Fever in pregnancy and risk of fetal death: a cohort study

Background Hyperthermia acts as a teratogen in some animals where it can induce resorption of the fetus and fetal death. Fever during pregnancy, especially in the period of embryogenesis, is also suspected as being a risk factor for fetal death in human beings. We did a large cohort study in Denmark to investigate this possibility. Methods We interviewed 24 040 women who were recruited in the first half of pregnancy to the Danish National Birth Cohort Study, and obtained information on the number of fever incidents during the first 16 weeks of pregnancy. For each fever episode, the highest measured body temperature, duration of incident, and gestational age were recorded. Outcomes of pregnancies were identified through linkage with the Civil Registration System and the National Discharge Registry. Cox's regression with time-dependent variables was used to estimate the relative risk of fetal death, taking delayed entry into account. Findings 1145 pregnancies resulted in a miscarriage or stillbirth (4.8%). During the first 16 pregnancy weeks 18.5% of the women experienced at least one episode of fever. However, we found no association between fever in pregnancy and fetal death before or after adjustment for known risk factors of fetal death (relative risk 0.95 [95% Cl 0.80-1.13]). This finding was consistent irrespective of measured maximum temperature, duration and number of fever incidents, or the gestational time of the fever incident, and was observed for fetal death in all three trimesters of pregnancy. Interpretation We found no evidence that fever in the first 16 weeks of pregnancy is associated with the risk of fetal death in clinically recognised pregnancies.