Literature

From Pages to Practice

By MaryAnn Wilbur, MD, MPH, MHS

Published July 20, 2022

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Ms. Cooper is a 32-year-old primigravida at 19 weeks and 2 days’ gestation, based on last menstrual period (LMP) and confirmed on 8-week ultrasound. She presented to the resident continuity clinic for routine prenatal care. You discuss how she is feeling and her upcoming anatomy sonogram and glucose tolerance test. Her blood pressure is 152/97 mm Hg. At her last visit 2 weeks ago, her blood pressure was also elevated at 146/88 mm Hg, but it was the first elevated blood pressure noted in her record. Ms. Cooper looks and feels well. How should you manage her hypertension? 

Recently, you have noticed several junior faculty managing pregnant patients with mild hypertension fairly aggressively by prescribing antihypertensive medication. However, the senior faculty member overseeing clinic stated that such patients should simply be monitored until blood pressures are in the higher range, due to concern about decreasing placental pressure and perfusion to the growing fetus. What does the evidence show?

The recently published Chronic Hypertension and Pregnancy (CHAP) Trial examined whether targeting a blood pressure of <140/90 mm Hg using antihypertensive medication reduced the incidence of adverse pregnancy outcomes without compromising fetal growth in 2400 pregnant women with mild hypertension (blood pressure between 140/90 and 160/105 mm Hg). The women were randomized before 23 weeks’ gestation to receive oral antihypertensives or observation and no treatment. 

The women in the treatment group were significantly less likely to experience the composite primary endpoint (including preeclampsia, preterm delivery <35 weeks, placental abruption, fetal death, or neonatal death). Notably, the infants in the two groups were similar in size, suggesting that hypertensive treatment did not decrease placental perfusion and cause low birth weight. The number needed to treat (NNT) to prevent one primary outcome was 14.7, supporting the conclusion that treating women with chronic mild hypertension during pregnancy improves obstetric outcomes.

One of the most important aspects of this trial is the generalizability of the results. The trial participants represented the racial and ethnic diversity of pregnant women in the U. S. with chronic hypertension.  Armed with the data from this large, multi-institution, well-balanced and represented trial, you initiate a conversation with your senior faculty colleague about the risks and benefits of actively managing Ms. Cooper’s hypertension and suggest starting her on medication to lower her blood pressure. You can also point to new guidelines that have been established, based on these data.  

The following NEJM Journal Watch summary provides more details of the study.

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Is Antihypertensive Therapy Beneficial for Pregnant Women with Mild Chronic Hypertension?

Marie Claire O'Dwyer, MB BCh BAO, MPH, reviewing Tita AT et al. N Engl J Med 2022 Apr 2

Optimal management of mild chronic hypertension in pregnancy is uncertain, because no consensus exists on ideal pregnancy blood pressure (BP) targets or thresholds for initiating pharmacotherapy. Pharmacologic blood pressure lowering might improve outcomes, but concerns persist about risk for fetal growth restriction.

This U.S. multicenter, open-label trial included 2400 women with mild chronic hypertension (defined as BP between 140/90 and 160/105 mm Hg) and singleton pregnancies of less than 23 weeks' gestation. Most participants (78%) had prepregnancy hypertension, and most already were taking medication; the other 22% received hypertension diagnoses during early pregnancy. Participants were randomized to active treatment (targeting a BP of <140/90 mm Hg) or to an untreated control group (unless BP rose to ≥160/105 mm Hg, at which time they were withdrawn from the trial). Labetalol or nifedipine generally were the first-line drugs. 

Mean achieved BP was lower in the active-treatment group than in the control group (130/79 vs. 133/82 mm Hg). The composite primary endpoint (i.e., preeclampsia with severe features, indicated preterm delivery <35 weeks, placental abruption, fetal death, or neonatal death) occurred significantly less frequently in the active-treatment group (30% vs. 37%); this difference was driven mainly by lower rates of preeclampsia with severe features (23% vs. 29%) and indicated preterm delivery <35 weeks (12% vs. 17%). No significant differences were noted between groups in percentage of babies who were small for gestational age.

Comment: Antihypertensive therapy improved clinically meaningful pregnancy outcomes and appeared to be safe in this study; 15 women required treatment to prevent 1 adverse outcome. The mean BP difference was modest, but perhaps active treatment prevented intermittent surges in BP that are not captured by occasional in-office measurements. The American College of Obstetrics and Gynecology recommends drug treatment only when BP reaches 160/110 mm Hg (Obstet Gynecol 2019; 133:215.), but I suspect that the current study will result in revisions of that guideline.

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MaryAnn Wilbur was a 2015-2016 NEJM Editorial Fellow. She is now a clinical fellow in Gynecologic Oncology at Johns Hopkins Hospital. MaryAnn graduated with a combined MD/MPH from Boston University in 2011 and completed residency training in Gynecology & Obstetrics at Johns Hopkins Hospital in June 2015. Her areas of interest include women’s health issues and health outcome disparities.