Foetal oestrogens and autism

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.

Fig. 1

Beeswarm plots illustrating the distribution of oestriol, oestradiol, oestrone and oestrone sulphate concentrations. Error bars represent the interquartile range, and the black dot represents the median; (n CTR = 177, n ASC = 98)

Fig. 2

Heatmap and dendrogram of the pairwise correlations between the steroid hormones assayed in amniotic fluid. Asterisk denotes statistical significance (q < 0.05), following correction via FDR. P progesterone, A androstenedione, T testosterone; P-OH 17-OH-progesterone, C cortisol, E-S oestrone sulphate, E2 oestradiol

Fig. 3

Standardised odds ratios (ORs) for autism diagnosis for all amniotic steroids assayed to date. Each hormone was standardised by its median and interquartile range, so that a one-unit increase in a hormone corresponded to the movement from the 25th to the 75th percentile of its range