Association Between Skin Barrier Development and Early-Onset Atopic Dermatitis: A Longitudinal Birth Cohort Study

To monitor skin barrier development from birth to 12 months including lipid structure, desquamatory protease activity, natural moisturizing factor, and transepidermal water loss to evaluate atopic dermatitis (AD) risk and development.Full term, healthy infants born at a single teaching hospital in United Kingdom were followed longitudinally for 12 months (180 in original cohort, 128 completed). The population largely consisted of infants of white ethnicity with family history of atopic disease.Skin was assessed on the maternity ward (<72 hours old) and at the home at 4 ± 2 weeks and 12 ± 1 month. The Neonatal Skin Condition Score at birth, visual examination of skin at all time points, and saliva at age 12 months for genomic analysis were obtained. Lipid structure, protease activity, natural moisturizing factor, and TEWL were assessed. Primary outcomes were the change in skin barrier function, molecular composition, and protease activity. Secondary outcomes were the incidence of AD, parental-reported skin rashes, frequency of FLG risk alleles, and association of skin barrier function, molecular composition, and protease activity measured at birth and 4 weeks with an AD diagnosis by 12 months. Statistical analyses were performed.Twenty-five (20%) infants developed AD by 12 months. Thirty-five percent of the AD population carried ≥1 common FLG variant allele (8% in no disease). Changes in skin development variables were noted beginning at 4 weeks of life. The investigators noted subtle differential skin barrier development between infants with and without disease before the onset of AD.This exploratory study utilizing a portfolio of remotely performed tests identified subtle differences in skin barrier maturation that predated the onset of AD. An FLG defect, reduced NMF, and drier skin surface at 4 weeks and reduced C-L protease activity and increased surface lipids were associated with development of AD at 12 months, highlighting the potential for these data collected in a community setting. Skin barrier maturation continues until at least 12 months, consistent with prior findings.This study highlights the possibility of using direct skin measurements and genotyping to greater understand risk of developing AD, of importance, as noted in this study, is that there is not always concordance between family history of atopy and development of AD. Strengths included the relatively noninvasive skin sampling and genotyping performed at the bedside, and in the community, and that identified differences in skin development were associated with increased risk of developing AD before its onset, which highlights their potential utility in identifying high-risk infants. Additional research is needed before tools such as these are ready to be clinically used, such as assessing for reproducibility of findings across a larger, more diverse cohort and of a greater duration to confirm the diagnosis of AD and disease severity; cost-benefit analysis of these proposed technologies; identification of additional AD-risk genotypes representative of the diversity of patients who develop AD; and if prophylactic interventions are to be considered as a result of these tests, a prospective study evaluating their safety and efficacy.