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).