Rouzha Zlatanova Pancheva ^1,2* Zoi Iliodromiti ³ George Moschonis ⁴ Eva Kontopoli ⁵ Eleni Karapati ³ Nicolaos Nicolaou ^6,7 Eva Karaglani ⁸ Mikaela Sekkidou ⁶ Simoneta Popova ⁹ Nataliya Usheva ¹⁰ Miglena Marinova ² PARASKEVI XEPAPADAKI ¹¹ OLYMPIA SARDELI ¹² Anastasia Kapetanaki ¹³ Nicoletta Iacovidou ¹⁴ Theodora Boutsikou ¹⁴ Evangelia Papathoma ¹⁵ Yannis Manios ^16,8

• ¹ Research Institute, Medical University “Prof. Dr. Paraskev Stoyanov”, Medical University of Varna, Varna, Bulgaria
• ² Department of Hygiene and Epidemiology, Faculty of Public Health, Medical University of Varna, “Prof. Dr. Paraskev Stoyanov”, Varna, Varna, Bulgaria
• ³ Neonatal Department, Medical School, Aretaieio Hospital, National and Kapodistrian University of Athens, Athens, Greece
• ⁴ Discipline of Food, Nutrition and Dietetics, Department of Sport, Exercise and Nutrition Sciences, School Allied Health, Human Services and Sport, La Trobe University, Melbourne VIC 3086, Australia
• ⁵ Independent researcher, Amersfoort, Netherlands
• ⁶ University of Nicosia Medical School, 2408 Nicosia, Cyprus
• ⁷ Asthma and Allergy Center, 4158 Limassol, Cyprus
• ⁸ Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece
• ⁹ Department of Hygiene and Epidemiology, Faculty of Public Health, Medical University of Varna, “Prof. Dr. Paraskev Stoyanov” Bulgaria, Varna, Varna, Bulgaria
• ¹⁰ Department of Social Medicine and Health Care Organization, Faculty of Public Health, Medical University Prof. Dr P. Stoyanov, Varna, Varna, Bulgaria
• ¹¹ Allergy Department, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece
• ¹² Third Department of Pediatrics, National and Kapodistrian University of Athens, ATTIKON General University Hospital, Athens, Greece
• ¹³ Helena Venizelou Hospital, Neonatology Department, Athens, Greece
• ¹⁴ Neonatal Department, National and Kapodistrian University of Athens, Aretaieio Hospital, Athens, Greece
• ¹⁵ Neonatal Intensive Care Unit, Alexandra University and State Maternity Hospital, Athens, Greece
• ¹⁶ Institute of Agri-food and Life Sciences, Hellenic Mediterranean University Research Centre, (Agro-Health), Heraklion, Greece

Background: Early life infections (ELIs), encompassing both viral and bacterial types, occur within the first six months of life. Influenced by genetic host factors and environmental conditions, the relationship between ELIs and subsequent allergic manifestations, particularly cow's milk protein allergy (CMPA) and atopic dermatitis (AD), is complex and not fully understood. Objective: The aim of the current study was to examine the potential interplay between nutrition, infections, and allergic manifestations in the first six months of life in infants with a family history of allergies, who were either exclusively breastfed (EBF) or fed a combination of breast milk and standard (SF) or partially hydrolyzed infant formula (pHF). Methods: The Allergy Reduction Trial (ART) is a multicenter, randomized controlled trial involving 551 participants. From birth, these participants were divided into three groups: Exclusive Breastfeeding (EBF), Partially Hydrolyzed Formula (pHF), and Standard Formula (SF). ELIs, defined as viral and bacterial infections occurring during the first 6 months, and outcomes (AD, CMPA) were recorded through questionnaires (i.e., SCORAD and CоMiSS) and clinical assessments. Results: The relative risk (RR) for CMPA in infants with ELIs was 0.20 (95% CI: 0.07-0.58), highlighting a protective effect of ELIs against CMPA development. Notably, the incidence of CMPA was significantly lower in infants who experienced ELIs compared to those without (3% vs. 13.4%, p=0.001), with no cases of CMPA observed at 6 months in exclusively breastfed (EBF) infants with ELIs. For AD, a trend was observed where the incidence was lower in infants with ELIs who were fed with pHF at 6.5%, compared to those fed with SF at 18.2% (p=0.092), suggesting a potential protective effect of ELIs in the pHF group against AD development. Conclusion: The study highlights a potential protective role of ELIs in reducing the risk of CMPA, particularly in EBF infants. Furthermore, it suggests a trend towards lower AD incidence in infants fed with pHF, highlighting the complex interplay between early microbial exposures, feeding practices, and immune development. Further research is warranted to unravel this challenging relationship and appropriately inform early life allergy prevention strategies