The New England Journal of Medicine MAY 04, 2022

Treatment for Mild Chronic Hypertension during Pregnancy (The CHAP Trial)

Tita AT, Szychowski JM, Boggess K, et al. (for the Chronic Hypertension and Pregnancy Trial Consortium)

Bottom Line

In pregnant women with mild chronic hypertension, initiating antihypertensive therapy to maintain blood pressure below 140/90 mm Hg significantly reduces the risk of composite adverse pregnancy outcomes without increasing the risk of small-for-gestational-age birth weight.

Key Findings

1. The primary composite outcome occurred in 30.2% of the active treatment group compared to 37.0% of the control group (adjusted risk ratio 0.82; 95% confidence interval 0.74 to 0.92; P<0.001).
2. Active treatment resulted in a lower incidence of pre-eclampsia with severe features (23.3% in the intervention group vs. 29.1% in the control group).
3. There was no statistically significant increase in the risk of small-for-gestational-age birth weight (birth weight below the 10th percentile for gestational age), occurring in 11.2% of the active treatment group versus 10.4% in the control group (P=0.56).
4. The treatment strategy improved overall pregnancy outcomes without compromising fetal growth.

Study Design

Design
RCT
Open-Label
Sample
2,408
Patients
Duration
34 wk
Median
Setting
Multicenter, US
Population Pregnant women with mild chronic hypertension (systolic BP 140–159 mm Hg or diastolic BP 90–104 mm Hg) at less than 23 weeks gestation.
Intervention Antihypertensive therapy targeted to a blood pressure goal of <140/90 mm Hg.
Comparator Usual care, where antihypertensive therapy was withheld unless blood pressure reached severe levels (≥160/105 mm Hg).
Outcome Composite of pre-eclampsia with severe features, medically indicated preterm birth at <35 weeks' gestation, placental abruption, or fetal/neonatal death.

Study Limitations

The trial was open-label, which could introduce bias in the management and reporting of outcomes, although the primary outcome was relatively objective.
The results may not be generalizable to all populations or settings, particularly those with limited access to standardized blood pressure monitoring or the specific medications used.
Long-term maternal and infant health outcomes beyond the immediate postpartum period were not the primary focus of this specific analysis.

Clinical Significance

The CHAP trial fundamentally shifted obstetric practice in the United States by providing robust evidence that treating mild chronic hypertension in pregnancy to a target of <140/90 mm Hg is beneficial, contradicting previous guidance that advised withholding treatment unless blood pressure reached severe levels (≥160/105 mm Hg). This approach is now the standard of care to mitigate risks of severe pre-eclampsia and preterm birth.

Historical Context

For decades, clinicians were cautious about treating mild chronic hypertension during pregnancy due to theoretical concerns that blood pressure lowering might impair placental perfusion and lead to fetal growth restriction (small-for-gestational-age infants). Consequently, guidelines often recommended expectant management unless hypertension reached severe thresholds. The CHAP trial addressed this long-standing clinical uncertainty with definitive evidence.

Guided Discussion

High-yield insights from every perspective

Med Student
Medical Student

What is the historical physiologic concern regarding the treatment of mild hypertension during pregnancy, and how does the CHAP trial's primary safety outcome address this?

Key Response

Historically, clinicians feared that lowering maternal blood pressure might reduce placental perfusion and lead to fetal growth restriction (small-for-gestational-age infants). The CHAP trial demonstrated that targeting a BP of <140/90 mmHg significantly reduced adverse pregnancy outcomes without increasing the risk of small-for-gestational-age birth weight (below the 10th percentile), effectively refuting the concern that tighter control harms fetal growth.

Resident
Resident

Prior to the CHAP trial, many guidelines suggested a threshold of 160/105 mmHg for initiating antihypertensive therapy. Based on this study, what is the new recommended treatment threshold and what are the preferred first-line medications for managing mild chronic hypertension in pregnancy?

Key Response

The CHAP trial supports initiating therapy at a threshold of 140/90 mmHg. The study primarily utilized labetalol and extended-release nifedipine as first-line agents, which have established safety profiles in pregnancy and were used to maintain BP below the target of 140/90 mmHg.

Fellow
Fellow

The CHAP trial reported a significant reduction in the composite primary outcome. Analyze the individual components of this composite: which specific maternal and neonatal outcomes drove the statistical significance, and what does this imply for MFM practice?

Key Response

The reduction in the primary composite outcome (preeclampsia with severe features, medically indicated preterm birth before 35 weeks, placental abruption, or fetal/neonatal death) was primarily driven by lower rates of preeclampsia with severe features and medically indicated preterm birth. This suggests that tighter BP control stabilizes the maternal vascular environment, delaying the onset of severe hypertensive complications that necessitate early delivery.

Attending
Attending

Given the 'pragmatic' nature of the CHAP trial, how should the findings be applied to patients with chronic hypertension who have comorbidities such as pre-existing diabetes or renal disease, who were also included in the cohort?

Key Response

The CHAP trial was designed to be broadly generalizable, including patients with diabetes and other comorbidities common in the chronic hypertensive population. Subgroup analyses suggested consistent benefits across these groups. For the attending physician, this reinforces that the <140/90 target is a robust standard of care for the diverse 'real-world' obstetric population, not just those with isolated hypertension.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD
PhD

Evaluate the implications of the 'open-label' pragmatic design of the CHAP trial versus a traditional double-blinded placebo-controlled trial. What are the specific risks to internal validity regarding the diagnosis of 'preeclampsia with severe features'?

Key Response

In an open-label trial, clinicians are aware of the treatment group, which may introduce ascertainment bias. Since 'preeclampsia with severe features' involves some clinical subjectivity, knowledge of the BP group could influence how often a clinician looks for or labels severe features. The CHAP trial mitigated this risk by using a blinded committee to adjudicate primary outcome events based on objective data.

Journal Editor
Journal Editor

While the CHAP trial is a landmark study, a critical reviewer might note the 21.7% primary outcome rate in the control group. How does the choice of a 'composite' endpoint impact the trial's power, and what are the editorial risks of including 'medically indicated preterm birth' in that composite?

Key Response

Composite endpoints increase statistical power by increasing the number of events. However, the risk is 'dilution' if one component is more subjective or less clinically significant than others. 'Medically indicated preterm birth' is influenced by clinician decision-making (which was unblinded in CHAP); if editors feel the delivery threshold was lower in one group, it could challenge the conclusion that the intervention itself improved biological outcomes.

Guideline Committee
Guideline Committee

How do the CHAP trial results necessitate an update to the ACOG Practice Bulletin No. 203, and what strength of recommendation should be assigned to the new <140/90 mmHg threshold?

Key Response

ACOG Practice Bulletin No. 203 (2019) previously recommended treatment only for BP ≥160/105 mmHg. Following CHAP, ACOG and SMFM issued a Practice Advisory (2022) recommending therapy for chronic hypertension at 140/90 mmHg. Given the large-scale, multicenter, randomized controlled nature of CHAP, this represents Level A evidence, justifying a 'Strong' recommendation for changing the threshold of care.

Clinical Landscape

Noteworthy Related Trials

2015

CHIPS Trial

n = 987 · NEJM

Tested

Less-tight control (target diastolic 100 mm Hg)

Population

Pregnant women with non-severe hypertension

Comparator

Tight control (target diastolic 85 mm Hg)

Endpoint

Composite of pregnancy loss or high-level neonatal care

Key result: Tight control did not significantly improve pregnancy outcomes compared with less-tight control, but it did reduce the risk of severe hypertension.
2019

ACOG Committee Opinion No. 767

n = N/A · Obstet Gynecol

Tested

Standard antihypertensive thresholds

Population

Pregnant women with chronic hypertension

Comparator

Historical management thresholds

Endpoint

Guideline recommendations

Key result: Established a threshold of 160/110 mm Hg for initiation of antihypertensive therapy in pregnant women.
2020

Preeclampsia Outcomes Trial (PETRA)

n = 228 · Hypertension

Tested

Antihypertensive therapy

Population

Pregnant women with mild chronic hypertension

Comparator

No antihypertensive therapy

Endpoint

Severe hypertension or preeclampsia

Key result: The trial suggested that treatment did not significantly reduce the rate of severe maternal or neonatal adverse outcomes.

Tailored to your role

Want this tailored to you?

Add your specialty or training stage to get role-specific takeaways and more questions.

Personalize this analysis