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

Abstract

Autism Spectrum Disorder (ASD) is phenotypically and etiologically heterogeneous, with evidence for genetic and environmental contributions to disease risk. Research has focused on the prenatal period as a time where environmental exposures are likely to influence risk for ASD. Epidemiological studies have shown significant associations between prenatal exposure to maternal immune activation (MIA), caused by infections and fever, and ASD. However, due to differences in study design and exposure measurements no consistent patterns have emerged revealing specific times or type of MIA exposure that are most important to ASD risk. No prior studies have examined prenatal MIA exposure and ASD risk in an under-represented minority population of African ancestry. To overcome these limitations, we estimated the association between prenatal exposure to fever and maternal infections and ASD in a prospective birth cohort of an understudied minority population in a city in the United States. No association was found between prenatal exposure to genitourinary infections or flu and the risk of ASD in a nested sample of 116 ASD cases and 988 typically developing controls in crude or adjusted analyses. Prenatal exposure to fever was associated with increased ASD risk (aOR = 2.02 [1.04 – 3.92]) after adjustment for educational attainment, marital status, race, child sex, maternal age, birth year, gestational age and maternal smoking. This effect may be specific to fever during the third trimester (aOR 2.70 [1.00 – 7.29]). Our findings provide a focus for future research efforts and ASD prevention strategies across diverse populations. Lay summary We looked at whether activation of the immune system during pregnancy increases the chance a child will develop ASD. We examined 116 children with ASD and 988 children without ASD that came from a predominantly low income, urban, minority population. We found that having the flu or genitourinary tract infections during pregnancy is not related to the child being diagnosed with ASD. However, we did find children were at increased risk for ASD when their mothers had a fever during pregnancy.

Cord and Early Childhood Plasma Adiponectin Levels and Autism Risk: A Prospective Birth Cohort Study

“…The demographic and clinical characteristics of mothers and children in this study are presented in the Table 1, and have also been documented in earlier studies from this cohort (Li et al 2016; Raghavan et al 2017; Brucato et al 2017; G. Wang et al 2014; G.…”

Maternal and Child Health Bureau’s Autism Research Program

“…16 In one study, authors found that prenatal exposure to fever, especially in the third trimester, was associated with the development of autism. 17 The results of this study may inform clinical strategies to reduce the incidence of maternal fever and support previous studies revealing a relationship between the prenatal environment and autism. Authors of another study reported the need to ensure optimal levels of folate and B 12 to reduce the risk of autism onset.…”

Infections in children with autism spectrum disorder: Study to Explore Early Development (SEED)

“…Our findings could also be the result of a continued in utero infection. Infection and fever in utero are potentially important factors in the development of ASD [Brucato et al, ; Hornig et al, ; Zerbo et al, ] and are being examined by another forthcoming SEED paper. From an etiological standpoint, the first 30 days of life could be particularly important for environmental effects, including infection or thermodysregulation, on neurodevelopment among children with ASD and should be evaluated in future studies.…”