Evidence establishing a link between prenatal and early-life stress and asthma development

Rosa, Maria José; Lee, Alison G.; Wright, Rosalind J.

doi:10.1097/aci.0000000000000421

Cited by 104 publications

(74 citation statements)

References 84 publications

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“…Asthma is a common chronic respiratory airway disease, affecting respiratory health throughout life. According to GINA (Global Initiative for Asthma), asthma prevalence is increasing in many countries, especially in childhood . It is estimated that around 300 million people worldwide are affected by the disease (around 4.5% of adults and 11% of children worldwide) .…”

Section: Introductionmentioning

confidence: 99%

Epigenome‐wide association studies in asthma: A systematic review

Edris

Dekker

Melén

et al. 2019

Clin Experimental Allergy

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Objective Asthma is a common chronic respiratory airway disease influenced by environmental factors and possibly their interaction with the human genome causing epigenetic changes. Epigenome‐wide association studies (EWAS) have mainly investigated DNA methylation and its association with disease or traits, exposure factors or gene expression. This systematic review aimed to identify all EWAS assessing differentially methylated sites associated with asthma in humans. Design Structured systematic literature search following PRISMA guidelines, Newcastle‐Ottawa Scale (NOS) for cohort studies was used for bias assessment. Data Sources We searched PubMed and Embase databases from 2005 to 2019. Eligibility Criteria Epigenome‐wide association studies testing association between differential methylation and asthma in humans. Results Overall, we identified 16 EWAS studies complying with our search criteria. Twelve studies were conducted on children, and 10 were conducted on sample sizes <150 subjects. Four hundred and nineteen CpGs were reported in children studies after correction for multiple testing. In the adult studies, thousands of differentially methylated sites were identified. Differential methylation in inflammatory‐related genes correlated with higher levels of gene expressions of inflammatory modulators in asthma. Differentially methylated genes associated with asthma included SMAD3, SERPINC1, PROK1, IL13, RUNX3 and TIGIT. Forty‐one CpGs were replicated at least once in blood samples, and 28 CpGs were replicated in nasal samples. Conclusion Although many differentially methylated CpGs in genes known to be involved in asthma have been identified in EWAS to date, we conclude that further studies of larger sample sizes and analyses of differential methylation between different phenotypes are needed in order to comprehensively evaluate the role of epigenetic factors in the pathophysiology and heterogeneity of asthma, and the potential clinical utility to predict or classify patients with asthma.

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Section: Introductionmentioning

confidence: 99%

Epigenome‐wide association studies in asthma: A systematic review

Edris

Dekker

Melén

et al. 2019

Clin Experimental Allergy

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“…Putative mechanisms linking stress in pregnancy and childhood wheezing and asthma—independent of an effect on infections—include a dysregulation of maternal and child hypothalamic‐pituitary‐adrenal axes and an immune dysregulation in offspring . However, this mechanism more easily explains an enhanced susceptibility to childhood atopic disorders, including asthma, rather than wheezing in infancy …”

Section: Discussionmentioning

confidence: 99%

“…Mental health during the last 4 weeks of pregnancy was assessed within 48 hours after birth, which might be a very hectic period for the mothers that may influence reporting and mental health assessment. We relied only on the GHQ‐12 questionnaire and not on a clinical psychiatric diagnosis that might better characterize long‐standing attributes of the respondent (trait), nor we had information on stressful life events experienced by mothers over their life course; these would lead to correlates of stress long after exposure, including altered cortisol levels and immune disruption . Information on outcomes was collected by self‐administered questionnaires, which is a widely accepted method of data collection in epidemiologic studies.…”

Section: Discussionmentioning

confidence: 99%

“…Putative mechanisms linking stress in pregnancy and childhood wheezing and asthma-independent of an effect on infections-include a dysregulation of maternal and child hypothalamic-pituitary-adrenal axes and an immune dysregulation in offspring. 31,32 However, this mechanism more easily explains an enhanced susceptibility to childhood atopic disorders, including asthma, rather than wheezing in infancy. 24 The main strength of our study is its prospective design: Since outcomes were ascertained after the occurrence of exposures, we could establish a clear temporal relationship between maternal mental health and childhood outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…We relied only on the GHQ-12 questionnaire and not on a clinical psychiatric diagnosis that might better characterize long-standing attributes of the respondent (trait), nor we had information on stressful life events experienced by mothers over their life course; these would lead to correlates of stress long after exposure, including altered cortisol levels and immune disruption. 31 Information on outcomes was collected by self-administered questionnaires, which is a widely accepted method of data collection in epidemiologic studies. Wheezing might be overestimated, as parents might label a single episode of noisy breathing as wheezing.…”

Section: Discussionmentioning

confidence: 99%

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Perinatal maternal mental health is associated with both infections and wheezing in early childhood

Rusconi

Gagliardi

Gori

et al. 2019

Pediatric Allergy Immunology

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Background Wheezing and infections are common during infancy, and the role of early‐life exposures in their development is still under investigation. We examined associations between maternal mental health in pregnancy and after delivery and subsequent offspring wheezing and infections. Methods We studied 2314 mother‐child pairs recruited in the Piccolipiù birth cohort (Italy) from 2011 to 2015. Maternal mental health was assessed in pregnancy and 12 months after delivery via the General Health Questionnaire‐12 (GHQ‐12). GHQ‐12 Likert scores were collapsed into low (below the upper tercile) and high (above). Risk ratios (RR) and 95% confidence intervals (CI) between each combination of scores—during pregnancy and 1 year after delivery—and outcomes were computed by log‐binomial regression models. Results High scores both in pregnancy and after delivery, compared with low scores in both periods, were associated with wheezing (RR: 1.35; 95% CI: 1.08, 1.69), recurrent (≥2 episodes) wheezing (1.35; 0.99, 1.83), any and recurrent (≥4 episodes) upper respiratory infections (1.20; 1.04, 1.41, and 1.45; 1.07, 1.97, respectively), lower respiratory infections (1.31; 1.08, 1.61), and diarrhea (1.49; 1.23, 1.80). High scores either during pregnancy or 1 year after delivery only were less consistently associated with outcomes. Conclusions Maternal mental health problems extending from pregnancy to the first year after delivery are associated with development of both wheezing and infections. As wheezing is mostly triggered by infections, increased infection susceptibility could represent a possible common biologic mechanism. This study confirms the importance of early‐life exposures on childhood health.

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Association of a Housing Mobility Program With Childhood Asthma Symptoms and Exacerbations

Pollack,

Roberts,

Peng

et al. 2023

JAMA

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ImportanceStructural racism has been implicated in the disproportionally high asthma morbidity experienced by children living in disadvantaged, urban neighborhoods. Current approaches designed to reduce asthma triggers have modest impact.ObjectiveTo examine whether participation in a housing mobility program that provided housing vouchers and assistance moving to low-poverty neighborhoods was associated with reduced asthma morbidity among children and to explore potential mediating factors.Design, Setting, and ParticipantsCohort study of 123 children aged 5 to 17 years with persistent asthma whose families participated in the Baltimore Regional Housing Partnership housing mobility program from 2016 to 2020. Children were matched to 115 children enrolled in the Urban Environment and Childhood Asthma (URECA) birth cohort using propensity scores.ExposureMoving to a low-poverty neighborhood.Main OutcomesCaregiver-reported asthma exacerbations and symptoms.ResultsAmong 123 children enrolled in the program, median age was 8.4 years, 58 (47.2%) were female, and 120 (97.6%) were Black. Prior to moving, 89 of 110 children (81%) lived in a high-poverty census tract (&gt;20% of families below the poverty line); after moving, only 1 of 106 children with after-move data (0.9%) lived in a high-poverty tract. Among this cohort, 15.1% (SD, 35.8) had at least 1 exacerbation per 3-month period prior to moving vs 8.5% (SD, 28.0) after moving, an adjusted difference of −6.8 percentage points (95% CI, −11.9% to −1.7%; P = .009). Maximum symptom days in the past 2 weeks were 5.1 (SD, 5.0) before moving and 2.7 (SD, 3.8) after moving, an adjusted difference of −2.37 days (95% CI, −3.14 to −1.59; P &lt; .001). Results remained significant in propensity score–matched analyses with URECA data. Measures of stress, including social cohesion, neighborhood safety, and urban stress, all improved with moving and were estimated to mediate between 29% and 35% of the association between moving and asthma exacerbations.Conclusions and RelevanceChildren with asthma whose families participated in a program that helped them move into low-poverty neighborhoods experienced significant improvements in asthma symptom days and exacerbations. This study adds to the limited evidence suggesting that programs to counter housing discrimination can reduce childhood asthma morbidity.

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Evidence establishing a link between prenatal and early-life stress and asthma development

Cited by 104 publications

References 84 publications

Epigenome‐wide association studies in asthma: A systematic review

Epigenome‐wide association studies in asthma: A systematic review

Perinatal maternal mental health is associated with both infections and wheezing in early childhood

Association of a Housing Mobility Program With Childhood Asthma Symptoms and Exacerbations

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