Prenatal maternal psychosocial stress and offspring’s asthma and allergic disease : a systematic review and meta-analysis

BACKGROUND: Prenatal maternal stress may influence offspring's atopic risk through sustained cortisol secretion resulting from activation of the hypothalamic-pituitary-axis (HPA), leading to Th2-biased cell differentiation in the fetus. We undertook a systematic review and meta-analysis investigating the relationship between prenatal maternal psychosocial stress and risk of asthma and allergy in the offspring. METHODS: We searched 11 electronic databases from 1960 to 2016, search the grey literature, and contacted experts in the field. Type of stress indicator included mood disorders, anxiety, exposure to violence, bereavement and socio-economic problems occurring during pregnancy, both objectively or subjectively measured. We included all possible asthma and IgE-mediated allergy outcomes. We conducted random-effects meta-analyses to synthesize the data. RESULTS: We identified 9,779 papers of which 30 studies (enrolling >6 million participants) satisfied inclusion criteria. The quality of 25 studies was moderate, four were strong, and one was weak. Maternal exposure to any type of stressors was associated with an increased risk of offspring atopic eczema/dermatitis (OR 1.34, 95%CI 1.22-1.47), allergic rhinitis (OR 1.30, 95%CI 1.04-1.62), wheeze (OR 1.34, 95%CI 1.16-1.54) and asthma (OR 1.15, 95%CI 1.04-1.27). Exposure to anxiety and depression had strongest effect compared to other stressors. Exposure during the third trimester had the greatest impact compared to first and second trimesters. The increased risk was stronger for early-onset and persistent than for late-onset wheeze. Bereavement of a child (HR 1.28, 95%CI 1.10-1.48) or a spouse (HR 1.40, 95%CI 1.03-1.90) increased the risk of offspring asthma. CONCLUSIONS: Exposure to prenatal maternal psychosocial stress was associated with increased risk, albeit modestly, of asthma and allergy in the offspring. The pronounced risk during the third trimester may represent cumulative stress exposure throughout pregnancy rather than trimester-specific effect. Our findings may represent a causal effect or a result of inherent biases in studies, particularly residual confounding.Institute for Advanced Social Research, University of TampereSchool of Health Sciences, University of TampereFarr Institute and Asthma UK Centre for Applied Research, University of EdinburghKnut & Alice Wallenberg FoundationMedical Research Council UKWallenberg Centre for Molecular and Translational Medicine, University of GothenburgStudent Awards Agency for ScotlandSwedish Initiative for Research on Microdata in the Social and Medical Sciences, SIMSAM 340-2013-5867Swedish Research Council for Health, Working Life and Welfare (Forte), COFAS Marie Curie, 2015-01208Accepte