Apgar score and risk of autism

Low Apgar score has been associated with higher risk for several neurological and psychiatric disorders, including cerebral palsy and intellectual disability. Studies of the association between Apgar score and autism spectrum disorder (ASD) have been inconsistent. We aimed to investigate (1) the association between low Apgar score at 5 min and risk for ASD, and (2) the modifying effects of gestational age and sex on this association in the largest multinational database of ASD. We included prospective data from 5.5 million individuals and over 33,000 cases of ASD from Norway, Sweden, Denmark and Western Australia who were born between 1984 and 2007. We calculated crude and adjusted risk ratios (RR) with 95% confidence intervals (95% CIs) for the associations between low Apgar score and ASD. All analyses for ASD were repeated for autistic disorder (AD). We used interaction terms and stratified analysis to investigate the effects of sex, gestational age, and birth weight on the association. In fully adjusted models, low Apgar scores (1-3) (RR, 1.42; 95% CI, 1.16-1.74), and intermediate Apgar scores (4-6) (RR, 1.50; 95% CI, 1.36-1.65) were associated with a higher RR of ASD than optimal Apgar score (7-10). The point estimates for low (RR, 1.88; 95% CI, 1.41-2.51) and intermediate Apgar score (RR, 1.54; 95% CI, 1.32-1.81) were larger for AD than for ASD. This study suggests that low Apgar score is associated with higher risk of ASD, and in particular AD. We did not observe any major modifying effects of gestational age and sex, although there seems to be substantial confounding by gestational age and birth weight on the observed association.