Data-driven discovery of mid-pregnancy immune markers associated with maternal lifetime stress: results from an urban pre-birth cohort

Whitney Cowell*, Elena Colicino, Alison G. Lee, Michelle Bosquet Enlow, Julie D. Flom, Cecilia Berin, Robert O. Wright, Rosalind J. Wright

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Changes to the maternal inflammatory milieu may be a mechanism through which maternal psychosocial stress is transmitted to the fetus. Research investigating a limited number of immune markers may miss important signals. We take a proteomics approach to investigate maternal lifetime stress and 92 biomarkers of immune system status. Participants were enrolled in an urban, dual-site (Boston, n = 301 and New York City, n = 110) pregnancy cohort. We measured maternal lifetime history of stress and trauma using the validated Life Stressor Checklist-Revised (LSC-R). We measured a panel of 92 immune-related proteins in mid-pregnancy serum using proximity extension assay technology. We leveraged the dual-site study design to perform variable selection and inference within the cohort. First, we used LASSO to select immune markers related to maternal stress among Boston mothers. Then, we performed OLS regression to examine associations between maternal stress and LASSO-selected proteins among New York City mothers. LASSO regression selected 19 immune proteins with non-null coefficients (CCL11, CCL23, CD244, CST5, CXCL1, CXCL5, CXCL10, CX3CL1, FGF-23, IL-5, IL-7, IL-10, IL-17C, MCP-2, MMP-1, SLAMF1, ST1A1, TNF-β, and TWEAK). Of these, only the chemotactic cytokine CX3CL1 (i.e. fractalkine) was significantly associated with maternal stress among the validation sample (percent change in LSC-R score per 1% increase in relative fractalkine expression: 0.74, 95% confidence interval: 0.19, 1.28). Expanding research suggests fractalkine plays an important role in many aspects of pregnancy and fetal development and is stress-sensitive. We found that maternal lifetime history of stress and trauma was significantly associated with elevated serum fractalkine levels during pregnancy.

Original languageEnglish (US)
Pages (from-to)349-358
Number of pages10
JournalStress
Volume23
Issue number3
DOIs
StatePublished - May 3 2020

Funding

This work was supported by the National Institutes of Health [grant numbers: R01 HL114396, R01 HL095606, P30 ES023515, and UG3 OD023337]. During the preparation of this manuscript, WJC was supported by T32 HD049311 and AGL was supported by K23 HL135349. We thank the Human Immune Monitoring Center at the Icahn School of Medicine at Mount Sinai (New York, NY) for proximity extension assay analysis services.

Keywords

  • CX3CL1
  • Immune
  • fractalkine
  • pregnancy
  • stress
  • trauma

ASJC Scopus subject areas

  • Physiology
  • Neuropsychology and Physiological Psychology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Behavioral Neuroscience

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