ALSPAC

The Avon Longitudinal Study of Parents and Children (“Children of the 90s”) is a population-based UK birth cohort of 14,701 children born in Avon in the early 1990s. Parents reported a typical itchy and/or flexural rash at 12 time points from 6 months to 16.5 years. A subset of children were genotyped, including for Filaggrin (FLG) null mutations. It is one of the main sources behind Eczema Trajectories and the Atopic March debate. The children were followed from birth rather than recruited from clinics, which makes it the best UK answer to “will my toddler grow out of it?”

ALSPAC [supports] Eczema Trajectories ALSPAC [relates] Eczema Prognosis

Eczema trajectories (Paternoster et al., JACI 2018). Eczema prevalence fell from 27% in the first year of life to 7% at 16.5 years. Using 9,894 children, together with the Dutch PIAMA cohort for replication, the analysis found six reproducible classes. The commonest affected class was early-onset-early-resolving (13–15%), clearing by about 6–7 years; it was more common in boys and only weakly linked to Asthma. Early-onset-persistent eczema (5–7%) carried most of the risk. In ALSPAC it had the strongest link to FLG null mutations (OR 4.31), maternal eczema (OR 3.16) and the genetic risk score. Asthma was reported by 29% of this class at age 7, versus 8% in unaffected or transient children (OR 5.50). Breastfeeding was associated with the two longest-lasting classes in ALSPAC but not in PIAMA, which the authors could not explain.

Filaggrin [causes] Eczema Trajectories Eczema Trajectories [relates] Asthma ALSPAC [relates] PIAMA

Atopic march and allergy findings. Belgrave et al. (PLOS Med 2014) pooled 9,801 children from ALSPAC and the Manchester MAAS cohort, assessed at ages 1, 3, 5, 8 and 11. They found that a classic eczema-then-wheeze-then-rhinitis “march” described only 3.1% of all children, about 7% of those with any symptoms. In the same cohort, Lack et al. (2003) linked peanut-oil-containing skin preparations used on inflamed infant skin with later peanut allergy (OR 6.8) (Peanut Oil Sensitisation).

ALSPAC [contradicts] Atopic March ALSPAC [supports] Peanut Oil Sensitisation

Conflict: [Paternoster et al., JACI 2018, ALSPAC] says most early-onset eczema resolves by school age (early-onset-persistent only 5–7%). [Margolis et al., JAMA Dermatol 2014, PEER Registry] says >80% of children aged 2–26 still had symptoms or used treatment. Unresolved (population vs treated-registry samples). Add to open_questions.

Connections

• Eczema Prognosis — cohort data on who outgrows eczema, source: Paternoster 2018
• Eczema Trajectories — six latent classes derived from ALSPAC, source: Paternoster 2018
• Atopic March — one of two cohorts in Belgrave 2014, source: Belgrave 2014
• Peanut Oil Sensitisation — Lack 2003 peanut-oil skin preparations OR 6.8 in ALSPAC preschoolers, source: Lack 2003
• Filaggrin — FLG null mutations OR 4.31 for early-onset-persistent class, source: Paternoster 2018
• Asthma — 29% asthma at age 7 in persistent class vs 8%, source: Paternoster 2018
• PIAMA — Dutch replication cohort, source: Paternoster 2018
• PEER Registry — contrasting persistence estimate, source: Margolis 2014