostication in CDH cases, existing fetal therapy modalities, and future directions. Recent findings Developments in the prenatal assessment and in-utero therapy of pregnancies complicated by congenital diaphragmatic hernia are rapidly evolving. Although ultrasound has been the mainstay of prenatal diagnosis, fetal MRI appears to be an increasingly important modality for severity classification. While fetal endoscopic tracheal occlusion (FETO) may have a role in the prenatal management of severe CDH cases, it is possible that future therapeutic paradigms will incorporate adjunct medical interventions with either stem cells or sildenafil in order to address the vascular effects of CDH on the developing lung. Summary Both animal and human data have shown that the pathophysiological underpinnings of CDH are multifactorial, and it appears that future prenatal assessments and therapies will likely be as well.

Anhydramnios secondary to anuria before 22 weeks of gestational age and congenital bilateral renal agenesis before 26 weeks of gestational age are collectively referred to as early-pregnancy renal anhydramnios. Early-pregnancy renal anhydramnios occurs in at least 1 in 2000 pregnancies and is considered universally fatal when left untreated because of severe pulmonary hypoplasia precluding ex utero survival The Renal Anhydramnios Fetal Therapy (RAFT) trial is a nonrandomized, nonblinded, multicenter clinical trial designed to assess the efficacy, safety, and feasibility of amnioinfusions for patients with pregnancies complicated by early-pregnancy renal anhydramnios. The primary objective of this study is to determine the proportion of neonates surviving to successful dialysis, defined as use of a dialysis catheter for ≥14 days.A consortium of 9 North American Fetal Therapy Network (NAFTNet) centers was formed, and the RAFT protocol was refined in collaboration with the NAFTNet Scientific Committee. Enrollment in the trial began in April 2020. Participants may elect to receive amnioinfusions or to join the nonintervention observational expectant management group. Eligible pregnant women must be at least 18 years of age with a fetal diagnosis of isolated early-pregnancy renal anhydramnios.In addition to the primary study objective stated above, secondary objectives include (1) to assess maternal safety and feasibility of the serial amnioinfusion intervention (2) to perform an exploratory study of the natural history of untreated early pregnancy renal anhydramnios (3) to examine correlations between prenatal imaging and lung specific factors in amniotic fluid as predictive of the efficacy of serial percutaneous amnioinfusions and (4) to determine short- and long-term outcomes and quality of life in surviving neonates and families enrolled in RAFT IMPLICATIONS: The RAFT trial is the first clinical trial to investigate the efficacy, safety, and feasibility of amnioinfusions to treat the survival-limiting pulmonary hypoplasia associated with anhydramnios. Although the intervention offers an opportunity to treat a condition known to be almost universally fatal in affected neonates, the potential burdens associated with end-stage kidney disease from birth must be acknowledged.gov identifier: NCT03101891.

INTRODUCTION The clinical importance of mass effect from congenital lung masses on the fetal heart is unknown. We aimed to report cardiac measurements in fetuses with congenital lung masses and to correlate lung mass severity/size with cardiac dimensions and clinical outcomes. METHODS Cases were identified from our institutional database between 2009 and 2016. We recorded atrioventricular valve (AVVz) annulus dimensions and ventricular widths (VWz) converted into z scores, ratio of aortic to total cardiac output (AoCO), lesion side, and congenital pulmonary airway malformation volume ratio (CVR). Respiratory intervention (RI) was defined as intubation, extracorporeal membrane oxygenation (ECMO), or use of surgical intervention prior to discharge. RESULTS Fifty-two fetuses comprised the study cohort. Mean AVVz and VWz were below expected for gestational age. CVR correlated with ipsilateral AVVz (RS = -.59, P < .001) and ipsilateral VWz (-0.59, P < .001). Lower AVVz and AoCO and higher CVR were associated with RI. No patient had significant structural heart disease identified postnatally. CONCLUSION In fetuses with left-sided lung masses, ipsilateral cardiac structures tend to be smaller, but in our cohort, there were no patients with structural heart disease. However, smaller left-sided structures may contribute to the need for RI that affects a portion of these fetuses.

Fetal lung masses complicate approximately 1 in 2000 live births. Our aim was to determine whether obstetric and neonatal outcomes differ by final fetal lung mass histology.A review of all pregnancies complicated by a prenatally diagnosed fetal lung mass between 2009 and 2017 at a single academic center was conducted. All cases included in the final analysis underwent surgical resection and histology diagnosis was determined by a trained pathologist. Clinical data were obtained from review of stored electronic medical records which contained linked maternal and neonatal records. Imaging records included both prenatal ultrasound and magnetic resonance imaging. Fisher's exact test was used for categorical variables and the Kruskal-Wallis test was used for continuous variables. The level of significance wasOf 61 pregnancies complicated by fetal lung mass during the study period, 45 cases underwent both prenatal care and postnatal resection. Final histology revealed 10 cases of congenital pulmonary airway malformation (CPAM) type 1, nine cases of CPAM type 2, and 16 cases of bronchopulmonary sequestration. There was no difference in initial, maximal, or final CPAM volume ratio between groups, with median final CPAM volume ratio of 0.6 for CPAM type 1, 0.7 for CPAM type 2, and 0.3 for bronchopulmonary sequestration (In our cohort, there was no significant association between histologic lung mass subtypes and any obstetric or neonatal morbidity including respiratory distress.

To investigate the effect of preterm gestational age (GA) on neonatal outcomes of gastroschisis and to compare the neonatal outcomes after spontaneous labor versus iatrogenic delivery both in the preterm and early term gestational periods.A retrospective study of prenatally diagnosed gastroschisis cases born at Loma Linda University Medical Center and Lucile Packard Children's Hospital (Loma Linda, CA) between January 2009 and October 2016. A total of 194 prenatally diagnosed gastroschisis cases were identified and included in the analysis. We compared infants delivered37 0/7 to those ≥37 0/7 weeks' gestation. Adverse neonatal outcome was defined as any of: sepsis, short bowel syndrome, prolonged ventilation, or death. Prolonged length of stay (LOS) was defined as ≥75th percentile value. Outcomes following spontaneous versus iatrogenic delivery were compared. Analyses were performed using chi-squared test or Fisher's exact test for categorical variables, and Student'sOne hundred and six neonates were born37 weeks and 88 at ≥37 weeks. Adverse outcome was statistically similar among those born37 weeks compared to ≥37 weeks (48 versus 34%,Neonates with gastroschisis delivered37 weeks had prolonged LOS whereas the rate of adverse neonatal outcomes was similar between those delivered preterm versus term. Neonates born after spontaneous preterm labor had a higher rate of bowel atresia compared to those born after planned iatrogenic preterm delivery.

To characterize factors associated with adverse neonatal outcomes in prenatally diagnosed omphalocele cases. Prenatally diagnosed omphalocele cases at a single referral center from 1 January 2009 to 31 December 2017 were retrospectively reviewed. Clinical variables and antenatal imaging measurements were collected. Associations between prenatal and neonatal characteristics and the adverse outcome of death or prolonged length of stay (LOS) were analyzed. Out of 63 fetal cases, 33 were live-born, > 50% had other anomalies, and neonatal mortality was 12%. Adverse outcomes were associated with neonatal variables, including lower median 1-min Apgar score, initial mechanical ventilation, and late-onset sepsis, but not approach to omphalocele closure. With multivariate analysis, death or prolonged LOS was associated only with low lung volumes by fetal MRI (OR 34 (3–422), p = 0.006). Low lung volumes by fetal MRI were associated with death or prolonged LOS in neonates with prenatally diagnosed omphalocele and may guide clinicians with counseling families.

Preterm birth (PTB) – delivery prior to 37-weeks gestation – disproportionately affects low-income and minority populations and leads to substantial infant morbidity and mortality. The time following a PTB represents an optimal window for targeted interventions that encourage mothers to prioritize their own health and that of their babies. Healthcare teams can leverage digital strategies to address maternal and infant needs in this postpartum period, both in the neonatal intensive care unit and beyond. We therefore developed PretermConnect, a mobile app designed to educate, engage, and empower women at risk for PTB. This article describes the participant-centered design approach of PretermConnect, with preliminary findings from focus groups and co-design sessions in different community settings and suggested future directions for mobile technologies in population health. Apps such as PretermConnect can mitigate social disadvantage by serving as remote monitoring tools, providing social support, preventing recurrent PTB and lowering infant mortality rates.

Early identification of pregnant women at risk for preeclampsia (PE) is important, as it will enable targeted interventions ahead of clinical manifestations. The quantitative analyses of plasma proteins feature prominently among molecular approaches used for risk prediction. However, derivation of protein signatures of sufficient predictive power has been challenging. The recent availability of platforms simultaneously assessing over 1000 plasma proteins offers broad examinations of the plasma proteome, which may enable the extraction of proteomic signatures with improved prognostic performance in prenatal care. The primary aim of this study was to examine the generalizability of proteomic signatures predictive of PE in two cohorts of pregnant women whose plasma proteome was interrogated with the same highly multiplexed platform. Establishing generalizability, or lack thereof, is critical to devise strategies facilitating the development of clinically useful predictive tests. A second aim was to examine the generalizability of protein signatures predictive of gestational age (GA) in uncomplicated pregnancies in the same cohorts to contrast physiological and pathological pregnancy outcomes. Serial blood samples were collected during the first, second, and third trimesters in 18 women who developed PE and 18 women with uncomplicated pregnancies (Stanford cohort). The second cohort (Detroit), used for comparative analysis, consisted of 76 women with PE and 90 women with uncomplicated pregnancies. Multivariate analyses were applied to infer predictive and cohort-specific proteomic models, which were then tested in the alternate cohort. Gene ontology (GO) analysis was performed to identify biological processes that were over-represented among top-ranked proteins associated with PE. The model derived in the Stanford cohort was highly significant (p = 3.9E–15) and predictive (AUC = 0.96), but failed validation in the Detroit cohort (p = 9.7E–01, AUC = 0.50). Similarly, the model derived in the Detroit cohort was highly significant (p = 1.0E–21, AUC = 0.73), but failed validation in the Stanford cohort (p = 7.3E–02, AUC = 0.60). By contrast, proteomic models predicting GA were readily validated across the Stanford (p = 1.1E–454, R = 0.92) and Detroit cohorts (p = 1.1.E–92, R = 0.92) indicating that the proteomic assay performed well enough to infer a generalizable model across studied cohorts, which makes it less likely that technical aspects of the assay, including batch effects, accounted for observed differences. Results point to a broader issue relevant for proteomic and other omic discovery studies in patient cohorts suffering from a clinical syndrome, such as PE, driven by heterogeneous pathophysiologies. While novel technologies including highly multiplex proteomic arrays and adapted computational algorithms allow for novel discoveries for a particular study cohort, they may not readily generalize across cohorts. A likely reason is that the prevalence of pathophysiologic processes leading up to the “same” clinical syndrome can be distributed differently in different and smaller-sized cohorts. Signatures derived in individual cohorts may simply capture different facets of the spectrum of pathophysiologic processes driving a syndrome. Our findings have important implications for the design of omic studies of a syndrome like PE. They highlight the need for performing such studies in diverse and well-phenotyped patient populations that are large enough to characterize subsets of patients with shared pathophysiologies to then derive subset-specific signatures of sufficient predictive power.

Objective To test the hypothesis that a fetal stratification pathway will effectively discriminate between infants at different levels of risk for surgical coarctation and reduce unnecessary medicalization. Study design We performed a pre-post nonrandomized study in which we prospectively assigned fetuses with prenatal concern for coarctation to 1 of 3 risk categories and implemented a clinical pathway for postnatal management. Postnatal clinical outcomes were compared with those in a historical control group that were not triaged based on the pathway. Results The study cohort comprised 109 fetuses, including 57 treated along the fetal coarctation pathway and 52 historical controls. Among mild-risk fetuses, 3% underwent surgical coarctation repair (0% of those without additional heart defects), compared with 27% of moderate-risk and 63% of high-risk fetuses. The combined fetal aortic, mitral, and isthmus z-score best discriminated which infants underwent surgery (area under the curve = 0.78; 95% CI, 0.66-0.91). Compared with historical controls, infants triaged according to the fetal coarctation pathway had fewer delivery location changes (76% vs 55%; P = .025) and less umbilical venous catheter placement (74% vs 51%; P = .046). Trends toward shorter intensive care unit stay, hospital stay, and time to enteral feeding did not reach statistical significance. Conclusions A stratified risk-assignment pathway effectively identifies a group of fetuses with a low rate of surgical coarctation and reduces unnecessary medicalization in infants who do not undergo aortic surgery. Incorporation of novel measurements or imaging techniques may improve the specificity of high-risk criteria.

To investigate factors associated with positive postpartum depression (PPD) screen in pregnancies complicated by fetal congenital cardiac anomaly.We reviewed all records of pregnancies complicated by fetal congenital cardiac anomaly receiving prenatal, intrapartum and postpartum care at our single center, October 2016-October 2019. Maternal, obstetric, and neonatal data were compared between women with and without a positive PPD screen at the 6-week postpartum visit.Out of 415 women referred for fetal congenital cardiac anomaly, 86 women had complete inclusion criteria. Twenty-four women (28%) had a positive PPD screen. The frequencies of planned future infant surgery (73.9 vs. 26.2%, p = 0.01) and neonatal death prior to postpartum visit (12.5 vs. 0%, p = 0.02) were significantly higher among women with a positive PPD screen.In pregnancies complicated by fetal congenital cardiac anomaly, mothers of infants with planned future surgery or neonatal death are at significant risk for postpartum depression.

Background Up to 84% of women who undergo operative vaginal delivery receive neuraxial analgesia. However, little is known about the association between neuraxial analgesia and neonatal morbidity in women who undergo operative vaginal delivery. The authors hypothesized that neuraxial analgesia is associated with a reduced risk of neonatal morbidity among women undergoing operative vaginal delivery. Methods Using United States birth certificate data, the study identified women with singleton pregnancies who underwent operative vaginal (forceps- or vacuum-assisted delivery) in 2017. The authors examined the relationships between neuraxial labor analgesia and neonatal morbidity, the latter defined by any of the following: 5-min Apgar score less than 7, immediate assisted ventilation, assisted ventilation greater than 6 h, neonatal intensive care unit admission, neonatal transfer to a different facility within 24 h of delivery, and neonatal seizure or serious neurologic dysfunction. The authors accounted for sociodemographic and obstetric factors as potential confounders in their analysis. Results The study cohort comprised 106,845 women who underwent operative vaginal delivery, of whom 92,518 (86.6%) received neuraxial analgesia. The proportion of neonates with morbidity was higher in the neuraxial analgesia group than the nonneuraxial group (10,409 of 92,518 [11.3%] vs. 1,271 of 14,327 [8.9%], respectively; P < 0.001). The unadjusted relative risk was 1.27 (95% CI, 1.20 to 1.34; P < 0.001); after accounting for confounders using a multivariable model, the adjusted relative risk was 1.19 (95% CI, 1.12 to 1.26; P < 0.001). In a post hoc analysis, after excluding neonatal intensive care unit admission and neonatal transfer from the composite outcome, the effect of neuraxial analgesia on neonatal morbidity was not statistically significant (adjusted relative risk, 1.07; 95% CI, 1.00 to 1.16; P = 0.054). Conclusions In this population-based cross-sectional study, a neonatal benefit of neuraxial analgesia for operative vaginal delivery was not observed. Confounding by indication may explain the observed association between neuraxial analgesia and neonatal morbidity, however this dataset was not designed to evaluate such considerations. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

OBJECTIVE To determine population-based risks of preterm birth associated with vasa previa. STUDY DESIGN Included were 945,950 singleton, live birth cesarean deliveries with and without vasa previa (gestational ages 24-41 weeks) in California between 2007 and 2012. Odds ratios (ORs) of preterm birth were estimated using logistic regression. RESULTS In total, 586 were complicated by vasa previa (0.06%). In total, 369 (63%) of those with vasa previa were delivered

Objective The aim of the study is to determine the prevalence of RASopathies in a polyhydramnios cohort selected by postnatal medical genetics evaluation. Methods In this retrospective study, we reviewed 622 pregnancies with polyhydramnios seen at Lucile Packard Children's Hospital between 2008-2017. The findings from 131 cases evaluated by Medical Genetics were included in our final analysis. Genetic testing information was extracted to determine the rate of chromosomal or single gene conditions focusing on the RASopathies. Additional variables collected were: maternal characteristics, ultrasound findings, and the severity and timing of diagnosis of polyhydramnios. Results Postnatal genetic testing or clinical examination identified a genetic disorder in 63 (48.1%) cases, more than half (n=33) of which had a single gene condition. Postnatal testing revealed an underlying RASopathy in 15 (11.5%) cases. An underlying RASopathy was significantly associated with the severity and timing of polyhydramnios (p Conclusion Focusing on a selected cohort postnatally evaluated by Medical Genetics, our study identified a chromosomal or genetic disorder in almost half of pregnancies complicated by polyhydramnios. Specifically, an underlying RASopathy was found in 11.5% of cases with 13/15 of these cases having additional ultrasound findings. This article is protected by copyright. All rights reserved.

Fetal ventriculomegaly may occur in isolation or as part of a broader syndrome. We aimed to determine the added value of magnetic resonance imaging (MRI) for informing the pre-natal and postnatal care of pregnancies complicated by ventriculomegaly (VM). Retrospective analysis of all cases of prenatally diagnosed VM referred to the fetal center at Lucile Packard Children’s Hospital Stanford 1/1/2009–6/1/2014 were reviewed. Ultrasound (US) and MRI findings were reviewed, and the added yield of MRI evaluated. A total of 91 cases of fetal VM were identified and 74 (81%) underwent MRI. In 62/74 (84%) cases, additional CNS or non-CNS findings, not seen on US, were discovered on MRI, of which 58 were CNS-related. Forty-six (62%) of the additional findings were considered clinically relevant, of which 45 were CNS-related. Fetal MRI identifies additional, clinically relevant CNS and non-CNS findings in a majority of cases of VM following initial US.

BACKGROUND Plasma cell-free RNA (cfRNA) encompasses a broad spectrum of RNA species that can be derived from both human cells and microbes. Because cfRNA is fragmented and of low concentration, it has been challenging to profile its transcriptome using standard RNA-seq methods. METHODS We assessed several recently developed RNA-seq methods on cfRNA samples. We then analyzed the dynamic changes of both the human transcriptome and the microbiome of plasma during pregnancy from 60 women. RESULTS cfRNA reflects a well-orchestrated immune modulation during pregnancy: an up-regulation of antiinflammatory genes and an increased abundance of antimicrobial genes. We observed that the plasma microbiome remained relatively stable during pregnancy. The bacteria Ureaplasma shows an increased prevalence and increased abundance at postpartum, which is likely to be associated with postpartum infection. We demonstrated that cfRNA-seq can be used to monitor viral infections. We detected a number of human pathogens in our patients, including an undiagnosed patient with a high load of human parvovirus B19 virus (B19V), which is known to be a potential cause of complications in pregnancy. CONCLUSIONS Plasma cfRNA-seq demonstrates the potential to simultaneously monitor immune response and microbial infections during pregnancy.

Importance Bilateral renal agenesis is a rare congenital anomaly associated with poor prognosis. Objective The aims of this article are to review and summarize evidence on prenatal diagnosis and outcomes of bilateral renal agenesis. Evidence acquisition A search was undertaken using PubMed and ClinicalTrials.gov databases from January 1, 1998, to September 1, 2018. Search terms include "prenatal diagnosis" OR "outcomes" AND "bilateral renal agenesis." Search was limited to English language. Results Fetal ultrasonography is the primary imaging modality for prenatal diagnosis of fetal urogenital tract abnormalities. However, ultrasonography is limited by several factors; it is operator dependent and associated with small field of view, has limited soft-tissue acoustic contrast, and is also influenced by patient habitus and fetal position. Color Doppler ultrasonography can be used as an adjunct to exclude bilateral renal agenesis by visualizing renal arteries. In the literature, prenatal magnetic resonance imaging has been reported to be equal to or superior to prenatal ultrasonography. Bilateral renal agenesis with oligohydramnios/anhydramnios is associated with a poor prognosis; perinatal death occurs secondary to pulmonary hypoplasia in the majority of cases. Conclusions Ultrasonography in combination with color Doppler ultrasonography permits the fetal urinary tract to be assessed in the first and early second trimester of gestation. The magnetic resonance imaging can be used as a complementary adjunctive modality in equivocal or inconclusive ultrasonographic findings.

BACKGROUND Our goal was to develop an approach that can systematically identify potential associations between medication prescribed in pregnancy and spontaneous preterm birth (sPTB) by mining large administrative "claims" databases containing hundreds of medications. One such association that we illustrate emerged with antiviral medications used for herpes treatment. METHODS IBM MarketScan® databases (2007-2016) were used. A pregnancy cohort was established using International Classification of Diseases (ICD-9/10) codes. Multiple hypothesis testing and the Benjamini-Hochberg procedure that limited false discovery rate at 5% revealed, among 863 medications, five that showed odds ratios (ORs)

OBJECTIVES To develop a machine-learning (ML) model for prediction of shoulder dystocia (ShD) and to externally validate the model's predictive accuracy and potential clinical efficacy in optimizing the use of Cesarean delivery in the context of suspected macrosomia. METHODS We used electronic health records (EHR) from the Sheba Medical Center in Israel to develop the model (derivation cohort) and EHR from the University of California San Francisco Medical Center to validate the model's accuracy and clinical efficacy (validation cohort). Subsequent to application of inclusion and exclusion criteria, the derivation cohort included 686 singleton vaginal deliveries, of which 131 were complicated by ShD, and the validation cohort included 2584 deliveries, of which 31 were complicated by ShD. For each of these deliveries, we collected maternal and neonatal delivery outcomes coupled with maternal demographics, obstetric clinical data and sonographic fetal biometry. Biometric measurements and their derived estimated fetal weight were adjusted (aEFW) according to gestational age at delivery. A ML pipeline was utilized to develop the model. RESULTS In the derivation cohort, the ML model provided significantly better prediction than did the current clinical paradigm based on fetal weight and maternal diabetes: using nested cross-validation, the area under the receiver-operating-characteristics curve (AUC) of the model was 0.793 ± 0.041, outperforming aEFW combined with diabetes (AUC = 0.745 ± 0.044, P = 1e-16 ). The following risk modifiers had a positive beta that was > 0.02, i.e. they increased the risk of ShD: aEFW (beta = 0.164), pregestational diabetes (beta = 0.047), prior ShD (beta = 0.04), female fetal sex (beta = 0.04) and adjusted abdominal circumference (beta = 0.03). The following risk modifiers had a negative beta that was

To assess the accuracy of different sonographic estimated fetal weight (EFW) cutoffs, and combinations of EFW and biometric measurements for predicting small for gestational age (SGA) in fetal gastroschisis.Gastroschisis cases from two centers were included. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated for different EFW cutoffs, as well as EFW and biometric measurement combinations.Seventy gastroschisis cases were analyzed. An EFW10% had 94% sensitivity, 43% specificity, 33% PPV and 96% NPV for SGA at delivery. Using an EFW cutoff of5% improved the specificity to 63% and PPV to 41%, but decreased the sensitivity to 88%. Combining an abdominal circumference (AC) or femur length (FL) z-score less than -2 with the total EFW improved the specificity and PPV but decreased the sensitivity.A combination of a small AC or FL along with EFW increases the specificity and PPV, but decreases the sensitivity of predicting SGA.

Objective To assess frequency of very low birth weight (VLBW) births at non-level III hospitals. Study design Retrospective cohort study using linked California birth certificate and discharge data of 2008 to 2010 for deliveries of singleton or first-born infant of multiple gestations with birth weight 400 to 1500 g. Delivery rates by neonatal level of care were obtained. Risk of delivery at non-level III centers was estimated in univariable and multivariable models. Results Of the 1 508 143 births, 13 919 (9.2%) were VLBW; birth rate at non-level III centers was 14.9% (8.4% in level I and 6.5% in level II). Median rate of VLBW births was 0.3% (range 0 to 4.7%) annually at level I and 0.5% (range 0 to 1.6%) at level II hospitals. Antepartum stay for >24 h occurred in 14.0% and 26.9% of VLBW births in level I and level II hospitals, respectively. Conclusion Further improvement is possible in reducing VLBW infant delivery at suboptimal sites, given the window of opportunity for many patients.

This work presents the workflow for generating single cell transcriptomes derived from primary human uterine and cervical tissue obtained during planned cesarean hysterectomies. In total, a catalogue of 310 single cell transcriptomes are obtained, cell types present in these biopsies are inferred, and specific genes defining each of the cellular types present in the tissue are identified. Further validation of the inferred cell identity is also demonstrated via meta-analysis of independent repositories in literature generated by bulk sequenced data of fluorescence-activated cell sorting sorted cells.

Objective We compared the prevalence of and risk factors for stillbirth and live birth at periviable gestational age (20–25 weeks). Study Design This is a cohort study of 2.5 million singleton births in California from 2007 to 2011. We estimated racial–ethnic prevalence ratios and used multivariable logistic regression for risk factor comparisons. Results In this study, 42% of deliveries at 20 to 25 weeks' gestation were stillbirths, and 22% were live births who died within 24 hours. The prevalence of delivery at periviable gestation was 3.4 per 1,000 deliveries among whites, 10.9 for blacks, 3.5 for Asians, and 4.4 for Hispanics. Nonwhite race–ethnicity, lower education, uninsured status, being U.S. born, older age, obesity, smoking, pre-pregnancy hypertension, nulliparity, interpregnancy interval, and prior preterm birth or stillbirth were all associated with increased risk of both stillbirth and live birth at 20 to 25 weeks' gestation, compared with delivery of a live birth at 37 to 41 weeks. Conclusion Inclusion of stillbirths and live births in studies of deliveries at periviable gestations is important.

Purpose of review To examine updates in fetal spina bifida surgical repair, as well as promising results emerging from translational medicine. Recent findings Although the Management of Myelomeningocele Study sponsored by the National Institutes of Health helped establish the neonatal benefits of prenatal spina bifida repair via uterine hysterotomy, also known as 'open' fetal surgery, fetoscopic approaches may yield better maternal and obstetric outcomes. Summary Spina bifida is a severe congenital malformation associated with significant neonatal and childhood morbidity and mortality. Although 'open' fetal spina bifida repair has become the standard prenatal surgical approach due to proven neonatal benefit, this approach is associated with significant maternal and obstetric risks. Recent developments from multidisciplinary clinical and translational research have highlighted the potential for novel fetoscopic surgical approaches to decrease maternal morbidity and reduce obstetric risks. Moreover, novel stem cell therapies coupled with in-utero medical approaches targeting the pathophysiological pathways associated with spina bifida are likely to make additional significant impact.

To examine associations with morbidly adherent placenta (MAP) among women with placenta previa.Women with MAP (cases) and previa alone (controls) were identified from a cohort of 236,714 singleton pregnancies with both first and second trimester prenatal screening, and live birth and hospital discharge records; pregnancies with aneuploidies and neural tube or abdominal wall defects were excluded. Logistic binomial regression was used to compare cases with controls.In all, 37 cases with MAP and 699 controls with previa alone were included. Risk for MAP was increased among multiparous women with pregnancy-associated plasma protein-A (PAPP-A) ⩾95th percentile (⩾2.63 multiple of the median (MoM); adjusted OR (aOR) 8.7, 95% confidence interval (CI) 2.8 to 27.4), maternal-serum alpha fetoprotein (MS-AFP) ⩾95th percentile (⩾1.79 MoM; aOR 2.8, 95% CI 1.0 to 8.0), and 1 and ⩾2 prior cesarean deliveries (CDs; aORs 4.4, 95% CI 1.5 to 13.6 and 18.4, 95% CI 5.9 to 57.5, respectively).Elevated PAPP-A, elevated MS-AFP and prior CDs are associated with MAP among women with previa.

Purpose of study Patients with neonatal urea cycle defects (UCDs) typically experience severe hyperammonemia during the first days of life, which results in serious neurological injury or death. Long-term prognosis despite optimal pharmacological and dietary therapy is still poor. The combination of intravenous sodium phenylacetate and sodium benzoate (Ammonul®) can eliminate nitrogen waste independent of the urea cycle. We report attempts to improve outcomes for males with severe ornithine transcarbamylase deficiency (OTCD), a severe X-linked condition, via prenatal intravenous administration of Ammonul and arginine to heterozygous carrier females of OTCD during labor. Methods used Two heterozygote OTCD mothers carrying male fetuses with a prenatal diagnosis of OTCD received intravenous Ammonul, arginine and dextrose-containing fluids shortly before birth. Maintenance Ammonul and arginine infusions and high-caloric enteral nutrition were started immediately after birth. Ammonul metabolites were measured in umbilical cord blood and the blood of the newborn immediately after delivery. Serial ammonia and biochemical analyses were performed following delivery. Summary of results Therapeutic concentrations of Ammonul metabolites were detected in umbilical cord and neonatal blood samples. Plasma ammonia and glutamine levels in the postnatal period were within the normal range. Peak ammonia levels in the first 24–48 h were 53 mcmol/l and 62 mcmol/l respectively. The boys did not experience neurological sequelae secondary to hyperammonemia and received liver transplantation at ages 3 months and 5 months. The patients show normal development at ages 7 and 3 years. Conclusion Prenatal treatment of mothers who harbor severe OTCD mutations and carry affected male fetuses with intravenous Ammonul and arginine, followed by immediate institution of maintenance infusions after delivery, results in therapeutic levels of benzoate and phenylacetate in the newborn at delivery and, in conjunction with high-caloric enteral nutrition, prevents acute hyperammonemia and neurological decompensation. Following initial medical management, early liver transplantation may improve developmental outcome.

Objective The objective of this study was to evaluate whether weekly administration of 17 α-hydroxyprogesterone caproate (17-OHPC) increases the number of women who achieve 34 weeks of gestation after preterm premature rupture of membranes (PPROM). Study Design We conducted a multicenter double-blind, randomized controlled trial of 17-OHPC versus placebo among women with PPROM. Women with singleton pregnancy, clinically confirmed PPROM, and without evidence of active infection or major fetal malformation between 240/7 and 320/7 weeks of pregnancy were offered enrollment. Women received weekly injections of 17-OHPC versus placebo until 340/7 weeks of gestation or delivery. The remainder of care was per hospital protocol. The primary outcome was achievement of 34 weeks of gestation. Secondary outcomes included length of latency and maternal and fetal outcomes. Results In this study, 21 women were enrolled. Eleven women received placebo and 10 received 17-OHPC. The study was closed prematurely secondary to poor enrollment. None of the women remained pregnant until 34 weeks of gestation. The median latency periods were 8 and 14.5 days for the placebo and 17-OHPC groups, respectively (p = 0.14). There were no differences in maternal or neonatal outcomes. Conclusion We did not identify any benefit from administration of 17-OHPC in pregnancies complicated by PPROM.

Cesarean delivery is one of the most common surgeries performed in the United States. In 2012, over 1.2 million cesarean deliveries were performed, accounting for 32.8% of all deliveries.1 Cesarean delivery has been implicated as an important explanatory factor for increasing rates of maternal morbidity, which includes venous thromboembolism, shock, and hemorrhage.2 As a consequence, multiple large-scale initiatives have been promoted by leading obstetric figures and organizations to reduce rates of maternal morbidity.3–5 Postoperative length of stay (LOS) after nonobstetric surgery has been identified as an important quality indicator of inpatient care.6–8 LOS after cesarean delivery may also be an important metric for evaluating the quality of peripartum and postpartum obstetric care. Unfortunately, studies investigating risk factors associated with prolonged LOS after a cesarean delivery are lacking. Such data could assist ongoing efforts aimed at reducing maternal morbidity after cesarean delivery and could be useful for evaluating postcesarean LOS as a quality measure related to obstetric practice. The primary aim of this study was to identify risk factors for prolonged postpartum LOS after cesarean delivery. Moreover, we sought to analyze the contribution of potentially modifiable risk factors on prolonged LOS to highlight areas where improvements in perioperative care could be made. We also performed a secondary analysis to identify risk factors for prolonged LOS for the entire delivery hospitalization period including the intrapartum period.

Objective Array comparative genomic hybridization (aCGH) is a molecular cytogenetic technique that is able to detect the presence of copy number variants (CNVs) within the genome. The detection rate of imbalances by aCGH compared to standard karyotyping and 22q11 microdeletion analysis by fluorescence in-situ hybridization (FISH), in the setting of prenatally-diagnosed cardiac malformations, has been reported in several studies. The objective of our study was to perform a systematic literature review and meta-analysis to document the additional diagnostic gain of using aCGH in cases of congenital heart disease (CHD) diagnosed by prenatal ultrasound examination, with the aim of assisting clinicians to determine whether aCGH analysis is warranted when an ultrasonographic diagnosis of CHD is made, and to guide counseling in this setting. Methods Articles in PubMed, EMBASE and Web of Science databases from January 2007 to September 2014 describing CNVs in prenatal cases of CHD were included. Search terms were: ‘array comparative genomic hybridization’, ‘copy number variants’ and ‘fetal congenital heart defects’. Articles regarding karyotyping or 22q11 deletion only were excluded. Results Thirteen publications (including 1131 cases of CHD) met the inclusion criteria for the analysis. Meta-analysis indicated an incremental yield of 7.0% (95% CI, 5.3–8.6%) for the detection of CNVs using aCGH, excluding aneuploidy and 22q11 microdeletion cases. Subgroup results showed a 3.4% (95% CI, 0.3–6.6%) incremental yield in isolated CHD cases, and 9.3% (95% CI, 6.6–12%) when extracardiac malformations were present. Overall, an incremental yield of 12% (95% CI, 7.6–16%) was found when 22q11 deletion cases were included. There was an additional yield of 3.4% (95% CI, 2.1–4.6%) for detecting variants of unknown significance (VOUS). Conclusions In this review we provide an overview of published data and discuss the benefits and limitations of using aCGH. If karyotyping and 22q11 microdeletion analysis by FISH are normal, using aCGH has additional value, detecting pathogenic CNVs in 7.0% of prenatally diagnosed CHD, with a 3.4% additional yield of detecting VOUS. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Caring for pregnant women with complex underlying medical conditions invariably leads to encounters with rather rare disorders. Such care is usually informed by limited published data, usually from single case reports or very small case series. This is the case when one seeks guidance regarding counseling and management of pregnant women with hormone secreting adrenal tumors. This article is protected by copyright. All rights reserved.

Multicystic dysplastic kidney (MCDK) is one of the most common anomalies detected by prenatal ultrasound. Our objective was to identify factors associated with severe adverse neonatal outcomes of prenatally diagnosed MCDK STUDY DESIGN: A retrospective review of prenatally diagnosed MCDK (1 January 2009 to 30 December 2014) from a single academic center was conducted. The primary outcome was death or need for dialysis among live-born infants. Associations between prenatal characteristics and outcome were analyzed by Fisher's exact test and Mann-Whitney test.A total of 53 cases of prenatally suspected MCDK were included, of which 46 cases were live-born and confirmed postnatally (38 survivors, 8 non-survivors). Prenatally diagnosed extrarenal anomalies, bilateral MCDK, contralateral renal anomalies, and anhydramnios were significantly associated with death or need for dialysis (all p 0.0001).Prenatally identified findings are associated with adverse neonatal outcome, and can guide counseling and management planning. In the absence of significant associated findings, prenatally diagnosed unilateral MCDK has a benign neonatal course.

Background Early detection of maladaptive processes underlying pregnancy-related pathologies is desirable because it will enable targeted interventions ahead of clinical manifestations. The quantitative analysis of plasma proteins features prominently among molecular approaches used to detect deviations from normal pregnancy. However, derivation of proteomic signatures sufficiently predictive of pregnancy-related outcomes has been challenging. An important obstacle hindering such efforts were limitations in assay technology, which prevented the broad examination of the plasma proteome. Objective The recent availability of a highly multiplexed platform affording the simultaneous measurement of 1310 plasma proteins opens the door for a more explorative approach. The major aim of this study was to examine whether analysis of plasma collected during gestation of term pregnancy would allow identifying a set of proteins that tightly track gestational age. Establishing precisely timed plasma proteomic changes during term pregnancy is a critical step in identifying deviations from regular patterns caused by fetal and maternal maladaptations. A second aim was to gain insight into functional attributes of identified proteins and link such attributes to relevant immunological changes. Study Design Pregnant women participated in this longitudinal study. In 2 subsequent sets of 21 (training cohort) and 10 (validation cohort) women, specific blood specimens were collected during the first (7–14 weeks), second (15–20 weeks), and third (24–32 weeks) trimesters and 6 weeks postpartum for analysis with a highly multiplexed aptamer-based platform. An elastic net algorithm was applied to infer a proteomic model predicting gestational age. A bootstrapping procedure and piecewise regression analysis was used to extract the minimum number of proteins required for predicting gestational age without compromising predictive power. Gene ontology analysis was applied to infer enrichment of molecular functions among proteins included in the proteomic model. Changes in abundance of proteins with such functions were linked to immune features predictive of gestational age at the time of sampling in pregnancies delivering at term. Results An independently validated model consisting of 74 proteins strongly predicted gestational age (P = 3.8 × 10–14, R = 0.97). The model could be reduced to 8 proteins without losing its predictive power (P = 1.7 × 10–3, R = 0.91). The 3 top ranked proteins were glypican 3, chorionic somatomammotropin hormone, and granulins. Proteins activating the Janus kinase and signal transducer and activator of transcription pathway were enriched in the proteomic model, chorionic somatomammotropin hormone being the top-ranked protein. Abundance of chorionic somatomammotropin hormone strongly correlated with signal transducer and activator of transcription-5 signaling activity in CD4 T cells, the endogenous cell-signaling event most predictive of gestational age. Conclusion Results indicate that precisely timed changes in the plasma proteome during term pregnancy mirror a proteomic clock. Importantly, the combined use of several plasma proteins was required for accurate prediction. The exciting promise of such a clock is that deviations from its regular chronological profile may assist in the early diagnoses of pregnancy-related pathologies, and point to underlying pathophysiology. Functional analysis of the proteomic model generated the novel hypothesis that chrionic somatomammotropin hormone may critically regulate T-cell function during pregnancy.

Blood circulates throughout the human body and contains molecules drawn from virtually every tissue, including the microbes and viruses which colonize the body. Through massive shotgun sequencing of circulating cell-free DNA from the blood, we identified hundreds of new bacteria and viruses which represent previously unidentified members of the human microbiome. Analyzing cumulative sequence data from 1,351 blood samples collected from 188 patients enabled us to assemble 7,190 contiguous regions (contigs) larger than 1 kbp, of which 3,761 are novel with little or no sequence homology in any existing databases. The vast majority of these novel contigs possess coding sequences, and we have validated their existence both by finding their presence in independent experiments and by performing direct PCR amplification. When their nearest neighbors are located in the tree of life, many of the organisms represent entirely novel taxa, showing that microbial diversity within the human body is substantially broader than previously appreciated.

To compare the efficacy of oral misoprostol to vaginal dinoprostone for labor induction in nulliparous women.Admissions for labor induction from January 2008 to December 2010 were reviewed. Patients receiving oral misoprostol were compared with those receiving vaginal dinoprostone. The primary outcome was time from induction agent administration to vaginal delivery. Secondary outcomes included vaginal delivery within 24 h, mode of delivery and maternal and fetal outcomes.A total of 680 women were included: 483 (71%) received vaginal dinoprostone and 197 (29%) received oral misoprostol. Women who received oral misoprostol had a shorter interval to vaginal delivery (27.2 vs 21.9 h, P0.0001) and were more likely to deliver vaginally in24 h (47% vs 64%, P=0.001). There was no increase in the rate of cesarean delivery or adverse maternal or neonatal outcomes.Labor induction with oral misoprostol resulted in shorter time to vaginal delivery without increased adverse outcomes in nulliparous women.

Objective: Approximately 10% of US couples are inter-racial/ethnic. Substantial variation in preterm birth (PTB) rates is seen when stratified by race/ethnicity, although most studies focused solely on maternal racial/ethnic demographics. Our aims were to analyze the contribution of paternal in addition to maternal race/ethnicity, and to evaluate risk of spontaneous PTB for previously understudied inter-racial/ethnic couples. Methods: California singleton live births from 2007 to 2010 were included. Race/ethnicity was determined based on self-report, obtained from birth certificates and defined as African American (AA), Hispanic, Asian, and White. Logistic regression was used to estimate odds ratios of spontaneous PTB at 20–23, 24–31, 32–36 and Results: Among 1,664,939 live births, 13% (n = 216,417) were born to inter-racial/ethnic couples. Compared to White–White couples, risk for spontaneous PTB was increased across all inter-racial/ethnic couples with a non-White mother, except when the father was Asian. Patterns of association were similar after stratification by previous PTB, hypertension and diabetes. Paternal race/ethnicity was also a significant risk factor for PTB. Conclusions: Increased risks for spontaneous PTB were seen in most inter-racial/ethnic couple groupings. In addition to maternal race/ethnicity, paternal race/ethnicity was a significant risk factor in many inter-racial/ethnic couplings. Identifying such different risk profiles based on both maternal and paternal race/ethnicity may offer new lines of research inquiry for the underlying etiologies of PTB.

To investigate the association between small-for-gestational age (SGA) and neurocognitive impairment at 2 years of corrected age among infants born at preterm gestational ages.A secondary analysis of a prospectively conducted NICHD/Maternal-Fetal Medicine Units BEAM trial. Non-anomalous pregnancies delivered before 37 weeks of gestation were included in the analysis. Neurocognitive outcomes at 2 years of corrected age were compared between infants who were SGA (10% for gestational age) and those appropriately grown (AGA). The primary outcome was a severe or moderate neurocognitive impairment at 2 years of corrected age among survivors, defined as either mental (MDI) or psychomotor (PDI) developmental index score70 for severe and85 for moderate impairment.Of 2299 preterm neonates 67 (3%) were SGA. SGA infants were more often twin pregnancies (31% vs 17%, P=0.003) and delivered more often by cesarean section (63% vs 40%, P0.001) at similar gestational ages (30.0±2.6 vs 29.5±2.8 weeks, P=0.11). At 2 years of corrected age, SGA and AGA survivors had similar rates of neurocognitive impairment (MDI70: 18% vs 18%, P=1.0; MDI85: 44% vs 46%, P=0.96; PDI70: 20% vs 15%, P=0.51; PDI85: 40% vs 34%, P=0.48).In this cohort, SGA at preterm gestational ages was associated with similar rates of neurocognitive impairment at two years of corrected age among surviving infants.

Background Limited understanding exists of risk factors for PPH post-vaginal delivery. Objective To identify risk factors for PPH post-vaginal delivery within a contemporary obstetric cohort. Study Design Retrospective case-control study. PPH was classified by an estimated blood loss ≥ 500 mL. Risk factors for PPH were identified using univariable and multivariable logistic regression. We secondarily investigated maternal outcomes and medical and surgical interventions for PPH management. Results The study cohort comprised 159 cases and 318 controls. Compared to a second stage duration

The objective of this article is to evaluate the utility of fetal lung mass imaging for predicting neonatal respiratory distress.Pregnancies with fetal lung masses between 2009 and 2014 at a single center were analyzed. Neonatal respiratory distress was defined as intubation and mechanical ventilation at birth, surgery before discharge, or extracorporeal membrane oxygenation (ECMO). The predictive utility of the initial as well as maximal lung mass volume and congenital pulmonary airway malformation volume ratio by ultrasound (US) and magnetic resonance imaging (MRI) was analyzed.Forty-seven fetal lung mass cases were included; of those, eight (17%) had respiratory distress. The initial US was performed at similar gestational ages in pregnancies with and without respiratory distress (26.4 ± 5.6 vs 22.3 ± 3 weeks, p = 0.09); however, those with respiratory distress had higher congenital volume ratio at that time (1.0 vs 0.3, p = 0.01). The strongest predictors of respiratory distress were maximal volume24.0 cmUltrasound and MRI parameters can predict neonatal respiratory distress, even when obtained before 24 weeks. Third trimester parameters demonstrated the best positive predictive value. © 2017 John WileySons, Ltd.

Objectives To determine the trends of cesarean delivery rate among twin pregnancies from 2006 to 2013. Study design This is a population-based, cross-sectional analysis of twin live births from United State birth data files of the National Center for Health Statistics for calendar years 2006 through 2013. We stratified the population based on the gestational age groups, maternal race/ethnicity, advanced maternal age (AMA) which was defined by age more than 35 years and within the standard birth weight groups (group 1: birth weight 500–1499 g, group 2: birth weight 1500–2499 g and group 3: birth weight >2500 g). We also analyzed the effect of different risk factors for cesarean delivery in twins. Results There were 1,079,102 infants born of twin gestations in the U.S. from 2006 to 2013, representing a small but significant increase in the proportion of twin births among all births (3.2% in 2006 versus 3.4% in 2013). The rate of cesarean delivery in twin live births peaked at 75.3% in 2009, and was significantly lower (74.8%) in 2013. The rate of the twin live birth with the breech presentation increased steadily from 26.3% in 2006 to 29.1% in 2013. For the fetus of the twin pregnancy presented as breech, the cesarean delivery rate peaked at 92.2% in 2010, falling slightly but significantly in the ensuing 3 years. The results demonstrated that the decrease in cesarean delivery rate was due to fewer cesareans in non-Hispanic white patients; all other ethnic subgroups showed increasing rates of cesarean delivery throughout the study. Gestational diabetes, gestational hypertension, previous cesarean delivery and breech presentation were all significant risk factors for cesarean delivery during the entire study period. Induction of labor and premature rupture of the membranes were associated with lower rates of cesarean delivery in twins. Conclusion The recent decrease in the cesarean delivery rate in twin gestation appears to be largely attributable to a decline in cesarean among pregnancies complicated by breech presentation in non-Hispanic white women, and may reflect a health care disparity that deserves further research.

The vast majority of prenatal genetic testing requires invasive sampling. However, this poses a risk to the fetus, so one must make a decision that weighs the desire for genetic information against the risk of an adverse outcome due to hazards of the testing process. These issues are not required to be coupled, and it would be desirable to discover genetic information about the fetus without incurring a health risk. Here we demonstrate that it is possible to non-invasively sequence the entire prenatal genome. Our results show that molecular counting of parental haplotypes in maternal plasma by shotgun sequencing of maternal plasma DNA allows the inherited fetal genome to be deciphered non-invasively. We also applied the counting principle directly to each allele in the fetal exome by performing exome capture on maternal plasma DNA before shotgun sequencing. This approach enables non-invasive exome screening of clinically relevant and deleterious alleles that were paternally inherited or had arisen as de novo germline mutations, and complements the haplotype counting approach to provide a comprehensive view of the fetal genome. Non-invasive determination of the fetal genome may ultimately facilitate the diagnosis of all inherited and de novo genetic disease.

OBJECTIVE: To estimate the effect of preterm premature rupture of membranes (PROM) on neonatal mortality. METHODS: A cross-sectional study using a state perinatal database (California Perinatal Quality Care Collaborative) was performed. Prenatal data, including ruptured membranes, corticosteroid administration, maternal age, maternal race, maternal hypertension, mode of delivery, and prenatal care, were recorded. Mortality rates were compared for neonates born between 24 and 34 weeks of gestation without preterm PROM to those with recent (less than 18 hours before delivery) and prolonged (more than 18 hours before delivery) preterm PROM. Neonatal sepsis rates were also examined. RESULTS: Neonates born between 24 0/7 and 34 0/7 weeks of gestation from 127 California neonatal intensive care units between 2005 and 2007 were included (N=17,501). When analyzed by 2-week gestational age groups, there were no differences in mortality rates between those born with and without membrane rupture before delivery. The presence of prolonged preterm PROM was associated with decreased mortality at 24 to 26 weeks of gestation (18% compared with 31% for recent preterm PROM; odds ratio [OR] 1.79; confidence interval [CI] 1.25–2.56) but increased mortality at 28 to 30 weeks of gestation (4% compared with 3% for recent preterm PROM; OR 0.44; CI 0.22, 0.88) when adjusted for possible confounding factors. Sepsis rates did not differ between those with recent or prolonged preterm PROM at any gestational age. CONCLUSION: The presence of membrane rupture before delivery was not associated with increased neonatal mortality in any gestational age group. The effects of a prolonged latency period were not consistent across gestational ages. LEVEL OF EVIDENCE: III

Approximately half of small for gestational age (SGA) cases are due to maternal or fetal pathology, and may result in significant neonatal morbidity and mortality. The estimated fetal weight (EFW) measurement is the cornerstone of ultrasonographic findings when diagnosing and managing SGA pregnancies. Our objective was to determine the ultrasound accuracy of EFW in SGA pregnancies.A retrospective chart review was performed of all pregnancies complicated by SGA from a single institution (Stanford University) over a 2-year-period (2004-2006). SGA was defined as EFWor = 10%. 98 neonates whose last ultrasound for EFW occurred within 7 days of delivery were included in the study. The absolute differences between the EFW and birthweight (BW) were analyzed, and the absolute percent errors were calculated as (EFW - BW)/BW x 100. The mean absolute differences and mean absolute percent errors were analyzed across all gestational ages (GA) and EFWs using one-way analysis of variance.The mean absolute percent error for the entire cohort was 8.7% (+/-6.3%). There was no statistically significant difference in the mean absolute percent error across all GAs (32 weeks, 32-36 weeks,36 weeks), and EFWs (1500 g, 1500-2000 g,2000 g).Ultrasound measurement of EFW in SGA pregnancies is consistent across all GAs and EFW measurements.

Pharmacogenomics, the study of specific genetic variations and their effect on drug response, will likely give rise to many applications in maternal–fetal and neonatal medicine; yet, an understanding of these applications in the field of obstetrics and gynecology and neonatal pediatrics is not widespread. This review describes the underpinnings of the field of pharmacogenomics and summarizes the current pharmacogenomic inquiries in relation to maternal–fetal medicine—including studies on various fetal and neonatal genetic cytochrome P450 (CYP) enzyme variants and their role in drug toxicities (for example, codeine metabolism, sepsis and selective serotonin reuptake inhibitor (SSRI) toxicity). Potential future directions, including alternative drug classification, improvements in drug efficacy and non-invasive pharmacogenomic testing, will also be explored.

We directly sequenced cell-free DNA with high-throughput shotgun sequencing technology from plasma of pregnant women, obtaining, on average, 5 million sequence tags per patient sample. This enabled us to measure the over- and underrepresentation of chromosomes from an aneuploid fetus. The sequencing approach is polymorphism-independent and therefore universally applicable for the noninvasive detection of fetal aneuploidy. Using this method, we successfully identified all nine cases of trisomy 21 (Down syndrome), two cases of trisomy 18 (Edward syndrome), and one case of trisomy 13 (Patau syndrome) in a cohort of 18 normal and aneuploid pregnancies; trisomy was detected at gestational ages as early as the 14th week. Direct sequencing also allowed us to study the characteristics of cell-free plasma DNA, and we found evidence that this DNA is enriched for sequences from nucleosomes.

Racial and ethnic disparities have been identified in the provision of neuraxial labor analgesia. These disparities may exist in other key aspects of obstetric anesthesia care. We sought to determine whether racial/ethnic disparities exist in mode of anesthesia for cesarean delivery (CD).Women who underwent CD between 1999 and 2002 at 19 different obstetric centers in the United States were identified from the Maternal-Fetal Medicine Units Network Cesarean Registry. Race/ethnicity was categorized as: Caucasian, African American, Hispanic, and Non-Hispanic Others (NHOs). Mode of anesthesia was classified as neuraxial anesthesia (spinal, epidural, or combined spinal-epidural anesthesia) or general anesthesia. To account for obstetric and non-obstetric covariates that may have influenced mode of anesthesia, multiple logistic regression analyses were performed by using sequential sets of covariates.The study cohort comprised 50,974 women who underwent CD. Rates of general anesthesia among racial/ethnic groups were as follows: 5.2% for Caucasians, 11.3% for African Americans, 5.8% for Hispanics, and 6.6% for NHOs. After adjustment for obstetric and non-obstetric covariates, African Americans had the highest odds of receiving general anesthesia compared with Caucasians (adjusted odds ratio [aOR] = 1.7; 95% confidence interval [CI], 1.5-1.8; P0.001). The odds of receiving general anesthesia were also higher among Hispanics (aOR = 1.1; 95% CI, 1.0-1.3; P = 0.02) and NHOs (aOR = 1.2; 95% CI, 1.0-1.4; P = 0.03) compared with Caucasians, respectively. In our sensitivity analysis, we reconstructed the models after excluding women who underwent neuraxial anesthesia before general anesthesia. The adjusted odds of receiving general anesthesia were similar to those in the main analysis: African Americans (aOR = 1.7; 95% CI, 1.5-1.9; P0.001); Hispanics (aOR = 1.2; 95% CI, 1.1-1.4; P = 0.006); and NHOs (aOR = 1.2; 95% CI, 1.0-1.5; P = 0.05).Based on data from the Cesarean Registry, African American women had the highest odds of undergoing general anesthesia for CD compared with Caucasian women. It is uncertain whether this disparity exists in current obstetric practice.

Objective To examine whether time of delivery influences the risk of neonatal morbidity among women with singleton pregnancies. Study Design Secondary analysis of data from the Maternal Fetal Medicine Units Network Factor V Leiden Mutation study. We categorized time of delivery as day (07:00–16:59), evening (17:00–23:59), and overnight (midnight-06:59). Severe neonatal morbidity was defined by at least one of the following: respiratory distress syndrome, transient tachypnea of the newborn, sepsis, seizures, neonatal intensive care admission, or a 5-minute APGAR ≤3. We calculated frequencies of severe neonatal morbidity by time of delivery. Multivariate analysis was performed to determine whether time of delivery was independently associated with severe neonatal morbidity. Results Among 4,087 women, 1,917 (46.9%) delivered during the day, 1,140 (27.9%) delivered in the evening, and 1,030 (25.2%) delivered overnight. We observed no significant differences in the rates of neonatal morbidity between delivery time periods (day: 12.3%; evening: 12.8%; overnight: 12.6%; p = 0.9). No significant association was observed between time of delivery and neonatal morbidity after adjustment for maternal, obstetric, and peripartum factors. Conclusion Our findings suggest that time of delivery is not associated with severe neonatal morbidity.