Abstract
Elevated latent prenatal steroidogenic activity has been found in the amniotic fluid of autistic boys, based on measuring prenatal androgens and other steroid hormones. To date, it is unclear if other prenatal steroids also contribute to autism likelihood. Prenatal oestrogens need to be investigated, as they play a key role in synaptogenesis and corticogenesis during prenatal development, in both males and females. Here we test whether levels of prenatal oestriol, oestradiol, oestrone and oestrone sulphate in amniotic fluid are associated with autism, in the same Danish Historic Birth Cohort, in which prenatal androgens were measured, using univariate logistic regression (n = 98 cases, n = 177 controls). We also make a like-to-like comparison between the prenatal oestrogens and androgens. Oestradiol, oestrone, oestriol and progesterone each related to autism in univariate analyses after correction with false discovery rate. A comparison of standardised odds ratios showed that oestradiol, oestrone and progesterone had the largest effects on autism likelihood. These results for the first time show that prenatal oestrogens contribute to autism likelihood, extending the finding of elevated prenatal steroidogenic activity in autism. This likely affects sexual differentiation, brain development and function.
Highlights
The male-biased prevalence of autism [1, 2], together with the finding that autistic girls have a higher mutational load than autistic boys [3,4,5], suggests that males have a higherThese authors contributed : Simon Baron-Cohen, Alexandros Tsompanidis
The same was found for the levels of oestriol and oestrone, with both hormones being significantly associated to an autism diagnosis using logistic regression (Oestriol: β = 0.025, q = 0.034; oestrone: β = 0.029, false discovery rate (FDR)-adjusted q = 0.031) (Table 2)
This study reports the first evidence that elevated levels of prenatal amniotic oestradiol, oestriol and oestrone are each associated with autism, with oestradiol levels being the most significant predictor of autism likelihood in univariate logistic regression models
Summary
The male-biased prevalence of autism [1, 2], together with the finding that autistic girls have a higher mutational load than autistic boys [3,4,5], suggests that males have a higher. Salivary testosterone during a brief period of postnatal steroid surge (‘mini-puberty’) did not correlate with autistic traits in toddlers [22] In both cases, testosterone was measured postnatally—in the neonatal period—rather than during the PMW, during which foetal testosterone is first produced and masculinisation of the brain and body commences. Univariate assessment of amniotic testosterone in a separate cohort of neurotypical children failed to reveal an association to autistic traits in childhood [23] This latter finding may reflect that the wider endocrine environment outside testosterone is significant for autism likelihood. We calculated standardised effect sizes for all hormones assayed to date in this cohort, in order to understand which amniotic fluid hormones make the largest contribution to autism likelihood
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