Prenatal fever and autism risk

Abstract

Some studies suggest that prenatal infection increases risk of autism spectrum disorders (ASDs). This study was undertaken in a prospective cohort in Norway to examine whether we could find evidence to support an association of the prenatal occurrence of fever, a common manifestation of infection, with ASD risk. Prospective questionnaires provided maternal exposure data; case status was established from clinical assessments and registry linkages. In a large, prospectively ascertained cohort of pregnant mothers and their offspring, we examined infants born ⩾32 weeks for associations between fever exposure in each trimester and ASD risk using logistic regression. Maternal exposure to second-trimester fever was associated with increased ASD risk, adjusting for presence of fever in other trimesters and confounders (adjusted odds ratio (aOR), 1.40; 95% confidence interval, 1.09–1.79), with a similar, but nonsignificant, point estimate in the first trimester. Risk increased markedly with exposure to three or more fever episodes after 12 weeks' gestation (aOR, 3.12; 1.28–7.63). ASD risk appears to increase with maternal fever, particularly in the second trimester. Risk magnified dose dependently with exposure to multiple fevers after 12 weeks' gestation. Our findings support a role for gestational maternal infection and innate immune responses to infection in the pathogenesis of at least some cases of ASD.

Prenatal exposure to fever is associated with autism spectrum disorder in the boston birth cohort

“…Zerbo et al and Hornig et al saw an association between fever and ASD risk at any time during pregnancy, consistent with the current study (Fig. ) [Zerbo et al, ; Hornig et al, ]. For exposure to maternal fever during pregnancy (prior to 32 weeks) or specifically during trimester 1 or 2, Aladottir et al did not find an association with ASD risk [Atladottir et al, ].…”

“…Our study showing increased ASD risk associated with fever is consistent with Zerbo et al and Hornig et al (Fig. 2) [Zerbo et al, 2013;Hornig et al, 2017] but not Atladottir et al [2012]. The prenatal exposure definition used by Atladottir et al included only data through week 32; however, the other studies, including our own, have used fever exposure for the entire pregnancy period (week 1 to birth).…”

“…That study further showed that risk was attenuated in mothers who took anti‐pyretic medications to control their fever, but remained elevated in mothers who did not [Zerbo et al, ]. A prospective study in Norway also found increased risk for ASD after prenatal fever exposure, as well as evidence of a dose–response relationship, with risk rising with multiple maternal fevers [Hornig et al, ]. Fever exposure has also been shown to adversely influence developing fetal health more generally [Dreier, Andersen, & Berg‐Beckhoff, ].…”

Understanding environmental contributions to autism: Causal concepts and the state of science

“…In another report, these researchers described 3‐fold increased autism risks after viral infection in the 1st trimester, or 40% higher bacterial infection in the 2nd trimester [Atladottir et al, ]. Two studies, including one prospective cohort, observed an association of ASD with fever in the 2nd trimester, primarily when not treated with an anti‐pyretic [Hornig et al, ; Zerbo et al, ]. Prolonged fever (a week or longer) appeared to confer a 3‐fold higher risk of autism in the Danish study.…”

Environmental influences on health and development: nutrition, substance exposure, and adverse childhood experiences

“…Zika virus, for example, exerts a change in the infant RNA through methylation changes . Infants exposed to maternal infection and febrile illness have more copy number variants and higher rates of autism spectrum disorder …”