High versus low medium chain triglyceride content of formula for promoting short-term growth of preterm infants.

Abstract

BACKGROUND\nIn-hospital growth of preterm infants remains a challenge in clinical practice. The high nutrient demands of preterm infants often lead to growth faltering.\xa0For preterm infants who cannot be fed maternal or donor breast\xa0milk or may require supplementation, preterm formulas with fat in the form of medium chain triglycerides (MCTs)\xa0or long chain triglycerides (LCTs)\xa0may be chosen to support nutrient utilization and to improve growth.\xa0MCTs are easily accessible to the preterm infant with an immature digestive system, and LCTs are beneficial for central nervous\xa0system development and visual function. Both have been incorporated into preterm formulas in varying amounts, but their effects on the preterm infant s short-term growth remain unclear. This is an update of a review originally published in 2002, then in 2007.\n\n\nOBJECTIVES\nTo determine the effects of formula containing high as opposed to low MCTs on early growth in preterm infants fed a diet consisting primarily of formula.\xa0 SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 8), in the Cochrane Library; Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, and Ovid MEDLINE(R); MEDLINE via PubMed for the previous year; and Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 16 September 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-RCTs.\n\n\nSELECTION CRITERIA\nWe included all randomized and quasi-randomized trials comparing the effects of feeding high versus low MCT formula (for a minimum of five days) on the short-term growth of preterm (< 37 weeks gestation) infants. We defined high MCT formula as 30% or more by weight, and low MCT formula as less than 30% by weight. The infants must be on full enteral diets, and the allocated formula must be the predominant source of nutrition.\n\n\nDATA COLLECTION AND ANALYSIS\nThe review authors assessed each study s quality and extracted data on growth parameters as well as adverse effects from included studies. All data used in analysis were continuous; therefore, mean differences with 95% confidence intervals were reported. We used the GRADE approach to assess the certainty of evidence.\n\n\nMAIN RESULTS\nWe identified 10 eligible trials\xa0(253\xa0infants) and extracted relevant growth data from 7 of these trials (136 infants). These studies were found to provide evidence of very low to low certainty. Risk of bias was noted, as few studies described specific methods for random sequence generation, allocation concealment, or\xa0blinding.\xa0We found no evidence of differences in short-term growth parameters when high and low MCT formulas were compared. As compared to low MCT formula, preterm infants fed high MCT formula showed little to no difference in weight gain velocity (g/kg/d) during the intervention, with a typical mean difference (MD) of -0.21\xa0g/kg/d (95% confidence interval (CI) -1.24 to 0.83; 6 studies, 118 infants; low-certainty evidence). The analysis for weight gain (g/d) did not show evidence of differences, with an MD of 0.00 g/d\xa0(95% CI -5.93 to 5.93;\xa01 study,\xa018 infants;\xa0very low-certainty evidence),\xa0finding an average weight gain of 20\xa0±\xa05.9 versus 20\xa0±\xa06.9 g/d for high and low MCT groups, respectively.\xa0We found that length gain showed\xa0no difference between low and high MCT formulas, with a typical MD of 0.10\xa0cm/week (95% CI -0.09 to 0.29; 3 studies, 61 infants; very low-certainty evidence).\xa0Head circumference gain also showed little to no difference during the intervention period, with an MD of\xa0-0.04 cm/week (95% CI -0.17 to\xa00.09; 3 studies, 61 infants; low-certainty evidence). Two studies reported skinfold thickness with different measurement definitions, and evidence was insufficient to determine if there was a difference\xa0(2\xa0studies, 32\xa0infants; very low-certainty evidence).\xa0There are conflicting data (5\xa0studies) as to formula tolerance, with 4 studies reporting narrative results of\xa0no observed clinical difference and 1 study reporting higher incidence of signs of\xa0gastrointestinal intolerance\xa0in high MCT formula groups.\xa0There is no evidence of effect on the incidence of\xa0necrotizing\xa0enterocolitis\xa0(NEC), based on small numbers in two trials.\xa0Review authors found no studies addressing\xa0long-term growth parameters or neurodevelopmental outcomes.\n\n\nAUTHORS CONCLUSIONS\nWe found evidence of very low to low\xa0certainty suggesting no differences among short-term growth data for infants fed\xa0low versus\xa0high MCT formulas. Due to lack of evidence and uncertainty, neither formula type could be concluded to improve short-term growth outcomes or have fewer\xa0adverse effects. Further studies are necessary because the results from included\xa0studies are imprecise due to small numbers and do not address important long-term outcomes. Additional research should aim to clarify effects on formula tolerance and on long-term growth and neurodevelopmental outcomes, and should include larger study populations to better evaluate effect on NEC incidence.