Mean Corpuscular Volume and Risk of Autism Spectrum Disorder

Autism spectrum disorder (ASD) can be diagnosed as early as 18 months old, but more reliably after two years. Notably, no laboratory test exists to identify mothers at higher risk of having a child who will later be diagnosed with ASD or to identify at-risk infants before the manifestation of symptoms. One frequently described risk factor for neurodevelopmental disorders is vitamin B12 and folate deficiency, which results in macrocytic anemias.

We evaluated whether increased mean corpuscular volume (MCV), an indicator of macrocytic anemias in the mother or child, is associated with increased odds of a subsequent ASD diagnosis. Maternal mean MCV (mMCV) was calculated from any value in the year before birth, and the mMCV for the child was calculated from any MCV value from birth until the end of the follow-up time. Odds ratios with 95% confidence intervals were estimated from logistic regression models.

A total of 3798 mothers (984 cases-ASD/2814 controls) and 9633 children (3206 cases-ASD/6427 controls) had at least one MCV value. The mMCV for the mother one year before birth was not associated with a later diagnosis of ASD in their children. In children, compared to the reference group (mMCV 76 femtoliters (fL)), an mMCV of 81 fL, 84 fL, and 91 fL was increased odds of ASD of 26%, 38%, and 32%, respectively.

The MCV can be a potential inexpensive biomarker to identify a subset of children at risk of ASD or other developmental disorders; this exploratory study can inform larger studies to determine the clinical utility of MCV.