A Prospective Birth Cohort Study on the Association Between Cord Blood Acylcarnitine Profile and Childhood Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

Objective: Mitochondria have been implicated in the etiology of autism spectrum disorder (ASD), but evidence for attention-deficit/hyperactivity disorder (ADHD) remains limited. Given the early onset of both ASD and ADHD and high degree of comorbidity, this study sought to examine the prospective association of 20 acylcarnitines in cord blood—a group of metabolites involved in mitochondrial fatty acid metabolism—with childhood risk of ASD, ADHD, and other neurodevelopmental disorders (NDDs). Method: This study includes 995 children (55% male participants, 58% non-Hispanic Black) from the Boston Birth Cohort. Acylcarnitines in cord blood were profiled using liquid chromatography–tandem mass spectrometry. Logistic regressions examined individual acylcarnitines and their 3 principal components (PC) in relation to childhood ADHD (n = 285), ASD (n = 86), and other NDDs (n = 246) compared to those in typically developing children (n = 378), with adjustment of maternal and child characteristics. Results: Children with higher levels of short-chain and long-chain acylcarnitines in cord blood (including C2, C3, C3-DC-CH3, C14, C16, C18, and C18:1) had a greater risk of childhood ADHD. The highest tertile of long-chain acylcarnitine PC scores was associated with 1.98 times odds of ADHD (adjusted OR = 1.98; 95% CI = 1.29-3.06), compared to the lowest tertile. A 1-unit increase in medium-chain PC scores was associated with 1.38 times odds of ASD (adjusted OR = 1.38; 95% CI = 1.01-1.90). Conclusion: This prospective birth cohort study found that cord blood acylcarnitines were associated with childhood risk of ASD, ADHD, and other NDDs, highlighting the important role of mitochondrial fatty acid metabolism in NDDs and potential targets for investigation and interventions. Plain language summary: Altered mitochondrial function has been associated with autism spectrum disorder (ASD), but evidence for attention-deficit/hyperactivity disorder (ADHD) remains limited. This prospective study of a racially diverse birth cohort (N = 995) found associations between increased levels of cord blood acylcarnitines—a group of metabolites involved in mitochondrial fatty acid metabolism—and a higher likelihood of ADHD and ASD diagnosis. These findings highlight the potential role of mitochondrial fatty acid metabolism in neurodevelopmental disorders and potential targets for investigation and interventions.