Relationships among Maternal Stress and Depression, Type 2 Responses, and Recurrent Wheezing at Age 3 Years in Low-Income Urban Families

Abstract

Rationale: Maternal depression and prenatal and early life stress may influence childhood wheezing illnesses, potentially through effects on immune development.

Objectives: To test the hypothesis that maternal stress and/or depression during pregnancy and early life are associated with recurrent wheezing and aeroallergen sensitivity and altered cytokine responses (enhanced type 2 or reduced virus-induced cytokine responses) from stimulated peripheral blood mononuclear cells at age 3 years.

Methods: URECA (Urban Environment and Childhood Asthma) is a birth cohort at high risk for asthma (n = 560) in four inner cities. Maternal stress, depression, and childhood wheezing episodes were assessed by quarterly questionnaires beginning at birth. Logistic and linear regression techniques were used to examine the relation of maternal stress/depression to recurrent wheezing and peripheral blood mononuclear cell cytokine responses at age 3 years.

Measurements and main results: Overall, 166 (36%) children had recurrent wheeze at age 3 years. Measures of maternal perceived stress at Years 2 and 3 were positively associated with recurrent wheeze (P < 0.05). Maternal depression (any year) was significantly associated with recurrent wheezing (P ≤ 0.01). These associations were also significant when considered in a longitudinal analysis of cumulative stress and depression (P ≤ 0.02). Neither stress nor depression was significantly related to aeroallergen sensitization or antiviral responses. Contrary to our original hypothesis, prenatal and Year 1 stress and depression had significant inverse associations with several type 2 cytokine responses.

Conclusions: In urban children at high risk for asthma, maternal perceived stress and depression were significantly associated with recurrent wheezing but not increased atopy or reduced antiviral responses.

Keywords: atopy; depression; inner city; stress; wheezing.

Figures

Figure 1.

Associations (odds ratios and 95% confidence intervals [CIs]) between stress and depression at each year and clinical outcomes at age 3 years. Relationships with recurrent wheeze are depicted in A, and relationships with atopy are shown in B. Solid circles indicate P < 0.05 after adjustment for mother’s race/ethnicity, prenatal smoking, maternal smoking in the first year of the child’s life, maternal asthma, child’s birth weight, birth season, number of previous live births, and child’s sex.

Figure 2.

Association (β estimates) between stress and depression at each year and cytokine responses at age 3 years. Innate and antiviral responses are shown in A, and adaptive and polyclonal responses in B. All cytokine responses have been log (base 10) transformed before inclusion in the model. Blue represents a positive association ranging from 0 to 3, and red represents a negative association ranging from −3 to 0, which can be interpreted as the resulting stress and depression increase/decrease associated with a 1-log-unit change in the immune response. The intensity of the color represents the strength of the association, and statistically significant relationships after correction for multiple comparisons are marked with an asterisk. In addition, any cytokine responses that do not show much variability (i.e., most responses are at the limit of detection) are marked with a diagonal white line. The analysis was adjusted for mother’s race/ethnicity, prenatal smoking, maternal smoking in the first year of the child’s life, maternal asthma, child’s birth weight, birth season, number of previous live births, and child’s sex. cr = cockroach extract; dm = dust mite extract; mab = CD3/αCD28 monoclonal antibody; pha = phytohemagglutinin; rv = rhinovirus; rsv = respiratory syncytial virus; tt = tetanus toxoid.