Birth Defects Linked to Mothers' Use of Cold Medicine

Norra MacReady

July 28, 2013

A woman's use of oral or nasal decongestants during the first trimester of pregnancy has been associated with an increased risk for certain birth defects, the authors of a new case-control study report.

The findings "support previously hypothesized associations between first-trimester exposure to phenylephrine and endocardial cushion defect, between first-trimester exposure to phenylpropanolamine and ear defects, and between first-trimester exposure to phenylpropanolamine and pyloric stenosis," lead author Wai-Ping Yau, PhD, from the Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, Massachusetts, and colleagues write in an article published in the July 15 issue of the American Journal of Epidemiology.

In an exploratory analysis of the association between specific intranasal decongestants and a range of birth defects, the authors observed an increased risk for pyloric stenosis related to the use of any intranasal decongestant and an increased risk for tracheoesophageal fistula and renal collecting system anomalies related to the use of imidazoline derivatives. These findings "warrant further exploration," the authors write.

They did not find an association between oral or intranasal decongestants and other conditions, such as ventricular septal defect, coarctation of the aorta, gastroschisis, and eye and ear defects, which have been reported in earlier studies.

In addition, they caution that even in cases in which an increased risk was found, the absolute number of cases was still very small. For example, "the baseline prevalence of endocardial cushion defect is about 0.34 per 1,000 live births; thus, even if phenylephrine exposure increased the risk 8-fold, the absolute risk of having an affected child still would be small (about 2.7 per 1,000 live births; i.e., 0.27%)."

Dr. Yau and colleagues identified many of the infants with birth defects (cases) from data gathered as part of the Slone Epidemiology Center Birth Defects Study (BDS) between January 1993 and January 2010. Initiated in 1976, the BDS is a multicenter case-control surveillance program of medication-related birth defects among infants born in the United States and Canada. During the study period, the researchers identified 12,734 cases, including some drawn from birth defects registries maintained in Massachusetts and New York State. They also included data on 7606 healthy infants (control) born at hospitals participating in the BDS and from a population-based sample of healthy infants born in Massachusetts.

The mothers were interviewed within 6 months of delivery about a variety of demographic and lifestyle characteristics, including exposure to all prescription and over-the-counter medications from 56 days before the last menstrual period through the end of pregnancy. The interviews were conducted by trained nurses, using highly structured questionnaires designed to ferret out detailed information on maternal medication use.

In the current study, Dr. Yau and colleagues analyzed these data for a possible association between birth defects and the use of all decongestants, oral and intranasal preparations, and preparations containing specific compounds such as phenylephrine or phenylpropanolamine.

They found evidence of 3 previously reported associations: between phenylephrine and endocardial cushion defect (odds ratio [OR], 8.0; 95% confidence interval [CI], 2.5 - 25.3; 4 exposed cases), between phenylpropanolamine and ear defects (OR, 7.8; 95% CI, 2.2 - 27.2; 4 exposed cases), and between phenylpropanolamine and pyloric stenosis (OR, 3.2; 95% CI, 1.1 - 8.8; 6 exposed cases).

In an exploratory analysis limited to the association between first-trimester use of intranasal decongestants and birth defects not previously associated with decongestant use, the authors found a relationship between pyloric stenosis and any intranasal decongestant (OR, 1.9; 95% CI, 1.0 - 3.5), and imidazoline derivatives specifically (OR, 2.2; 95% CI, 1.1 - 4.5); between tracheoesophageal fistula and imidazoline derivatives (OR, 3.3; 95% CI, 1.2 - 8.9); and between renal collecting system anomalies and the oxymetazoline (OR, 3.1; 95% CI, 1.3 - 6.9).

Siobahn Dolan, MD, medical advisor to the March of Dimes, praised the study for its size and detail but added that it illustrates some of the problems that plague research on the relationship between maternal medication use and birth defects. One of these is recall bias. "When a woman has a baby with a heart defect, she may rack her brain to determine what she might have done wrong," Dr. Dolan told Medscape Medical News. "Those mothers may remember things differently than the control mothers." She suggested that the women who took decongestants also may have had poorer health in general, which may have affected their pregnancies.

In addition, the analysis may have been hindered by the relative scarcity of cases. "Birth defects are rare — it's a challenge to understand them," said Dr. Dolan, who is also professor of clinical obstetrics and gynecology at the Albert Einstein College of Medicine, Bronx, New York. "This study adds additional data, but we need more, because the causes of birth defects are complex."

Still, she said, "This study points out that women should adhere strictly to dosing guidelines, to talk to their doctors about what they're taking, and to consider healthy alternatives."

This work was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The Pharmacoepidemiology Program at the Harvard School of Public Health and the Slone Epidemiology Center receive support from various pharmaceutical companies, some of which could manufacture products included in these analyses. These analyses were not supported by any pharmaceutical manufacturer. Dr. Yau was supported by the National University of Singapore-Overseas Postdoctoral Fellowship. Until August of 2012, one coauthor owned stock in Johnson & Johnson (<$20,000 value), which manufactures decongestant and acetaminophen products. Dr. Dolan has disclosed no relevant financial relationships.

Am J Epidemiol. 2013;178:98-108. Abstract

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