Maternal hypertension, medication use, and hypospadias in the National Birth Defects Prevention Study

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.

Fig. 1

Proportion of mothers reporting specific classes of antihypertensive medications among those reporting early pregnancy use. Van Zutphen. Maternal Hypertension and Hypospadias. Obstet Gynecol 2014.

Fig. 2

Associations between early pregnancy antihypertensive medication use, late initiation of antihypertensive medication, untreated hypertension, and hypospadias stratified by low birth weight and preterm birth. *Women taking medications used to treat hypertension, who did not report hypertension, were excluded from the analysis. †Adjusted for site, maternal age, race/ethnicity, parity, fertility treatment, pre-pregnancy diabetes, gestational diabetes, and multiple births. ‡Adjusted using the step-down Bonferroni method. OR, odds ratio; CI, confidence interval. Van Zutphen. Maternal Hypertension and Hypospadias. Obstet Gynecol 2014.