Early‐Life Diet and Persistent Atopic Dermatitis: A Nationwide Cohort Study

Atopic dermatitis (AD) typically presents during early childhood and often resolves with aging. However, approximately 20% of cases persist beyond age 8 [1]. Previous studies on dietary interventions for AD have yielded variable results and have yet to provide a definitive answer regarding the influence of dietary modifications on persistent AD [1-5]. This study investigated the role of early-life dietary factors in the risk of persistent AD beyond preschool age. Using data from the Korean National Health Insurance Service, 608,943 children born between 2008 and 2010 who were diagnosed with AD before age 7 were followed up until age 9. Dietary factors were assessed through health examinations at seven stages: 4–6, 9–12, 18–24, 30–36, 42–48, 54–60, and 66–71 months. Persistent AD was defined as the presence of medical visits for AD over 3 years between ages 7 and 9, while AD resolution was defined as the absence of such visits. Potential confounding factors, including sex, AD onset age, household income, maternal AD history, and AD severity, were adjusted for. Among all children with AD, 131,525 (21.6%) cases of persistent AD were detected (Table S1). We investigated the association between dietary factors and persistent AD (Table 1). At 4–6 months, children exclusively fed breast milk (adjusted odds ratio [aOR] 1.07; 95% confidence interval [CI], 1.06–1.09) or special formula milk (aOR, 1.16; 95% CI, 1.04–1.30) had higher odds of AD persistence. The negative effect of prolonged breastfeeding persisted even after adjusting for maternal AD history, supporting the hygiene hypothesis that breast milk's immunologic properties might hinder immune system development by maintaining Th-2 dominance [6]. At the 9–12 months follow-up, those who had started complementary feeding after 6 months of age showed higher odds of AD persistence (aOR, 1.08; 95% CI, 1.06–1.10). Therefore, our findings suggest that limiting the duration of exclusive breastfeeding and introducing complementary feeding before age 6 months might be beneficial in reducing the risk of persistent AD. Similar patterns were seen at 18–24, 30–36, 42–48, 54–60, and 66–70 months: picky eating habits, obese or overweight, consuming ≤ 2 meals per day (irregular eating habit), and daily drinking over 200 mL of fruit juice or sugary drinks were linked to higher odds of persistent AD. Considering that various dietary habits are interrelated, in the mutually adjusted model (Model 2), late initiation of complementary feeding, picky eating, and being obese or overweight were identified as relatively more important dietary determinants of persistent AD. The overall findings remained consistent in the analysis where each variable was divided into specific responses (Table S2). Complementary food introduction at age > 6 months Foods included in complementary feeding We further investigated the association between dietary changes and persistent AD (Figure 1). At 4–6 and 9–12 months, switching from breastfeeding to powdered formula was associated with lower AD odds (aOR, 0.94; 95% CI, 0.91–0.98) compared with continuous exclusive breastfeeding. At 18–24, 42–48, and 54–60 months, shifting from diversified to picky eating was associated with higher AD odds (aOR, 1.04; 95% CI, 1.01–1.06), whereas maintaining picky eating also showed higher odds (aOR, 1.08; 95% CI, 1.04–1.12) compared with consistent diversified eating. Transitioning from picky to diversified eating had similar odds (aOR, 1.03; 95% CI, 0.99–1.06) to continuous diversified eating. At 30–36 and 42–48 months, increasing meal frequency from ≤ 2 to 3 times per day had lower AD odds (aOR, 0.94; 95% CI, 0.89–0.99). From 30 to 71 months, children who became (aOR, 1.08; 95% CI, 1.05–1.11) or remained overweight or obese (aOR, 1.09; 95% CI, 1.04–1.15) had higher AD odds than those maintaining normal weight. Transitioning from overweight or obese to normal weight showed similar AD odds to those consistently maintaining a normal weight (aOR, 1.03; 95% CI, 0.99–1.08 ). These results indicate that changes in eating habits and weight status were associated with varying odds of AD, even after the establishment of irregular eating patterns or altered BMI status. Overall, regular and diversified eating habits in early life were associated with lower odds of persistent AD. This study underscores the significance of fostering healthy dietary habits early in life to mitigate the burden of persistent AD beyond preschool age. Specifically, our findings suggest that early complementary feeding with limited exclusive breastfeeding, regular diverse eating habits, and healthy weight maintenance may help reduce persistent AD risk. A future prospective study that rigorously considers reverse causality based on the temporal relationship between health examination time points and the presence of AD is needed. J.S.L., S.R.K., S.I.C., and D.H.L. conceived and designed the study. S.R.K. performed the statistical analysis. J.S.L. and S.R.K. drafted the report. S.I.C. and D.H.L. contributed to data acquisition. All authors contributed to data interpretation and critical review of the paper. This research used data (NHIS-2021-4-023) from the National Health Insurance Service (NHIS) and was supported by the Korean Atopic Dermatitis Association. The findings and conclusions of this study are solely those of the authors and do not necessarily represent the official position of the NHIS. This study was approved by the Institutional Review Board of the Seoul National University Hospital (IRB no. E-2102-153-1199). The requirement for obtaining informed consent was exempted due to the stringent confidentiality protocols implemented for the NHIS cohort database. The authors declare no conflicts of interest. The data that support the findings of this study are available from the Korean National Health Insurance Service (NHIS). Restrictions apply to the availability of these data, which were used under license for this study. Data are available with the permission of the Korean National Health Insurance Service (NHIS). Table S1. Characteristics of the study participants Table S2. Determinants of persistent atopic dermatitis in detail at age 7–9 years in children. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. 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