Association of cumulative early medical events and neurodevelopmental conditions through a common latent factor—A population‐based twin study

Background The cumulative effect of early medical events has been shown to be associated with autism. It is unclear whether this effect is specific to autism or if it is associated to other neurodevelopmental conditions (NDCs) as well. Methods We established a registry‐linked population‐based twin cohort of 10,254 pairs within the child and adolescent twin study in Sweden. Participants were evaluated for symptoms of autism, attention deficit hyperactivity disorder, tics, and learning difficulties at age 9. Three early medical events previously associated with autism, beyond familial confounding (low birth weight, congenital malformations, and perinatal respiratory stress), were summed up creating an individual cumulative exposure load. Confirmatory Factor Analysis was performed on the measure of NDCs and a standardized common latent NDC factor was regressed on level of cumulative exposure. Results Cumulative exposure to early medical events was associated with a non‐linear increase in the common latent NDC factor, ß = 0.12 (95% CI, 0.07–0.17) for exposure level 1, ß = 0.25 (0.17–0.33) for exposure level 2, and ß = 0.62 (0.34–0.90) for exposure level 3. In a monozygotic twin difference analysis, with familial confounding being fully accounted for, the whole exposure effect was captured by the common factor, with residual associations fully attenuated for all four NDC outcomes, at all levels of cumulative exposure. Conclusion The result suggests a possibly causal environmental pathway. The cumulative effect of early medical events previously associated with autism, are not specific for autism, but rather associated with NDCs in a broad sense.