Periconceptional Fever/Influenza Linked to Specific Congenital Birth Defects

From Reuters Health Information CME

News Author: Megan Brooks
CME Author: Désirée Lie, MD, MSEd

NEW YORK (Reuters Health) February 4, 2011 — New research confirms that women who develop influenza or a fever of 101°F or higher during the periconceptional period are at increased risk of delivering a baby with certain congenital heart defects, most notably right-sided obstructive lesions in all infants and atrioventricular septal defects (AVSD) in infants with Down syndrome.

However, maternal use of antipyretic agents in the setting of fever or influenza may attenuate these associations, the researchers reported in the January 24 online issue of The Journal of Pediatrics.

Dr. Adolfo Correa, Medical Officer in the National Center on Birth Defects and Developmental Disabilities, part of the Centers for Disease Control and Prevention, in Atlanta, Georgia, led the study.

"Although our findings are consistent with a few previous studies, the literature on the associations we found is still somewhat limited for drawing conclusive clinical implications," Dr. Correa noted in an e-mail to Reuters Health.

"Further efforts are needed to corroborate our findings and to elucidate the reasons for the observed associations. From a precautionary perspective, women planning to become pregnant should avoid exposure to influenza or other febrile illnesses and seek preconception care," the researcher added.

Maternal febrile illness and hyperthermia have been linked to a variety of birth defects, especially those involving the central nervous system, Dr. Correa and colleagues note in their report. Associations between maternal fever and hyperthermia with congenital heart defects are "less clear-cut," they say.

Moreover, while associations between congenital heart defects and some viral illnesses, particularly rubella, have been well documented, studies on the role of influenza in risk of congenital heart defects have yielded mixed results.

Dr. Correa and colleagues investigated associations between maternal fever and influenza and congenital heart defects using data from the Baltimore-Washington Infant Study, an epidemiologic study of congenital heart defects conducted between 1981 and 1989 in Maryland, Washington DC, and northern Virginia.

Cases were 2,361 infants with congenital heart defects and controls were 3,435 infants without congenital heart defects.

Participating mothers were asked whether they had a fever of 101°F or higher, had influenza, or used an antipyretic agent (acetaminophen, salicylate, or nonsteroidal anti-inflammatory agent) during the period extending from 3 months prior to pregnancy through the end of the third month of pregnancy.

For congenital heart defects overall, no significant associations were found with fever, influenza, or fever/influenza.

However, for specific defects, significant associations were found for right-sided obstructive defects and maternal fever (OR 2.04), influenza (OR 1.75) and fever/influenza (OR 1.69).

These findings were most notable for tricuspid atresia in the setting of fever (OR 7.54), influenza (OR 6.04), and fever/influenza (OR 5.46) and for pulmonary atresia with intact ventricular septum in the setting of influenza (OR 2.71) and fever/influenza (OR 2.80), the researchers reported.

And in infants with Down syndrome, the authors found significant associations between atrioventricular septal defects and periconceptional fever (OR 1.92), influenza (OR 1.66) and fever/influenza (OR 1.66). No significant associations were evident between other cardiac phenotypes and fever, influenza or both.

Maternal antipyretic use tended to decrease these associations, as mentioned.

Dr. Correa and colleagues say the link between fever and influenza and AVSD only in infants with Down syndrome may be "spurious" or it may represent an "important gene-environment interaction that warrants further investigation."

J Pediatr. Published online January 24, 2011. Abstract
Clinical Context

Congenital heart defects continue to be a leading cause of morbidity and mortality in children, and maternal exposures during pregnancy may contribute to the risk for such defects. Maternal fever has been linked to birth defects, especially those of the central nervous system, and studies have noted an almost 2-fold increase in the risk for aggregate congenital heart defects with maternal fever and influenza.

This is a case-control study of infants in a population-based cohort to examine the association between maternal fever or influenza during the 3 months before and after conception and the risk for congenital heart defects.