Human Milk Fortifier Research Articles

Case–control study of milk curd obstruction in newborn infants in a tertiary surgical neonatal intensive care unit

BackgroundMilk curd obstruction (MCO), in which milk becomes inspissated, is a rare, serious, complication of preterm birth. Case reports implicate male sex and bovine-derived human milk fortifier (HMF) use as...

Effect of Human Milk Fortifiers, Medium-chain Triglyceride Oil, Minerals, and Vitamin Supplements on the Osmolality of Pasteurized Donor Human Milk

Aim: We aimed to study the changes in osmolality of pasteurized donor human milk (PDHM) after the addition of four human milk fortifiers (HMFs), medium-chain triglyceride (MCT) oil, minerals, and vitamin supplements commonly used in neonates. Methods: The osmolality of 25 ml of PDHM was measured after the addition of 1 g each of HMF and 0.5 ml of MCT oil separately with a calibrated osmometer. The osmolality of 5 ml of PDHM was measured after the addition of minerals and vitamin supplements in therapeutic doses separately. All these measurements were carried out at 10 min, 30 min, and 2 h by a technician who was blinded to the fortifiers, minerals, and vitamin supplements used. Results: The osmolality of PDHM was 256 mOsm/kg (range = 256–259 mOsm/kg), which increased with all four HMFs tested, but remained below 450 mOsm/kg as recommended by the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). Proprietary fortifiers increased the osmolality of PDHM to a maximum of 429 mOsm/kg (range = 306–429 mOsm/kg). However, there was no change in the osmolality with MCT oil. A maximum increase in osmolality was observed with the addition of calcium phosphate syrup to PDHM (1181 mOsm/kg). The addition of multivitamins and Vitamin D3 in therapeutic doses increased osmolality (range = 552–753 mOsm/kg) beyond the safety limits of ESPGHAN recommendation. Conclusions: HMFs increased the osmolality of PDHM but were within the safety limits of ESPGHAN recommendation. MCT oil did not affect the osmolality of PDHM. Minerals and vitamin supplements added in therapeutic dosages significantly increased the osmolality of PDHM. Minerals and vitamin supplements need to be appropriately diluted to keep osmolality below 450 mOsm/kg to ensure safety. Future research should focus on manufacturing fortifiers and supplements with low osmolality to ensure safety.

Adverse effects of human milk fortifier on preterm neonates in a neonatal intensive care unit of a tertiary care hospital, Karachi.

Objective: To determine adverse effects of Human Milk Fortifier on Preterm neonates in a Neonatal Intensive Care Unit. Study Design: Descriptive study. Setting: Indus Hospital NICU in Karachi. Period: Mar 2022 to September 2023. Methods: Aimed to investigate the adverse effects of HMF on 139 preterm neonates. The study excluded infants with congenital anomalies. Adverse effects, including Necrotizing Enterocolitis (NEC), metabolic acidosis, feeding intolerance, and other complications, were monitored. Results: The findings revealed that feeding intolerance was the most common adverse effect of HMF. Mild metabolic acidosis and NEC were also observed. These results are consistent with previous studies and may be attributed to the high osmolality of feeds following fortification with HMF. Despite the well-established role of HMF in promoting weight gain in preterm infants, the study underscores the importance of closely monitoring its use. Conclusion: Careful consideration of the potential risks and benefits of HMF is essential before prescribing it to preterm neonates. Future research with larger sample sizes and controlled designs is needed to validate these findings and explore strategies to mitigate the adverse effects of HMF in NICU settings.

Peptidomic profile of human milk as influenced by fortification with different protein sources: An in vitro dynamic digestion simulation

Fortification of human milk (HM) is often necessary to meet the nutritional requirements of preterm infants. The present experiment aimed to establish whether the supplementation of HM with either an experimental donkey milk-derived fortifier containing whole donkey milk proteins, or with a commercial bovine milk-derived fortifier containing hydrolyzed bovine whey proteins, affects peptide release differently during digestion. The experiment was conducted using an in vitro dynamic system designed to simulate the preterm infant's digestion followed by digesta analysis by means of LC-MS-MS. The different fortifiers did not appear to influence the cumulative intensity of HM peptides. Fortification had a differential impact on the release of either donkey or bovine bioactive peptides. Donkey milk peptides showed antioxidant/ACE inhibitory activities, while bovine peptides showed opioid, dipeptil- and propyl endo- peptidase inhibitory and antimicrobial activity. A slight delay in peptide release from human lactoferrin and α-lactalbumin was observed when HM was supplemented with donkey milk-derived fortifier.

Maternal, neonatal, and nutritional risk factors for medical and surgical necrotizing enterocolitis.

To identify maternal and neonatal risk factors associated with progression to surgery or death after diagnosis of NEC. Forty-seven demographic and clinical factors were evaluated across 216 validated cases of NEC occurring between 2010-2020. Nutrition at NEC onset was evaluated in 149 cases. The binary outcome of surgical NEC (progressing to surgery or death) vs. medical NEC (resolved with antibiotic/bowel rest) was compared across variables. Elevated CRP, rapidly decreasing platelet counts, inotropic medication, intubation, and positive blood cultures within 24 h of diagnosis were associated with progression to surgery/death. Infants with surgical NEC had higher abdominal circumferences at birth. Maternal milk intake and receipt of human milk fortifiers were associated with medical NEC, and infants receiving fortified, maternal milk showed the lowest progression to surgery/death. The index of suspicion should be heightened for surgical NEC when these risk factors are present.

Exploring Current Practices, Challenges, and Innovations in the Nutrition and Feeding of Neonates, Including the Use of Human Milk, Fortifiers, and Formula: A Clinical Study

ABSTRACT Background: Neonatal nutrition plays a crucial role in the growth and development of infants, particularly in the neonatal intensive care unit (NICU) where specialized care is essential. This study aims to explore current practices, challenges, and innovations in the nutrition and feeding of neonates, focusing on the utilization of human milk, fortifiers, and formula. Materials and Methods: A retrospective clinical study was conducted at a tertiary care NICU over a period of two years. Data were collected from medical records of neonates admitted to the unit. Information regarding feeding practices, types of milk (human milk, fortified human milk, or formula), fortification protocols, and associated clinical outcomes were analyzed. Results: A total of 150 neonates were included in the study. The majority (85%) received some form of human milk during their NICU stay, with 60% exclusively receiving human milk. Among those receiving human milk, 40% required fortification with a human milk fortifier due to inadequate growth parameters. Formula supplementation was necessary in 25% of cases due to maternal lactation insufficiency or medical contraindications to human milk. The mean duration of parenteral nutrition was 10 days, with a median time to full enteral feeds of 14 days. Infants receiving exclusively human milk demonstrated a lower incidence of necrotizing enterocolitis (NEC) compared to those receiving formula (5% vs. 12%, P < 0.05). Conclusion: Human milk remains the preferred source of nutrition for neonates in the NICU setting, associated with lower rates of NEC and improved clinical outcomes. However, fortification with human milk fortifiers or supplementation with formula is often necessary to meet the nutritional requirements of preterm infants. Further research is needed to optimize fortification protocols and improve long-term outcomes in this vulnerable population.

Use of human milk fortifier in preterm infants in the community: practical experience from clinical cases

Use of human milk fortifier in preterm infants in the community: practical experience from clinical cases

Reducing extrauterine growth restriction in very preterm neonates: A before-after intervention study.

Focus on preterm nutrition strategies is imperative. Extrauterine growth restriction (EUGR) is a clinically relevant, but seemingly elusive consequence, often used to benchmark and compare outcomes. This before-after observational study was designed to study the effect of a multipronged updated "nutrition care bundle" in very preterm infants on rate of EUGR compared with a cohort from a previous period. Eligible participants were neonates born at <32 weeks' gestation who completed care in the unit; a retrospective group from a previous period and a prospective cohort after implementation of the bundle were included. The bundle constituted of three key areas: (1) aggressive parenteral nutrition with high-dose amino acids and lipids from day 1, (2) "rapid-escalation" enteral feed regimens including earlier introduction of human milk fortifier (at 40-ml/kg/day feeds), and (3) colostrum mouth paint and structured oromotor stimulation to promote oral feeding. EUGR was defined as a z score difference of >-1 in weight for postmenstrual age (PMA) at discharge and at birth. Data of 116 infants were retrieved for the retrospective group; 103 infants were included in the prospective group. EUGR was reduced from 71% to 58% (P = 0.039) after implementation of the bundle. Infants in the prospective group achieved full oral feeds at earlier PMA (P < 0.001) and were discharged at earlier PMA (P = 0.002). The proportion of neonates with EUGR was reduced significantly after implementation of the revised nutrition care bundle. Achievement of full oral feeds and discharge readiness were earlier in the prospective group.

Testing the reported long-term advantages of protein-fortified human milk in very low birth weight neonates

Preterm infants are at-risk for extrauterine growth restriction and downward percentile-crossing between birth and discharge. Increased energy and protein intake through fortification of human milk during the first weeks of life has been associated with improved short-term growth and better developmental outcomes. The aim of this study was to evaluate whether these benefits persist up to children school age. The study was designed as an observational study. During hospitalization, 22 very low birth weight preterm infants were fed with increasing protein fortification of human milk (protein supplemented group, PSG). As a control group (CG), 11 preterm infants were fed with standard nutrition regimen. At children school age (9–11 years), we assessed anthropometric data (weight, height, BMI), global health (renal function), and specific psychological outcomes (Child Behavior Checklist 6–18). A global homogeneity between CG and PSG groups emerged: we found no significant differences in weight, height, and BMI, nor in internalizing symptom outcomes (all ps &amp;gt; 0.05). However, mothers reported significantly higher externalizing symptoms for the PSG infants compared to CG infants. Therefore, neonatal enteral protein supplementation in very low birth weight preterm infants leads to no positive nor adverse consequences in long-term assessment, suggesting that benefits are restricted to the neonatal term and first years of age.

Immediate fortification of human milk with a bovine milk-derived human milk fortifier in very low birth weight infants: a randomized clinical trial

ObjectiveDouble-blind randomized control trial of early addition of a bovine milk-derived human milk fortifier (HMF) in very low birth weight (VLBW) infants (NCT05228535).MethodsVLBW infants were randomized to receive bovine milk-derived HMF with first feedings or delayed fortification at 80 ml/kg/day. Anthropometrics were assessed weekly through 36 weeks postmenstrual age (PMA). Unadjusted and adjusted (race, gender, gestational age, and birth weight) differences between study arms were examined using two-sample t-test and ANCOVA, respectively.ResultsFifty-two VLBW infants (57% female, 60% Black) were enrolled. Baseline demographics did not differ between groups. Weight velocity at DOL 28 did not differ between study arms. Secondary outcomes including NPO occurrence, incidence of metabolic acidosis, NEC, retinopathy, or late-onset sepsis did not differ between groups.ConclusionImmediate fortification of enteral feedings with a bovine milk-derived HMF appears safe and well-tolerated although no clear growth benefit could be established.

Efficacy of human milk fortification in low-birth-weight infants; A randomized controlled trial

Introduction: Low Birth Weight (LBW), less than 2500grams, has significant effect on baby survival and growth. A good supportive care in addition to breastfeeding is very important. Breast milk fortification role is under research. Aims; To study the Efficacy of Human Milk Fortification in Low-Birth-Weight Infants Materials and Methods: This RCT was conducted at Department of pediatrics Lady Reading Hospital, Peshawar, Pakistan, from October 2021 to March 2022. A total of 60 low birth weight neonates were randomly allocated into two arms (group A fortified) and (group B unfortified) through non probability consecutive sampling technique. One group was given fortified expressed breast milk with 1g sachet of Human Milk Fortifier (HMF). The second group was fed with unfortified breast milk only. Babies were monitored every two-weekly with Biochemical markers. Data was analyzed through descriptive and inferential means using independent T Test. Results: The mean weight of neonates in the supplemented group was 2273.83g (Mean SD = 2273.83g 182.83g) and in the control group it was 2176.67g (Mean SD = 2176.67g 181.86g). Result shows that infants given human milk fortifier gain more weight as compared to breast milk. Statistical analysis also showed significant difference (P value 0.017) Conclusion: It is concluded that use of human fortified milk is helpful in gaining weight in low birth weight infants. It also improves serum calcium and protein levels.

Growth and Neurodevelopmental Outcomes of Preterm Infants Born < 26 Weeks Gestation before and after Implementation of a Nutrition-Care Bundle.

This study aimed to assess the impact of a nutrition-care bundle on growth and neurodevelopmental outcomes of micro-preterm infants born in a level III neonatal intensive care unit (NICU) by two years corrected age. A nutrition-care bundle emphasizing the prompt initiation of parenteral nutrition at birth, initiation of enteral feeds within 6 h after birth, and early addition of human milk fortifiers was implemented in 2015 for infants born < 26 weeks gestation. This before-and-after study evaluated growth and neurodevelopmental outcomes in infants born between 2012-2013 (before-nutrition-bundle, BNB) and 2016-2017 (after-nutrition-bundle, ANB). A total of 145 infants were included in the study. Infants in the ANB group (n = 73) were smaller (birthweight and gestational age), and there were more male infants and multiples included compared to the BNB group (n = 72). Enteral feeds and fortifiers started earlier in the ANB group. Growth velocity and weight z-score changes were similar in both groups during NICU stay and post-discharge. Systemic steroid use, but not cohort, was linked to lower Bayley scores across all domains. Implementing a nutrition-care bundle was not consistently associated with improved weight gain and neurodevelopmental outcomes in the micro-preterm infant population, possibly due to ongoing high-quality nutritional care by the clinical team.

Mineral supplementation for very preterm infants fed fortified human milk.

The safety and feasibility of human milk fortification with bovine colostrum (BC) were investigated in very preterm infants (FortiColos trial, NCT03537365). The BC product contained lower calcium, phosphate, and iron levels compared to the conventional fortifier (CF). We tested whether fortification with BC plus extra phosphate was sufficient to support the infants' mineral status assessed by blood biochemistry. In a randomised controlled trial (FortiColos, NCT03537365), mineral status was compared after fortification with BC versus CF. Blood calcium, phosphate, and haemoglobin were determined before and up to 3 weeks after the start of fortification (at the mean age of 8-9 days). The maximum supplemental doses of calcium, phosphate, and iron given were retrieved from patient medical records. Results were adjusted for gestational age,birth weight, and enteral nutrition with the mother's own milk and/or donor human milk. Blood values of calcium, phosphate, and haemoglobin were similar between groups. Infants in both groups required supplementation with calcium and phosphate, but infants fed BC required higher maximum doses of phosphate and calcium (p < 0.05) to maintain acceptable blood values. Regardless of fortification groups, the most immature (<29 weeks of gestation) and small for gestational ageinfants showed a higher risk for requiring additional phosphate (odds ratio [OR]: 3.9, p < 0.001; OR: 2.14, p = 0.07, respectively). The use of BC as a fortifier for human milk requires additional phosphate and calcium relative to a CF. Regardless of the fortification product, the most immature and small infants require additional mineral supplementation.

Glucose-regulatory hormones and growth in very preterm infants fed fortified human milk

BackgroundBovine colostrum (BC) contains a range of milk bioactive components, and it is unknown how human milk fortification with BC affects glucose-regulatory hormones in very preterm infants (VPIs). This study aimed to investigate the associations between hormone concentrations and fortification type, birth weight (appropriate/small for gestational age, AGA/SGA), milk intake, postnatal age, and body growth.Methods225 VPIs were randomized to fortification with BC or conventional fortifier (CF). Plasma hormones were measured before, one and two weeks after start of fortification. ΔZ-scores from birth to 35 weeks postmenstrual age were calculated.ResultsCompared with CF, infants fortified with BC had higher plasma GLP-1, GIP, glucagon, and leptin concentrations after start of fortification. Prior to fortification, leptin concentrations were negatively associated with growth, while IGF-1 concentrations associated positively with growth during fortification. In AGA infants, hormone concentrations generally increased after one week of fortification. Relative to AGA infants, SGA infants showed reduced IGF-1 and leptin concentrations.ConclusionFortification with BC increased the plasma concentrations of several glucose-regulatory hormones. Concentrations of IGF-1 were positively, and leptin negatively, associated with growth. Glucose-regulatory hormone levels were affected by birth weight, milk intake and postnatal age, but not closely associated with growth in VPIs.ImpactLittle is known about the variation in glucose-regulatory hormones in the early life of very preterm infants (VPIs).This study shows that the levels of glucose-regulatory hormones in plasma of VPIs are highly variable and modified by birth weight (appropriate or small for gestational age, AGA or SGA), the type of fortifier, enteral nutritional intake, and advancing postnatal age.The results confirm that IGF-1 levels are positively associated with early postnatal growth in VPIs, yet the levels of both IGF-1 and other glucose-regulatory hormones appeared to explain only a small part of the overall variation in growth rates.

The Effect of Unadjusted Mineral Supplementation on Bone Health of Preterm Infants Fed Fortified Human Milk: An Exploratory Analysis

Background: In standard fortification of human milk (HM), the HM macronutrient content is assumed, and a fixed amount of a multinutrient fortifier is added to achieve recommended nutrient intakes. In target fortification, the HM macronutrient content is regularly measured, guiding the addition of modular macronutrient supplements to the fortified HM, to achieve the nutritional targets more precisely. Objective: The study aimed to investigate whether this addition of modular supplements, unaccompanied by mineral supplementation, predispose to metabolic bone disease (MBD). Methods: This is a secondary analysis of a larger study of infants born with &lt;33 weeks gestational age. Fortifications based on the assumed (Group 1) or measured (Group 2) of the HM macronutrient content were compared, using low serum phosphate levels as an indicator of MBD, and length growth as a surrogate of bone growth. Results: Eighty-four infants were included, 35 in Group 1 and 49 in Group 2. During the exposure period, infants of Group 2 received higher mean fat (6.1 vs. 5.3 g/kg/day, P &lt; 0.001) and carbohydrate (13.0 vs. 11.7 g/kg/day, P &lt; 0.001) intakes; in addition, they exhibited lower mean serum phosphate (5.5 vs. 6.0 mg/dL, P = 0.022) and faster mean length velocity (1.06 vs. 0.89 cm/week, P = 0.003). Conclusions: These findings suggest that feeding fortified HM with extra fat and carbohydrate content, unaccompanied by mineral supplementation, promotes increased bone growth, as indicated by accelerated length growth, but with insufficiently mineralized osteoid, indicated by low serum phosphate levels. Intervention studies using direct biomarkers of bone mass content and mineral density are necessary to corroborate our findings.

Association of Fortification with Human Milk versus Bovine Milk-Based Fortifiers on Short-Term Outcomes in Preterm Infants-A Meta-Analysis.

This meta-analysis assessed short-term outcomes after using human milk-derived fortifiers (HMFs) compared with bovine milk fortifiers (BMFs) in preterm infants fed an exclusive human milk (HM) diet, either mother's own milk (MOM) or donor human milk (DHM). We searched PubMed, Embase, Google Scholar, CENTRAL and CINHAL between January 2015 and August 2023 for studies reporting outcomes in infants with ≤28 weeks gestation and/or birthweight ≤ 1500 g on an exclusive human milk diet fortified with HMF versus BMF. The primary outcomes were death and NEC (stage ≥ 2). Four studies with a total of 681 infants were included. Mortality was significantly lower in infants fed with an HM-HMFs diet (four studies, 681 infants; RR = 0.50, 95% CI = 0.26-0.94; p = 0.03; I2 = 0%), NEC was similar between the two groups (four studies, 681 infants; RR = 0.48, 95% CI = 0.20-1.17; p = 0.11; I2= 39%). BPD was higher in the HM-BMFs group (four studies, 663 infants; RR = 0.83, 95% CI = 0.69-1.000; p = 0.05, I2 = 0%), although not statistically significant. No differences were found for sepsis (RR = 0.97, 95% CI = 0.66-1.42; p = 0.96; I2 = 26%) or combined ROP (four studies, 671 infants; RR = 0.64, 95% CI = 0.53-1.07; p = 0.28; I2 = 69%). An HM-HMFs diet could possibly be associated with decreased mortality with no association with NEC, BPD, sepsis, or ROP. This meta-analysis was limited by the small number of studies included. However, the results should not be refuted for this reason as they provide an impetus for subsequent clinical trials to assess the observed associations.

Effect of novel human milk oligosaccharides-based human milk fortifier containing lactoferrin, docosahexaenoic acid, and arachidonic acid on the growth of preterm infants with birth weight of 700–1800 g

Background: Premature infants with low birth weight are at risk of growth failure and neurodevelopmental impairment. Human milk oligosaccharides (HMOs) are bioactive components of human milk that may enhance growth and development. The novel HMO-based human milk fortifier (HMoF), which also contains lactoferrin, docosahexaenoic acid (DHA), and arachidonic acid (ARA), can help provide a safer nutritional option for the growth of premature infants. Materials and Methods: We conducted a non-comparative observational study using data from multiple centers that used novel HMO-based HMF (HMoF) in premature infants (n=14) with birth weights of 700–1800 g. The primary outcome of the study was to assess tolerability (in terms of feed tolerance), and secondary outcomes included growth outcomes defined by weight, length, and head circumference during the stay in the NICU and at discharge. Results: A cohort consisting of 14 infants with a mean gestational age of 30.21±2.04 weeks and a birth weight of 1246.36±39.98 g comprised the study. During the study period, incidences of feed interruptions due to feed intolerability were nil, and no infant presented with any signs of adverse effects. The novel HMO-based HMF (HMoF)-fed infant cohort had a mean weight gain of 21.89±5.23 g/day, a mean length gain of 1.01±0.48 cm/week, and mean head circumference gain of 0.89±0.32 cm/week. The mean growth velocity recorded was 16.03±1.73 g/kg/day. Conclusions: Novel HMO-based HMF (HMoF) containing lactoferrin, DHA, and ARA demonstrated acceptable feed tolerance and weight gain without any clinically significant adverse effects. Data indicates that the novel HMoF containing lactoferrin, DHA, and ARA is a safe option for supporting the growth of preterm babies. However, further studies are needed to compare novel HMO-based HMF (HMoF) with standard HMF in a randomized controlled trial.

Does Early Fortification of Human Milk Decrease Time to Regain Birth Weight as Compared to Late Fortification Among Preterm Infants? - A Randomized Controlled Trial.

To compare the duration required to regain birth weight following early fortification of human milk vs. late fortification among preterm infants. This randomized controlled trial included hemodynamically stable 120 preterm infants (≤32 wk of gestation). The intervention and comparator groups received standard fortification with human milk fortifier when enteral feeds reached 30ml/kg/d (early fortification) and 80ml/kg/d (late fortification) respectively. Neonates in both the groups received feed increments as per standard NICU protocol. Anthropometric measurements (weight, length, and head circumference) at birth and during postnatal follow-up were done following standard precautions and plotted on the sex-specific Fenton growth charts. Primary outcome was the mean duration required to regain birth weight. Secondary outcomes included weight gain velocity, linear growth, increase in head circumference and occurrence of sepsis, feed intolerance and necrotizing enterocolitis. Preterm neonates who received early fortification regained birth weight earlier compared to those in the late fortification group (10.13 ± 2.90 vs. 11.26 ± 3.06, p <0.05). The weight gain velocity, linear growth and increase in head circumference were better in the early fortification group. There was no increased risk of culture proven sepsis, feed intolerance and necrotizing enterocolitis in the early fortification group compared to late fortification. Standard fortification with human milk fortifier when enteral feeds reach 30ml/kg/d helps preterm neonates regain birth weight earlier. Early fortification is well tolerated and safe for the population studied.

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.