Objective To investigate the distribution of known factors for preterm birth (PTB) by severity of maternal underweight; to investigate the risk adjusted relationship between severity of underweight and PTB and to assess if the relationship differed by gestational age. Design Retrospective cohort study. Setting State of California, USA. Methods Maternally linked hospital and birth certificate records of 950,356 California deliveries in 2007–2010 were analyzed. Singleton live births of women whose pre-pregnancy body mass index (BMI) was underweight (<18.5 kg/m2) or normal (18.50–24.99 kg/m2) were analyzed. Underweight BMI was further categorized as: severe (<16.00), moderate (16.00–16.99) or mild (17.00–18.49). PTB was grouped as 22–27, 28–31, 32–36 or <37 weeks (compared with 37–41 weeks). Adjusted multivariable Poisson regression modeling was used to estimate relative risk for PTB. Main outcome measures Risk of PTB. Results 72,686 (7.6%) women were underweight. Increasing severity of underweight was associated with increasing percent PTB: 7.8% (n=4421) in mild, 9.0% (n=1001) in moderate and 10.2% (475) in severe underweight. The adjusted relative risk of PTB also significantly increased: aRR=1.22 (95%CI: 1.19–1.26) in mild, aRR=1.41 (95%CI: 1.32–1.50) in moderate and aRR=1.61 (95%CI: 1.47–1.76) in severe underweight. These findings were similar in spontaneous PTB, medically indicated PTB, and the gestational age groupings. Conclusion Increasing severity of maternal pre-pregnancy underweight BMI was associated with increasing risk adjusted PTB at <37 weeks. This increasing risk was of similar magnitude in spontaneous and medically indicated births and in preterm delivery at 28–31 and at 32–36 weeks of gestation.

We examined whether variants in genes related to sex hormone biosynthesis and metabolism were associated with hypospadias in humans. We examined 332 relatively common tagSNPs in 20 genes. Analyses included 633 cases (84 mild, 322 moderate, 212 severe, 15 undetermined severity) and 855 population-based non-malformed male controls born in California from 1990–2003. We used logistic regression models to estimate odds ratios (OR) and 95 percent confidence intervals (CI) for each SNP. Several of the 332 studied SNPs had p<0.01: one in CYP3A4, four in HSD17B3, one in HSD3B1, 2 in STARD3 10 in SRD5A2 and seven in STS. In addition, haplotype analyses gave several associations with p<0.01. For HSD17B3, 14-SNP and 5-SNP blocks had ORs of 1.5 (95% CI 1.1, 2.0, p<0.001) and 2.8 (95% CI 1.6, 4.8, p<0.001), respectively. For SRD5A2, 9-SNP, 3-SNP and 8-SNP blocks had ORs of 1.7 (95% CI 1.3, 2.2, p<0.001), 1.4 (95% CI 1.1, 1.8, p=0.008) and 1.5 (95% CI 1.2, 1.9, p=0.002), respectively. Our study indicates that several genes that contribute to sex hormone biosynthesis and metabolism are associated with hypospadias risk.

Thyroid disease is a common problem among women of reproductive age but often goes undiagnosed. Maternal thyroid disease has been associated with increased risk of craniosynostosis. We hypothesized that known risk factors for thyroid disease would be associated with risk of craniosynostosis among women not diagnosed with thyroid disease. Analyses included mothers of 1,067 cases and 8,494 population-based controls who were interviewed for the National Birth Defects Prevention Study. We used multivariable logistic regression to estimate adjusted odds ratios (AOR) and 95% confidence intervals (CI). After excluding women with diagnosed thyroid disease, younger maternal age (AOR 0.7, 95% CI 0.6–0.9, for <25 years versus 25–29), black or other race-ethnicity (AOR 0.3, 95% CI 0.2–0.4 and AOR 0.6, 95% CI 0.4–0.8, respectively, relative to non-Hispanic whites), fertility medications or procedures (AOR 1.5, 95% CI 1.2–2.0), and alcohol consumption (AOR 0.8, 95% CI 0.7–0.9) were associated with risk of craniosynostosis, based on confidence intervals that excluded 1.0. These associations with craniosynostosis are consistent with the direction of their association with thyroid dysfunction (i.e., younger age, black race-ethnicity and alcohol consumption are associated with reduced risk and fertility problems are associated with increased risk of thyroid disease). This study thus provides support for the hypothesis that risk factors associated with thyroid dysfunction are also associated with risk of craniosynostosis. Improved understanding of the potential association between maternal thyroid function and craniosynostosis among offspring is important given that craniosynostosis carries significant morbidity and that thyroid disease is under-diagnosed and potentially modifiable.

Objective: To assess the relationship between maternal body mass index (BMI) and pregnancyrelated venous thromboembolism (VTE). Design: Cohort study. Setting & population: 2,449,133 women with singleton pregnancies who underwent delivery hospitalization in California between 2008 and 2012. Methods: Association of prepregnancy BMI and the risk of an antepartum and postpartum VTE was examined using logistic regression, with normal BMI as reference. Main outcome measures: Antepartum and postpartum VTE related hospitalization.

(BJOG. 2019;126:581–588) Obesity is a risk factor for pregnancy-related venous thromboembolism (VTE), a leading cause of maternal death. Recommendations for VTE prevention specific to maternal body mass index (BMI) are limited and inconsistent across various organizations such as the Royal College of Obstetricians and Gynecologists and the American College of Obstetricians and Gynecologists. The aim of this study was to examine the association between maternal BMI and pregnancy-related VTE.