Asthma Meds Associated With Increase in Some Birth Defects?

Troy Brown

January 16, 2012

January 16, 2012 — A recent study found a statistically significant increase in the risk for isolated esophageal atresia, isolated anorectal atresia, and omphalocele in infants whose mothers used asthma medications within the month before conception or during the first 3 months of pregnancy.

Shao Lin, PhD, from the Center for Environmental Health, New York State Department of Health, Troy, and colleagues reported their study results in an article published online January 16 in Pediatrics.

The researchers used data collected for the National Birth Defects Prevention Study, an ongoing, multicenter, population-based, case-control study of the causes of birth defects that has been collecting data from 10 states in the United States since 1997 by conducting interviews with mothers and analyzing DNA obtained from cheek swabs from family members. That study includes both infants with 1 or more specified birth defects (diaphragmatic hernia, esophageal atresia, small intestinal atresia, anorectal atresia, neural tube defects, omphalocele, or limb deficiencies) and control infants without those birth defects.

For this study, the researchers analyzed data from a case group consisting of 2853 live births, stillbirths, or elective terminations with estimated dates of delivery from October 1, 1997, through December 31, 2005, and with 1 or more of the identified birth defects. The control group comprised 6726 infants born alive and without birth defects during the same period, randomly selected from birth hospital information or birth certificates.

Dr. Lin's team concentrated on periconceptional use of anti-inflammatory medications, bronchodilators, or both. They defined exposure as use of asthma medication once or more from 1 month before conception through the third month of gestation. Mothers who described their medication use as only "as needed" and who could not provide an exact time frame for use were excluded from the study.

The investigators used chi-square analysis to calculate the relationship between maternal characteristics and each birth defect, adjusting for confounders including age, parity, race/ethnicity, education, alcohol use, smoking, sex, folic acid use, and fever in the first trimester.

The study found a statistically significant association between isolated esophageal atresia and bronchodilator use only (adjusted odds ratio [aOR], 2.39; 95% confidence interval [CI], 1.23 - 4.66). The aORs for esophageal atresia and anti-inflammatory use only (aOR, 1.61; 95% CI, 0.69 - 3.76) and for use of both bronchodilators and anti-inflammatory medications (aOR, 2.93; 95% CI, 0.88 - 9.75) were elevated, but were not statistically significant.

There was a statistically significant increase in the risk for isolated anorectal atresia associated with anti-inflammatory use only (aOR, 2.12; 95% CI, 1.09 - 4.12).

Use of both bronchodilators and anti-inflammatory medications was associated with a statistically significant increase in the risk for isolated omphalocele (aOR, 4.13; 95% CI, 1.43 - 11.95).

The medications studied were not significantly associated with 6 other birth defects studied (neural tube defects, anencephaly, spina bifida, small intestinal atresia, limb deficiency, and diaphragmatic hernia).

Infants with either VATER (vertebral defects, anorectal atresia, tracheoesophageal fistula, esophageal atresia, and renal defects) syndrome or VACTERL (vertebral anomalies, anal atresia, cardiovascular anomalies, tracheoesophageal fistula, esophageal atresia, renal and/or radial anomalies, and limb defects) association were studied as a separate group, but because only 1 VACTERL case was exposed to any asthma medication, no further analysis was done.

The researchers performed a stratified analysis by time of medication use, using the periconceptional period and the period from the fourth through ninth month of gestation. The positive associations were found only in infants of women who took the medications during the periconceptional period, and not in infants whose mothers took the medications only in the fourth through ninth months of pregnancy.

The authors write that from 60% to 67% of mothers of infants with esophageal atresia, anorectal atresia, and omphalocele used bronchodilators during their entire pregnancy, although these data were not shown.

"With the interview information available for analysis, we were unable to distinguish between the effects of asthma and those of asthma medications; however, we did observe that mothers with possible indicators of uncontrolled asthma or severe asthma episodes (eg, use of multiple bronchodilators) were at higher risk for delivering a child with 1 of the defects studied than those who used 1 bronchodilator," the authors write.

"When regular use of bronchodilators is required, an activated inflammatory process is implied; thus, use of bronchodilators throughout pregnancy might indicate that these mothers had frequent or ongoing inflammatory exacerbations during pregnancy," they add.

Noting the importance of controlling asthma during pregnancy, the authors write, "The current clinical guidelines and specific recommendations for aggressive asthma management during pregnancy should remain unchanged."

"Given the low baseline prevalence of these defects, if the observed association proved to be causal, the absolute risks of asthma medications on these rare defects would be small," they conclude.

The study was supported by the Centers for Disease Control and Prevention. The authors have disclosed no relevant financial relationships.

Pediatrics. Published online January 16, 2012.

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