Results
Among 6346 eligible deliveries, there were 3017 (48%) where the woman had taken labetalol, 1834 (29%) methyldopa, 1105 (17%) nifedipine, and 390 (6%) other β-blockers. Figure 1 shows the impact of inclusion and exclusion criteria on the study population.
Mean maternal age was 33.6 years, 87% had chronic hypertension, and the mean gestational age at the index fill was 18.4 weeks. Many women (37%) were taking antihypertensive medication continuously prior to the index fill, and mean BPs prior to the index fill suggest that their hypertension was on average fairly well controlled. Table 1 shows baseline characteristics by treatment group, and Table S4 provides more detailed information for an expanded list of baseline characteristics. Table S5 shows characteristics by treatment group after IPTW and demonstrates that overall, these were well balanced (standardized mean difference < 0.1), except for those characteristics included in the outcome model, which are not expected to be balanced by IPTW. After IPTW, the group exposed to other β-blockers looked modestly different from the other groups, likely due to this group’s small size. Table S6 and Figure S1 describe the distributions of propensity scores and weights.
Most women did not switch medications after their index fill. The proportion of women who later filled a different medication was 15% overall, ranging from 11 to 22% for different exposure groups.
Table 2 provides crude counts of outcomes by treatment group. Figure 2 shows the risk of maternal and neonatal outcomes comparing different medications, with labetalol as the referent group. We present weighted prevalences for outcomes after accounting for confounders together with adjusted ORs and 95% CIs. For SGA < 10thpercentile, risk was lower with methyldopa than labetalol (weighted prevalence 13.6% vs. 16.6%; aOR 0.77, 95% CI 0.63 to 0.92), and the association was stronger for birthweight < 3rd percentile (aOR 0.57, 95% CI 0.39 to 0.80). The mean birthweight after IPTW was 3002 ± 797 g for labetalol, 3060 ± 788 g for methyldopa, 3033 ± 798 g for nifedipine, and 2944 ± 791 g for other β-blockers.
Preterm delivery was slightly more common with nifedipine than labetalol (28.5% vs. 26.0%; aOR 1.25, 95% CI 1.06 to 1.46), as was NICU admission (25.9% vs. 23.3%; aOR 1.21, 95% CI 1.02 to 1.43). β-blockers other than labetalol were associated with higher risk of preterm delivery (aOR 1.58, 95% CI 1.07 to 2.23). Methyldopa and labetalol conveyed similar risks of preterm delivery and NICU admission. After IPTW, the mean gestational age at delivery was 37.6 ± 2.8 weeks for labetalol, 37.6 ± 2.8 weeks for methyldopa, 37.4 ± 2.8 weeks for nifedipine, and 37.4 ± 2.8 weeks for other β-blockers.
There was no significant association between medication type and risk of preeclampsia (overall or with severe features), maternal ICU admission, or stillbirth/termination.
Results of sensitivity and subgroup analyses are shown in Supplementary Figures S2-S4. Results did not change when we restricted the population to women with chronic hypertension, who made up 87% of the population. Results also did not change when we excluded women with pregestational diabetes. Some findings appeared qualitatively different when we limited analyses to new users; in this group, there was a suggestion of lower risk for many outcomes with methyldopa than with labetalol, with aORs around 0.5 to 0.7 (though most were not statistically significant).