Case-ControlMolecular autism2023

Sex-specific and sex-independent steroid-related biomarkers in early second trimester maternal serum associated with autism.

Deborah A Bilder, Whitney Worsham, Scott Sullivan and 4 others

PMID 37573326

WHAT IT FOUND

Lower early second trimester maternal SHBG was associated with autism in offspring.

Higher estradiol did not hold after adjustment overall, but appeared in term pregnancies and male offspring.

Key findings

01Lower maternal serum SHBG in early second trimester was associated with autism in offspring, and the association remained after adjustment (adjusted odds ratio 0.65 per 50 nmol/L, 95% CI 0.55 to 0.78, p < 0.001).

02Higher maternal estradiol was not significant in the adjusted overall model (adjusted odds ratio 1.08 per 100 pg/ml, p = 0.07), but was significant in term pregnancies (adjusted odds ratio 1.17, p = 0.01) and male offspring (adjusted odds ratio 1.13, p = 0.04).

03Free and total testosterone showed no significant associations with autism.

STILL TO COME

How it was doneWhat they found

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What it does not show

Only 136 offspring were analysed, and both groups were enriched for prenatal metabolic syndrome exposure, so the sample does not represent a typical pregnancy population. The study is observational, so it cannot show that low SHBG or high estradiol causes autism. The adjusted overall estradiol result was not significant, and the positive estradiol findings came from subgroup analyses. Differences by prenatal metabolic syndrome exposure did not reach statistical significance, which may reflect insufficient statistical power. Batch handling limited comparison of prenatal metabolic syndrome exposure between preterm and term autism plus prenatal metabolic syndrome offspring. The sample came from a racially and ethnically homogeneous Utah population, so results may not generalise. Autism status was identified from billing codes and special education records rather than study-based diagnostic assessment. No inflammatory biomarkers were measured, so possible immune mechanisms could not be assessed.

Declared interests

The supplied text names funding from the University of Utah Neuroscience Initiative. It does not report a commercial sponsor or treatment company involved in the study.

The easy way to misread this

Do not use these serum biomarkers as clinical screening tests for autism or conclude that they cause autism. The study found associations in a small, enriched research sample, and the adjusted overall estradiol association was not significant.

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The study

Participants
136 offspring (68 with autism, 68 without autism)
Certainty of evidence
Low

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    Deborah A Bilder, Whitney Worsham, Scott Sullivan, et al. Sex-specific and sex-independent steroid-related biomarkers in early second trimester maternal serum associated with autism. Molecular autism. 2023.

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