Protein hydrolysate versus standard formula for preterm infants. 2017

Derek Hang Cheong Ng, and Joel Klassen, and Nicholas D Embleton, and William McGuire
Hull York Medical School & Centre for Reviews and Dissemination, University of York, York, UK.

When human milk is not available for feeding preterm infants, protein hydrolysate rather than standard cow's milk formulas (with intact proteins) are often used because they are perceived as being tolerated better and less likely to lead to complications. However, protein hydrolysate formulas are more expensive than standard formulas, and concern exists that their use in practice is not supported by high-quality evidence. To assess the effect of feeding preterm infants with hydrolysed formula (versus standard cow's milk formulas) on the risk of feed intolerance, necrotising enterocolitis, and other morbidity and mortality in preterm infants. We used the standard Cochrane Neonatal search strategy including electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 4), Ovid MEDLINE, Ovid Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (to April 2017), as well as conference proceedings and previous reviews. Randomised and quasi-randomised controlled trials that compared feeding preterm infants with protein hydrolysate versus standard (non-hydrolysed) cow's milk formula. Two review authors assessed trial eligibility and risk of bias and extracted data independently. We analysed treatment effects as described in the individual trials and reported risk ratios and risk differences for dichotomous data, and mean differences for continuous data, with respective 95% confidence intervals (CI). We used a fixed-effect model in meta-analyses and explored potential causes of heterogeneity in sensitivity analyses. We assessed quality of evidence at the outcome level using the GRADE approach. We identified 11 trials for inclusion in the review. All trials were small (total participants 665) and had various methodological limitations including uncertainty about methods to ensure allocation concealment and blinding. Most participants were clinically stable preterm infants of gestational age less than about 34 weeks or birth weight less than about 1750 g. Fewer participants were extremely preterm, extremely low birth weight, or growth-restricted. Most trials found no effects on feed intolerance assessed variously as mean prefeed gastric residual volume, incidence of abdominal distention or other concerning gastrointestinal signs, or time taken to achieve full enteral feeds (meta-analysis was limited because studies used different measures). Meta-analysis found no effect on the risk of necrotising enterocolitis (typical risk ratio 1.10, 95% CI 0.36 to 3.34; risk difference 0.00, 95% CI -0.03 to 0.04; 5 trials, 385 infants) (low quality evidence; downgraded for imprecision and design weaknesses). The identified trials provide only low quality evidence about the effects of feeding preterm infants with protein hydrolysate versus standard formula. The existing data did not support conclusions that feeding with protein hydrolysate affects the risk of feed intolerance or necrotising enterocolitis. Further large, pragmatic trials are needed to provide more reliable and precise estimates of effectiveness and cost-effectiveness.

UI MeSH Term Description Entries
D007230 Infant, Low Birth Weight An infant having a birth weight of 2500 gm. (5.5 lb.) or less but INFANT, VERY LOW BIRTH WEIGHT is available for infants having a birth weight of 1500 grams (3.3 lb.) or less. Low Birth Weight,Low-Birth-Weight Infant,Birth Weight, Low,Birth Weights, Low,Infant, Low-Birth-Weight,Infants, Low-Birth-Weight,Low Birth Weight Infant,Low Birth Weights,Low-Birth-Weight Infants
D007231 Infant, Newborn An infant during the first 28 days after birth. Neonate,Newborns,Infants, Newborn,Neonates,Newborn,Newborn Infant,Newborn Infants
D007234 Infant, Premature A human infant born before 37 weeks of GESTATION. Neonatal Prematurity,Premature Infants,Preterm Infants,Infant, Preterm,Infants, Premature,Infants, Preterm,Premature Infant,Prematurity, Neonatal,Preterm Infant
D008892 Milk The off-white liquid secreted by the mammary glands of humans and other mammals. It contains proteins, sugar, lipids, vitamins, and minerals. Cow Milk,Cow's Milk,Milk, Cow,Milk, Cow's
D011492 Protein Hydrolysates A complex mixture of OLIGOPEPTIDES, PEPTIDES, and free AMINO ACIDS that are produced by partial or extensive hydrolysis. Protein Hydrolysate,Hydrolysate, Protein,Hydrolysates, Protein
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000073923 Food Intolerance Digestive system disorder where a particular food irritates the digestive tract or cannot be properly digested (i.e., due to a lack of a digestive enzyme). It differs from FOOD HYPERSENSITIVITY which is an immune system disorder, usually due to specific proteins in food. http://my.clevelandclinic.org/health/articles/problem-foods-is-it-an-allergy-or-intolerance. Food, Sensitivity,Intolerance, Food
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016032 Randomized Controlled Trials as Topic Works about clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Clinical Trials, Randomized,Controlled Clinical Trials, Randomized,Trials, Randomized Clinical
D041943 Infant Formula Formulations for the nutrition of infants that are substituted for BREAST MILK. Baby Formula,Baby Formulas,Formula, Baby,Formula, Infant,Formulas, Baby,Formulas, Infant,Infant Formulas

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