Individualized target fortification of breast milk with protein, carbohydrates, and fat for preterm infants: A double-blind randomized controlled trial

Abstract

Background & aims: In preterm infants, natural variation of breast milk composition makes it difficult to achieve recommended macronutrient intakes with standard fortification. Evidence suggests that nutritional deficiency induces poor postnatal growth. This study investigates impacts of target fortification on preterm growth and metabolism by adjusting breast milk macronutrients. Methods: This study was conducted as a single-centre, double-blind, randomized controlled trial for infants <30 gestational weeks. The control group received standard fortification and the intervention group received standard plus target fortification adding modular protein, lipids, and carbohydrates. Breast milk content was measured 3x/week using a validated near-infrared bedside spectrometer (NIRS). Modulars were added to achieve recommended values. To assess total nutrient intake, all 2810 native breast milk samples were analyzed -protein and fat using bedside-NIRS, lactose using tandem mass spectrometry (UPLC-MS/MS). Body composition was measured using air displacement plethysmography. Primary outcome was weight gain during the first 21 days of intervention. Results: Baseline characteristics, morbidities, and total fluid intake were not different between groups (intervention n ¼ 52, control n ¼ 51). The intervention group infants had higher macronutrient intakes, weight gain (21.2 ± 2.5 vs 19.3 ± 2.4 g/kg/d, mean difference: 1.9 g/kg/d, 95% CI: 0.9 -2.9), and body weight. Infants in the intervention group from mothers with below-average breast milk protein content showed greatest impact on weight at 36 weeks (2580 ± 280 g vs 2210 ± 300 g), length, head circumference, fat, and fat-free mass. Also, feeding intolerance was less frequent, blood urea was higher, and triglycerides were lower. Conclusions: This study provides evidence that target fortification of breast milk with low macronutrient content enhances the quality of nutrition and growth and is feasible in clinical routine.

Growth Benefits of Own Mother’s Milk in Preterm Infants Fed Daily Individualized Fortified Human Milk

“…Improving HM fortification by IHMF through the use of infrared technology and extra protein and energy supplementation may be one of the strategies to optimize the nutritional composition of HM to meet the nutritional needs of preterm infants, especially when DM is used. It was demonstrated that IHMF decreases the variability linked to HM content and safely optimizes protein and energy intake [19,21,49,50]. Premature infants fed with low macronutrient content HM benefit the most from IHMF, with improved growth outcomes.…”

Avoiding Postnatal Growth Retardation by Individualized Fortification of Breast Milk: Implications for Somatic and Neurodevelopmental Outcomes

“…Preliminary findings from a larger randomized controlled trial evaluating individualized target fortification in preterm infants suggest that individualized fortification improved intake of fat, protein, and carbohydrates compared with standard fortification. 9 Target fortification also increased caloric intake and improved growth outcomes, such as weight gain and growth velocity. The impact on growth was most pronounced in a subgroup of infants who received breast milk with a lower protein content than average (Fig.…”

Optimizing Early Neonatal Nutrition and Dietary Pattern in Premature Infants

“…Instead, growth rates similar to intrauterine trajectories can be achieved by rapid increases in enteral feeding volume and by achieving full enteral nutrition within 5–7 days of birth even in extremely low gestational age neonates [ 48 , 49 ]. However, even if weight gain along intra-uterine trajectories is achieved, very preterm infants still show insufficient lean body mass growth and an increased fraction of body fat at term-equivalent age [ 52 , 53 ]. This can be interpreted as a lack of essential nutrients required to achieve parenchymal and muscle mass growth as in utero [ 54 ].…”

“…In a recent review including 7 RCTs with a total of 521 participants, increased growth rates for weight, length and head circumference were found with moderate to low evidence following individualized compared to standard non-individualized fortification [ 35 ]. In 2021, a double-blind, randomized controlled trial was conducted in 103 preterm infants <30 weeks comparing standard versus targeted fortification with modular proteins, lipids, and carbohydrates [ 52 ]. The targeted fortification group had higher macronutrient intakes and higher average growth velocity across the first 21 days of intervention (21.2 ± 2.5 vs. 19.3 ± 2.4 g/kg/d).…”

“…The targeted fortification group had higher macronutrient intakes and higher average growth velocity across the first 21 days of intervention (21.2 ± 2.5 vs. 19.3 ± 2.4 g/kg/d). Not surprisingly, infants born to mothers with a low breast milk protein content showed the greatest benefit from targeted fortification regarding their weight at 36 weeks, length, head circumference, fat and fat-free mass [ 52 ]. Likewise, donor milk often contains low levels of protein, suggesting targeted fortification to improve growth [ 75 , 76 ].…”