Prenatal and postnatal stress and asthma in children: Temporal- and sex-specific associations

Abstract

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.

Association of prenatal and early childhood stress with reduced lung function in 7-year-olds

“…Our results support the previously reported associations between maternal stress assessed using the same NLE measure and child asthma risk by age 6 years which also found that boys were more susceptible to both pre- and postnatal maternal stress 36 . It may be the case that different types of stress have variable impact on lung development and may effect girls and boys differently, as demonstrated for other disorders 50 .…”

“…Disturbed regulation of stress systems [e.g., HPA axis, autonomic nervous system (ANS)] may modulate offspring immune function starting in utero 31 , leading to altered systemic cytokine production 32,33 . Chronic maternal or caregiver stress in pregnancy and the early childhood period have been associated with persistent wheeze 34,35 and asthma 36,37 in early childhood as well as factors that may initiate or potentiate inflammation in the lung (e.g. HPA axis disruption, enhanced nonspecific and allergen-specific lymphocyte proliferation, differential cytokine expression) 38–40 .…”

Sex Differences in Vulnerability to Prenatal Stress: a Review of the Recent Literature

“…A second paper by this group ( N  = 765) showed a sex-dependent association whereby PNLEs were associated with increased odds of asthma at age 4 in boys but not girls. However, among girls, there was evidence of a combined effect of prenatal and postnatal stress on the odds of asthma [58•]. In the third study ( N  = 417), there was a sex-specific association whereby PNLEs were positively associated with risk for lifetime wheeze at age 4 among boys only [59].…”

“…Among female offspring, there was greater evidence for positive associations between PNMS and early childhood difficulties with cognitive [48, 67] and motor development [41•, 66], and adulthood cardiovascular disease risk [60]. In contrast, we uncovered greater evidence for PNMS sensitivity in male offspring for early childhood wheezing/asthma [58•, 59], externalizing pathology [39, 54], and schizophrenia spectrum disorders [42•]. It is noteworthy that males have a greater risk in the general population for all of the adverse health outcomes showing male-biased PNMS programming effects in this review (early childhood asthma/wheezing [58•, 59, 74], externalizing pathology [39, 54, 75], and schizophrenia spectrum disorders [42•, 76]).…”

“…In contrast, we uncovered greater evidence for PNMS sensitivity in male offspring for early childhood wheezing/asthma [58•, 59], externalizing pathology [39, 54], and schizophrenia spectrum disorders [42•]. It is noteworthy that males have a greater risk in the general population for all of the adverse health outcomes showing male-biased PNMS programming effects in this review (early childhood asthma/wheezing [58•, 59, 74], externalizing pathology [39, 54, 75], and schizophrenia spectrum disorders [42•, 76]). It may be that PNMS contributes to, or exacerbates, vulnerabilities for these sexually dimorphic health conditions [77].…”