Expanding Understanding of the HPA Axis in Prenatal Programming: An Examination of Maternal DHEA

• In Event: Prenatal Programming: Physiological and Neurodevelopmental Consequences

Abstract

Characteristics of the intrauterine environment play a fundamental role in programming the fetus for life after birth. There is an extensive body of literature examining the effects of the prenatal maternal hypothalamic-pituitary-adrenal (HPA) axis and its end product, cortisol, on neurodevelopmental outcomes (Bosquet Enlow et al., 2017; Davis et al., 2007; Talge, Neal, & Glover, 2007). However, dehydroepiandosterone (DHEA) is an additional HPA axis product that has largely been ignored in the context of human pregnancy and may provide a more complete understanding of how the prenatal maternal HPA axis shapes developmental outcomes. Cortisol and DHEA are strikingly similar in terms of how they are synthesized and released and both have shared genomic and non-genomic effects. Furthermore, there is evidence that assessing the synergistic effects of cortisol and DHEA provides more nuanced insights into the role of HPA axis function in fetal development (Kamin & Kertes, 2017). Despite the potential for this approach to significantly further our understanding of fetal programming, very few studies have examined these combined effects. The current study tested the hypothesis that DHEA is an additional HPA axis product that plays a critical role in fetal programming. Specifically, we assessed the unique and joint effects of prenatal maternal cortisol and DHEA on the development of emotionality in infants. The study consisted of 124 mother-child dyads. Cortisol and DHEA were measured via hair collection at 15 weeks (early gestation) and 35 weeks (late gestation) using liquid chromatography tandem mass spectrometry (LC-MS/MS; conducted in the Dresden LabService GmbH lab at Technische Universität Dresden). Observational assessments of infant positive and negative emotionality were collected when infants were six months old using the Laboratory Temperament Assessment Battery (Lab-TAB) Puppet Show and the Still-Face paradigm, respectively. As expected based on the existing literature, late gestation cortisol concentrations were positively associated with infant negative emotionality (r = .21, p = .052) at six months. There was a positive association between both early and late gestation DHEA and positive emotionality (r = .27, p = .008; r = .20, p = .046, respectively). To investigate the moderating role of DHEA in the association between prenatal maternal cortisol and infant emotionality, we conducted moderation analyses using the PROCESS Macro for SPSS. There was a robust, positive association between late gestation cortisol and negative emotionality at low levels of DHEA (B = 1.13, p = .009, 95% CI[.30, 1.97]; Figure 1) that was not observed at higher levels. Similarly, the association between late gestation cortisol and positive emotionality approached statistical significance when levels of DHEA were low (B = -0.45, p = .087, 95% CI[-.98, .07]; Figure 2), but not high. These findings demonstrate that prenatal exposure to maternal DHEA may shape the development of infant emotionality, supporting the hypothesis that DHEA plays a role in fetal programming. Further, associations between maternal cortisol and infant emotionality were dependent on levels of DHEA. Therefore, our understanding of how prenatal maternal HPA axis products contribute to offspring neurodevelopmental outcomes may be enhanced by the consideration of DHEA.

Authors

• Natasha Bailey, University of Virginia - Charlottesville
  Presenting Author

• Curt Sandman, University of California, Irvine

• Elysia Poggi Davis, University of Denver

• Laura Glynn, Chapman University