Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

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

Journal of Perinatology volume 41, pages 232–239 (2021)Cite this article

Subjects

A Correction to this article was published on 23 June 2020

This article has been updated

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Chest pH decreased significantly overtime for full-term infants (p < 0.05) but not for premature infants by GLM analyses.
Fig. 2: Chest TEWL did not differ by study day for either premature or full-term infants via GLM with the linear regression lines calculated from the mean values.

Similar content being viewed by others

Change history

References

  1. Evans NJ, Rutter N. Development of the epidermis in the newborn. Biol Neonate. 1986;49:74–80.

    Article  CAS  PubMed  Google Scholar 

  2. Cartlidge P. The epidermal barrier. Semin Neonatol. 2000;5:273–80.

    Article  CAS  PubMed  Google Scholar 

  3. Rutter N. Clinical consequences of an immature barrier. Semin Neonatol. 2000;5:281–7.

    Article  CAS  PubMed  Google Scholar 

  4. Eichenfield LF, Hardaway CA. Neonatal dermatology. Curr Opin Pediatr. 1999;11:471–4.

    Article  CAS  PubMed  Google Scholar 

  5. Harpin VA, Rutter N. Barrier properties of the newborn infant’s skin. J Pediatr. 1983;102:419–25.

    Article  CAS  PubMed  Google Scholar 

  6. Okah FA, Wickett RR, Pickens WL, Hoath SB. Surface electrical capacitance as a noninvasive bedside measure of epidermal barrier maturation in the newborn infant. Pediatrics. 1995;96:688–92.

    CAS  PubMed  Google Scholar 

  7. Agren J, Sjors G, Sedin G. Ambient humidity influences the rate of skin barrier maturation in extremely preterm infants. J Pediatr. 2006;148:613–7.

    Article  PubMed  Google Scholar 

  8. Sedin G, Hammarlund K, Stromberg B. Transepidermal water loss in full-term and pre-term infants. Acta Paediatr Scand Suppl. 1983;305:27–31.

    Article  CAS  PubMed  Google Scholar 

  9. Agren J, Sjors G, Sedin G. Transepidermal water loss in infants born at 24 and 25 weeks of gestation. Acta Paediatr. 1998;87:1185–90.

    Article  CAS  PubMed  Google Scholar 

  10. Nonato LB, Lund CH, Kalia YN, Guy RH. Transepidermal water loss in 24 and 25 weeks gestational age infants. Acta Paediatr. 2000;89:747–8.

    Article  CAS  PubMed  Google Scholar 

  11. Kalia YN, Nonato LB, Lund CH, Guy RH. Development of skin barrier function in premature infants. J Investig Dermatol. 1998;111:320–6.

    Article  CAS  PubMed  Google Scholar 

  12. Visscher M, Odio M, Taylor T, White T, Sargent S, Sluder L, et al. Skin care in the NICU patient: effects of wipes versus cloth and water on stratum corneum integrity. Neonatology. 2009;96:226–34.

    Article  PubMed  Google Scholar 

  13. Narendran V, Visscher MO, Abril I, Hendrix SW, Hoath SB. Biomarkers of epidermal innate immunity in premature and full-term infants. Pediatr Res. 2010;67:382–6.

    Article  CAS  PubMed  Google Scholar 

  14. Lawn JE, Zupan, J., Begkoyian, G., Knippenberg, R. Newborn survival. In: Jamison D, Breman J, Beasham A, Alleyne G, Cleason M, Evans DB, editors. Disease control priroities in developing countries, 2nd ed. Washington, DC: The World Bank and Oxford University Press; 2006, pp. 531–49.

  15. Rutter N. The immature skin. Eur J Pediatr. 1996;155 Suppl 2:S18–20.

    Article  PubMed  Google Scholar 

  16. Parra JL, Paye M. EEMCO guidance for the in vivo assessment of skin surface pH. Skin Pharmacol Appl Skin Physiol. 2003;16:188–202.

    Article  CAS  PubMed  Google Scholar 

  17. De Paepe K, Houben E, Adam R, Wiesemann F, Rogiers V. Validation of the VapoMeter, a closed unventilated chamber system to assess transepidermal water loss vs. the open chamber Tewameter. Skin Res Technol. 2005;11:61–9.

    Article  PubMed  Google Scholar 

  18. Nuutinen J, Alanen E, Autio P, Lahtinen MR, Harvima I, Lahtinen T. A closed unventilated chamber for the measurement of transepidermal water loss. Skin Res Technol. 2003;9:85–9.

    Article  PubMed  Google Scholar 

  19. Rogiers V. EEMCO guidance for the assessment of transepidermal water loss in cosmetic sciences. Skin Pharmacol Appl Skin Physiol. 2001;14:117–28.

    Article  CAS  PubMed  Google Scholar 

  20. Odio MR, O’Connor RJ, Sarbaugh F, Baldwin S. Continuous topical administration of a petrolatum formulation by a novel disposable diaper. 2. Effect on skin condition. Dermatology. 2000;200:238–43.

    Article  CAS  PubMed  Google Scholar 

  21. Green M, Carol B, Behrendt H. Physiologic skin pH patterns in infants of low birth weight. The onset of surface acidification. Am J Dis Child. 1968;115:9–16.

    Article  CAS  PubMed  Google Scholar 

  22. Visscher MO, Chatterjee R, Munson KA, Pickens WL, Hoath SB. Changes in diapered and nondiapered infant skin over the first month of life. Pediatr Dermatol. 2000;17:45–51.

    Article  CAS  PubMed  Google Scholar 

  23. Fox C, Nelson D, Wareham J. The timing of skin acidification in very low birth weight infants. J Perinatol. 1998;18:272–5.

    CAS  PubMed  Google Scholar 

  24. Kanti V, Bonzel A, Stroux A, Proquitte H, Buhrer C, Blume-Peytavi U, et al. Postnatal maturation of skin barrier function in premature infants. Skin Pharmacol Physiol. 2014;27:234–41.

    Article  CAS  PubMed  Google Scholar 

  25. Hoeger PH, Enzmann CC. Skin physiology of the neonate and young infant: a prospective study of functional skin parameters during early infancy. Pediatr Dermatol. 2002;19:256–62.

    Article  PubMed  Google Scholar 

  26. Yosipovitch G, Maayan-Metzger A, Merlob P, Sirota L. Skin barrier properties in different body areas in neonates. Pediatrics. 2000;106:105–8.

    Article  CAS  PubMed  Google Scholar 

  27. Visscher MO, Narendran V, Pickens WL, LaRuffa AA, Meinzen-Derr J, Allen K, et al. Vernix caseosa in neonatal adaptation. J Perinatol. 2005;25:440–6.

    Article  PubMed  Google Scholar 

  28. Schmid-Wendtner MH, Korting HC. The pH of the skin surface and its impact on the barrier function. Skin Pharmacol Physiol. 2006;19:296–302.

    Article  PubMed  Google Scholar 

  29. Rippke F, Schreiner V, Schwanitz HJ. The acidic milieu of the horny layer: new findings on the physiology and pathophysiology of skin pH. Am J Clin Dermatol. 2002;3:261–72.

    Article  PubMed  Google Scholar 

  30. Holleran WM, Takagi Y, Uchida Y. Epidermal sphingolipids: metabolism, function, and roles in skin disorders. FEBS Lett. 2006;580:5456–66.

    Article  CAS  PubMed  Google Scholar 

  31. Hachem JP, Roelandt T, Schurer N, Pu X, Fluhr J, Giddelo C, et al. Acute acidification of stratum corneum membrane domains using polyhydroxyl acids improves lipid processing and inhibits degradation of corneodesmosomes. J Investig Dermatol. 2010;130:500–10.

    Article  CAS  PubMed  Google Scholar 

  32. Hatano Y, Man MQ, Uchida Y, Crumrine D, Scharschmidt TC, Kim EG, et al. Maintenance of an acidic stratum corneum prevents emergence of murine atopic dermatitis. J Investig Dermatol. 2009;129:1824–35.

    Article  CAS  PubMed  Google Scholar 

  33. Hachem JP, Crumrine D, Fluhr J, Brown BE, Feingold KR, Elias PM. pH directly regulates epidermal permeability barrier homeostasis, and stratum corneum integrity/cohesion. J Investig Dermatol. 2003;121:345–53.

    Article  CAS  PubMed  Google Scholar 

  34. Fluhr JW, Kao J, Jain M, Ahn SK, Feingold KR, Elias PM. Generation of free fatty acids from phospholipids regulates stratum corneum acidification and integrity. J Invest Dermatol. 2001;117:44–51.

    Article  CAS  PubMed  Google Scholar 

  35. Aly R, Shirley C, Cunico B, Maibach HI. Effect of prolonged occlusion on the microbial flora, pH, carbon dioxide and transepidermal water loss on human skin. J Investig Dermatol. 1978;71:378–81.

    Article  CAS  PubMed  Google Scholar 

  36. Puhvel SM, Reisner RM, Amirian DA. Quantification of bacteria in isolated pilosebaceous follicles in normal skin. J Investig Dermatol. 1975;65:525–31.

    Article  CAS  PubMed  Google Scholar 

  37. Elias PM. The how, why and clinical importance of stratum corneum acidification. Exp Dermatol. 2017;26:999–1003.

    Article  PubMed  Google Scholar 

  38. McAleer MA, Jakasa I, Raj N, O’Donnell CPF, Lane ME, Rawlings AV, et al. Early-life regional and temporal variation in filaggrin-derived natural moisturizing factor, filaggrin-processing enzyme activity, corneocyte phenotypes and plasmin activity: implications for atopic dermatitis. Br J Dermatol. 2018;179:431–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Visscher MO, Barai N, LaRuffa AA, Pickens WL, Narendran V, Hoath SB. Epidermal barrier treatments based on vernix caseosa. Skin Pharmacol Physiol. 2011;24:322–9.

    Article  PubMed  Google Scholar 

  40. Chittock J, Cooke A, Lavender T, Brown K, Wigley A, Victor S, et al. Development of stratum corneum chymotrypsin-like protease activity and natural moisturizing factors from birth to 4 weeks of age compared with adults. Br J Dermatol. 2016;175:713–20.

    Article  CAS  PubMed  Google Scholar 

  41. Minami-Hori M, Honma M, Fujii M, Nomura W, Kanno K, Hayashi T, et al. Developmental alterations of physical properties and components of neonatal-infantile stratum corneum of upper thighs and diaper-covered buttocks during the 1st year of life. J Dermatol Sci. 2014;73:67–73.

    Article  PubMed  Google Scholar 

  42. Nikolovski J, Stamatas GN, Kollias N, Wiegand BC. Barrier function and water-holding and transport properties of infant stratum corneum are different from adult and continue to develop through the first year of life. J Investig Dermatol. 2008;128:1728–36.

    Article  CAS  PubMed  Google Scholar 

  43. Visscher MO, Chatterjee R, Ebel JP, LaRuffa AA, Hoath SB. Biomedical assessment and instrumental evaluation of healthy infant skin. Pediatr Dermatol. 2002;19:473–81.

    Article  PubMed  Google Scholar 

  44. Visscher M, Maganti S, Munson KA, Bare DE, Hoath SB. Early adaptation of human skin following birth: a biophysical assessment. Skin Res Technol. 1999;5:213–20.

    Article  Google Scholar 

  45. Mauro T, Holleran WM, Grayson S, Gao WN, Man MQ, Kriehuber E, et al. Barrier recovery is impeded at neutral pH, independent of ionic effects: implications for extracellular lipid processing. Arch Dermatol Res. 1998;290:215–22.

    Article  CAS  PubMed  Google Scholar 

  46. Visscher M, Odio M, Taylor T, White T, Sargent S, Sluder L, et al. Skin care in the NICU patient: effects of wipes versus cloth & water on sc integrity. Neonatology. 2009;96:226–34.

    Article  PubMed  Google Scholar 

  47. Gustin J, Bohman L, Ogle J, Chaudhary T, Li L, Fadayel G, et al. Use of an emollient-containing diaper and pH-buffered wipe regimen restores skin pH and reduces residual enzymatic activity. Pediatr Dermatol. 2020. https://doi.org/10.1111/pde.14169. [Epub ahead of print].

  48. Blume-Peytavi U, Lavender T, Jenerowicz D, Ryumina I, Stalder JF, Torrelo A, et al. Recommendations from a European Roundtable Meeting on best practice healthy infant skin care. Pediatr Dermatol. 2016;33:311–21.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Horikoshi T, Matsumoto M, Usuki A, Igarashi S, Hikima R, Uchiwa H, et al. Effects of glycolic acid on desquamation-regulating proteinases in human stratum corneum. Exp Dermatol. 2005;14:34–40.

    Article  CAS  PubMed  Google Scholar 

  50. Visscher M, Narendran V. Neonatal infant skin: development, structure and function. Newborn Infant Nurs Rev. 2014;14:135–41.

    Article  Google Scholar 

  51. Elias PM. The how, why and clinical importance of stratum corneum acidification. Exp Dermatol. 2017;26:999–1003.

    Article  PubMed  Google Scholar 

  52. Scott IR, Harding CR. Filaggrin breakdown to water binding compounds during development of the rat stratum corneum is controlled by the water activity of the environment. Dev Biol. 1986;115:84–92.

    Article  CAS  PubMed  Google Scholar 

  53. Cau L, Pendaries V, Lhuillier E, Thompson PR, Serre G, Takahara H, et al. Lowering relative humidity level increases epidermal protein deimination and drives human filaggrin breakdown. J Dermatol Sci. 2017;86:106–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Rutter N. Percutaneous drug absorption in the newborn: hazards and uses. Clin Perinatol. 1987;14:911–30.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Partial funding for this work was provided by a grant from The Procter & Gamble Company, Cincinnati, OH.

Author information

Authors and Affiliations

  1. Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Marty O. Visscher & Vivek Narendran

  2. College of Medicine, University of Cincinnati, Cincinnati, OH, USA

    Marty O. Visscher & Vivek Narendran

  3. The Procter & Gamble Company, Cincinnati, OH, USA

    Andrew N. Carr

Authors
  1. Marty O. Visscher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrew N. Carr
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vivek Narendran
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MOV—substantial contribution to study design, study execution, data acquisition, data analysis, and data interpretation; literature review, paper preparation, and review with critical revision; approval of final version. ANC—substantial contribution to evaluation of analysis strategies, data interpretation; paper preparation and review with critical revision; approval of final version. VN—substantial contribution to evaluation of analysis strategies, data interpretation, discussion of clinical relevance; paper preparation and review with critical revision; approval of final version.

Corresponding author

Correspondence to Marty O. Visscher.

Ethics declarations

Conflict of interest

VN has no conflicts of interests to disclose. The authors with disclosures to report are as follows: A member of MOV’s family owns stock in The Procter & Gamble Company. ANC is an employee of The Procter & Gamble Company.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Visscher, M.O., Carr, A.N. & Narendran, V. Premature infant skin barrier maturation: status at full-term corrected age. J Perinatol 41, 232–239 (2021). https://doi.org/10.1038/s41372-020-0704-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-020-0704-3

Search

Advanced search

Quick links