Safety of Antihypertensive Medication for the Management of Non-Severe Gestational Hypertension Among Pregnant Individuals in Botswana-Emulating a Series of Target Trials.

BACKGROUND

Data on antihypertensive medication for non-severe gestational hypertension may suffer from immortal time and selection bias. Emulating target trials can prevent these biases by aligning follow-up with treatment initiation.

OBJECTIVES

We estimated the safety of antihypertensive medication initiation for the treatment of non-severe gestational hypertension on adverse birth outcomes in Botswana using sequential target trial emulation.

METHODS

Data from the Tsepamo study (2014-2022), capturing birth outcomes at government delivery sites in Botswana, was used to examine antihypertensive medication initiation ≥ 24 weeks gestation for non-severe gestational hypertension (140-159 systolic or 90-109 diastolic blood pressure ≥ 20 weeks gestation without chronic hypertension). Sequential weekly target trial emulation compared initiation versus no initiation during 24-35 weeks' gestation on the risk of stillbirth and birth of infant small for gestational age (SGA), with secondary outcomes including very SGA, preterm birth, very preterm birth, neonatal death, and severe gestational hypertension. For each trial, eligible individuals were without chronic hypertension, had not previously initiated antihypertensive medication and had ≥ 2 non-severe blood pressure readings, at least one within 1 week of trial start. Log-binomial models estimated gestational week-specific and pooled risk ratios (RR) with 95% confidence intervals (CI) using bootstrapping.

RESULTS

Of eligible individuals, there were 1676 antihypertensive initiator 'person-trials' and 5211 non-initiator 'person-trials'. In the pooled analysis, the adjusted RR for stillbirth and SGA comparing initiators to non-initiators was 0.92 (0.68, 1.19) and 1.09 (0.97, 1.23), respectively. The pooled adjusted RR for secondary outcomes were: very SGA, 1.05 (95% CI 0.88, 1.25); preterm birth, 1.09 (95% CI 0.96, 1.22); very preterm birth, 1.05 (95% CI 0.78, 1.47); neonatal death, 1.23 (95% CI 0.68, 2.24); severe gestational hypertension, 0.88 (95% CI 0.74, 1.07).

CONCLUSIONS

In this retrospective cohort study, antihypertensive medication initiation between 24 and 35 weeks' gestation for non-severe gestational hypertension was not associated with increased risk of adverse birth outcomes.