Fever in Pregnancy and Risk of Fetal Death: A Cohort Study

Abstract

Many studies of animals, including primates, indicate that hyperthermia during pregnancy is associated with fetal death and possibly lethal malformations. There are suggestions that in humans, either endogenous (febrile) hyperthermia or external heating may be linked with neural tube defects. This cohort study interviewed 24,040 women in Denmark during the first half of pregnancy to document febrile episodes in the first 16 weeks of gestation. The incidence of miscarriage or stillbirth during the 18-month study period was 4.8%. Nearly one in five women, 18.5%, reported at least one episode of fever, and about 45% of those reporting a peak temperature had had fever of 39°C or higher. Fever had lasted 2 to 3 days in a majority of women and 4 days or longer in nearly one fourth of the study group. Close to 10% of women reported more than one febrile episode. The risk of fetal death in women reporting fever in the first 16 gestational weeks was no higher than in those without fever, and this result was unchanged after adjusting for numerous factors: maternal age, parity, previous miscarriages, and the use of tobacco, alcohol, and coffee during pregnancy. When including pregnancies ending with induced abortion on indication in the fetal death group, the relative risk of fetal death in women reporting fever was 0.99 (95% CI, 0.84-1.16). There were no differences in fetal death in any trimester of pregnancy or for any specified period within the first 16 weeks. Taking the maximum temperature into account also made no difference. Neither the days of fever nor the number of febrile episodes correlated with fetal death. The lack of a relationship between early gestational fever and fetal death held when only women who were interviewed while pregnant and followed up prospectively were considered. This large-scale cohort study failed to show that fever in the first 16 weeks of pregnancy increases the risk of fetal death, and the investigators believe that pregnant women may be reassured on this point.