What are the factors that contribute to the development of autism spectrum disorder?

Genetics, epigenetics, and environmental factors are all implicated in the development of ASD.^[1]

From a genetic standpoint, ASD is associated with a number of identifiable genetic variants (e.g., polygenic variants, single nucleotide variants, noncoding variants), and as many as 102 genes have been identified as ASD risk factors.^[2][3]

Maternal/paternal health and toxic exposure are also associated with the development of ASD. Such exposures may modulate the expression of the genetic factors that place an individual at higher risk for ASD. Examples include maternal infections (particularly in the second and third trimesters of pregnancy),^[4] prenatal exposure to valproate^[5] (an anti-seizure drug), older maternal and paternal age,^[6][7][8] maternal hypertension, ^[9] maternal obesity,^[10][11] neonatal jaundice,^[12] elevated maternal c-reactive protein,^[13] and maternal polycystic ovary syndrome^[14], all of which have been associated with an increased risk of ASD in offspring.

An often-discussed potential risk factor for ASD is vaccination, whether that be the vaccine itself (e.g., MMR) or the vaccine constituents (e.g., thimerosal). There is no evidence to support this association, and multiple epidemiological studies and systematic reviews show no causal relationship between vaccination and ASD.^[15][16][17]