Study shows treating preexisting high BP in pregnancy improves outcomes

While 2 to 4% of pregnant women suffer from chronic hypertension (high blood pressure) prior to pregnancy, it still is controversial to use medications to control high blood pressure during pregnancy. Mild chronic hypertension in pregnancy is associated with up to a 5-fold increase in preeclampsia, preterm birth, placental abruption, low birthweight and perinatal death. And determining the proper blood pressure to alleviate those risks without compromising blood flow to the fetus is still not agreed upon.

For decades there was a concern that there would need to be a trade-off: lowering maternal blood pressure was believed to possibly come at the expense of fetal growth without a meaningful accompanying maternal health benefit. A team of maternal-fetal medicine specialists across the country, including researchers from Baylor College of Medicine, have found that safe-in-pregnancy medications targeted to keep maternal blood pressure at under 140/90 mmHg would improve maternal outcomes without compromising growth or well-being of the baby.

The findings, published in the New England Journal of Medicine, provide comprehensive, evidence-based data for treating non-severe forms of chronic hypertension during pregnancy.

The results are from the Chronic Hypertension and Pregnancy, or CHAP, trial, a consortium of more than 60 clinical sites across the United States, including Baylor and Texas Children’s Hospital. The consortium was led by the University of Alabama at Birmingham. The trial evaluated the effects of prescribing blood pressure medication to pregnant women with mild chronic hypertension.

“Our CHAP trial is a game changer and will provide clear guidance for obstetricians and maternal-fetal medicine specialists. Using antihypertensive medications known to be safe in pregnancy (such as the beta blocker labetalol or the calcium channel blocker nifedipine) to control maternal high blood pressure under 140/90 has clear and demonstrated benefits to not only the mom but also to her baby. This is a superb example that we can reduce maternal morbidity and mortality without a trade-off for the developing fetus or newborn. In other words, families do not need to choose between mom and baby health: both are accomplishable,” said Dr. Kjersti Aagaard, professor in the Department of Obstetrics and Gynecology, co-author of the paper and principal investigator at Baylor and Texas Children’s.

“In light of the new data, it is important that we reevaluate current recommendations, update practice guidelines and begin treating most, if not all, pregnant women with chronic hypertension with medication,” said Alan Tita, professor of obstetrics and gynecology in the UAB Marnix E. Heersink School of Medicine, principal investigator for the CHAP trial and lead author of the paper.

The CHAP consortium, with clinical and data coordinating centers in the UAB departments of obstetrics and gynecology and biostatistics and Center for Women’s Reproductive Health, launched the CHAP program in 2014 with funding from the National Institutes of Health’s Heart, Lung and Blood Institute. From September 2015 to March 2021, CHAP enrolled more than 2,400 pregnant women with known mild chronic hypertension, whose blood pressure was greater than 140/90 mmHg but less than 160/105 mmHg.

Notably, the CHAP trial is one of the most comprehensive and diverse studies of its kind. The Black patient population is disproportionately affected by chronic hypertension, and almost 50% of study participants were Black mothers.

“We screened a total of 29,772 women in order to randomize 2,419 women across the clinical sites. Our goal was to enroll those who disproportionately suffer from maternal chronic hypertension and its consequences, and our enrollment cohort was compromised of 48% of Black mothers, 20% Hispanic mothers and 28% non-Hispanic white mothers,” Aagaard said.

Trial parameters, results

Participants were randomized into active and standard treatment groups. The active group was prescribed blood pressure medication, mostly labetalol or nifedipine, to keep blood pressure below 140/90 mmHg. The standard group received medication only if a participant developed more severe hypertension, or a blood pressure greater than 160/105 mmHg. Participants were evaluated in routine clinic visits through six weeks after delivery.

There was an almost 20% decrease in pregnancy complications for women treated with medication compared to the standard group. Complications included severe preeclampsia and preterm births before 35 weeks’ gestation.

Preeclampsia, a pregnancy complication that occurs after 20 weeks’ gestation, affects up to 8% of pregnancies in the United States but affects more than 30% of pregnant women with chronic hypertension. It is characterized by hypertension and sometimes signs of damage to other organ systems, such as the brain, liver and kidneys. In the active group, severe preeclampsia was reduced for some, up to 29%.

Preterm births before 35 weeks’ gestation were were significantly reduced in the active group by about 16%. Babies born before 35 weeks have an increased chance for short-term morbidities, long-term health complications and intellectual and developmental disabilities.

Additionally, the active group saw reductions in frequency of severe maternal hypertension, any preeclampsia with or without severe features, and any preterm birth before 37 weeks. There was slight or no difference in maternal cardiovascular complications and neonatal complications between the two study groups. Importantly, newborn size also was not affected by treatment.

“Not only did our CHAP trial provide clear clinical guidance for obstetricians and maternal-fetal medicine specialists, but by nearly 50% of our participants enrolled being Black we are providing crucial information to folks most likely to disproportionally suffer,” Aagaard said. “By participating in the CHAP trial, these women provided the evidence we needed to ultimately improve pregnancy outcomes with chronic hypertension. We appreciate all of our pregnant study participants, and thank them.”

NIH adds to CHAP funding

The National Institutes of Health recently awarded additional funding to the CHAP consortium in September 2021 to follow mothers enrolled in the program until five to 10 years following their completion of the trial to examine the long-term trajectory of hypertension and cardiovascular outcomes. Additional funding to study preeclampsia epigenetics using samples from the CHAP trial was also awarded in February 2022. These studies, including a potential study of childhood outcomes, will provide a more comprehensive view of the effects of treatment of chronic hypertension with medication during pregnancy.

The CHAP consortium included more than 60 clinical sites across the United States. Baylor College of Medicine and Texas Children’s Hospital, Columbia University, University of North Carolina-Chapel Hill, University of Pennsylvania, University of Texas at Houston, Duke University, Stanford University, WakeMed Hospital, University of California-San Francisco, St. Luke’s Health Network, University of Oklahoma, MetroHealth System, Indiana University, Drexel University, University of Utah, University of Texas Southwestern, Intermountain Healthcare, Ochsner Baptist Medical Center, Christiana Care Health Services, University of Texas Medical Branch, UnityPoint Health - Meriter Hospital, Marshfield Clinic, St. Peters University Hospital, Washington University, University of Mississippi Medical Center-Jackson, Magee Women’s Hospital, and University of Pittsburgh were among the partners with UAB in the project.