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. 2021 Jul 8;12(1):51.
doi: 10.1186/s13229-021-00453-7.

Maternal steroid levels and the autistic traits of the mother and infant

A Tsompanidis  1 , E Aydin  2 , E Padaigaitė  2   3 , G Richards  2   4 , C Allison  2 , G Hackett  5 , T Austin  5 , R Holt #  2 , S Baron-Cohen #  2
Affiliations

Maternal steroid levels and the autistic traits of the mother and infant

A Tsompanidis et al. Mol Autism. .

Abstract

Background: Prenatal sex steroids have been associated with autism in several clinical and epidemiological studies. It is unclear how this relates to the autistic traits of the mother and how early this can be detected during pregnancy and postnatal development.

Methods: Maternal serum was collected from pregnant women (n = 122) before or during their first ultrasound appointment [mean = 12.7 (SD = 0.7) weeks]. Concentrations of the following were measured via immunoassays: testosterone, estradiol, dehydroepiandrosterone sulphate, progesterone; and sex hormone-binding globulin which was used to compute the free fractions of estradiol (FEI) and testosterone (FTI). Standardised human choriogonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A) values were obtained from clinical records corresponding to the same serum samples. Mothers completed the Autism Spectrum Quotient (AQ) and for their infants, the Quantitative Checklist for Autism in Toddlers (Q-CHAT) when the infants were between 18 and 20 months old.

Results: FEI was positively associated with maternal autistic traits in univariate (n = 108, Pearson's r = 0.22, p = 0.019) and multiple regression models (semipartial r = 0.19, p = 0.048) controlling for maternal age and a diagnosis of PCOS. Maternal estradiol levels significantly interacted with fetal sex in predicting infant Q-CHAT scores, with a positive relationship in males but not females (n = 100, interaction term: semipartial r = 0.23, p = 0.036) after controlling for maternal AQ and other covariates. The opposite was found for standardised hCG values and Q-CHAT scores, with a positive association in females but not in males (n = 151, interaction term: r = -0.25, p = 0.005).

Limitations: Sample size of this cohort was small, with potential ascertainment bias given elective recruitment. Clinical covariates were controlled in multiple regression models, but additional research is needed to confirm the statistically significant findings in larger cohorts.

Conclusion: Maternal steroid factors during pregnancy are associated with autistic traits in mothers and their infants.

Keywords: Autism; Autistic Traits; Estradiol; Interaction; Pregnancy; Prenatal; Sex.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of the study, showing different cohort sizes for each comparison of autistic traits (AQ or Q-CHAT) to prenatal measurements (steroid hormones or placental markers)
Fig. 2
Fig. 2
Violin-boxplots showing the distribution of A maternal autistic traits (AQ) and B free estradiol levels (FEI), according to clinical history of hirsutism. Women that reported two or more body areas affected had significantly higher levels of both AQ (p = 0.021) and FEI (p = 0.025)
Fig. 3
Fig. 3
Heatmap and dendrogram of the pairwise correlations of the log-transformed hormone concentrations. Values indicate the Pearson's correlation coefficients
Fig. 4
Fig. 4
Scatterplots with linear fit-models for A the association between maternal free estradiol (FEI) and AQ score, and B the association between maternal estradiol and Q-CHAT; separate linear models are presented for each sex and show significant interactions with infant sex in the case of infant Q-CHAT
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