Chronic Hypertension, Perinatal Mortality, and the Impact of Preterm Delivery: A Population-Based Study in the United States, 2015-2018

Objective: To estimate the association between chronic hypertension and perinatal mortality and evaluate the extent to which this risk is impacted by preterm delivery. Design: Cross-sectional analysis. Setting: US, 2015-2018. Population: Singleton births from 20-44 weeks’ gestation. Main outcomes and measures: We derived the risk of perinatal mortality in relation to chronic hypertension from fitting log-linear Poisson models with robust variance. Risk ratios (RR) and 95% confidence intervals (CI) were estimated after adjusting for confounders. The impact of misclassifications and unmeasured confounding biases were assessed. Causal mediation analysis was performed to quantify the impact of preterm delivery on the association. Results: Of the 15,090,678 singleton births, perinatal mortality was 22.5 per 1000 births in chronic hypertensive pregnancies compared to 8.2 per 1000 births in normotensive pregnancies (adjusted RR 2.05, 95% CI 2.00, 2.10). Corrections for exposure misclassification and unmeasured confounding biases substantially increased the risk estimate. Although, causal mediation analysis revealed that most of the effect of chronic hypertension on perinatal mortality was mediated through preterm delivery, the perinatal mortality rates were highest at early term, term, and late term gestations, suggesting that a planned early term delivery at 37-386/7 weeks may optimally balance risk in these pregnancies. Additionally, 87% (95% CI 84, 90) of perinatal deaths could be eliminated if preterm deliveries, as a result of chronic hypertension were prevented. Conclusions: Chronic hypertensive pregnancies are associated with increased risk for perinatal mortality. Planned early term delivery and targeting modifiable risk factors for chronic hypertension may reduce perinatal mortality rates.