Prenatal Influenza or Fever and Risk of Autism/Autism Spectrum Disorders

Background:  

Maternal infections during pregnancy have been suggested to be associated with autism. However, to what extent prenatal influenza plays a role has not been well-investigated in epidemiological studies.

Objectives:  

To determine if maternal influenza infection or fever during pregnancy is associated with increased risk of autism/autism spectrum disorders.

Methods:  

The analysis is part of a large population-based case control study known as the Childhood Autism Risk from Genetics and Environment (CHARGE) Study. 462 children with autism/autism spectrum disorders, 136 with developmental disorders but not autism, and 265 typically developed children born in California age between 2 and 5 years at the time of recruitment were included. Diagnostic category for all participants was determined by standardized clinical assessments. The two main exposures, maternal influenza and fever during pregnancy, were both assessed by telephone interviews. We conducted two types of analyses. One set of analysis was performed applying sampling weights and another without. The weights were determined based on the probabilities of participating in the study taking into account both the three case group sampling strata and a set of socio-demographic variables. Multivariate logistic regression models were fitted to the data to obtain odds ratios (ORs) with their 95% confidence intervals (CI) as measures of association and precision between the main exposures and autism. 

Results:  

We did not find a strong association between maternal influenza during pregnancy and autism (OR 1.52, 95% CI 0.81 – 2.85) or developmental delay (2.32, 95% CI 0.72 - 7.42) after applying the sampling weights in the analysis. The unweighted analysis showed similar results.

More mothers of children with autism reported having fever during pregnancy than those of children with typical development in the analysis where the sampling weights were applied (OR = 1.86 95% CI 1.14 - 3.02). Second trimester showed the strongest association (OR=2.13 95% CI 1.00 - 4.52). However, in the analysis where we did not apply the sampling weights, the OR of the association between fever and autism did not reach statistical significance (1.25, 95% CI 0.81 – 1.92).

Conclusions:    

In our analyses, maternal influenza showed no association with autism or developmental delay, but fever during pregnancy was associated with autism in our weighted analysis, which corrects for selection bias to some degree. We consider these results to be preliminary and more analyses will be performed.