Maternal influenza during pregnancy and risk of congenital abnormalities in offspring

BACKGROUND: The teratogenic effect of influenza viruses is currently being debated, and we examined the large population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA) to study the possible association between maternal influenza and various congenital abnormalities (CAs). METHODS: The 1980-1996 HCCSCA includes 22,843 newborns or fetuses with CAs, and 38,151 matched controls (newborn infants without any abnormalities). RESULTS: In the case group, 1328 (5.8%) mothers had influenza at some time during their pregnancies compared to 1838 (4.8%) mothers in the control group (adjusted prevalence odds ratios [PORs], 1.3; 95% confidence interval [CI], 1.2-1.4). In the calculation of the adjusted PORs, the use of antifever drugs and maternal employment status were considered. When cases and their matched controls were compared, there was a higher prevalence of maternal influenza during the second and/or third month of pregnancy for the group of newborns with cleft lip +/- palate (adjusted POR, 3.2; 95% CI, 2.0-5.3), neural-tube defects (adjusted POR, 1.9; 95% CI, 1.1-3.3), and cardiovascular malformations (adjusted POR, 1.7; 95% CI, 1.3-2.3). However, a direct teratogenic effect from influenza viruses appears to be unlikely, and we suggest that the higher prevalence of the CAs indicated above can be explained mainly by fever, because this risk was reduced by the use of antifever drugs. Periconceptional folic acid supplementation also showed some preventive effect for these CAs. CONCLUSIONS: The indirect teratogenic effect of maternal influenza during pregnancy may be restricted by appropriate medical treatment (e.g., antifever drugs) and periconceptional folic acid supplementation.