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Background <p>Pregnant individuals may receive antenatal corticosteroids for various conditions, including congenital adrenal hyperplasia (to prevent virilisation in female fetuses) and preterm birth risk (to hasten fetal maturation and improve perinatal survival). This narrative review aimed to evaluate the evidence of sexually-dimorphic offspring outcomes following antenatal corticosteroids for such conditions and explore the potential underlying mechanisms.</p> Methods <p>A comprehensive MEDLINE search identified twenty-eight studies for inclusion: seven focused on congenital adrenal hyperplasia and twenty-one focused on preterm birth risk.</p> Results <p>For congenital adrenal hyperplasia, evidence suggests that antenatal corticosteroids are associated with sexually-dimorphic outcomes across cognition, behaviour and brain structure. Females demonstrated more consistently negative outcomes, particularly within the congenital adrenal hyperplasia-affected population, where females were exposed to longer treatment durations than males. The outcomes for males were more heterogenous. For preterm birth, some studies suggest preterm males remain at increased risk for mortality and morbidity, while in term-born infants, females may have worse outcomes. The nature of these effects, however, differed with antenatal corticosteroid types, and conflicting findings also existed. Potential mechanisms for sexually-dimorphic outcomes include differences in placental enzyme and receptor expression and activity, fetal hypothalamic-pituitary-adrenal (HPA) axis function, and susceptibility to developing respiratory conditions.</p> Conclusions <p>The current literature suggests potential sex differences following antenatal corticosteroids, which differ between congenital adrenal hyperplasia and preterm birth risk. Owing to surmounting evidence of negative outcomes and the retracting use of antenatal corticosteroids for congenital adrenal hyperplasia, further research will be challenging. Whereas studies concerning sexually-dimorphic responses to antenatal corticosteroids for preterm birth risk are essential, given their widespread use. Further research in this area may help to understand whether the clinical management of preterm birth should be adjusted according to sex.</p>

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Sexually-dimorphic offspring outcomes following antenatal corticosteroids: a review of the evidence for congenital adrenal hyperplasia and preterm birth risk

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月3日

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  • Lulu Y. L. Birch,
  • Amanda N. Sferruzzi-Perri

摘要

Background

Pregnant individuals may receive antenatal corticosteroids for various conditions, including congenital adrenal hyperplasia (to prevent virilisation in female fetuses) and preterm birth risk (to hasten fetal maturation and improve perinatal survival). This narrative review aimed to evaluate the evidence of sexually-dimorphic offspring outcomes following antenatal corticosteroids for such conditions and explore the potential underlying mechanisms.

Methods

A comprehensive MEDLINE search identified twenty-eight studies for inclusion: seven focused on congenital adrenal hyperplasia and twenty-one focused on preterm birth risk.

Results

For congenital adrenal hyperplasia, evidence suggests that antenatal corticosteroids are associated with sexually-dimorphic outcomes across cognition, behaviour and brain structure. Females demonstrated more consistently negative outcomes, particularly within the congenital adrenal hyperplasia-affected population, where females were exposed to longer treatment durations than males. The outcomes for males were more heterogenous. For preterm birth, some studies suggest preterm males remain at increased risk for mortality and morbidity, while in term-born infants, females may have worse outcomes. The nature of these effects, however, differed with antenatal corticosteroid types, and conflicting findings also existed. Potential mechanisms for sexually-dimorphic outcomes include differences in placental enzyme and receptor expression and activity, fetal hypothalamic-pituitary-adrenal (HPA) axis function, and susceptibility to developing respiratory conditions.

Conclusions

The current literature suggests potential sex differences following antenatal corticosteroids, which differ between congenital adrenal hyperplasia and preterm birth risk. Owing to surmounting evidence of negative outcomes and the retracting use of antenatal corticosteroids for congenital adrenal hyperplasia, further research will be challenging. Whereas studies concerning sexually-dimorphic responses to antenatal corticosteroids for preterm birth risk are essential, given their widespread use. Further research in this area may help to understand whether the clinical management of preterm birth should be adjusted according to sex.