Maternal polyunsaturated fatty acids and risk for autism spectrum disorder in the MARBLES high-risk study

Prior research studies suggest that maternal polyunsaturated fatty acids could have protective effects on neurodevelopmental outcomes. The objective of this study was to examine associations between maternal polyunsaturated fatty acid intake during pregnancy and risk for autism spectrum disorder and other non-typical development in a prospective cohort. Eligible women already had a child with autism spectrum disorder and were planning a pregnancy or were pregnant with another child. Children were clinically assessed longitudinally and diagnosed at 36 months. Maternal polyunsaturated fatty acid intake during pregnancy was estimated using food frequency questionnaires. Maternal third-trimester plasma polyunsaturated fatty acid concentration was measured by gas chromatography. In all, 258 mother–child pairs were included. Mothers consuming more total omega-3 in the second half of pregnancy were 40% less likely to have children with autism spectrum disorder (relative risk = 0.6, 95% confidence interval: 0.3–0.98). No significant associations were observed between maternal third-trimester plasma polyunsaturated fatty acid subtype concentrations and risk of autism spectrum disorder. However, higher plasma eicosapentaenoic acid and docosahexaenoic acid concentrations were associated with lower non-typical development risk (relative risk ranging from 0.47 to 0.88). This study provides suggestive evidence of associations between risk of autism spectrum disorder in the children and maternal omega-3 intake in late pregnancy but not with third-trimester plasma polyunsaturated fatty acids. Further research is needed to evaluate these potential relationships. Lay abstract Prior studies suggest that maternal polyunsaturated fatty acids intake during pregnancy may have protective effects on autism spectrum disorder in their children. However, they did not examine detailed timing of maternal polyunsaturated fatty acid intake during pregnancy, nor did they evaluate plasma concentrations. This study investigates whether maternal polyunsaturated fatty acids in defined time windows of pregnancy, assessed by both questionnaires and biomarkers, are associated with risk of autism spectrum disorder and other non-typical development in the children. Food frequency questionnaires were used to estimate maternal polyunsaturated fatty acid intake during the first and second half of pregnancy. Gas chromatography measured maternal plasma polyunsaturated fatty acid concentrations in the third trimester. In all, 258 mother–child pairs from a prospective cohort were included. All mothers already had a child with autism spectrum disorder and were planning a pregnancy or pregnant with another child. Children were clinically assessed longitudinally and diagnosed at 36 months. For polyunsaturated fatty acid intake from questionnaires, we only found mothers consuming more omega-3 in the second half of pregnancy were 40% less likely to have children with autism spectrum disorder. For polyunsaturated fatty acid concentrations in the third-trimester plasma, we did not observe any statistical significance in relation to the risk of autism spectrum disorder. However, our study confirmed associations from previous studies between higher maternal docosahexaenoic acid and eicosapentaenoic acid plasma concentrations in the late pregnancy and reduced risk for non-typical development. This study markedly advanced understandings of whether and when maternal polyunsaturated fatty acid intake influences risk for autism spectrum disorder and sets the stage for prevention at the behavioral and educational level.