Tuesday, May 1, 2018

Congenital abnormalities of the male reproductive system and risk of autism spectrum disorders

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.

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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