Use of Fertility Therapies In Association with Autism Spectrum Disorders In Children of the Nurses' Health Study II

Background: Despite great interest in the long-term effects of fertility therapies, little is known about the relationship of various fertility treatments in association with autism and related conditions.

Objectives: To determine the association between maternal use of fertility therapies, including ovulation-inducing drugs and assisted reproductive therapy,  as well as other types of therapies, and risk of having a child with an autism spectrum disorder (ASD), and to further examine these associations by advanced maternal age and diagnostic subgroup.

Methods: This was a nested case-control study among participants in the Nurses’ Health Study II, a cohort over 116,000 women aged 25-42 at baseline who have provided information on reproductive, health, and lifestyle factors through mailed biennial questionnaires since 1989.   In 2005, participants were asked whether they ever had a child diagnosed with ASD.  The diagnoses were confirmed by mailing a supplementary questionnaire  and by conducting the Autism Diagnostic Interview-Revised in a subgroup.   Controls were randomly selected by frequency matching to case children's year of birth. Conditional logistic regression, stratified by child’s year of birth, was used to assess the relation between reported fertility therapy and ASD. 

Results: Nine percent of the 495 cases and 7% of 2,512 controls indicated use of fertility therapy for the index pregnancy; overall, use of different types of therapies was similar between the two groups. No significant associations were seen in the primary analysis.  In the subgroup of women with maternal age > 35 years (n=1,010, including 162 cases), use of OID was associated with an increased ASD risk, but this association did not reach conventional significance after adjusting for potential confounders (OR 1.81, 95% 0.95-3.47). Results were similar by diagnostic subgroup, except that within the advanced maternal age group, OID and AI were significantly associated with mild ASD but not autism.

Conclusions: In this large cohort of nurses, fertility therapies, including ART, do not appear to increase risk of having a child with an autism spectrum disorder. However, the associations observed with ovulation inducing drug use and artificial insemination warrant further investigation, particularly within the subgroup of older mothers, for whom these exposures are more common.