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

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 = 52, control n = 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.

Individualized Postnatal Growth Trajectories for Preterm Infants.

BACKGROUND: Growth of preterm infants is monitored using fetal charts despite individual trajectories being downshifted postnatally by adaptational processes. The study aims to compare different approaches to create individualized postnatal trajectories. METHODS: Three approaches to achieve growth similar to healthy term infants at 42+0/7 weeks postmenstrual age (PMA) on World Health Organization growth standards (WHOGS) (target weight) were tested by comparing trajectories obtained by: 1) following birth percentiles (Birth-Weight-Percentile Approach); 2) following percentiles achieved at day of life 21 (Postnatal-Percentile Approach); 3) using day-specific fetal median growth velocities starting at day of life 21 (Fetal-Median-Growth Approach [FMGA]). The primary outcome was delta weight (ΔW), defined as difference between target weight (WHOGS) at 42+0/7 weeks and weight predicted by trajectories. The secondary outcome was ΔW vs %fat mass in a cohort of 20 disease-free surviving very low-birth-weight infants. RESULTS: Birth-Weight-Percentile and Postnatal-Percentile Approach showed high ΔW; FMGA alone reduced ΔW. Introducing a factor to FMGA to reflect the transition to extrauterine conditions (Growth-Velocity Approach [GVA]) minimized ΔW. GVA merged with target and best normalized for body composition related to ΔW. CONCLUSIONS: GVA provides an evidence-based approach for individualized growth trajectories. GVA is based on physiologic data and that healthy preterm infants adjust their postnatal trajectory below their birth percentile. GVA may reflect a biologic principle because it matches consistently with WHOGS at 42+0/7 weeks for all preterm infants from 24 to 34 weeks. This concept could become a bedside tool to aid clinicians in monitoring growth, guiding nutrition, and minimizing chronic adult disease risks as a consequence of unguided, inappropriate growth.

Target fortification of breast milk: how often should milk analysis be done?

Target fortification (TFO) reduces natural macronutrient variation in breast milk (BM). Daily BM analysis for TFO increases neonatal intensive care unit work load by 10-15 min/patient/day and may not be feasible in all nurseries. The variation of macronutrient intake when BM analysis is done for various schedules was studied. In an observational study, we analyzed 21 subsequent samples of native 24-h BM batches, which had been prepared for 10 healthy infants (gestational age 26.1 ± 1.3 weeks, birth weight: 890 ± 210 g). Levels of protein and fat (validated near-infrared milk analyzer), as well as lactose (UPLC-MS/MS) generated the database for modelling TFO to meet recommendations of European Society for Paediatric Gastroenterology Hepatology and Nutrition. Intake of macronutrients and energy were calculated for different schedules of BM measurements for TFO (n = 1/week; n = 2/week; n = 3/week; n = 5/week; n = 7/week) and compared to native and fixed dose fortified BM. Day-to-day variation of macronutrients (protein 20%, carbohydrate 13%, fat 17%, energy 10%) decreased as the frequency of milk analysis increased and was almost zero for protein and carbohydrate with daily measurements. Measurements two/week led to mean macronutrient intake within a range of ± 5% of targeted levels. A reduced schedule for macronutrient measurement may increase the practical use of TFO. To what extent the day-to-day variation affects growth while mean intake is stable needs to be studied.