Neonatal Genetic Variation in Steroid Metabolism and Key Respiratory Function Genes and Perinatal Outcomes in Single and Multiple Courses of Corticosteroids

To evaluate the association of steroid metabolism and respiratory gene polymorphisms in neonates exposed to antenatal corticosteroids (ACS) with respiratory outcomes, small for gestational age (SGA) and response to repeat ACS

Association between Features of Spontaneous Late Preterm Labor and Late Preterm Birth

Objective This study aimed to evaluate the association between clinical and examination features at admission and late preterm birth. Study Design The present study is a secondary analysis of a randomized trial of singleton pregnancies at 34 0/7 to 36 5/7 weeks' gestation. We included women in spontaneous preterm labor with intact membranes and compared them by gestational age at delivery (preterm vs. term). We calculated a statistical cut-point optimizing the sensitivity and specificity of initial cervical dilation and effacement at predicting preterm birth and used multivariable regression to identify factors associated with late preterm delivery. Results A total of 431 out of 732 (59%) women delivered preterm. Cervical dilation ≥ 4 cm was 60% sensitive and 68% specific for late preterm birth. Cervical effacement ≥ 75% was 59% sensitive and 65% specific for late preterm birth. Earlier gestational age at randomization, nulliparity, and fetal malpresentation were associated with late preterm birth. The final regression model including clinical and examination features significantly improved late preterm birth prediction (81% sensitivity, 48% specificity, area under the curve = 0.72, 95% confidence interval [CI]: 0.68-0.75, and p -value < 0.01). Conclusion Four in 10 women in late-preterm labor subsequently delivered at term. Combination of examination and clinical features (including parity and gestational age) improved late-preterm birth prediction

The association among cytochrome P450 3A, progesterone receptor polymorphisms, plasma 17-alpha hydroxyprogesterone caproate concentrations, and spontaneous preterm birth

Background Infants born <37 weeks’ gestation are of public health concern since complications associated with preterm birth are the leading cause of mortality in children <5 years of age and a major cause of morbidity and lifelong disability. The administration of 17-alpha hydroxyprogesterone caproate reduces preterm birth by 33% in women with history of spontaneous preterm birth. We demonstrated previously that plasma concentrations of 17-alpha hydroxyprogesterone caproate vary widely among pregnant women and that women with 17-alpha hydroxyprogesterone caproate plasma concentrations in the lowest quartile had spontaneous preterm birth rates of 40% vs rates of 25% in those women with higher concentrations. Thus, plasma concentrations are an important factor in determining drug efficacy but the reason 17-alpha hydroxyprogesterone caproate plasma concentrations vary so much is unclear. Predominantly, 17-alpha hydroxyprogesterone caproate is metabolized by CYP3A4 and CYP3A5 enzymes. Objective We sought to: (1) determine the relation between 17-alpha hydroxyprogesterone caproate plasma concentrations and single nucleotide polymorphisms in CYP3A4 and CYP3A5; (2) test the association between progesterone receptor single nucleotide polymorphisms and spontaneous preterm birth; and (3) test whether the association between plasma concentrations of 17-alpha hydroxyprogesterone caproate and spontaneous preterm birth varied by progesterone receptor single nucleotide polymorphisms. Study Design In this secondary analysis, we evaluated genetic polymorphism in 268 pregnant women treated with 17-alpha hydroxyprogesterone caproate, who participated in a placebo-controlled trial to evaluate the benefit of omega-3 supplementation in women with history of spontaneous preterm birth. Trough plasma concentrations of 17-alpha hydroxyprogesterone caproate were measured between 25-28 weeks of gestation after a minimum of 5 injections of 17-alpha hydroxyprogesterone caproate. We extracted DNA from maternal blood samples and genotyped the samples using TaqMan (Applied Biosystems, Foster City, CA) single nucleotide polymorphism genotyping assays for the following single nucleotide polymorphisms: CYP3A4*1B, CYP3A4*1G, CYP3A4*22, and CYP3A5*3; and rs578029, rs471767, rs666553, rs503362, and rs500760 for progesterone receptor. We adjusted for prepregnancy body mass index, race, and treatment group in a multivariable analysis. Differences in the plasma concentrations of 17-alpha hydroxyprogesterone caproate by genotype were evaluated for each CYP single nucleotide polymorphism using general linear models. The association between progesterone receptor single nucleotide polymorphisms and frequency of spontaneous preterm birth was tested using logistic regression. A logistic model also tested interaction between 17-alpha hydroxyprogesterone caproate concentrations with each progesterone receptor single nucleotide polymorphism for the outcome of spontaneous preterm birth. Results The association between CYP single nucleotide polymorphisms *22, *1G, *1B, and *3 and trough plasma concentrations of 17-alpha hydroxyprogesterone caproate was not statistically significant (P =.68,.44,.08, and.44, respectively). In an adjusted logistic regression model, progesterone receptor single nucleotide polymorphisms rs578029, rs471767, rs666553, rs503362, and rs500760 were not associated with the frequency of spontaneous preterm birth (P =.29,.10,.76,.09, and.43, respectively). Low trough plasma concentrations of 17-alpha hydroxyprogesterone caproate were statistically associated with a higher frequency of spontaneous preterm birth (odds ratio, 0.78; 95% confidence ratio, 0.61–0.99; P =.04 for trend across quartiles), however no significant interaction with the progesterone receptor single nucleotide polymorphisms rs578029, rs471767, rs666553, rs503362, and rs500760 was observed (P =.13,.08,.10,.08, and.13, respectively). Conclusion The frequency of recurrent spontaneous preterm birth appears to be associated with trough 17-alpha hydroxyprogesterone caproate plasma concentrations. However, the wide variation in trough 17-alpha hydroxyprogesterone caproate plasma concentrations is not attributable to polymorphisms in CYP3A4 and CYP3A5 genes. Progesterone receptor polymorphisms do not predict efficacy of 17-alpha hydroxyprogesterone caproate. The limitations of this secondary analysis include that we had a relative small sample size (n = 268) and race was self-reported by the patients

Timing of Elective Repeat Cesarean Delivery at Term and Maternal Perioperative Outcomes

(Obstet Gynecol. 2011;117(2 Pt 1):280–286