Prenatal Origins of Child Health: Independent and Joint Effects of Maternal Distress and Exposure to Air Pollution on Immune-Related Outcomes

Abstract

Objective: The aim of this dissertation was to examine, both independently and jointly, the association of prenatal exposure to maternal depression and air pollution with immune responses in the neonate at birth, and with the child’s risk of developing acute lower respiratory illnesses (ALRI) in the first three years of life. Methods: We studied women recruited in early pregnancy into the Project Viva longitudinal cohort. Women reported depressive symptoms in mid-pregnancy (Edinburgh Postnatal Depression Scale) and depression history by questionnaire. We estimated black carbon (BC) and fine particulate matter (PM2.5) exposures, residential proximity to major roadways, and near-residence traffic density, averaged over pregnancy. Neonatal immune responses (lymphocyte proliferation and cytokine production) were assayed from cord blood mononuclear cells (CBMC) collected at birth. Information on ALRI was collected by questionnaire at age 1, 2, and 3. We examined independent and joint associations of depression and air pollution with immune parameters, using multivariable linear or Tobit regression analyses. We examined associations of maternal depression with frequency of ALRI by age 3, and effect modification by residential proximity to a major roadway during pregnancy, using negative binomial and relative risk regression analyses. Results: After adjustment for confounders, levels of the anti-inflammatory cytokine IL-10 were substantially lower in cord blood from ever versus never depressed women after stimulation with mitogen or antigen (% difference: Bla g2 -41.4, p=0.027; Der f1 -36.0, p=0.071; PHA -24.2, p=0.333). CBMC production of IL-10, and of the predominantly pro-inflammatory cytokines IL-6 and TNF-a, were all decreased when mothers were exposed to higher levels of PM2.5 during pregnancy. When included in models with PM2.5, maternal depression independently predicted lower IL-10 concentrations. Frequency of ALRI in the first three years of life was higher in ever versus never depressed women (rate ratio 1.35, 95% CI 1.09, 1.61). Proximity to road and mother’s depression independently predicted risk of respiratory illness. Conclusion: Maternal psychosocial factors should be considered when evaluating impacts of environmental contaminants such as air pollution on the health of developing children, especially in vulnerable communities where psychosocial stressors and higher exposures to environmental toxicants are likely to coincide.