Commercial Human Milk Fortifier Research Articles

Human Milk Fortifier After Neonatal Intensive Care Unit Discharge Improves Human Milk Usage Rates for Preterm Infants

BackgroundA common neonatal intensive care unit (NICU) discharge feeding strategy for preterm infants with growth failure who are fed exclusively expressed human milk (EHM) has been to enrich mother’s own milk with formula powder or supplement 2–3 feeds per day with formula. However, this strategy displaces human milk from the diet. Our NICU recently adopted the standard practice of adding commercial human milk fortifier (HMF) to human milk feedings after discharge. ObjectivesWe aimed to compare breastfeeding rates and growth using the aforementioned 2 strategies. MethodsPreterm infants (<34 wk of gestation at birth) exclusively feeding EHM fortified with HMF at 2 weeks before discharge were included in this retrospective study. The HMF group (n = 92) continued fortifying with HMF at home, whereas the historical comparison group (n = 35) received our previous guidance to enrich or supplement using postdischarge formula. ResultsRates of human milk exclusivity after discharge decreased significantly less in the HMF group than those in the historical comparison group (to 83% compared with 39% at the first outpatient visit and 27% compared with 6%, respectively, at the second outpatient visit). Rates of any EHM feedings were also significantly higher in the HMF group. Fenton z-scores for weight, length, and head circumference were not significantly different between the groups. ConclusionsContinuing EHM fortification with HMF after NICU discharge, rather than enriching or supplementing with postdischarge infant formula, increases rates of feeding EHM for ≥3 mo but does not affect growth.

Displacement of human milk during fortification: An experimental study.

This study quantified the displacement of human milk by commercial human milk fortifiers (HMFs) and infant formulas. Commercial liquid HMFs and powder infant formulas were added to pasteurized pooled donor human milk in triplicate, stirred, and weighed. The difference in weight between unfortified and fortified human milk at 22, 24, 26, 27, 28, and 30 kcal/ounce was calculated. The displacement of human milk by liquid HMFs and powder infant formulas and powder HMF was highly associated with energy density. A human milk-derived HMF displaced significantly more human milk when compared with bovine milk-derived HMFs at equivalent energy densities. Similarly, powder infant formulas displaced less human milk when compared with a powder HMF, and the addition of hydrolyzed powder infant formulas resulted in less human milk displacement when compared with nonhydrolyzed powder infant formulas. The displacement of human milk by commercial liquid HMFs and infant formulas must be considered when selecting a fortifying strategy.

Effect of fortifiers on the osmolality of preterm human milk

ABSTRACTBackground: The nutritional content of preterm human milk (HM) can be increased by adding human milk fortifier (HMF). Premature formula (PF) has been used as an alternative to HMF due to the high cost of HMF in some countries. However, the osmolality of HM after fortification remains a matter of concern.Aim: To evaluate the osmolality of fortified preterm HM.Methods: This was a cross-sectional study. HM was collected from 28 mothers of infants with a gestational age of <32 weeks or birthweight <1500 g. Expressed HM was divided into (i) pure HM; (ii) HM+PF to 24 kcal/oz; (iii) HM+PF to 28 kcal/oz; and (iv) HM+HMF to 24 kcal/oz + protein powder 0.5 g/100 ml.Results: Twenty-eight samples of preterm HM were analysed. The mean (SD) osmolality of baseline HM was 297.6 (9.7) mOsm/kg. Mean osmolality of preterm HM after fortification with PF to 24 and 28 kcal/oz was 357.2 (11.1) and 419.9 (18.8) mOsm/kg, respectively. The mean osmolality after fortification with HMF plus protein powder was 464.1 (18.8) mOsm/kg. Repeated-measures ANOVA was used to compare osmolality between pure HM and HM fortified with different fortifiers. All pairwise comparisons by the Bonferroni method were statistically significant (p < 0.001).Conclusions: The osmolality of preterm HM fortified with PF up to 28 kcal/oz does not exceed the American Academy of Paediatrics recommendation of 450 mOsm/kg. The addition of extra protein to preterm HM fortified with commercial HMF must be cautiously considered due to the risk of excessively high osmolality.

Effect of Increased Enteral Protein Intake on Growth in Human Milk–Fed Preterm Infants

Protein, supplied in currently available commercial fortifiers, may be inadequate to meet the requirements of very preterm infants; in addition, intraindividual and interindividual variability of human milk protein and energy content potentially contribute to unsatisfactory early postnatal growth. To determine effects on growth of different levels of enteral protein supplementation in predominantly human milk-fed preterm infants. This randomized clinical and partially blinded single-center trial was conducted in a neonatal tertiary referral center in Germany. Sixty preterm infants (gestation <32 weeks and weight <1500 g at birth) were recruited from October 2012 to October 2014 and included 35% of 173 eligible infants. Median (interquartile range [IQR]) gestational age at birth was 29.9 (28.7-31.2) weeks. All analyses were conducted in an intention-to-treat population. Infants were randomly assigned to either a lower-protein (adding 1 g of bovine protein/100 mL of breast milk through a commercial human milk fortifier; n = 30) or a higher-protein group at a median (IQR) postnatal age of 7 (6-8) days. The higher-protein group (n = 30) received either standardized higher-protein supplementation (study fortifier adding 1.8 g of bovine protein/100 mL of breast milk [n = 15]) or individualized high-protein supplementation based on protein and fat content of administered breast milk (n = 15). Study interventions were continued for a median (IQR) of 41 (30-57) days and until definite discharge planning. Primary outcome was weight gain (g/kg/d) from birth to the end of intervention. Sixty preterm infants (gestation <32 weeks and weight <1500 g at birth), 33 girls, were recruited from October 2012 to October 2014 and included 35% of 173 eligible infants. Median (IQR) gestational age at birth was 29.9 (28.7-31.2) weeks. Demographic characteristics and hospital courses were similar in both groups, and birth weights ranged from 580 to 1495 g in the lower-protein group and 490 to 1470 g in the higher-protein group. Weight gain was similar in the lower- and higher-protein groups: mean (95% CI), 16.3 g/kg/d (15.4-17.1 g/kg/d) in the lower-protein group vs 16.0 g/kg/d (15.1-16.9 g/kg/d) in the higher-protein group) (P = .70), despite an increase in actual protein intake by 0.6 g/kg/d (0.4-0.7 g/kg/d) (P < .001). Head circumference and lower leg longitudinal growth were also similar, as was the proportion of cumulative total enteral feeding volume provided as breast milk: median (IQR) proportion of breast milk, 92% (79%-98%) in the lower-protein group vs 94% (62%-99%) in the higher-protein group (P = .89). An increase in protein intake by 0.6 g/kg/d to a mean intake of 4.3 g/kg/d did not further enhance growth of very preterm infants with a median birth weight of 1200 g, who achieved near-fetal growth rates. This might point to a ceiling effect for enteral protein intake with respect to its influence on growth. clinicaltrials.gov Identifier: NCT01773902.

Experimental study showed that adding fortifier and extra-hydrolysed proteins to preterm infant mothers' milk increased osmolality.

Measuring milk osmolality after adjustable fortification is clinically relevant, as values exceeding recommended safety thresholds might result in gastrointestinal consequences. The aim of this study was to evaluate the effect of four fortification levels and storage time on the osmolality of human milk. This was an experimental study using 71 spare samples of fresh breastmilk collected from 31 mothers of preterm infants. Osmolality was measured before and after adding commercial human milk fortifier containing dextrinomaltose and hydrolysed proteins at four different concentrations. Measurements were performed at various points during the 23hours after fortification. The mean basal osmolality of the 71 human milk samples was 296±14 milliosmoles (mOsm)/kg, and these remained stable over a period of 23hours. Just after fortification, the four fortified formulas showed higher osmolalities than the nonfortified human milk, ranging between 384±14 and 486±15 mOsm/kg, respectively (p<0.01). This osmolality increased significantly from 20minutes to 23hours after fortification (p<0.05). Adding fortifier and extra-hydrolysed proteins to human preterm milk increased osmolality, and these osmolality levels also increased with time. We recommend evaluating the risk of hyperosmolality when a higher fortification level is needed, to avoid gastrointestinal problems.

Effect of Fortifiers and Additional Protein on the Osmolarity of Human Milk

The present guidelines of the American Academy of Pediatrics recommend that osmolarity not exceed 450 mOsm/kg (or approximately an osmolarity of 400 mOsm/L) for breast milk or infant formulae, to minimize the risk factors for necrotizing enterocolitis. A commercial protein supplement has been developed to meet special protein requirements (4.0-4.5 g · kg(-1) · day(-1)) of infants with a birth weight <1000 g. Because its effect on osmolarity has not been systematically studied, we characterized the effects of fortification on the osmolarity of human milk (HM). Osmolarity of fresh and processed HM was measured at baseline, after fortification with a commercial HM fortifier and after further supplementation with additional protein increasing in 0.5-g steps up to 4.0 g. Measurements were performed immediately after adding fortifier and/or protein and after 24 hours. In addition, changes in osmolarity were determined after adding therapeutic additives such as iron, multivitamin supplement, and calcium-phosphorus capsules. Native HM samples (n = 84) had 297 mOsm/L, (median; 95% confidence interval 295-299 mOsm/L). Adding HM fortifier increased osmolarity up to 436 mOsm/L (95% confidence interval 431-441 mOsm/L). Additional protein supplementation increased osmolarity by 23.5 mOsm/L per 0.5-g step, up to a maximum of 605 mOsm/L. Pasteurization decreased osmolarity by 20-30 mOsm/L (P < 0.001), and storage for 24 hours slightly increased osmolarity (by 11.5 mOsm/L P = 0.0002). Therapeutic additives increased osmolarity up to 868 mOsm/L. Adding HM fortifier and additional protein to HM increased osmolarity to >400 mOsm/L and therefore above the recommended threshold. Because of the excessive increase in osmolarity combinations of HM + fortifier and additional protein should not be applied together with multivitamins or other additives.

An intention to achieve better postnatal in-hospital-growth for preterm infants: Adjustable protein fortification of human milk

ObjectiveWe assessed the effect of human milk (HM) fortification with extra protein supplement by an adjustable protein fortification method according to the weekly blood urea nitrogen (BUN) levels on growth in hospitalized preterm infants. MethodA prospective observational intervention study in 58 preterms born ≤32weeks of gestation and fed with breast milk was conducted. Preterms who were given a commercial HM fortifier which provides an additional protein of 0.8g/3 scales according to the standard feeding strategy served as a historical control group. Infants who were given extra protein in addition to the HM fortifier with another commercial protein supplement which provides an additional protein of 2.2g/1 scale comprised the intervention group. Additional protein supplementation was adjusted according to BUN levels weekly in the intervention group. Weight gain velocities (g/kg/day), length, head circumferences (HC) gain velocities (mm/day) and daily growth indexes for weight, height and HC (percentage per day) were calculated. ResultsThe median amount of daily enteral protein intake [4 (3.4–4.6) vs. 2.78 (2.1–3.1) g/kg/day, p<0.0001] was significantly higher in the interventional group. Length (p=0.008) and HC (p<0.0001) gain velocities were significantly higher in the intervention group. Daily growth indexes for weight (2.2% vs. 1.8%, p=0.026), for length (0.4% vs. 0.3%, p=0.027) and for HC (0.48% vs. 0.36% per day, p=0.003) were significantly higher in the intervention group. ConclusionA higher protein intake by adjustable protein fortification method without energy or volume change leads to improved postnatal in-hospital-growth in very low birth weight infants.

Design and Characterization of a Human Milk Product for the Preterm Infant

It is necessary to fortify human milk to promote optimal growth of the very preterm infant. However, the addition of non-human milk components to human milk is not ideal because of the risk of feeding intolerance and necrotizing enterocolitis. Human milk products (HMP) are an alternative to commercially available fortifiers, but their preparation is likely to result in modifications to the qualities of human milk. Ten batches of HMP were prepared with the aim of meeting a desired protein:energy ratio of 3.0 g of protein/100 kcal. Ultrafiltration was used to produce a skim milk concentrate, to which cream was then added to produce the final HMP. Characterization of HMP and human milk fortified with commercial human milk fortifiers (Nutriprem [Cow & Gate, Limerick, Ireland] and S-26 SMA human milk fortifier [Wyeth Nutrition, Baulkham Hills, NSW, Australia]) included quantifying macronutrient content, osmolality, microbial content, and particle distribution. Average protein:energy ratio of the final batch was 2.93 +/- 0.10 g of protein/100 kcal, equating to an inaccuracy of 2.5% relative to the desired ratio of 3.0 g of protein/100 kcal. Significantly greater fat (P < 0.01), lower lactose (P < 0.001), and lower osmolality (P < 0.001) were characteristic of the HMP compared to human milk fortified with either commercial fortifier. Microbial growth occurred during preparation of HMP but did not exceed 10(5) colony-forming units/mL, and pasteurization of human milk prevented contamination in 80% of batches. HMP can be designed to accurately target the protein and energy requirements of the preterm infant, but modifications of the macronutrient, biochemical, structural, and microbial characteristics of human milk may affect the quality of the final product.

Enteral Nutrition Support of the Preterm Infant in the Neonatal Intensive Care Unit

The delivery of a preterm baby is a nutrition emergency. Growth and the accumulation of nutrient reserves are higher during the third trimester of pregnancy than at any other time during the life cycle. Enteral nutrition is the preferred mode of support and human milk the preferred source of enteral nutrition. Human milk is highly digestible and contains many anti-infective components, which confer a lower risk of infection. The mother of a preterm infant requires education, equipment, and encouragement to successfully initiate and sustain lactation. Human milk requires nutrient fortification to meet the protein and mineral needs of the rapidly growing preterm infant. Commercial human milk fortifiers are available. If human milk is unavailable or the volume is insufficient, preterm formulas are available. Preterm formulas have different sources of macronutrients and greater density of all nutrients than formulas intended for term newborns. Preterm infants benefit from early enteral feedings with slow but steady increases in feedings to achieve full support. Infants born at <35 weeks gestational age are supported with tube feedings. A transition to feedings at the breast or to bottle feedings is gradually made as the baby matures. Nutrient recommendations specific to the preterm infant are available. Special products and feeding strategies exist to respond to common medical conditions that can complicate nutrition management. Optimal nutrition care of the preterm infant offers the opportunity to improve outcomes for children.

Nutritional support and bronchopulmonary dysplasia

Nutritional support of extremely low-birth-weight infants has a critical role in the prevention, amelioration and recovery from bronchopulmonary dysplasia (BPD). Despite studies demonstrating the importance of providing adequate energy, protein and certain nutrients, no evidence-based nutritional guidelines exist. Attempts to improve outcomes with nutritional supplementation have been unsuccessful. These have included nutrients to enhance protection from oxidative lung injury (vitamin E, selenium, N-acetyl cysteine, superoxide dismutase), to improve surfactant function (inositol) and to improve pulmonary cell growth and differentiation (vitamin A). Only vitamin A has shown modest benefit. After infants with BPD move to the convalescent phase of their neonatal intensive care unit (NICU) stay, they continue to require extra energy and protein to grow at appropriate rates. Enriched formulas have shown promise, but standard supplementation schemes with commercial human milk fortifiers may be inadequate to meet the infant's needs. Efforts to individualize the amount of fortification guided by twice-weekly blood urea nitrogen determinations have led to improved gains in weight, length and head circumference.

The Effect of Calcium Salts, Ascorbic Acid and Peptic pH on Calcium, Zinc and Iron Bioavailabilities from Fortified Human Milk using an in vitro Digestion/Caco-2 Cell Model

The calcium, zinc, and iron bioavailabilities of human milk with commercial and noncommercial human milk fortifiers (HMFs) were evaluated under a variety of conditions: peptic digestion at pH 2 and pH 4, supplementation of ascorbic acid, and addition of three calcium salts. The noncommercial HMFs consisted of casein phosphopeptides (CPPs), alpha-lactalbumin, colostrum, and hydrolyzed whey protein concentrate (WPC). They were mixed with human milk (HM) and calcium, zinc, and iron were added. Ascorbic acid (AA) was added in certain studies. The commercial HMFs were Nestlé FM-85, Similac HMF (SHMF), and Enfamil HMF (EHMF). All HMFs were compared to S-26/SMA HMF. Results showed that the peptic pH (2 vs. 4) had no effect on mineral bioavailability. Addition of different calcium salts had no effect on calcium cell uptake and cell ferritin levels (an indicator of iron uptake), however, the addition of calcium glycerophosphate/gluconate increased zinc uptake by Caco-2 cells. Addition of AA significantly increased ferritin levels, with no effect on calcium or zinc uptake. Among the commercial HMFs, FM-85 was significantly lower in zinc uptake than S-26/SMA, and HM+EHMF was significantly higher than HM+S-26/SMA. Cell ferritin levels were significantly higher for HM+S-26/SMA than for all other commercial fortifiers. None of the commercial HMFs were different from HM+S-26/SMA in calcium uptake.

P1098 BACTERIAL GROWTH RATES IN HUMAN MILK CONTAINING POWDERED FORTIFIERS

Introduction: While commercially sterile liquid formulas should be used for feeding preterm infants, most commercial human milk fortifiers are powdered. New guidelines indicate that fortified human milk may be fed for up to 4 hr after preparation, although no data have validated this recommendation. This study was designed to assess growth rates of Enterobacter sakazakii and resident aerobic flora from human milk during a 6 hr incubation in standard preterm formula and fresh human milk with and without powdered fortifiers. Methods: Eight mothers of preterm infants provided fresh samples of expressed milk. Samples were refrigerated immediately and processed within 24 hr. Aliquots of human milk were mixed with one of two commercial fortifiers according to label instructions (1 packet per 25 ml). Aliquots of preterm formula, human milk, and fortified human milk were divided into 2 samples; one sample was inoculated with 103 cfu/ml E. sakazakii and the other was not. All samples were incubated at room temperature; colony counts of E. sakazakii and total aerobic bacteria were enumerated at baseline (0 hr), 2, 4, and 6 hr, using selective Violet Red Bile Glucose Agar and non-selective Trypticase Soy Agar (TSA). Data were analyzed using repeated measures of analysis of variance. Results: Fresh human milk had higher counts of aerobic bacteria than did preterm formula or fortifiers. After controlling for milk or formula, culture media, and inoculation method, overall bacteria counts from 0 to 4 hr increased 0.16 log cfu/ml. The effect of time on bacterial counts was similar for all factors. Representative data for resident flora in human milk samples (TSA) are shown:Table 1: Number of Bacteria (log cfu/ml; mean ± SE)Conclusion: Bacterial growth in expressed human milk containing powdered fortifiers is similar to growth in human milk alone, with negligible changes occurring up to 6 hr. These data support current guidelines that recommend using fortified human milk for up to 4 hr after preparation.

Utilization of supplemental iron by premature infants fed fortified human milk*

We measured red blood cell iron incorporation (RBC‐inc) in 13 human milk‐fed premature infants (birthweight 1037 ± 289 g, gestational age 27 ± 2 wk, weight at start of study 1571 ± 426 g) who were receiving full tube‐feedings of human milk fortified with a commercial human milk fortifier (FortHM). The relative RBC‐inc of supplemental iron (2 mg/kg/d of ferrous sulfate) was assessed using 57Fe sulfate mixed directly into a 24‐h volume of FortHM, and 54Fe sulfate given as a bolus between two FortHM feedings the next day. RBC‐inc was similar between the two methods of supplemental iron administration (4.7 ± 2.5% vs 4.6 ± 1.5%, respectively). Although these values are lower than RBC‐inc expected from iron native to human milk, the relatively large amount of iron in the supplements contributed most of the iron incorporated into RBC by the infants. There was a significant positive correlation between the reticulocyte count and RBC‐inc. As the high nutrient (especially calcium) content of the FortHM did not interfere with iron utilization, adding iron directly to FortHM, or incorporating it into commercial fortifiers, may be a practical method to provide iron to premature infants. □Human milk, iron absorption, premature infants, stable isotopes

Utilization of supplemental iron by premature infants fed fortified human milk.

We measured red blood cell iron incorporation (RBC-inc) in 13 human milk-fed premature infants (birthweight 1037 +/- 289 g, gestational age 27 +/- 2 wk, weight at start of study 1571 +/- 426 g) who were receiving full tube-feedings of human milk fortified with a commercial human milk fortifier (FortHM). The relative RBC-inc of supplemental iron (2 mg/kg/d of ferrous sulfate) was assessed using 57Fe sulfate mixed directly into a 24-h volume of FortHM, and 54Fe sulfate given as a bolus between two FortHM feedings the next day. RBC-inc was similar between the two methods of supplemental iron administration (4.7 +/- 2.5% vs 4.6 +/- 1.5%, respectively). Although these values are lower than RBC-inc expected from iron native to human milk, the relatively large amount of iron in the supplements contributed most of the iron incorporated into RBC by the infants. There was a significant positive correlation between the reticulocyte count and RBC-inc. As the high nutrient (especially calcium) content of the FortHM did not interfere with iron utilization, adding iron directly to FortHM, or incorporating it into commercial fortifiers, may be a practical method to provide iron to premature infants.

Iron Absorption by Human Milk-fed Premature Infants Receiving Supplemental Iron ♦ 1551

To evaluate optimal methods of delivering iron (Fe) to human milk (HM)-fed preterm infants, we measured Fe utilization by 8 HM-fed premature infants[birth weight 1.0 (0.2) kg, gestational age 27 (2) wk, weight at start of study 1.4 (0.3) kg] who were receiving full feedings of human milk fortified with a commercial human milk fortifier. Supplemental Fe was given daily for 7-14 days before the study as 2 mg/kg of ferrous sulfate administered between feedings. On the first study day, 57Fe (2 mg/kg) which had been premixed with a 24-hour supply of fortified HM was fed to the infants, and 58Fe (70 mcg) was administered intravenously (IV). On study day 2, no Fe was mixed with the HM, but 54Fe (2 mg/kg) was administered as ferrous sulfate by orogastric gavage between feedings. Two weeks later, a 1-mL blood sample was collected and red blood cell incorporation (RBC-inc) was calculated from measurement of the isotope enrichment performed using magnetic sector thermal ionization mass spectrometry. Percent absorption was calculated by dividing the RBC-inc of 54Fe and 57Fe by the RBC-inc of 58Fe. All data are mean (SD).

Nitrogen, Fat, Ca, P, Mg and Cu Plasma Levels and Balance of VLBW-Infants Fed with Formula or Own Mother's Milk Enriched with Evaporated Human Milk or Commercial Human Milk Fortifier (HMF) 1512

We developed an evaporated human milk (EHM) that can be used as a fully homologous human milk fortifier (Nutr. Res. 1996; 16: 769-72). After human milk evaporation the nutrient levels increased an average of 3 to 4 times, except for fat and lactose. A prospective study was conducted on 56 VLBW-infants (birth weight <1500g) to evaluate the plasma levels and nutrient balance of N, fat, Ca, P, Mg, Zn and Cu. Infants were included in the study as soon as they were tolerating full feds on 160 ml/kg/d. They were divided in 3 groups. Those whose mother had enough breast milk were randomly divided into two groups, each receiving one of two fortifiers: EHM (1/4 EHM, 3/4 own mother's milk, 18 infants) or a commercial HMF (Eoprotin 4%, Milupa GmbH & Co. Kg, Germany, 18 infants). If the mother had no milk they received preterm formula [FOR group]: (Prematil, Milupa GmbH & Co. Kg, Germany, 20 infants). Blood was collected on the 1st and after 30 days of study. 72hs balance was performed after one week. The team that provided care for the infants and administered the different formulas was unaware of the type of diet that was being offered. Regarding plasma levels, the EHM group showed lower levels of P (4.4± 0.6 mg/dl vs 7.2±1.0mg/dl [HMF] and 6.7±1.1mg/dl [FOR] and higher levels of alkaline phosphatase(1312±783 IU vs 611±182 IU [HMF] and 531±171IU[FOR]. Other plasma levels were similar between groups. Infants fed own mother's milk presented similar retention of nutrients with different fortifiers and better nutrient retention as compared to formula for fat, Ca, P and Cu. Formula and commercial HMF fed infants presented adequate plasma levels and nutrient retention. EHM as used,was inadequate regarding P levels. The use of higher volumes of the evaporated human milk or addition of P must be analyzed before the use of this absolutely homologous way of feeding VLBW-infants is recommended.

Acceptability and Growth of VLBW-Infants Fed with Own Mother's Milk Enriched with a Natural or Commercial Human Milk Fortifier (HMF) † 1370

Acceptability and Growth of VLBW-Infants Fed with Own Mother's Milk Enriched with a Natural or Commercial Human Milk Fortifier (HMF) † 1370