Teratogen Update: Fever in Pregnancy

Maternal fever is a common occurrence during pregnancy, but evidence increasingly links even transient hyperthermia to adverse fetal outcomes.

This review examines data from animal and human studies on the association between maternal hyperthermia and structural birth defects, neurodevelopmental disorders, fetal growth restriction, and pregnancy loss.

A narrative review of published literature evaluating maternal hyperthermia and pregnancy outcomes was conducted, including both experimental animal models and observational human studies.

The teratogenic effects appear to be dose- and timing-dependent, with greatest vulnerability during the first trimester. Reported associations including neural tube defects, craniofacial anomalies, and congenital heart defects as well as neurodevelopmental disorders, fetal growth restriction, and pregnancy loss. Proposed mechanisms include heat-induced cellular stress and maternal immune activation, both of which can disrupt embryonic development. Folic acid supplementation and antipyretic use are associated with reduced risk.

Although the evidence is derived from observational studies and limited by difficulty of measuring temperatures, the consistency of findings from different models support the biologic plausability of a teratogenic effect of maternal fever. The variability in exposure assessment and confounding factors, including maternal comorbidities, remain important limitations.

Maternal fever is a potentially modifiable risk factor for advere pregnancy outcomes. Preventative strategies that include preconception folic acid supplementation and maternal fever management are supported by the current literature. Further research is needed to define critical exposure windows and the impact of materanal comorbidities.