First-Trimester Use of Certain Drugs Linked to Birth Defect


A woman's use of aspirin, ibuprofen or decongestants during the first trimester of pregnancy appears to significantly increase the risk of gastroschisis, a birth defect of the abdominal wall, according to a new study by the California Birth Defects Monitoring Program.

The study also found that women exposed to organic solvents during early pregnancy--whether at work or at home--had more than double the risk of having babies with gastroschisis, a condition in which a tear in the abdomen allows the intestines to protrude. Babies can die without immediate corrective surgery.

Moreover, the study found an increased association between the birth defect and high exposures to colorants, such as permanent hair dyes and nail polish, especially if handled frequently and without use of protective gear.

While 16% of the mothers of normal infants surveyed said they were exposed to colorants in the first trimester, 29% of women whose babies had gastroschisis handled colorants, including furniture paints or fabric dyes.

"In the workplace, there are rules and regulations about exposures that you don't have in the home," said Dr. Claudine P. Torfs, the lead author of the new study, which appears in the current issue of Teratology. "It may be that people should worry also about their hobbies. People should consider that if they are going to do a lot of [the activity] that they may be exposing themselves to a teratogen."

Gastroschisis occurs in about one out of every 4,500 births, and almost always among women younger than 25. Of the 130 or so cases reported annually in California, one-third involve teenage mothers.

Although complex and costly, about $44,000 per case, most babies who are treated promptly recover and suffer no permanent repercussions.

While several factors are thought to cause the defect, younger pregnant women, in particular, should be warned against exposures to the substances cited in the new study, Torfs said.

"This defect is highly correlated with age," Torfs said. "The younger the age, the higher the risk. But other things are also probably associated with gastroschisis. There are probably many causes."

Indeed, cocaine use, cigarette smoking and X-ray exposures are also known to increase the risk of gastroschisis, said Dr. Martha Werler, an expert in gastroschisis at the Slone Epidemiology Unit at Boston University.

But, she added: "This information having to do with over-the-counter drugs is interesting because, although the risk may not be as high [as cocaine, for example], these exposures are more widespread. This study should draw attention to the fact that we really need to study these over-the-counter medications further."

The study was able to identify other risk factors by matching the mothers of babies with gastroschisis with a group of women who were similar in age, race and economic status but had healthy infants.

Overall, 110 mothers of afflicted infants and 220 mothers of normal infants were surveyed. All the babies were born from 1988 to 1990. The women were interviewed extensively on their preconception and first-trimester use of medications and exposure to solvents, colorants and X-rays.

The study found that women who had taken aspirin or ibuprofen during the first trimester were four times as likely to have a baby with gastroschisis.

The use of decongestants, particularly those with pseudoephedrine and phenylpropanolamine, doubled the risk of having a baby with the defect.

The extra risk found with these medications was not due to the mother's reason for taking them, such as a fever or virus, Torfs said.

Mothers exposed to organic solvents--such as benzene, propane, glycol and some aerosol propellants--had more than double the risk of having babies with gastroschisis. These solvents are commonly used in auto work, furniture stripping and painting. Antibiotics and anti-nauseants were not found to increase the risk. In addition, use of acetaminophen (which was used in the first trimester by 25% of the women in both groups) did not elevate the risk.

The association between gastroschisis and aspirin, ibuprofen and decongests has been suspected for some time because smaller studies have demonstrated a link and because there is a plausible explanation for how the substances cause harm.

Aspirin and ibuprofen are vasoconstrictors, substances that reduce blood flow. It is thought that fetal exposure some time during the fifth through eighth week of gestation may cause a disruption of the blood flow to the part of the abdomen that is weakened in gastroschisis. This could allow the tear in the abdomen, Torfs said.

"There is an exquisite time for teratogens to exert their effects," she said. "Exposure a day before or a day later may not have an effect."

Studies of pregnant women in certain occupations have indicated a link between gastroschisis and solvents, particularly in the computer industry where solvents are used heavily. But the study sheds new light on the possible danger of some hobbies.

But a weakness in the study is that it required women to recall what substances they may have been exposed to and when. In many cases, an industrial hygienist was consulted to estimate what chemicals were used and how much exposure occurred.

"It's tough to get accurate information on things like solvents," Werler noted. "It's a good attempt. But whether or not people are exposed to high or low levels is a tough call."


The Gastroschisis Figures

A new study shows that several popular over-the-counter medications as well as heavy exposure to solvents, paints and dyes can significantly increase the risk of gastroschisis, a birth defect of the abdominal wall. The defect is also much more common in babies whose mothers are 25 or younger.

Mothers of normal babies

Took aspirin: 1.4%

Took ibuprofen: 1.4%

Took decongestants: 5.5%

Exposed to organic solvents: 10%

Exposed to colorants: 16%

Mothers of babies with gastroschisis:

Took aspirin: 6.4%

Took ibuprofen: 5.5%

Took decongestants: 11.8%

Exposed to organic solvents: 25%

Exposed to colorants: 29%

* Source: California Birth Defects Monitoring Program

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