Maternal fever and birth outcome: A prospective study

Abstract

Although maternal fever has been implicated as a human teratogen in several studies, no prospective study has adequately addressed the full spectrum of 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 retardation, or pregnancy loss. Using a prospective cohort study design, we ascertained women who had called the California Teratogen Information Service and Clinical 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 who 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 pregnant women who reported having no fever at any time in pregnancy were enrolled 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 interval, 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 had a high fever during the critical period for neural tube closure carried fetuses with anencephaly compared to none in the low fever group or controls. Specific minor defects were found more frequently in the high fever group compared to controls and were consistent with the pattern of defects previously reported in a retrospective case series. In addition, stillbirth occurred 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 for extended periods of time in the first month of pregnancy should be considered at increased risk for neural tube defects and should be provided appropriate counseling.

Acute respiratory infections during pregnancy and congenital abnormalities: a population‐based case‐control study

“…There were two other CA‐groups: posterior cleft palate and multiple CA which showed an association with medically recorded ARI during the first trimester of pregnancy and this association was near to the level of significance at the comparison of cases and malformed controls. If the association between ARI and these CA‐groups, particularly EA ± TF is causal, it is necessary to clarify whether it may be connected with fever‐hyperthermia (Chambers et al . 1998), hypoxia (Gordon et al .…”

Evidence for an Interaction Between Familial Liability and Prenatal Exposure to Infection in the Causation of Schizophrenia

“…The possibility of a direct effect, of either the infectious organism itself or the associated high fever, should be considered. Hyperthermia during pregnancy has been shown to significantly increase the risk of a range of negative pregnancy outcomes, including major structural malformations, such as neural tube defects (37)(38)(39)(40). However, since most urinary tract infections are not accompanied by bloodstream infection, even in pregnancy a direct effect of the infection is unlikely (34)(35)(36).…”

Pandemic Influenza and Pregnant Women: Summary of a Meeting of Experts

“…14 Data are less certain for other birth defects and adverse outcomes, but associations have been documented in some studies. [15][16][17] Two studies suggest that the risk for birth defects associated with fever might be mitigated by antipyretic medications or multivitamins that contain folic acid. 15,18 The presence of maternal fever during labor has been shown to be a risk factor for adverse neonatal and developmental outcomes, including neonatal seizures, encephalopathy, cerebral palsy, and neonatal death.…”