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Cited by 705Pregnancy and preeclampsia studiesBlood Pressure and Hypertension StudiesPregnancy and Medication Impact

Antihypertensive drug therapy for mild to moderate hypertension during pregnancy

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Abalos, Edgardo, Duley, Lelia, Steyn, D Wilhelm·2014·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd002252.pub3PMC PMC6517078
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Abstract

BACKGROUND: Antihypertensive drugs are often used in the belief that lowering blood pressure will prevent progression to more severe disease, and thereby improve pregnancy outcome. This Cochrane Review is an updated review, first published in 2001 and subsequently updated in 2007 and 2014. OBJECTIVES: To assess the effects of antihypertensive drug treatments for women with mild to moderate hypertension during pregnancy. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (13 September 2017), and reference lists of retrieved studies. SELECTION CRITERIA: All randomised trials evaluating any antihypertensive drug treatment for mild to moderate hypertension during pregnancy, defined as systolic blood pressure 140 to 169 mmHg and/or diastolic blood pressure 90 to 109 mmHg. Comparisons were of one or more antihypertensive drug(s) with placebo, with no antihypertensive drug, or with another antihypertensive drug, and where treatment was planned to continue for at least seven days. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: For this update, we included 63 trials (data from 58 trials, 5909 women), with moderate to high risk of bias overall.We carried out GRADE assessments for the main 'antihypertensive drug versus placebo/no antihypertensive drug' comparison only. Evidence was graded from very low to moderate certainty, with downgrading mainly due to design limitations and imprecision.For many outcomes, trials contributing data evaluated different hypertensive drugs; while we did not downgrade for this indirectness, results should be interpreted with caution.Antihypertensive drug versus placebo/no antihypertensive drug (31 trials, 3485 women)Primary outcomes: moderate-certainty evidence suggests that use of antihypertensive drug(s) probably halves the risk of developing severe hypertension (risk ratio (RR) 0.49; 95% confidence interval (CI) 0.40 to 0.60; 20 trials, 2558 women), but may have little or no effect on the risk of proteinuria/pre-eclampsia (average risk ratio (aRR) 0.92; 95% CI 0.75 to 1.14; 23 trials, 2851 women; low-certainty evidence). Moderate-certainty evidence also shows that antihypertensive drug(s) probably have little or no effect in the risk of total reported fetal or neonatal death (including miscarriage) (aRR 0.72; 95% CI 0.50 to 1.04; 29 trials, 3365 women), small-for-gestational-age babies (aRR 0.96; 95% CI 0.78 to 1.18; 21 trials, 2686 babies) or preterm birth less than 37 weeks (aRR 0.96; 95% CI 0.83 to 1.12; 15 trials, 2141 women). SECONDARY OUTCOMES: we are uncertain of the effect of antihypertensive drug(s) on the risk of maternal death, severe pre-eclampsia, or eclampsia, orimpaired long-term growth and development of the baby in infancy and childhood, because the certainty of this evidence is very low. There may be little or no effect on the risk of changed/stopped drugs due to maternal side-effects, or admission to neonatal or intensive care nursery (low-certainty evidence). There is probably little or no difference in the risk of elective delivery (moderate-certainty evidence).Antihypertensive drug versus another antihypertensive drug (29 trials, 2774 women)Primary outcomes: beta blockers and calcium channel blockers together in the meta-analysis appear to be more effective than methyldopa in avoiding an episode of severe hypertension (RR 0.70; 95% CI 0.56 to 0.88; 11 trials, 638 women). There was also an increase in this risk when other antihypertensive drugs were compared with calcium channel blockers (RR 1.86; 95% CI 1.09 to 3.15; 5 trials, 223 women), but no evidence of a difference when methyldopa and calcium channel blockers together were compared with beta blockers (RR1.18, 95% CI 0.95 to 1.48; 10 trials, 692 women). No evidence of a difference in the risk of proteinuria/pre-eclampsia was found when alternative drugs were compared with methyldopa (aRR 0.78; 95% CI 0.58 to 1.06; 11 trials, 997 women), with calcium channel blockers (aRR: 1.24, 95% CI 0.70 to 2.19; 5 trials, 375 women), or with beta blockers (aRR 1.21, 95% CI 0.88 to 1.67; 12 trials, 1107 women).For the babies, we found no evidence of a difference in the risk oftotal reported fetal or neonatal death (including miscarriage) when comparing other antihypertensive drugs with methyldopa (aRR 0.77, 95% CI 0.52 to 1.14; 22 trials, 1791 babies), with calcium channel blockers (aRR 0.90, 95% CI 0.52 to 1.57; nine trials, 700 babies), or with beta blockers (aRR: 1.23, 95% CI 0.81 to 1.88; 19 trials, 1652 babies); nor in the risk for small-for-gestational age in the comparison with methyldopa (aRR 0.79, 95% CI 0.52 to 1.20; seven trials, 597 babies), with calcium channel blockers (aRR 1.05, 95% CI 0.64 to 1.73; four trials, 200 babies), or with beta blockers (average RR 1.13, 95% CI 0.80

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  • Maternal risks of hypertension in pregnancy include placental abruption, stroke, multiple organ failure (liver, kidney), and disseminated vascular coagulation.

    “Maternal risks include placental abruption, stroke, multiple organ failure (liver, kidney), disseminated vascular coagulation.”

    From 2020 International Society of Hypertension Global Hypertension Practice Guidelines (2020) · cites this paper as [126]

    The Methods section lists placental abruption, stroke, liver or renal failure, and disseminated intravascular coagulation as maternal outcomes. It does not say that liver and kidney failure occur together as multiple-organ failure; it says “liver or renal failure.” No page number is available in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Hypertension in pregnancy affects 5%-10% of pregnancies worldwide.

    “Hypertension in pregnancy is a condition affecting 5%-10% of pregnancies worldwide.”

    From 2020 International Society of Hypertension Global Hypertension Practice Guidelines (2020) · cites this paper as [126]

    The plain-language summary in the Background (page unavailable) says that up to one in 10 women have above-normal blood pressure readings during pregnancy. This supports the upper end of the claimed frequency, but the passage does not establish a 5% lower bound or specify a worldwide estimate. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Risks of preeclampsia are fetal growth restriction and preterm birth.

    “Risks are fetal growth restriction, preterm birth.”

    From 2020 International Society of Hypertension Global Hypertension Practice Guidelines (2020) · cites this paper as [126]

    The Methods and Discussion (pages unavailable) identify fetal growth restriction or small-for-gestational-age birth and preterm birth as outcomes considered in pregnancies with mild to moderate hypertension. They do not establish that these are specifically risks caused by preeclampsia; preeclampsia is treated as a separate outcome in the review. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • Fetal risks of hypertension in pregnancy include intrauterine growth retardation, preterm birth, and intrauterine death.

    “Fetal risks include intrauterine growth retardation, preterm birth, intrauterine death.”

    From 2020 International Society of Hypertension Global Hypertension Practice Guidelines (2020) · cites this paper as [126]

    The Background (page unavailable) says very high blood pressure can seriously affect a baby's growth and health, and identifies preterm delivery and fetal growth as concerns motivating treatment. The Discussion (page unavailable) examines preterm birth, small-for-gestational-age babies, and fetal or neonatal death in women with hypertension. It does not specifically establish intrauterine death as a risk of hypertension, and its death measure includes neonatal deaths and miscarriage. (LLM, conf=0.79)

    Experimental — accuracy not yet measured

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Authors
Abalos, E., Duley, L., & Steyn, D. W.
Affiliations
  • Centro Rosarino de Estudios Perinatales (AR)
  • Queen's Medical Centre (GB)
  • Stellenbosch University (ZA)
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2014-02-06
Volume
10
Issue
2
Pages
CD002252-CD002252
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd002252.pub3
PMC
PMC6517078
OpenAlex
W1627293103
Cited by
705
References
4
Citations by year
2026: 3 · 2025: 17 · 2024: 36 · 2023: 50 · 2022: 42 · 2021: 42 · 2020: 41 · 2019: 44 · 2018: 46 · 2017: 52 · 2016: 49 · 2015: 46 · 2014: 45 · 2013: 28 · 2012: 27
FWCI
10.23
Type
journal article
Language
en
Update notices
new_version (2018-10-01)
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute for Health and Care Research
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
Keywords
antihypertensive drugs, hypertensive disorders of pregnancy, preeclampsia, proteinuria, blood pressure reduction, drug safety in pregnancy, maternal outcomes, fetal outcomes, placental growth restriction, macrosomia, fetal growth restriction, placental abruption
MeSH terms
Antihypertensive Agents, Female, Humans, Hypertension, Pregnancy, Pregnancy Complications, Cardiovascular, Placebo Effect, Randomized Controlled Trials as Topic

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