Maternal digit ratio (2D:4D), autistic traits, and autism spectrum disorder in offspring: A case-control study

Prenatal androgen exposure has been proposed as a biological mechanism contributing to autism spectrum disorder (ASD). The second-to-fourth digit ratio (2D:4D) is a non-invasive biomarker of prenatal sex hormone balance. This study examined whether maternal 2D:4D ratios differ between mothers of children with ASD and controls, and whether maternal digit ratios are associated with maternal autistic traits and ASD severity in offspring.

The study included 102 children newly diagnosed with ASD and their mothers, and 69 age- and sex-matched typically developing controls and their mothers. Maternal autistic traits were assessed using the Autism Spectrum Quotient (AQ), and ASD severity in children was evaluated with the Childhood Autism Rating Scale (CARS). Maternal right- and left-hand 2D:4D ratios were measured using digital calipers, and Dr-l values were calculated. Group comparisons, correlation analyses, and multiple linear regression were conducted.

Mothers of children with ASD exhibited significantly lower right- and left-hand 2D:4D ratios and Dr-l values compared to controls. In the ASD group, maternal left-hand 2D:4D ratios were negatively correlated with maternal AQ total scores, whereas no association was found with children's CARS scores. Regression analysis showed that lower maternal left-hand 2D:4D ratio and lower maternal educational level significantly predicted higher maternal AQ scores.

Reduced maternal 2D:4D ratios, particularly in the left hand, are associated with increased autistic traits in mothers of children with ASD, but not with ASD severity in offspring. These findings support a role for prenatal androgen exposure in intergenerational vulnerability to autistic traits and highlight maternal 2D:4D ratio as a potential biomarker relevant to ASD-related phenotypes.