Maternal and neonatal outcomes associated with treating hypertension in pregnancy at different thresholds

Introduction: In the United States, there has been controversy over whether treatment of mild-to-moderate hypertension during pregnancy conveys more benefit than risk.

Objective: The objective of the study was to compare risks and benefits of treatment of mild-to-moderate hypertension during pregnancy.

Methods: This retrospective cohort study included 11,871 pregnant women with mild-to-moderate hypertension as defined by blood pressure (BP) values from three Kaiser Permanente regions between 2005 and 2014. Data were extracted from electronic health records. Dynamic marginal structural models with inverse probability weighting and informative censoring were used to compare risks of adverse outcomes when beginning antihypertensive medication treatment at four BP thresholds (≥155/105, ≥150/100, ≥145/95, ≥140/90 mm Hg) compared with the recommended threshold in the United States at that time, ≥160/110 mm Hg. Outcomes included preeclampsia, preterm birth, small-for-gestational-age (SGA), Neonatal Intensive Care Unit (NICU) care, and stillbirth. Primary analyses allowed 2 weeks for medication initiation after an elevated BP. Several sensitivity and subgroup (i.e., race/ethnicity and pre-pregnancy body mass index) analyses were also conducted.

Results: In primary analyses, medication initiation at lower BP thresholds was associated with greater risk of most outcomes. Comparing the lowest (≥140/90 mm Hg) to the highest BP threshold (≥160/110 mm Hg), we found an excess risk of preeclampsia (adjusted Risk Difference (aRD) 38.6 per 100 births, 95% Confidence Interval (CI): 30.6, 46.6), SGA (aRD: 10.2 per 100 births, 95% CI: 2.6, 17.8), NICU admission (aRD: 20.2 per 100 births, 95% CI: 12.6, 27.9), and stillbirth (1.18 per 100 births, 95% CI: 0.27, 2.09). The findings did not reach statistical significance for preterm birth (aRD: 2.5 per 100 births, 95% CI: -0.4, 5.3). These relationships were attenuated and did not always reach statistically significance when comparing higher BP treatment thresholds to the highest threshold (i.e., ≥160/110 mm Hg). Sensitivity and subgroup analyses produced similar results.

Conclusions: Initiation of antihypertensive medication at mild-to-moderate BP thresholds (140-155/90-105 mm Hg; with the largest risk consistently associated with treatment at 140/90 mm Hg) may be associated with adverse maternal and neonatal outcomes. Limitations include inability to measure medication adherence.