Interpretation
An understanding of the perinatal risks associated with chronic hypertension is largely informed by older studies. For example, a prior population based study from the US, which utilized Nationwide Inpatient Sample data from 1995-2008, reported a higher risk for stillbirth (odds ratio [OR] 2.31, 95% CI 2.11, 2.53) for pregnancies complicated by chronic hypertension compared to normotensive pregnancies.(6) In a population‐based prospective cohort study from Sweden (1992-2004), an increase in stillbirth risk (OR 2.71, 95% CI 1.96, 3.73) and neonatal death (OR 2.89, 95% CI 1.95, 4.30) was observed.(21) The results of our study, which showed increased perinatal mortality associated with chronic hypertension, are consistent with these studies, yet the magnitude of risk was larger. After adjusting for bias due to misclassification and unmeasured confounders, we found the risk of perinatal mortality was 4.86 (95% CI 3.42, 5.98), which was largely due to stillbirth at term gestations. The reason for this difference is uncertain, but may be due to advances in neonatal care that minimize the risk of neonatal deaths.
The mediation analysis suggested that a substantial driver of perinatal mortality risk is preterm delivery. Although most deliveries in our cohort occurred at term, there was an association between chronic hypertension and preterm delivery. A prior population based study from the US found the odds of preterm delivery for chronic hypertensive versus normotensive pregnancies was 3.01 (95% CI 2.88, 3.14).(6) A meta-analysis on chronic hypertension and pregnancy outcomes showed that pregnancies complicated by chronic hypertension are at a higher risk of preterm delivery <37 weeks’ gestation (RR 2.7, 95% CI 1.9, 36).(8) Most often the preterm births are medically indicated secondary to superimposed preeclampsia or fetal growth restriction.(40, 41) This study suggests that, if possible, avoiding preterm delivery in pregnancies complicated by chronic hypertension may have large impact on perinatal mortality.
The results of our study are consistent with prior work(42) and professional society recommendations(43) that suggest the optimal timing of delivery for pregnancies complicated by chronic hypertension is 37-38 weeks. It is critical to avoid early preterm delivery in these pregnancies (due to preterm delivery-associated complications and long-term chronic health conditions), but term and late term pregnancies also carry high risk of stillbirth. Despite national efforts to avoid early term deliveries,(44) findings from this study suggest early term deliveries may minimize the risks of stillbirths associated with chronic hypertension.
Women with chronic hypertension often have risk factors, such as advanced maternal age, obesity, and tobacco smoking,(1, 45, 46) which, in turn, increase the risks of adverse perinatal outcomes.(47-51) Public health strategies that target modifiable risk factors to reduce the burden of chronic hypertension may be the best strategy to reduce perinatal mortality associated with this disease. The mediation analysis quantified the preventable proportion of perinatal deaths associated with chronic hypertension by eliminating preterm deliveries associated with chronic hypertension, and most of perinatal deaths could be avoided.
While this study improves our understanding of the magnitude of chronic hypertension’s impact on perinatal mortality, there is a need for further study: (i) to develop preventive strategies such as weight loss and preconception blood pressure management for women at risk; (ii) to assess the effectiveness of these strategies on perinatal outcomes; and (iii) to evaluate whether treating mild chronic hypertension in pregnancy has the potential to reduce the risk of adverse pregnancy outcomes.(52)