PS-P07-1: TERATOGENIC RISK OF FIRST TRIMESTER EXPOSURE TO ANTIHYPERTENSIVES, INCLUDING AMLODIPINE AND METHYLDOPA: AN ANALYSIS OF AN ADMINISTRATIVE DATABASE 2010–2019

Abstract

Objective: No firm conclusions on the teratogenic risk of antihypertensives have been drawn, although methyldopa and amlodipine are relatively frequently prescribed in the first trimester (FT) in Japan [1]. The primary objective was to evaluate the teratogenic risk of FT exposure to antihypertensives, including amlodipine and methyldopa. Design and method: This study used a large claims database from JMDC Inc. The dates of pregnancy onset and delivery were estimated using published algorithms [2] and infant birth months. The prevalence of antihypertensive prescriptions during pregnancy was described in 91,390 women who gave birth between 2010 and 2019. The time trends of antihypertensive prescription were evaluated using a multivariate logistic regression model adjusted for maternal age. The teratogenic risk of FT antihypertensive exposure was evaluated in 1,185 women diagnosed with hypertensive disorders in the FT. The teratogenic risk of FT exposure to amlodipine and methyldopa was evaluated in 178 women who were prescribed antihypertensives in the FT. Logistic regression analysis was used to estimate the odds ratios (ORs) for overall major congenital malformations (MCMs). The results were presented for analyses adjusted for multiple confounding factors. The MCMs in claims were validated and the overall positive predictive value was 91.5% [3]. Results: Antihypertensives were prescribed to 278 (0.30%) women during their FT. The prescription prevalence in the FT was highest for methyldopa (0.13%), followed by amlodipine (0.06%), oral hydralazine (0.03%), and nifedipine (0.02%). Antihypertensives were prescribed to 2,955 (3.23%) pregnant women. Nifedipine (0.99%) was the most frequently prescribed oral antihypertensive medication, with a significant increase in annual prevalence (P < 0.0001), followed by methyldopa (0.78%), hydralazine (0.34%), and furosemide (0.14%) during pregnancy. Nicardipine (0.83%) was the most frequently prescribed injectable antihypertensive agent, with a significant increase in annual prevalence (P < 0.0001), followed by furosemide (0.42%), nitroglycerin (0.26%), and hydralazine (0.20%) during pregnancy. The adjusted OR (aOR) of MCMs in the FT prescription of any antihypertensive medication was 1.096 (95% confidence interval [CI], 0.612–1.964). The aORs of MCMs in the FT prescription of amlodipine and methyldopa were 1.161 (95% CI, 0.347–3.882) and 0.937 (0.313–2.809), respectively. Conclusions: FT exposure to antihypertensive drugs, including amlodipine and methyldopa, was not associated with MCM risk in infants. REFERENCE 1. Pharmacoepidemiol Drug Saf 2018; 27:1325–1334.2. Pharmacoepidemiol Drug Saf 2018; 27:751–762.3. Pharmacoepidemiol Drug Saf 2021; 30:975–978.