Natural moisturizing factors in children with and without eczema: Associations with lifestyle and genetic factors

J Eur Acad Dermatol Venereol. 2022 Feb;36(2):255-262. doi: 10.1111/jdv.17787. Epub 2021 Dec 4.


Background: Filaggrin-derived natural moisturizing factors (NMF) play an important role in skin barrier function and in atopic dermatitis (AD). Its deficiency is associated with dry skin and increased surface pH. Studies on childhood environmental exposures and associations with NMF levels are scarce.

Objectives: To investigate previous exposures and genetic factors and their associations with NMF levels in young children.

Methods: In a case-control study nested in a prospective birth cohort (Odense Child Cohort), 169 healthy controls (HC) and 99 children with AD were included consecutively at the age of 7 years based on previous responses from questionnaires administered at 18 months, 3 years and 5 years, pertaining to past medical history, including allergy-specific questions. NMF levels were measured via a stratum corneum tape-stripping technique, genotyping for filaggrin (FLG) gene variants was performed and data on external exposures, including usage of moisturizer and topical steroids, antibiotics and early pet exposures, were obtained from questionnaires.

Results: Natural moisturizing factors levels were significantly lower in AD participants compared to HC (P < 0.001). This significance persisted after stratifying for AD subgroups of present AD, current AD during the last year and previous AD (P < 0.001, P = 0.039, P = 0.009 respectively). There was a significant association between NMF and FLG genotype (P = 0.016, P = 0.002 for HC, AD respectively). NMF levels were negatively correlated with early age moisturizer use (<18 months, P = 0.001) in HC but not significant in AD.

Conclusions: We found decreased levels of NMF with early moisturizer use and a genetic influence of the FLG variant on these levels. NMF was decreased in the AD subgroup with previous AD compared with HC, which could suggest the persistence of a Th2 cytokine milieu suppressing these levels.

MeSH terms

  • Birth Cohort
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Eczema* / genetics
  • Filaggrin Proteins*
  • Humans
  • Infant
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / metabolism
  • Life Style
  • Mutation
  • Prospective Studies
  • Skin / metabolism


  • Filaggrin Proteins
  • Intermediate Filament Proteins