Treating Mild Chronic Hypertension in Pregnancy May Reduce Risk of Neonatal, Fetal Outcomes

Alan T. Tita, MD, PhD

Treating mild, chronic hypertension in pregnant women decreased risk of preeclampsia, medically-indicated preterm birth, placental abruption and fetal or neonatal death by approximately 18%, according to new data.

In a late-breaking abstract presented at the American College of Cardiology (ACC) 2022 Scientific Sessions in Washington, DC, investigators from the Chronic Hypertension and Pregnancy (CHAP) Trial Consortium reported that treating blood pressure to achieve <140/90 mmHg with antihypertensive therapy in pregnant women was not only efficacious in reducing risk of composite adverse neonatal and fetal outcomes, but safe against risk of affected gestational-age birth weight.

The findings provide supporting evidence toward treating pregnant women with antihypertensive treatment—a controversial strategy which prior to the CHAP data was not supported by findings showing benefit for maternal, fetal or neonatal outcomes.

Led by Alan T. Tita, MD, PhD, of the University of Alabama Birmingham’s Department of Obstetrics and Gynecology and the Center for Women’s Reproductive Health, the CHAP investigators sought to establish data on targeting a blood pressure of <140/90 mmHg for pregnant women with mild chronic hypertension, and the incidence of adverse pregnancy outcomes associated with such care.

“There is consensus to treat pregnant women with severe hypertension, but for women with mild chronic hypertension (which is typically defined as a blood pressure of <160/110 mm Hg), it is unclear whether to withhold antihypertensive medication until the increase in blood pressure is severe or to continue the patient’s previously established therapy,” they wrote.

The team conducted the open-label, multicenter, randomized trial by assigning pregnant women with <160/100 mmHg blood pressure and singleton fetuses (gestational age, <23 weeks) to either recommended antihypertensive treatment or no such treatment unless severe hypertension (≥160 mmHg systolic pressure or ≥105 mmHg diastolic pressure) developed.

They sought a primary outcome of composite adverse pregnancy events across the 2 treatment arms, including preeclampsia with severe features, medically-indicated preterm birth at <35 weeks’ gestation, placental abruption, fetal death or neonatal death. Their primary safety outcome was gestational-age birth weight scoring below the 10th percentile.

Key secondary outcomes included composites of serious neonatal and maternal complications, preeclampsia, and prevalence of preterm births.

The trial included 2408 pregnant women, split 1:1 to either active treatment (n = 1208) or control (n = 1200). Mean participant age was 32.3 years old across both arms; approximately half (47.5%) were non-Hispanic Black. More than 82% of each arm had been previously pregnant, and mean baseline blood pressure was 134.2/83.9 and 133.7/83.4, respectively.

Tita and colleagues observed the composite primary outcome events in 30.2% of women in the active treatment group, versus 37.0% of women in the control group, indicating an adjusted risk ratio (RR) of 0.82 (95% CI, 0.74 – 0.92; P <.001). Treated women also fared better by incidence of the following outcomes:

• Serious maternal complications (2.1% vs 2.8%; RR, 0.75; 95% CI, 0.45 – 1.26)
• Severe neonatal complications (2.0% vs 2.6%; RR, 0.77; 95% CI, 0.45 – 1.30)
• Preeclampsia (24.4% vs 31.1%; RR, 0.79; 95% CI, 0.69 – 0.89)
• Preterm birth (27.5% vs 31.4%; RR, 0.87; 95% CI, 0.77 – 0.99)

For the primary safety outcome, investigators observed a 4% increased risk of small-for-gestational-age birth weights below the 10th percentile for the active-treatment group versus control: 11.2% versus 10.4% (adjusted RR, 1.04; 95% CI, 0.82 – 1.31; P = .76).

“It was determined that 14 to 15 patients would need to receive active treatment to prevent one primary-outcome event,” investigators wrote. “There were no significant between-group differences in the safety outcome of newborns who were under either the 10th percentile or the 5th percentile for gestational-age weight.”

In an editorial accompanying the CHAP data, Michael F. Greene, MD, and Winfred W. Williams, MD, of the Departments of Obstetrics and Gynecology and Medicine at Massachusetts General Hospital, highlighted the growing burden of hypertension in pregnant women.

“The rate of hypertension during pregnancy has been rising inexorably over 5 decades in parallel with the strongly associated covariates of a maternal age of more than 35 years and the presence of overweight or obesity, factors that were present in 55.9% of women who gave birth in 2019,” they wrote. “In addition, hypertension is more than twice as common in Black women as in White women.”

Though they cautioned the “relatively large” number of secondary outcomes observed in the CHAP trial warrant further interpretation, findings showing a decreased risk of progression to severe hypertension with early-initiated antihypertensive therapy are consistent with growing literature.

“The most exciting finding in this trial (possibly the result of the large enrollment) is the apparent reduction in the incidence of various measures of preeclampsia in the active-treatment group, findings that have not been observed in eight previous randomized trials, including CHIPS,” they wrote. “…If the results are confirmed in subsequent studies, such outcomes would be a compelling reason to change the recommendations for clinical practice regarding the treatment of mild hypertension during pregnancy.”

The study, “Treatment for Mild Chronic Hypertension during Pregnancy,” was presented at ACC 2022.