Angiotensin-Converting Enzyme Inhibitors and the Risk of Congenital Malformations
Open accessAbstract
OBJECTIVE: To examine the association between first-trimester angiotensin-converting enzyme (ACE) inhibitor exposure and the risk of overall major congenital, cardiac, and central nervous system malformations. METHODS: We used a cohort of completed pregnancies linked to liveborn neonates derived from Medicaid claims from 2000 to 2010. We examined the risk of malformations associated with first-trimester exposure to an ACE inhibitor. Propensity score-based methods were used to control for potential confounders including maternal demographics, medical conditions, exposure to other medications, and measures of health care utilization. RESULTS: The cohort included 1,333,624 pregnancies, of which 4,107 (0.31%) were exposed to ACE inhibitors during the first trimester. The prevalence of overall malformations in the ACE inhibitor-exposed pregnancies was 5.9% compared with 3.3% in the unexposed (unadjusted relative risk, 1.82; 95% confidence interval [CI] 1.61-2.06), of cardiac malformations was 3.4% compared with 1.2% (relative risk 2.95, 95% CI 2.50-3.47), and of central nervous system malformations was 0.27% compared with 0.18% (relative risk 1.46, 95% CI 0.81-2.64). After restricting the cohort to pregnancies complicated by chronic hypertension (both exposed and unexposed) and accounting for other confounding factors, there was no significant increase in the risk of any of the outcomes assessed. Relative risks associated with first-trimester ACE inhibitor exposure were 0.89 (95% CI 0.75-1.06) for overall malformations, 0.95 (95% CI 0.75-1.21) for cardiac malformations, and 0.54 (95% CI 0.26-1.11) for CNS malformations. CONCLUSIONS: After accounting for confounders, among women with hypertension, exposure to ACE inhibitors during the first trimester was not associated with an increased risk of major congenital malformations.
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A large study found that after adjusting for confounders, first trimester ACE inhibitor exposure does not appear to be associated with congenital malformations.
“A large study found that after adjusting for confounders, first trimester ACE inhibitor exposure does not appear to be associated with congenital malformations (128).”
From 15. Management of Diabetes in Pregnancy: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [128]
The association with exposure during the first trimester is less consistent.
“The association with exposure during the fi rst trimester, however, is less consistent.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [68]
Other studies did not demonstrate an association with ACEi use in the first trimester after adjusting for underlying disease characteristics, particularly first-trimester hypertension.
“there were other studies that did not demonstrate such an association with ACEi use in the fi rst trimester, after adjusting for underlying disease characteristics, particularly fi rst-trimester hypertension. 68”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [68]
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- Authors
- Bateman, B. T., Patorno, E., Desai, R. J., Seely, E. W., Mogun, H., Dejene, S. Z., Fischer, M. A., Friedman, A. M., Hernandez-Diaz, S., & Huybrechts, K. F.
- Affiliations
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- Obstetrics & Gynecology
- Published
- 2017-01
- Volume
- 129
- Issue
- 1
- Pages
- 174-184
- ISSN
- 0029-7844 (ISSN-L)
- PMC
- PMC5177460
- OpenAlex
- W2560010172
- Cited by
- 102
- References
- 30
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 11 · 2023: 8 · 2022: 18 · 2021: 15 · 2020: 13 · 2019: 10 · 2018: 16 · 2017: 2 · 2016: 1
- FWCI
- 9.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (K24HL096141)
- National Institute of Mental Health (R01MH100216, K01MH099141)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K08HD075831)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Keywords
- ACE inhibitors, congenital malformations, first trimester drug exposure, cardiac anomalies, central nervous system malformations, maternal hypertension, prenatal drug exposure
- MeSH terms
- Congenital Abnormalities, Adult, Angiotensin-Converting Enzyme Inhibitors, Central Nervous System, Chronic Disease, Female, Heart Defects, Congenital, Humans, Hypertension, Pregnancy, Pregnancy Trimester, First, Risk Factors, United States, Cohort Studies, Prevalence, Case-Control Studies, Young Adult, Propensity Score
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