Lactase treated feeds to promote growth and feeding tolerance in preterm infants

Very low birth weight preterm infants are often fed through a tube into a vein (parenterally) as adequate growth and nutrition is important for lung and brain development. Early feeding via the gut (enterally) stimulates motility and digestive activity and is associated with improved growth, but this is not always possible. Lactase is an intestinal enzyme that helps digest milk and is slow to develop in preterm infants after birth. Breast milk contains components that help with lactose digestion. Lactose intolerance is often managed in infants born at term with low-lactose or lactose-free formulas, but these do not fulfil the nutrition requirements for preterm infants. Feeding intolerance leaves residual feeds in the stomach prior to the next scheduled feeding and causes abdominal distension, bile stained fluid in the lungs (aspirates), and vomiting. Preparations of lactase could potentially be added to formula or breast milk for preterm infants. There was not a significant effect on weight gain in the one randomized controlled trial identified that investigated addition of lactase. The review authors searched the medical literature thoroughly but found only this one high quality trial enrolling 130 preterm infants. No adverse effects were noted and lactase treated feeds appeared to be well tolerated.

Authors' conclusions: 

The only randomized trial to date provides no evidence of significant benefit to preterm infants from adding lactase to their feeds. Further research regarding effectiveness and safety are required before practice recommendations can be made. Randomized controlled trials comparing lactase versus placebo treated feeds and enrolling infants when enteral feeds are introduced are required. The primary and secondary outcomes for effectiveness and safety should include those identified in this review.

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Background: 

Successful transition from parenteral nutrition to full enteral feedings during the immediate neonatal period is associated with improved growth in preterm infants. Lactase is the last of the major intestinal disaccharidases to develop in preterm infants. Because of inadequate lactase activity, preterm infants are unable to digest lactose. Lactase preparations could potentially be used to hydrolyse lactose in formulas and breast milk to minimize lactose malabsorption in preterm infants.

Objectives: 

To assess the effectiveness and safety of the addition of lactase to milk compared to placebo or no intervention for the promotion of growth and feeding tolerance in preterm infants.

Primary outcomes: weight gain expressed as grams/kg/day, growth expressed as weight, length and head circumference percentile for postmenstrual age (PMA), assessed at birth and at 40 weeks PMA, days to achieve full enteral feeds. Secondary outcomes: several common outcomes associated with preterm birth, and adverse effects.

Search strategy: 

Electronic and manual searches were conducted in January 2005 of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2004, Issue 4), MEDLINE (1966 to Jan 2005), EMBASE (1980 to Jan 2005) and CINAHL (1982 to Jan 2005), personal files, bibliographies of identified trials and abstracts by the Pediatric Academic Societies' Meetings and the European Society of Pediatric Research Meetings published in Pediatric Research. The searches were repeated in May 2012 of The Cochrane Library, MEDLINE, EMBASE and CINAHL and abstracts from the Pediatric Academic Societies' Annual Meetings from 2000 to 2012 (Abstracts2View). The Web of Science was searched using the only previously identified trial by Erasmus 2002 as the starting point to search for additional trials that cited this trial.

Selection criteria: 

Types of studies: randomized or quasi-randomized controlled trials. Participants: preterm infants < 37 weeks PMA. Intervention: addition of lactase to milk versus placebo or no intervention.

Data collection and analysis: 

The standard methods of the Cochrane Neonatal Review Group were followed independently by the review authors to assess study quality and report outcomes. Treatment effects, calculated using Review Manager 5, included risk ratio (RR), risk difference (RD) and mean difference (MD), all with 95% confidence intervals (CI). A fixed-effect model was used for meta-analyses. We did not perform heterogeneity tests as only one study was identified.

Main results: 

The repeat searches conducted in May 2012 did not identify any additional studies for inclusion. One study enrolling 130 infants of 26 to 34 weeks PMA (mean postnatal age at entry 11 days) was identified and no identified study was excluded. The study was a double blind randomized controlled trial of high quality. Lactase treated feeds were initiated when enteral feedings provided > 75% of daily intake. None of the primary outcomes outlined in the protocol for this review and only one of the secondary outcomes, necrotizing enterocolitis (NEC) were reported on. The RR for NEC was 0.32 (95% CI 0.01 to 7.79); the RD was -0.02 (95% CI -0.06 to 0.03) (a reduction which was not statistically significant). There was a statistically significant increase in weight gain at study day 10 in the lactase treated feeds group but not at any other time points. Overall, there was not a statistically significant effect on weight gain. No adverse effects were noted.

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