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.

Is preeclampsia associated with fetal malformation? A review and report of original research

“…There were five other reports (published between 2008 and 2014) where investigators found an association between hypospadias and preeclampsia also in growth restricted fetuses [20–24]. The common theme as to the pathophysiology of hypospadias in infants delivered of women with preeclampsia was placental insufficiency.…”

“…The common theme as to the pathophysiology of hypospadias in infants delivered of women with preeclampsia was placental insufficiency. How placental insufficiency might interfere with closure of the urethra was unclear [20–24]. …”

Comparison of live-birth defects after luteal-phase ovarian stimulation vs. conventional ovarian stimulation for in vitro fertilization and vitrified embryo transfer cycles

“…Infants born to mothers with reported maternal diseases, such as gestational diabetes mellitus (13,14), hypertension (15), and thyroid disorders (16,17), or adverse environmental exposure (18)(19)(20)(21)(22) during pregnancy, were excluded from this analysis because of the possible association of these factors with birth defects. The final data, involving 2,060 live-born infants, delivered after IVF with ICSI and FET, were stratified into groups according to the method of ovarian stimulation: 587 births after LPS, 1,257 births after the standard GnRH-a short protocol, and 216 births after mild ovarian stimulation.…”

Hypertensive Emergencies in Pregnancy

“…21 These include congenital heart disease, esophageal atresia, and hypospadias. [21][22][23] In a systematic review and metaanalysis, Ramakrishnan and colleagues 21 found that congenital anomalies were more common in both treated and untreated hypertension, although the risk was greater in treated hypertension. Van Zutphen and colleagues 23 demonstrated a higher incidence of hypospadias in untreated hypertension and hypertension treated with nonselective b-blockers, specifically labetalol and propranolol.…”

“…In these women, delivery can be delayed for 48 hours for administration of corticosteroids for fetal lung maturity in the absence of uncontrollable severe hypertension, eclampsia, pulmonary edema, placental abruption, disseminated intravascular coagulation, or nonreassuring fetal status. The management of preeclampsia with severe features before viability (23)(24) weeks in most centers) should involve consultation with a specialist in maternalfetal medicine.…”