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March 08, 2021
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Hypertensive disorders of pregnancy associated with maternal premature mortality

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Among mothers, those who had hypertensive disorders of pregnancy had increased risk for premature mortality, according to research published in the Journal of the American College of Cardiology.

The connection was strongest in women who experienced hypertensive disorders of pregnancy (HDP) during multiple pregnancies or those who also reported low birth weight, according to the researchers.

Graphical depiction of data presented in article
Among mothers, those who had hypertensive disorders of pregnancy had increased risk for premature mortality. Data was derived from Wang YX, et al. J Am Coll Cardiol. 2021;doi:10.1016/j.jacc.2021.01.018.

“Together, these findings suggest that although the previously described progression of HDPs to chronic hypertension to increased cardiovascular morbidity and mortality is undoubtedly important, it may not be the primary pathway through which HDPs affect health and, ultimately, mortality,” Yi-Xin Wang, MD, PhD, research fellow in the department of nutrition at the Harvard T.H. Chan School of Public Health, and colleagues wrote. “To our knowledge, our study is the first to explore the effect of change in HDP status throughout a woman’s reproductive life span on mortality.”

Using data from the Nurses’ Health Study II, researchers identified 88,395 parous nurses during 28 years of follow-up (mean prepregnancy BMI, 21 kg/m2) to determine the effect of gestational hypertension and preeclampsia on premature mortality.

Risk for mortality

Overall, 2,387 participants died before age 70 years, which included 1,141 cancer deaths and 212 CVD deaths.

In the overall cohort, 14% of women experienced an HDP such as gestational hypertension or preeclampsia in at least one pregnancy.

Researchers observed that women who experienced an HDP had increased risk for premature death during follow-up (HR = 1.42; 95% CI, 1.28-1.58). This association was slightly attenuated after adjustment for potential confounding factors and diet, lifestyle and reproductive characteristics (HR = 1.31; 95% CI, 1.18-1.46) after pregnancy.

According to the study, no effect modification was observed for factors, including age at first birth, breastfeeding duration, parity, parental history of CVD, antihypertension treatment, subsequent development of diabetes, prepregnancy vs. current BMI, physical activity, diet quality and smoking status.

In an analysis of cause-specific mortality, HDPs were associated with elevated risk for premature CVD mortality (HR = 2.26; 95% CI, 1.67-3.07) but not premature cancer mortality (HR = 0.97; 95% CI, 0.82-1.15).

Among less common causes of death, HDPs were associated with risk for death from the following:

  • infectious disease (HR = 2.77; 95% CI, 1.38-5.54);
  • respiratory diseases (HR = 2.26; 95% CI, 1.29-3.98);
  • nervous system diseases (HR = 2.51; 95% CI, 1.33-4.72);
  • metabolic/immunity disorders (HR = 4.85; 95% CI, 2.29-10.27); and
  • symptoms, signs or ill-defined conditions (HR = 1.72; 95% CI, 1.13-2.6).

“Pregnant women with heart disease and obesity should be educated about these risks, and health care providers should ensure that dietary advice [and] weight-gain recommendations [are given], and that obesity and other comorbidities are addressed as part of routine care,” Candice Silversides, MD, cardiologist at Mount Sinai and Toronto General Hospital, said in a press release. “Postpartum surveillance is important in pregnant women with obesity because of the increased risk of complications during this time period.”

Subgroup analysis

Women who experienced HDPs after a normotensive pregnancy (adjusted HR = 1.82; 95% CI, 1.22-2.69) or during first and subsequent pregnancies were at the higher risk for premature death compared with women with normotension in all pregnancies (aHR = 1.23; 95% CI, 0.74-2.04). However, this increased risk for premature death appeared to be driven by a small number of women who experienced HDPs in two or more pregnancies or simultaneous low birth weight, the researchers wrote.

“The relation of HDPs and CVD mortality could be partly explained by some shared risk factors of HDPs and CVD, such as insulin resistance and systemic inflammation,” the researchers wrote. “In addition, the pathological processes implicated in HDPs, including angiogenic imbalance, complement activation, inflammation and hemodynamic changes, may also contribute directly to cardiac stress that exceeds normal pregnancy, leading to overt cardiac damage.”