Birth Injuries e-Resource

According to the research, one-third of the birth defects identified in newborns born to women who were prescribed ACE inhibitors in the firs trimester, involved the heart, one-quarter involved the limbs or face, and one-tenth of the defects involved the brain or spinal cord.

In the study, the researchers examined pharmacy records and data from the Tennessee Medicaid database for the years between 1985 and 2000, which allowed them to review records of ACE inhibitors prescribed for women during the first trimester as well as infant outcomes.

In reaching their results, the researchers compared newborns exposed to ACE inhibitors with a cohort of infants whose mothers received other high blood pressure drugs in the first trimester, and a group of newborns who were not exposed to any hypertension medications.

Some experts expressed alarm at finding such serious adverse events in a study on drugs that have already been on the market for a quarter of a century. In an editorial accompanying the study in JAMA, Dr J M Friedman, MD, PhD, from the University of British Columbia in Vancouver, Canada, said more research on the teratogenic potential of ACE inhibitors in pregnancy is called for.

"This is not the last word on the subject," he wrote, "but it is shocking to realize that it is almost the first."

"Birth defects caused by teratogenic treatments are preventable," Dr Friedman states, "and babies and their mothers are being harmed unnecessarily because we do not know enough about which treatments to use and which to avoid."

"Further study is needed to determine the precise risk and its relationship to individual drugs," he advises, "but the increase appears to be great enough to require discussion with all women of reproductive age who are prescribed ACE inhibitors."

"Detailed fetal ultrasonography and echocardiography at about 18 weeks of gestation," he says, "should be offered to women who have taken such drugs in the first trimester of pregnancy."

"A woman who learns she is pregnant while taking an ACE inhibitor," he warns, "should immediately be switched to another antihypertensive agent to minimize the risk of fetopathy."

But the findings of this study are not actually new. A surveillance study in 2002, of Michigan Medicaid recipients involving 86 newborns exposed to captopril during the first trimester found 4 newborns (4.7%) had major birth defects, including one cardiovascular anomaly, one polydactyly, one limb reduction defect, and one hypospadias.

In addition, ACE inhibitors have long been associated with serious birth defects in infants born to mothers who used the drugs during the second and third trimester of pregnancy. Back on March 13, 1992, the FDA announced that all ACE inhibitors, "will be required to carry a "boxed warning" on the label for women in the advanced stages of pregnancy."

"At the agency's request," the FDA said in a press release, "six pharmaceutical companies are simultaneously sending out a "Dear Doctor" letter emphasizing that women who take the drug in the second and third trimesters of pregnancy are running the risk of causing significant harm to fetuses, including kidney failure and face or skull deformities."

For several years before that announcement, the labeling on ACE inhibitors had warned about the dangers of their use by pregnant women, but nonetheless, additional cases of birth defects continued to be reported. "More than 50 cases of fetal harm have been reported over the past several years," the FDA stated.

"The warnings in the labeling," its press release stated, "are therefore being strengthened by including a boxed warning and other changes."

At the time, pharmacists were also alerted to the label changes and were provided stickers to paste on ACE inhibitor prescription bottles that read, "If you become pregnant consult your doctor promptly about switching to a different drug."