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1.
Optimizing individual nutrition in preterm very low birth weight infants: double-blinded randomized controlled trial.
Brion, LP, Rosenfeld, CR, Heyne, R, Brown, LS, Lair, CS, Petrosyan, E, Jacob, T, Caraig, M, Burchfield, PJ
Journal of perinatology : official journal of the California Perinatal Association. 2020;(4):655-665
Abstract
OBJECTIVE In preterm neonates fed human milk, fortification may be adjusted by (1) optimization, based on growth rate and serum nutrient analyses, or (2) individualization, based on serial milk nutrient analyses. The primary aim was to determine whether individualized plus optimized nutrition (experimental) improves velocity of weight gain and linear growth from birth to endpoint (36 weeks postmenstrual age or discharge) when compared with optimized nutrition alone (controls). STUDY DESIGN Double-blinded parallel group randomized trial in 120 neonates <29 weeks gestational age (GA) or <35 weeks and small for GA (birth weight < 10th centile). RESULT Weight-gain velocity (13.1 ± 2.1, n = 57 controls, vs. 13.0 ± 2.6 g kg-1 day-1, n = 59 experimental, P = 0.87), linear growth (0.9 ± 0.2, n = 55, vs. 0.9 ± 0.2 cm week-1, n = 52, P = 0.90) and frequency of weight/length disproportion (2% vs. 2%, P = 0.98) were similar in both groups. CONCLUSIONS Individualized plus optimized nutrition does not improve weight gain, linear growth, or weight/length disproportion at endpoint versus optimized nutrition alone.
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2.
Individualized Human Milk Fortification to Improve the Growth of Hospitalized Preterm Infants.
Quan, M, Wang, D, Gou, L, Sun, Z, Ma, J, Zhang, L, Wang, C, Schibler, K, Li, Z
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2020;(4):680-688
Abstract
BACKGROUND Human milk (HM) is the first choice for preterm infants, but exclusive HM feeding is inadequate for the growth of very preterm infants. The hypothesis of this trial is that infants fed according to an individualized fortification regimen will have higher protein intake and improved weight gain velocity (WGV). METHODS A prospective, randomized, controlled study was conducted. Infants <34 weeks of gestational age were enrolled when enteral feeding volume reached 60 mL/kg/d and were randomly allocated to the individualized fortification (IF) group or the standard fortification group. The IF group was fed using a regimen that featured modifying HM fortifier and supplemental protein powder based on the protein concentration in HM, current body weight of infants, and blood urea nitrogen (fortification level was set as L-1, L0, L1, L2, L3; the amount of HM fortifier and protein powder were determined accordingly). RESULTS Between September 2012 and August 2016, 51 preterm infants completed the study. In the IF group, 62.5% (15/24) of preterm infants were fed with HM fortified to level 1, 29.2% (7/24) to level 2, and 12.5% (3/24) to level 3. The WGV of the third week in the IF group was greater than the standard group (20.8 ± 7.9 vs 14.9 ± 4.5 g/kg/d, P = 0.022). CONCLUSION About two-thirds of preterm infants needed to adjust the HM fortification to a higher level. The WGV of infants in the IF group was better than that of the standard group in the third week of this study.
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Human milk oligosaccharides and their association with late-onset neonatal sepsis in Peruvian very-low-birth-weight infants.
Torres Roldan, VD, Urtecho S, M, Gupta, J, Yonemitsu, C, Cárcamo, CP, Bode, L, Ochoa, TJ
The American journal of clinical nutrition. 2020;(1):106-112
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Abstract
BACKGROUND Oligosaccharides are the third most abundant component in human milk. They are a potential protective agent against neonatal sepsis. OBJECTIVES We aimed to explore the association between human milk oligosaccharides (HMOs) and late-onset sepsis in very-low-birth-weight infants, and to describe the composition and characteristics of HMOs in Peruvian mothers of these infants. METHODS This is a secondary data analysis of a randomized clinical trial. We conducted a retrospective cohort study of mothers and their very-low-birth-weight (<1500 g) infants with ≥1 milk sample and follow-up data for >30 d. HMOs were measured by high performance liquid chromatography (HPLC). We used factor analysis and the Mantel-Cox test to explore the association between HMOs and late-onset neonatal sepsis. RESULTS We included 153 mother-infant pairs and 208 milk samples. Overall, the frequency of the secretor phenotype was 93%. Secretors and nonsecretors were defined by the presence and near-absence of α1-2-fucosylated HMOs, respectively. The most abundant oligosaccharides were 2'-fucosyllactose, lacto-N-fucopentaose (LNFP) I, and difucosyllacto-N-tetraose in secretors and lacto-N-tetraose and LNFP II in nonsecretors. Secretors had higher amounts of total oligosaccharides than nonsecretors (11.45 g/L; IQR: 0.773 g/L compared with 8.04 g/L; IQR: 0.449 g/L). Mature milk samples were more diverse in terms of HMOs than colostrum (Simpson's Reciprocal Diversity Index). We found an association of factor 3 in colostrum with a reduced risk of late-onset sepsis (HR: 0.63; 95% CI: 0.41, 0.97). Fucosyl-disialyllacto-N-hexose (FDSLNH) was the only oligosaccharide correlated to factor 3. CONCLUSIONS These findings suggest that concentrations of different HMOs vary from one individual to another according to their lactation period and secretor status. We also found that FDSLNH might protect infants with very low birth weight from late-onset neonatal sepsis. Confirming this association could prove 1 more mechanism by which human milk protects infants against infections and open the door to clinical applications of HMOs.This trial was registered at clinicaltrials.gov as NCT01525316.
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Effects of Targeted Versus Adjustable Protein Fortification of Breast Milk on Early Growth in Very Low-Birth-Weight Preterm Infants: A Randomized Clinical Trial.
Bulut, O, Coban, A, Uzunhan, O, Ince, Z
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2020;(2):335-343
Abstract
BACKGROUND Breast milk is preferred for the feeding of very low-birth-weight (VLBW) infants, but it does not meet nutrition requirements unless it is fortified. Adequate protein intake to maintain the growth of preterm infants cannot be provided by standard fortification methods because of variation in the protein content of human milk. Individualization is necessary to achieve target protein intakes. The goal of this study was to compare the effects of 2 different methods of individualized protein fortification of breast milk on the early growth of VLBW preterm infants. METHODS In a prospective observational study, VLBW preterm infants ≤32 weeks of gestational age were randomized into 2 groups according to the method of breast milk fortification. Anthropometric measurements were performed in both groups weekly for 4 weeks to compare their growth. RESULTS During the trial period, the daily protein intake (targeted vs adjustable fortification groups) was (median [range]) 4.5 (4.4-4.6) vs 4.01 (3.5-4.4) g/kg/d (P = 0.001); the daily weight gains (g/d and g/kg/d; mean ± SD) were 25.7 ± 3.9 vs 22.2 ± 6.4 g/d (P = 0.048) and 23.1 ± 4.3 vs 18.7 ± 4.3 g/kg/d (P = 0.014); and the weekly increase in head circumference was 9.8 ± 1.5 vs 8.4 ± 2.1 mm/wk (P = 0.040). All parameters were significantly higher in the targeted than the adjustable fortification group. CONCLUSIONS Individualized protein fortification using the targeted method for VLBW preterm infants had more positive effects on short-term growth compared with the adjustable fortification method.
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Effects of a nutrient-dense formula compared with a post-discharge formula on post-discharge growth of preterm very low birth weight infants with extrauterine growth retardation: a multicentre randomised study in China.
Yu, MX, Zhuang, SQ, Gao, XY, Tong, XM, Yue, SJ, Shi, LP, Chen, DM, Liang, K
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2020;(4):557-565
Abstract
BACKGROUND Post-discharge optimal growth and nutritional intake have beneficial effects for neurodevelopment in preterm very low birth weight infants (VLBWIs) with extrauterine growth retardation (EUGR). The present study aimed to compare the effects of a nutrient-dense formula (NDF) to a post-discharge formula (PDF) on post-discharge growth of preterm VLBWIs with EUGR. METHODS Forty-eight preterm VLBWIs with EUGR at discharge were randomised to receive NDF (100 kcal per 100 mL; 2.6 g protein per 100 mL) or PDF (74 kcal per 100 mL; 1.95 g protein per 100 mL) for 1-6 months until body weight reached the 50th percentile on growth charts with corrected age. Volume, nutrient intake, anthropometry and biochemistry data were collected. RESULTS Volume intake was lower in the NDF group than the PDF group during the first 2 months of feeding (P = 0.039 and 0.018, respectively).There were no significant differences in volume intake during months 2-6 of feeding. Energy, protein, carbohydrate and fat intake were higher in the NDF group during months 1-6 of feeding. There were no significant differences in weight, length, and head circumference Z-scores during months 1-6 between the two groups. The △length Z-score from discharge to month 6 was significantly higher in the NDF group than the PDF group (P = 0.043). No differences existed between the two groups with respect to biochemistry. CONCLUSIONS After discharge, preterm VLBWIs with EUGR fed a NDF gain anthropometric parameter Z-scores similar to those for a PDF within 6 months of follow-up. A NDF leading to gain in length requires further follow-up.
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Postnatal N‑acetylcysteine does not provide neuroprotection in extremely low birth weight infants: A follow-up of a randomized controlled trial.
Kiuru, A, Ahola, T, Klenberg, L, Tommiska, V, Lano, A, Kleemola, P, Haavisto, A, Fellman, V
Early human development. 2019;:13-17
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Influence of Parenteral Nutrition Delivery Techniques on Growth and Neurodevelopment of Very Low Birth Weight Newborns: A Randomized Trial.
Aldakauskienė, I, Tamelienė, R, Marmienė, V, Rimdeikienė, I, Šmigelskas, K, Kėvalas, R
Medicina (Kaunas, Lithuania). 2019;(4)
Abstract
Background and Objectives: In very low birth weight (VLBW) newborns, parenteral nutrition (PN) is delivered via a peripheral venous catheter (PVC), a central venous catheter (CVC), or a peripherally inserted central venous catheter (PICC). Up to 45% of PICCs are accompanied by complications, the most common being sepsis. A PVC is an unstable PN delivery technique requiring frequent change. The growth and neurodevelopment of VLBW newborns may be disturbed because of catheters used for early PN delivery and complications thereof. The aim of the conducted study was to evaluate the effect of two PN delivery techniques (PICC and PVC) on anthropometric parameters and neurodevelopment of VLBW newborns. Materials and Methods: A prospective randomized clinical trial was conducted in VLBW (≥750⁻<1500 g) newborns that met the inclusion criteria and were randomized into two groups: PICC and PVC. We assessed short-term outcomes (i.e., anthropometric parameters from birth until corrected age (CA) 36 weeks) and long-term outcomes (i.e., anthropometric parameters from CA 3 months to 12 months as well as neurodevelopment at CA 12 months according to the Bayley II scale). Results: In total, 108 newborns (57 in the PICC group and 51 in the PVC group) were randomized. Short-term outcomes were assessed in 47 and 38 subjects, and long-term outcomes and neurodevelopment were assessed in 38 and 33 subjects of PICC and PVC groups, respectively. There were no differences observed in anthropometric parameters between the subjects of the two groups in the short- and long-term. Mental development index (MDI) < 85 was observed in 26.3% and 21.2% (p = 0.781), and psychomotor development index (PDI) < 85 was observed in 39.5% and 54.5% (p = 0.239) of PICC and PVC subjects, respectively. Conclusions: In the short- and long-term, no differences were observed in the anthropometric parameters of newborns in both groups. At CA 12 months, there was no difference in neurodevelopment in both groups.
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Neurodevelopment of children born very preterm and/or with a very low birth weight: 8-Year follow-up of a nutritional RCT.
Ruys, CA, Bröring, T, van Schie, PEM, van de Lagemaat, M, Rotteveel, J, Finken, MJJ, Oostrom, KJ, Lafeber, HN
Clinical nutrition ESPEN. 2019;:190-198
Abstract
BACKGROUND Children born very preterm are at risk for cognitive deficits and motor impairment. Enhanced protein intake immediately after very preterm birth has been associated with favorable growth and improved neurodevelopment. It is unknown whether increased protein intake after discharge from the hospital affects long-term neurodevelopment. OBJECTIVE The primary objective was to assess neurodevelopment from infancy to 8 years in preterm-born children who received either protein-enriched formula (PDF), standard term formula (TF), or human milk (HM) after discharge. The secondary objective was to assess the correlation between outcomes obtained at 24 months corrected age (CA) and at 8 years. METHODS This RCT included 152 children born very preterm (gestational age ≤32 weeks) and/or with a very low birth weight (≤1500 g) of whom 102 were randomly assigned to receive PDF (n = 54) or TF (n = 48) from term age to 6 months CA. A control group of infants fed HM (n = 50) was also included. Neurodevelopmental outcomes were assessed at 24 months CA (cognitive and motor functioning; n = 123) and at 8 years (estimated Full Scale Intelligence Quotient, visual-motor skills, verbal memory, attention, and motor functioning; n = 76). RESULTS The PDF and TF groups were not significantly different in neurodevelopmental outcomes. The HM group had a better cognitive score compared with the PDF group: at 24 months CA 92.9 ± 12.5 vs. 105.2 ± 18.6, P < 0.001 and at 8 years 98.1 ± 11.3 vs. 105.8 ± 9.1, P = 0.017 (P = 0.002 and P = 0.080, respectively, after adjustment for parental educational level). Correlations between outcomes at 24 months CA and 8 years were weak: r = 0.35 and r = 0.37 for cognitive and motor outcomes, respectively. CONCLUSIONS PDF did not improve long-term neurodevelopmental outcomes as compared with TF. However, these results should be interpreted with caution considering the substantial attrition at follow-up. Furthermore, the correlation between outcomes at different ages was weak, emphasizing the need for long-term follow-up of nutritional intervention studies in preterm-born children.
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Cost-Effectiveness of Supplemental Donor Milk Versus Formula for Very Low Birth Weight Infants.
Trang, S, Zupancic, JAF, Unger, S, Kiss, A, Bando, N, Wong, S, Gibbins, S, O'Connor, DL, ,
Pediatrics. 2018;(3)
Abstract
OBJECTIVES To determine the cost-effectiveness of supplemental donor human milk (DHM) versus preterm formula (PTF) for very low birth weight (VLBW, <1500 g) infants from a societal perspective to 18 months' corrected age. METHODS This prospective cost-effectiveness analysis of 363 VLBW infants was conducted for a randomized control trial. Infants recruited from October 2010 to December 2012 were fed DHM or PTF whenever mother's milk was unavailable. Formal health care costs for initial hospitalization and readmissions were obtained from standardized cost-accounting systems and physician fees. Informal and nonhealth care sector costs (eg, caregiver transportation, labor market earnings) were calculated from parent reports. RESULTS Mean infant birth weight was 996 (SD, 272) grams. Incidence of necrotizing enterocolitis (NEC) differed between groups (all stages 3.9% DHM, 11.0% PTF; P = .01). Costs to 18 months did not differ with a mean (95% confidence interval) of 217 624 (197 697-237 551) and 217 245 (196 494-237 995) 2015 Canadian dollars in the DHM and PTF groups. Postdischarge costs were lower in the DHM (46 440 [40 648-52 233]) than PTF group (55 102 [48 269-61 934]) (P = .04), driven by parent lost wages. DHM cost an additional $5328 per case of averted NEC. CONCLUSIONS In a high mother's milk use setting, total costs from a societal perspective to 18 months of providing supplemental DHM versus PTF to VLBW infants did not differ, although postdischarge costs were lower in the DHM group. Although supplemental DHM was not cost-saving, it reduced NEC supporting its use over PTF.
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Effect of Differential Enteral Protein on Growth and Neurodevelopment in Infants <1500 g: A Randomized Controlled Trial.
Dogra, S, Thakur, A, Garg, P, Kler, N
Journal of pediatric gastroenterology and nutrition. 2017;(5):e126-e132
Abstract
OBJECTIVE The aim of the study was to determine whether higher enteral protein intake leads to improved head growth at 40 weeks postmenstrual age (PMA) in preterm infants <32 weeks or 1500 g. METHODS Randomized controlled trial in which 120 infants were assigned to either group A with higher enteral protein intake achieved by fortification with higher protein containing fortifier (1 g/100 mL expressed breast milk) or to group B with lower enteral protein intake where fortification was done with standard available protein fortifier (0.4 g /100 mL expressed breast milk). RESULTS The mean (standard deviation) protein intake was higher in group A as compared to group B; 4.2 (0.47) compared with 3.6 (0.37) g · kg · day, P < 0.001. At 40 weeks PMA, the mean (standard deviation) weekly occipitofrontal circumference gain was significantly higher in group A as compared to group B; 0.66 (0.16) compared with 0.60 (0.15) cm/week (mean difference 0.064, 95% confidence interval [0.004-0.123], [P = 0.04]). Weight growth velocity in group A was 11.95 (2.2) g · kg · day as compared to 10.78 (2.6) g · kg · day in group B (mean difference 1.10, 95% confidence interval [0.25-2.07], [P = 0.01]). No difference was observed in the length between the 2 groups. There was no difference in growth indices and neurodevelopmental outcomes at 12 to 18 months corrected age in the 2 groups. CONCLUSIONS Fortification of expressed human milk with fortifier containing higher protein results in better head growth and weight gain at 40 weeks PMA in preterm infants <32 weeks or 1500 g without any benefits on long-term growth and neurodevelopment at 12 to 18 months corrected age (CTRI/2014/06/004661).