Human Milk Fortifier Research Articles

Using a new human milk fortifier to optimize human milk feeding among very preterm and/or very low birth weight infants: a multicenter study in China

BackgroundHuman milk fortifier (HMF) composition has been optimized recently. But clinical evidence of its safety and efficacy is limited in Chinese population. The aim of this study was to evaluate effects of a new HMF in growth, nutritional status, feeding intolerance, and major morbidities among very preterm (VPT) or very low birth weight (VLBW) infants in China.MethodsVPT/VLBW infants admitted from March 2020 to April 2021 were prospectively included in the experimental (new HMF, nHMF) group, who received a new powdered HMF as a breast milk feeding supplement during hospitalization. Infants in the control group (cHMF) admitted from January 2018 to December 2019, were retrospective included, and matched with nHMF group infants for gestational age and birth weight. They received other kinds of commercially available HMFs. Weight gain velocity, concentrations of nutritional biomarkers, incidence of major morbidities, and measures of feeding intolerance were compared between the two groups.ResultsDemographic and clinical characteristics of infants in nHMF and cHMF groups were comparable. Weight gain velocity had no significant difference between the nHMF (14.0 ± 3.5 g/kg/d) and the cHMF group (14.2 ± 3.8 g/kg/d; P = 0.46). Incidence of morbidities, including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, culture-confirmed sepsis, and feeding intolerance during hospitalization between nHMF and cHMF, were similar (all P-values > 0.05). The time to achieve full enteral feeding [13.5 (10, 21) days] in the nHMF group was significantly shorter than that in the cHMF group [17 (12, 23) days, HR = 0.67, 95%CI: 0.49, 0.92; P = 0.01]. Compared with cHMF group, the decrease of blood urea nitrogen level over time in nHMF group was smaller (β = 0.6, 95%CI:0.1, 1.0; P = 0.01).ConclusionsThe new HMF can promote growth of preterm infants effectively without increasing the incidence of major morbidity and feeding intolerance. It can be used feasible in Chinese VPT/VLBW infants.Trial registrationThis study was registered on ClinicalTrials.gov (NCT04283799).

Human milk cream alters intestinal microbiome of preterm infants: a prospective cohort study.

In very low birth weight (VLBW) infants, human milk cream added to standard human milk fortification is used to improve growth. This study aimed to evaluate the impact of cream supplement on the intestinal microbiome of VLBW infants. Whole genome shotgun sequencing was performed on stool (n = 57) collected from a cohort of 23 infants weighing 500-1250 grams (control = 12, cream = 11). Both groups received an exclusive human milk diet (mother's own milk, donor human milk, and donor human milk-derived fortifier) with the cream group receiving an additional 2 kcal/oz cream at 100 mL/kg/day of fortified feeds and then 4 kcal/oz if poor growth. While there were no significant differences in alpha diversity, infants receiving cream significantly differed from infants in the control group in beta diversity. Cream group samples had significantly higher prevalence of Proteobacteria and significantly lower Firmicutes compared to control group. Klebsiella species dominated the microbiota of cream-exposed infants, along with bacterial pathways involved in lipid metabolism and metabolism of cofactors and amino acids. Cream supplementation significantly altered composition of the intestinal microbiome of VLBW infants to favor increased prevalence of Proteobacteria and functional gene content associated with these bacteria. We report changes to the intestinal microbiome associated with administration of human milk cream; a novel supplement used to improve growth rates of preterm very low birth weight infants. Since little is known about the impact of cream on intestinal microbiota composition of very low birth weight infants, our study provides valuable insight on the effects of diet on the microbiome of this population. Dietary supplements administered to preterm infants in neonatal intensive care units have the potential to influence the intestinal microbiome composition which may affect overall health status of the infant.

Lyophilized (freeze-dried) human milk for preterm infants: a scoping review.

Freeze-drying (FD), or lyophilization, is commonly used to preserve foods. FD offers potential to create a human milk-derived human milk fortifier, and an alternative to freeze-storing human milk. However, processing human milk is known to affect its components. This scoping review explores the effect of FD on the; macronutrient, micronutrient, vitamin, bioactive components, microbes and anti-microbial factors in human milk, and studies where lyophilized human milk has been given to newborn infants. 48 articles were identified after full text review. FD human milk reduces the fat globule size and as well as the quantity of enzymes, vitamin C and immunoglobulin. Common serum electrolyte disturbances have been reported when preterm infants' are fed FD human milk however it appears a promising method to avoid exposure of preterm infants' to cows' milk. Due to limited data, further studies exploring the safety and efficacy of FD human milk in preterm infants are needed.

Comparative Growth Outcomes in Very Low Birth Weight Infants: Evaluating Different Feeding Strategies.

To assess the growth pattern of preterm, very low birth weight (VLBW) appropriate for gestational age (AGA) infants on three different feeding regimens. This prospective open label three-arm parallel randomized controlled trial was conducted at neonatal intensive care unit, Kasturba Hospital, Manipal. One hundred twenty VLBW (weight between 1000-1500g and gestational age 28-32 wk) preterm AGA infants admitted from April 2021 through September 2022 were included. Three feeding regimens were compared: Expressed breast milk (EBM); EBM supplemented with Human milk fortifier (HMF); EBM supplemented with Preterm formula feed (PTF). Primary outcome measure was assessing the growth parameters such as weight, length, head circumference on three different feeding regimens at birth 2, 3, 4, 5 and 6 wk/discharge. Secondary outcomes included incidence of co-morbidities and cost-effectiveness. Of 112 infants analyzed, Group 2 supplemented with HMF showed superior growth outcomes by 6th wk/discharge of intervention, with mean weight of 2053±251g, mean length of 44.6±1.9cm, and mean head circumference of 32.9±1.4cm. However, infants in Group 3, supplemented with PTF, registered mean weight of 1968±203g, mean length of 43.6±2.0cm, and mean head circumference of 32.0±1.6cm. Infants exclusively on EBM presented with mean weight of 1873±256g, mean length of 43.0±2.0cm and mean head circumference of 31.4±1.6cm. Addition of 1 g of HMF to 25 ml of EBM in neonates weighing 1000-1500 g showed better weight gain and head circumference at 6 wk/discharge, which was statistically significant. However, no significant differences in these parameters were observed at postnatal or 2, 3, 4, and 5 wk.

Analyzing the Responses of Enteric Bacteria to Neonatal Intensive Care Supplements.

In the neonatal intensive care unit, adequate nutrition requires various enteral products, including human milk and formula. Human milk is typically fortified to meet increased calorie goals, and infants commonly receive vitamin mixes, iron supplements, and less frequently, thickening agents. We examined the growth of 16 commensal microbes and 10 pathobionts found in the premature infant gut and found that formula, freshly pasteurized milk, and donated banked milk generally increased bacterial growth. Fortification of human milk significantly elevated the growth of all microbes. Supplementation with thickeners or NaCl in general did not stimulate additional growth. Vitamin mix promoted the growth of several commensals, while iron promoted growth of pathobionts. These data indicate that pathobionts in the preterm gut have significant growth advantage with preterm formula, fortified donor milk, and supplemented iron and suggest that the choice of milk and supplements may impact the infant gut microbiota.

Laboratory scale production of a powdered, multi-nutrient human milk fortifier

The objective of this study was to demonstrate the feasibility of producing a powdered, multi-nutrient breast milk fortifier made from donated human milk with a target energy (400 kcal 100 g−1 powder) and protein (40 g protein 100 g−1 powder) composition, supplementation of selected micronutrients, and acceptable solubility and osmolality for clinical use. Three combinations of ultrafiltration (UF) and diafiltration (DF) steps, using either a polyethersulphone (PES) or polyvinylidene fluoride (PVDF) membrane with 50 kDa molecular mass cut-off, were compared to determine the most efficient process to achieve the target product composition. A process combining one UF and two DF steps using the PVDF membrane was found to be most efficient, resulting in a freeze-dried product with a final average composition of protein, fat and carbohydrates of 40.7, 11.3 and 47.1 g 100 g−1, respectively.

Taking Human Milk Fortification to the Next Level.

Taking Human Milk Fortification to the Next Level.

Preterm Formula, Fortified or Unfortified Human Milk for Very Preterm Infants, the PREMFOOD Study: A Parallel Randomised Feasibility Trial

Objective: Uncertainty exists regarding optimal supplemental diet for very preterm infants if the mother’s own milk (MM) is insufficient. We evaluated feasibility for a randomised controlled trial (RCT) powered to detect important differences in health outcomes. Methods: In this open, parallel, feasibility trial, we randomised infants 25+0–31+6 weeks of gestation by opt-out consent to one of three diets: unfortified human milk (UHM) (unfortified MM and/or unfortified pasteurised human donor milk (DM) supplement), fortified human milk (FHM) (fortified MM and/or fortified DM supplement), and unfortified MM and/or preterm formula (PTF) supplement from birth to 35+0 weeks post menstrual age. Feasibility outcomes included opt-outs, adherence rates, and slow growth safety criteria. We also obtained anthropometry, and magnetic resonance imaging body composition data at term and term plus 6 weeks (opt-in consent). Results: Of 35 infants randomised to UHM, 34 to FHM, and 34 to PTF groups, 21, 19, and 24 infants completed imaging at term, respectively. Study entry opt-out rate was 38%; 6% of parents subsequently withdrew from feeding intervention. Two infants met predefined slow weight gain thresholds. There were no significant between-group differences in term total adipose tissue volume (mean [SD]: UHM: 0.870 L [0.35 L]; FHM: 0.889 L [0.31 L]; PTF: 0.809 L [0.25 L], p = 0.66), nor in any other body composition measure or anthropometry at either timepoint. Conclusions: Randomisation to UHM, FHM, and PTF diets by opt-out consent was acceptable to parents and clinical teams, associated with safe growth profiles and no significant differences in body composition. Our data provide justification to proceed to a larger RCT.

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.

Comparison of Effect of Human Milk Fortification with Preterm Formula Powder Vs Human Milk Fortification with Human Milk Fortifier on the Growth of Very Low Birth Weight Newborns

Aim: The primary aim of this scientific inquiry was to comprehensively assess how the nourishment of Very Low Birth Weight (VLBW) newborns could be improved by supplementing their diet with either human milk fortifier or preterm formula powder. Methods: A randomized controlled trial was carried out at RTEH Muzaffargarh NICU, which involved the participation of 72 preterm infants weighing between 1.2 kg and 1.6 kg at birth. The infants were randomly allocated into two groups: one received human milk fortified with preterm formula powder. In contrast, the other group received human milk fortified with a human milk fortifier. Throughout the study, weight, length, and head circumference measurements were taken for all participants. Results: There were no significant differences in gestational ages between HMF and preterm formula groups (p=0.057), nor in gender distribution (p=0.369 for males). Post-intervention, Group A experienced significant increases in birth weight (p=0.0021) and head circumference (p=0.004), but not in length. In the control group, changes in weight, head circumference, and length did not reach statistical significance. Conclusion: Human milk fortification with preterm formula powder appears to promote similar or even better growth outcomes in VLBW infants when compared to traditional fortification with human milk fortifier. However, more research is needed to confirm these findings and assess any potential long-term impacts. Keywords: Human Milk Fortification, Preterm Formula Powder, Very Low Birth Weight Infants, Growth Outcomes, Randomized Controlled Trial.

Benefits of use of human milk fortifier in preterm infants in the community: Practical experience from a case study series

Benefits of use of human milk fortifier in preterm infants in the community: Practical experience from a case study series

Evaluation of the Use of Dedicated Technicians and Bar Code Scanning Technology for Fortified Human Milk Feeding Preparation in a Single Neonatal Intensive Care Unit to Reduce Risk of Adverse Events

Evaluation of the Use of Dedicated Technicians and Bar Code Scanning Technology for Fortified Human Milk Feeding Preparation in a Single Neonatal Intensive Care Unit to Reduce Risk of Adverse Events

BREAST MILK FORTIFICATION FOR PRETERM INFANTS

Mother’s own milk is the optimal food for infants. It is characterized not only by a unique balanced composition of nutrients, but also by essential biological properties, which is especially important for preterm infants. If there is no mother’s milk or it is amount is not enough to meet daily needs, it is recommended to use donor human milk (HM) instead. However, donor HM is commonly obtained from the women who delivered at term and often does not contain enough protein to promote proper growth of preterm infants. Whether donor milk or the mother’s own milk, human milk fortifi cation is essential to meet the nutrient needs for growth and development of these preterm infants, who are at high risk of growth retardation during hospital stay. There are several strategies and commercially available HM fortifi ers that can be used to maintain the desired growth rate. Standard HM fortifi cation, which is currently most commonly used in neonatal intensive care units, may not meet the increased protein needs of a signifi cant proportion of very low birth weight infants.Instead, individualized fortifi cation can optimize nutrient intake. It is possible to individualize the food supply with the help of regulated or targeted HM fortifi cation. The quality and origin of commercially available HM fortifi ers are also important. To implement an individualized approach to the fortifi cation of HM, the use of milk analyzers can be useful. However, the clinical benefi ts of individual approaches to breast milk fortifi cation and the use of diff erent commercially available HM fortifi ers remain largely unknown. This review presents the results of the most important studies that infl uence clinical practice and describes current approaches to HM fortifi cation with relevant practical recommendations.

Human milk fortification and use of infant formulas to support growth in the neonatal intensive care unit.

Newborn infants require adequate nutrition to achieve full potential growth and development. Early life nutrition and health impacts long-term outcomes through adulthood. Human milk is the optimal source of nutrition during the first 6 months of life. However, infants admitted to the neonatal intensive care unit (NICU) often have comorbidities that create more or different nutrition demands than healthy newborns. There are different strategies to meet the nutrition needs of sick newborns, including use of parenteral nutrition, human milk fortifiers (HMFs), and infant formulas. Multinutrient HMFs are frequently used to achieve the higher nutrition demands of preterm infants. They are available in various presentations, such as human milk- or cow milk-derived, liquid or powder, and acidified or nonacidified, each of which has different risks and benefits associated with its use. Infant formulas are available to meet a demand when mother's own milk or donor breast milk is not available or sufficient, and there are also specialty formulas for infants with certain diseases that present unique nutrition needs. This review is focused on the use of HMFs to support the unique nutrition requirements of preterm infants for healthy growth, as well as the indications for the use of formulas among infants in the NICU.

Growth Trends of Very Low Birth Weight Preterm Infants Receiving Donor Human Milk Fortified with Bovine Human Milk Fortifier and a Supplemental Protein Modular

Growth Trends of Very Low Birth Weight Preterm Infants Receiving Donor Human Milk Fortified with Bovine Human Milk Fortifier and a Supplemental Protein Modular

Transient Hypoglycemia and Biochemical Differences in Infants Less Than 1,250 G at Birth Fed Human Milk with Human Milk-Derived Fortifier versus Cow Milk-Derived Fortifier.

Fortification of human milk (HM) with either human milk-derived fortifier (HMDF) or cow milk-derived fortifier (CMDF) is important in preterm infants. The objective is to compare the incidence of hypoglycemia, and biochemical values in infants less than 1,250 g at birth fed HMDF versus CMDF. It is a retrospective cohort study on infants less than 1,250 g at birth who were fed with HMDF or CMDF. Hypoglycemia was defined as blood glucose (BG) level equal to or less than 60 mg/dL within 72 hours of full enteral feeds when off total parenteral nutrition and intravenous fluids. Ninety infants were enrolled (HMDF = 61, CMDF = 29). HMDF group had a higher rate of hypoglycemia (46 vs. 24%; p = 0.048) after achievement of full enteral feeding. The median minimum BG was lower (61 vs. 71; p ≤ 0.01), while blood urea nitrogen (12 vs. 6; p ≤ 0.01) and albumin (3.1 vs. 2.7; p ≤ 0.01) were higher in HMDF group compared with CMDF. At full enteral feedings in infants less than 1,250 g at birth, an HMDF diet may predispose to hypoglycemia needing intervention. Close monitoring of BG levels once off parenteral nutrition is recommended. · Exclusive human milk (EHM) feeding results in better nutritional indices.. · EHM feeding at higher calorie/ounce improves growth.. · Blood glucose needs to be monitored when off TPN during EHM feeding..

Osmolality of fortified donor human milk: An experimental study.

We quantify the osmolality of human milk fortified with human milk fortifiers (HMFs), powder infant formulas and protein additives. Commercial liquid HMFs and powder infant formulas were added to pasteurized pooled donor human milk in triplicate and stirred. The osmolality of unfortified and fortified human milk at 22, 24, 26, 27, 28, and 30 kcal/oz (0.73, 0.8, 0.87, 0.9, 0.93, and 1 kcal/ml, respectively) was determined using freezing-point depression. The osmolality of fortified human milk associated with energy density in a linear relationship regardless of the fortification strategies. Multiple liquid HMFs and every powder infant formula exceeded the osmolality threshold of 450 mOsm/kg H2 O within the energy densities tested. The osmolality of fortified human milk is highly variable and should be considered when selecting a fortifying agent for human milk.

Real-world evidence regarding the growth of very premature infants with small for gestational age after birth: a multicenter survey in China

BackgroundTo analyze the real-world growth pattern of very premature infants (VPI) with small for gestational age (SGA) after birth by using the ΔZ value of weight at discharge.MethodsThe clinical data were collected from 28 hospitals in China from September 2019 to December 2020. They were divided into the EUGR(Extrauterine Growth Restriction) and the non-EUGR group according to the criterion of ΔZ value of weight at discharge < –1.28.ResultsThis study included 133 eligible VPI with SGA. Following the criterion of ΔZ value, the incidence of EUGR was 36.84% (49/133). The birth weight, the 5-min Apgar score, and the proportion of male infants in the EUGR group were lower (P < 0.05). The average invasive ventilation time, cumulative duration of the administration of antibiotics, blood transfusion time, blood transfusion ratio, and total days of hospitalization were significantly higher in the EUGR group (P < 0.05). In the EUGR group, several factors exhibited higher values (P < 0.05), including the initiation of enteral feeding, the volume of milk supplemented with human milk fortifier (HMF), the duration to achieve complete fortification, the cumulative duration of fasting, the duration to achieve full enteral feeding, the length of parenteral nutrition (PN), the number of days required to attain the desired total calorie intake and oral calorie intake, as well as the age at which birth weight was regained. The average weight growth velocity (GV) was significantly lower in the EUGR group (P < 0.001). The incidences of patent ductus arteriosus with hemodynamic changes (hsPDA), neonatal necrotizing enterocolitis (NEC) stage≥ 2, late-onset sepsis (LOS), and feeding intolerance (FI) in the EUGR group were higher (P < 0.05). Multivariate logistic regression analysis showed that birth weight, male, and GV were the protective factors, while a long time to achieve full-dose fortification, slow recovery of birth weight, and NEC stage ≥2 were the independent risk factors.ConclusionSGA in VPI can reflect the occurrence of EUGR more accurately by using the ΔZ value of weight at discharge. Enhancing enteral nutrition support, achieving prompt and complete fortification of breast milk, promoting greater GV, reducing the duration of birth weight recovery, and minimizing the risk of NEC can contribute to a decreased occurrence of EUGR.Trial registrationCHICTR, ChiCTR1900023418. Registered 26/05/2019, http://www.chictr.org.cn.

Survival of Bioactive Milk Proteins Across Digestion in Preterm Infants Fed with Human Milk and Bovine Milk Fortifier

Survival of Bioactive Milk Proteins Across Digestion in Preterm Infants Fed with Human Milk and Bovine Milk Fortifier

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.