Sensitivity analyses
The prevalence of gestational hypertension was 7.7% with a median gestational age at diagnosis of 37+0 weeks (interquartile range 34+2 to 38+6weeks). A high dose of calcium-based antacids (≥1 g/day) in gestational weeks 0-19 was associated with an increased risk of gestational hypertension (adjusted RR 1.6 [95% CI 1.2-2.1], Table S4). Use of calcium-based antacids after gestational week 19 and use of PPIs in early and late pregnancy was not associated with the risk of gestational hypertension (Tables S4 and S5).
Within the PRIDE Study, 38.4% of women (N = 2,078) was at high risk of developing preeclampsia. Among these women, excess risks for exposure in early and mid-pregnancy were more evident compared to the total population with an adjusted RR of 2.3 (95% CI 1.2-4.4) for low-dose calcium-based antacids in gestational weeks 0-16 and 2.2 (95% CI 1.2-4.3) for any PPI use in gestational weeks 0-33 (Table S6). The latter was attributable to PPI use in gestational weeks 17-33, as no increased risk was observed for PPI use in gestational weeks 0-16 (adjusted RR 1.4 [95% CI 0.5-4.3]). We did not observe associations between late-onset preeclampsia and any calcium-based antacid use (adjusted HR 0.7 [95% CI 0.3-1.3]) or PPI use (adjusted HR 2.1 [95% CI 0.8-5.2]) after gestational week 33 among women at high risk of developing preeclampsia (Table S7). Restricting the analyses to women who did not use calcium-containing supplements during pregnancy (N=1,482) did not materially change the results, although these analyses were hampered by small numbers (Tables S8 and S9).