Ran S. Rotem; Gabriel Chodick; Michael Davidovitch; Russ
Hauser; Brent A. Coull; Marc G. Weisskopf.
Congenital Abnormalities of the Male Reproductive System and Risk of
Autism Spectrum Disorders. Am J
Epidemiol. 2018;187(4):656-663.
Abstract
Androgens have an extensive influence on brain development
in regions of the brain that are relevant for autism spectrum disorder (ASD),
yet their etiological involvement remains unclear. Hypospadias (abnormal
positioning of the urethral opening) and cryptorchidism (undescended testes)
are 2 relatively common male birth defects that are strongly associated with
prenatal androgen deficiencies. Having either disorder is a proxy indicator of
atypical gestational androgen exposure, yet the association between these
disorders and autism has not been extensively studied. We analyzed male
singleton live births (n = 224,598) occurring from January 1, 1999, through
December 31, 2013, in a large Israeli health-care organization. Boys with
autism, cryptorchidism, and hypospadias were identified via International
Classification of Diseases, Ninth Revision, codes, with further verification of
autism case status by review of medical records. In multivariable-adjusted
analyses, the odds ratio for ASD among boys with either condition was 1.62 (95%
confidence interval (CI): 1.44, 1.82). The odds ratio for boys with
cryptorchidism only was 1.55 (95% CI: 1.34, 1.78), and that for boys with
hypospadias only was 1.65 (95% CI: 1.38, 1.98). ASD risk was not elevated among
unaffected brothers of hypospadias or cryptorchidism cases, despite familial
aggregation of all 3 conditions, providing some indication for the possibility
of pregnancy-specific risk factors driving the observed associations. Results
suggest that in-utero hypoandrogenicity could play a role in ASD etiology.
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