Background: Atopic diseases are estimated to affect 30-40% of the global population. However, the potential protective effect of hypoallergenic infant formula against conditions such as atopic dermatitis (AD), cow’s milk protein allergy (CMPA), and asthma remains uncertain. Objective: To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating hypoallergenic formula for atopic disease prevention in high-risk infants. The primary outcome was AD and secondary outcomes were CMPA and asthma. Methods: A systematic review and meta-analysis was conducted according to PRISMA 2020. RCTs involving high-risk infants were identified through PubMed, Cochrane Library, and Web of Science. Exclusion criteria included interventions not initiated at birth, enrolment of sick infants, and non-RCTs. Pooled Relative Risks (RR) with 95% confidence intervals (CI) were calculated using a random-effects model. Results: We included 9 RCTs that enrolled high-risk infants. The meta-analysis found a borderline significant protective effects of AD (RR=0.78 [0.59-1.03], p=0.059; I 2=46.5%), a significant protective effect of hypoallergenic formula in prevention of CMPA (RR=0.51 [0.27-0.97], p=0.0228; I 2=37.3%), and no significant risk reduction for asthma (RR=0.78 [0.51-1.20], p=0.059; I 2=37.5%). Conclusion: This systematic review and meta-analysis found no statistically significant protective effect of hypoallergenic formula for AD or asthma, though a non-significant trend toward risk reduction was observed. A significant risk reduction was seen for CMPA (RR≈0.5), although not all diagnoses were confirmed by oral food challenge. These findings suggest potential patient-specific benefits, but larger, well-designed RCTs are needed to confirm them.

Background: The Western dietary pattern (WDP) is linked to socioeconomic status (SES) and has been proposed as a risk factor for childhood asthma. Objective: We aimed to investigate the interplay between SES and WDP during pregnancy and early childhood on risk of childhood asthma. Methods: We analyzed 594 mother–child pairs from the COPSAC 2010 cohort. Maternal food frequency questionnaires (FFQs) were completed during pregnancy, and children were followed for asthma/wheeze until age 10 years. Untargeted plasma metabolomics profiles were obtained at pregnancy week 24 and child ages 6 and 18 months. A WDP score derived from FFQs was used to compute WDP metabolite scores using sparse partial least squares (sPLS). Associations between WDP and asthma/wheeze and their interactions with SES were evaluated by regression models. Replication was performed in 772 mother–child pairs from VDAART with comparable metabolomics data and in 388 children from COPSAC 2000 with neonatal dried blood spot metabolomics. Results: In COPSAC 2010, SES was inversely correlated with WDP (r = –0.40 to –0.14; P < .01). Significant WDP–SES interactions were observed for multiple asthma/wheeze outcomes ( P < .05). Among children with low SES, higher maternal WDP FFQ-scores were associated with an increased risk of recurrent wheeze until 3yrs (aHR=1.29 [1.03–1.60], p=0.023) and asthma until 10yrs (aHR=1.32 [1.06–1.65], p=0.015) and higher child WDP metabolite-score were associated with asthma until 10yrs (aHR=1.87 [1.21–2.90], p=0.005). No significant WDP–SES interactions were observed in the replication cohorts; however, low SES was independently associated with asthma/wheeze in VDAART, and higher WDP-scores were associated with increased risk in COPSAC 2000 among low-SES children. Conclusions: WDP during pregnancy and early childhood is associated with increased risk of childhood asthma/wheeze dependent on SES.

Longitudinal sensitization patterns in childhood and adolescence

Background: Early exposure to allergens through a defect skin barrier has been proposed as a mechanism for inducing sensitization and development of allergic diseases. We hypothesized that early-onset, severe atopic dermatitis (AD) is associated with development of aeroallergen sensitization and allergic rhinitis. Methods: We included 368 children from the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC 2000) at-risk mother-child cohort. AD was diagnosed prospectively based on Hanifin&Rajka’s criteria and severity assessed using the Scoring Atopic Dermatitis (SCORAD) index. Early-onset AD was defined as debut ≤1 year, late-onset as debut from 1-6 years. Aeroallergen sensitization and allergic rhinitis were diagnosed at ages 6-7 and 12 years. Associations between early-onset and late-onset AD and allergy endpoints were calculated using general estimating equations (GEE) models to compute the overall odds ratios (OR) for both time points. Results: Early-onset AD (yes/no) and severity (SCORAD) were associated with development of aeroallergen sensitization during childhood; GEE OR=1.68 [1.08; 2.62], p=0.02 and 1.08 [1.03; 1.12], p<0.001, whereas late-onset was not; GEE OR=1.65 [0.92; 2.94], p=0.08 and 1.01 [0.97; 1.06], p=0.55. The same trend was seen for allergic rhinitis with significant association between early-onset AD and allergic rhinitis; GEE OR=1.56 [1.01; 2.41], p=0.04 and severity; GEE OR=1.09 [1.05; 1.13], p<0.001, whereas late-onset AD showed no association. The effects on sensitization and rhinitis of early-onset vs. late-onset AD severity were significantly different: p-interaction sensitization=0.03 and p-interaction rhinitis<0.01. Conclusion: Increasing severity of early-onset AD, but not late-onset AD, associates with aeroallergen sensitization and allergic rhinitis later in childhood.