An interventional study of Retention of Vernix Caseosa After Birth and Removal of Vernix Caseosa After Birth in Atopic Dermatitis, sponsored by Pontificia Universidad Catolica de Chile. Not yet recruiting at 2 sites in Chile. Open to participants aged 0 Days and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-27.
Sponsored by Pontificia Universidad Catolica de Chile · Not applicable, Interventional, and Prevention
Atopic dermatitis (AD), also known as eczema, is a common chronic inflammatory skin disease that usually begins in infancy and causes significant itching, discomfort, and sleep disturbance. It affects up to one in five children worldwide and represents a growing public-health problem. Research has shown that genetic and environmental factors contribute to its development, especially those related to skin-barrier integrity and the skin microbiome during early life. Preventing AD before it starts-known as primary prevention-has become an important goal.
Vernix caseosa is a naturally occurring, white, creamy substance that covers the skin of newborns at birth. It forms during the last trimester of pregnancy and plays a key role in protecting and hydrating the baby's skin before and after birth. Vernix contains water, lipids, and proteins with antimicrobial and anti-inflammatory properties. Despite these potential benefits, in many hospitals vernix is routinely removed soon after delivery as part of standard newborn cleaning or bathing practices. However, there is little scientific evidence to support early removal, and some studies suggest that keeping vernix on the skin for longer may help the newborn's skin barrier function and reduce colonization by harmful bacteria.
The PROTEGO Study (Post-Partum Retention of Vernix Caseosa for Primary Prevention of Atopic Dermatitis, Guarding Skin Integrity and Fostering a Healthy Microbiome) is a randomized controlled clinical trial designed to test whether delaying the removal of vernix caseosa after birth can help prevent atopic dermatitis and improve skin health during the first year of life.
A total of 1,383 mother-infant pairs will be enrolled from three maternity hospitals in Santiago, Chile. Participants will be randomly assigned to one of two groups:
All infants will be followed for 12 months with regular clinical assessments, standardized skin evaluations, and collection of biological samples. The main outcome will be the cumulative incidence of atopic dermatitis, diagnosed using modified UK Working Party criteria and/or Hanifin \& Rajka criteria at 12 months of age. Secondary outcomes include skin-barrier measurements (transepidermal water loss, skin pH, and natural moisturizing factor), the composition of the skin microbiome, and early signs of allergic or infectious diseases.
This study will provide high-quality evidence on whether preserving vernix caseosa after birth is a simple, safe, cost-effective and natural strategy to strengthen the newborn's skin barrier and reduce the risk of eczema and related conditions. The results could help improve newborn-care practices and promote skin health in early life worldwide.
Scientific Rationale:
Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disorder that typically begins in early childhood and is characterized by pruritic eczematous lesions, epidermal barrier dysfunction, and immune dysregulation. Its prevalence is rising globally, affecting 10-35 % of children in industrialized countries. In Chile, epidemiological studies show that 18-22 % of school-aged children and up to one third of toddlers have physician-diagnosed AD, indicating a substantial and increasing disease burden. AD is often the first manifestation of the "atopic march," leading to food allergy, asthma, and allergic rhinitis.
Although several biologic and small-molecule therapies have recently transformed the management of moderate-to-severe AD, these treatments remain costly, inaccessible for most patients, and do not prevent disease onset. Therefore, identifying effective and feasible primary prevention strategies is a major unmet need.
Current understanding of AD pathogenesis highlights three interacting domains: (1) structural and biochemical defects of the epidermal barrier; (2) skewed type-2 immune responses; and (3) altered skin microbiota with increased colonization by Staphylococcus aureus. Defects in epidermal proteins such as filaggrin (FLG) increase transepidermal water loss (TEWL) and permeability to allergens and microbes, while immune activation and microbial imbalance perpetuate inflammation. Because these abnormalities emerge early in life-often before clinical symptoms-interventions targeting skin-barrier maturation and microbial balance during the neonatal period may reduce AD incidence.
Vernix Caseosa as a Natural Barrier Protector:
Vernix caseosa (VC) is a unique biofilm-like substance produced in utero by fetal sebaceous glands and composed of water (≈ 80 %), lipids (≈ 10 %), and proteins (≈ 10 %) intermingled with corneocytes. It covers the fetus during the third trimester, protecting the skin from maceration in the amniotic environment and promoting terminal differentiation of the stratum corneum. VC exhibits semipermeable and antimicrobial properties, functioning as a physiological barrier and innate immune interface. Its lipids include ceramides, cholesterol, and free fatty acids-key constituents of postnatal epidermal barrier repair-while its proteins include antimicrobial peptides such as LL-37, psoriasin, RNase 7, and lysozyme, as well as enzymes involved in lipid metabolism.
Despite these potential benefits, in many institutions worldwide VC is routinely removed within hours after birth as part of standard newborn cleaning procedures. Early removal eliminates a biologically active matrix that may support optimal skin barrier transition from intrauterine to extrauterine life. Small randomized and observational studies suggest that delaying vernix removal increases skin hydration, lowers skin pH, and may reduce bacterial colonization by S. aureus and E. coli, but evidence is limited by short follow-up and small sample sizes and no studies have evaluated its long-term impact on incidence of atopic dermatitis and other conditions.
The PROTEGO trial aims to test whether retaining vernix caseosa after birth, compared with its routine early removal, reduces the risk of developing AD during the first year of life and improves biophysical and microbiological indicators of skin health.
Study Design:
PROTEGO is a multicenter, randomized, controlled, parallel-group clinical trial with assessor blinding. The trial will enroll 1,383 pregnant women and their newborns from three high-volume maternity hospitals in Santiago, Chile. Eligible participants are healthy mothers ≥ 18 years of age with singleton pregnancies and expected delivery of a healthy neonate (≥ 34 weeks, birthweight ≥ 2000 g). After written informed consent, eligible newborns are randomized at the level of the 12-hour nursing shift-episode: newborns born during a given shift receive that shift's assignment (vernix retention or removal, 1:1), determined in advance via a centralized interactive response technology (IRT) system (app.studyrandomizer.com). Randomization is stratified by clinical site and shift type (day/night). Because masking of the delivery team and parents is not feasible, the study will use single-blind assessment, ensuring that investigators evaluating outcomes remain unaware of group assignment. Participants will be followed from birth to 12 months through scheduled visits (at 24-96 h; 7 days; and 1, 3, 6, 9, and 12 months).
Safety and Monitoring:
Retention or removal of VC are standard practices varying between institutions and are considered a minimal-risk intervention. Potential risks include mild skin irritation, transient erythema, or theoretical risk of hypothermia if bathing is delayed excessively. These will be mitigated by standard neonatal thermal-care protocols and skin monitoring. Adverse events (AEs) and serious adverse events (SAEs) will be actively monitored and reported according to institutional and national regulations.
Expected Impact:
If vernix retention proves effective, this trial could introduce a simple, low-cost, and universally applicable strategy for the primary prevention of atopic dermatitis. Because the intervention involves modifying routine newborn care rather than introducing new drugs or devices, it has high translational potential for maternity wards worldwide, especially in low- and middle-income settings.
Beyond its clinical endpoint, PROTEGO will generate valuable mechanistic insights into early-life skin-barrier biology, the neonatal microbiome, and gene-environment interactions (e.g., FLG variants). The integrated biophysical, microbiological, and transcriptomic datasets may illuminate new pathways linking perinatal skin care and immune development. PROTEGO is the first large-scale randomized controlled trial evaluating whether the simple act of preserving vernix caseosa after birth can prevent atopic dermatitis. By combining clinical follow-up with state-of-the-art barrier and microbiome analyses, this study seeks to redefine evidence-based newborn-skin care and contribute to global efforts to reduce the burden of allergic and inflammatory diseases from the very beginning of life.
Exclusion Criteria:
After delivery, visible blood and fluids are gently wiped from the newborn's skin while leaving the vernix caseosa intact. Bathing or cleansing with water or oil is delayed for at least 24 hours (preferably up to 7 days) according to the study protocol. Excess vernix may be lightly spread across the body surface to ensure even coverage. Standard thermal care, skin-to-skin contact, and other routine newborn procedures are maintained. No emollients or cleansers are applied during the retention period.
Other: Retention of Vernix Caseosa After Birth
Within two hours after birth, newborns receive standard hospital cleansing with sterile water and vegetable oil or petroleum jelly to completely remove vernix caseosa, blood, and other residues. The procedure follows routine postnatal care practices at each participating site. After cleaning, usual thermal care, dressing, and parental skin-to-skin contact are continued. No experimental procedures or restrictions are applied beyond standard care.
Other: Removal of Vernix Caseosa After Birth
Retention of vernix caseosa on the newborn's skin after birth by avoiding early cleaning or bathing for ≥24 hours, allowing it to dry and absorb naturally.
Early removal of vernix caseosa from the newborn's skin within the first two hours after birth by washing the child with water and petroleum jelly or vegetable oil, as is standard practice in study hospitals.
Cumulative incidence of atopic dermatitis at 1 year of age
Proportion of infants who meet the diagnostic criteria for atopic dermatitis at 12 months of age, assessed using the modified UK Working Party criteria and/or Hanifin \& Rajka criteria, evaluated by a trained assessor blinded to group allocation.
Time frame: 12 months
Incidence of Atopic Dermatitis (Hanifin & Rajka Criteria Only)
Proportion of infants diagnosed with atopic dermatitis at 12 months using only the Hanifin \& Rajka criteria.
Time frame: 12 months.
Cumulative Incidence of Atopic Dermatitis (Modified UK Working Party Criteria Only)
Proportion of infants diagnosed with atopic dermatitis using only the modified UK Working Party criteria for atopic dermatitis at any study contact until 12 months.
Time frame: 0-12 months
Cumulative Incidence of Infant Eczema
Proportion of infants with any eczema skin lesions (clinician or parent-reported) up to 12 months of age.
Time frame: 0-12 months
Atopic dermatitis diagnosed by trained physician
Diagnosis of atopic dermatitis by a trained physician using standard clinical criteria at 12 months of age
Time frame: 12 months
Parent-reported atopic dermatitis
Parental report of a physician diagnosis of atopic dermatitis collected via standardized questionnaire.
Time frame: 0-12 months
Cumulative incidence of atopic dermatitis by CEQ at 12 months
Cumulative incidence of AD diagnosed using the Children's Eczema Questionnaire (CEQ).
Time frame: 0-12 months
Use of topical anti-inflammatory medications
Any reported use of atopic dermatitis topical medications, such as corticosteroids or calcineurin inhibitors, during the first 12 months of age.
Time frame: 0-12 months
Time to onset of AD based on parent-reported age at first appearance among infants with AD
Time to onset of AD based on parent-reported age at first appearance among infants with AD.
Time frame: From birth to 12 months of age
AD severity measured by the Patient-Oriented Eczema Measure (POEM) among infants with AD
AD severity measured by the Patient-Oriented Eczema Measure (POEM) among infants with AD.
Time frame: From birth to 12 months of age
Severity of Atopic Dermatitis (SCORAD) among infants with AD
Severity of Atopic Dermatitis (SCORAD) among infants with AD at 12 months of age.
Time frame: 12 months of age
Global AD severity based on parental assessment among infants with AD
Global AD severity based on parental assessment among infants with AD.
Time frame: From birth to 12 months of age
Interaction of intervention with visible vernix caseosa (VC) at birth
Evaluate the effects of the amount of visible VC on the incidence of AD in the intervention and control groups.
Time frame: 0-12 months
Interaction of intervention with FLG loss-of-function mutations
Evaluate the effects of FLG loss-of-function mutations on the incidence of AD in the intervention and control groups.
Time frame: 0-12 months
Dynamics of Staphylococcal Colonization
Cumulative incidence of positive Staphylococcus aureus (and other Staphylococcal species) identification on the skin during the first year of life.
Time frame: 0-12 months
Transepidermal water loss (TEWL) at 24-96 hours of age
Measurement of transepidermal water loss (TEWL) at 24-96 hours of age
Time frame: 24-96 hours
Transepidermal water loss (TEWL) at 12 months of age
Measurement of transepidermal water loss (TEWL) at 12 months of age.
Time frame: 12 months of age
Skin pH at 24-96 hours of age
Measurement of skin pH at 24-96 hours of age.
Time frame: 24-96 hours of age
Skin pH at 12 months of age
Measurement of skin pH at 12 months of age.
Time frame: 12 months of age
Epidermal natural moisturizing factor (NMF) concentration at 12 months.
Epidermal natural moisturizing factor (NMF) concentration in tape stripping samples at 12 months of age.
Time frame: 12 months of age
Newborn temperature regulation
Serial measurements of body temperature during the first 24 hours of life.
Time frame: 0-24 hours of life
Serious bacterial infections
Incidence of serious bacterial infections at 28 and 90 days.
Time frame: 28 and 90 days of life
Skin infections during infancy
Cumulative incidence of bacterial skin infections during the first 12 months of life.
Time frame: 0-12 months
Parent-reported food allergy incidence
Cumulative incidence of food allergy based on Parent-reported immediate symptoms of food allergy.
Time frame: 12 months
Physician-diagnosed food allergy incidence
Cumulative incidence of food allergy based on parent-reported physician-diagnosed food allergy confirmed by skin-prick test, specific IgE, or oral food challenge.
Time frame: 12 months
Parental Acceptability of Vernix Retention vs. Removal
Acceptability and satisfaction with assigned intervention assessed via parental questionnaire.
Time frame: 12 months
Type-2 immunity biomarkers in stratum corneum transcriptomics
Comparison of gene-expression markers of type-2 immunity in the stratum corneum at 12 months between VC retention and early removal groups.
Time frame: 12 months of age
Plan to share: Undecided — Individual participant data will be shared upon reasonable request.
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Pontificia Universidad Catolica de Chile