Fortified Milk Research Articles

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.

Nutritional interventions to prevent retinopathy of prematurity.

Very preterm infants are at high risk of growth failure. Poor weight gain is a prominent risk factor for retinopathy of prematurity (ROP) and optimizing nutrition could potentially promote growth and reduce ROP. Most infants at risk of ROP need parenteral nutrition initially and studies of enhanced parenteral provision of lipids and amino acids have suggested a beneficial effect on ROP. Higher amino acid intake was associated with lower incidence of hyperglycemia, a risk factor for ROP. For very preterm infants, providing unpasteurized fortified raw maternal breast milk appears to have a dose-dependent preventive effect on ROP. These infants become deficient in arachidonic acid (ArA)and docosahexaenoic acid(DHA) after birth when the maternal supply is lost. Earlier studies have investigated the impact of omega-3 fatty acids on ROP with mixed results. In a recent study, early enteral supplementation of ArA 100 mg/kg/d and DHA 50 mg/kg/d until term equivalent age reduced the incidence of severe ROP by 50%. IMPACT: Previous reviews of nutritional interventions to prevent morbidities in preterm infants have mainly addressed bronchopulmonary dysplasia, brain lesions and neurodevelopmental outcome. This review focusses on ROP. Neonatal enteral supplementation with arachidonic acid and docosahexaenoic acid, at levels similar to the fetal accretion rate, has been found to reduce severe ROP by 50% in randomized controlled trials.

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.

Hibiscus sabdariffa-loaded nanostructured lipid carriers (NLC) for fortified nutraceutical milks

The Hibiscus sabdariffa (H. sabdariffa) belongs to the Malvaceae family, and originates from Africa. It is characterized by a high polyphenols content (e.g., quercetin and anthocyanins), and has recognized bioactivity, that makes this plant an interesting resource for possible addition of its extracts to dairy beverages and obtain functional beverages. Nonetheless, it may be observed that many of these phenolic compounds are not stable depending on the environmental conditions. In this work, we propose the use of nanostructured lipid carriers (NLC) as a carrier for the loading of H. sabdariffa extracts, for further incorporation in daily beverages. Polyphenols-enriched extracts from H. sabdariffa were obtained using two distinct extraction approaches: by (i) microwave-assisted extraction (MAE), or by (ii) pressurized liquid extraction (PLE). The obtained extracts were then loaded into NLC to obtain two distinct samples identified as: HS-MAE-NLC and HS-PLE-NLC. The developed nanoparticles were then incorporated into a dairy beverage for the production of fortified milks identified with the same names. The long-term stability, texture properties and in vitro release profile were evaluated. The results show that the fortified milks, HS-MAE-NLC and HS-PLE-NLC, were stable under stress conditions attributed to the enhanced stability provided by the protein content present in the milk. The in vitro release profile of quercetin and anthocyanins from NLC-enriched dairy beverage was more prolonged than the milk containing the non-loaded extract, fitting better to the Korsmeyers–Peppas model. From our results, NLC may be considered a potential approach to formulate photoprotective, anti-inflammatory, and antioxidant bioactives from H. sabdariffa adding the extracts into dairy beverages to increase their bioavailability, and bioactivity.

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.

Fortification of Milk with Omega-3 Fatty Acids Using Novel Bioactive-Carrier Hollow Solid Lipid Micro- and Nanoparticles for Improved Omega-3 Stability and Bioaccessibility

Fortification of Milk with Omega-3 Fatty Acids Using Novel Bioactive-Carrier Hollow Solid Lipid Micro- and Nanoparticles for Improved Omega-3 Stability and Bioaccessibility

Variability in Diagnosis and Management of Hypoglycemia in Neonatal Intensive Care Unit.

Hypoglycemia, the most common metabolic derangement in the newborn period remains a contentious issue, not only due to various numerical definitions, but also due to limited therapeutical options which either lack evidence to support their efficacy or are increasingly recognized to lead to adverse reactions in this population. This study aimed to investigate neonatologists' current attitudes in diagnosing and managing transient and persistent hypoglycemia in newborns admitted to the Neonatal Intensive Care Unit (NICU). A web-based electronic survey which included 34 questions and a clinical vignette was sent to U.S. neonatologists. There were 246 survey responses with most respondents using local protocols to manage this condition. The median glucose value used as the numerical definition of hypoglycemia in first 48 hours of life (HOL) for symptomatic and asymptomatic term infants and preterm infants was 45 mg/dL (2.5 mmol/L; 25-60 mg/dL; 1.4-3.3 mmol/L), while after 48 HOL the median value was 50 mg/dL (2.8 mmol/L; 30-70 mg/dL; 1.7-3.9 mmol/L). There were various approaches used to manage transient and persistent hypoglycemia that included dextrose gel, increasing caloric content of the feeds using milk fortifiers, using continuous feedings, formula or complex carbohydrates, and use of various medications such as diazoxide, glucocorticoids, and glucagon. There is still large variability in current practices related to hypoglycemia. Further research is needed not only to provide evidence to support the values used as a numerical definition for hypoglycemia, but also on the efficacy of current strategies used to manage this condition. · Numerical definition of glucose remains variable.. · Strategies managing transient and persistent hypoglycemia are diverse.. · There is a need for further research to investigate efficacy of various treatment options..

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.

Feeding Management and Palate Repair Timing in Infants with Cleft Palate with and without Pierre Robin Sequence: A Multisite Study.

Compare the feeding management practices in infants with cleft palate with and without Pierre Robin sequence (PRS) and determine if specific feeding difficulties or interventions predict delayed palate repair. Retrospective cross-sectional study. Seventeen cleft palate teams contributed data. 414 infants were included in this study: 268 infants with cleft palate only and 146 infants with cleft palate and PRS. Data were collected via parent interview and electronic health records. Outcomes for the primary objective included categorical data for: history of poor growth, feeding therapy, milk fortification, use of enteral feeding, and feeding difficulties. The outcome for the secondary objective was age in months at primary palate repair. Infants with PRS had a significantly higher prevalence of feeding difficulties (81% versus 61%) and poor growth (29% versus 15%) compared to infants with cleft palate only. Infants with PRS received all feeding interventions-including feeding therapy, milk fortification, and enteral feeding-at a significantly higher frequency. Infants with PRS underwent primary palate repair at a mean age of 13.55 months (SD = 3.29) which was significantly (P < .00001) later than infants with cleft palate only who underwent palate repair at a mean age of 12.05 months (SD = 2.36). Predictors of delayed palate repair included diagnosis of PRS as well as Hispanic ethnicity and a history of poor growth. These findings can be used to establish clinical directives focused on providing early, multimodal feeding interventions to promote optimal growth and timely palate repair for infants with PRS.

The Use of a Novel Donkey Milk-Derived Human Milk Fortified in the Neonatal Period Had No Effect on the Frequency of Allergic Manifestations During the First Years of Life: The "Fortilat Trial" Follow-Up.

Background: Since human milk contents does not meet the high need of very low birth weight infants, fortification of breast milk is a standard practice for this population. As donkey milk has been long considered for children allergic to cow's milk proteins due to its low allergic properties, a new donkey milk-derived fortifier (DF) has been recently evaluated as a valid alternative to bovine milk-derived fortifier (BF). It seems to improve feeding tolerance when compared with standard BF, with similar neurodevelopmental and auxological outcome at 18 months of age. The aim of this study is to evaluate the development of allergic manifestations occurring in the population of the "Fortilat Trial" at 6-8 years of age. Methods: Allergic manifestations were assessed by an ad hoc questionnaire administered to families. The occurrence of asthma, allergic rhinitis and oculorhinitis, rashes and atopic dermatitis, food allergies, accesses to an emergency department for allergic reactions, and the need of antihistamine have been investigated. Results: In total, 113 infants were enrolled in the study (BF arm: n = 60, DF arm: n = 53). No difference in risk was observed between the two groups for all the considered outcomes. In conclusion, our data suggest that DF does not impact the development of allergic manifestations in the first years of life. Clinical Trial Registration number: ISRCT N70022881.

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.

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.

Milk fortified with chitooligosaccharide–gallic acid conjugate and its liposome: characterisation, storage stability, and in vitro digestibility

SummaryThe effects of chitooligosaccharide–gallic acid conjugate (CGC) and its liposome (CGLP) at two levels (1.25 and 2.50%, w/v) on quality and shelf‐life of milk kept at 4 °C were studied. Microbial counts including total viable, pathogenic and spoilage bacteria were the lowest for CGC‐fortified milk, especially when 2.50% (w/v) was used (CGC‐2.50) than remaining samples (P &lt; 0.05). Lower thiobarbituric acid reactive substances and peroxide values were obtained for CGC‐2.50 than other samples (P &lt; 0.05). However, higher acidity values and decreased pH and lightness were noticed in the aforementioned sample (P &lt; 0.05). Moreover, all fortified milk samples had higher bioactivities during in vitro digestion, in which CGC‐2.50 had the highest bioactivities (P &lt; 0.05). Higher retention of unsaturated fatty acids content in CGC‐2.50 was obtained than other counterparts (P &lt; 0.05). Therefore, CGC efficiently extended milk shelf‐life with high acceptability at 4 °C for a minimum of 6 days, whereas control had a shelf‐life of less than 4 days.

Nano casein-pectin complex: exploring physicochemical, organoleptic properties, and LAB viability in skimmed milk and low-fat yoghurt.

Protein complexes with a nutritional value, heat stability, and gelling properties with no negative impact on culture viability have promising application prospects in the fermentation industry. The aim of the study was to investigate the possibility of applying physical modification seeking high-protein-fortified yoghurt production using the nano casein-pectin NCP complex as an active colloidal system with enhanced structural and thermal properties and monitor the quality properties of the physicochemical, heat stability, rheological, starter culture viability and sensory evaluation of fortified products comparing with the plain control throughout the cold storage. High-energy ball milling (HEBM) technique was used to produce nanoparticles of casein powder and smaller particles of pectin individually, and particle size and zeta potential was assessed. Deferent Nano casein-pectin (NCP) complex formulations were prepared, their physicochemical properties were assessed including protein quality via Amino Acid Analyzer (AAA), viscosity, thermogravimetric analysis (TGA), and then used in fortification of skimmed milk and low-fat yoghurt to monitor the fortification effects. The particle sizes showed to be ≈166 nm and 602.6 nm for nano-casein and pectin, respectively. Milk fortification with the NCP complex has significantly increased the nutritional value represented in increased protein content (7.19 g/100 g in NCP5); Ca, P, and S content (2,193.11, 481.21, and 313.77 ppm); and amino acid content with first limiting amino acids; histidine (0.89 mg/g), methionine (0.89 mg/g), and low content of hydrophobic amino acids (HAAs) may cause aggregation. NPC fortification enhanced physicochemical properties announced in enhanced viscosity (62. mP.s in NCP5) and heat stability (up to 200°C) compared with control skimmed milk (SM). NCP yoghurt fortification significantly increased protein content to 11 mg/100 g in T5, enhanced viscosity to 48.44 mP.s in T3, decreased syneresis to 16% in T5, and enhanced LAB viability which was translated in preferable sensorial properties. Applying fortification with nanoparticles of the casein-pectin (NCP) complex balanced the amino acid content and improved physicochemical, rheological, nutritional, and sensorial properties and LAB viability, which can be recommended further in functional food applications.

Curds in the way: A milk curd obstruction review and normal sonographic bowel appearances using a novel scoring system in neonates on fortified breast milk feeds.

Fortified expressed breast milk (FEBM) is a standard of care for premature and low birth weight neonates, but comes with an elevated risk of a rare but re-emergent pathology called milk curd obstruction (MCO). Little is known about normal sonographic appearances of bowel contents in this feeding setting, making the recognition of abnormalities difficult. Thus, we aimed to describe appearances that may be considered typical pre- and post-fortifier inclusion. Ten neonates of <32 weeks' gestation or a birth weight of <1,800 g recruited from Auckland City Hospital Neonatal Intensive Care between 1/5/2019 and 10/9/2019 received bowel ultrasounds within 24 h before and 10-14 days after starting FEBM. Bowel contents in six abdominal regions were assigned scores of 1-6 based on increasing solidification. Lower gestational age was correlated with more solid contents on the pre-fortifier ultrasound (P = 0.02). Fortifier was significantly associated with increasing solidity, particularly in the left abdomen (P < 0.001). The left lower quadrant and rectum accounted for much of this change (P = 0.012 and P = 0.002). One subject who subsequently developed a clinical picture consistent with early MCO had uniquely demonstrated non-rectal solid contents (score 6). The interobserver kappa score for two assessors was 0.91 (95% CI 0.94-0.99) on still images. This small cohort demonstrated increasing bowel content solidification after breast milk fortification using a novel ultrasound scoring system with good interobserver agreement. Non-rectal solid contents (score 6) appeared atypical. Ultrasound shows promise for its non-irradiating diagnostic utility in the setting of early milk curd disease evaluation of the premature neonate.

Idiopathic infantile hypercalcemia with a &lt;i&gt;CYP24A1 &lt;/i&gt;variant triggered by vitamin D supplementation in fortified milk: a case report

Idiopathic infantile hypercalcemia with a &lt;i&gt;CYP24A1 &lt;/i&gt;variant triggered by vitamin D supplementation in fortified milk: a case report

Milk fortification with a complex of iron with ascorbic acid for control of iron deficiency anemia ‎

Milk fortification with a complex of iron with ascorbic acid for control of iron deficiency anemia ‎

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.

Influence of dairy matrix on the prebiotic effects of inulin related to gut metabolic activity and bone health.

Inulin is a well-recognized prebiotic ingredient established to modulate the gut microbiome and its metabolic functionality. However, little is known about how the food matrix interacts with the prebiotic efficacy of inulin. The aim of the present study was to investigate the interaction between the food matrix (milk vs. yogurt) and the gut microbiome modulatory effects of inulin and its influence on calcium bioavailability as reflected in bone mineralization. For this purpose, a 6-week dietary intervention was conducted in healthy young growing male rats (n = 36) which received a diet matrix that included: (1) milk, (2) milk supplemented with 5% inulin, (3) yogurt, or (4) yogurt supplemented with 5% inulin. All diets were limited in calcium content and provided a daily intake of 46 mg calcium per rat. We found that inulin fortification of a yogurt diet exerted a larger effect on gut fermentation as reflected in pH and the generation of acetate in the distal part of the intestine and feces compared with inulin fortification of milk. Inulin was also associated with a higher acetate concentration in plasma when supplied in yogurt compared with milk. No effects of inulin supplementation were found on bone parameters. In conclusion, the present study suggested that the prebiotic efficacy of inulin is higher when supplied in a fermented dairy product than milk. However, neither adding inulin to yogurt or milk affected bone mineralization or the bone structure.

Taking Human Milk Fortification to the Next Level.

Taking Human Milk Fortification to the Next Level.