Supplementation Of Human Milk Research Articles

Human Milk and Dietary Supplements Differentially Modulate Microbial Communities of Stool Isolated from Term and Preterm Infants

Background: After birth, the term neonatal gut becomes colonized by commensal bacteria that benefit host health. Premature infants, however, are prone to abnormal colonization that increases the risk for neonatal intestinal disease such as necrotizing enterocolitis (NEC). Breastfeeding confers a lower risk for NEC, and this is likely due to prebiotics, probiotics, and anti-inflammatory cytokines present in breast milk. Despite the known associations of NEC with gut microbiota and breastfeeding, the exact interactions between preterm gut microbes and various milk types remains relatively unexplored. Furthermore, Lactobacillus are frequently included in probiotic supplements, but the interplay between Lactobacillus, milk, and NEC is not fully understood. Hypothesis: We hypothesize that in in vitro models of preterm gut microbiota, human breast milk exerts an overall beneficial modulatory effect on bacterial composition. We also suspect that the anti-inflammatory properties of Lactobacillus are enhanced when treated with fresh breast milk compared to formula. Methods: Stool samples from preterm infants were incubated anaerobically in mini-bioreactors overnight at 37°C to establish complex communities. The next day, they were supplemented with fresh milk with or without fortifier, donor milk with or without fortifier, formula, vitamin mix, iron mix, or water and incubated for another 24 hrs. Bacterial gDNA was examined by qPCR and back-calculated to colony-forming units (CFUs) to quantify bacterial composition. To examine the effect of milk on Lactobacillus metabolites, we monocultured six Lactobacillus ( L. acidophilus, L. breve, L. johnsonii, L. paracasei, L. reuteri, and L. rhamnosus) in a defined medium supplemented with fresh milk, formula, or water. After overnight incubation, supernatants were collected for nontargeted metabolomics. The supernatant was also applied to preterm intestinal organoids to examine epithelial responses. Results: Formula significantly elevated Bifidobacterium and Streptococcus, while fresh and donor milk caused upward trends in Lactobacillus and Bifidobacterium. LC-MS/MS data revealed that in the presence of fresh breast milk but not formula, at least one Lactobacillus strain demonstrated increased levels of anti-inflammatory metabolites such as γ-glutamylphenylalanine, ascorbic acid, vaccenic acid, hydroxyphenylacetic acid, or indoleacrylic acid. Conclusions: These data indicate that different milk types and supplements variably affect bacterial growth and metabolites in the preterm gut. This study was supported in part by the NIH K01DK123195 (MAE), NATS NIH KL2TR001452 (KEC) and UL1TR001450 (KEC) grants. This study does not represent the offcial view of the NIH. This study was also supported in part by the David and Laura Stone Endowment for Advancement in Neonatal Medicine (KEC). The Texas Children’s Hospital Department of Pathology provides salary support to the Texas Children’s Microbiome Center-Metabolomics and Proteomics Mass Spectrometry Laboratory staff, and purchased all of the reagents, the consumables and durable supplies, and the LC-MS/MS equipment described herein (TH). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Human Milk-The Biofluid That Nourishes Infants from the First Day of Life.

Human milk is a biofluid with a unique composition among mammalian milks. Besides this milk's major components, its bioactive compounds, like hormones, immune factors, and oligosaccharides, are unique and important for infant growth and development. The best form of nutrition for term and preterm infants is the mother's own milk. However, in the absence of the mother's own milk, donor milk should be made available. Milk banks support neonatal intensive care units by providing preterm infants with human milk that generally has reasonable nutritive value for this sensitive population. However, neither mother's own milk nor donor milk has sufficient energy content for the growth of preterm babies, so adequate human milk supplementation is crucial for their progress. Due to the different characteristics of human breast milk, as well as ubiquitous environmental pollutants, such as microplastics, new methods are required for monitoring the quality and characteristics of human milk, which will lay a solid foundation for the further development and progress of human milk research.

Fat Supplementation of Human Milk with MCT Oil for Promoting Weight Gain in Preterm Infants

Background: The addition of medium chain triglycerides is preferable as they are more easily digested and quickly absorb in bloodstream than long chain fat and provide ready supply of energy by increasing fatty acid bioavailability. Modular products like micro lipids and medium-chain triglyceride (MCT) oils are now focused as a fat supplementation. The rate of weight gain with MCT is not well known, and there is very less research done in Pakistan. Objective: To determine the effect of MCT oil supplemented human milk compared with un supplemented human milk fed to preterm infants on promoting weight gain. Study Design: Randomized controlled trial Study Setting: This study was conducted in Department of Neonatology, Children Hospital, PIMS, Islamabad, Pakistan from 20th August 2022 to 20th February 2023. Methodology: The study conducted after approval from institutional ethical committee. A total of 160 preterm infants fulfilling the inclusion criteria and enrolled in the study after informed consent from parents. The patients were receiving enteral feeding of human milk within neonatology department of hospital was included and they were randomly assigned to Group NF (receiving 20 ml of human milk without MCT oil), Group F (receiving 20ml of human milk with 1 ml of MCT oil fat). Primary outcomes were including growth in term of weight gain at measured at 1st ,5th and 10th day of MCT oil intake after hospital admission. Secondary outcome included feeding intolerance, diarrhoea, sepsis and necrotising enterocolitis. All the data was collected in the form of a questionnaire. The statistical analysis was done by using SPSS version 20. Results: One sixty very low birth weight infants were analyzed in this study. All infants were randomly divided into two groups: F and NF, the demographic details. The weight of infants was measured on first day, fifth day and tenth day and noted that the frequency of infants improved the weight gain after taking human milk without fat supplementation or human milk with fat supplementation. We found the gradually infants more increasing their weights in Group F as compared to Group NF. On tenth day 75% infants reaches between1400-1490 gm weight (p<0.001). The average daily gain in weight of Group F infants (g/kg). 12.2 Group A, 13.6 in group B were calculated on day first. The average daily weight was shifted in Group B from 13.6 to 14.9 on day fifth then it was further increased as 15.6 in Group C, and 15.8 in Group D. Practical Implication: The fat in the milk of humans is a significant source of energy. In an underdeveloped State like Pakistan that is short on resources, (MCT) oil can be a useful substitute for MCT due to its high MCT content. Few research studies have been conducted into this area thus far. Previous studies have had a low number of participants and produced contradictory findings. Therefore, this study was carried out to compare the efficacy of feeding preterm infants human milk supplemented with MCT oil to that of feeding them human milk without the supplement. Conclusion: Our study shows the average weight gain in those infants fed fat supplementation of MCT oil added in breast milk. The study provides data regarding the selection and use of fat supplemented human milk over non-supplemented human milk and this reduces the morbidity and mortality rate due to insufficiency of nutrients. Keyword: Fat supplementation, MCT oil, breast milk, preterm infants, weight gain rate.

Relationship Between Maternal COVID-19 Infection and In-Hospital Exclusive Breastfeeding for Term Newborns

ObjectiveTo evaluate the relationship between maternal COVID-19 infection and the odds of in-hospital exclusive breastfeeding for term newborns. DesignRetrospective descriptive quantitative. SettingA large, urban hospital with more than 6,000 births annually. SampleTerm newborns born between March 1, 2020, and March 31, 2021 (N = 6,151). MethodsWe retrospectively extracted data from electronic health records to evaluate the relationship of maternal COVID-19 infection with the odds of in-hospital exclusive breastfeeding using univariate analysis and logistic regression models. The covariates included insurance type, race/ethnicity, glucose gel administration, length of stay, newborn gestational age, newborn birth weight, and maternal COVID-19 infection. ResultsMaternal COVID-19 infection was not significantly related to the odds of in-hospital exclusive breastfeeding (p = .138) after adjustment for covariates in the logistic regression model. However, when newborns who received pasteurized donor human milk supplementation were excluded from the logistic regression model, maternal COVID-19 infection significantly decreased the odds of in-hospital exclusive breastfeeding (p = .043). ConclusionMaternal COVID-19 infection was not significantly related to the odds of in-hospital exclusive breastfeeding when newborns received donor human milk supplementation. Access to donor human milk for supplementation for term newborns may protect the odds of in-hospital exclusive breastfeeding.

Effects of Total Enteral Nutrition on Early Growth, Immunity, and Neuronal Development of Preterm Infants.

The feeding of colostrum and mother’s transitional milk improves immune protection and neurodevelopmental outcomes. It also helps with gut maturation and decreases the risks of infection. The supply of nutrients from human milk (HM) is not adequate for preterm infants, even though preterm mother’s milk contains higher concentrations of protein, sodium, zinc, and calcium than mature HM. The human milk fortifiers, particularly those with protein, calcium, and phosphate, should be used to supplement HM to meet the necessities of preterm infants. The management of fluid and electrolytes is a challenging aspect of neonatal care of preterm infants. Trace minerals such as iron, zinc, copper, iodine, manganese, molybdenum, selenium, chromium, and fluoride are considered essential for preterm infants. Vitamins such as A, D, E, and K play an important role in the prevention of morbidities, such as bronchopulmonary dysplasia, retinopathy of prematurity, and intraventricular hemorrhage. Therefore, supplementation of HM with required nutrients is recommended for all preterm infants.

Is Lactoferrin Supplementation Beneficial for All Preterm Infants?

Human milk (HM) has antibacterial properties due to the presence of immune-modulators, including lactoferrin (LF). This study will determine effect(s) of HM maturation, fortification, and storage conditions on LF levels and its antibacterial properties. HM samples (n = 30) were obtained from preterm and term mothers. The LF levels were analyzed by ELISA, and the antibacterial activity was measured after inoculation with Escherichia coli. The highest level of LF in preterm HM was observed in the first week of lactation. However, storage of preterm HM at 4°C decreased LF levels significantly. Both LF levels and antibacterial activity in preterm HM was lower compared with term HM, but significantly higher than donor HM even after HM-based fortification. LF supplementation of donor HM improved its antibacterial activity. Preterm infants fed donor HM, formula, or stored HM at 4°C may benefits from LF supplementation to improve HM antibacterial properties. · Milk LF levels vary with storage and maturity.. · Donor milk is deficient in LF even after adding HM-based fortification.. · Donor HM and formula fed infants may benefit from LF..

Clinical Characteristics and Breastfeeding Outcomes in Term Dyads Following In-Hospital Supplementation with Pasteurized Donor Human Milk or Formula.

Background: Pasteurized donor human milk (PDHM) supplementation for healthy infants is an emerging practice. Little is known about demographics or breastfeeding outcomes for dyads whose mothers choose PDHM versus formula. Research Aims: To identify relationships between in-hospital supplementation choice and (1) dyad characteristics and breastfeeding intent, and (2) breastfeeding outcomes at 1 month. Materials and Methods: This exploratory prospective cohort study surveyed healthy dyads requiring medically indicated supplementation. Participants completed questionnaires including demographics, breastfeeding intent, and self-efficacy during hospitalization, and self-efficacy and lactation outcomes at 1 month. Results: Of 39 participants, 24 (62%) supplemented with formula and 15 (38%) with PDHM. Formula dyads were more likely than PDHM dyads to have a delivery body mass index (BMI) ≥30 kg/m2 (58% versus 20%, p = 0.02), and less likely to have attained greater than a college degree (33% versus 7%, p = 0.02); formula dyads also reported lower breastfeeding intent scores (12.0 versus 15.5, p = 0.002). Breastfeeding self-efficacy scores were similar but decreased for both groups over 1 month. At 1 month, mothers who chose formula were more likely to continue to provide breast milk to their infants (84% versus 72%). Direct breastfeeding rates were similar (72% versus 68%); of participants directly breastfeeding at 1 month, PDHM dyads were 1.5 times more likely to provide maternal expressed milk. Conclusions: Differences in maternal education, BMI, and breastfeeding intent were found between feeding groups. Results suggest an association between PDHM choice and initial breastfeeding intent and breastfeeding self-efficacy and provision of maternal expressed milk at 1 month.

Protein supplementation of human milk for promoting growth in preterm infants.

Preterm infants require high protein intake to achieve adequate growth and development. Although breast milk feeding has many benefits for this population, the protein content is highly variable, and inadequate to support rapid infant growth. This is a 2020 update of a Cochrane Review first published in 1999. To determine whether protein-supplemented human milk compared with unsupplemented human milk, fed to preterm infants, improves growth, body composition, cardio-metabolic, and neurodevelopmental outcomes, without significant adverse effects. We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 8) in the Cochrane Library and MEDLINE via PubMed on 23 August 2019. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Published and unpublished RCTs were eligible if they used random or quasi-random methods to allocate hospitalised preterm infants who were being fed human milk, to additional protein supplementation or no supplementation. Two review authors independently abstracted data, assessed risk of bias and the quality of evidence at the outcome level, using GRADE methodology. We performed meta-analyses, using risk ratio (RR) for dichotomous data, and mean difference (MD) for continuous data, with their respective 95% confidence intervals (CIs). We used a fixed-effect model and had planned to explore potential causes of heterogeneity via subgroup or sensitivity analyses. We included six RCTs, involving 204 preterm infants. The risk of bias for most methodological domains was unclear as there was insufficient detail reported. Low-quality evidence showed that protein supplementation of human milk may increase in-hospital rates of growth in weight (MD 3.82 g/kg/day, 95% CI 2.94 to 4.7; five RCTs, 101 infants; I² = 73%), length (MD 0.12 cm/wk, 95% CI 0.07 to 0.17; four RCTs, 68 infants; I² = 89%), and head circumference (MD 0.06 cm/wk, 95% CI 0.01 to 0.12; four RCTs, 68 infants; I² = 84%). Protein supplementation may lead to longer hospital stays (MD 18.5 days, 95% CI 4.39 to 32.61; one RCT, 20 infants; very low-quality evidence). Very low quality evidence means that the effect of protein supplementation on the risk of feeding intolerance (RR 2.70, 95% CI 0.13 to 58.24; one RCT, 17 infants), or necrotizing enterocolitis (RR 1.11, 95% CI 0.07 to 17.12; one RCT, 76 infants) remains uncertain. No data were available about the effects of protein supplementation on neurodevelopmental outcomes. Low-quality evidence showed that protein supplementation of human milk, fed to preterm infants, increased short-term growth. However, the small sample sizes, low precision, and very low-quality evidence regarding duration of hospital stay, feeding intolerance, and necrotising enterocolitis precluded any conclusions about these outcomes. There were no data on outcomes after hospital discharge. Our findings may not be generalisable to low-resource settings, as none of the included studies were conducted in these settings. Since protein supplementation of human milk is now usually done as a component of multi-nutrient fortifiers, future studies should compare different amounts of protein in multi-component fortifiers, and be designed to determine the effects on duration of hospital stay and safety, as well as on long-term growth, body composition, cardio-metabolic, and neurodevelopmental outcomes.

Carbohydrate supplementation of human milk to promote growth in preterm infants.

Preterm infants are born with low glycogen stores and require higher glucose intake to match fetal accretion rates. In spite of the myriad benefits of breast milk for preterm infants, it may not adequately meet the needs of these rapidly growing infants. Supplementing human milk with carbohydrates may help. However, there is a paucity of data on assessment of benefits or harms of carbohydrate supplementation of human milk to promote growth in preterm infants. This is a 2020 update of a Cochrane Review first published in 1999. To determine whether human milk supplemented with carbohydrate compared with unsupplemented human milk fed to preterm infants improves growth, body composition, and cardio-metabolic and neurodevelopmental outcomes without significant adverse effects. We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 8) in the Cochrane Library and MEDLINE via PubMed on 22 August 2019. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Published and unpublished controlled trials were eligible if they used random or quasi-random methods to allocate preterm infants in hospital fed human milk to supplementation or no supplementation with additional carbohydrate. Two review authors independently abstracted data and assessed trial quality and the quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. We planned to perform meta-analyses using risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, with their respective 95% confidence intervals (CIs). We planned to use a fixed-effect model and to explore potential causes of heterogeneity via sensitivity analyses. We contacted study authors for additional information. One unblinded, quasi-randomised controlled trial (RCT) assessing effects of carbohydrate supplementation of human milk in the form of a prebiotic in 75 preterm infants was eligible for inclusion in this review. We identified two publications of the same trial, which reported different methods regarding blinding and randomisation. Study authors confirmed that these publications pertain to the same trial, but they have not yet clarified which method is correct. We were unable to reproduce analyses from the data presented. At 30 days of age, the mean weight of preterm infants in the trial was greater in the prebiotic carbohydrate-supplemented group than in the unsupplemented group (MD 160.4 grams, 95% CI 12.4 to 308.4 grams; one RCT, N = 75; very low-quality evidence). We found no evidence of a clear difference in risk of feeding intolerance (RR 0.64, 95% CI 0.36 to 1.15; one RCT, N = 75 infants; very low-quality evidence) or necrotising enterocolitis (NEC) (RR 0.2, 95% CI 0.02 to 1.3; one RCT, N = 75 infants; very low-quality evidence) between the prebiotic-supplemented group and the unsupplemented group. Duration of hospital stay was shorter in the prebiotic group than in the control group at a median (range) of 16 (9 to 45) days (95% CI 15.34 to 24.09) and 25 (11 to 80) days (95% CI 25.52 to 34.39), respectively. No other data were available for assessing effects of carbohydrate supplementation on short- and long-term growth, body mass index, body composition, and neurodevelopmental or cardio-metabolic outcomes. We found insufficient evidence on the short- and long-term effects of carbohydrate supplementation of human milk in preterm infants. The only trial included in this review presented very low-quality evidence, and study authors provided uncertain information about study methods and analysis. The evidence may be limited in its applicability because researchers included a small sample of preterm infants from a single centre. However, the outcomes assessed are common to all preterm infants, and this trial demonstrates the feasibility of prebiotic carbohydrate supplementation in upper-middle-income countries. Future trials should assess the safety and efficacy of different types and concentrations of carbohydrate supplementation for preterm infants fed human milk. Although prebiotic carbohydrate supplementation in preterm infants is currently a topic of active research, we do not envisage that further trials of digestible carbohydrates will be conducted, as this is currently done as a component of multi-nutrient human milk fortification. Hence we do not plan to publish any further updates of this review.

Fat supplementation of human milk for promoting growth in preterm infants.

As preterm infants do not experience the nutrient accretion and rapid growth phase of the third trimester of pregnancy, they are vulnerable to postnatal nutritional deficits, including of fat. Consequently, they require higher fat intakes compared to their full term counterparts to achieve adequate growth and development. Human milk fat provides the major energy needs of the preterm infant and also contributes to several metabolic and physiological functions. Although human milk has many benefits for this population, its fat content is highly variable and may be inadequate for their optimum growth and development. This is a 2020 update of a Cochrane Review last published in 2000. To determine whether supplementation of human milk with fat compared with unsupplemented human milk fed to preterm infants improves growth, body composition, cardio-metabolic, and neurodevelopmental outcomes without significant adverse effects. We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 8) in the Cochrane Library and MEDLINE via PubMed on 23 August 2019. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Published and unpublished randomised controlled trials were eligible if they used random or quasi-random methods to allocate preterm infants fed human milk in hospital to supplementation or no supplementation with additional fat. No new randomised controlled trials matching the selection criteria were found but we extracted data from the previously included trial due to changes in review outcomes from when the protocol was first published. Two reviewers independently abstracted data, assessed trial quality, and the quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. We planned to perform meta-analyses using risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with their respective 95% confidence intervals (CIs). We planned to use a fixed-effect model and to explore potential causes of heterogeneity via sensitivity analyses. One randomised trial involving 14 preterm infants was included. There was no evidence of a clear difference between the fat-supplemented and unsupplemented groups in in-hospital rates of growth in weight (MD 0.6 g/kg/day, 95% CI -2.4 to 3.6; 1 RCT, n = 14 infants, very low-quality evidence), length (MD 0.1 cm/week, 95% CI -0.08 to 0.3; 1 RCT, n = 14 infants, very low-quality evidence) and head circumference (MD 0.2 cm/week, 95% CI -0.07 to 0.4; 1 RCT n = 14 infants, very low-quality evidence). There was no clear evidence that fat supplementation increased the risk of feeding intolerance (RR 3.0, 95% CI 0.1 to 64.3; 1 RCT, n = 16 infants, very low-quality evidence). No data were available regarding the effects of fat supplementation on long-term growth, body mass index, body composition, neurodevelopmental, or cardio-metabolic outcomes. The one included trial suggests no evidence of an effect of fat supplementation of human milk on short-term growth and feeding intolerance in preterm infants. However, the very low-quality evidence, small sample size, few events, and low precision diminishes our confidence that these results reflect the true effect of fat supplementation of human milk in preterm infants, and no long-term outcomes were reported. Further high-quality research should evaluate the effect on short and long-term growth, neurodevelopmental and cardio-metabolic outcomes in the context of the development of multicomponent fortifiers. Optimal dosage, adverse effects, and delivery practices should also be evaluated.

Urinary Metabolomic Profile of Preterm Infants Receiving Human Milk with Either Bovine or Donkey Milk-Based Fortifiers

Fortification of human milk (HM) for preterm and very low-birth weight (VLBW) infants is a standard practice in most neonatal intensive care units. The optimal fortification strategy and the most suitable protein source for achieving better tolerance and growth rates for fortified infants are still being investigated. In a previous clinical trial, preterm and VLBW infants receiving supplementation of HM with experimental donkey milk-based fortifiers (D-HMF) showed decreased signs of feeding intolerance, including feeding interruptions, bilious gastric residuals and vomiting, with respect to infants receiving bovine milk-based fortifiers (B-HMF). In the present ancillary study, the urinary metabolome of infants fed B-HMF (n = 27) and D-HMF (n = 27) for 21 days was analyzed by 1H NMR spectroscopy at the beginning (T0) and at the end (T1) of the observation period. Results showed that most temporal changes in the metabolic responses were common in the two groups, providing indications of postnatal adaptation. The significantly higher excretion of galactose in D-HMF and of carnitine, choline, lysine and leucine in B-HMF at T1 were likely due to different formulations. In conclusion, isocaloric and isoproteic HM fortification may result in different metabolic patterns, as a consequence of the different quality of the nutrients provided by the fortifiers.

Clinical and Sociodemographic Factors Associated With Human Donor Milk Supplementation in Term Newborns.

To identify differences between healthy term newborns supplemented with human donor milk (HDM) and those supplemented with infant formula. We hypothesized that sociodemographic and clinical distinctions exist between newborns receiving different milk types. This retrospective study included term newborns admitted to the postpartum unit between March 2017 and April 2019 with ≥1 supplemental feeding with HDM or formula for indications other than hypoglycemia. Maternal and newborn data were abstracted from the electronic medical record. Five hundred eighty-four dyads met inclusion criteria. More newborns received supplementation with formula than with HDM (57.7% vs 42.3%; P < .001). Infants undergoing phototherapy who required supplementation were more likely to receive HDM (P < .001). Newborns born to white and non-Hispanic mothers were more likely to receive HDM than those born to African American (adjusted odds ratio [aOR] 5.6; P = .007), Hispanic (aOR 3.0; P = .001), or Asian American mothers (aOR 2.7; P = .007). Newborns born to primiparous women (aOR 1.6; P = .03), those born to women with private insurance (aOR 3.7; P < .001), and those born via cesarean delivery (aOR 2.0; P < .001) were more likely to receive HDM. HDM use was more likely in primary English- or Spanish-speaking households (aOR 8.5; P = .009). Newborns receiving their first supplemental feeding during the day (aOR 1.9; P = .001) were more likely to be supplemented with HDM. There are clinical and sociodemographic differences between healthy term newborns supplemented with HDM and formula. These findings reveal that there are disparities in current supplementation practices for healthy newborns.

Disparities in Donor Human Milk Supplementation Among Well Newborns.

Donor human milk supplementation for healthy newborns has increased. Racial-ethnic disparities in supplementation have been described in the neonatal intensive care unit but not in the well newborn setting. The aim of this study was to identify maternal characteristics associated with donor human milk versus formula supplementation in the well newborn unit. This retrospective cohort study includes dyads of well newborns and their mothers (N = 678) who breastfed and supplemented with formula (n = 372) or donor human milk (n = 306) during the birth hospitalization at a single hospital in the midwestern United States. Maternal characteristics and infant feeding type were extracted from medical records. Chi-square and logistic regression were used to examine associations between maternal characteristics and feeding type. Nonwhite women were less likely to use donor human milk. Compared to non-Hispanic white women, the largest disparity was with Hispanic (adjusted odds ratio [OR] = 0.28, 95% CI [0.12, 0.65]), then non-Hispanic black (adjusted OR = 0.32, 95% CI [0.13, 0.76]) and Asian women (adjusted OR = 0.34, 95% CI [0.16, 0.74]). Lower donor human milk use was associated with primary language other than English and public versus private insurance. The goal of improving public health through breastfeeding promotion may be inhibited without targeting donor human milk programs to these groups. Identifying the drivers of these disparities is necessary to inform person-centered interventions that address the needs of women with diverse backgrounds.

An economic analysis of human milk supplementation for very low birth weight babies in the USA

BackgroundAn exclusive human milk diet (EHMD) using human milk based products (pre-term formula and fortifiers) has been shown to lead to significant clinical benefits for very low birth weight (VLBW) babies (below 1250 g). This is expensive relative to diets that include cow’s milk based products, but preliminary economic analyses have shown that the costs are more than offset by a reduction in the cost of neonatal care. However, these economic analyses have not completely assessed the economic implications of EHMD feeding, as they have not considered the range of outcomes affected by it.MethodsWe conducted an economic analysis of EHMD compared to usual practice of care amongst VLBW babies in the US, which is to include cow's milk based products when required. Costs were evaluated from the perspective of the health care payer, with societal costs considered in sensitivity analyses.ResultsAn EHMD substantially reduces mortality and improves other health outcomes, as well as generating substantial cost savings of $16,309 per infant by reducing adverse clinical events. Cost savings increase to $117,239 per infant when wider societal costs are included.ConclusionsAn EHMD is dominant in cost-effectiveness terms, that is it is both cost-saving and clinically beneficial, for VLBW babies in a US-based setting.

Effectiveness of Donor Human Milk Supplementation for the Treatment of Hypoglycemia in the Breastfed Infant

Effectiveness of Donor Human Milk Supplementation for the Treatment of Hypoglycemia in the Breastfed Infant

Protein supplementation of human milk for promoting growth in preterm infants: Summaries of Nursing Care-Related Systematic Reviews from the Cochrane Library.

Protein supplementation of human milk for promoting growth in preterm infants: Summaries of Nursing Care-Related Systematic Reviews from the Cochrane Library.

Carbohydrate supplementation of human milk to promote growth in preterm infants.

Preterm infants are born with low glycogen stores and require higher glucose intake to match fetal accretion rates. In spite of the myriad benefits of breast milk for preterm infants, it may not adequately meet the needs of these rapidly growing infants. Supplementing human milk with carbohydrates may help. However, there is a paucity of data on assessment of benefits or harms of carbohydrate supplementation of human milk to promote growth in preterm infants. This is a 2018 update of a Cochrane Review first published in 1999. To determine whether human milk supplemented with carbohydrate compared with unsupplemented human milk fed to preterm infants improves growth, body composition, and cardio-metabolic and neurodevelopmental outcomes without significant adverse effects. We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 8), MEDLINE via PubMed (1966 to 21 February 2018), Embase (1980 to 21 February 2018), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 21 February 2018). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials. Published and unpublished controlled trials were eligible if they used random or quasi-random methods to allocate preterm infants in hospital fed human milk to supplementation or no supplementation with additional carbohydrate. Two review authors independently abstracted data and assessed trial quality and the quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. We planned to perform meta-analyses using risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, with their respective 95% confidence intervals (CIs). We planned to use a fixed-effect model and to explore potential causes of heterogeneity via sensitivity analyses. We contacted study authors for additional information. One unblinded, quasi-randomised controlled trial (RCT) assessing effects of carbohydrate supplementation of human milk in the form of a prebiotic in 75 preterm infants was eligible for inclusion in this review. We identified two publications of the same trial, which reported different methods regarding blinding and randomisation. Study authors confirmed that these publications pertain to the same trial, but they have not yet clarified which method is correct. We were unable to reproduce analyses from the data presented. At 30 days of age, the mean weight of preterm infants in the trial was greater in the prebiotic carbohydrate-supplemented group than in the unsupplemented group (MD 160.4 grams, 95% CI 12.4 to 308.4 grams; one RCT, N = 75; very low-quality evidence). We found no evidence of a clear difference in risk of feeding intolerance (RR 0.64, 95% CI 0.36 to 1.15; one RCT, N = 75 infants; very low-quality evidence) or necrotising enterocolitis (NEC) (RR 0.2, 95% CI 0.02 to 1.3; one RCT, N = 75 infants; very low-quality evidence) between the prebiotic-supplemented group and the unsupplemented group. Duration of hospital stay was shorter in the prebiotic group than in the control group at a median (range) of 16 (9 to 45) days (95% CI 15.34 to 24.09) and 25 (11 to 80) days (95% CI 25.52 to 34.39), respectively. No other data were available for assessing effects of carbohydrate supplementation on short- and long-term growth, body mass index, body composition, and neurodevelopmental or cardio-metabolic outcomes. We found insufficient evidence on the short- and long-term effects of carbohydrate supplementation of human milk in preterm infants. The only trial included in this review presented very low-quality evidence, and study authors provided uncertain information about study methods and analysis. The evidence may be limited in its applicability because researchers included a small sample of preterm infants from a single centre. However, the outcomes assessed are common to all preterm infants, and this trial demonstrates the feasibility of prebiotic carbohydrate supplementation in upper-middle-income countries. Future trials should assess the safety and efficacy of different types and concentrations of carbohydrate supplementation for preterm infants fed human milk. Although prebiotic carbohydrate supplementation in preterm infants is currently a topic of active research, we do not envisage that further trials of digestible carbohydrates will be conducted, as this is currently done as a component of multi-nutrient human milk fortification. Hence we do not plan to publish any further updates of this review.

Protein supplementation of human milk for promoting growth in preterm infants.

Preterm infants require high protein intake to achieve adequate growth and development. Although breast milk feeding has many benefits for this population, the protein content is highly variable, and inadequate to support rapid infant growth. This is a 2018 update of a Cochrane Review first published in 1999. To determine whether protein-supplemented human milk compared with unsupplemented human milk, fed to preterm infants, improves growth, body composition, cardio-metabolic, and neurodevelopmental outcomes, without significant adverse effects. We used the standard search strategy of Cochrane Neonatal to search CENTRAL, MEDLINE via PubMed, Embase, and CINAHL (February 2018). We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials (RCT) and quasi-randomised trials. Published and unpublished RCTs were eligible if they used random or quasi-random methods to allocate hospitalised preterm infants who were being fed human milk, to additional protein supplementation or no supplementation. Two review authors independently abstracted data, assessed risk of bias and the quality of evidence at the outcome level, using GRADE methodology. We performed meta-analyses, using risk ratio (RR) for dichotomous data, and mean difference (MD) for continuous data, with their respective 95% confidence intervals (CIs). We used a fixed-effect model and had planned to explore potential causes of heterogeneity via subgroup or sensitivity analyses. We included six RCTs, involving 204 preterm infants. Low-quality evidence showed that protein supplementation of human milk increased in-hospital rates of growth in weight (MD 3.82 g/kg/day, 95% CI 2.94 to 4.7; five RCTs, 101 infants; I² = 73%), length (MD 0.12 cm/wk, 95% CI 0.07 to 0.17; four RCTs, 68 infants; I² = 89%), and head circumference (MD 0.06 cm/wk, 95% CI 0.01 to 0.12; four RCTs, 68 infants; I² = 84%). There was no evidence of a clear difference in rate of growth of skin fold thickness between the supplemented and unsupplemented groups (triceps MD 0.06 mm/wk, 95% CI -0.09 to 0.21; one RCT, 20 infants; or subscapular MD 0.00 mm/wk, 95% CI -0.17 to 0.17; one RCT, 20 infants). Protein supplementation led to longer hospital stays (MD 18.5 days, 95% CI 4.39 to 32.61; one RCT, 20 infants; very low-quality evidence), and higher blood urea nitrogen concentrations compared to the unsupplemented group (MD 0.95 mmol/L, 95% CI 0.81 to 1.09; four RCTs, 81 infants; I² = 56%). Very low-quality evidence did not show that protein supplementation clearly increased the risk of feeding intolerance (RR 2.70, 95% CI 0.13 to 58.24; one RCT, 17 infants), or necrotizing enterocolitis (RR 1.11, 95% CI 0.07 to 17.12; one RCT, 76 infants), or clearly altered serum albumin concentrations (MD 2.5 g/L, 95% CI -5.66 to 10.66; one RCT, 11 infants), compared with the unsupplemented groups. No data were available about the effects of protein supplementation on long-term growth, body mass index, body composition, neurodevelopmental, or cardio-metabolic outcomes. Low-quality evidence showed that protein supplementation of human milk, fed to preterm infants, increased short-term growth. However, the small sample sizes, low precision, and very low-quality evidence regarding duration of hospital stay, feeding intolerance, and necrotising enterocolitis precluded any conclusions about these outcomes. There were no data on outcomes after hospital discharge. Our findings may not be generalisable to low-resource settings, as none of the included studies were conducted in these settings.Since protein supplementation of human milk is now usually done as a component of multi-nutrient fortifiers, future studies should compare different amounts of protein in multi-component fortifiers, and be designed to determine the effects on duration of hospital stay and safety, as well as on long-term growth, body composition, cardio-metabolic, and neurodevelopmental outcomes.

Fat supplementation of human milk for promoting growth in preterm infants.

As preterm infants do not experience the nutrient accretion and rapid growth phase of the third trimester of pregnancy, they are vulnerable to postnatal nutritional deficits, including of fat. Consequently, they require higher fat intakes compared to their full term counterparts to achieve adequate growth and development. Human milk fat provides the major energy needs of the preterm infant and also contributes to several metabolic and physiological functions. Although human milk has many benefits for this population, its fat content is highly variable and may be inadequate for their optimum growth and development. This is a 2018 update of a Cochrane Review last published in 2000. To determine whether supplementation of human milk with fat compared with unsupplemented human milk fed to preterm infants improves growth, body composition, cardio-metabolic, and neurodevelopmental outcomes without significant adverse effects. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 1), MEDLINE via PubMed (1966 to 08 February 2018), Embase (1980 to 08 February 2018), and CINAHL (1982 to 08 February 2018). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Published and unpublished randomised controlled trials were eligible if they used random or quasi-random methods to allocate preterm infants fed human milk in hospital to supplementation or no supplementation with additional fat. No new randomised controlled trials matching the selection criteria were found but we extracted data from the previously included trial due to changes in review outcomes from when the protocol was first published. Two reviewers independently abstracted data, assessed trial quality, and the quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. We planned to perform meta-analyses using risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with their respective 95% confidence intervals (CIs). We planned to use a fixed-effect model and to explore potential causes of heterogeneity via sensitivity analyses. One randomised trial involving 14 preterm infants was included. There was no evidence of a clear difference between the fat-supplemented and unsupplemented groups in in-hospital rates of growth in weight (MD 0.6 g/kg/day, 95% CI -2.4 to 3.6; 1 RCT, n = 14 infants, very low-quality evidence), length (MD 0.1 cm/week, 95% CI -0.08 to 0.3; 1 RCT, n = 14 infants, very low-quality evidence) and head circumference (MD 0.2 cm/week, 95% CI -0.07 to 0.4; 1 RCT n = 14 infants, very low-quality evidence). There was no clear evidence that fat supplementation increased the risk of feeding intolerance (RR 3.0, 95% CI 0.1 to 64.3; 1 RCT, n = 16 infants, very low-quality evidence). No data were available regarding the effects of fat supplementation on long-term growth, body mass index, body composition, neurodevelopmental, or cardio-metabolic outcomes. The one included trial suggests no evidence of an effect of fat supplementation of human milk on short-term growth and feeding intolerance in preterm infants. However, the very low-quality evidence, small sample size, few events, and low precision diminishes our confidence that these results reflect the true effect of fat supplementation of human milk in preterm infants, and no long-term outcomes were reported. Further high-quality research should evaluate the effect on short and long-term growth, neurodevelopmental and cardio-metabolic outcomes in the context of the development of multicomponent fortifiers. Optimal dosage, adverse effects, and delivery practices should also be evaluated.

Protein Supplementation of Human Milk for Promoting Growth in Preterm Infants; A Cochrane Systematic Review

Protein Supplementation of Human Milk for Promoting Growth in Preterm Infants; A Cochrane Systematic Review