Diabetes Metab Res Rev. 2021 Nov;37(8):e3453. doi: 10.1002/dmrr.3453. Epub 2021 Apr 13.
Increased risk of major congenital malformations in early pregnancy use of angiotensin-converting-enzyme inhibitors and angiotensin-receptor-blockers: a meta-analysis.
Diabetes/metabolism research and reviews
Jennifer Fu, George Tomlinson, Denice S Feig
Affiliations
Affiliations
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
- University Health Network, Toronto, Ontario, Canada.
- Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada.
- Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada.
PMID: 33779043
DOI: 10.1002/dmrr.3453
Abstract
AIMS: To evaluate the risk of adverse fetal outcomes after exposure to angiotensin converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) in first trimester of pregnancy, by conducting a systematic review and meta-analysis.
MATERIALS AND METHODS: A systematic literature search was conducted using Medline, Embase, Cochrane and PubMed from inception to 25 November 2019. Studies were included if they evaluated pregnancies exposed to ACE-Is or ARBs, reported fetal outcomes, and compared these outcomes with a control group. Pooled odds ratios (ORs) were estimated using inverse variance-weighted random effects model. The protocol was registered with the PROSPERO International Prospective Register of Systematic Reviews (CRD42020160566).
RESULTS: Studies reporting on 6234 pregnancies exposed to ACE-Is or ARBs, 4104 pregnancies exposed to other oral antihypertensives, and 1,872,733 pregnancies without exposure were included in the meta-analysis. ACE-I or ARB exposed pregnancies, compared to non-exposed controls, had higher risk of major congenital malformations (OR 1.82; 95% confidence interval [CI]: 1.42-2.34), cardiovascular malformations (OR 2.50; 95% CI: 1.62-3.87) and stillbirths (OR 1.75; 95% CI: 1.21-2.53). There was no difference in congenital malformations observed between pregnancies exposed to other antihypertensives compared to non-exposed controls (OR 0.96; 95% CI: 0.69-1.33).
CONCLUSIONS: Women exposed to ACE-Is or ARBs during early pregnancy had higher risk of adverse fetal outcomes, including malformations and stillbirths, than non-exposed controls. This increased risk was independent of underlying maternal hypertension, as those exposed to other antihypertensives did not exhibit a higher risk than healthy controls. Women planning for pregnancy using these medications, including those with diabetic nephropathy, should be counselled appropriately.
© 2021 John Wiley & Sons Ltd.
Keywords: angiotensin-converting enzyme inhibitors; angiotensin-receptor antagonists; diabetes mellitus; meta-analysis; pregnancy; pregnancy outcomes
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