Blood Pressure Meds and Birth Defects Possible Link Studied

Blood pressure medications known as ACE inhibitors cannot be considered safe to take even in the first trimester of pregnancy and should be avoided altogether by pregnant women, according to a report in the New England Journal of Medicine.

For years, physicians have known these commonly prescribed blood pressure medications are not safe during the second and third trimesters due to their association with birth defects.

So, physicians have routinely switched women to other medications once they find out they were pregnant. An estimated 5 percent to 8 percent of women develop high blood pressure, or hypertension, during pregnancy, according to the March of Dimes.

While both genetic and environmental factors, or a combination of the two, can lead to defects, the cause of about 70 percent is unknown, according to the March of Dimes.

Take Care - Avoid Altogether

But the new study suggests the wisest course is to avoid ACE inhibitor (angiotensin-converting enzyme) medications during the entire pregnancy.

"We found there was a three-fold increased [overall] risk of birth defects to infants whose mothers took ACE inhibitors the first trimester, compared to infants whose mothers took no blood pressure medication," says study author Dr. William O. Cooper.

Dr. Cooper is an associate professor of pediatrics at Vanderbilt University School of Medicine.

The study results prompted the US Food and Drug Administration (FDA) to hold a news briefing.

Experts say more research is needed before any assessment of ACE inhibitor use in early pregnancy can be made, say Drs. Robert Temple and Sandra L. Kweder of the FDA.

"If women are thinking about becoming pregnant, they should talk to their doctors" about the most appropriate blood pressure medication, says Dr. Temple.

The study found the risk of cardiovascular defects was nearly four times higher in children of women who took ACE inhibitors, compared with children of women who did not take any blood pressure medicine.

In addition, central nervous system birth defects were four times higher among the children of women who took ACE inhibitors.

Fetal exposure to other blood pressure medications during the first trimester did not produce an increased risk of birth defects, the study found.

Dr. Cooper and his colleagues studied 29,507 infants, all enrolled in Tennessee Medicaid and born between 1985 and 2000.

The researchers identified 209 babies exposed to ACE inhibitors during the first trimester only; 202 exposed to other types of blood pressure-lowering medicine during the first trimester alone; and 29,096 infants with no exposure to blood-pressure drugs during at any time during the pregnancy.

Then, the researchers identified major birth defects from hospitalization claims and vital records during the first year of life.

"We adjusted for other factors known to be associated with birth defects, such as diabetes," notes Dr. Cooper.

Major birth defects were found in 856 babies, or 2.9 percent; 203 had more than one defect.

Problems included cardiovascular defects; musculoskeletal defects such as upper limb difficulties; gastrointestinal problems; central nervous system defects such as spina bifida; and urologic defects.

More Study Needed for Certainty

It is not known how ACE inhibitors increase the risk of birth defects, says Dr. Cooper.

"ACE inhibitors inhibit an enzyme, that is how they affect blood pressure," he says. "This same enzyme is present in the fetal heart, kidney, and brain during the time the organs are being formed.

"Interfering with that angiotensin enzyme function during the period of organ formation could interfere with the proper formation of organs," notes Dr. Cooper.

In an accompanying editorial in the journal, Dr. Jan Friedman of the University of British Columbia, Vancouver, Canada, discusses the relative lack of information on potential problems caused by ACE inhibitor use early in pregnancy.

Animal studies have not found an increased risk of birth defects, but he added that "there actually has been very little information available to answer this question."

Dr. Friedman says more research is needed.

Of the Cooper study, he says, "This is not the last word on the subject, but it is shocking to realize it is almost the first."

Dr. Friedman also noted the difficulty of determining a risk-benefit profile for a mother and fetus when prescribing a medication for a pregnant patient.

The risks to an unborn baby are unknown for more than 90 percent of the prescription drugs approved in the US between 1980 and 2000, he notes, citing a 2002 report in the journal Obstetrics and Gynecology.

"Women of childbearing age put on an ACE inhibitor should discuss [with their physician] the possibility that these drugs can cause birth defects if they become pregnant," he says.

Each year in the US, an estimated 120,000 babies are born with birth defects, such as cystic fibrosis, Down syndrome, heart defects, cleft lip and palate, and other problems.

Always consult your physician for more information.