Abstract
The origins of the male preponderance in autism incidence remain unclear. The idea that perinatal factors associated with sex differentiation (e.g., steroid hormone pathways) may increase the possibility of the emergence of autism is complementary to the hypothesis that female individuals are intrinsically less likely to develop autism. Empirical evidence for the mechanistic roles of in utero steroid hormones in autism etiology is accumulating but inconsistent. We conducted a systematic review using rigorous criteria for the measurements of steroids and vitamin D exposure, to summarize the potential contributing roles of prenatal and early postnatal steroids and vitamin D alterations to the emergence of autism. We searched PubMed, PsychInfo, Scopus, and included 22 studies for qualitative synthesis. Among them, six studies examined the association of autism diagnoses in offspring and levels of steroids and precursor steroid hormones in the fetal environment, eight studies examined the associations between autism and maternal and fetal blood vitamin D levels during pregnancy and at birth, and eight studies examined the associations between offspring autism diagnoses and maternal hyperandrogenemia diagnosed before pregnancy. We identified promising and complex results regarding the relations between steroid metabolism and autism. The interpretation of findings was limited by the mostly observational study designs, insufficient investigation of the effects of offspring sex, confounders and their cumulative effects on the development of the child, and unclear impact of the timing of steroids exposure and their effects on fetal neurodevelopment.
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The current study is a systematic review. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
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Meng-Chuan Lai received support for this work from the Academic Scholars Award from the Department of Psychiatry, University of Toronto and the Canadian Institutes of Health Research Sex and Gender Science Chair (GSB 171373). He has received editorial honorarium from SAGE Publications. Other authors did not receive support from any organization for the submitted work, and had no relevant financial or non-financial interests to disclose.
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Amestoy, A., Baudrillard, C., Briot, K. et al. Steroid hormone pathways, vitamin D and autism: a systematic review. J Neural Transm 130, 207–241 (2023). https://doi.org/10.1007/s00702-022-02582-6
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DOI: https://doi.org/10.1007/s00702-022-02582-6