High-throughput allele-specific expression across 250 environmental conditions

Gene-by-environment (GxE) interactions determine common disease risk factors and biomedically relevant complex traits. However, quantifying how the environment modulates genetic effects on human quantitative phenotypes presents unique challenges. Environmental covariates are complex and difficult to measure and control at the organismal level, as found in GWAS and epidemiological studies. An alternative approach focuses on the cellular environment using in vitro treatments as a proxy for the organismal environment. These cellular environments simplify the organism-level environmental exposures to provide a tractable influence on subcellular phenotypes, such as gene expression. Expression quantitative trait loci (eQTL) mapping studies identified GxE interactions in response to drug treatment and pathogen exposure. However, eQTL mapping approaches are infeasible for large-scale analysis of multiple cellular environments. Recently, allele-specific expression (ASE) analysis emerged as a powerful tool to identify GxE interactions in gene expression patterns by exploiting naturally occurring environmental exposures. Here we characterized genetic effects on the transcriptional response to 50 treatments in five cell types. We discovered 1455 genes with ASE (FDR \u3c 10%) and 215 genes with GxE interactions. We demonstrated a major role for GxE interactions in complex traits. Genes with a transcriptional response to environmental perturbations showed sevenfold higher odds of being found in GWAS. Additionally, 105 genes that indicated GxE interactions (49%) were identified by GWAS as associated with complex traits. Examples include GIPR–caffeine interaction and obesity and include LAMP3–selenium interaction and Parkinson disease. Our results demonstrate that comprehensive catalogs of GxE interactions are indispensable to thoroughly annotate genes and bridge epidemiological and genome-wide association studies

Risk of Uterine Rupture and Placenta Accreta With Prior Uterine Surgery Outside of the Lower Segment

Objective—Women with a prior myomectomy or prior classical cesarean delivery are often delivered early by cesarean due to concern for uterine rupture. Although theoretically at increased risk for placenta accreta, this risk has not been well quantified. Our objective was to estimate and compare the risks of uterine rupture and placenta accreta in women with prior uterine surgery. Methods—Women with prior myomectomy or prior classical cesarean delivery were compared to women with a prior low transverse cesarean to estimate rates of both uterine rupture and placenta accreta. Results—One hundred seventy-six women with a prior myomectomy, 455 with a prior classical cesarean delivery, and 13,273 women with a prior low transverse cesarean were evaluated. Mean gestational age at delivery differed by group (p0.99) or in the prior classical cesarean delivery group (0.88%, p=0.13). Placenta accreta occurred in 0% (95% CI 0-1.98%) of prior myomectomy compared with 0.19% in the low transverse cesarean group (p>0.99) and 0.88% in the prior classical cesarean delivery group (p=0.01 relative to low transverse cesarean). The adjusted OR for the prior classical cesarean delivery group (relative to low transverse cesarean) was 3.23 (1.11-9.39) for uterine rupture and 2.09 (0.69-6.33) for accreta. The frequency of accreta for those with previa was 11.1% for the prior classical cesarean delivery and 13.6% for low transverse cesarean groups (p>0.99=1.0). Conclusion—A prior myomectomy is not associated with higher risks of either uterine rupture or placenta accreta. The absolute risks of uterine rupture and accreta after prior myomectomy are low

Association of Recorded Estimated Fetal Weight and Cesarean Delivery in Attempted Vaginal Delivery at Term:

To evaluate the association between documentation of estimated fetal weight, and its value, with cesarean delivery

Relationship Between Excessive Gestational Weight Gain and Neonatal Adiposity in Women With Mild Gestational Diabetes Mellitus:

To evaluate the relationships between excessive gestational weight gain, neonatal adiposity, and adverse obstetric outcomes in women with mild gestational diabetes mellitus (GDM)

Prediction of Spontaneous Preterm Birth Among Nulliparous Women With a Short Cervix

To evaluate whether demographic and sonographic factors associated with spontaneous preterm birth (sPTB) among nulliparous women with a cervical length (CL) < 30 mm could be combined into an accurate prediction model for sPTB

Is There a Threshold Oral Glucose Tolerance Test Value for Predicting Adverse Pregnancy Outcome?

To determine whether there is a threshold 3-hour OGTT value associated with accelerated risk of adverse pregnancy outcomes

Association of Cervical Effacement With the Rate of Cervical Change in Labor Among Nulliparous Women

OBJECTIVE: To assess the association of cervical effacement with the rate of intrapartum cervical change among nulliparous women. METHODS: We conducted a secondary analysis of a prospective trial of intrapartum fetal pulse oximetry. For women who had vaginal deliveries, interval-censored regression was used to estimate the time to dilate at 1-cm intervals. For each given centimeter of progressive cervical dilation, women were divided into those who had achieved 100% cervical effacement and those who had not. The analysis was performed separately for women in spontaneous labor and those who were given oxytocin. RESULTS: A total of 3,902 women were included in this analysis, 1,466 (38%) who underwent labor induction, 1,948 (50%) who underwent labor augmentation (combined for the analysis), and 488 (13%) who labored spontaneously. For women in spontaneous labor, the time to dilate 1 cm was shorter for those who were 100% effaced starting at 4 cm of cervical dilation (P=.01 to <.001). For women who received oxytocin, the time to dilate 1 cm was shorter for those who were 100% effaced throughout labor (P<.001). CONCLUSION: The rate of cervical dilation among nulliparous women is associated with not only the degree of cervical dilation, but also with cervical effacement. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00098709

Carpenter-Coustan Compared With National Diabetes Data Group Criteria for Diagnosing Gestational Diabetes

Use of Carpenter-Coustan compared to National Diabetes Data Group (NDDG) criteria increases the number of women diagnosed with GDM by 30-50%, but whether treatment of this milder GDM reduces adverse outcomes is unknown. We explored the effects of the diagnostic criteria used on the benefits of GDM treatment

Haptoglobin Phenotype, Preeclampsia Risk and the Efficacy of Vitamin C and E Supplementation to Prevent Preeclampsia in a Racially Diverse Population

Haptoglobin's (Hp) antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH). This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393) and a case-control cohort (703 cases, 1,406 controls). The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01) in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia

The Obstetric and Neonatal Implications of a Low Value on the 50-g Glucose Screening Test

To assess the relationship between a low 50-g 1-hour glucose loading test (GLT) and maternal and neonatal outcomes in women without diabetes