The Risk Reduction Effect of a Nutritional Intervention With a Partially Hydrolyzed Whey-Based Formula on Cow's Milk Protein Allergy and Atopic Dermatitis in High-Risk Infants Within the First 6 Months of Life: The Allergy Reduction Trial (A.R.T.), a Multicenter Double-Blinded Randomized Controlled Study

Nicolaos Nicolaou; Rouzha Pancheva; Eva Karaglani; Mikaela Sekkidou; Miglena Marinova-Achkar; Simoneta Popova; Margarita Tzaki; Anastasia Kapetanaki; Nicoletta Iacovidou; Theodora Boutsikou; Zoi Iliodromiti; Vassiliki Papaevangelou; Olympia Sardeli; Paraskevi Xepapadaki; Evangelia Papathoma; Inge Thijs-Verhoeven; Urszula Kudla; Laurien H Ulfman; Anne Schaafsma; Yannis Manios

doi:10.3389/fnut.2022.863599

The Risk Reduction Effect of a Nutritional Intervention With a Partially Hydrolyzed Whey-Based Formula on Cow's Milk Protein Allergy and Atopic Dermatitis in High-Risk Infants Within the First 6 Months of Life: The Allergy Reduction Trial (A.R.T.), a Multicenter Double-Blinded Randomized Controlled Study

Front Nutr. 2022 May 25:9:863599. doi: 10.3389/fnut.2022.863599. eCollection 2022.

Authors

Nicolaos Nicolaou^{1

2}, Rouzha Pancheva³, Eva Karaglani⁴, Mikaela Sekkidou¹, Miglena Marinova-Achkar³, Simoneta Popova³, Margarita Tzaki⁵, Anastasia Kapetanaki⁵, Nicoletta Iacovidou⁶, Theodora Boutsikou⁶, Zoi Iliodromiti⁶, Vassiliki Papaevangelou⁷, Olympia Sardeli⁷, Paraskevi Xepapadaki⁸, Evangelia Papathoma⁹, Inge Thijs-Verhoeven¹⁰, Urszula Kudla¹⁰, Laurien H Ulfman¹⁰, Anne Schaafsma¹⁰, Yannis Manios^{4

11}

Affiliations

¹ Asthma and Allergy Centre, Limassol, Cyprus.
² University of Nicosia Medical School, Nicosia, Cyprus.
³ Department of Hygiene and Epidemiology, Faculty of Public Health, Medical University of Varna, Varna, Bulgaria.
⁴ Department of Nutrition & Dietetics, School of Health Science & Education, Harokopio University, Athens, Greece.
⁵ General Hospital Elena Venizelou, Athens, Greece.
⁶ Neonatal Department, National and Kapodistrian University of Athens, Aretaieio Hospital, Athens, Greece.
⁷ Third Department of Pediatrics, National and Kapodistrian University of Athens, ATTIKON General University Hospital, Athens, Greece.
⁸ Allergy Department, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece.
⁹ Neonatal Intensive Care Unit, Alexandra University and State Maternity Hospital, Athens, Greece.
¹⁰ FrieslandCampina, Amersfoort, Netherlands.
¹¹ Institute of Agri-Food and Life Sciences, Hellenic Mediterranean University Research Centre, Heraklion, Greece.

Abstract

Background: The role of partially hydrolyzed formulas (pHF) as part of nutritional interventions to prevent the development of allergic manifestations (AM) is questioned, and efficacy of each specific pHF should be substantiated.

Objective: To investigate the risk-reduction effect of a whey-based pHF on the development of cow's milk protein allergy (CMPA) and atopic dermatitis (AD) in infants at high-risk for allergy within the first 6 months of life.

Materials and methods: In a multicenter double-blinded randomized controlled setting, healthy non-exclusively breastfed full-term infants, received either a specific whey-based pHF or a standard cow's milk-based formula (SF) and were clinically assessed for AM at 2, 4, and 6 months of age, supported by the objective scoring tools SCORAD and CoMiSS. CMPA was confirmed by open food challenge. Intention-to-Treat (ITT) and Per-Protocol (PP) analyses were performed.

Results: Of 331 randomized subjects (ITT analysis set), 160 received the pHF and 171 the SF. Six (3.8%) infants in the pHF and 12 (7%) in the SF group developed CMPA (p = 0.186). AD incidence was significantly lower in those receiving pHF as compared to SF (10.6% vs. 18.7%, p = 0.024) with a relative risk (RR, 95% CI) of 0.54 (0.32, 0.92), in particular when adjusting for family history of AD [6.5% vs. 27.3%, RR 0.24 (0.07, 0.78), p = 0.018] representing a risk reduction of 76%. The PP analysis showed similar results.

Conclusion: This specific whey-based pHF reduced the risk of AD development, particularly in those with a family history of AD, and tended to reduce the development of CMPA in non-exclusively breastfed infants at high-risk for allergy. The A.R.T. study suggests that this particular pHF may contribute to measures aimed at prevention of allergic manifestations. However, further studies are needed to confirm this risk-reduction effect.

Keywords: allergy prevention; atopic dermatitis; cow milk allergy; high-risk infants; nutritional intervention; partially hydrolyzed formula; randomized controlled trial.

Copyright © 2022 Nicolaou, Pancheva, Karaglani, Sekkidou, Marinova-Achkar, Popova, Tzaki, Kapetanaki, Iacovidou, Boutsikou, Iliodromiti, Papaevangelou, Sardeli, Xepapadaki, Papathoma, Thijs-Verhoeven, Kudla, Ulfman, Schaafsma and Manios.