Nonprescription Drugs
Could Pose Risk in Pregnancy

By AMY DOCKSER MARCUS
Staff Reporter of THE WALL STREET JOURNAL
March 2, 2004; Page D1

Doctors have focused on identifying prescription drugs that pose risks for pregnant women ever since the 1960s, when thousands of children were born with devastating birth defects after their mothers took thalidomide for morning sickness. But the medical profession has only recently begun to pay close attention to the potential risks of over-the-counter drugs.

Women frequently assume that, if medications don't require a prescription, they are safe to take during pregnancy. But most medicines have been tested only for use in the general adult population.

And though most over-the-counter drugs contain warnings advising pregnant women to consult a doctor before using them, many women do not do so. Even when they do, the physician often has little more than anecdotal experience to rely on in providing guidance.

No one is suggesting that among the many pills sold over-the-counter there is a drug likely to cause the numbers and severity of birth defects that thalidomide did. And the odds of delivering a baby with defects appear to be extremely low even for women who take such drugs.

But some health-care practitioners have grown concerned by the results of recent studies of some popular over-the-counter medications, such as pseudoephedrine (commonly sold under the brand name Sudafed), acetaminophen (commonly sold as Tylenol), and ibuprofen (commonly sold as Advil).

While small and far from conclusive, some of the studies suggest that women who use pseudoephedrine in their first trimester may have a higher risk of having a baby born with gastroschisis, a rare defect in the abdominal wall that results in abdominal organs bulging outside the body -- especially when pseudoephedrine is used in combination with acetaminophen. Aspirin, too, has been linked to an increased risk for gastroschisis in a number of studies. Gastroschisis, which occurs in only one out of 10,000 live births, can be repaired but requires surgery, usually right after birth. Ibuprofen and other nonsteroidal anti-inflammatory drugs have been linked to the premature closure of the fetal ductus when used in the third trimester. More studies are in the works.

According to figures kept by birth defect research groups, the incidence of women using nonprescription medicines to treat headaches, colds, upset stomachs and other ailments typical during pregnancy is on the rise. Researchers at Boston University have found that over 20% of pregnant women use four or more drugs during their pregnancy, with over-the-counter medicines being the most common. Sixty-one percent of pregnant women studied reported using acetaminophen; 16% used aspirin; 10% used ibuprofen.

"It is not enough to identify high-risk drugs. There could be many drugs that pose only moderately increased risks of birth defects but because they are so widely used, the potential health impact could be very great,'' says Allen A. Mitchell of the Slone Epidemiology Center at Boston University, who wrote a widely discussed paper late last year in the New England Journal of Medicine calling attention to the public health issue posed by the growing use of over-the-counter medications during pregnancy.

The American College of Obstetricians and Gynecologists doesn't have guidelines for what doctors should tell pregnant patients about over-the-counter drugs. Laura Riley, who heads the group's practices committee, said that most obstetricians tell patients that Tylenol is safe and that all other drugs should be discussed.

The fact is, doctors and drug regulators acknowledge, there is really very little known about the effect of many drugs -- prescription or over-the-counter -- on a developing fetus, partly because pregnant women are discouraged, or often barred, from participating in clinical trials. "If most pregnant women knew how little data there are on the use of drugs in pregnancy, they would be surprised and appalled," says Sandra Kweder, deputy director of the Office of New Drugs at the Food and Drug Administration.

In an effort to get more hard data, the FDA says it is increasingly asking companies to set up pregnancy registries after a drug goes to market to monitor the outcomes of pregnancies of women taking it. The agency is also working on changing the regulations for prescription-drug labeling to include more detailed information about the latest epidemiological data.

Last month, the American Academy of Allergy, Asthma, and Immunology, a professional group for allergists and immunologists, proposed a new surveillance system, funded by the pharmaceutical industry, to collect information on all asthma and allergy medications -- both prescription and over-the-counter -- that pregnant women use.

BENEFIT VS. RISK The following groups can provide more information about the use of over-the-counter and prescription medications during pregnancy: group Phone number/WEB SITE What They Offer Organization of Teratology Services 866-626-OTIS/ www.otispregnancy.org Consultations and fact sheets on exposures to various medicines. Recruiting for studies of rheumatoid arthritis drugs. March of Dimes www.modimes.org Information on birth defects, lists of local chapters to contact. Pregnancy Registries www.fda.gov/womens/ Lists on-going pregnancy registries seeking participants. Motherisk Program 416-813-6780/ www.motherisk.org Counseling for pregnant women concerned about exposure to medications.

Over 150,000 babies in the U.S. are born each year with a serious birth defect. While some causes of birth defects have been linked to such things as chromosomal and genetic problems, the reason is unknown in the vast majority of cases. Many doctors believe that a combination of a person's genetic makeup and environmental factors, including smoking or exposure to certain medications, may play a role in causing many birth defects. They also say that not everyone will react in the same way to a drug, meaning a particular medicine may increase risk in some women but not in everyone.

There have been a number of recent studies looking at pseudoephedrine, a drug found in nasal decongestants such as Pfizer Inc.'s Sudafed, and whether it increases a woman's risk of having a child with gastroschisis or small intestinal atresia, a serious but rare congenital defect of the small intestine that also requires surgery to fix. In a 2002 study done by Boston University's Slone group, women who used products that contained both pseudoephedrine and acetaminophen had a 4.2-fold increase in risk of having a child with gastroschisis and a threefold risk of having a baby with small intestinal atresia. Women who took these medications and also smoked were at even higher risk.

Bob Mennella, the chief safety officer for Pfizer, which makes Sudafed, said that the company monitors the performance of all of its drugs closely, and reports any adverse events that they learn about to the FDA. "Based on our review of the literature and our own safety database, we do not see any signal that leads us to be concerned about pseudoephedrine," said Dr. Mennella. He added that Sudafed contains a warning that if a woman is pregnant or breast-feeding, she should consult a physician before using the product.

Other companies also point to their warning labels. Fran Sullivan, spokesman for Wyeth Consumer Healthcare, the over-the-counter division of Wyeth, says that Advil's packaging not only advises pregnant and breast-feeding women to consult a health professional first, but also states: "It is especially important not to use ibuprofen during the last three months of pregnancy unless definitely directed to do so by a doctor because it may cause problems in the unborn child or complications during delivery."

In Drugs in Pregnancy and Lactation, a reference book consulted by doctors when advising pregnant women, Tylenol is listed as a category B drug, meaning that animal studies have not demonstrated any risk but that no controlled studies have been done in pregnant women. Mary Mortensen, executive director of medical and regulatory affairs for McNeil Consumer & Specialty Pharmaceuticals, makers of Tylenol, which also has warning labels urging consultation with a doctor, says the drug has a long safety track record.

Even women who check first with their doctors say it is often difficult to get conclusive information. Leni Bartolomey, 36 years old, is pregnant with her fourth child and has been experiencing gastric reflux. "I had it with every pregnancy but it's really worse this time," says the San Diego woman. She wanted to take GlaxoSmithKline's antacid, Gaviscon. Her doctor's office told her it was OK to take it, but when she pressed the issue, she was informed that the assessment was based only on anecdotal experience with other patients.

She ended up taking the medicine after calling a counseling service, which told her about some studies indicating that antacids like Gaviscon are generally considered low risk to take during pregnancy. Ms. Bartolomey, who is due in September, ended up taking the drug, but she's glad she did the additional research. "It was important to me to know what had happened to more women who took the drug than the one or two people in my doctor's office," she says.

Write to Amy Dockser Marcus at amy.marcus@wsj.com

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