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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 (Ile462Val AA>AG/GG), GSTT1(del), and CYP2A6 (Lys160His 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.

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: II.

Objective: To estimate the incidence of puerperal mastitis requiring hospital admission and to describe demographic and obstetric risk factors for this condition. We also sought to identify trends in bacteriology among isolates obtained from breast abscesses and breast-milk aspirates, with a focus on treatment strategies used for community-acquired methicillin-resistant Staphylococcus aureus (MRSA)., Methods: Patients with puerperal mastitis who were admitted to a county-based teaching hospital between January 1997 and December 2005 were identified by International Classification of Diseases, 9th Revision, codes (675.1, 675.2). Data collected included demographic characteristics, clinical presentation, treatment, duration of admission, premorbid antibiotic exposure, and bacteriology. Demographic variables and obstetric outcomes were compared with all other pregnant women delivered at our hospital., Results: One hundred twenty-seven of 136,459 women delivered at our teaching hospital were admitted for puerperal mastitis (9.3 [95% confidence interval (CI) 7.8-11.1] per 10,000 deliveries). The incidence of mastitis only during the study period was 6.7 (95% CI 5.4-8.3) per 10,000 deliveries, and the incidence of mastitis with breast abscess was 2.6 (95% CI 1.8-3.6) per 10,000 deliveries. Puerperal mastitis was significantly associated with younger women (23.4 years compared with 25.1 years, P<.001) and decreased parity (P=.02). Clinically significant breast abscess (n=35, 28%) was seen most commonly with community-acquired MRSA (n=18, 67%) during the data-collection period. The majority (15 [56%]) of women with culture-proven MRSA did not receive antibiotic therapy to which this organism was sensitive. They were discharged without complication, and there were no treatment failures., Conclusion: Community-acquired MRSA was most commonly associated with breast abscess. The empiric use of antibiotics ineffective against community-acquired MRSA did not adversely affect the outcomes in this study.

Objective: To evaluate whether women who agree to future use of their biologic specimens for genetic studies reflect the larger study population from which they are derived., Methods: Women were questioned as to the future disposition of their maternal and fetal DNA samples upon enrollment in a multicenter, observational study originally designed to identify factor V Leiden mutation carriers and prospectively ascertain the estimated rate of pregnancy-related venous thromboembolism and adverse pregnancy outcome. Univariate and multivariate analyses was carried out on the 5,003 of 5,188 enrolled women who indicated their desire regarding future disposition of their DNA samples., Results: Among these 5,003 women, 20.1% desired that their samples be discarded and not available for future genetic studies. Multivariate analysis demonstrated that women who agreed to subsequent use of samples were less likely African-American (odds ratio [OR] 0.6, 95% confidence interval [CI] 0.4-0.7) or Hispanic (OR 0.4, 95% CI 0.3-0.5), and more likely to use tobacco (OR 1.2, 95% CI 1.0-1.6) than those who desired that their samples be discarded., Conclusion: Genetic samples from women agreeing to their use in a sample repository may not be representative of the index study cohort. This should be considered in their subsequent interpretation and generalizability., Level of Evidence: III.

Objective: We sought to estimate the frequency of pregnancy-related thromboembolic events among carriers of the factor V Leiden (FVL) mutation without a personal history of thromboembolism, and to evaluate the impact of maternal and fetal FVL mutation carriage or other thrombophilias on the risk of adverse outcomes., Methods: Women with a singleton pregnancy and no history of thromboembolism were recruited at 13 clinical centers before 14 weeks of gestation from April 2000 to August 2001. Each was tested for the FVL mutation, as was the resultant conceptus after delivery or after miscarriage, when available. The incidence of thromboembolism (primary outcome), and of other adverse outcomes, was compared between FVL mutation carriers and noncarriers. We also compared adverse outcomes in a secondary nested carrier-control analysis of FVL mutation and other coagulation abnormalities. In this secondary analysis, we defined carriers as women having one or more of the following traits: carrier for FVL mutation, protein C deficiency, protein S deficiency, antithrombin III deficiency, activated protein C resistance, or lupus anticoagulant-positive, heterozygous for prothrombin G20210A or homozygous for the 5,10 methylenetetrahydrofolate reductase mutations. Carriers of the FVL mutation alone (with or without activated protein C resistance) were compared with those having one or more other coagulation abnormalities and with controls with no coagulation abnormality., Results: One hundred thirty-four FVL mutation carriers were identified among 4,885 gravidas (2.7%), with both FVL mutation status and pregnancy outcomes available. No thromboembolic events occurred among the FVL mutation carriers (0%, 95% confidence interval 0-2.7%). Three pulmonary emboli and one deep venous thrombosis occurred (0.08%, 95% confidence interval 0.02-0.21%), all occurring in FVL mutation noncarriers. In the nested carrier-control analysis (n = 339), no differences in adverse pregnancy outcomes were observed between FVL mutation carriers, carriers of other coagulation disorders, and controls. Maternal FVL mutation carriage was not associated with increased pregnancy loss, preeclampsia, placental abruption, or small for gestational age births. However, fetal FVL mutation carriage was associated with more frequent preeclampsia among African-American (15.0%) and Hispanic (12.5%) women than white women (2.6%, P = .04), adjusted odds ratio 2.4 (95% confidence interval 1.0-5.2, P = .05)., Conclusion: Among women with no history of thromboembolism, maternal heterozygous carriage of the FVL mutation is associated with a low risk of venous thromboembolism in pregnancy. Neither universal screening for the FVL mutation, nor treatment of low-risk carriers during pregnancy is indicated., Level of Evidence: II-2.