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TARGET FORTIFICATION OF BREAST MILK WITH PROTEIN, CARBOHYDRATE, AND FAT FOR PRETERM INFANTS IMPROVES GROWTH OUTCOMES: A DOUBLE-BLIND RANDOMIZED CONTROLLED TRIAL / TARGET FORTIFICATION FOR PRETERM INFANTS

Background: Breast milk is an ideal source of nutrition for newborns as it provides nutrients required for growth in addition to numerous bioactive factors which help to develop an infant’s immune system. However, the macronutrient content of breast milk alone is not able to support preterm infant’s rapid growth needs and requires supplementation with fortifiers. There is strong evidence that the current practice of standard fortification (SF) may lead to nutritional deficits and consequently increases an infant’s risk of inadequate postnatal growth. Furthermore, the natural variation of breast milk composition makes it increasingly difficult to provide recommended macronutrient intakes with the SF. Individualized approaches, like adjustable fortification or target fortification (TFO), have been proposed to improve growth during hospitalization. A recent pilot trial demonstrated that TFO, which individually adjusts deficient macronutrient content after SF by analyzing the breast milk for native protein, carbohydrate and fat, is feasible in clinical practice and significantly reduces variation of macronutrient intakes.
Objectives: To compare the response of preterm infants to feedings of breast milk with either SF or SF+TFO with respect to: 1) weight at 36 weeks’ post-menstrual age and growth velocity during hospitalization; 2) head circumference, length and body composition; and 3) the relationship between preterm infant’s weight or growth velocity and their macronutrient intake factors including protein intake and protein:energy (P:E) ratio.
Methods: This was a single-center, double-blind randomized controlled trial completed at McMaster Children’s Hospital’s Level III NICU with a study period of at least 21 days. Preterm infants (n=103) born at <30 weeks of gestation and tolerating full enteral intakes of breast milk were enrolled and randomized to the Control (SF only) or Intervention (SF+TFO) groups. Native breast milk samples were collected for all infants on each study day and were analyzed for protein, carbohydrate and fat content. In the Control group, SF was provided using Enfamil (Mead Johnson, IL) human milk fortifier at the recommended dosage. In the Intervention group, after the addition of SF, modular macronutrient fortifiers were added based on analysis of the mother’s milk to reach target values based on ESPGHAN recommendations. Adjustment of the modular fortifiers was done three times per week. The primary outcomes were weight at 36 weeks’ PMA and growth velocity during the study period. Head circumference, length and body composition were also assessed at term-equivalent age. Subgroup analysis, stratified around the median protein levels after SF, also compared the growth outcomes between Control and Intervention groups. Multiple regression analysis models examined the effect of macronutrient intake factors and infant characteristics on weight, average growth velocity and daily weight gain.
Results: Infants fed with SF+TFO had significantly higher protein (p<0.001), carbohydrate (p<0.001) and fat intakes (p<0.01) in addition to higher protein:energy and carbohydrate:non-protein energy (CHO:NPE) ratios (p<0.001) compared to those fed with SF alone. The average weight at 36 weeks’ PMA and growth velocity during the 21-day study period were higher for infants in the Intervention group (p<0.001). The Intervention group had significantly higher fat-mass (p<0.05) as well as more fat-free mass than the Control group at term-equivalent age (TEA), but were still within normal limits when compared to normative data from our NICU. At TEA, infants fed with TFO also showed significantly higher change in z-scores from birth for length when compared to infants fed SF with low-protein intakes (p<0.05). Change in head circumference z-scores were not statistically significant between groups. Higher average protein intakes and P:E ratios were each positively associated with higher weight at 36 weeks’ PMA (p<0.05). Moreover, higher daily weight gain was positively associated with higher daily protein intake from the previous study day (p<0.05). The absolute difference in day-to-day macronutrient intakes, however, were not significant predictors of daily weight gain.
Conclusions: This study shows that target fortification of breast milk is promising as an individualized approach to improve the quality of nutrition for preterm infants. By addressing the variation and deficits of macronutrients that occur after standard fortification, infants were able to achieve higher body weight and faster weight gain. In the short term, target fortification may reduce the preterm infant’s risk for sub-optimal postnatal growth. These improved growth outcomes also have positive clinical implications on infant’s long-term health and development. Protein intake and the P:E ratio were identified as important factors for growth and should be considered in nutritional management and future fortification strategies for breast milk fed preterm infants. / Thesis / Master of Science (MSc)

Identiferoai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/22123
Date January 2017
CreatorsBhatia, Akshdeep S
ContributorsFusch, Christoph, Medical Sciences
Source SetsMcMaster University
LanguageEnglish
Detected LanguageEnglish
TypeThesis

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