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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

Effects of Autologous Fat and ASCs on Swine Hypertrophic Burn Scars: A Multimodal Quantitative Analysis.

Background: Hypertrophic scar formation is unpredictable and poorly understood, afflicting both the pediatric and adult populations. Treatment methods with conservative and invasive approaches have low rates of compliance and high rates of morbidity. The purpose of this study was to test a reproducible scar model and investigate a new technique of scar modification through the use of adipose- derived progenitor stromal cells (ASCs). Methods: Twenty thermal deep-partial thickness contact burns were created on the dorsum of three 8-week-old domestic swine and allowed to mature for 10 weeks. Scars were then injected with 2 cc saline, expanded autologous ASCs, or 2 cc fresh lipoaspirate and sampled at 2 week intervals up to 10 weeks postinjection. Volumetric analysis with a 3-D scanner, mechanical elasticity testing through negative pressure transduction, and standardized photography evaluation with Image J was performed. RNA sequencing was performed on scar tissue samples, cultured cells, and fresh lipoaspirate to determine relevant gene transcription regulation. Immunohistochemistry was used to verify expression level changes within the scars. Results: Volumetric analysis demonstrates a reduction in average scar thickness at 6 weeks when injected with ASCs (-1.6 cc3) and autologous fat (-1.95 cc3) relative to controls (-0.121 cc3; P < 0.05). A decrease in overall tissue compliance is observed with fat or ASC injection when compared with unburned skin at 8 weeks (35.99/37.94 versus 49.36 mm Hg × mm; P < 0.01). RNA sequencing demonstrates altered regulation of fibroblast gene expression and a decreased inflammatory profile when scars are injected with autologous fat/ASCs over controls. Conclusion: Early results suggest that autologous fat and/or ASCs may improve healing of hypertrophic scarring by altering the cellular and structural components during wound remodeling up to 20 weeks after injury. This may have beneficial applications in early treatment of large or cosmetically sensitive immature burn scars.

Skin Color and Pigmentation in Ethnic Skin.

Skin coloration is highly diverse, partly due to the presence of pigmentation. Color variation is related to the extent of ultraviolet radiation exposure, as well as other factors. Inherent skin coloration arises from differences in basal epidermal melanin amount and type. Skin color is influenced by both the quantity and distribution of melanocytes. The effectiveness of inherent pigmentation for protecting living cells also varies. This article discusses skin color, pigmentation, and ethnicity in relation to clinical practice. Color perception, skin typing/classification, and quantitation of pigmentation are reviewed in relation to ethnicity, environmental stresses/irritants, and potential treatment effects.

Infantile hemangioma status by dynamic infrared thermography: A preliminary study.

BACKGROUND: Infantile hemangiomas (IH) are initially warm due to increased proliferation and perfusion then involute with apoptosis and reduced perfusion. Objective quantitative evaluation of IH treatment response is essential for improving outcomes. We applied a functional imaging method, dynamic infrared (IR) thermography, to investigate IH status versus control skin and over time. MATERIALS AND METHODS: A preliminary prospective observational study was conducted among 25 subjects with superficial or mixed IHs (< 19 months) over 59 clinic visits. Infrared images of IHs and control sites, standardized color images, and three-dimensional images were obtained. Tissue responses following application and removal of a cold stress were recorded with video IR thermography. Outcomes included areas under the curve during cooling (AUCcool ) and rewarming (AUCrw ) and thermal intensity distribution maps. RESULTS: AUCcool and AUCrw were significantly higher and cooling rate slower for IHs versus uninvolved tissue indicating greater heat, presumably due to greater perfusion and metabolism for the IH. IR distribution maps showed specific areas of high and low temperature. Significant changes in IH thermal activity were reflected in the difference (AUCcool - AUCrw ), with 6.2 at 2.2 months increasing to 37.6 at 12.8 months. IH cooling rate increased with age, indicating slower recovery, and interpreted as reduced proliferation and/or involution. CONCLUSIONS: Dynamic IR thermography was a well-tolerated, quantitative functional imaging modality appropriate for the clinic, particularly when structural changes, i.e., height, volume, color, were not readily observed. It may assist in monitoring progress, individualizing treatment, and evaluating therapies. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov (Identifier NCT02061735).

Face Masks for Noninvasive Ventilation: Fit, Excess Skin Hydration, and Pressure Ulcers.

BACKGROUND: Pressure ulcers (stages III and IV) are serious safety events (ie, never events). Healthcare institutions are no longer reimbursed for costs to care for affected patients. Medical devices are the leading cause of pediatric pressure ulcers. Face masks for noninvasive ventilation were associated with a high percentage of pressure ulcers at our institution. METHODS: A prospective cohort study investigated factors contributing to pressure ulcer development in 50 subjects using face masks for noninvasive ventilation. Color imaging, 3-dimensional surface imaging, and skin hydration measurements were used to identify early skin compromise and evaluate 3 interventions to reduce trauma: (1) a silicone foam dressing, (2) a water/polyethylene oxide hydrogel dressing, and (3) a flexible cloth mask. A novel mask fit technique was used to examine the impact of fit on the potential for skin compromise. RESULTS: Fifty subjects age 10.4 ± 9.1 y participated with color images for 22, hydration for 34, and mask fit analysis for 16. Of these, 69% had diagnoses associated with craniofacial anomalies. Stage I pressure ulcers were the most common injury. Skin hydration difference was 317 ± 29 for sites with erythema versus 75 ± 28 for sites without erythema (P < .05) and smallest for the cloth mask (P < .05). Fit distance metrics differed for the nasal, oronasal, and face shield interfaces, with threshold distances being higher for the oronasal mask than the others (P < .05). Areas of high contact were associated with skin erythema and pressure ulcers. CONCLUSIONS: This fit method is currently being utilized to select best-fit masks from available options, to identify the potential areas of increased tissue pressure, and to prevent skin injuries and their complications. Improvement of mask fit is an important priority for improving respiratory outcomes. Strategies to maintain normal skin hydration are important for protecting tissue integrity.

Quantitation of baby wipes lotion transfer to premature and neonatal skin.

Exposure to topically applied substances occurs routinely in premature and hospitalized infant care. Safety determinations are most accurate when exposures are based on appropriately designed studies to capture variations in practice patterns and population heterogeneity. Current safety assessments may not reflect actual practice resulting in overly conservative or understated default assumptions for toxicological determinations. We quantified the amount of baby wipes lotion transferred to premature and term neonatal skin as grams/kg body weight/day. We observed the soil type and number of wipes used for skin cleansing and measured lotion transfer from one wipe applied to freshly clean, dry skin. A Bayesian imputation approach was applied to compute lotion exposure and produce summary statistics. Model covariates were age and weight at evaluation, gender, soil type, soil amount, and number of diaper changes per day. Lotion transfer was measured for 66 premature and 55 term neonates with 449 and 254 evaluations, respectively. The wipes per day was 12.52 overall (all infants and soils), 12.78 for premature and 12.21 for term neonates. Lotion transfer was 0.20 g/kg/day (95th percentile) overall, 0.21 for premature and 0.19 for term neonates. The statistical and experimental methodology represents an effective strategy for determining exposure and assessing risk.

Newborn infant skin: physiology, development, and care.

Infant skin is critical to the newborn child's transition from the womb environment to the journey to self-sufficiency. This review provides an integrative perspective on the skin development in full term and premature infants. There is a particular focus on the role of vernix caseosa and on the implications of skin development for epidermal penetration of exogenous compounds. Healthy full-term newborn skin is well-developed and functional at birth, with a thick epidermis and well-formed stratum corneum (SC) layers. Transepidermal water loss is very low at birth, equal to, or lower than adults, indicating a highly effective skin barrier. Vernix facilitates SC development in full-term infants through a variety of mechanisms including physical protection from amniotic fluid and enzymes, antimicrobial effects, skin surface pH lowering, provision of lipids, and hydration. Premature infants, particularly those of very low birth weight, have a poor skin barrier with few cornified layers and deficient dermal proteins. They are at increased risk for skin damage, increased permeability to exogenous agents and infection. The SC barrier develops rapidly after birth but complete maturation requires weeks to months. The best methods for caring for infant skin, particularly in the diaper region, are described and related to these developmental changes.