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Obstetrics & Gynecology:
doi: 10.1097/AOG.0000000000000103
Contents: Original Research

Maternal Hypertension, Medication Use, and Hypospadias in the National Birth Defects Prevention Study

Van Zutphen, Alissa R. PhD; Werler, Martha M. ScD; Browne, Marilyn M. PhD; Romitti, Paul A. PhD; Bell, Erin M. PhD; McNutt, Louise-Anne PhD; Druschel, Charlotte M. MD, MPH; Mitchell, Allen A. MD; for the National Birth Defects Prevention Study

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Abstract

OBJECTIVE: To investigate whether antihypertensive classes and specific medications in early pregnancy increase the risk of severe hypospadias and to assess prior associations detected for late-treated and untreated hypertension in the National Birth Defects Prevention Study.

METHODS: Using telephone interviews from mothers of 2,131 children with severe hypospadias and 5,129 nonmalformed male control children for 1997–2009 births in a population-based case–control study, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) with multivariable logistic regression. We adjusted P values to account for multiple testing.

RESULTS: Forty-eight (2.3%) case and 70 (1.4%) control mothers reported early pregnancy antihypertensive treatment, 45 (2.1%) case and 31 (0.6%) control mothers reported late treatment, and 315 (14.8%) case and 394 (7.7%) control mothers reported untreated hypertension. Selective β-blockers, centrally acting agents, renin–angiotensin system-acting agents, diuretics, and specific medications, methyldopa and atenolol, were not associated with hypospadias. Nonselective β-blockers (adjusted OR 3.22, 95% CI 1.47–7.05) were associated with hypospadias; however, P values adjusted for multiple testing were not statistically significant. We confirmed prior findings for associations between hypospadias and untreated hypertension (adjusted OR 2.09, 95% CI 1.76–2.48) and late initiation of treatment (adjusted OR 3.98, 95% CI 2.41–6.55). The increased risks would translate to severe hypospadias prevalences of 11.5, 17.7, and 21.9 per 10,000 births for women with untreated hypertension, nonselective β-blocker use, and late initiation of treatment, respectively.

CONCLUSION: Our study suggests a relationship between hypospadias and the severity of hypertension.

LEVEL OF EVIDENCE: II

© 2014 by The American College of Obstetricians and Gynecologists.

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