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The ductus arteriosus (DA) is a unique fetal vascular shunt, which allows blood to bypass the developing lungs in utero. After birth, changes in complex signaling pathways lead to constriction and permanent closure of the DA. The persistent patency of the DA (PDA) is a common disorder in preterm infants, yet the underlying causes of PDA are not fully defined. Although limits on the availability of human DA tissues prevent comprehensive studies on the mechanisms of DA function, mouse models have been developed that reveal critical pathways in DA regulation. Over 20 different transgenic models of PDA in mice have been described, with implications for human DA biology. Similarly, we enumerate 224 human single‐gene syndromes that are associated with PDA, including a small subset that consistently feature PDA as a prominent phenotype. Comparison and functional analyses of these genes provide insight into DA development and identify key regulatory pathways that may serve as potential therapeutic targets for the management of PDA. [ABSTRACT FROM AUTHOR]

Objective To assess the risk of adverse fetal outcomes following exposure to individual immunosuppressive drugs in pregnant women with chronic immune-mediated diseases. Methods Health plan data were obtained from the Tennessee Medicaid and Kaiser Permanente Northern California and Southern California claims databases, with linkage to both vital records and medical records. Women with inflammatory arthropathies, those with systemic lupus erythematosus, and those with inflammatory bowel disease who filled prescriptions for immunosuppressive treatments during pregnancy were included. Major congenital malformations, fetal deaths, and life-threatening neonatal complications were identified from the electronic data and validated with medical record review. Results The cohort included 608 infants, including 437 with exposure to immunosuppressive drugs during the mother's pregnancy (402 during the first trimester, and 35 during the second and third trimester only) and 171 whose mothers filled prescriptions for immunosuppressive treatments before, but not during, pregnancy. There were 25 pregnancies (4.1% of the cohort) with confirmed major congenital malformations, and 10 fetal deaths (1.6% of the cohort). Among 113 preterm infants with exposures during pregnancy, 23 (20.4%) had life-threatening neonatal complications, and among 485 term infants, 10 (2.1%) had life-threatening complications. Compared to the reference group (treatment before, but not during, pregnancy), the risk ratios (RRs) for adverse fetal outcomes associated with immunosuppressive treatments (by exposure category) during pregnancy included the following: methotrexate (RR 1.39, 95% confidence interval [95% CI] 0.43-4.53), tumor necrosis factor inhibitors (RR 0.98, 95% CI 0.38-2.55), hydroxychloroquine (RR 1.33, 95% CI 0.69-2.55), and other immunosuppressive medications (RR 0.98, 95% CI 0.48-1.98). Conclusion In this study, there was no evidence of a large increase in risk of adverse fetal outcomes from first-trimester exposure to immunosuppressive medications, although the confidence intervals for the risk ratios were wide. Further studies will be needed as use of these medications increases over time. [ABSTRACT FROM AUTHOR]

Obesity disproportionately affects Latina women. Common genetic variants are convincingly associated with body mass index (BMI) and may be used to create genetic risk scores (GRS) for obesity that could define genetically influenced forms of obesity and alter response to clinical trial interventions. The objective of this study was (1) to identify the frequency and effect size of common obesity genetic variants in Latina women; (2) to determine the clinical utility of a GRS for obesity with Latina women participating in a community-based clinical trial. DNA from 85 Latina women was genotyped for eight genetic variants previously associated with BMI in Caucasians, but not yet assessed in Latina populations. The main outcome measure was the correlation of GRS (sum of eight risk alleles) with BMI, waist circumference, and percent body fat. A majority (83%) of participants had a BMI ≥25. Frequency of loci near FTO, MC4R, and GNPDA2 were lower in Latinas than Caucasians. Association of each locus with BMI was lower in Latinas compared to Caucasians with no significant correlations with BMI. We conclude that an eight locus GRS has no clinical utility for explaining obesity or predicting response to intervention in Latina women participating in a clinical trial. Clin Trans Sci 2011; Volume 4: 323-327 [ABSTRACT FROM AUTHOR]