Apgar score and risk of autism

Amirhossein Modabbernia,Mika Gissler,Richard Francis,Kim Carter,Abraham Reichenberg,Sven Sandin,Helen Leonard,Erik T Parner,Diana Schendel,Raz Gross,Mady Hornig,Michaeline Bresnahan

doi:10.1007/s10654-018-0445-1

Abstract

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.

Highlights

The etiology of autism spectrum disorder (ASD) is still poorly understood
The point estimates for low (RR, 1.88; 95% confidence intervals (95% CIs), 1.41–2.51) and intermediate Apgar score (RR, 1.54; 95% CI, 1.32–1.81) were larger for autistic disorder (AD) than for ASD
Using the largest multinational population-based ASD database to investigate the association between 5-min Apgar score and ASD, we found a 75–80% increase in risk of ASD in neonates with low to intermediate Apgar score compared with neonates with optimal Apgar score

Summary

Introduction

The etiology of autism spectrum disorder (ASD) is still poorly understood. Evidence implies a strong genetic component for ASD [1], but a key role for the environment and its interaction with genetic factors has been suggested [2, 3]. Extended author information available on the last page of the article assesses the neonatal well-being status based on heart rate, respiration, color, muscle tone, and reflex irritability after delivery. It is assessed ubiquitously in every newborn around the world and can be considered an invaluable, if not optimal source of information about neonatal status immediately after birth. The studies used different designs and varying set of variables as potential covariates/confounders in the adjusted analysis, which makes the pooled estimates difficult to interpret Because both ASD and low Apgar score (\ 4) are rare events, earlier attempts to address this association has been hampered by limited sample size

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