Medical History of Discordant Twins Indicates Environmental Etiologies of Autism
Objectives: The objective of this study was to investigate associations between ASD and early medical events and characteristics, in twins. In particular, the aim was to test the hypothesis of an environmental cumulative effect on ASD risk.
Methods: A total of 80 MZ twin pairs (13 were discordant for clinical ASD diagnosis) and 46 dizygotic (DZ) twin pairs, were examined for intra-pair differences in early medical events (e.g., obstetric and neonatal factors, first year infections) using anamnestic survey data. First, differences in early medical events were investigated using multisource medical records in the rare subsample of MZ twin pairs qualitatively discordant for ASD and matched typically developing (TD) pairs (N=52). Second, identified intra-pair differences specific to ASD diagnoses were tested in relation to autistic traits in an independent sample of quantitative discordant pairs (N=200), applying generalized estimating equations analyses.
Results: Intra-pair differences in both clinical ASD (Z=-2.85, p= .004) and autistic traits (β=78.18, p=.002) were associated with the cumulative load of early medical events when controlling for IQ and ADHD comorbidity in MZ pairs. This association was particularly driven by increased infant dysregulation (feeding, sleeping abnormalities, excessive crying and worriedness). No significant association were found in DZ pairs.
Conclusions: Early dysregulation, and foremost the cumulative load of early medical events, may index children at risk of ASD owing to non-shared environmental contributions. Findings could facilitate screening and early detection of ASD.