Dataset Information

Dynamic trends in skin barrier function from birth to age 6 months and infantile atopic dermatitis: A Chinese prospective cohort study.

ABSTRACT:

Background

Skin barrier functions develop after birth and may be related to skin disorders in infants. We aimed to assess associations between dynamic trends of four skin barrier functional parameters in early life with infant atopic dermatitis (AD).

Methods

Based on the prospective cohort MKNFOAD (NCT02889081), we examined transepidermal water loss (TEWL), stratum corneum hydration (SCH), skin pH, and sebum content at five anatomical sites (cheek, forehead, forearm, abdomen, and lower leg) in 418 term infants at birth, 42 days, and 6 months. Trend differences by sex and association with AD at age 1 year were tested using variance analyses. Associations of the parameters with AD risk were tested using discrete time survival analysis, adjusting extensive covariates including parental history of allergy, infant's sex, birth weight (kg), and delivery mode. Odds ratios (ORs) and 95% confidence interval (CIs) were reported.

Results

Overall TEWL and SCH appeared trends of increase while skin surface pH and sebum content showed trends of decrease within the first six postnatal months. Sex differences were significant for sebum content only (p < 0.001). After adjustment for parental and children covariates, cheek TEWL at birth (OR = 1.26, 95% CI 1.00-1.57, p = 0.045) and 42 days (OR = 1.52, 95% CI 1.17-1.97, p = 0.002) were significantly associated with increased AD risk. Associations were not observed between SCH, skin pH, and sebum content at birth or 42 days with AD.

Conclusions

Skin barrier functions of Chinese term infants varied nonlinearly after birth. Higher postnatal TEWL levels in early life indicate higher risk of early-onset AD.

SUBMITTER: Ye Y

PROVIDER: S-EPMC8254580 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Atopic dermatitis (AD) is a widely spread cutaneous chronic disease characterised by sensitive reactions (eg. eczema) to normally innocuous elements. Although relatively little is understood about its underlying mechanisms due to its complexity, skin barrier dysfunction has been recognised as a key factor in the development of AD. Skin barrier homeostasis requires tight control of the activity of proteases, called kallikreins (KLKs), whose activity is regulated by a complex network of protein interactions that remains poorly understood despite its pathological importance. Characteristic symptoms of AD include the outbreak of inflammation triggered by external (eg. mechanical and chemical) stimulus and the persistence and aggravation of inflammation even if the initial stimulus disappears. These characteristic symptoms, together with some experimental data, suggest the presence of positive feedback regulation for KLK activity by inflammatory signals. We developed simple mathematical models for the KLK activation system to study the effects of feedback loops and carried out bifurcation analysis to investigate the model behaviours corresponding to inflammation caused by external stimulus. The model analysis confirmed that the hypothesised core model mechanisms capture the essence of inflammation outbreak by a defective skin barrier. Our models predicted the outbreaks of inflammation at weaker stimulus and its longer persistence in AD patients compared to healthy control. We also proposed a novel quantitative indicator for inflammation level by applying principal component analysis to microarray data. The model analysis reproduced qualitative AD characteristics revealed by this indicator. Our results strongly implicate the presence and importance of feedback mechanisms in KLK activity regulation. We further proposed future experiments that may provide informative data to enhance the system-level understanding on the regulatory mechanisms of skin barrier in AD and healthy individuals.