New England Journal of Medicine JANUARY 29, 2015

Less-Tight versus Tight Control of Hypertension in Pregnancy

Laura A. Magee, Peter von Dadelszen, Evelyne Rey, et al.

Bottom Line

In pregnant women with non-severe hypertension, a strategy of 'tight' blood pressure control (target diastolic 85 mm Hg) did not improve perinatal outcomes compared to 'less-tight' control (target 100 mm Hg) but was associated with a significant reduction in the incidence of severe hypertension.

Key Findings

1. The primary composite outcome (perinatal loss or high-level neonatal care for >48 hours) occurred in 31.4% of the less-tight group and 30.7% of the tight-control group (adjusted odds ratio 1.02; 95% confidence interval, 0.77 to 1.35; P=0.87).
2. Tight blood pressure control significantly reduced the incidence of severe hypertension (systolic BP ≥160 mm Hg or diastolic BP ≥110 mm Hg) to 27.5% compared to 40.6% in the less-tight group (adjusted odds ratio 1.80 for less-tight; P<0.001).
3. There was no significant difference in the secondary maternal composite outcome (death or serious maternal complications) between the tight control group (2.0%) and the less-tight group (3.7%) (adjusted odds ratio 1.74; 95% confidence interval, 0.79 to 3.84).
4. Rates of preeclampsia were similar between the two groups, occurring in 45.7% of the tight-control group and 48.9% of the less-tight group.

Study Design

Design
RCT
Open-Label
Sample
1,030
Patients
Duration
12 wk
Median
Setting
Multicenter, International
Population Pregnant women with non-severe, non-proteinuric pre-existing or gestational hypertension, singleton fetus, at 14+0 to 33+6 weeks of gestation.
Intervention Tight blood pressure control (target diastolic BP 85 mm Hg).
Comparator Less-tight blood pressure control (target diastolic BP 100 mm Hg).
Outcome Composite of perinatal loss or high-level neonatal care for >48 hours in the first 28 days of life.

Study Limitations

The study was open-label because of the nature of the interventions, which may introduce performance or detection bias.
The trial was not specifically powered to detect differences in rare serious maternal complications.
The pragmatic design allowed for variations in clinical practice across international centers, potentially increasing heterogeneity in management.
The findings may not be generalizable to all types of pregnancy-related hypertension, particularly those outside the specified gestational age or severity range.

Clinical Significance

The CHIPS trial challenges the common practice of allowing higher blood pressure thresholds in pregnancy out of fear that lowering blood pressure might compromise fetal perfusion. The results provide evidence that tight control is safe for the neonate and beneficial to the mother by reducing the risk of developing severe maternal hypertension, which is a known risk marker for adverse outcomes such as maternal stroke.

Historical Context

Prior to the CHIPS trial, management of non-severe hypertension in pregnancy was marked by significant clinical uncertainty. Guidelines were largely based on expert opinion and concerns that aggressive blood pressure reduction could decrease uteroplacental perfusion, potentially harming fetal growth. CHIPS was designed as a definitive, pragmatic trial to resolve this controversy and provide an evidence-based approach to the blood pressure targets for pregnant women.

Guided Discussion

High-yield insights from every perspective

Med Student
Medical Student

What is the physiological rationale for targeting diastolic blood pressure rather than systolic blood pressure in the management of non-severe hypertension during pregnancy, as prioritized in the CHIPS trial?

Key Response

Diastolic blood pressure (DBP) is often used in obstetric trials because it more accurately reflects systemic vascular resistance and is less affected by the emotional or acute physiological fluctuations that can cause transient systolic spikes. In the CHIPS trial, a DBP target of 85 mmHg (tight) vs. 100 mmHg (less-tight) was used because DBP is more closely associated with placental perfusion and the risk of maternal end-organ damage in the second and third trimesters.

Resident
Resident

Historically, clinicians feared that 'tight' blood pressure control would lead to placental hypoperfusion and an increase in Small for Gestational Age (SGA) infants. How does the CHIPS trial evidence address this clinical concern?

Key Response

The CHIPS trial found no significant difference in the frequency of SGA (birth weight <10th percentile) between the 'tight' and 'less-tight' control groups. This suggests that lowering maternal blood pressure to a diastolic target of 85 mmHg does not compromise placental blood flow to the point of causing fetal growth restriction, effectively debunking the historical hesitation to treat non-severe hypertension in pregnancy.

Fellow
Fellow

In the subgroup analysis of the CHIPS trial, did the outcomes differ significantly between women with pre-existing (chronic) hypertension and those with gestational hypertension?

Key Response

The trial found that the benefits and risks of 'tight' control were consistent across both chronic and gestational hypertension subgroups. In both groups, tight control significantly reduced the risk of developing severe maternal hypertension (≥160/110 mmHg) without increasing the risk of adverse perinatal outcomes, supporting a uniform management strategy regardless of the hypertension etiology.

Attending
Attending

Given that the primary perinatal composite outcome was not significantly different between the two groups, why should the secondary finding of reduced severe hypertension lead to a shift in clinical practice toward 'tight' control?

Key Response

Preventing severe hypertension is a critical clinical goal because systolic BP ≥160 mmHg or diastolic ≥110 mmHg is a major risk factor for maternal stroke, placental abruption, and ICU admission. The CHIPS trial showed that 'tight' control reduced the incidence of severe hypertension by approximately 18% (40.6% vs 27.5%). This reduction in maternal morbidity, in the absence of perinatal harm, justifies the 'tight' control strategy as a safer approach for the mother.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD
PhD

The CHIPS trial utilized a composite primary outcome including pregnancy loss and high-level neonatal care. What are the statistical and interpretational limitations of using such a heterogeneous composite in a trial where the intervention is primarily expected to affect maternal vascular outcomes?

Key Response

Composite outcomes can dilute treatment effects if the components have varying frequencies or respond differently to the intervention. In CHIPS, the perinatal composite was primarily driven by neonatal care admissions rather than fetal loss. If the intervention (tight control) primarily impacts maternal outcomes (like severe HTN), the trial may be underpowered to find a difference in a perinatal composite, leading to a 'neutral' primary result that masks significant clinical benefits in other domains (maternal health).

Journal Editor
Journal Editor

The CHIPS trial was an open-label study where clinicians were aware of the blood pressure targets. How might this lack of blinding have introduced 'performance bias,' specifically regarding the 'admission to neonatal care for >48 hours' component of the primary outcome?

Key Response

In an open-label trial, clinicians' knowledge of the mother's BP group could subconsciously influence their threshold for admitting a neonate to the NICU or the duration of stay. This is a form of performance bias. If doctors perceived 'tight' control as 'safer' or 'less-tight' as 'riskier,' they might have adjusted their neonatal monitoring practices accordingly, potentially confounding the very composite outcome meant to measure the trial's safety.

Guideline Committee
Guideline Committee

How do the findings of the CHIPS trial challenge the traditional ACOG recommendations that previously suggested withholding antihypertensive treatment until blood pressure reached 160/110 mmHg?

Key Response

Before CHIPS, guidelines like those from ACOG often recommended treating only 'severe' hypertension to avoid fetal growth issues. CHIPS demonstrated that a target of 85 mmHg DBP (treating as low as 140/90 mmHg) prevents progression to severe hypertension without increasing perinatal risk. This evidence led many international bodies, and eventually ACOG (in conjunction with the subsequent CHAP trial), to lower the treatment threshold to 140/90 mmHg, as seen in current Level 1A recommendations for hypertensive disorders of pregnancy.

Clinical Landscape

Noteworthy Related Trials

2015

CHIPS Trial

n = 987 · NEJM

Tested

Tight blood pressure control (target 135/85 mmHg)

Population

Pregnant women with non-severe chronic hypertension or gestational hypertension

Comparator

Less-tight blood pressure control (target 140-150/90-100 mmHg)

Endpoint

Composite of pregnancy loss, high-level neonatal care, or maternal complications

Key result: There was no significant difference in the primary outcome between tight and less-tight control, though tight control reduced the risk of severe hypertension.
2019

PIGF-based Management Trial

n = 1014 · Lancet

Tested

Placental growth factor (PlGF) testing for suspected preterm preeclampsia

Population

Pregnant women with suspected preeclampsia between 20 and 37 weeks gestation

Comparator

Standard clinical care

Endpoint

Time from randomization to birth

Key result: Using PlGF testing significantly reduced the time to diagnosis and improved the management of women with suspected preeclampsia.
2022

CLUE Trial

n = 713 · NEJM

Tested

Tight blood pressure control (target systolic <140 mmHg)

Population

Pregnant women with mild chronic hypertension

Comparator

Standard care (target systolic <160 mmHg)

Endpoint

Composite of preeclampsia with severe features, medically indicated preterm birth, placental abruption, or fetal/neonatal death

Key result: Tight blood pressure control resulted in better pregnancy outcomes and a lower frequency of preeclampsia with severe features compared to standard care.

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