Clinical

Nitrofurantoins may pose little risk of birth defects

Last Updated: 2013-01-31 17:45:11 -0400 (Reuters Health)

By Rob Goodier

NEW YORK (Reuters Health) - Nitrofurantoins may hold little risk for birth defects when taken during pregnancy, a large observational study in Norway suggests.

The risk of jaundice climbed when infants were exposed to nitrofurantoins during their last 30 days in utero. Otherwise, the antimicrobial drugs, commonly prescribed for urinary tract infection, were not associated with negative pregnancy outcomes or perinatal complications when given in pregnancy, including the first trimester, according to Dr. Hedvig Nordeng and colleagues at the University of Oslo and the Norwegian Institute of Public Health.

The researchers published the results in the February edition of the journal Obstetrics and Gynecology, available online now.

"It's very reassuring that there is probably not any risk of major congenital malformation associated with nitrofurantoin exposure in the first trimester," Dr. Michael Greene, OB-GYN at Massachusetts General Hospital, Boston, Mass., who was not involved in the study, told Reuters Health by phone.

Dr. Nordeng's team studied a Norwegian national birth registry and a national prescription database to find 5,794 women exposed to nitrofurantoins at different stages during their pregnancy. They compared the patients to 20,643 women who were treated for UTI with a different antimicrobial drug as a control group, and also to 130,889 women who were not exposed to antimicrobials during their pregnancy.

The researchers first looked at 1,334 women exposed to nitrofurantoins in the first trimester and found no higher risk of major malformations or cardiovascular defects compared the other two control groups. Those control groups included 5,800 women exposed to pivmecillinam to treat UTI, and more than 130,000 who were not exposed.

Then, looking at exposures at any time throughout pregnancy, the researchers found no associations with negative outcomes, with the exception of jaundice. The rate of jaundice with in utero exposure to nitrofurantoin within 30 days of delivery was 10.8%, compared to 8.8% in infants exposed to other antimicrobials and 8.1% in unexposed infants. The differences were statistically significant.

Dr. Nordeng's research apparently contradicts results from a study published in 2009 in JAMA Pediatrics (formerly Archives of Pediatric & Adolescent Medicine) by Dr. Krista Crider and colleagues at the U.S. Centers for Disease Control and Prevention in Atlanta, Georgia.

Dr. Crider's study found that nitrofurantoins were associated with malformations, including eye defects, cleft lip and palate, and cardiovascular defects.

The discrepancy may lie in the differences between the two studies' designs and sample sizes, Dr. Nordeng says. For example, Dr. Crider's team asked women to report on their medication retrospectively. That method may be more error-prone than using a prescription database like the Norwegian study did, Dr. Nordeng says.

Another consideration may be that Dr. Crider's study found modest effect sizes, Dr. Greene says.

"Nobody really got terribly bent out of shape when the Crider paper was published and they didn't stop prescribing these things. I would say that in the big picture, the Crider paper is consistent with the Nordeng study," Dr. Greene said.

Dr. Crider declined to comment, saying that as a CDC employee she is not permitted to comment on other people's research.

"Our results, however, are in accordance with most published studies where there was no increased risk for birth defects when women took nitrofurantoin," Dr. Nordeng said.

He added, "Women need to know that treatment of UTI in pregnancy with antibiotics has clear maternal and fetal benefits."

SOURCE: http://bit.ly/WB8gFq

Obstet Gynecol 2013.