Most associations of early‐life environmental exposures and genetic risk factors poorly differentiate between eczema phenotypes: the Generation R Study

Abstract

SummaryBackgroundChildhood eczema is variable in onset and persistence.ObjectivesTo identify eczema phenotypes during childhood, and their associations with early‐life environmental and genetic factors.MethodsIn this study of 5297 children from a multiethnic population‐based prospective cohort study, phenotypes based on parent‐reported physician‐diagnosed eczema from age 6 months to 10 years were identified using latent class growth analysis. Information on environmental factors was obtained using postal questionnaires. Four filaggrin mutations were genotyped and a risk score was calculated based on 30 genetic variants. Weighted adjusted multinomial models were used for association analyses.ResultsWe identified the following five eczema phenotypes: never (76%), early transient (8%), mid‐transient (6%) and late transient (8%) and persistent eczema (2%). Early transient and persistent eczema were most common in first‐born children, those with a parental history of eczema, allergy or asthma and those with persistent wheezing [range of odds ratio (OR): 1.37, 95% confidence interval (CI) 1.07–1.74 and OR 3.38, 95%CI 1.95–5.85]. Early transient eczema was most common in male children only (OR 1·49, 95% CI 1·18–1·89). Children with late transient or persistent eczema were more often of Asian ethnicity (OR 2·04, 95% CI 1·14–3·65 and OR 3·08, 95% CI 1·34–7·10, respectively). Children with early, late transient and persistent eczema more often had a filaggrin mutation or additional risk alleles (range OR: 1.07, 95%CI 1.02–1.12 and OR 2.21, 95%CI 1.39–3.50). Eczema phenotypes were not associated with maternal education, breastfeeding, day care attendance and pet exposure.ConclusionsFive eczema phenotypes were identified in a multiethnic paediatric population with limited differences in risk profiles, except for sex and ethnicity. What's already known about this topic? Two previous studies in longitudinal birth cohorts identified four and six different eczema phenotypes, predominantly in children of European ethnicity. What does this study add? Five eczema phenotypes were identified in a multiethnic paediatric population using latent class growth analysis.Children with early transient and persistent eczema were most often first‐born children and had persistent wheezing, filaggrin mutation or additional risk alleles.Previously known eczema risk factors had limited differentiating capabilities for eczema phenotypes, except for the association of early transient eczema with male children, and late transient and persistent eczema with Asian ethnicity.

Eczema phenotypes and risk of allergic and respiratory conditions in school age children

“…Full models were adjusted for parental history of allergy, asthma or eczema, maternal education, parity, child's sex, ethnicity and breastfeeding. Italic values indicate statistical significance at the α = 0.05 level showed an association of the four most common filaggrin mutations in Europeans with early and late transient eczema, but not with persistent eczema [10]. Unfortunately, we were not able to study filaggrin mutations as mediators for the association of eczema phenotypes with asthma and allergic conditions due to lack of power.…”

“…[9]. As previously described, in children with available data on at least 3 time points between age 6 months to 10 years, latent class growth analysis was used to assign children to their latent classes based on their respective posterior probabilities [10]. Five eczema phenotypes were identified based on the various eczema trajectories: never, early transient, mid-transient, late transient and persistent eczema (Additional file 1: Figure S2).…”

Associations of eczema phenotypes with emotional and behavioural problems from birth until school age. The Generation R Study

“…In children with available data on physician-diagnosed eczema on at least three timepoints, we previously identified five eczema phenotypes, namely never, early transient, mid-transient, late transient and persistent eczema. 13 The children were assigned to the eczema phenotype for which they had the highest posterior probability. Data on ever having eczema were collected by parentreported questionnaires at 10 years of age: 'Has your child ever had eczema diagnosed by a doctor?…”

“…At the ages of 1Á5, 3 and 6 years, the preschool CBCL version for children aged 1Á5-5 years (CBCL/1Á5-5) was used. 17 At the age of 10 years, the school-age version of the CBCL for children aged 6-18 years was used (CBCL/ [6][7][8][9][10][11][12][13][14][15][16][17][18].…”

“…9 Eczema phenotypes take into account the variability of eczema onset and persistence within and between individuals over time. 13 Using eczema phenotypes might clarify which children with eczema in early life are most at risk of emotional and behavioural problems later in life. Additionally, bidirectional analyses could reveal whether eczema leads to emotional and behavioural problems or the reverse.…”