Artificial Reproductive Technology Exposure in Children with Autism Spectrum Disorders and Their Siblings

Background: Both the prevalence of autism spectrum disorders (ASD) and the use of artificial reproductive technologies (ART) have risen in the last decades.  There is limited research on the association of ASD and ART.

Objectives: 1) To explore the association between ART use and risk of ASD.  2) To determine the relationship between ART use and intellectual disability among children with ASD.  3) To assess differences in paternal age by ART exposure status among probands with ASD.

Methods: This study reviews the history of ART use in probands with ASD and their unaffected siblings through a self-reported parental survey administered via the internet by the Interactive Autism Network (IAN).  The final sample consisted of 1048 probands with ASD (mean age= 6.4 years, SD= 3.2, 75.4% male), 41% autism, 39% PPD-NOS, 19.4% Asperger’s) and 744 siblings without ASD (mean age= 7.4 years, SD= 3.5, 82.7% males)

Results: The prevalence of ART was 5.8% (N=61) among the probands with ASD (N=1048) and 4.6% (N= 34) among the unaffected siblings (N= 744).  Children with ASD were more likely to have been exposed to ART when compared with their unaffected siblings without reaching statistical significance in this small sample (crude odds ratio (cOR) = 1.29, p= 0.244).  There was no significant difference in the gender of the probands with ASD versus their unaffected siblings.  The paternal age at birth was statistically significant higher in children with ASD (paternal age: mean= 36 years, range 26-49 years) versus their unaffected siblings (paternal age: mean= 32.7 years, range 15-55 years) (p< 0.001).  The type of ASD diagnosis and the gender did not significantly differ between the two groups.

Comparison of the ASD probands with ART (N=61) versus those without ART (N=987) showed no statistical significant difference in the type of ASD diagnosis and in the gender. A significantly higher percentage of the probands with ASD and a history of ART had cognitive intelligence quotient (IQ) scores in the range of intellectual disability (35.7%) when compared with the ASD probands with no history of ART (19.5%), p < 0.05.

The age of ASD diagnosis among probands with ART was significantly lower by a mean difference of approximately 1 year in comparison to those without ART, p < 0.05.  A higher paternal age at birth was observed among ASD probands with ART (36.9 + 6.7 years) versus ASD without ART group (32.7 + 6.4 years), p < 0.001.

Conclusions: More probands with ASD were exposed to ART in comparison to their unaffected siblings in this study population.  Probands with ASD conceived by ART were diagnosed with ASD at a younger age than those without ART exposure.  The percentage of ASD probands with intellectual disability was 1.8 times greater among individuals with ASD conceived through ART in comparison to those naturally conceived.