Maternal fever and birth outcome: A prospective study

Although maternal fever has been implicated as a human teratogen in several studies, no prospective study has adequately addressed the full spectrum o f birth outcomes following such exposure in pregnancy. The purpose of this study was to determine whether or not maternal fever is associated with an increased risk for structural malformations, prematurity, growth retardatio n, or pregnancy loss. Using a prospective cohort study design, we ascertain ed women who had called the California Teratogen Information Service and Cl inical Research Program between 1979-1996 with questions regarding fever in a current pregnancy. Of these women, 115 who reported a fever of at least 38.9 degrees C lasting for at least 24 h (high fever group) and 147 women w ho reported a fever of either less than 38.9 degrees C or lasting less than 24 h (low fever group) were enrolled in the cohort. An additional 298 preg nant women who reported having no fever at any time in pregnancy were enrol led in a control group. All pregnancies were followed in a similar fashion, and outcomes were compared among the three groups. The combined prevalence of all major structural malformations was increased, but not significantly so, in the offspring of women who had a high fever in the first trimester of pregnancy compared to those with a lower fever or to controls (relative risk 1.80 for high fever group compared to controls; 95% confidence interva l, 0.54, 6.03; relative risk 1.21 for low fever group compared to controls; 95% confidence interval, 0.36, 4.03). However, 2/34 or 5.9% of women who h ad a high fever during the critical period for neural tube closure carried fetuses with anencephaly compared to none in the low fever group or control s. Specific minor defects were found more frequently in the high fever grou p compared to controls and were consistent with the pattern of defects prev iously reported in a retrospective case series. In addition, stillbirth occ urred more frequently in the high fever group compared to controls (2.6% vs . 0%). These data support the conclusion that high maternal fever early in pregnancy is a human teratogen. Women who experience fevers of 38.9 degrees C or higher far extended periods of time in the first month of pregnancy s hould be considered at increased risk for neural tube defects and should be provided appropriate counseling. (C) 1998 Wiley-Liss, Inc.