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

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.

Improving newborn skin health: Effects of diaper care regimens on skin pH and erythema.

BACKGROUND/OBJECTIVE: Newborn infant skin is functional but immature, and diapering products can play a significant role in infant diapered skin health. Previous work demonstrated a regimen consisting of a diaper with an emollient and apertures on the inner liner (topsheet) with an acidic, pH-buffered wipe (Regimen A) lowered newborn skin pH and reduced the enzymatic activity on skin post-stool cleaning versus a regimen without these features (Regimen B). This study extends these findings to determine the impact of Regimen A on diaper area erythema severity over a 2-week use period. METHODS: This IRB-approved, blinded, randomized, crossover study enrolled newborn infants >7 days and ≤8 weeks. Participants exclusively used two unique diaper and wipe combinations, Regimen A and Regimen B (non-emollient, non-aperture containing topsheet and wipe with limited buffering capacity), each for 14 days and preceded by a 3-day washout regimen. RESULTS: Diapered skin pH was reduced during Regimen A use to values similar to that of a non-diapered control site (chest), while use of Regimen B was associated with a more alkaline skin pH. Regimen A resulted in significantly fewer severe erythema episodes. At the site of highest erythema, the perianal space, the average erythema score was significantly lower and more newborns were free of erythema while using Regimen A vs. Regimen B (P < .05). CONCLUSIONS: These findings demonstrate that diapering products can have a significant impact on newborn skin. They reinforce the need to support the physiological normalization of skin pH and protection from skin irritation and damage.

Use of an emollient-containing diaper and pH-buffered wipe regimen restores skin pH and reduces residual enzymatic activity.

BACKGROUND/OBJECTIVES: Diaper dermatitis is one of the most frequent skin conditions affecting infants and is associated with elevated skin pH, exposure to urine and feces, and increased fecal protease and lipase activity, resulting in stratum corneum barrier damage and increased risk of infection. The study aim was to determine the impact of two diaper and wipe regimens on newborn infant skin pH and residual enzyme activity after stool cleaning. METHODS: Two diaper and wipe regimens were compared in a randomized, single-blinded crossover study. Regimen A paired an emollient-containing diaper with an acidic, pH-buffered wipe. Regimen B was a non-emollient diaper and wipe with limited buffering capacity. A 3-day washout period preceded each 3-day regimen use period. Skin pH at the perianal/buttocks interface (PBI), genital region, and undiapered chest control were measured at baseline and day 3. Skin swabs were collected for residual enzyme activity after a stool cleaning event. RESULTS: Diapered skin pH at the PBI was similar to undiapered skin after 3 days of use for Regimen A, while PBI pH for Regimen B was elevated versus control. PBI pH was lower for Regimen A versus Regimen B. After a stool cleaning, PBI skin pH for Regimen A was lower immediately and had lower residual enzyme activity versus Regimen B (P < .05), and the pH-lowering effect was sustained up to 60 minutes. CONCLUSIONS: These results suggest that the use of an emollient-containing diaper with a pH-buffered wipe creates conditions favorable to optimum diapered skin health.

Impact of sunflower seed oil versus mustard seed oil on skin barrier function in newborns: a community-based, cluster-randomized trial.

BACKGROUND: Natural vegetable oils are widely used for newborn massage in many low resource settings. Animal models indicated that sunflower seed oil (SSO) can accelerate skin barrier recovery following damage, while other oils, including mustard oil (MO), may cause further skin barrier damage. The objective was to compare the effects of two SSO and MO used for routine massage on skin integrity in premature and full-term neonates. METHODS: This community-based cluster randomized controlled trial included 995 neonates assigned to full body massage with sunflower seed oil (SSO, intervention) or mustard seed oil (MO, standard practice) from July 2012-May 2014 in Sarlahi, Nepal. Skin integrity measures were evaluated over 28 days, including skin condition (erythema, rash, dryness), skin surface pH, stratum corneum (SC) cohesion/protein concentration, and transepidermal water loss (TEWL). Overall means and rates of change in these skin measures were compared between oil groups using bivariate random-effects models. RESULTS: 500 and 495 live born neonates received repeated massage with MO and SSO, respectively. Skin pH decreased more quickly for SSO than MO in the first week of life, with a difference in mean daily reductions of 0.02 (95% CI: 0.002-0.040). Erythema, rash and dryness increased (worsened) over days 1-14 then decreased by day 28, with no significant oil group differences. TEWL increased over time, with no significant oil group differences. Gestational age did not modify the effect; the slightly faster decrease in skin pH among SSO infants was similar in magnitude between term and preterm infants. CONCLUSIONS: Oil type may contribute to differences in skin integrity when neonates are massaged regularly. The more rapid acid mantle development observed for SSO may be protective for neonates in lower resource settings. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01177111); registered August 6th, 2010.

Conformational positioning improves sleep in premature infants with feeding difficulties.

OBJECTIVE: To determine whether premature infants' sleep organization, total sleep time, and arousals may be modulated while on a conformational positioner that provides boundaries, customized positioning, and containment compared with standard positioning (standard crib mattress). STUDY DESIGN: A proof of concept trial using a within subject crossover design was conducted among 25 premature infants with feeding difficulties. Infants of 31.5 weeks gestational age served as their own control during overnight polysomnography at postconceptual age 38.4 weeks. Each baby received both interventions (order randomized), 1 for each one-half of the 10.5-hour study. RESULTS: Use of the conformational positioner resulted in higher sleep efficiency of 61% vs 54% for the standard mattress (P < .05). The interventions did not differ for percent active sleep, percent quiet sleep, percent indeterminate sleep, or spontaneous arousals. Sleep efficiency was higher on the conformational positioner than standard positioning for surgical subjects and for subjects with necrotizing enterocolitis or gastroschisis (n = 10). The surgical subjects (n = 9) had lower sleep efficiency, lower percentage of active sleep, and more spontaneous arousals compared with the nonsurgical group. CONCLUSIONS: The use of the conformational positioner improved sleep efficiency vs the standard mattress in premature infants with feeding difficulties. Infants requiring surgery or with gastrointestinal diagnoses may be more susceptible to environmental stress.

Behavioral observation differentiates the effects of an intervention to promote sleep in premature infants: a pilot study.

PURPOSE: Sleep and ongoing cycling of sleep states are required for neurosensory processing, learning, and brain plasticity. Many aspects of neonatal intensive care environments such as handling for routine and invasive procedures, bright lighting, and noise can create stress, disrupt behavior, and interfere with sleep in prematurely born infants. The study empirically investigated whether a 30-minute observation of infant sleep states and behavior could differentiate an intervention to promote sleep in premature infants with feeding difficulties relative to conventional care (standard positioning, standard crib mattress [SP]). We included an intervention to determine the ability of the method to discriminate treatments and generate a benchmark for future improvements. The intervention, a conformational positioner (CP), is contoured around the infant to provide customized containment and boundaries. To more fully verify the 30-minute observational sleep results, standard polysomnography was conducted simultaneously and sleep outcomes for the 2 modalities were compared. SUBJECTS: In a randomized crossover clinical trial, 25 infants, 31.5 ± 0.6 weeks' gestational age and 38.4 ± 0.6 weeks at the study, with gastrointestinal conditions or general feeding difficulties used each intervention during an overnight neonatal intensive care unit sleep study. METHODS: Infant sleep states and behaviors were observed during two 30-minute periods--that is, on the positioner and mattress--using the naturalistic observation of newborn behavior. Two certified developmental care nurses assessed sleep state, self-regulatory, and stress behaviors during 2-minute intervals and summed over 30 minutes. Sleep characteristics from standard polysomnography were measured at the time of behavior observations. RESULTS: Infants on CP spent significantly less time in alert, active awake, or crying states by observation compared with SP. Surgical subjects spent more time awake, active awake, or crying and displayed a higher number of behavior state changes than the nonsurgical infants. The percentage of time in observed deep sleep and quiet sleep was correlated with both percentage sleep efficiency (r = 0.78) and fewer state shifts per hour (r = -0.65) from electroencephalogram (EEG). Sleep efficiency by EEG was greater on CP versus SP. CONCLUSIONS: The CP enabled sleep compared with the standard mattress (SP) over 30-minute observation periods. Sleep status from behavioral observation was verified by standard EEG-based sleep techniques. Behavioral observation of sleep states may be a useful strategy for measuring the effectiveness of strategies to facilitate sleep in premature infants. Surgical subjects may benefit from additional interventions to promote sleep.

Assessment of diaper dermatitis using a novel electronic health record-embedded scale.

OBJECTIVE: Quantify the evolution and severity of neonatal skin injury, specifically diaper skin compromise, by embedding a validated skin integrity evaluation into the electronic health record (EHR). METHODS: Retrospective longitudinal cohort analysis of 747 patients stratified by gestation: 22-27, 28-31, 32-24, and 35-37 weeks, from birth to discharge. Primary outcomes were time to first perineal erythema, duration as percent days with erythema, and severity as maximum score. Data were analyzed using generalized linear models and multiple linear regression methods. RESULTS: Seventy percent had erythema and, of these, 34% had at least one high score with bleeding. Days with erythema ranged from 34-44% (p < 0.05). Days to first erythema were inversely correlated with gestational age. Risks for severe injury included short time to first erythema, 5 or more stools/day, infection, and Caucasian race/ethnicity. CONCLUSIONS: The EHR-based scale can be readily implemented to mitigate diaper skin compromise in premature infants.

Impact of topical applications of sunflower seed oil on neonatal mortality and morbidity in southern Nepal: a community-based, cluster-randomised trial.

INTRODUCTION: Hospital-based studies have demonstrated topical applications of sunflower seed oil (SSO) to skin of preterm infants can reduce nosocomial infections and improve survival. In South Asia, replacing traditional mustard with SSO might have similar benefits. METHODS: 340 communities in Sarlahi, Nepal were randomised to use mustard oil (MO) or SSO for community practice of daily newborn massage. Women were provided oil in late pregnancy and the first month post partum, and visited daily through the first week of life to encourage massage practice. A separate data collection team visited on days 1, 3, 7, 10, 14, 21 and 28 to record vital status and assess serious bacterial infection. RESULTS: Between November 2010 and January 2017, we enrolled 39 479 pregnancies. 32 114 live births were analysed. Neonatal mortality rates (NMRs) were 31.8/1000 (520 deaths, 16 327 births) and 30.5/1000 (478 deaths, 15 676 births) in control and intervention, respectively (relative risk (RR)=0.95, 95% CI: 0.84, 1.08). Among preterm births, NMR was 90.4/1000 (229 deaths, 2533 births) and 79.2/1000 (188 deaths, 2373 births) in control and intervention, respectively (RR=0.88; 95% CI: 0.74, 1.05). Among preterm births <34 weeks, the RR was 0.83 (95% CI: 0.67, 1.02). No statistically significant differences were observed in incidence of serious bacterial infection. CONCLUSIONS: We did not find any neonatal mortality or morbidity benefit of using SSO instead of MO as emollient therapy in the early neonatal period. Further studies examining whether very preterm babies may benefit are warranted. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT01177111).

Skin Care for the Extremely Low-Birthweight Infant.

Extremely low-birthweight (ELBW) infants are at increased risk for infection because the innate immune function of their skin is underdeveloped as they lack a competent epidermal barrier. Thus, neonatal clinicians need to pay careful attention to skin care practices, particularly for periviable infants. In this review, we describe the challenges of skin care in ELBW infants and summarize strategies to prevent skin injury, minimize damage when it occurs, and enhance cutaneous innate immunity.

Multimodal quantitative analysis of early pulsed-dye laser treatment of scars at a pediatric burn hospital.

BACKGROUND: The pulsed-dye laser (PDL) is a potential adjunctive therapy for treatment of hyperemic and hypertrophic scars. OBJECTIVE: To compare the effects of early PDL treatment plus compression therapy (CT) with those of CT alone in patients undergoing burn scar reconstruction with split-thickness grafts on an extremity. METHODS: Laser treatments were applied to one half of the graft seam. Standard CT was applied to both halves. Laser treatment was repeated at 6-week intervals until one half reached sufficient clinical improvements. Each half was evaluated just before treatments using quantitative measures of color, scar height, biomechanical properties and clinical features using the Vancouver Scar Scale (VSS). RESULTS: Less quantitative scar erythema and height and greater tissue elasticity were observed after two or three treatments for PDL plus compression than with compression alone. VSS scores showed greater improvement for vascularity, pliability, pigmentation, and height for PDL plus compression than for compression alone. CONCLUSION: PDL treatment in combination with CT appears to reduce scar hyperemia and height and normalize the biomechanical properties of burn-related scars.

Epidermal Immunity and Function: Origin in Neonatal Skin.

The fascinating story of epidermal immunity begins in utero where the epidermal barrier derives from the ectoderm and evolves through carefully orchestrated biological processes, including periderm formation, keratinocyte differentiation, proliferation, cornification, and maturation, to generate a functional epidermis. Vernix caseosa derives from epidermal cells that mix with sebaceous lipids and coat the fetus during late gestation, likely to provide conditions for cornification. At birth, infants dramatically transition from aqueous conditions to a dry gaseous environment. The epidermal barrier begins to change within hours, exhibiting decreased hydration and low stratum corneum (SC) cohesion. The SC varied by gestational age (GA), transformed over the next 2-3 months, and differed considerably versus stable adult skin, as indicated by analysis of specific protein biomarkers. Regardless of gestational age, the increased infant SC proteins at 2-3 months after birth were involved in late differentiation, cornification, and filaggrin processing compared to adult skin. Additionally, the natural moisturizing factor (NMF), the product of filaggrin processing, was higher for infants than adults. This suggests that neonatal skin provides innate immunity and protection from environmental effects and promotes rapid, continued barrier development after birth. Functional genomic analysis showed abundant differences across biological processes for infant skin compared to adult skin. Gene expression for extracellular matrix, development, and fatty acid metabolism was higher for infant skin, while adult skin had increased expression of genes for the maintenance of epidermal homeostasis, antigen processing/presentation of immune function, and others. These findings provide descriptive information about infant epidermal immunity and its ability to support the newborn's survival and growth, despite an environment laden with microbes, high oxygen tension, and irritants.

Neonatal skin maturation--vernix caseosa and free amino acids.

Neonatal skin hydration decreases rapidly postnatally and then increases, indicating adaptive changes in stratum corneum water handling properties. Transition from high to low humidity at birth may initiate filaggrin proteolysis to free amino acids. Neonatal skin with vernix caseosa retained is more hydrated than skin with vernix removed. This study examines the potential roles of free amino acids and vernix in postnatal adaptation of infant stratum corneum in vivo. Specifically, the ontogeny of free amino acid generation in neonatal stratum corneum and the role of vernix caseosa in postnatal adaptation were examined using high performance liquid chromatography. Free amino acids were quantified for infant skin samples collected at (i) birth and 1 month and (ii) birth and 24 hours after vernix caseosa retention or removal and compared to neonatal foreskin, vernix caseosa, and adult stratum corneum using t-tests, analysis of variance, or univariate procedures. Free amino acids were extremely low at birth, significantly higher 1 month later but lower than in adults. Vernix caseosa retention led to significantly higher free amino acids 24 hours after birth compared to infants with vernix caseosa removed, and it paralleled the higher stratum corneum hydration of vernix caseosa-retained skin. Vernix caseosa contained free amino acids, with glutamic acid and histidine levels higher than in infants. Free amino acids in vernix caseosa-retained skin appear to originate from vernix caseosa. Free amino acids were lower in neonatal foreskin than adult forearm stratum corneum. Arginine was higher than citrulline at birth, but levels were comparable in older infants. The free amino acid increase at 1 month may be initiated by the humidity transition at birth and supports results in animals. The findings have implications for infant skin care practices.

Epidermal barrier treatments based on vernix caseosa.

BACKGROUND/AIMS: Premature infants lack the vernix caseosa, have an incompetent stratum corneum (SC) barrier and are predisposed to infection. Use of topical agents to improve barrier function has had mixed outcomes. The aim was to determine the effect of vernix versus common barrier creams on the rate and quality of the epidermal barrier repair following controlled wounding. METHODS: Minor wounds were created with (1) laser ablation in the minipig and (2) tape stripping of mother's volar skin as a model for premature skin. Native vernix was applied to the mother's tape-stripped skin. Treatments were no occlusion (NO), vernix and a petrolatum-based cream (PBC) in the pig, and NO, vernix, PBC, an oil-in-water cream (OWC), a semipermeable film (SP) and full occlusion (FO) in adults. RESULTS: Outcomes for both trials were barrier recovery and skin hydration (moisture accumulation rate, MAT), initial hydration, erythema and dryness in adults. Vernix and PBC produced greater barrier repair than NO in the pig. SP produced greater recovery than NO and FO in adults. Vernix yielded greater recovery than FO and was similar to PBC, OWC and NO. Vernix had a directionally higher MAT than OWC and directionally higher initial hydration than NO. CONCLUSIONS: The findings suggest that vernix-based topical creams would be effective for the treatment of epidermal wounds and show promise to augment SC repair and maturation in infants.

Premature infant skin barrier maturation: status at full-term corrected age.

OBJECTIVE: To evaluate the effects of gestational age (GA) and postnatal age on skin barrier integrity by comparing premature infants at full-term corrected age with infants born at term. STUDY DESIGN: Parallel comparison of chest skin in 36 premature infants with 39 full-term infants using daily measures of transepidermal water loss (TEWL), skin pH, erythema and rash, over 2 weeks. RESULT: Chest skin pH was significantly lower for premature infants, indicating that acid mantle formation had occurred in the premature versus full-term infants. Chest TEWL was significantly higher for premature versus full-term infants over 2 weeks, suggesting that even 7-8 weeks after birth, skin integrity is poorer in premature infants. CONCLUSION: Skin barrier properties of premature infants at adjusted full-term age differ from full-term infants, suggesting that epidermal barrier development depends on GA and time from birth. These maturational differences may influence premature infant response to topical agents.

Birthweight and Environmental Conditions Impact Skin Barrier Adaptation in Neonates Receiving Natural Oil Massage.

INTRODUCTION: Skin interventions have been implemented to reduce neonatal mortality, demonstrating the skin's role in neonatal innate immunity. We examined the impact of birthweight and environmental conditions on skin integrity in infants receiving oil massage in rural Nepal. METHODS: In a community-based cluster randomized controlled trial, 991 premature and full-term infants were grouped by birthweight as: (1) 920-1,560 g, (2) 1,570-2,450 g, (3) 2,460-2,990 g, and (4) 3,000-4,050 g and by high or low heat index (HI). Skin integrity was measured as erythema, rash, dryness, pH, protein concentration, and transepidermal water loss (TEWL). RESULTS: Skin pH was higher for the smallest (group 1) than the largest infants (group 4) and higher for group 2 than 3 and 4. Arm and leg rash differed for all 4 groups, with the least amount of rash for the smallest babies. Erythema was lower for group 1 than all others. The lower day 1 values for pH, TEWL and protein at high versus low HI remained lower over 28 days. The pH reduction was faster at high HI. Erythema (arm, leg) was more severe at high HI. Rash severity was greater at high HI for arms and legs every day. CONCLUSIONS: Birthweight influenced the skin response to oil massage. The smallest infants had the lowermost skin irritation, suggesting diminished ability to mount an inflammatory response. High HI may be protective for premature infants in low resource settings.

Newborn infant skin gene expression: Remarkable differences versus adults.

At birth, human infants are poised to survive in harsh, hostile conditions. An understanding of the state of newborn skin development and maturation is key to the maintenance of health, optimum response to injury, healing and disease. The observational study collected full-thickness newborn skin samples from 27 infants at surgery and compared them to skin samples from 43 adult sites protected from ultraviolet radiation exposure, as the standard for stable, mature skin. Transcriptomics profiling and gene set enrichment analysis were performed. Statistical analysis established over 25,000 differentially regulated probe sets, representing 10,647 distinct genes, in infant skin compared to adult skin. Gene set enrichment analysis showed a significant increase in 143 biological processes (adjusted p < 0.01) in infant skin, versus adult skin samples, including extracellular matrix (ECM) organization, cell adhesion, collagen fibril organization and fatty acid metabolic process. ECM organization and ECM structure organization were the biological processes in infant skin with the lowest adjusted P-value. Genes involving epidermal development, immune function, cell differentiation, and hair cycle were overexpressed in adults, representing 101 significantly enriched biological processes (adjusted p < 0.01). The processes with the highest significant difference were skin and epidermal development, e.g., keratinocyte differentiation, keratinization and cornification intermediate filament cytoskeleton organization and hair cycle. Enriched Gene Ontology (GO) biological processes also involved immune function, including antigen processing and presentation. When compared to ultraviolet radiation-protected adult skin, our results provide essential insight into infant skin and its ability to support the newborn's preparedness to survive and flourish, despite the infant's new environment laden with microbes, high oxygen tension and potential irritants. This fundamental knowledge is expected to guide strategies to protect and preserve the features of unperturbed, young skin.

Mechanistic effects of long-term ultraviolet B irradiation induce epidermal and dermal changes in human skin xenografts.

UVB irradiation has been reported to induce photoaging and suppress systemic immune function that could lead to photocarcinogenesis. However, because of the paucity of an UVB-induced photodamaged skin model, precise and temporal mechanism(s) underlying the deleterious effects of long-term UVB exposure on human skin have yet to be delineated. In this study, we established a model using human skin xenografted onto severe combined immunodeficient mice, which were subsequently challenged by repeated UVB irradiation for 6 weeks. Three-dimensional optical image analysis of skin replicas and noninvasive biophysical measurements illustrated a significant increase in skin surface roughness, similar to premature photoaging, and a significant loss of skin elasticity after long-term UVB exposure. Resembling authentically aged skin, UVB-exposed samples exhibited significant increases in epithelial keratins (K6, K16, K17), elastins, and matrix metalloproteinases (MMP-1, MMP-9, MMP-12) as well as degradation of collagens (I, IV, VII). The UVB-induced deterioration of fibrous keratin intermediate filaments was also observed in the stratum corneum. Additionally, similarities in gene expression patterns between our model and chronologically aged skin substantiated the plausible relationship between photodamage and chronological age. Furthermore, severe skin photodamage was observed when neutralizing antibodies against TIMP-1, an endogenous inhibitor of MMPs, were administered during the UVB exposure regimen. Taken together, these findings suggest that our skin xenograft model recapitulates premature photoaged skin and provides a comprehensive tool with which to assess the deleterious effects of UVB irradiation.

Biomarkers of epidermal innate immunity in premature and full-term infants.

Epidermal innate immunity is a complex process involving a balance of pro- and anti-inflammatory cytokines, structural proteins, and specific antigen presenting cells occurring against a background of neuroendocrine modulators such as cortisol. In this study, a multiplex array system was used to simultaneously determine multiple molecular factors critical for development of epidermal innate immune function from the skin surface of premature and term infants, healthy adults, and vernix caseosa. Samples were analyzed for Keratin 1,10,11, Keratin 6, involucrin, albumin, fibronectin and cortisol, and cytokines IL-1, TNFalpha, IL-6, IL-8, MCP1, IP10, IFNgamma, and IL-1 receptor antagonist. Keratin 1,10,11 was decreased and involucrin was increased in infants versus adults. All infants had elevated IL1alpha and reduced TNFalpha versus adults. IL-6, IL-8, and MCP1 were significantly increased in premature versus term infants and adults. Skin surface cortisol and albumin were significantly elevated in premature infants. The biomarker profile in premature infants was unique with differences in structural proteins, albumin, and cytokines IL-6, IL-1beta, IL-8, and MCP1. The higher infant IL1alpha may be associated with skin barrier maturation. The significant elevations in skin surface cortisol for preterm infants may reflect a neuroendocrine response to the stress of premature birth.

Stem cell factor-KIT signalling plays a pivotal role in regulating pigmentation in mammalian hair.

Hair greying is one of the most distinct but least comprehended features of senescence. The signalling of stem cell factor (SCF) and its receptor KIT has been documented to regulate essential roles in the maintenance of embryonic melanocyte lineages and postnatal cutaneous melanogenesis, although little is known about its detailed mechanisms in postnatal hair pigmentation. To address this, anagen human hair follicles and C57BL/6 murine pelage were analysed in this study. Molecular biological analyses of murine follicular skin indicated a significant increase of membrane-bound SCF expression, reaching its peak 8-16 days after anagen induction in concert with the escalation of cutaneous tyrosinase activity and corresponding pigmentation. Administration of KIT-neutralizing antibody abolished MITF and tyrosinase expressions, resulting in a reversible hair depigmentation in murine regenerated hair and human hair organ culture. Quantitative RT-PCR of human hair follicles indicated that KIT expression as well as the expression of several melanogenic factors, including MITF, was significantly lower in unpigmented than in pigmented follicles. Taken together, these data revealed a pivotal role of SCF-KIT signalling in the maintenance of human hair follicle melanogenesis during the anagen cycle and its involvement in physiological ageing of the hair follicle pigmentary unit.