Maternal fever, multivitamin use, and selected birth defects: evidence of interaction?

Multivitamin use has been associated with lower risks for some birth defects. We evaluated whether multivitamin use modified birth defect risks associated with febrile illness, a common and possibly teratogenic exposure.

From the population-based Atlanta Birth Defects Case-Control Study (1968-1980) we selected seven defects (neural tube defects, cleft lip and palate, cardiac outflow tract defects, ventricular septal defects, atrial septal defects, omphalocele, and limb deficiencies) because of their inverse relation with multivitamin supplement use documented in previous analyses. We defined four exposure categories from combinations of multivitamin use (periconceptional use compared with no use) and febrile illness (early pregnancy compared with no illness). The reference category was no multivitamin use and no illness.

Febrile illness with no multivitamin use was associated with generally increased risk for the seven defects and the combined group (odds ratio = 2.1, 1.7, 1.5, 1.9, 2.9, 4.4, 3.3, and 2.3, respectively). With multivitamin use, however, the risk estimates associated with febrile illness were generally lower (odds ratio = 0.6, 1.1, 0.0, 1.5, 0.0, 0.8, 0.0, and 0.8, respectively). Some of the associated 95% confidence intervals included one.

The pattern of findings suggests that multivitamin use might decrease the risk associated with febrile illness.