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Fetal testosterone and early autism spectrum disorder related neurodevelopmental outcomes
Dissertation   Open access

Fetal testosterone and early autism spectrum disorder related neurodevelopmental outcomes

Bo Y. Park
Doctor of Philosophy (Ph.D.), Drexel University
Jun 2015
DOI:
https://doi.org/10.17918/etd-6363
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Abstract

Public Health
Aims: Despite widely acknowledged sex bias in Autism Spectrum Disorders (ASD), the underlying mechanisms are largely unknown. The goal of this dissertation was to examine whether differences in prenatal testosterone levels are a possible mechanism underlying the observed ASD sex difference. This was accomplished through three specific aims. First, meconium was examined as a novel prenatal androgen matrix to compare androgen levels across alternate matrices obtained at the delivery time point. Second, the association between cord blood testosterone and ASD-related 12 month phenotype was estimated in a high ASD risk cohort of multiplex families. Last, we investigated the relationship between widely used antimicrobials product use with potential androgenic activity and early autistic phenotypes. Methods: Studies were based in the Early Autism Risk Longitudinal Investigation (EARLI) cohort, an enriched risk cohort following pregnant mothers who previously had a child with ASD diagnosis. Prenatal information on potential exposures, confounders, effect modifiers and two relevant biologic samples, cord blood and meconium, and early ASD-related behavioral phenotypes in the children born into the cohort were available for analysis. Results: Testosterone (T) sex difference was observed in both cord blood and meconium and there was weak correlation between cord blood and meconium androgens. Umbilical cord blood T had a weak positive association with ASD related phenotype at 12 months. We found that the association of prenatal testosterone and early ASD-related phenotype varied by the sex of older child with ASD (proband). 12 month autistic traits were unrelated to either prenatal or postpartum use of products that contain TCS or TCC. Conclusion: Meconium and cord blood were both good media to measure prenatal androgen levels may be capturing different prenatal exposure windows. The association of prenatal testosterone early ASD-related phenotype was substantially different by proband sex indicating that androgen mediated mechanisms might be more important in families with female ASD in the pedigree. We found no evidence of an association between exposure to TCS/TCC and early ASD-related phenotype.

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