Associations Between the 2nd to 4th Digit Ratio and Autism Spectrum Disorder in Population-Based Samples of Boys and Girls: Findings from the Study to Explore Early Development.

This was an observational comparison, so it cannot show that prenatal hormone exposure caused ASD. The digit ratio is only a proxy for fetal testosterone and possibly estradiol, and the paper says its validity as a proxy is supported by limited evidence. Most contacted families were not enrolled, and the authors note that low response means selection bias should be considered. The analysis excluded the non-ASD developmental disability group, so it does not show whether digit ratios differ between ASD and other developmental disabilities. Dysmorphology classification was not available for the whole control group or most of the developmental disability group. Female subgroup analyses were limited by small samples, especially for ASD with birth defects or genetic disorders and dysmorphic ASD in the complete restricted sample. Hand scans were used instead of direct measurement, and scans may produce lower digit ratios, although the authors expect this to affect cases and controls similarly. The children were young, and the authors note that digit ratio may change slightly with age. Some maternal and perinatal factors were assessed by excluding affected children rather than by including all factors in adjusted models, because some models were unstable in small subgroups.

All authors report no conflicts of interest for this study.

Do not read a low right-hand digit ratio in boys as evidence that ASD is caused by high fetal testosterone. The male right-hand difference was small and did not remain statistically significant after adjustment, and boys with ASD plus a birth defect or genetic disorder showed large adjusted differences.