Atopic DermatitisPROTEGONCT07333378
Retention of Vernix Caseosa in Newborns for Primary Prevention of Atopic Dermatitis
A study testing Retention of Vernix Caseosa After Birth and Removal of Vernix Caseosa After Birth in people with Atopic Dermatitis, run by Pontificia Universidad Catolica de Chile at 2 sites in Chile.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 0 days and olderHealthy volunteers can take part
- Conditions the study is for
- Atopic Dermatitis
- What is being tested?
- Retention of Vernix Caseosa After Birth and Removal of Vernix Caseosa After Birth
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,383 participants
- Where
- 2 sitesChile
- Study dates
- 29 Sep 2026to 31 Mar 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 days and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- pregnant mother aged 18 and older, who is able to provide informed consent for participation
- delivery of a healthy, singleton newborn (vaginal or cesarean) at one of the study sites.
- parents are able and willing to comply with the study schedule and procedures
Who cannot join
- birthweight <2000 g
- prematurity younger than 34 weeks of gestation
- multiple gestation / multiple births
- maternal HIV-positivity
- clinical and/or laboratory diagnosis of chorioamnionitis.
- need for neonatal hospitalization or presence of an acute illness (e.g., neonatal respiratory distress syndrome) within the first 24 hours of life.
- severe and generalized congenital skin disorder (e.g., congenital ichthyosis).
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Chile2 sites, 2 recruiting
- Not yet recruiting
Clínica San Carlos de Apoquindo
Las Condes, RM
Arturo Borzutzky, M.D., +56223543753, aborzutz@uc.cl
- Recruiting
Hospital Clínico Universidad Católica
Santiago, RM
Arturo Borzutzky, M.D., +56223543753, aborzutz@uc.cl
Carolina Barrientos, R.N., +56944895388, protego@uc.cl
About this study
Official title: Post-partum Retention of Vernix Caseosa for Primary Prevention of Atopic Dermatitis, Guarding Skin Integrity and Fostering a Healthy Microbiome.
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.
Read more
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:
- Retention group: Vernix caseosa will be left on the skin and allowed to dry naturally; the baby's first bath will be delayed according to the study protocol.
- Removal group: Vernix will be removed following current hospital practice using gentle cleaning with water and oil or petroleum jelly shortly after birth.
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.
Read the detailed description
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.
- Conditions
- Atopic Dermatitis
- Being tested
- Retention of Vernix Caseosa After Birth, Removal of Vernix Caseosa After Birth
- Keywords
- vernix caseosa, primary prevention, newborn, eczema, atopic dermatitis, skin infections, Staphylococcus aureus
- Medical subject headings
- Dermatitis, Atopic, Eczema, Cellulitis, Staphylococcal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Retention of Vernix Caseosa After BirthOther
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.
Removal of Vernix Caseosa After BirthOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Retain vernix caseosa | Experimental | 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. Receives: Other: Retention of Vernix Caseosa After Birth |
| Early removal of vernix caseosa | Other | 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. Receives: Other: Removal of Vernix Caseosa After Birth |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (19)
Incidence of Atopic Dermatitis (Hanifin & Rajka Criteria Only)
Proportion of infants diagnosed with atopic dermatitis at 12 months using only the Hanifin \& Rajka criteria.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 12 months
Parent-reported atopic dermatitis
Parental report of a physician diagnosis of atopic dermatitis collected via standardized questionnaire.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 24-96 hours
Transepidermal water loss (TEWL) at 12 months of age
Measurement of transepidermal water loss (TEWL) at 12 months of age.
Measured: 12 months of age
Skin pH at 24-96 hours of age
Measurement of skin pH at 24-96 hours of age.
Measured: 24-96 hours of age
Skin pH at 12 months of age
Measurement of skin pH at 12 months of age.
Measured: 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.
Measured: 12 months of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2026
- Study start29 Sep 2026
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (29)Papers the sponsor has linked to this study.
- Other trials for Atopic DermatitisStudies of the same condition, open and under way.
- More trials run by Pontificia Universidad Catolica de ChileThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicenter, randomized, controlled, parallel-group trial conducted in three maternity hospitals in Santiago, Chile. Mother-infant pairs are assigned 1:1 to either vernix retention (experimental) or vernix removal (control). In the retention arm, vernix caseosa is left on the skin and bathing is delayed ≥24 h; in the control arm, vernix is removed within 2 hours per standard care. Randomization occurs at the level of the 12-hour nursing shift-episode: eligible newborns born during a given shift receive that shift's assignment (vernix retention or removal, 1:1), determined in advance via a centralized IRT system (app.studyrandomizer.com). Randomization is stratified by clinical site and shift type (day/night); mode of delivery and parental atopy history are analyzed as covariates rather than stratification factors.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 1,383 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pontificia Universidad Catolica de Chile
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07333378
- Sponsor's protocol ID
- 230610001
- Other IDs
- 1241933
- Acronym
- PROTEGO
- Status last verified
- Sep 2026
- First submitted
- 5 Dec 2025
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Individual participant data will be shared upon reasonable request.
Publications
Endre KMA, Landro L, LeBlanc M, Gjersvik P, Lodrup Carlsen KC, Haugen G, Hedlin G, Jonassen CM, Nordlund B, Rudi K, Skjerven HO, Staff AC, Soderhall C, Vettukattil R, Rehbinder EM. Diagnosing atopic dermatitis in infancy using established diagnostic criteria: a cohort study. Br J Dermatol. 2022 Jan;186(1):50-58. doi: 10.1111/bjd.19831. Epub 2021 May 6.
PubMed 33511639Tejos-Bravo M, Venegas L, Iturriaga C, Sabatini N, Martin C, Pérez-Mateluna G, Urzúa M, Cabalín C, Dossi MT, Del Barrio P, Majerson D, Silva-Valenzuela S, Vera-Kellet C, Borzutzky A. Alterations in skin physiology are associated with disease severity in Chilean patients with atopic dermatitis. European Academy of Allergy and Immunology Congress 2019. Lisbon, Portugal. June 1-5, 2019.
Ahmed SOM. Vernix Caseosa: Benefits and Clinical Implications in Neonatal Care;A Study Conducted at Almak Nimr University Hospital, Shendi, Sudan. Int J Environ Sci. 2025; 11(469-475).
Blume-Peytavi U, Cork MJ, Faergemann J, Szczapa J, Vanaclocha F, Gelmetti C. Bathing and cleansing in newborns from day 1 to first year of life: recommendations from a European round table meeting. J Eur Acad Dermatol Venereol. 2009 Jul;23(7):751-9. doi: 10.1111/j.1468-3083.2009.03140.x.
PubMed 19646134Wisniewski JA, Phillipi CA, Goyal N, Smith A, Hoyt AEW, King E, West D, Golden WC, Kellams A. Variation in Newborn Skincare Policies Across United States Maternity Hospitals. Hosp Pediatr. 2021 Sep;11(9):1010-1019. doi: 10.1542/hpeds.2021-005948.
PubMed 34462323Henningsson A, Nystrom B, Tunnell R. Bathing or washing babies after birth? Lancet. 1981 Dec 19-26;2(8260-61):1401-3. doi: 10.1016/s0140-6736(81)92812-9.
PubMed 6118769Bergstrom A, Byaruhanga R, Okong P. The impact of newborn bathing on the prevalence of neonatal hypothermia in Uganda: a randomized, controlled trial. Acta Paediatr. 2005 Oct;94(10):1462-7. doi: 10.1111/j.1651-2227.2005.tb01821.x.
PubMed 16299878Jha AK, Baliga S, Kumar HH, Rangnekar A, Baliga BS. Is There a Preventive Role for Vernix Caseosa?: An Invitro Study. J Clin Diagn Res. 2015 Nov;9(11):SC13-6. doi: 10.7860/JCDR/2015/14740.6784. Epub 2015 Nov 1.
PubMed 26674069Cabalin C, Dibarrart M, Nunez-Rosales JJ, Faunes M, Avaca M, Avalos P, Fabres J, Alvarez-Figueroa MJ, Vera-Kellet C, Silva-Valenzuela S, Saez CG, Borzutzky A. Vernix caseosa reveals mechanistic clues linking maternal obesity to atopic dermatitis pathogenesis. J Allergy Clin Immunol. 2024 Mar;153(3):860-867.e1. doi: 10.1016/j.jaci.2023.09.042. Epub 2023 Dec 2.
PubMed 38048884Akinbi HT, Narendran V, Pass AK, Markart P, Hoath SB. Host defense proteins in vernix caseosa and amniotic fluid. Am J Obstet Gynecol. 2004 Dec;191(6):2090-6. doi: 10.1016/j.ajog.2004.05.002.
PubMed 15592296Yoshio H, Tollin M, Gudmundsson GH, Lagercrantz H, Jornvall H, Marchini G, Agerberth B. Antimicrobial polypeptides of human vernix caseosa and amniotic fluid: implications for newborn innate defense. Pediatr Res. 2003 Feb;53(2):211-6. doi: 10.1203/01.PDR.0000047471.47777.B0.
PubMed 12538777Marchini G, Lindow S, Brismar H, Stabi B, Berggren V, Ulfgren AK, Lonne-Rahm S, Agerberth B, Gudmundsson GH. The newborn infant is protected by an innate antimicrobial barrier: peptide antibiotics are present in the skin and vernix caseosa. Br J Dermatol. 2002 Dec;147(6):1127-34. doi: 10.1046/j.1365-2133.2002.05014.x.
PubMed 12452861Holm T, Rutishauser D, Kai-Larsen Y, Lyutvinskiy Y, Stenius F, Zubarev RA, Agerberth B, Alm J, Scheynius A. Protein biomarkers in vernix with potential to predict the development of atopic eczema in early childhood. Allergy. 2014 Jan;69(1):104-12. doi: 10.1111/all.12308. Epub 2013 Nov 11.
PubMed 24205894Tollin M, Jagerbrink T, Haraldsson A, Agerberth B, Jornvall H. Proteome analysis of vernix caseosa. Pediatr Res. 2006 Oct;60(4):430-4. doi: 10.1203/01.pdr.0000238253.51224.d7. Epub 2006 Aug 28.
PubMed 16940245Svendsen EK, Grundt I. Total lipids and lipid pattern in amniotic fluid and vernix caseosa. A preliminary report. Acta Obstet Gynecol Scand. 1966;45(S9):80-3. doi: 10.3109/00016346609158604. No abstract available.
PubMed 5958408
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Post-partum Retention of Vernix Caseosa for Primary Prevention of Atopic Dermatitis, Guarding Skin Integrity and Fostering a Healthy Microbiome.
- ClinicalTrials.gov ID
- NCT07333378
- Acronym / sponsor ID
- PROTEGO / 230610001
- Conditions
- Atopic Dermatitis
- Keywords
- vernix caseosa, primary prevention, newborn, eczema, atopic dermatitis, skin infections, Staphylococcus aureus
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,383 participants (estimated)
- Lead sponsor
- Pontificia Universidad Catolica de ChileUniversity, hospital or other
- Study start
- 29 Sep 2026 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Mar 2028 (estimated)
- First posted
- 12 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Retention group: Vernix caseosa will be left on the skin and allowed to dry naturally; the baby's first bath will be delayed according to the study protocol.
- Removal group: Vernix will be removed following current hospital practice using gentle cleaning with water and oil or petroleum jelly shortly after birth.
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.
Detailed description
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Multicenter, randomized, controlled, parallel-group trial conducted in three maternity hospitals in Santiago, Chile. Mother-infant pairs are assigned 1:1 to either vernix retention (experimental) or vernix removal (control). In the retention arm, vernix caseosa is left on the skin and bathing is delayed ≥24 h; in the control arm, vernix is removed within 2 hours per standard care. Randomization occurs at the level of the 12-hour nursing shift-episode: eligible newborns born during a given shift receive that shift's assignment (vernix retention or removal, 1:1), determined in advance via a centralized IRT system (app.studyrandomizer.com). Randomization is stratified by clinical site and shift type (day/night); mode of delivery and parental atopy history are analyzed as covariates rather than stratification factors.
| Arm | Type | Receives |
|---|---|---|
| Retain vernix caseosa | Experimental | Other: Retention of Vernix Caseosa After BirthAfter 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. |
| Early removal of vernix caseosa | Other | Other: Removal of Vernix Caseosa After BirthWithin 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. |
Who may qualify
- Ages
- 0 days and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- pregnant mother aged 18 and older, who is able to provide informed consent for participation
- delivery of a healthy, singleton newborn (vaginal or cesarean) at one of the study sites.
- parents are able and willing to comply with the study schedule and procedures
Key exclusion criteria (7 listed)
- birthweight <2000 g
- prematurity younger than 34 weeks of gestation
- multiple gestation / multiple births
- maternal HIV-positivity
- clinical and/or laboratory diagnosis of chorioamnionitis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Retention of Vernix Caseosa After BirthRetention 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. | Other | Retain vernix caseosa |
| Removal of Vernix Caseosa After BirthEarly 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. | Other | Early removal of vernix caseosa |
Primary outcome
Cumulative incidence of atopic dermatitis at 1 year of age
Time frame: 12 months
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.
19 secondary outcomes
Incidence of Atopic Dermatitis (Hanifin & Rajka Criteria Only)
Time frame: 12 months.
Cumulative Incidence of Atopic Dermatitis (Modified UK Working Party Criteria Only)
Time frame: 0-12 months
Cumulative Incidence of Infant Eczema
Time frame: 0-12 months
Atopic dermatitis diagnosed by trained physician
Time frame: 12 months
Parent-reported atopic dermatitis
Time frame: 0-12 months
Cumulative incidence of atopic dermatitis by CEQ at 12 months
Time frame: 0-12 months
Use of topical anti-inflammatory medications
Time frame: 0-12 months
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
Time frame: From birth to 12 months of age
Severity of Atopic Dermatitis (SCORAD) among infants with AD
Time frame: 12 months of age
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
Time frame: 0-12 months
Interaction of intervention with FLG loss-of-function mutations
Time frame: 0-12 months
Dynamics of Staphylococcal Colonization
Time frame: 0-12 months
Transepidermal water loss (TEWL) at 24-96 hours of age
Time frame: 24-96 hours
Transepidermal water loss (TEWL) at 12 months of age
Time frame: 12 months of age
Skin pH at 24-96 hours of age
Time frame: 24-96 hours of age
Skin pH at 12 months of age
Time frame: 12 months of age
Epidermal natural moisturizing factor (NMF) concentration at 12 months.
Time frame: 12 months of age
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2026.
- Background: PubMed 33511639Endre KMA, Landro L, LeBlanc M, Gjersvik P, Lodrup Carlsen KC, Haugen G, Hedlin G, Jonassen CM, Nordlund B, Rudi K, Skjerven HO, Staff AC, Soderhall C, Vettukattil R, Rehbinder EM. Diagnosing atopic dermatitis in infancy using established diagnostic criteria: a cohort study. Br J Dermatol. 2022 Jan;186(1):50-58. doi: 10.1111/bjd.19831. Epub 2021 May 6.
- BackgroundTejos-Bravo M, Venegas L, Iturriaga C, Sabatini N, Martin C, Pérez-Mateluna G, Urzúa M, Cabalín C, Dossi MT, Del Barrio P, Majerson D, Silva-Valenzuela S, Vera-Kellet C, Borzutzky A. Alterations in skin physiology are associated with disease severity in Chilean patients with atopic dermatitis. European Academy of Allergy and Immunology Congress 2019. Lisbon, Portugal. June 1-5, 2019.
- BackgroundAhmed SOM. Vernix Caseosa: Benefits and Clinical Implications in Neonatal Care;A Study Conducted at Almak Nimr University Hospital, Shendi, Sudan. Int J Environ Sci. 2025; 11(469-475).
- Background: PubMed 19646134Blume-Peytavi U, Cork MJ, Faergemann J, Szczapa J, Vanaclocha F, Gelmetti C. Bathing and cleansing in newborns from day 1 to first year of life: recommendations from a European round table meeting. J Eur Acad Dermatol Venereol. 2009 Jul;23(7):751-9. doi: 10.1111/j.1468-3083.2009.03140.x.
- Background: PubMed 34462323Wisniewski JA, Phillipi CA, Goyal N, Smith A, Hoyt AEW, King E, West D, Golden WC, Kellams A. Variation in Newborn Skincare Policies Across United States Maternity Hospitals. Hosp Pediatr. 2021 Sep;11(9):1010-1019. doi: 10.1542/hpeds.2021-005948.
- Background: PubMed 6118769Henningsson A, Nystrom B, Tunnell R. Bathing or washing babies after birth? Lancet. 1981 Dec 19-26;2(8260-61):1401-3. doi: 10.1016/s0140-6736(81)92812-9.
- Background: PubMed 16299878Bergstrom A, Byaruhanga R, Okong P. The impact of newborn bathing on the prevalence of neonatal hypothermia in Uganda: a randomized, controlled trial. Acta Paediatr. 2005 Oct;94(10):1462-7. doi: 10.1111/j.1651-2227.2005.tb01821.x.
- Background: PubMed 26674069Jha AK, Baliga S, Kumar HH, Rangnekar A, Baliga BS. Is There a Preventive Role for Vernix Caseosa?: An Invitro Study. J Clin Diagn Res. 2015 Nov;9(11):SC13-6. doi: 10.7860/JCDR/2015/14740.6784. Epub 2015 Nov 1.
- Background: PubMed 38048884Cabalin C, Dibarrart M, Nunez-Rosales JJ, Faunes M, Avaca M, Avalos P, Fabres J, Alvarez-Figueroa MJ, Vera-Kellet C, Silva-Valenzuela S, Saez CG, Borzutzky A. Vernix caseosa reveals mechanistic clues linking maternal obesity to atopic dermatitis pathogenesis. J Allergy Clin Immunol. 2024 Mar;153(3):860-867.e1. doi: 10.1016/j.jaci.2023.09.042. Epub 2023 Dec 2.
- Background: PubMed 15592296Akinbi HT, Narendran V, Pass AK, Markart P, Hoath SB. Host defense proteins in vernix caseosa and amniotic fluid. Am J Obstet Gynecol. 2004 Dec;191(6):2090-6. doi: 10.1016/j.ajog.2004.05.002.
- Background: PubMed 12538777Yoshio H, Tollin M, Gudmundsson GH, Lagercrantz H, Jornvall H, Marchini G, Agerberth B. Antimicrobial polypeptides of human vernix caseosa and amniotic fluid: implications for newborn innate defense. Pediatr Res. 2003 Feb;53(2):211-6. doi: 10.1203/01.PDR.0000047471.47777.B0.
- Background: PubMed 12452861Marchini G, Lindow S, Brismar H, Stabi B, Berggren V, Ulfgren AK, Lonne-Rahm S, Agerberth B, Gudmundsson GH. The newborn infant is protected by an innate antimicrobial barrier: peptide antibiotics are present in the skin and vernix caseosa. Br J Dermatol. 2002 Dec;147(6):1127-34. doi: 10.1046/j.1365-2133.2002.05014.x.
- Individual participant dataSharing planned: Undecided. Individual participant data will be shared upon reasonable request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Retention of Vernix Caseosa After Birth and Removal of Vernix Caseosa After Birth in people with Atopic Dermatitis, run by Pontificia Universidad Catolica de Chile at 2 sites in Chile.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Chile. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Arturo Borzutzky, M.D (+56223543753, aborzutz@uc.cl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cumulative incidence of atopic dermatitis at 1 year of age (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07333378, which also lists 29 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2026.