Perinatal & Pediatric
A series of emulated target trials to estimate the safety of antihypertensives for the management of non-severe gestational hypertension among pregnant individuals in Botswana Julia DiTosto* Julia DiTosto Rebecca Zash Denise Jacobson Modiegi Diseko Gloria Mayondi Judith Mabuta Mompati Mmalane Joseph Makhema Shahin Lockman Roger Shapiro Ellen Caniglia
Antihypertensive therapy is critical for management of non-severe gestational hypertension (HTN), yet potential fetal consequences are unclear. Standard analyses may be subject to immortal time and selection bias. Conducting a series of emulated target trials (ETT) can avoid these biases by aligning start of follow-up with therapy initiation.
The Tsepamo Study has evaluated birth outcomes at government delivery sites in Botswana since 2014. We investigated antihypertensive therapy initiation ≥24 weeks gestation for management of non-severe gestational HTN on stillbirth and small-for-gestational-age (SGA) by conducting 16 sequential ETT of therapy initiation versus no initiation during each week from 24-39 weeks’ gestation. For each ETT, pregnant individuals with no history of HTN were eligible if they had not previously initiated therapy and had ≥1 elevated non-severe blood pressure reading (140-159 mm Hg systolic or 90-109 mm Hg diastolic) within 1 week of each ETT start. Log-binomial models were used to calculate RR and 95% CI. Results were pooled across all trials with bootstrapping to obtain CIs. Sensitivity analyses applied more stringent eligibility criteria (i.e., excluding preeclampsia and requiring >1 elevated blood pressure at baseline).
Of 28,608 individuals, 9,524 (33.3%) initiated antihypertensives between 24-39 weeks’ gestation. Comparing initiation to no initiation, the pooled RR was 1.18 (1.07-1.40) for stillbirth and 1.15 (1.08-1.27) for SGA. RRs varied by week of ETT start (Fig) and were sensitive to definition of eligibility criteria. For stillbirth, the pooled RR was 1.07 (0.87, 1.23) when excluding preeclampsia and 0.90 (0.34, 1.32) when requiring >1 elevated blood pressure at baseline.
Our results suggest initiation of antihypertensive therapy for non-severe gestational HTN may increase risk of stillbirth and SGA. Results were sensitive to eligibility criteria definitions, suggesting potential for unmeasured confounding by HTN severity.
