Prenatal maternal stress predicts reductions in CD4+ lymphocytes, increases in innate-derived cytokines, and a Th2 shift in adolescents: Project Ice Storm

Physiol Behav. 2015 May 15;144:137-45. doi: 10.1016/j.physbeh.2015.03.016. Epub 2015 Mar 14.


The relationship between psychological stress and immunity is well established, but it is not clear if prenatal maternal stress (PNMS) affects the development of the immune system in humans. Our objective was to determine the extent of this influence in a sample of teenagers whose mothers were pregnant during the 1998 Quebec ice storm. As part of a longitudinal study of PNMS, we measured the objective stress exposure and subjective distress of the women soon after the disaster. We obtained blood samples from 37 of their children when they were 13years old to measure cell population percentages and mitogen-induced cytokine production. We found that the mothers' objective degree of PNMS exposure significantly predicted reductions in total and CD4+ lymphocyte proportions, increases in TNF-α, IL-1β, and IL-6 levels, and an enhancement of the Th2 cytokines IL-4 and IL-13. Sex and timing of PNMS exposure during gestation were also associated with some outcomes. These results show that PNMS is a programming factor that can produce long-lasting consequences on immunity, potentially explaining non-genetic variability in immune-related disorders. This information contributes to the understanding of the mechanisms underlying the influence of PNMS on immune-mediated disorders in humans.

Keywords: Cytokines; Fetus; Immunity; Lymphocytes; Ontogeny; Prenatal stress; Programming.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • CD4-Positive T-Lymphocytes / pathology*
  • Cohort Studies
  • Cytokines / metabolism*
  • Female
  • Flow Cytometry
  • Humans
  • Linear Models
  • Male
  • Predictive Value of Tests
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / pathology
  • Prenatal Exposure Delayed Effects* / physiopathology
  • Prenatal Exposure Delayed Effects* / psychology
  • Statistics, Nonparametric
  • Stem Cells / pathology
  • Stress, Psychological / etiology*
  • Stress, Psychological / pathology*
  • Th2 Cells / pathology*


  • Cytokines