Biomarkers of neonatal skin barrier adaptation reveal substantial differences compared to adult skin

Abstract

Background The objective of this study was to measure skin characteristics in premature (PT), late preterm (LPT), and full-term (FT) neonates compared with adults at two times (T1, T2). Methods Skin samples of 61 neonates and 34 adults were analyzed for protein biomarkers, natural moisturizing factor (NMF), and biophysical parameters. Infant groups were: <34 weeks (PT), 34–<37 weeks (LPT), and ≥37 weeks (FT). Results Forty proteins were differentially expressed in FT infant skin, 38 in LPT infant skin, and 12 in PT infant skin compared with adult skin at T1. At T2, 40 proteins were differentially expressed in FT infants, 38 in LPT infants, and 54 in PT infants compared with adults. All proteins were increased at both times, except TMG3, S100A7, and PEBP1, and decreased in PTs at T1. The proteins are involved in filaggrin processing, protease inhibition/enzyme regulation, and antimicrobial function. Eight proteins were decreased in PT skin compared with FT skin at T1. LPT and FT proteins were generally comparable at both times. Total NMF was lower in infants than adults at T1, but higher in infants at T2. Conclusions Neonates respond to the physiological transitions at birth by upregulating processes that drive the production of lower pH of the skin and water-binding NMF components, prevent protease activity leading to desquamation, and increase the barrier antimicrobial properties. Impact Neonates respond to the transitions at birth by upregulating processes that drive the production of lower pH of the skin and NMF, prevent protease activity leading to desquamation, and increase the antimicrobial properties of the barrier. The neonatal epidermal barrier exhibits a markedly different array of protein biomarkers both shortly after birth and 2–3 months later, which are differentially expressed versus adults. The major biomarker-functional classes included filaggrin processing, protease inhibitor/enzyme regulators, antimicrobials, keratins, lipids, and cathepsins. The findings will guide improvement of infant skin care practices, particularly for the most premature infants with the ultimate goals mitigating nosocomial infection.

Newborn infant skin gene expression: Remarkable differences versus adults

“…SERPINB3 gene expression was elevated in infant tissues, consistent with the previous report of the gene product being higher in the outer SC of infants versus adults [ 19 ]. Higher levels of SERPINB3 regulate cysteine proteases, and, later, transglutaminases and epidermal homeostasis [ 58 ].…”

“…Gene expression of PI3, S100A8, S100A9, S100A7, SERPINB3 and SERPINB4 are of particular interest based on our previous comparison of infant and adult SC samples using proteomic analysis [ 19 ]. PI3 regulates peptidase and endopeptidase activity.…”

“…The differences in epidermal barrier gene expression are consistent with previous reports wherein measures of skin function, such as hydration, skin surface pH, TEWL, and visual dryness/scaling, have allowed drawing the conclusion that infant epidermal barrier maturation/adaptation continues for weeks to months following birth [ 32 , 33 ]. They may also explain the relatively reduced SC cohesion and lower antimicrobial peptide levels soon after birth [ 19 ].…”

“…In a previous report, we described neonatal skin barrier adaptation and functional integrity using targeted proteomic skin biomarker analysis from the outer SC [ 19 ]. At birth, neonatal skin showed upregulation of processes allowed by the lower pH of infant skin.…”

Epidermal Immunity and Function: Origin in Neonatal Skin

“…Subsequently, targeted proteomic analysis of skin surface (stratum corneum) biomarkers and established biophysical measures of barrier function were used to determine changes over time. The cohorts included 61 newborn infants grouped by GA, specifically: premature <34 wks GA (PT), late premature ≥34-< 37 wks GA (LPT), and full-term ≥ 37 wks GA (FT) ( Visscher et al, 2020 ). Infant biomarkers were compared to adult values (i.e., a widely studied, established steady-state condition subject parents, n = 34) at two-time points, 4–8 days after birth, and 2–3 months later when the three infant groups were at comparable gestational ages of 46–48 weeks.…”