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

Elective repeat cesarean delivery at 37 or 38 weeks compared to 39 completed weeks’ gestation is associated with adverse neonatal outcomes. We assessed whether delivery prior to 39 weeks is justifiable on the basis of decreased adverse maternal outcomes

White’s Classification of Maternal Diabetes and Vaginal Birth After Cesarean Delivery Success in Women Undergoing a Trial of Labor

To estimate the rate of vaginal birth after cesarean delivery (VBAC) success in diabetic women based on White’s Classification

Effect of Antibiotic Exposure on Nugent Score Among Pregnant Women With and Without Bacterial Vaginosis

OBJECTIVE: To evaluate whether vaginal flora is altered by antibiotic exposure and associated with a risk of preterm birth, particularly among women with initially normal vaginal flora. METHODS: This was a secondary analysis of a randomized trial of metronidazole and erythromycin for the prevention of preterm birth among women with a positive fetal fibronectin test. Vaginal swabs for Nugent Gram stain score were collected for classification of bacterial vaginosis before and after antibiotic exposure and read at a central laboratory. Change in Nugent score was assessed for women with (score 7 or higher) or without (score lower than 7) bacterial vaginosis. Linear regression analysis evaluated whether change in Nugent score was associated with preterm birth. RESULTS: Two-hundred women without and 69 women with bacterial vaginosis had Gram stain performed before and after antibiotic therapy. Median Nugent score for all women declined from 4.0 to 2.0 after antibiotic therapy, p<0.001. Nugent score declined both for those without (from 2.0 to 1.5, p=0.11) and more dramatically, those with bacterial vaginosis (from 8.0 to 3.0, p<0.01). The components of the Nugent score that were affected by antibiotic exposure were similar among women with and without bacterial vaginosis. Antibiotic exposure and the change in Nugent score were unrelated to preterm birth among bacterial vaginosis-negative women. CONCLUSION: Antibiotic exposure is not associated with preterm birth and does not worsen Nugent score among women with normal vaginal flora and positive fetal fibronectin

Prothrombin Gene G20210A Mutation and Obstetric Complications

OBJECTIVE: To estimate whether maternal carriage of the prothrombin gene G20210A mutation is associated with pregnancy loss, preeclampsia, placental abruption, or small for gestational age (SGA) neonates in a low-risk, prospective cohort. METHODS: This was a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development factor V Leiden study, a multicenter, prospective, observational cohort of 5,188 unselected singleton gestations. A total of 4,167 first-trimester samples were available for analysis and were tested for the prothrombin G20210A mutation. Obstetric complications were compared between women with and without the prothrombin G20210A mutation by univariable and multivariable analysis. RESULTS: A total of 157 (3.8%) women had the prothrombin gene mutation (156 heterozygous and one homozygous). Carriers of the prothrombin G20210A mutation had similar rates of pregnancy loss, preeclampsia, SGA neonates, and abruption compared with noncarriers. Results were similar in a multivariable analysis controlling for age, race, prior pregnancy loss, prior SGA neonates, and family history of thromboembolism. Three thromboembolic events occurred in women testing negative for the mutation. CONCLUSION: There was no association between the prothrombin G20210A mutation and pregnancy loss, preeclampsia, abruption, or SGA neonates in a low-risk, prospective cohort. These data raise questions about the practice of screening women without a history of thrombosis or adverse pregnancy outcomes for this mutation. LEVEL OF EVIDENCE: I

Pharmacogenomics of Maternal Tobacco Use: Metabolic Gene Polymorphisms and Risk of Adverse Pregnancy Outcomes

OBJECTIVE: To assess whether functional maternal or fetal genotypes along well-characterized metabolic pathways (ie, CYP1A1, GSTT1, and CYP2A6) may account for varying associations with adverse outcomes among pregnant women who smoke. METHODS: DNA samples from 502 smokers and their conceptuses, alongside women in a control group, were genotyped for known functional allelic variants of CYP1A1 (Ile(462)Val AA>AG/GG), GSTT1(del), and CYP2A6 (Lys(160)His T>A). Modification of the association between smoking and outcome by genotype was evaluated. Outcomes included birth weight, pregnancy loss, preterm birth, small for gestational age, and a composite outcome composed of the latter four components plus abruption. RESULTS: No interaction between maternal or fetal genotype of any of the polymorphisms and smoking could be demonstrated. In contrast, the association of smoking with gestational age–adjusted birth weight (birth weight ratio) was modified by fetal GSTT1 genotype (P for interaction=.02). Fetuses with GSTT1(del) had a mean birth weight reduction among smokers of 262 g (P=.01), whereas in fetuses without the GSTT1(del) the effect of tobacco exposure was nonsignificant (mean reduction 87 g, P=.16). After adjusting for confounding, results were similar. CONCLUSION: Fetal GSTT1 deletion significantly and specifically modifies the effect of smoking on gestational age–corrected birth weight

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

OBJECTIVE: 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. STUDY DESIGN: This candidate gene study is a secondary analysis of women enrolled in a randomized controlled trial of single versus weekly courses of ACS. Nineteen single nucleotide polymorphisms (SNPs) in 13 steroid metabolism and respiratory function genes were evaluated. DNA was extracted from placenta or fetal cord serum and analyzed with TaqMan genotyping. Each SNP was evaluated for association via logistic regression with respiratory distress syndrome (RDS), CPAP/ventilator use (CPV) and SGA. RESULTS: CRHBP, CRH and CRHR1 minor alleles were associated with an increased risk of SGA. HSD11B1 and SCNN1B minor alleles were associated with an increased likelihood of RDS. Carriage of minor alleles in SerpinA6 was associated with an increased risk of CPV. CRH and CRHR1 minor alleles were associated with a decreased likelihood of CPV. CONCLUSION: Steroid metabolism and respiratory gene SNPs are associated with respiratory outcomes and SGA in patients exposed to ACS. Risks for respiratory outcomes are affected by minor allele carriage as well as by treatment with multiple ACS

The Relationship of Asthma-Specific Quality of Life During Pregnancy to Subsequent Asthma and Perinatal Morbidity

OBJECTIVE: To determine whether asthma-specific quality of life during pregnancy is related to asthma exacerbations and to perinatal outcomes. METHODS: This was a secondary analysis of data from a randomized controlled trial of inhaled beclomethasone versus theophylline in the treatment of moderate asthma during pregnancy. The Juniper Asthma Quality of Life Questionnaire (AQLQ) was administered to patients at enrollment. Exacerbations were defined as asthma symptoms requiring a hospitalization, unscheduled medical visit, or oral corticosteroid course. RESULTS: Quality of life assessments were provided by 310 of the 385 participants who completed the study. There was more than a 25% decrease in the odds of a subsequent asthma exacerbation for every 1-point increase in AQLQ score for the overall score (odds ratio [OR] 0.73, 95% confidence interval [CI] 0.55–0.96), emotion domain (OR 0.72, 95% CI 0.59–0.88), and symptoms domain (OR 0.73, 95% CI 0.57–0.94). These relationships were not significantly influenced by initial symptom frequency or forced expiratory volume in 1 s (FEV(1)). No significant relationships were demonstrated between enrollment AQLQ scores and preeclampsia, preterm birth, low birth weight, or small for gestational age. CONCLUSION: Asthma-specific quality of life in early pregnancy is related to subsequent asthma morbidity during pregnancy but not to perinatal outcomes

Admixture Mapping to Identify Spontaneous Preterm Birth Susceptibility Loci in African Americans

OBJECTIVE: Preterm birth is 1.5 times more common in African American (17.8%) than European American women (11.5%), even after controlling for confounding variables. We hypothesize that genetic factors may account for this disparity and can be identified by admixture mapping. METHODS: This is a secondary analysis of women with at least one prior spontaneous preterm birth enrolled in a multicenter prospective study. DNA was extracted and whole-genome amplified from stored saliva samples. Self-identified African American patients were genotyped with a 1,509 single nucleotide polymorphism (SNP) commercially-available admixture panel. A logarithm of odds) locus-genome score of 1.5 or higher was considered suggestive and 2 or higher was considered significant for a disease locus. RESULTS: One-hundred seventy-seven African American women with one or more prior spontaneous preterm births were studied. One-thousand four-hundred fifty SNPs were in Hardy-Weinberg equilibrium and passed quality filters. Individuals had a mean of 78.3–87.9% African-American ancestry for each SNP. A locus on chromosome 7q21–22 was suggestive of an association with spontaneous preterm birth before 37 weeks of gestation (three SNPs with logarithm of odds scores 1.50–1.99). This signal strengthened when women with at least one preterm birth before 35.0 (eight SNPs with logarithm of odds scores greater than 1.50) and before 32.0 weeks of gestation were considered (15 SNPs with logarithm of odds scores greater than 1.50). No other areas of the genome had logarithm of odds scores higher than 1.5. CONCLUSIONS: Spontaneous preterm birth in African American women may be genetically mediated by a susceptibility locus on chromosome 7. This region contains multiple potential candidate genes including collagen type 1-alpha-2 gene and genes involved with calcium regulation

Placental villous hypermaturation is associated with idiopathic preterm birth

Pregnancy complications such as intra-amniotic infection, preeclampsia, and fetal intrauterine growth restriction (IUGR) account for most cases of preterm birth (PTB), but many spontaneous PTB cases do not have a clear etiology. We hypothesize that placental insufficiency may be a potential cause of idiopathic PTB

Influence of Maternal Asthma and Asthma Severity on Newborn Morphometry

Objective. To determine if maternal asthma or asthma severity affects newborn morphometry. Study Design. A secondary analysis was performed on data collected in a multicenter prospective observational cohort study of asthma in pregnancy. Patients enrolled included women with asthma stratified by severity of disease and controls. Asthma severity was defined according to the classification proposed by the National Asthma Education Program (NAEP) Report of the Working Group on Asthma and Pregnancy, modified to include medication requirements. Newborn morphometry measurements included birth weight (BW) and multiples of the median birth weight (BW-MOM), head circumference (HC), length (L), HC:BW ratio, and ponderal index (PI). Results. Of 2480 patients there were 828 nonasthmatic controls, 828 with mild, 775 with moderate, and 49 with severe disease. Comparing all groups, there were statistically significant differences in maternal age (p < .001), race (p = .005), parity (p = .006), prepregnancy weight (p = .028), and medical care source (p = .001), with the severe asthma group having the highest mean maternal age (25.7 years), and proportion of African Americans (71.4%), proportion of multiparous patients (63.3%), and proportion of patients receiving government assistance (85.7%). When the control group was excluded from the comparisons, differences in prepregnancy weight and medical care source were no longer significant. BW-MOM and L did not differ between groups. The HC:BW ratio increased with asthma severity (p = .029) and was increased compared to controls (p = .010). This remained significant after controlling for confounding variables (both p <.001). HC was statistically significantly different between all groups (p = .032), as well as among women with varying degrees of asthma severity (p = .013), which was not clinically significant. After covariates adjustment, HC was not significantly different among all groups (p = .228), nor the asthma groups (p = .144). Conclusion. Asthma severity is associated with an increased HC:BW ratio. Severity was not found to impact HC, BW-MOM, L, or PI independently. However, the magnitudes of the effects were too small to suggest a clinically significant effect of asthma on neonatal morphometry in this large prospectively studied sample