title: Association between domestic water hardness, chlorine, and atopic dermatitis risk in early life: A population-based cross-sectional study.
abstract: Domestic water hardness and chlorine have been suggested as important risk factors for atopic dermatitis (AD).
  
  
  
  We sought to examine the link between domestic water calcium carbonate (CaCO3) and chlorine concentrations, skin barrier dysfunction (increased transepidermal water loss), and AD in infancy.
  
  
  
  We recruited 1303 three-month-old infants from the general population and gathered data on domestic water CaCO3 (in milligrams per liter) and chlorine (Cl2; in milligrams per liter) concentrations from local water suppliers. At enrollment, infants were examined for AD and screened for filaggrin (FLG) skin barrier gene mutation status. Transepidermal water loss was measured on unaffected forearm skin.
  
  
  
  CaCO3 and chlorine levels were strongly correlated. A hybrid variable of greater than and less than median levels of CaCO3 and total chlorine was constructed: a baseline group of low CaCO3/low total chlorine (CaL/ClL), high CaCO3/low total chlorine (CaH/ClL), low CaCO3/high total chlorine (CaL/ClH) and high CaCO3/high total chlorine (CaH/ClH). Visible AD was more common in all 3 groups versus the baseline group: adjusted odds ratio (AOR) of 1.87 (95% CI, 1.25-2.80; P = .002) for the CaH/ClL group, AOR of 1.46 (95% CI, 0.97-2.21; P = .07) for the CaL/ClH, and AOR of 1.61 (95% CI, 1.09-2.38; P = .02) for the CaH/ClH group. The effect estimates were greater in children carrying FLG mutations, but formal interaction testing between water quality groups and filaggrin status was not statistically significant.
  
  
  
  High domestic water CaCO3 levels are associated with an increased risk of AD in infancy. The influence of increased total chlorine levels remains uncertain. An intervention trial is required to see whether installation of a domestic device to decrease CaCO3 levels around the time of birth can reduce this risk.
authors.affiliation: Population Health Research Institute, St George's, University of London, London, United Kingdom.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Perkin
authors.affiliation: Children's Allergies Department, Division of Asthma, Allergy and Lung Biology, King's College London, London, United Kingdom.
authors.forename: Joanna
authors.initials: J
authors.lastname: Craven
authors.affiliation: Children's Allergies Department, Division of Asthma, Allergy and Lung Biology, King's College London, London, United Kingdom.
authors.forename: Kirsty
authors.initials: K
authors.lastname: Logan
authors.affiliation: Population Health Research Institute, St George's, University of London, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Strachan
authors.affiliation: Children's Allergies Department, Division of Asthma, Allergy and Lung Biology, King's College London, London, United Kingdom.
authors.forename: Tom
authors.initials: T
authors.lastname: Marrs
authors.affiliation: Children's Allergies Department, Division of Asthma, Allergy and Lung Biology, King's College London, London, United Kingdom.
authors.forename: Suzana
authors.initials: S
authors.lastname: Radulovic
authors.affiliation: Centre for Dermatology and Genetic Medicine, Division of Molecular Medicine, University of Dundee, Dundee, United Kingdom.
authors.forename: Linda E
authors.initials: LE
authors.lastname: Campbell
authors.affiliation: Centre for Dermatology and Genetic Medicine, Division of Molecular Medicine, University of Dundee, Dundee, United Kingdom.
authors.forename: Stephanie F
authors.initials: SF
authors.lastname: MacCallum
authors.affiliation: Centre for Dermatology and Genetic Medicine, Division of Molecular Medicine, University of Dundee, Dundee, United Kingdom.
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
authors.affiliation: Children's Allergies Department, Division of Asthma, Allergy and Lung Biology, King's College London, London, United Kingdom.
authors.forename: Gideon
authors.initials: G
authors.lastname: Lack
authors.affiliation: Children's Allergies Department, Division of Asthma, Allergy and Lung Biology, King's College London, London, United Kingdom; St John's Institute of Dermatology, Guy's and St Thomas' Hospital NHS Foundation Trust, London, United Kingdom. Electronic address: carsten.flohr@kcl.ac.uk.
authors.forename: Carsten
authors.initials: C
authors.lastname: Flohr
mesh_terms: D000328:Adult; D017668:Age of Onset; D002119:Calcium Carbonate / Q000009:adverse effects / Q000737:chemistry; D002713:Chlorine / Q000009:adverse effects* / Q000737:chemistry; D015897:Comorbidity; D003430:Cross-Sectional Studies; D003876:Dermatitis, Atopic / Q000453:epidemiology* / Q000209:etiology*; D005260:Female; D000091344:Filaggrin Proteins; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007381:Intermediate Filament Proteins / Q000235:genetics; D008297:Male; D018811:Maternal Exposure; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D011159:Population Surveillance; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D015995:Prevalence; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology; D014867:Water / Q000009:adverse effects* / Q000737:chemistry; D055815:Young Adult
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D014867:Water; D002713:Chlorine; D002119:Calcium Carbonate
keywords: Filaggrin; atopic dermatitis; eczema; transepidermal water loss; water hardness