Abstract

BACKGROUND: Several studies have identified an association between water hardness and atopic eczema (AE), however, there is a paucity of longitudinal data in early life. OBJECTIVES: To examine whether water hardness is associated with an increased risk of AE and skin barrier dysfunction in infants and to assess effect modification by filaggrin (FLG) loss-of-function variants. METHODS: We performed a longitudinal analysis of data from infants in the Enquiring About Tolerance (EAT) study, who were enrolled at 3 months and followed up until 36 months of age. RESULTS: Of 1,303 infants enrolled in the EAT study, 91.3% (n=1,189) attended the final clinic visit and 94.0% (n=1,225) of participants' families completed the 36-month questionnaire. Of these, 761 (58.4%) developed AE by 36 months. There was no overall association between exposure to harder (>255 mg/L calcium carbonate [CaCO3 ]) versus softer (≤255 mg/L CaCO3 ) water: Adjusted hazard ratio (HR) 1.07 95% CI 0.92, 1.24. However, there was an increased incidence of AE in infants with FLG mutations exposed to hard water: adjusted HR 2.72 95% CI 2.03, 3.66, with a statistically significant interaction between hard water, FLG and risk of AE (HR 2.72 95% CI 2.03, 3.66) and TEWL (0.0081 g/m2 /h per mg/L CaCO3 95% CI 0.00028, 0.016). CONCLUSIONS: There is evidence of an interaction between water hardness and FLG gene mutations in the development of infantile AE.