Meta-Analysis of the Effects of Prenatal Stress on Offspring Glucocorticoid Levels

By Maryna Mullerman’20

Figure 1. Prenatal stress affected offspring sensitivity regardless of life history parameters.

The Hypothalamic Pituitary Adrenal (HPA)-axis is an important pathway that mediates the relationship between prenatal stress and later offspring development. Glucocorticoids—the final steroid hormones in the HPA-axis released by the cortex of the adrenal gland — are closely associated with prenatal stress in humans. To investigate the strength of this association among different animal species, Zaneta M. Thayer and researchers from Dartmouth University conducted a meta-analysis of existing studies that described the effects of prenatal stress on glucocorticoid levels in 14 vertebrate animal species, including mammals, birds, and amphibians.

The study involved a review of publications on prenatal exposure, including observed and experimentally administered stressors. The researchers measured the effect size (d) with correlation for small sample sizes (d’) and constructed a phylogeny of all species in the sample. Life history traits, such as body size and gestation length, were retrieved from published research. The study utilized Bayesian models of probability for each estimated parameter and applied Egger’s regression — a method used to detect small study bias — to evaluate publication bias.

A positive overall effect size of parental stress on glucocorticoid levels was observed in offspring. Life history parameters showed that body size increases caused effect size decreases. However, an increase in brain size increased the effect size. The researchers found that the effect size from experimental studies was larger than that from the observational studies. The highest proportion of variance was explained mostly by the random effect and phylogenic history. In mammals, life history traits were not significant moderators of effect size. After stressor exposure, offspring glucocorticoid recovery evoked the greatest effect sizes.
The study indicated that parental stress affected offspring sensitivity regardless of life history parameters. Thus, species with different life histories had similar capacities for parental stress effects. The association strength depended on whether the study was experimental or observational. The researchers analyzed an important evolutionary aspect of ancient HPA-axis and its output. This study was limited to the effects of prenatal stress on glucocorticoid hormones. More research is needed to evaluate the impact of other triggers that can lead to changes in the release of glucocorticoids.



  1. Z. M. Thayer, et. al., Impact of prenatal stress on offspring glucocorticoid levels: a phylogenetic meta-analysis across 14 vertebrate species. Scientific Reports 8, (2018). doi: 10.1038/s41598-018-23169-w.
  2. Image retrieved from:….0…1c.1.64.psy-ab..0.4.379.0..0i67k1.59.z8uDic-QOpM#imgrc=W-rmKwszizo8yM

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