BACKGROUND Temporal- and sex-specific effects of perinatal stress have not been examined for childhood asthma. OBJECTIVES We examined associations between pre- and/or postnatal stress and children's asthma (n=765) and effect modification by sex in a prospective cohort study. METHODS Maternal negative life events (NLEs) were ascertained prenatally and postpartum. NLEs scores were categorized as 0, 1-2, 3-4, or ≥5 to assess exposure-response relationships. We examined effects of pre- and postnatal stress on children's asthma by age 6 years modeling each as independent predictors; mutually adjusting for prenatal and postnatal stress; and finally considering interactions between pre- and postnatal stress. Effect modification by sex was examined in stratified analyses and by fitting interaction terms. RESULTS When considering stress in each period independently, among boys a dose-response relationship was evident for each level increase on the ordinal scale prenatally (OR=1.38, 95% CI 1.06, 1.79; p-for-trend=0.03) and postnatally (OR=1.53, 95% CI 1.16, 2.01; p-for-trend=0.001); among girls only the postnatal trend was significant (OR=1.60, 95% CI 1.14, 2.22; p-for-trend=0.005). Higher stress in both the pre- and postnatal periods was associated with increased odds of being diagnosed with asthma in girls [OR=1.37, 95% CI 0.98, 1.91 (pinteraction=0.07)] but not boys [OR=1.08, 95% CI 0.82, 1.42 (pinteraction=0.61)]. CONCLUSIONS While boys were more vulnerable to stress during the prenatal period, girls were more impacted by postnatal stress and cumulative stress across both periods in relation to asthma. Understanding sex and temporal differences in response to early life stress may provide unique insight into asthma etiology and natural history.

Prenatal PM exposure during sensitive windows is associated with increased risk of child asthma, especially in boys concurrently exposed to elevated maternal stress.

Background Previously, we reported that prenatal exposures to polycyclic aromatic hydrocarbons (PAH) and postnatal environmental tobacco smoke (ETS) in combination were associated with respiratory symptoms at ages 1 and 2 years. Here, we hypothesized that children exposed to both prenatal PAH and ETS may be at greater risk of asthma and seroatopy at ages 5 to 6 years, after controlling for current pollution exposure. Methods Prenatal PAH exposure was measured by personal air monitoring over 48 hrs. ETS exposure, respiratory symptoms and asthma at ages 5–6 years were assessed through questionnaire. Immunoglobulin (Ig) E was measured by Immunocap. Results A significant interaction between prenatal PAH and prenatal (but not postnatal) ETS exposure on asthma (p<0.05), but not IgE, was detected. Among children exposed to prenatal ETS, a positive nonsignificant association was found between prenatal PAH exposure and asthma (OR 1.96, 95% CI [0.95–4.05]). Among children without exposure to prenatal ETS, a negative nonsignificant association was found between prenatal PAH exposure and asthma (OR 0.65, 95% CI [0.41–1.01]). Prenatal PAH exposure was not associated with asthma or IgE at age 5 to 6 years. Conclusions Combined prenatal exposure to PAH and ETS appears to be associated with asthma but not seroatopy at age 5–6. Exposure to PAH alone does not appear associated with either asthma or seroatopy at age 5 to 6 years. Discerning the differential effects between ETS exposed and ETS nonexposed children requires further study.

Mechanistic studies that more comprehensively assess biomarkers reflecting alterations across interrelated stress response systems and associated regulatory processes, in both pregnant women and young children, could be highly informative. Leveraging high-throughput systems-wide technologies to include epigenomics (e.g., DNA methylation, microRNAs), transcriptomics, and microbiomics as well as integrated multiomics are needed to advance this field of science. Understanding stress-induced physiological changes occurring during vulnerable life periods that contribute to chronic respiratory disease risk could lead to the development of preventive strategies and novel therapeutic interventions.

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