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

  • Jenna L. RiisEmail author
  • Douglas A. Granger
  • Han Woo
  • Kristin Voegtline
  • Janet A. DiPietro
  • Sara B. Johnson
Special Issue: Salivary Bioscience



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.


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 (nfemale = 25, nmale=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.


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.


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.


Prenatal maternal cortisol Salivary cytokine HPA axis Neuroendocrine-immune Sex differences 


Funding information

This research was supported by KO1DA027229-01 from National Institutes of Health/National Institute on Drug Abuse to SBJ and National Institutes of Health/National Institute of Child Health and Human Development award R01 HD27592 to JAD.

Compliance with Ethical Standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent was obtained from all individual participants included in the study.

Conflict of Interest

In the interest of full disclosure, DAG is founder and chief scientific and strategy advisor at Salimetrics LLC and Salivabio LLC and these relationships are managed by the policies of the committees on conflict of interest at the Johns Hopkins University School of Medicine and the University of California at Irvine.


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Copyright information

© International Society of Behavioral Medicine 2019

Authors and Affiliations

  • Jenna L. Riis
    • 1
    • 2
    Email author
  • Douglas A. Granger
    • 1
    • 2
    • 3
    • 4
  • Han Woo
    • 5
  • Kristin Voegtline
    • 5
  • Janet A. DiPietro
    • 3
  • Sara B. Johnson
    • 3
    • 5
  1. 1.School of Social EcologyUniversity of California, IrvineIrvineUSA
  2. 2.Institute for Interdisciplinary Salivary Bioscience ResearchUniversity of California, IrvineIrvineUSA
  3. 3.Johns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  4. 4.Johns Hopkins University School of NursingBaltimoreUSA
  5. 5.Johns Hopkins School of MedicineBaltimoreUSA

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