College of Graduate Studies: Theses & Dissertations

Term of Award

Spring 2026

Degree Name

Doctor of Public Health in Epidemiology (Dr.P.H.)

Document Type and Release Option

Dissertation (open access)

Copyright Statement / License for Reuse

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Department

Department of Biostatistics, Epidemiology, and Environmental Health Sciences

Committee Chair

Kelly Sullivan

Committee Member 1

Logan Cowan

Committee Member 2

Dziyana Nazaruk

Abstract

Given the developmental vulnerability of early childhood and the rising prevalence of autism spectrum disorder, it’s crucial to investigate how typical biological responses, such as fever and maternal inflammation, might relate to autism spectrum disorder (ASD) risk. However, previous findings have been inconsistent, and the relationship remains unclear. This dissertation aimed to investigate the role of inflammation and fever in the neurodevelopmental origins of ASD by examining prenatal and postnatal exposures. The data were taken from the National Children's Study, which prospectively enrolled women and followed children after birth. The main outcome was the child’s Modified Checklist for Autism in Toddlers (M-CHAT) autism screening results recorded as a dichotomous variable. The exposure was a history of fever days reported among children at 6, 12, 18, and 24 months of age. Based on a cohort of 823 children, the cumulative incidence of autism was 6.7%. Children with ≥3 days of fever by 6 months had significantly higher odds of autism (aOR = 2.82; 95% CI: 1.04–7.66). At 24 months, ≥4 fever days increased the odds of autism risk by more than twice (aOR = 2.35; 95% CI: 1.15–4.78). Children with fever at both 12 and 24 months had nearly triple the odds (aOR = 2.86; 95% CI: 1.48–5.52), indicating that timing and recurrence of fever are critical factors. Additionally, the analysis of maternal antenatal C-reactive protein (CRP) in 131 mother-child pairs revealed a positive, but statistically nonsignificant, association with ASD risk. Both prenatal and postnatal results were confounded by child and maternal sociodemographic factors, notably the child’s sex, maternal education, and income level. This work provides evidence that immune responses, both during pregnancy and in early childhood, may contribute to increased ASD risk. The postnatal findings in children ≤2 years highlight potential vulnerability of the developing brain to immune activation, while the prenatal analysis illustrates the complex interplay between biological markers and neurodevelopmental disorders. Future research with larger, clinically confirmed cohorts is necessary to clarify these relationships and explore underlying immune mechanisms that could inform early monitoring and preventive strategies.

Research Data and Supplementary Material

No

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