Safe and efficient practice of parenteral nutrition in neonates and children aged 0-18 years - The role of licensed multi-chamber bags.

Parenteral nutrition (PN) is recognized as a complex high-risk therapy. Its practice is highly variable and frequently suboptimal in pediatric patients. Optimizing care requires evidence, consensus-based guidelines, audits of practice, and standardized strategies. Several pediatric scientific organizations, expert panels, and authorities have recently recommended that standardized PN should generally be used over individualized PN in the majority of pediatric patients including very low birth weight premature infants. In addition, PN admixtures produced and validated by a suitably qualified institution are recommended over locally produced PN. Licensed multi chamber bags are standardized PN bags that comply with Good Manufacturing Practice and high-quality standards for the finished product in the frame of their full manufacturing license. The purpose of this article is to review the practical aspects of PN and the evidence for using such multi-chamber bags in pediatric patients. It highlights the safety characteristics and the limitations of the different PN practices and provides some guidance for ensuring safe and efficient therapy in pediatric patients.

Enteral Nutrition in Preterm Infants (2022): A Position Paper From the ESPGHAN Committee on Nutrition and Invited Experts.

OBJECTIVES: To review the current literature and develop consensus conclusions and recommendations on nutrient intakes and nutritional practice in preterm infants with birthweight <1800 g. METHODS: The European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee of Nutrition (CoN) led a process that included CoN members and invited experts. Invited experts with specific expertise were chosen to represent as broad a geographical spread as possible. A list of topics was developed, and individual leads were assigned to topics along with other members, who reviewed the current literature. A single face-to-face meeting was held in February 2020. Provisional conclusions and recommendations were developed between 2020 and 2021, and these were voted on electronically by all members of the working group between 2021 and 2022. Where >90% consensus was not achieved, online discussion meetings were held, along with further voting until agreement was reached. RESULTS: In general, there is a lack of strong evidence for most nutrients and topics. The summary paper is supported by additional supplementary digital content that provide a fuller explanation of the literature and relevant physiology: introduction and overview; human milk reference data; intakes of water, protein, energy, lipid, carbohydrate, electrolytes, minerals, trace elements, water soluble vitamins, and fat soluble vitamins; feeding mode including mineral enteral feeding, feed advancement, management of gastric residuals, gastric tube placement and bolus or continuous feeding; growth; breastmilk buccal colostrum, donor human milk, and risks of cytomegalovirus infection; hydrolyzed protein and osmolality; supplemental bionutrients; and use of breastmilk fortifier. CONCLUSIONS: We provide updated ESPGHAN CoN consensus-based conclusions and recommendations on nutrient intakes and nutritional management for preterm infants.

Comparative study of preterm infants fed new and existing human milk fortifiers showed favourable markers of gastrointestinal status.

AIM: This study examined the influence of different human milk fortifiers on biomarkers of gastrointestinal immaturity and inflammation in preterm infants. METHODS: We report secondary outcomes from a controlled, double-blind, randomised, parallel group study conducted from 2011 to 2014 in neonatal intensive care units at 11 metropolitan hospitals in France, Belgium, Germany, Switzerland and Italy. Preterm infants born at up to 32 weeks or weighing up to 1500 g were randomised to a new powdered human milk fortifier (n = 77) or a control fortifier (n = 76) for a minimum of 21 days. We analysed faecal markers of gut inflammation, namely alpha-1 antitrypsin and calprotectin, and maturity, namely elastase-1. RESULTS: Faecal alpha-1 antitrypsin was slightly lower in the new than control fortifier group after 21 days of full enteral feeding, with a geometric mean and standard deviation of 1.52 ± 1.32 vs 1.82 ± 1.44 mg/g stools (P = .01). There was no significant difference in faecal calprotectin (median [Q1-Q3] of 296 [136-565] µg/g stools in both groups combined at study day 21). Faecal elastase-1 was lower in the new fortifier than control fortifier group (202.5 ± 1.6 vs 257.7 ± 1.5 µg/g stools, P = .016). CONCLUSION: Mean values for each parameter were within the ranges in healthy term infants, indicating favourable markers of gastrointestinal status in both groups. In addition, for faecal calprotectin, the relatively high concentration observed in preterm infants fed fortified human milk suggests that the threshold level for detecting necrotising enterocolitis should be revised.

Partially Hydrolysed Whey-Based Formulae with Reduced Protein Content Support Adequate Infant Growth and Are Well Tolerated: Results of a Randomised Controlled Trial in Healthy Term Infants.

The current study aimed to investigate growth, safety and tolerance of partially hydrolysed infant formulae in healthy full-term infants. Fully formula-fed infants were randomised ≤14 days of age to receive a partially hydrolysed whey formula with 2.27 g protein/100 kcal (pHF2.27) or the same formula with 1.8 g or 2.0 g protein/100 kcal (pHF1.8 and pHF2.0) until 4 months of age. The primary outcome was equivalence in daily weight gain within margins of ± 3 g/day; comparison with WHO Child Growth Standards; gastrointestinal tolerance parameters and number of (serious) adverse events were secondary outcomes. A total of 207 infants were randomised, and 61 (pHF1.8), 46 (pHF2.0) and 48 (pHF2.27) infants completed the study per protocol. Equivalence in daily weight gain was demonstrated for the comparison of pHF1.8 and pHF2.27, i.e., the estimated difference was -1.12 g/day (90% CI: [-2.72; 0.47]) but was inconclusive for the comparisons of pHF2.0 and pHF2.27 with a difference of -2.52 g/day (90% CI: [-4.23; -0.81]). All groups showed adequate infant growth in comparison with the World Health Organization (WHO) Child Growth Standards. To conclude, the evaluated partially hydrolysed formulae varying in protein content support adequate growth and are safe and well tolerated in healthy infants.

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

The influence of types of human milk (HM)-raw own mother's milk (OMM), pasteurized OMM, and donor milk (DM)-was evaluated for growth in premature infants fed exclusively HM with controlled nutritional intakes using daily individualized HM fortification (IHMF). Growth and nutritional intakes were prospectively collected in preterm infants (<32 weeks) fed IHMF and compared in infants fed predominantly (≥75%) OMM and DM. The influence of HM types (raw OMM, pasteurized OMM, and DM) on growth were also evaluated in the whole population. One-hundred and one preterm infants (birth weight 970 ± 255 g, gestational age 27.8 ± 1.9 weeks) were included. Energy (143 ± 8 vs. 141 ± 6 kcal/kg/day; p = 0.15) and protein intakes (4.17 ± 0.15 vs. 4.15 ± 0.14 g/kg/day; p = 0.51) were similar in both groups. Infants receiving predominantly OMM (n = 37), gained significantly more weight (19.8 ± 2.0 vs. 18.2 ± 2.2 g/kg/day; p = 0.002) and length (1.17 ± 0.26 vs. 0.99 ± 0.36 cm/week; p = 0.020) than those fed predominantly DM (n = 33). Stepwise multivariate analysis (n = 101) suggests that raw OMM was the major determinant of growth, contributing 22.7% of weight gain. Length gain was also related to OMM (raw + pasteurized) intakes, explaining 4.0% of length gain. In conclusion, at daily controlled similar protein and energy intakes, OMM had significant beneficial effects on weight and length versus DM in VLBW infants. This difference could be partially explained by the use of raw OMM.

Correction: Billeaud et al. "Effects on Fatty Acid Metabolism of a New Powdered Human Milk Fortifier Containing Medium-Chain Triacylglycerols and Docosahexaenoic Acid in Preterm Infants" Nutrients 2018, 10, 690.

The authors wish to make a correction to the published version of their paper [...].

Reply: "Letter to the Editor Re: Billeaud et al. Nutrients 2018, 10, 690".

We thank Bernard and colleagues for their careful reading and interest in our article Effects on Fatty Acid Metabolism of a New Powdered Human Milk Fortifier Containing Medium-Chain Triacylglycerols and Docosahexaenoic Acid in Preterm Infants [...].

Effects on Fatty Acid Metabolism of a New Powdered Human Milk Fortifier Containing Medium-Chain Triacylglycerols and Docosahexaenoic Acid in Preterm Infants.

Preterm infants require fortification of human milk (HM) with essential fatty acids (FA) to ensure adequate post-natal development. As part of a larger randomized controlled study, we investigated FA metabolism in a subset of 47 clinically stable preterm infants (birth weight ≤1500 g or gestational age ≤32 weeks). Infants were randomized to receive HM supplemented with either a new HM fortifier (nHMF; n = 26) containing 12.5 g medium-chain FA (MCFA), 958 mg linoleic acid (LA), 417 mg α-linolenic acid (ALA), and 157 mg docosahexaenoic acid (DHA) per 100 g of powder (in compliance with the latest guidelines) or a fat-free HMF (cHMF; n = 21). Plasma phospholipid (PL) and triacylglycerol (TAG), and red blood cell phosphatidylcholine (RBC-PC) and phosphatidylethanolamine (RBC-PE) FA profiles were assessed before and after 21 days of feeding. In the nHMF group, significantly increased levels of n-9 monounsaturated fatty acids were observed, formed most likely by elongation and desaturation of dietary saturated fatty acids present in HM. ALA fortification increased ALA assimilation into plasma TAG. Similarly, DHA fortification enriched the DHA content in RBC-PE, which, in this compartment, was not associated with lower arachidonic acid levels as observed in plasma TAG and phospholipids. RBC-PE, a reliable indicator of FA metabolism and accretion, was the most sensitive compartment in this study.

Serum Magnesium Levels in Preterm Infants Are Higher Than Adult Levels: A Systematic Literature Review and Meta-Analysis.

Magnesium (Mg) is an essential mineral in the body, impacting the synthesis of biomacromolecules, bone matrix development, energy production, as well as heart, nerve, and muscle function. Although the importance of Mg is evident, reference values for serum Mg (sMg) in pediatric patients (more specifically, in neonates) are not well established. This systematic literature review and meta-analysis (using 47 eligible studies) aims to quantify normal and tolerable ranges of sMg concentrations during the neonatal period and to highlight the factors influencing Mg levels and the importance of regulating sMg levels during pregnancy and birth. In newborns without Mg supplementation during pregnancy, magnesium levels at birth (0.76 (95% CI: 0.52, 0.99) mmol/L) were similar to that of mothers during pregnancy (0.74 (95% CI: 0.43, 1.04) mmol/L), but increased during the first week of life (0.91 (95% CI: 0.55, 1.26) mmol/L) before returning to adult levels. This pattern was also seen in newborns with Mg supplementation during pregnancy, where the average was 1.29 (95% CI: 0.50, 2.08) mmol/L at birth and 1.44 (95% CI: 0.61, 2.27) mmol/L during the first week of life. Factors influencing these levels include prenatal Mg supplementation, gestational age, birth weight, renal maturity/function, and postnatal Mg intake. Elevated Mg levels (>2.5 mmol/L) have been associated with an increased risk of mortality, admission into intensive care, hypotonia, hypotension, and respiratory depression but sMg concentrations up to 2.0 mmol/L appear to be well tolerated in neonates, requiring adequate survey and minimal intervention.

Growth and Nutritional Biomarkers of Preterm Infants Fed a New Powdered Human Milk Fortifier: A Randomized Trial.

OBJECTIVES: The aim of this study was to assess growth and nutritional biomarkers of preterm infants fed human milk (HM) supplemented with a new powdered HM fortifier (nHMF) or a control HM fortifier (cHMF). The nHMF provides similar energy content, 16% more protein (partially hydrolyzed whey), and higher micronutrient levels than the cHMF, along with medium-chain triglycerides and docosahexaenoic acid. METHODS: In this controlled, multicenter, double-blind study, a sample of preterm infants ≤32 weeks or ≤1500 g were randomized to receive nHMF (n = 77) or cHMF (n = 76) for a minimum of 21 days. Weight gain was evaluated for noninferiority (margin = -1 g/day) and superiority (margin = 0 g/day). Nutritional status and gut inflammation were assessed by blood, urine, and fecal biochemistries. Adverse events were monitored. RESULTS: Adjusted mean weight gain (analysis of covariance) was 2.3 g/day greater in nHMF versus cHMF; the lower limit of the 95% CI (0.4 g/day) exceeded both noninferiority (P < 0.001) and superiority margins (P = 0.01). Weight gain rate (unadjusted) was 18.3 (nHMF) and 16.8 g ·â€Škg ·â€Šday (cHMF) between study days 1 and 21 (D1-D21). Length and head circumference (HC) gains between D1 and D21 were not different. Adjusted weight-for-age z score at D21 and HC-for-age z score at week 40 corrected age were greater in nHMF versus cHMF (P = 0.013, P = 0.003 respectively). nHMF had higher serum blood urea nitrogen, pre-albumin, alkaline phosphatase, and calcium (all within normal ranges; all P ≤ 0.019) at D21 versus cHMF. Both HMFs were well tolerated with similar incidence of gastrointestinal adverse events. CONCLUSIONS: nHMF providing more protein and fat compared to a control fortifier is safe, well-tolerated, and improves the weight gain of preterm infants.

Use of donor milk in the neonatal intensive care unit.

Own mother's milk is the first choice in feeding preterm infants and provides multiple short- and long-term benefits. When it is unavailable, donor human milk is recommended as the first alternative. Donor milk undergoes processing (i.e. pasteurization) to reduce bacteriological and viral contaminants but influences its bioactive properties with potentially fewer benefits than raw milk. However, there is no clinical evidence of health benefit of raw compared to pasteurized human milk, and donor milk maintains documented advantages compared to formula. Nutrient content of donor and own mother's milk fails to meet the requirements of preterm infants. Adequate fortification is necessary to provide optimal growth. There are significant challenges in providing donor milk for premature infants; therefore, specific clinical guidelines for human milk banks and donor milk use in the neonatal intensive care unit should be applied and research should focus on innovative solutions to process human milk while preserving its immunological and nutritional components. In addition, milk banks are not the only instrument to collect, process and store donor milk but represent an excellent tool for breastfeeding promotion.

Recombinant Bile Salt-Stimulated Lipase in Preterm Infant Feeding: A Randomized Phase 3 Study.

INTRODUCTION: Feeding strategies are critical for healthy growth in preterm infants. Bile salt-stimulated lipase (BSSL), present in human milk, is important for fat digestion and absorption but is inactivated during pasteurization and absent in formula. This study evaluated if recombinant human BSSL (rhBSSL) improves growth in preterm infants when added to formula or pasteurized breast milk. PATIENTS AND METHODS: LAIF (Lipase Added to Infant Feeding) was a randomized, double-blind, placebo-controlled phase 3 study in infants born before 32 weeks of gestation. The primary efficacy variable was growth velocity (g/kg/day) during 4 weeks intervention. Follow-up visits were at 3 and 12 months. The study was performed at 54 centers in 10 European countries. RESULTS: In total 415 patients were randomized (rhBSSL n = 207, placebo n = 208), 410 patients were analyzed (rhBSSL n = 206, placebo n = 204) and 365 patients were followed until 12 months. Overall, there was no significantly improved growth velocity during rhBSSL treatment compared to placebo (16.77 vs. 16.56 g/kg/day, estimated difference 0.21 g/kg/day, 95% CI [-0.40; 0.83]), nor were secondary endpoints met. However, in a predefined subgroup, small for gestational age infants, there was a significant effect on growth in favor of rhBSSL during treatment. The incidence of adverse events was higher in the rhBSSL group during treatment. CONCLUSIONS: Although this study did not meet its primary endpoint, except in a subgroup of infants small for gestational age, and there was an imbalance in short-term safety, these data provide insights in nutrition, growth and development in preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov NCT01413581.

Hydrolyzed Proteins in Preterm Infants.

Milk proteins are an essential component of the diet of preterm infants who have high requirements. Hydrolyzed proteins (HPs) have been introduced in infants' formulas (HPFs) to treat gastrointestinal disorders and to prevent allergic diseases. Several studies have evaluated the adequacy of HPs in preterm infants. Protein source significantly influences plasma amino acid concentrations. Protein utilization and efficiency are usually lower with HPFs compared to formulas with intact proteins. When protein intake is similar, a lower weight gain is generally observed with HPFs and a 10% increase in protein content is usually necessary to compensate for this reduction in protein utilization. Mineral absorption may also be reduced and no data exist for trace elements and vitamins. Most HPFs are associated with accelerated gastrointestinal transit time and softer stools but without clear benefit on feeding tolerance. Preterm infants seem to be at similar risk of allergic diseases than term infants, but the preventive effect of HPFs has not been sufficiently explored in preterm infants. Most modern HPFs designed for preterm infants are well tolerated and have adapted their nutrient content to improve nutrient absorption and retention. However, their benefits and safety have not been demonstrated and, therefore, further high-quality studies are needed.

Should Partial Hydrolysates Be Used as Starter Infant Formula? A Working Group Consensus.

Partially hydrolyzed formulas (pHFs) are increasingly used worldwide, both in the prevention of atopic disease in at-risk infants and in the therapeutic management of infants with functional gastrointestinal manifestations. Because prevention is always preferable to treatment, we reviewed the literature aiming to find an answer for the question whether pHF may be recommended for feeding all infants if breast-feeding is not possible. PubMed and Cochrane databases were searched up to December 2014. In addition, to search for data that remained undetected by the searches, we approached authors of relevant articles and major producers of pHFs asking for unpublished data. Because few data were found, nonrandomized, controlled trials and trials in preterm infants were included as well. Overall, only limited data could be found on the efficacy and safety of pHF in healthy term infants. Available data do not indicate that pHFs are potentially harmful for healthy, term infants. With respect to long-term outcomes, particularly referring to immune, metabolic and hormonal effects, data are, however, nonexistent. From a regulatory point of view, pHFs meet the nutrient requirements to be considered as standard formula for term healthy infants. Cost, which is different from country to country, should be considered in the decision-making process. Based on limited available data, the use of pHF in healthy infants is safe with regard to growth. The lack of data, in particular for metabolic consequences and long-term outcomes, is, however, the basis for our recommendation that health authorities should develop and support long-term follow-up studies. Efficacy and long-term safety data are required before a recommendation of this type of formula for all infants can be made.

Electrolyte and Mineral Homeostasis After Optimizing Early Macronutrient Intakes in VLBW Infants on Parenteral Nutrition.

OBJECTIVES: The aim of the present study was to evaluate electrolyte and mineral homeostasis in very-low-birth-weight (VLBW) infants who received high protein and energy intakes with a unique standardized parenteral nutrition solution containing electrolytes and minerals from birth onward. METHODS: Prospective cohort study in 102 infants with birth weight <1250 g. The evolution of plasma biochemical parameters was described during the first 2 weeks of life. RESULTS: During the first 3 days of life, mean parenteral intakes were 51 ±â€Š8 kcal · kg · day with 2.7 ±â€Š0.4 g · kg · day of protein, 1.1 ±â€Š0.2 mmol · kg · day of sodium and potassium, and 1.3 ±â€Š0.2 mmol · kg · day of calcium and phosphorus. Afterwards, most nutritional intakes (parenteral and enteral) met growth requirements. No infant developed a hyperkalemia >7 mmol/L, and a hypernatremia >150 mmol/L occurred only in 15.7% of the infants. In contrast, hyponatremia <130 mmol/L and hypokalemia <3 mmol/L occurred in 30.4% and 8.8% of the infants, respectively. The initial neonatal metabolic acidosis rapidly resolved in most infants and only 2.0% developed a base deficit >10 mmol/L after day 3 of life. Early hypocalcemia <1.8 mmol/L occurred in 13.7% of the infants. In contrast, hypophosphatemia <1.6 mmol/L occurred in 37.3% and hypercalcemia >2.8 mmol/L occurred in 12.7% of the infants. CONCLUSIONS: Increasing early protein and energy intakes in VLBW infants in the first week of life improves electrolyte homeostasis. It also increases the phosphorus requirements with a calcium-to-phosphorus ratio ≤1.0 (mmol/mmol) and the potassium and sodium requirements to avoid the development of a refeeding-like syndrome. These data suggest that the parenteral nutrition guidelines for VLBW infants for the first week of life need to be revised.

A Belgian consensus-statement on growing-up milks for children 12-36 months old.

UNLABELLED: Growing-up milks (GUM) are milk-based drinks with low protein and added minerals and vitamins intended for children 12-36 months. Since the advantages of GUM are heavily debated, we reviewed the literature. A literature search was done using the classic databases (Pubmed, Embase, Cochrane) on the use of GUM in 12- to 36-month-old young children. Only limited data are available. GUM have a highly variable composition as their marketing is not regulated. Nevertheless, all papers conclude that GUM help to cover nutritional requirements of 12- to 36-month-old infants. CONCLUSION: Appropriate intakes of macro- and micronutrients in 1- to 3-year-old children have long-term health benefits. Present diets offered to toddlers do in general not meet the requirements. Supplemented foods are therefore helpful, of which GUM is a possibility.

Intrauterine-like growth rates can be achieved with premixed parenteral nutrition solution in preterm infants.

Growth failure in neonatal intensive care units is a major challenge for pediatricians and neonatologists. The use of early "aggressive" parenteral nutrition (PN), with >2.5 g/(kg ·d) of amino acids and at least 40 kcal/(kg ·d) of energy from the first day of life, has been shown to provide nutritional intakes in the range recommended by international guidelines, reducing nutritional deficit and the incidence of postnatal growth restriction in preterm infants. However, nutritional practices and adherence to recommendations may vary in different hospitals. Two ready-to-use (RTU), premixed parenteral solutions (PSs) designed for preterm infants have been prospectively evaluated: a binary RTU premixed PS from our hospital pharmacy and a commercially premixed 3-chamber bag (Baxter Healthcare). These premixed PSs provide nitrogen and energy intakes in the range of the most recent recommendations, reducing or eliminating the early cumulative nutritional deficit in very-low-birth-weight infants, and avoiding the development of postnatal growth restriction. A further rationale for RTU premixed PSs is that preterm infants require balanced PN that contains not only amino acids and energy but also minerals and electrolytes from the first day of life in order to reduce the incidence of metabolic disorders frequently reported in extremely-low-birth-weight infants during the early weeks of life.

Initial amino acid intake influences phosphorus and calcium homeostasis in preterm infants--it is time to change the composition of the early parenteral nutrition.

BACKGROUND: Early aggressive parenteral nutrition (PN), consisting of caloric and nitrogen intake soon after birth, is currently proposed for the premature baby. Some electrolyte disturbances, such as hypophosphatemia and hypercalcemia, considered unusual in early life, were recently described while using this PN approach. We hypothesize that, due to its impact on cell metabolism, the initial amino acid (AA) amount may specifically influence the metabolism of phosphorus, and consequently of calcium. We aim to evaluate the influence of AA intake on calcium-phosphorus metabolism, and to create a calculation tool to estimate phosphorus needs. METHODS: Prospective observational study. Phosphate and calcium plasma concentrations and calcium balance were evaluated daily during the first week of life in very preterm infants, and their relationship with nutrition was studied. For this purpose, infants were divided into three groups: high, medium and low AA intake (HAA, MAA, LAA). A calculation formula to assess phosphorus needs was elaborated, with a theoretical model based on AA and calcium intake, and the cumulative deficit of phosphate intake was estimated. RESULTS: 154 infants were included. Hypophosphatemia (12.5%) and hypercalcemia (9.8%) were more frequent in the HAA than in the MAA (4.6% and 4.8%) and in the LAA group (0% and 1.9%); both p<0.001. DISCUSSION: Calcium-phosphorus homeostasis was influenced by the early AA intake. We propose to consider phosphorus and calcium imbalances as being part of a syndrome, related to incomplete provision of nutrients after the abrupt discontinuation of the placental nutrition at birth (PI-ReFeeding syndrome). We provide a simple tool to calculate the optimal phosphate intake. The early introduction of AA in the PN soon after birth might be completed by an early intake of phosphorus, since AA and phosphorus are (along with potassium) the main determinants of cellular growth.

Variability in human milk composition: benefit of individualized fortification in very-low-birth-weight infants.

BACKGROUND: Preterm infants fed fortified human milk (HM) grow more slowly than those fed preterm formulas. These differences could be related to the variability in the macronutrient composition of expressed HM, resulting in inadequate nutrient intake in relation to the estimated needs of the preterm infants. OBJECTIVES: The aim of this article was to show the variability in HM composition from an infant's own mother's milk (OMM) or pooled HM from the milk bank. The second objective was to evaluate the advantages of individual fortification on nutritional intakes over standard fortification. DESIGN: The macronutrient composition of 428 OMM, 138 HM pools from single donors, 224 pools from multiple donors, and 14 pools from colostral milk was determined by using a mid-infrared analyzer. Individualized fortification was performed after analysis of the milk samples in 2 steps: adjustment of fat content up to 4 g/dL, followed by the addition of an HM fortifier to provide 4.3 g · kg(-1) · d(-1) according to the daily prescribed volume of feeding. Nutritional intakes resulting from the individualized fortification were compared with calculated intakes resulting from standard fortification (HM fortifier: 4 packets/dL). RESULTS: The variability in contents of fat, protein, and energy was high for all types of HM samples. Compared with standard fortification, individual fortification significantly reduced the variability in nutritional intakes, allowing the maintenance of protein intake and the protein:energy ratio in the range of the nutritional recommendations. CONCLUSIONS: The variability in expressed HM with respect to its protein and energy content is high. This variability persists after standard fortification, possibly resulting in under- or overnutrition. Because both over- and undernutrition confer risks in later development, individualized fortification optimizes protein and energy intake.