Do prenatal estrogen levels affect autism risk?

High levels of latent prenatal steroidogenic activity have been found in the amniotic fluid of autistic boys, but it remains unclear if other prenatal steroids also contribute to risk of autism. A recent study inNature examined whether levels of prenatal estriol, estradiol, estrone, and estrone sulphate in amniotic fluid are associated with autism.

Participants in the study were 98 boys with autism and 177 controls from the Danish Historic Birth Cohort born between 1993 and 1999. All had amniotic fluid samples corresponding to amniocentesis procedures performed between 14 and 16 weeks of gestational age. The authors assayed the samples for estriol, estradiol, estrone, and estrone sulphate using liquid chromatography-tandem mass spectroscopy.

No significant differences were found between the groups in maternal age at birth, paternal age at birth, birth weight, gestational week at amniocentesis or storage time. However, univariate logistic regression showed that higher estradiol levels were the most predictive of an autism diagnosis (ß = 0.029, Benjamini-Hochberg false discovery rate [FDR]-adjusted q = 0.031). Estriol and estrone levels also were significantly associated with autism diagnosis (estriol: ß = 0.025, FDR-adjusted q =0.034; estrone: ß = 0.029; FDR-adjusted q = 0.031). Estrone sulphate was nominally significant but did not maintain statistical significance following false discovery rate correction.

When examining androgens and cortisol in the same subset of samples, only progesterone was a significant predictor of autism diagnosis, following univariate logistic regression and correction via FDR (ß = 0.053, FDR-adjusted q = 0.031).

The authors believe this study provides the first evidence that elevated levels of prenatal amniotic estradiol, estriol, and estrone are associated with autism, although estradiol levels were the most significant predictor in univariate logistic regression models. Ob/gyns may want to consider counseling women with higher levels of prenatal estradiol on the associated risks.