Update on the gestational effects of maternal hyperthermia

Objectives: I plan to review the types of defects caused by gestational hyperthermia. Hyperthermia-induced malformations in animals and humans involve many organs and structures, particularly the central nervous system, as well as other defects. The type of defect is related to the timing of the hyperthermic insult, and the underlying mechanisms include cell death, membrane disruption, vascular disruption, and placental infarction.

Methods: Review of recent epidemiologic studies (2005-2020) has confirmed an association between gestational hyperthermia and birth defects.

Results: There are strong associations between neural tube defects and maternal fever, and other studies have demonstrated associations between first trimester hyperthermia and an increased risk for cardiovascular defects, oral clefts, isolated congenital ear defects, cataracts, hypospadias, renal anomalies, possibly anorectal malformations, and congenital anomalies in general, suggesting that this association between maternal hyperthermia and birth defects in humans is causal. The first prospective evaluation of maternal fever was reported in 1998, and this study confirmed findings from previous case-control studies and case series regarding the magnitude and duration of elevated maternal body temperature in relation to an increased risk for neural tube defects as well as a specific pattern of malformation.

Conclusions: The consistency of findings across these different study designs supports the causal nature of the relationship between maternal fever and specific birth defects. This review summarizes the recent human evidence documenting the gestational effects of maternal hyperthermia.

Keywords: anorectal defects; birth defects; cardiovascular defects; congenital anomalies; craniofacial defects; ear defects; eye defects; hypospadias renal anomalies; maternal febrile illnesses; maternal hyperthemia; neural tube defects; oral clefts.