Prenatal Maternal Distress and Allergic Diseases in Offspring: Review of Evidence and Possible Pathways.

Recent studies have suggested a close association between prenatal maternal distress and allergic diseases in the offspring. We selected relevant birth-cohort or national registry studies using a keyword search of the PubMed database and summarized current evidence on the impact of prenatal maternal distress on the development of offspring's allergic diseases. Moreover, we postulated possible pathways linking prenatal distress and allergic diseases based on relevant human and animal studies. Both dysregulated hypothalamic-pituitary-adrenal axis and increased oxidative stress may cause structural (altered brain/lung development) and functional (skewed immune development) changes, which may predispose the fetus to developing allergic diseases during childhood. Although many facts are yet to be discovered, changes in the placental response and epigenetic modification are presumed to mediate the whole process from maternal distress to allergic diseases. Maternal prenatal distress can also interact with other physical or environmental factors, including familial or physical factors, indoor and outdoor pollutants, and early childhood psychological distress. The gut-microbiome-brain axis and the role of the microbiome as an immune modulator should be considered when investigating the stress-allergy relationship and exploring potential intervention modalities. Further research is needed, and particular attention should be given to defining the most vulnerable subjects and critical time periods. To this end, studies exploring relevant biomarkers are warranted, which can enable us to explore adequate intervention strategies.