Preterm Infant Formula Research Articles

Nutrition of Preterm Infants After Hospital Discharge

Growth failure in preterm infants remains extremely common despite advances in neonatal care. Many, or even a majority, leave the hospital with weights below the 10th centile for age. Because of this, the possibility of nutritional interventions to improve postdischarge growth has been considered. A variety of interventions have been tested in randomized controlled trials in formula-fed infants. Although the studies vary in design and in the intervention used, on balance the evidence supports the use of fortified formulas in formula-fed preterm infants after hospital discharge. Specially designed postdischarge formulas and preterm infant formulas seem equally efficacious. The situation for infants fed human milk is much less clear. Although the postdischarge growth in human milk-fed infants is not as good as in formula-fed infants, no interventions have been examined in human milk-fed infants in a randomized study, to our knowledge. We are unaware of any evidence that any of the commonly proposed nutritional interventions in human milk-fed infants after hospital discharge are either safe or efficacious. In the absence of such evidence, it seems prudent to avoid untested interventions in this population and to concentrate our efforts on the encouragement of breast-feeding after hospital discharge.

Assessment and Management Considerations for Oral Feeding of the Premature Infant on the Neonatal Intensive Care Unit

Assessment and Management Considerations for Oral Feeding of the Premature Infant on the Neonatal Intensive Care Unit

Donor breast milk versus infant formula for preterm infants: systematic review and meta-analysis

Objectives: To compare the effect of donor breast milk with infant formula in preterm infants. Separate comparisons with formula were made for donor breast milk that was: (1) given as...

Free Sugar and Sugar Alcohol Concentrations in Human Breast Milk

The goal was to determine the free sugars and polyols in human breast milk, both term and preterm, for comparison with formula milks. Methodology was developed for the measurement of the free sugars and polyols in breast milk. There were 16 samples collected from women who delivered at term and 17 samples from women delivering preterm. For purposes of comparison, samples were also collected from four commercial formulas for term infants and eight from commercial formulas for preterm infants as well as one sample of cows' milk. All samples were frozen immediately and analyzed by high-performance liquid chromatography techniques. Except for lactose concentrations, no significant differences were detected for all other sugars and polyols between term and preterm breast milk samples. Within breast milk samples, two patterns emerged, with one group containing additional elution peaks for compounds not yet identified. A second group did not contain these compounds. There were a number of significant differences between breast milk and formulas, particularly for inositol, glycerol, glucose, and galactose. All milks contained significant concentrations of mannose. There are no significant differences among breast milk samples for free sugar and polyol concentrations except lactose. However, some milk contains additional peaks that could be of dietary or genetic origin. Formula milk has relatively high concentrations of glucose and galactose compared with breast milk, suggesting some lactose hydrolysis.

High Protein Pre-Term Infant Formula: Effect on Nutrient Balance, Metabolic Status and Growth

Several lines of evidence suggest that formula with protein content of 3.0 g/100 kcal does not fully meet the protein needs of very-low-birth weight infants. Our purpose was to compare nitrogen balance, metabolic status and growth in infants fed a standard (3.0 g/100 kcal; RegPro) and high (3.6 g/100 kcal; HiPro) protein infant formula. Infants were fed both formulas, each formula for one week in balanced cross-over design. Metabolic status was monitored throughout. Nutrient balance and plasma amino acids were determined at the end of each week. Data were analysed using a linear mixed model. Eighteen infants were studied. Nine infants received the RegPro and nine received HiPro formula first. Nitrogen intake, absorption and retention were greater with the HiPro formula. None of the infants developed uremia or metabolic acidosis but retinol-binding-protein and weight gain were greater with the HiPro formula. Increased protein accretion paralleled by better weight gain without evidence of metabolic stress indicates that a formula with a protein content of 3.6 g/100 kcal better meets protein needs in these rapidly-growing infants. Further studies are needed to determine whether these short-term outcomes will be translated into long-term benefits.

Considerations and approaches in determining the protein and energy composition of preterm infant formulas

Optimal early nutritional support is considered a crucial issue in the care of the preterm infant, particularly of those with very low- or extremely low-brithweight. Unfortunately, this goal is seldom satisfactorily attained. Several conditions such as hypoxia, acidosis, patent ductus arteriosus, drug therapy, reduced intestinal motility may interfere with an adequate nutritional delivery in the early neonatal period. Moreover, there is still concern about metabolic and intestinal tolerance of the currently suggested intakes and a lack of uniformity in the nutritional program among different NICUs. Finally, the vast majority of the available preterm formulas are not fully adequate to the real nutritional needs of these infants. Inadequate protein content and inappropriate protein energy ratio of most preterm formulas represent a matter of major concern, since there is a strict relationship between formula composition and the quantity and quality of weight gain. As a consequence there is a need of at least two milk formulas for different preterm infants: one for LBW and VLBW infants, the other for preterm infants weighing >1500 g.

Considerations and approaches in determining the protein and energy composition of preterm infant formulas

Considerations and approaches in determining the protein and energy composition of preterm infant formulas

Free Amino Acids in Full‐Term and Pre‐Term Human Milk and Infant Formula

Although the nutritional value of human milk has been thoroughly studied, few reports describing its free amino acid (FAA) content have been published. Although infant formulas are designed to approximate the nutrient composition of human milk, the content and concentration of free amino acids are unknown. We compared the FAA concentrations of milk from mothers of preterm and full-term infants with those in several infant formulas. Human milk was obtained during three different stages of lactation (colostral, transitional and mature milk). Sixty-seven samples were collected from 44 healthy mothers of term infants and 23 mothers of premature infants 29 to 36 weeks gestation (mean 33 weeks). Two brands of powdered term formula (TF-A and TF-B) and two brands designed for preterm infants (PTF-A and PTF-B )were also studied. Ion exchange chromatography was used for free amino acid analysis. The mean concentration of total FAA in human milk was significantly higher than any of the infant formulas (8139 micromol/L for pre-term human milk; 3462 micromol/L for full term human milk; TF-A, 720 micromol/L; TF-B, 697 micromol/L; PTF-A, 820 micromol/L; PTF-B, 789 micromol/L) (P <0.01). FAA concentration in term and premature human colostral milk was significantly higher than in human transitional and mature milks (P <0.01). In comparing individual FAAs, there were significant differences in concentrations between term human milk and preterm milk except for phosphoethanolamine, hydroxyproline, asparagine, and alpha-amino-eta-butyric acid. There were significant differences in all FAA concentrations between all human milks and infant formulas (P <0.05), but no significant differences were found among the study formulas. The concentration of FAA is high in human colostral milk and decreases through the transitional and mature milk stages. FAA is higher in all human milks than in infant formulas.

Dietary PUFA for Preterm and Term Infants: Review of Clinical Studies

Human milk contains n-3 and n-6 LCPUFA (long chain polyunsaturated fatty acids), which are absent from many infant formulas. During neonatal life, there is a rapid accretion of AA (arachidonic acid) and DHA (docosahexaenoic acid) in infant brain, DHA in retina and of AA in the whole body. The DHA status of breast-fed infants is higher than that of formula-fed infants when formulas do not contain LCPUFA. Studies report that visual acuity of breast-fed infants is better than that of formula-fed infants, but other studies do not find a difference. Cognitive development of breast-fed infants is generally better, but many sociocultural confounding factors may also contribute to these differences. The effect of dietary LCPUFA on FA status, immune function, visual, cognitive, and motor functions has been evaluated in preterm and term infants. Plasma and RBC FA status of infants fed formulas supplemented with both n-3 and n-6 LCPUFA was closer to the status of breast-fed infants than to that of infants fed formulas containing no LCPUFA. Adding n-3 LCPUFA to preterm-infant formulas led to initial beneficial effects on visual acuity. Few data are available on cognitive function, but it seems that in preterm infants, feeding n-3 LCPUFA improved visual attention and cognitive development compared with infants receiving no LCPUFA. Term infants need an exogenous supply of AA and DHA to achieve similar accretion of fatty acid in plasma and RBC (red blood cell) in comparison to breast-fed infants. Fewer than half of all studies have found beneficial effects of LCPUFA on visual, mental, or psychomotor functions. Improved developmental scores at 18 mo of age have been reported for infants fed both AA and DHA. Growth, body weight, and anthropometrics of preterm and term infants fed formulas providing both n-3 and n-6 LCPUFA fatty acids is similar in most studies to that of infants fed formulas containing no LCPUFA. A larger double-blind multicenter randomized study has recently demonstrated improved growth and developmental scores in a long-term feeding study of preterm infants. Collectively, the body of literature suggests that LCPUFA is important to the growth and development of infants. Thus, for preterm infants we recommend LCPUFA intakes in the range provided by feeding of human milk typical of mothers in Western countries. This range can be achieved by a combination of AA and DHA, providing an AA to DHA ratio of approximately 1.5 and a DHA content of as much as 0.4%. Preterm infants may benefit from slightly higher levels of these fatty acids than term infants. In long-term studies, feeding more than 0.2% DHA and 0.3% AA improved the status of these fatty acids for many weeks after DHA; AA was no longer present in the formula, enabling a DHA and AA status more similar to that of infants fed human milk. The addition of LCPUFA in infant formulas for term infants, with appropriate regard for quantitative and qualitative qualities, is safe and will enable the formula-fed infant to achieve the same blood LCPUFA status as that of the breast-fed infant.

Effect of Gastric Digestion pH on Iron, Zinc, and Calcium Dialyzability from Preterm and Term Starting Infant Formulas

ABSTRACT: Iron, zinc, and calcium dialyzability from preterm and term starting infant formulas were determined after in vitro digestion, using special gastric conditions prevailing in preterm and newborn infants. Mineral dialyzability was studied using pH 2.0,3.5, and 4.5 for gastric digestion. The effect of gastric pH was more important on iron dialyzability (FeD) and zinc dialyzability (ZnD) than on calcium dialyzability (CaD). The effect on iron dialyzability was remarkable in fluid formulations with high digestibility: FeD was 18% to 20% when gastric digestion was made at pH 2, decreasing to 3% when made at pH 4.5. In most powder infant formulas with the lowest digestibility, FeD remained close to 10% despite variations in gastric digestion pH. Percent zinc dialyzability (ZnD%) steadily decreased when gastric digestion pH increased. At each pH, percent iron dialyzability (FeD%) and ZnD% from human milk were higher than those from infant formulas. Evaluation of mineral dialyzability from these infant formulas, using a gastric digestion pH prevailing in preterm and newborn infants, can provide valuable information on mineral availability.

Higher urinary excretion of essential amino acids in preterm infants fed protein hydrolysates

Protein hydrolysates have been introduced in preterm formulae, but it is not clear whether they are needed for the feeding of preterm infants. We designed a randomized, controlled trial to test the effects of a preterm formula with hydrolysed cow's milk proteins on short-term growth and urinary and plasma amino acids levels. Infants with a birthweight < or = 1750 g and gestational age < or = 34 wk fed a conventional preterm infant formula (formula B) or a hydrolysed formula (formula A). Weight was measured daily; length, head circumference, mid-arm circumference and total skinfold thickness were measured weekly. Blood and urine were analysed for amino acid concentrations at start, 14 and 28 d. Twenty-one infants met the criteria for randomization. The daily feeding volumes were: formula A 172.8 +/- 5.6 vs formula B 170.1 +/- 2.8 ml/kg/d. Infants fed with formula A showed slower weight gain (17.4 +/- 3.4 vs 20.5 +/- 3.3 g/kg/d; p = 0.045) and lower mean change in Z-scores for weight (-0.18 +/- 0.16 vs 0.00 +/- 0.09; p = 0.009) and for head circumference (-0.06 +/- 0.13 vs 0.06 +/- 0.13; p = 0.049). After 14 d, infants receiving formula A had statistically significant higher urinary levels of essential amino acids compared to infants receiving formula B. Our results support the hypothesis of less nutritional value of hydrolysed versus conventional preterm formulae. Higher renal excretion of essential amino acids may be one of the mechanisms involved. These findings must be confirmed by further studies with larger sample sizes and protein hydrolysates with different degrees of hydrolysis.

Bone mineralization and growth are enhanced in preterm infants fed an isocaloric, nutrient-enriched preterm formula through term

Because recent data on the effects of mineral concentrations in preterm infant formula on bone mineralization are lacking, recommendations for the mineral content of preterm infant formula differ greatly between committees. The goal of the study was to assess the effects of an isocaloric, nutrient-enriched preterm formula, which was fed from the age when full enteral feedings were tolerated through expected term, on bone mineralization in preterm infants. We conducted a prospective, randomized, double-blind study in healthy, preterm infants (gestational age of 28-32 wk) who were fed either a control preterm formula (n=20) or an isocaloric, nutrient-enriched preterm formula (n=21) until 3 mo of age (ie, approximate expected term). Serum calcium indexes were taken throughout the study, and bone mass was determined by using dual-energy X-ray absorptiometry at hospital discharge and expected term. A total of 37 infants (experimental formula, n=19; control formula, n=18) completed the study. Compared with control subjects, infants fed the experimental formula had 25% and 40% higher intakes of calcium and phosphorus, respectively. Serum calcium, phosphorus, osteocalcin, and alkaline phosphatase concentrations and urinary collagen type I cross-linked N-telopetide concentrations were not significantly different between the groups at any time point. The bone mineral content of infants fed the experimental formula was 23% (P=0.039) and 35% (P=0.002) higher at hospital discharge and expected term, respectively. Bone mineralization at hospital discharge and expected term was significantly higher in preterm infants fed the isocaloric, nutrient-enriched formula than in those fed control formula. Continuation of the experimental formula beyond hospital discharge, through expected term, further improved bone mineralization.

Nutrition du nourrisson et diversification alimentaire

After an overview of infant nutritional requirements, this paper deals with the various feeding alternatives offered to the newborn, putting forward the definite health benefits of breast-feeding for the first months of life. The diverse types of infant formulas are then described, classical ones as well as those designed for the alleviation of peculiar alimentary disorders (gastro-esophageal reflux, lactose maldigestion, diarrhea, food allergies…). A special attention is paid to the specific nutritional needs of premature babies and infant formulas designed to meet these requirements. To conclude, the introduction of weaning (solid) foods throughout the first two years of life is described.

ABFP'S 2005 COMPUTER-BASED EXAMINATIONS

<h3>BACKGROUND</h3> Low levels of circulating thyroid hormones have been associated with poorer general and neurodevelopmental outcome in preterm babies and it has been speculated that the association is causal. Low levels of circulating thyroid hormone have been reported after inadequate intake of iodine in preterm infants being fed milk formula. <h3>AIM</h3> To investigate whether increased iodine intake from supplemented preterm formula would improve thyroid hormone levels in preterm babies (this study) and hence improve neurodevelopmental status (planned subsequent study). <h3>METHOD</h3> A total of 121 preterm infants were entered into a randomised controlled trial of standard (68 μg/l) versus increased (272 μg/l) iodine in preterm formula. <h3>RESULTS</h3> The two groups were comparable at recruitment. No evidence of an effect of the intervention on thyroid hormone levels was seen up to 41 weeks after conception. <h3>CONCLUSION</h3> Calls for increased iodine content of preterm infant formulas are not justified by this study. <h3>Key message</h3> Increasing milk iodine content in line with the latest recommendations for preterm babies had no effect on thyroid hormone levels in the perinatal period

Bacteriological screening of expressed breast milk revealed a high rate of bacterial contamination in Chinese women

A screening programme for expressed breast milk (EBM) revealed the alarming fact that our study group had the highest rate of contamination ever reported. The programme started in July 2002 and involved a group of Chinese women whose premature babies were in the neonatal intensive care unit. EBM was considered to be contaminated if there was any growth of pathogens, including Gram-negative bacteria, enterococci or Staphylococcus aureus, or if the total bacterial count was >10 5 cfu/mL. Of 59 samples from 23 mothers, 63% were contaminated. This high contamination rate could be due to the Chinese tradition of avoiding bathing for one month after childbirth. Previous studies have shown that feeding EBM rather than premature infant formula milk has advantages in terms of decreased incidence of necrotizing enterocolitis and neonatal sepsis. However, in this population, with such a high incidence of contaminated EBM, this may not be the case. Further studies to compare EBM with premature infant formula in this population are required.

Zinc homeostasis in premature infants does not differ between those fed preterm formula or fortified human milk.

The objectives of this study were to compare zinc homeostasis in premature infants enterally fed with either preterm infant formula or fortified human milk; to examine interrelationships of variables of zinc homeostasis; and to examine the findings in relation to estimated zinc requirements of preterm infants. Zinc homeostasis was studied in 14 infants (8 male), with mean gestational age of 31 wk and birth weight appropriate for gestational age, who were exclusively fed either preterm formula (n = 9) or own mother's milk with human milk fortifier (n = 5). Zinc stable isotopes were administered intravenously ((70)Zn) and orally as an extrinsic label ((67)Zn) over multiple feeds for determination of fractional absorption by dual isotope tracer ratio in urine; endogenous fecal zinc was determined by isotope dilution; and exchangeable zinc pool (EZP) size was estimated from linear regression of log-transformed urine (70)Zn enrichment data. Results indicated no significant differences in the variables of zinc homeostasis between the feeding groups; data for all subjects were thus combined. Mean (+/- SD) fractional absorption was 0.26 +/- 0.07; net absorbed zinc 0.43 +/- 0.25 mg/d (0.31 +/- 0.19 mg/kg/d). Mean EZP was 20 +/- 10 mg/kg, and was positively correlated with total absorbed zinc and with net absorbed zinc. Feeding type and total absorbed zinc were significantly related to daily weight gain (p = 0.003). Current zinc intakes from fortified human milk or formula are associated with acceptable weight gain, but whether the observed net zinc absorption was optimal in the human milk group cannot be definitively determined from these data.

Risk of hypervitaminosis D from prolonged feeding of high vitamin D premature infant formula.

Most premature infant formulas marketed in Japan have high vitamin D content. Potential for vitamin D intoxication was assessed in premature infants with prolonged feeding of such a premature formula vitamin D content, 2700 IU/L. Serum vitamin D, calcium and phosphorus, and urinary calcium, were measured in 12 very premature infants fed premature infant formula, regular formula (vitamin D content; 460 IU/L), and/or mother's milk. Concentrations of 25(OH)D in sera associated with sole feeding of premature infant formula (n = 40) were significantly higher than sera corresponding to regular formula or breast milk (n = 25; 175 versus 115 nmol/L, P <0.0001). No sample showed a serum 25(OH)D concentration below 25 nmol/L. Of 65 samples, 49 (75.4%) showed 25(OH)D concentrations exceeding 100 nmol/L, but serum calcium and phosphorus concentrations were normal. Unexpectedly, urinary calcium correlated negatively with serum 25(OH)D. In prolonged feeding of premature infant formula with high vitamin D, it was concluded that it could cause a high blood concentration of vitamin D in premature infants, and also that in these infants urine calcium is not a reliable indicator of excessive vitamin D intake.

P1140 ENERGY EXPENDITURE IN PRETERM INFANTS SUPPLEMENTED WITH CANOLA OIL VERSUS MEDIUM-CHAIN TRIGLYCERIDE OIL

Introduction: Medium chain triglycerides (MCT) are often used as caloric supplement in preterm infants; commercial Canola oil (CO) (mostly comprised of long chain triglycerides) is at times used as an inexpensive alternative. The effect of fat supplementation to the diet of preterm infants upon fat absorption and energy expenditure (EE) has not been systematically investigated. Specifically, these 2 sources of fat (MCT and CO) have not been compared in this regard. The aim of this study was to compare intestinal fat losses and EE in healthy growing preterm infants supplemented with either CO or MCT oil. We hypothesized that inestinal fat losses and EE are lower in preterm infants supplemented with MCT oil than in those supplemented with CO. Methods: Six preterm infants were studied in a randomized, crossover design at the time they were able to tolerate full feeds (breastmilk or preterm infant formula). Gestational age ranged from 28–34 weeks, and birthweight from 920–1160g. Infants were randomized to supplementation with either 34Kcal (4g) CO/kg/day or 34Kcal (4.4g) MCT oil/kg/day for 3 days followed by 3 days of the other oil. EE was measured at baseline, after 3 days of the first oil supplementation and after 3 days of the alternate oil supplementation, using the Deltatrac II metabolic monitor (Datex-Omeda, Helsinki, Finand) based upon indirect calorimetry. Three 72-hours stool samples were collected: at baseline, and after each type of oil supplementation, for determination of fat content, using the method of Van de Kamer. Analyses are by paired Wilcoxon test, data are mean ± SD. Results: The coefficient of added fat absorption was 99.5±0.9% of the MCT oil, vs 90.0±16.2% of the CO (p=0.056). EE increased after CO supplementation (thermic effect of feeding) by 4.33±5.96 Kcal/kg/d and by 4.17±3.97 Kcal/kg/d after MCT (non significant). Thus, after correction for net additional energy intake (taking into account fat losses and thermic effect of feeding), energy retained from 34 Kcal/kg of added fat was 26.1±6.9 Kcal/kg/d after CO and 30.1±5.0 Kcal/kg/d after MCT (p=0.09). Conclusion: MCT oil is better absorbed then CO in growing preterm infants. The metabolic cost of absorption of MCT oil and CO are similar. Although energy retained from CO might be lower than that from MCT, the difference is biologically small, and CO might represent an inexpensive alternative to MCT.

A modified vitamin regimen for vitamin B2, A, and E administration in very-low-birth-weight infants.

Very-low-birth-weight (VLBW; birth weight, <1,500 g) infants receive preterm infant formulas and parenteral multivitamin preparations that provide more riboflavin (vitamin B2) than does human milk and more than that recommended by the American Society of Clinical Nutrition. VLBW infants who are not breast-fed may have plasma riboflavin concentrations up to 50 times higher than those in cord blood. The authors examined a vitamin regimen designed to reduce daily riboflavin intake, with the hypothesis that this new regimen would result in lower plasma riboflavin concentrations while maintaining lipid-soluble vitamin levels. Preterm infants with birth weight < or =1,000 g received either standard preterm infant nutrition providing 0.42 to 0.75 mg riboflavin/kg/day (standard group), or a modified regimen providing 0.19 to 0.35 mg/kg/day (modified group). The modified group parenteral vitamin infusion was premixed in Intralipid. Enteral feedings were selected to meet daily riboflavin administration guidelines. Plasma riboflavin, vitamin A, and vitamin E concentrations were measured weekly by high-performance liquid chromatography. Data were analyzed with the independent t test, chi, and analysis of variance. The 36 infants (17 standard group, 19 modified group) had birth weight and gestational age of 779 +/- 29 g and 25.5 +/- 0.3 weeks (mean +/- SEM) with no differences between groups. Modified group infants received 38% less riboflavin (0.281 +/- 0.009 mg/kg/day), 35% more vitamin A (318.3 +/- 11.4 microg/kg/day), and 14% more vitamin E (3.17 +/- 0.14 mg/kg/day) than standard group infants. Plasma riboflavin rose from baseline in both groups but was 37% lower in the modified group during the first postnatal month (133.3 +/- 9.9 ng/mL). Riboflavin intake and plasma riboflavin concentrations were directly correlated. Plasma vitamin A (0.222 +/- 0.022 microg/mL) and vitamin E (22.26 +/- 1.61 /mL) concentrations were greater in the modified group. The modified vitamin regimen resulted in reduced riboflavin intake and plasma riboflavin concentration, suggesting plasma riboflavin concentration is partially dose dependent during the first postnatal month in VLBW infants. Modified group plasma vitamin A and vitamin E concentrations were greater during the first month, possibly because the vitamins were premixed with parenteral lipid emulsion. Because of the complexity of this protocol, the authors suggest that a parenteral multivitamin product designed for VLBW infants which uses weight-based dosing should be developed.

A Modified Vitamin Regimen for Vitamin B2, A, and E Administration in Very‐Low–Birth‐Weight Infants

ABSTRACTIntroduction:Very‐low–birth‐weight (VLBW; birth weight, &lt;1,500 g) infants receive preterm infant formulas and parenteral multivitamin preparations that provide more riboflavin (vitamin B2) than does human milk and more than that recommended by the American Society of Clinical Nutrition. VLBW infants who are not breast‐fed may have plasma riboflavin concentrations up to 50 times higher than those in cord blood. The authors examined a vitamin regimen designed to reduce daily riboflavin intake, with the hypothesis that this new regimen would result in lower plasma riboflavin concentrations while maintaining lipid‐soluble vitamin levels.Methods:Preterm infants with birth weight ≤1,000 g received either standard preterm infant nutrition providing 0.42 to 0.75 mg riboflavin/kg/day (standard group), or a modified regimen providing 0.19 to 0.35 mg/kg/day (modified group). The modified group parenteral vitamin infusion was premixed in Intralipid®. Enteral feedings were selected to meet daily riboflavin administration guidelines. Plasma riboflavin, vitamin A, and vitamin E concentrations were measured weekly by high‐performance liquid chromatography. Data were analyzed with the independent t test, χ2, and analysis of variance.Results:The 36 infants (17 standard group, 19 modified group) had birth weight and gestational age of 779 ± 29 g and 25.5 ± 0.3 weeks (mean ± SEM) with no differences between groups. Modified group infants received 38% less riboflavin (0.281 ± 0.009 mg/kg/day), 35% more vitamin A (318.3 ± 11.4 μg/kg/day), and 14% more vitamin E (3.17 ± 0.14 mg/kg/day) than standard group infants. Plasma riboflavin rose from baseline in both groups but was 37% lower in the modified group during the first postnatal month (133.3 ± 9.9 ng/mL). Riboflavin intake and plasma riboflavin concentrations were directly correlated. Plasma vitamin A (0.222 ± 0.022 μg/mL) and vitamin E (22.26 ± 1.61 /mL) concentrations were greater in the modified group.Conclusions:The modified vitamin regimen resulted in reduced riboflavin intake and plasma riboflavin concentration, suggesting plasma riboflavin concentration is partially dose dependent during the first postnatal month in VLBW infants. Modified group plasma vitamin A and vitamin E concentrations were greater during the first month, possibly because the vitamins were premixed with parenteral lipid emulsion. Because of the complexity of this protocol, the authors suggest that a parenteral multivitamin product designed for VLBW infants which uses weight‐based dosing should be developed.