Some blood pressure drugs previously thought to be safe when taken early in pregnancy now appear to substantially raise the risk of major birth defects, doctors say.
Babies whose mothers took ACE inhibitors in their first trimester were more than twice as likely to be born with serious heart and brain problems than those not exposed to any pressure-lowering medicines, a large study in Tennessee found. Other types of blood pressure drugs did not raise the risk to babies.
The research raises troubling questions about the lack of safety data for many drugs prescribed to pregnant women.
About 8 percent of pregnant women develop high blood pressure, which can lead to a heart attack or stroke.
Exactly how many pregnant women take ACE inhibitors or another blood pressure medication is unclear. However, a national survey found the number of ACE inhibitor prescriptions given to women of childbearing age increased from 1.4 million in 1995 to 2.7 million in 2002, the latest data available.
ACE inhibitors already carry a strong Food and Drug Administration "black box" warning about their dangers in the later stages of pregnancy, and the label says the drugs should be discontinued when pregnancy is detected. But little has been known about their early effects.
Based on the new findings, taking these drugs during early pregnancy "cannot be considered safe and should be avoided," lead researcher Dr. William Cooper, a Vanderbilt University pediatrician, said in Thursday's New England Journal of Medicine.
The FDA said more research is needed before it considers changing the warning label to specifically include the risks during the first trimester. But the agency is notifying doctors and patients about the dangers through its Web site.
Doctors said expectant mothers should not stop treatment, because uncontrolled high blood pressure can harm them and the fetus, but should immediately switch to other drugs. Women contemplating pregnancy were advised to ask their doctors about their options.
"This is a wake-up call. We need to learn more about these drugs to offer better advice to pregnant women," said Dr. J.M. Friedman, a medical geneticist at the University of British Columbia who had no role in the study.
ACE inhibitors have been on the market for 25 years, but little research has been done on their effects during early pregnancy with the exception of animal experiments and small human studies. The drugs work by relaxing blood vessels and increasing blood flow to the heart.
Last year, U.S. sales of ACE inhibitors topped $3.8 billion, with about 150 million prescriptions filled, according to IMS Health, a pharmaceutical information company. The top-sellers include Lotrel, Altace and Lisinopril.
In the study, researchers studied Medicaid records on 29,507 Tennessee infants born between 1985 and 2000. Of those, 411 had mothers who took a blood pressure drug at least once during their first trimester, including 209 who took ACE inhibitors.
About 7 percent of babies exposed to ACE inhibitors developed major birth defects compared with about 2 percent whose mothers took no drugs or other blood pressure medication, such as water pills, calcium channel blockers or beta blockers.
The most common defects included holes in the heart and neurological and kidney problems.
Researchers found no increased risk among babies whose mothers took another type of blood pressure medication. But they said it is premature to declare those drugs safe to use during early pregnancy.
"It's a sobering finding," said Dr. Robyn Barst, a pediatric cardiologist at Columbia University and spokeswoman for the American Heart Association. "It highlights our lack of data on many drugs that we think are perfectly safe."
The study was partly funded by the FDA. Three co-authors reported receiving support or fees from Novartis AG or Pfizer Inc. Novartis makes Lotrel. Pfizer makes the calcium blocker Norvasc.
In an accompanying editorial, Friedman of the University of British Columbia said the ACE inhibitor study points to a larger problem about the lack of safety data available on most new drugs when they receive government approval.
The FDA acknowledged it was imperfect system. Dr. Robert Temple, the agency's associate director for medical policy, said the government is trying to improve its detection of harmful effects through patient registries and other studies.
"The only way to discover (risks) is through long-term use. That's a little uncomfortable. It means you only learn about what drugs do to pregnancies after the drug's been used for a long time," Temple said.
In the early 1990s, the FDA required pharmaceutical companies to put warning stickers on ACE inhibitors after the agency received a few reports from women whose babies were harmed. The label warned that ACE inhibitors can cause skull deformities, kidney failure, lung problems and even fetal death when taken in the last two-thirds of pregnancy.
On the Net:
New England Journal of Medicine: www.nejm.org
Food and Drug Administration: www.fda.gov