Family History of Atopy Predicts Atopic Dermatitis Risk in First 2 Years of Life

Baby with infantile eczema
Baby with infantile eczema
Patients with a positive family history of atopy had an almost 3-fold greater risk for developing atopic dermatitis, regardless of common FLG mutation status.

Family history of atopy has been identified as a significant risk factor for atopic dermatitis (AD) in children, suggest study data published in the European Journal of Pediatrics. Household humidity levels, secondhand smoke exposure, and maternal education level were also associated with AD risk.

Investigators conducted a prospective birth cohort study at the Lausanne University Hospital (CHUV) in Lausanne, Switzerland. The study enrolled full-term neonates born to the CHUV from January 2010 to November 2012. Follow-up visits were conducted at days 1, 3, 7 and 1, 3, 6, 12, and 24 months after birth. The primary outcome measure was development of AD within the first 2 years of life. Medical and lifestyle questionnaires were administered to parents at birth, 12 months, and 24 months; nutrition questionnaires were completed at ages 1, 6, 12, 18, and 24 months. Cord blood samples were collected at birth for filaggrin genotyping. A subset of patients was tested by Sanger sequencing for 4 of the most common filaggrin mutations associated with AD: c.2282del4, p.R501X, p.R2447X, and p.S3247X. Hazard ratios (HRs) for AD were constructed by Cox regression for each potential risk factor.  

The final study cohort comprised 149 infants (78 boys; 100% white), of whom 36 developed AD. Mean age at AD onset was 9.4 months (median, 6 months; range, 1-24 months). Filaggrin genotyping was performed on 29 infants with AD and 45 infants without AD. The 4 tested mutations were relatively uncommon in study participants. There was 1 infant with AD and 1 control patient who carried the R501X mutation; 1 infant with AD carried the 2282del14 mutation; 1 infant with AD carried the R2447X mutation; and 1 control patient carried the S3247X mutation.

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Family history of atopy was the most significant risk factor for AD in adjusted analyses (HR, 2.77; 95% CI, 1.14-6.73; P =.02), regardless of filaggrin mutation status. Regarding socioeconomic factors, higher home humidity level (HR, 0.27; 95% CI, 0.08-0.89) and passive smoking (HR, 0.42; 95% CI, 0.21-0.86) predicted lower risk for AD. These associations persisted in subgroup and multivariate analyses. Notably, in subgroup analyses, passive smoking predicted lower AD risk in infants of mothers with high education levels (HR, 0.21; 95% CI, 0.069-0.62) but higher AD risk in infants of mothers with low education levels (HR, 2.8; 95% CI, 0.60-13.0). Household income appeared to increase AD risk in univariate analyses, although the association was not significant. Duration of breastfeeding, age at introduction of solid foods, and the introduction of allergenic foods (eg, fish, egg, seafood, milk) did not appear to affect AD risk.

These data describe family history of atopy as the most significant risk factor for atopic dermatitis. Filaggrin mutations were not prevalent in the study cohort and did not appear to influence the effect of family history on AD risk. Household humidity and secondhand smoke exposure appeared to decrease AD risk. Of note, the study population was restricted to newborns of Caucasian descent, due to the racial/ethnic makeup of the source genotyping population. Genetic mutation data for AD were available only for patients of Caucasian descent. Further research is necessary to elucidate AD risk profiles in infants of non-Caucasian descent. “Our findings highlight the likely contribution of both genetic and epigenetic factors to AD pathogenesis, as well as complex gene-environment interactions,” investigators wrote.

Reference

Gallay C, Meylan P, Mermoud S, et al. Genetic predisposition and environmental factors associated with the development of atopic dermatitis in infancy: A prospective birth cohort study [published online March 6, 2020]. Eur J Pediatr. doi: 10.1007/s00431-020-03616-5