Infant Formulas With Partially or Extensively Hydrolyzed Milk Proteins for the Prevention of Allergic Diseases: A Systematic Review and Meta-Analysis of Clinical Trials

Abstract

Infant Formulas With Partially or Extensively Hydrolyzed Milk Proteins for the Prevention of Allergic Diseases: A Systematic Review and Meta-Analysis of Clinical Trials Xiaoxu Li 1 , Tingchao He 2,3 , Sufang Duan 2,3 , Jinghong Liang 1 , Gang Feng 3,4 , Fang Li 2,3 , Zhenyu Shen 6 , Wenhui Ye 5 , Biao Liu 5 , Bibo Jiang 1 , Yujing Chen 1 , Nan Liu 1 , Ignatius Man-Yau Szeto 3,4,* , Li Cai 1,7,** 1 Department of Maternal and Child Health, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong Province, China; 2 Inner Mongolia Dairy Technology Research Institute, Hohhot, China; 3 Inner Mongolia Yili Industrial Group, Yili Maternal and Infant Nutrition Institute (YMINI), Beijing, China; 4 National Center of Technology Innovation for Dairy, Hohhot, China; 5 Inner Mongolia Yili Industrial Group, Hohhot, China; 6 The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China; 7 Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, China ABSTRACT Despite the widely recommended usage of partially hydrolyzed formula (PHF) or extensively hydrolyzed formula (EHF) of milk protein for preventing allergic diseases (ADs), clinical studies have been inconclusive regarding their efficacy compared with that of cow's milk formula (CMF) or breast milk (BM). We aimed to systematically evaluate the effects of PHF or EHF compared with those of CMF or BM on risk of ADs (cow's milk allergy, allergic rhinitis, eczema, asthma, wheeze, food allergy, and sensitization) in children. We searched PubMed, Embase, Cochrane Library, and Web of Science for clinical trials published from inception to 21 October, 2022. We used the Grading of Recom mendations Assessment, Development, and Evaluation (GRADE) approach to grade the strength of evidence. Overall, 24 trials (10,950 infants) were included, 17 of which specifically included high-risk infants. GRADE was low for the evidence that, compared with CMF, infants early fed with EHF had lower risk of cow's milk allergy at age 0–2 y [relative risk (RR): 0.62; 95% CI: 0.39, 0.99]. Moderate evidence supported that PHF and EHF reduced risk of eczema in children aged younger or older than 2 y, respectively (RR: 0.71; 95% CI: 0.52, 0.96; and RR: 0.79; 95% CI: 0.67, 0.94, respectively). We also identified moderate systematic evidence indicating that PHF reduced risk of wheeze at age 0–2 y compared with CMF (RR: 0.50; 95% CI: 0.29, 0.85), but PHF and EHF increased the risk compared with BM (RR: 1.61; 95% CI: 1.11, 2.31; and RR: 1.64; 95% CI: 1.26, 2.14). Neither PHF nor EHF had significant effects on other ADs in children of any age. In conclusion, compared with CMF, PHF, or EHF had different preventive effect on cow's milk allergy, eczema, and wheeze. Compared with BM, both PHF and EHF may increase risk of wheeze but not other ADs. Given that most trials included only high-risk infants, more research on non–high risk infants is warranted before any generalization is attempted. This protocol was registered at PROSPERO as CRD42022320787. Keywords: allergy, prevention, partially hydrolyzed milk protein formula, extensively hydrolyzed milk protein formula, meta-analysis