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.

Umbilical Cord Milking Versus Delayed Cord Clamping in Infants 28 to 32 Weeks: A Randomized Trial.

OBJECTIVES: To determine whether rate of severe intraventricular hemorrhage (IVH) or death among preterm infants receiving placental transfusion with UCM is noninferior to delayed cord clamping (DCC). METHODS: Noninferiority randomized controlled trial comparing UCM versus DCC in preterm infants born 28 to 32 weeks recruited between June 2017 through September 2022 from 19 university and private medical centers in 4 countries. The primary outcome was Grade III/IV IVH or death evaluated at a 1% noninferiority margin. RESULTS: Among 1019 infants (UCM n = 511 and DCC n = 508), all completed the trial from birth through initial hospitalization (mean gestational age 31 weeks, 44% female). For the primary outcome, 7 of 511 (1.4%) infants randomized to UCM developed severe IVH or died compared to 7 of 508 (1.4%) infants randomized to DCC (rate difference 0.01%, 95% confidence interval: (-1.4% to 1.4%), P = .99). CONCLUSIONS: In this randomized controlled trial of UCM versus DCC among preterm infants born between 28 and 32 weeks' gestation, there was no difference in the rates of severe IVH or death. UCM may be a safe alternative to DCC in premature infants born at 28 to 32 weeks who require resuscitation.

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.

Timing of Antenatal Steroid Administration and Effects on the Newborn Infant: A Retrospective Study.

OBJECTIVE: The timing of antenatal steroids (ANS) on short- and long-term effects on newborn infants was evaluated. STUDY DESIGN: This study was conducted at the University of Cincinnati Medical Center Level-III Neonatal Intensive Care Unit by reviewing the medical records of all women with history of ANS exposure from January 2015 to December 2018. We compared outcomes of newborns delivered within the ideal therapeutic window of 24 hours to 7 days (within window [WW]) after administration to those exposed and delivered outside the therapeutic window (outside window primary group [OWP]). Outcomes included anthropometrics, blood sugars, thyroid hormone profile, and neonatal morbidities. RESULTS: A total of 669 patients were identified as having received at least two doses of ANS. Two-thirds of them delivered within the ideal therapeutic window. Significant differences were found in anthroprometrics including lower birth weight, shorter length, and smaller head circumferences in those born within the window compared with those outside the window. Derangements in glucose homeostasis requiring treatment and elevations of thyroid stimulating hormone (TSH) were seen in infants born outside the ideal therapeutic window compared with those born within the therapeutic window. No differences were found in neonatal morbidities including severe intraventricular hemorrhage (sIVH), necrotizing enterocolitis (NEC), need for resuscitation, exogenous surfactant administration, continuous positive airway pressure (CPAP), mechanical ventilation, bronchopulmonary dysplasia (BPD), or periventricular leukomalacia (PVL). After controlling for selected covariates, only birth length was different between the groups. CONCLUSION: Effects on anthropometrics, glucose homeostasis, and thyroid function support the need to develop new or refine existing risk stratification systems to time the administration of antenatal steroids. Better targeting of women and fetuses may confer the benefits of systemic corticosteroids while mitigating the risks of adverse effects. KEY POINTS: · The timing of antenatal steroids on short and long-term effects on newborn infants was evaluated.. · Differences were found in anthroprometrics, glucoses, and thyroid function.. · No differences were found in neonatal morbidities..

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.

Predictors of the Provision of Mother's Milk Feedings in Newborns Admitted to the Neonatal Intensive Care Unit.

Background: Breast milk reduces morbidity and mortality in infants admitted to neonatal intensive care unit (NICU). Objectives: We determined predictors of procuring mother's own milk (MOM) among NICU-admitted newborn-mother dyads: (1) initiation of any milk expression; (2) initiation of milk expression within 6 hours of birth; (3) MOM as the first enteral feeding; (4) colostrum for oral care within 36 hours of birth if not yet orally fed; and (5) provision of MOM at 21 days of life or discharge, whichever occurred first. Methods: We performed a retrospective chart review of NICU-admitted newborn-mother dyads at an urban medical center from June 1, 2018-May 31, 2019. We excluded infants not directly admitted to the NICU, those never enterally fed, multiple gestations if not the first to be discharged, and infants discharged to a nonbiological caregiver. We used chi-square analysis to examine unadjusted associations between independent variables and MOM outcomes and then used logistic regression to determine the adjusted odds ratio and 95% confidence interval (AOR [95% CI]) for predictors of MOM outcomes. Results: There were 341 mother-infant dyads who met inclusion criteria and 71% of these mothers initiated milk expression. Smoking, multiparity, gestational diabetes, and Hepatitis C lowered the odds for at least one MOM outcome; whereas mothers who delivered at 28-32 weeks versus ≥33 weeks, and infants with birthweight <1,500 g versus 1,500-2,500 g had higher odds for at least one MOM outcome. Conclusion: Maternal/infant dyad characteristics may predict some, but not all NICU breastfeeding outcomes. This suggests that hospital practices may influence these outcomes and can inform future interventions.

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.

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.

Imaging reveals distinct textures at three infant skin sites and reflects skin barrier status.

BACKGROUND: Infant diaper dermatitis (DD) is a prevalent condition due to multiple, interactive factors including increased skin hydration, irritant exposure, and increased skin pH. We examined diaper dermatitis vs within diaper and non-diaper controls over time and characterized the association of skin color and texture relative to skin barrier integrity, hydration, and pH. MATERIALS AND METHODS: The prospective study included 46 infants with DD at well-child visits. Skin integrity was evaluated over 15 days, including visual skin condition, rate of stratum corneum transepidermal water accumulation, hydration, pH, and skin color and texture from high-resolution digital skin surface images. Effects by site and time were evaluated with general linear models. RESULTS: Six distinct texture patterns were observed. All three sites differed significantly for texture class frequency. Normal dermatoglyphics were more frequent for non-diaper vs both within diaper and rash sites. Dermatoglyphics with marked furrows or lines (class 3) were common within diaper vs rash but not for non-diaper vs within diaper. Streaks were highest for DD and lowest for non-diaper. Flat regions were more frequent DD. Barrier integrity, that is, moisture accumulation rate, was lower for normal dermatoglyphics than streaks or flat texture. DD severity decreased over 15 days. Barrier properties of within diaper and non-diaper areas were not well-differentiated. CONCLUSION: The incidence of streak texture in the within diaper high magnification images was high despite being visually normal. This finding suggests that it is an "early indicator" of skin damage and may be clinically useful for early detection and treatment.

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.

Provider Perceptions of Bubble Continuous Positive Airway Pressure and Barriers to Implementation in a Level III Neonatal Unit in South India.

BACKGROUND: Bubble continuous positive airway pressure (bCPAP) is a simple, safe, and cost-effective strategy to provide respiratory support to newborns with respiratory distress syndrome in resource-limited settings. PURPOSE: To understand whether implementation of bCPAP, relative to other modes of respiratory support in the care of newborns with respiratory distress syndrome, increases positive attitudes about its potential for consistent and widespread use among providers in neonatal intensive care units (NICUs) of lower middle-income countries. METHODS: Semistructured qualitative interviews with 14 healthcare providers, including 5 neonatal nurses, 2 respiratory therapists, 5 postgraduate trainees in pediatrics, and 2 attending physicians, were conducted at a level III NICU in south India where bCPAP had been in consistent use for 6 years. Interviews were transcribed and then coded and categorized using NVivo 10 Software (QSR International, Victoria, Australia). FINDINGS: Categories that emerged from our data include (1) perceived indications, (2) learning curve, (3) perceived costs, (4) perceived shortages, and (5) barriers to use. Providers believed that bCPAP was easy to learn and that it helped empower neonatal nurses in decision-making process. Participants provided a nuanced perspective of cost-benefit associated with bCPAP and that it helped make optimal use of limited resources. Participants identified several barriers to the implementation of bCPAP. IMPLICATIONS FOR PRACTICE: Providers of a level III NICU in a lower- to middle-income country viewed the use of bCPAP favorably. Addressing context-specific barriers will be important for the successful widespread implementation of bCPAP. IMPLICATIONS FOR RESEARCH: Further research will need to focus on whether bCPAP can be safely implemented at level II NICUs.Video Abstract Available at https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx.

Impact of Early Sodium Supplementation on Hyponatremia and Growth in Premature Infants: A Randomized Controlled Trial.

BACKGROUND: We tested the hypothesis that sodium supplementation in early preterm infants prevents late-onset hyponatremia and improves growth without increasing common morbidities during birth hospitalization. MATERIALS AND METHODS: This was a randomized, masked controlled trial of 4 mEq/kg/d of sodium (intervention) versus sterile water (placebo) from days-of-life 7 to 35 in infants born at <32 weeks corrected gestational age. The primary outcome was weight gain in the first 6 weeks of life. Secondary outcomes included weekly serum sodium concentrations, growth in body length and head circumference, and complications of prematurity during birth hospitalization. RESULTS: Fifty-three infants with an average corrected gestational age of 28.5 ± 2.4 weeks were randomized. Infants receiving the intervention had fewer (P = .012) reports of serum sodium concentrations <135 mmol/L and greater velocity of weight gain during the study period, mean (SD) 26.9 (3.1) vs 22.9 (4.7) g/kg/day, P = .012. At 6 weeks of age, infants <28 weeks' gestation who received sodium supplementation had greater percentage weight change from birth, mean (SD) 193% (22%) vs 173% (10%), P = .041, and maintained fetal reference birth percentile for body weight more often (P = .002) compared with infants receiving placebo. Growth in length and head circumference was not significantly different between study arms. No increase in common prematurity-related morbidities was detected in infants who received supplemental sodium chloride. CONCLUSION: Sodium supplementation of enteral feedings in very premature infants averts hyponatremia and enhances weight gain.

Variation in Neonatal Inpatient Charges at the State and Local Level.

In an analysis of all Ohio newborn infants discharged home alive between 2007 and 2012, the authors identified that significant variation in hospital charges (among Medicare Severity Diagnostic Related Group categorizations), previously identified nationally, persists at the state and local levels among term and preterm infants (p <.0001). Additionally, the authors identified variation in length of stay among infants with extreme immaturity or respiratory distress syndrome (p <.0001). Charge data remain the best available proxy for closely guarded hospital cost figures; increased pricing transparency would further support comparison of hospital newborn care costs.

The Ontogeny of Skin.

Significance: During gestation, fetal skin progresses from a single layer derived from ectoderm to a complex, multi-layer tissue with the stratum corneum (SC) as the outermost layer. Innate immunity is a conferred complex process involving a balance of pro- and anti-inflammatory cytokines, structural proteins, and specific antigen-presenting cells. The SC is a part of the innate immune system as an impermeable physical barrier containing anti-microbial lipids and host defense proteins. Postnatally, the epidermis continually replenishes itself, provides a protective barrier, and repairs injuries. Recent Advances: Vernix caseosa protects the fetus during gestation and facilitates development of the SC in the aqueous uterine environment. The anti-infective, hydrating, acidification, and wound-healing properties post birth provide insights for the development of strategies that facilitate SC maturation and repair in the premature infant. Critical Issues: Reduction of infant mortality is a global health priority. Premature infants have an incompetent skin barrier putting them at risk for irritant exposure, skin compromise and life-threatening infections. Effective interventions to accelerate skin barrier maturation are compelling. Future Directions: Investigations to determine the ontogeny of barrier maturation, that is, SC structure, composition, cohesiveness, permeability, susceptibility to injury, and microflora, as a function of gestational age are essential. Clinicians need to know when the premature skin barrier becomes fully competent and comparable to healthy newborn skin. This will guide the development of innovative strategies for optimizing skin barrier development.