Long-Term Associations Between Prenatal Maternal Cortisol and Child Neuroendocrine-Immune Regulation

Background: Advancing understanding of the developmental origins of neuroendocrine-immune (NEI) functioning is key to elucidating the biological mechanisms involved in health and disease risk across the lifespan. This study examined whether prenatal maternal hypothalamic-pituitary-adrenal (HPA) activity moderates child NEI relations and explored the consistency of this moderating effect across gestation. Methods: Pregnant women participated in five prenatal study visits from 24 to 38 weeks gestation. At each visit, women provided a saliva sample. In a 5-year follow-up study, children (n_female = 25, n_male=20) provided four saliva samples and participated in behavioral assessments and challenge tasks. Prenatal maternal saliva samples were assayed for cortisol. Child saliva samples were assayed for cortisol and cytokines (IL-1β, IL-6, IL-8, TNFα) as indices of HPA and inflammatory activity. Multilevel mixed-effects models examined the moderation of child NEI relations by prenatal maternal cortisol. Results: Among males, average prenatal maternal cortisol did not moderate child NEI relations. Among females, average prenatal maternal cortisol moderated some child NEI relations with higher prenatal cortisol associated with more positive cortisol-cytokine relations at age five. When examined by gestational time point, there were more significant NEI moderation effects by maternal cortisol from later gestation (≥ 30 weeks) than earlier. Conclusions: The findings suggest prenatal maternal HPA activity may moderate child NEI functioning. Additional research conducted with more heterogeneous and larger samples is needed to fully understand these relations. Furthering our knowledge of NEI development has important research and clinical implications, particularly for understanding and addressing conditions with inflammatory pathophysiologies, such as depression and cardiovascular disease.