Maternal Dietary Fat and Fatty Acid Intake in Association with Autism Spectrum Disorder

Background:   Polyunsaturated fats, including omega-3 fatty acids, are essential for fetal brain development.  While prior work has examined potential associations between maternal fish intake and child developmental outcomes, it is not known how maternal fat and fatty acid intake from other sources may influence risk of autism spectrum disorder (ASD).

Objectives: To determine whether maternal intake of fats and fatty acids influences risk of ASD using prospectively collected dietary information.

Methods:   We utilized data from the Nurses’ Health Study II (NHS II), a large prospective cohort with questionnaires mailed every 2 years since 1989 to over 116,000 nurses in the United States. Dietary information was collected in 1991, 1995, 1999, and 2003 from a validated 131-item Food Frequency Questionnaire. 27,516 NHS II participants had a child born between 1991-2007; for the primary analysis, women who did not return at least one of two NHS II questionnaires with information on ASD, and those who did not have an FFQ completed before the child’s birth were excluded. Major types of fats and fatty acids were categorized into quartiles. We further explored risk in individuals with the top and bottom 10% of intake, as well as those in the lowest 5% of the distribution of intake. Intake of fish and use of fish oil supplements was also assessed. Binomial regression was used to obtain crude and multivariate adjusted risk ratios for the association between maternal dietary fat and ASD.

Results: 18,045 women, including 317 who reported a child with ASD, were included in primary analyses. In adjusted analyses, risk of having a child with ASD decreased with increasing polyunsaturated fat intake (RR for the highest vs. the lowest quartile =0.67, 95% CI 0.49, 0.92; p for trend = 0.008); nearly identical protective associations were seen for the top quartiles of omega-6 and linoleic fatty acid intake.  Overall, intake of omega-3 fatty acids was not associated with risk of ASD, although the results of exploratory analyses suggested a possible increase in risk among women with the lowest 5% of intake of omega-3 fatty acid  (RR= 1.53, 95% CI 1.00, 2.32), and for those with the lowest 10% of intake of alpha-linoleic acid (ALA) in particular (RR=1.42, 95% CI 1.04, 1.95). These associations appeared to strengthen when assessed in women for whom dietary information referred to pregnancy (n=5,884, including only 86 cases; RR for omega-3=2.42, 95% CI 1.19, 4.91; RR for ALA=2.23, 95% CI 1.30, 3.84).  Neither fish intake nor intakes of total fat, monounsaturated, trans, or saturated fat, or fat from animal, vegetable, and dairy sources, or other fatty acids, were significantly associated with ASD.  In a secondary analysis, results were similar when including women with FFQs collected during lactation.

Conclusions: The preliminary results of this large longitudinal investigation suggest that maternal intake of polyunsaturated fatty acids may influence risk of having a child with ASD. In particular, low intakes of essential fatty acids linoleic and alpha-linolenic may increase risk. Further work should assess maternal intake of these fats during pregnancy.