ACEI and ARB use in pregnancy an increasing concern

Despite being known teratogenic agents contraindicated in pregnancy, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) are being increasingly prescribed to women with hypertension during their childbearing years. This is leading to increased exposure to ACEIs and ARBs at the time of conception and during early pregnancy, and to an increased risk of serious birth defects and other adverse pregnancy outcomes, according to results of a study presented at the American College of Cardiology’s 59th annual scientific session.

“They should not be used in women of childbearing potential at all,” recommended Vellore J. Karthikeyan, MD, University Department of Medicine, City Hospital, Birmingham, United Kingdom.

Dr. Karthikeyan reviewed women visiting the antenatal hypertension clinic at City Hospital since 1990 when ACEIs first became available and identified 86 pregnancies in 82 women who were taking one of these agents at the time of conception or who had been prescribed one during early pregnancy. Among the 66 women taking an ACEI and 20 taking an ARB, the median pregnancy duration of exposure was 8 weeks of gestation. “In all cases we recommended immediate cessation at the first visit and prescribed safer alternatives as necessary,” he said, adding that many of the women required no antihypertensive therapy during their pregnancies. Most of the cases of ACEI or ARB use during pregnancy occurred after 2002, and the women reported being unaware that they should not be taking the drugs.

There was a high rate of adverse outcomes including 4 early miscarriages, 5 late intrauterine or early neonatal deaths, 3 cases of oligohydramnios, and 7 infants with developmental defects including trisomy 13, craniosynostosis, ventricular septal defect, sensorineural deafness, microcephaly, hypospadias, and hypotonia. One patient elected to terminate her pregnancy because of fears of teratogenic effects. The incidence of low birth weight was also high with 47% of infants being below the 25th weight percentile. The median birth weight was 2.38 kg and the median ponderal index was 23.1 kg/m³.

Some of the developmental defects such as deafness may be directly related to ACEI or ARB use, but the cause of others cannot be definitely attributed to the agents, researchers said. In addition, this was a fairly high-risk population; median age was 35 years, 21 women had diabetes, 6 had gestational diabetes, and 4 had renal disease.