Maternal fever during early pregnancy and the risk of oral clefts

Abstract

An increased risk of birth defects after hyperthermic exposures has been confirmed in animal studies, but population studies have yielded inconsistent results. Oral clefts are a common birth defect and have been associated with these exposures in some of these studies. In this study, data from the National Birth Defects Prevention Study was used to evaluate the association of maternal report of febrile illness in early pregnancy and the risk of oral clefts. All oral cleft cases born between 1997 and 2004 were compared with nonmalformed controls born in the same geographical region during the same time period. Mothers reporting febrile illness during pregnancy were stratified by fever grade and antipyretic use. Logistic regression models were used to generate crude and adjusted odds ratios for exposure to fever and association with each oral cleft phenotype. The dataset included 5821 controls, 1567 cases of cleft lip with or without cleft palate (CL+/-P) and 835 cases of cleft palate only. A modestly increased risk was observed for isolated CL+/-P (odds ratio, 1.28; 95% confidence interval, 1.01-1.63). Stratification by fever grade (body temperature <101.5 degrees or > or =101.5 degrees F) did not yield significant differences in risk. Risk estimates were higher among women who reported a fever, but did not take antipyretics to control their fever, particularly for nonisolated compared with isolated oral clefts. This finding suggests that adequate control of fever may diminish the deleterious effects of fever in cases of oral cleft.

The Problem of Confounding in Studies of the Effect of Maternal Drug Use on Pregnancy Outcome

“…It is also possible that adequate antibiotic treatment is given for a secondary infection following a virus infection which could have increased the birth defect risk. Secondary effects of the infection can also be considered, for example, the possible harmful effects of high fever [35]. …”

Cleft lip and palate: understanding genetic and environmental influences

“…These exposures include hyperthermia, 99 stress, maternal obesity, occupational exposures, ionizing radiation and infection 10 . Pregnancy planning has been shown to have a protective effect and the basis of this observation needs to be more deeply explored.…”

Fever in pregnancy and the risk of congenital malformations: a cohort study

“…Several case-control studies in human beings have associated fever in pregnancy with among other neural tube defects [11–14], cardiac malformations [15–18], oral clefts [19, 20], and renal malformations [21]. The nature of the specific malformations appears to depend on the extent, duration and timing of maternal fever [7], and it is therefore important to include information about the timing of these febrile episodes.…”