Key Point: Prolonged fever during gestation tripled risk of ASD.

Autism After Infection, Febrile Episodes, and Antibiotic Use During Pregnancy: An Exploratory Study

Pediatrics. Published online November 12, 2012. (doi: 10.1542/peds.2012-1107). Hjördis Ósk Atladóttir, MD, PhD, Tine Brink Henriksen, MD, PhD, and Erik T. Parner, PhD, University of Aarhus, Aarhus, Denmark. Diana E. Schendel, PhD, Centers for Disease Control, Atlanta, GA, USA.


OBJECTIVES: Results of animal studies suggest that maternal immune activation during pregnancy causes deficiencies in fetal neurodevelopment. Infectious disease is the most common path to maternal immune activation during pregnancy. The goal of this study was to determine the occurrence of common infections, febrile episodes, and use of antibiotics reported by the mother during pregnancy and the risk for autism spectrum disorder (ASD) and infantile autism in the offspring.

METHODS: We used a population-based cohort consisting of 96,736 children aged 8 to 14 years and born from 1997 to 2003 in Denmark. Information on infection, febrile episodes, and use of antibiotics was self-reported through telephone interviews during pregnancy and early postpartum. Diagnoses of ASD and infantile autism were retrieved from the Danish Psychiatric Central Register; 976 children (1%) from the cohort were diagnosed with ASD.

RESULTS: Overall, we found little evidence that various types of mild common infectious diseases or febrile episodes during pregnancy were associated with ASD/infantile autism. However, our data suggest that maternal influenza infection was associated with a twofold increased risk of infantile autism, prolonged episodes of fever caused a threefold increased risk of infantile autism, and use of various antibiotics during pregnancy were potential risk factors for ASD/infantile autism.

CONCLUSIONS: Our results do not suggest that mild infections, febrile episodes, or use of antibiotics during pregnancy are strong risk factors for ASD/infantile autism. The results may be due to multiple testing; the few positive findings are potential chance findings.