Cohort studies that compared exposure to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers during the first trimester of pregnancy versus no exposure or exposure to other antihypertensives were eligible for inclusion. Eligible studies were required to provide sufficient data for meta-analysis. Studies that reported on minor malformations, growth retardation, death or functional abnormalities were not eligible for inclusion. Case control and cohort studies not providing sufficient data for meta-analysis were eligible for inclusion in the qualitative analysis.
The primary outcome was presence of major congenital malformation (defined as serious or major structural or mental defect that could have adverse effects on health or development).
Some included cohort studies excluded mothers with diabetes, previous exposure to known teratogens, or a history of chromosomal/genetic defects. Other antihypertensives included calcium channel blockers, beta blocking agents, anti-adrenergic drugs, drugs acting on arteriolar smooth muscles, and diuretics. Mothers treated with antihypertensives were reported to be older, more likely to smoke, have a higher body mass index, and be more likely to take other medications for comorbid conditions.
Two reviewers independently screened studies for inclusion, with disagreements resolved through consensus.