Second-trimester growth velocities in twin and singleton pregnancies.

OBJECTIVE: Previous small studies used individualized growth assessment (IGA) to characterize prenatal growth velocities of singletons and twins. We aimed to compare second-trimester growth velocities of individual anatomical parameters between monochorionic diamniotic (MCDA) twins, dichorionic diamniotic (DCDA) twins and singleton fetuses in a larger study. METHODS: This was a study of a novel cohort of 222 MCDA twins and previously published cohorts of 40 DCDA twins and 118 singletons with serial ultrasound data. Fetal biometric measurements of biparietal diameter, head circumference, abdominal circumference and femur diaphysis length from prenatal ultrasound examinations were used to calculate second-trimester growth velocities using direct calculation or linear regression analysis. Linear fit was assessed based on the coefficient of determination (R2 ). Mean growth velocities and variances were compared among the three groups. RESULTS: The majority of cases underwent three second-trimester ultrasound examinations with fetal biometry available. All fetuses had linear growth, with R2 > 99% for all parameters. Only 1-2% of all MCDA and DCDA anatomical parameters had abnormal growth velocity scores outside the 95% reference range for singletons. There were no significant differences in mean growth velocity for any parameter between MCDA twins and singletons. Femur diaphysis length growth velocity was significantly lower in DCDA twins than in both MCDA twins and singletons. There were no other significant differences among the groups. CONCLUSIONS: Expanding on prior work using IGA, we found that second-trimester growth velocity of the four major anatomical parameters overall was similar between twins and singletons and between MCDA and DCDA twins, supporting the use of singleton-derived growth standards for IGA in twins. Twin growth potential appears to be similar to that of singletons in the second trimester, suggesting that subsequent growth divergence may be due to third-trimester physiological or pathological changes in twin pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Development and validation of a machine-learning model for prediction of shoulder dystocia.

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 < -0.02, i.e. they were protective of ShD: adjusted biparietal diameter (beta = -0.08) and maternal height (beta = -0.03). In the validation cohort, the model outperformed aEFW combined with diabetes (AUC = 0.866 vs 0.784, P = 0.00007). Additionally, in the validation cohort, among the subgroup of 273 women carrying a fetus with aEFW ≥ 4000 g, the aEFW had no predictive power (AUC = 0.548), and the model performed significantly better (0.775, P = 0.0002). A risk-score threshold of 0.5 stratified 42.9% of deliveries to the high-risk group, which included 90.9% of ShD cases and all cases accompanied by maternal or newborn complications. A more specific threshold of 0.7 stratified only 27.5% of the deliveries to the high-risk group, which included 63.6% of ShD cases and all those accompanied by newborn complications. CONCLUSION: We developed a ML model for prediction of ShD and, in a different cohort, externally validated its performance. The model predicted ShD better than did estimated fetal weight either alone or combined with maternal diabetes, and was able to stratify the risk of ShD and neonatal injury in the context of suspected macrosomia. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Maternal characteristics and mid-pregnancy serum biomarkers as risk factors for subtypes of preterm birth.

OBJECTIVE: To examine the relationship between maternal characteristics, serum biomarkers and preterm birth (PTB) by spontaneous and medically indicated subtypes. DESIGN: Population-based cohort. SETTING: California, United States of America. POPULATION: From a total population of 1 004 039 live singleton births in 2009 and 2010, 841 665 pregnancies with linked birth certificate and hospital discharge records were included. METHODS: Characteristics were compared for term and preterm deliveries by PTB subtype using logistic regression and odds ratios adjusted for maternal characteristics and obstetric factors present in final stepwise models and 95% confidence intervals. First-trimester and second-trimester serum marker levels were analysed in a subset of 125 202 pregnancies with available first-trimester and second-trimester serum biomarker results. MAIN OUTCOME MEASURE: PTB by subtype. RESULTS: In fully adjusted models, ten characteristics and three serum biomarkers were associated with increased risk in each PTB subtype (Black race/ethnicity, pre-existing hypertension with and without pre-eclampsia, gestational hypertension with pre-eclampsia, pre-existing diabetes, anaemia, previous PTB, one or two or more previous caesarean section(s), interpregnancy interval ≥ 60 months, low first-trimester pregnancy-associated plasma protein A, high second-trimester α-fetoprotein, and high second-trimester dimeric inhibin A). These risks occurred in 51.6-86.2% of all pregnancies ending in PTB depending on subtype. The highest risk observed was for medically indicated PTB <32 weeks in women with pre-existing hypertension and pre-eclampsia (adjusted odds ratio 89.7, 95% CI 27.3-111.2). CONCLUSIONS: Our findings suggest a shared aetiology across PTB subtypes. These commonalities point to targets for further study and exploration of risk reduction strategies. TWEETABLE ABSTRACT: Findings suggest a shared aetiology across preterm birth subtypes. Patterns may inform risk reduction efforts.

Array comparative genomic hybridization and fetal congenital heart defects: a systematic review and meta-analysis.

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.

Genomic microarray in fetuses with increased nuchal translucency and normal karyotype: a systematic review and meta-analysis.

OBJECTIVE: To estimate the incremental yield of detecting copy number variants (CNVs) by genomic microarray over karyotyping in fetuses with increased nuchal translucency (NT) diagnosed by first-trimester ultrasound. METHODS: This was a systematic review conducted in accordance with PRISMA criteria. We searched PubMed, Ovid MEDLINE and Web of Science for studies published between January 2009 and January 2015 that described CNVs in fetuses with increased NT, usually defined as ≥ 3.5 mm, and normal karyotype. Search terms included: fetal or prenatal, nuchal translucency or cystic hygroma or ultrasound anomaly, array comparative genomic hybridization or copy number variants, with related search terms. Risk differences were pooled to estimate the overall and stratified microarray incremental yield using RevMan. Quality assessment of included studies was performed using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2) checklist. RESULTS: Seventeen studies met the inclusion criteria for analysis. Meta-analysis indicated an incremental yield of 5.0% (95% CI, 2.0-8.0%) for the detection of CNVs using microarray when pooling results. Stratified analysis of microarray results demonstrated a 4.0% (95% CI, 2.0-7.0%) incremental yield in cases of isolated NT and 7.0% (95% CI, 2.0-12.0%) when other malformations were present. The most common pathogenic CNVs reported were 22q11.2 deletion, 22q11.2 duplication, 10q26.12q26.3 deletion and 12q21q22 deletion. The pooled prevalence for variants of uncertain significance was 1%. CONCLUSION: The use of genomic microarray provides a 5.0% incremental yield of detecting CNVs in fetuses with increased NT and normal karyotype.

Mode of anaesthesia for preterm Caesarean delivery: secondary analysis from the Maternal-Fetal Medicine Units Network Caesarean Registry.

BACKGROUND: Preterm delivery is often performed by Caesarean section. We investigated modes of anaesthesia and risk factors for general anaesthesia among women undergoing preterm Caesarean delivery. METHODS: Women undergoing Caesarean delivery between 24(+0) and 36(+6) weeks' gestation were identified from a multicentre US registry. The mode of anaesthesia was classified as neuraxial anaesthesia (spinal, epidural, or combined spinal and epidural) or general anaesthesia. Logistic regression was used to identify patient characteristic, obstetric, and peripartum risk factors associated with general anaesthesia. RESULTS: Within the study cohort, 11 539 women had preterm Caesarean delivery; 9510 (82.4%) underwent neuraxial anaesthesia and 2029 (17.6%) general anaesthesia. In our multivariate model, African-American race [adjusted odds ratio (aOR)=1.9; 95% confidence interval (CI)=1.7-2.2], Hispanic ethnicity (aOR=1.5; 95% CI=1.2-1.8), other race (aOR=1.4; 95% CI=1.1-1.9), and haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome or eclampsia (aOR=2.8; 95% CI=2.2-3.5) were independently associated with receiving general anaesthesia for preterm Caesarean delivery. Women with an emergency Caesarean delivery indication had the highest odds for general anaesthesia (aOR=3.5; 95% CI=3.1-3.9). For every 1 week decrease in gestational age at delivery, the adjusted odds of general anaesthesia increased by 13%. CONCLUSIONS: In our study cohort, nearly one in five women received general anaesthesia for preterm Caesarean delivery. Although potential confounding by unmeasured factors cannot be excluded, our findings suggest that early gestational age at delivery, emergent Caesarean delivery indications, hypertensive disease, and non-Caucasian race or ethnicity are associated with general anaesthesia for preterm Caesarean delivery.

Single- versus double-layer hysterotomy closure at primary caesarean delivery and bladder adhesions.

OBJECTIVE: To determine the association between single-layer (one running suture) and double-layer (second layer or imbricating suture) hysterotomy closure at primary caesarean delivery and subsequent adhesion formation. DESIGN: A secondary analysis from a prospective cohort study of women undergoing first repeat caesarean section. SETTING: Department of Obstetrics and Gynecology, Stanford University, Stanford, CA, USA. POPULATION: One hundred and twenty-seven pregnant women undergoing first repeat caesarean section. METHODS: Patient records were reviewed to identify whether primary caesarean hysterotomies were closed with a single or double layer. Data were analysed by Fisher's exact tests and multivariable logistic regression. MAIN OUTCOME MEASURE: Prevalence rate of pelvic and abdominal adhesions. RESULTS: Of the 127 women, primary hysterotomy closure was single layer in 56 and double layer in 71. Single-layer hysterotomy closure was associated with bladder adhesions at the time of repeat caesarean (24% versus 7%, P = 0.01). Single-layer closure was associated in this study with a seven-fold increase in the odds of developing bladder adhesions (odds ratio, 6.96; 95% confidence interval, 1.72-28.1), regardless of other surgical techniques, previous labour, infection and age over 35 years. There was no association between single-layer closure and other pelvic or abdominal adhesions. CONCLUSIONS: Primary single-layer hysterotomy closure may be associated with more frequent bladder adhesions during repeat caesarean deliveries. The severity and clinical implications of these adhesions should be assessed in large prospective trials.

Out-of-hospital births in California 1991-2011.

OBJECTIVE: We investigated the frequencies and characteristics of out-of-hospital births in a 20-year period in California, where 1 of every 7 births in the United States occurs. STUDY DESIGN: Birth certificate records of deliveries in California between 1991 and 2011 were analyzed. Out-of-hospital births were assessed by year, parity, gestational age and maternal race/ethnicity. RESULTS: In the 20-year period there were 10 593,904 deliveries, of which 46 243 occurred out of hospital (0.44%). Out-of-hospital births decreased from 0.54 to 0.38% per year between 1991 and 2004, and increased from 0.41% in 2005 to 0.61% in 2011. In contrast, preterm out-of-hospital births declined from 7.2% in 2006 to 5.0% in 2011. The frequency of vaginal birth after cesarean in the out-of-hospital birth cohort increased from 1.2% (n=19) in 1996 to 4.2% (n=82) in 2011. CONCLUSION: California birth records from a 20-year period show an increase in out-of-hospital births from years 2005 to 2011, following a period of decline from 1991 to 2004.

Association between small-for-gestational age and neurocognitive impairment at two years of corrected age among infants born at preterm gestational ages: a cohort study.

OBJECTIVE: 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. STUDY DESIGN: 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 score <70 for severe and <85 for moderate impairment. RESULTS: 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%, P<0.001) 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 (MDI <70: 18% vs 18%, P=1.0; MDI <85: 44% vs 46%, P=0.96; PDI <70: 20% vs 15%, P=0.51; PDI <85: 40% vs 34%, P=0.48). CONCLUSION: 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.

Postpartum hemorrhage following vaginal delivery: risk factors and maternal outcomes.

OBJECTIVE: Limited understanding of risk factors exists for postpartum hemorrhage (PPH) post-vaginal delivery. The aim of this study was 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 with a second-stage duration <2 h, a second stage⩾3 h was associated with PPH (adjusted odds ratio=2.3; 95% CI=1.2 to 4.6). No other clinical or obstetric variables were identified as independent risk factors for PPH. Among cases, 4% received red blood cells and 1% required intensive care admission. CONCLUSION: Although PPH-related morbidity may be uncommon after vaginal delivery, PPH should be anticipated for women after a second stage ⩾3 h.

Opportunities for maternal transport for delivery of very low birth weight infants.

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.

Utility of third trimester sonographic measurements for predicting SGA in cases of fetal gastroschisis.

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: Seventy gastroschisis cases were analyzed. An EFW<10% had 94% sensitivity, 43% specificity, 33% PPV and 96% NPV for SGA at delivery. Using an EFW cutoff of <5% 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. CONCLUSION: A combination of a small AC or FL along with EFW increases the specificity and PPV, but decreases the sensitivity of predicting SGA.

Maternal serum markers, characteristics and morbidly adherent placenta in women with previa.

OBJECTIVE: To examine associations with morbidly adherent placenta (MAP) among women with placenta previa. STUDY DESIGN: 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. RESULT: 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). CONCLUSION: Elevated PAPP-A, elevated MS-AFP and prior CDs are associated with MAP among women with previa.

Oral misoprostol versus vaginal dinoprostone for labor induction in nulliparous women at term.

OBJECTIVE: To compare the efficacy of oral misoprostol to vaginal dinoprostone for labor induction in nulliparous women. STUDY DESIGN: 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. RESULT: 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, P<0.0001) and were more likely to deliver vaginally in <24 h (47% vs 64%, P=0.001). There was no increase in the rate of cesarean delivery or adverse maternal or neonatal outcomes. CONCLUSION: Labor induction with oral misoprostol resulted in shorter time to vaginal delivery without increased adverse outcomes in nulliparous women.

Utilization of available prenatal screening and diagnosis: effects of the California screen program.

OBJECTIVE: In 2009, the California Genetic Disease Branch introduced an aneuploidy screening program allowing Medi-Cal (state insured) patients access to state-sponsored first-trimester screening. The objective of this study was to assess the effect of greater access to prenatal screening on available resources at a single center. STUDY DESIGN: Data of prenatal screening and diagnostic procedures performed 4 months before the introduction of the program were compared with those of 12 months following the introduction. RESULT: Between December 2008 and March 2010, 7689 women underwent first trimester screening, 1286 underwent amniocentesis and 398 underwent chorionic villus sampling. When a comparison was made between the 4 months before and the 12 months after the program's introduction, a greater number of nuchal translucency (NT) examinations was seen to have been performed (384 per month vs 513 per month, P=0.001). Prenatal diagnostic procedures did not increase, but a greater proportion was performed for positive screen results. CONCLUSION: Introduction of the California screening program was associated with increased NT procedures and fewer invasive procedures for advanced maternal age.

Maternal-fetal and neonatal pharmacogenomics: a review of current literature.

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.