Objective

Small for gestational age (SGA) preterm infants (PT) are at greatest risk for growth failure. Our objective was to assess the impact of an exclusive human milk diet (HUM) on growth velocities and neonatal morbidities from birth to discharge in a SGA population.

Study design

Multicenter, retrospective cohort study, subgroup analysis of SGA PT comparing a cow’s milk diet (CMD) with HUM diet.

Results

At birth 420 PT were classified as SGA (197 CMD group, 223 HUM group). Demographics and anthropometric measurements were similar. HUM group PT showed improvement in length Z score at discharge (p = 0.024) and reduction in necrotizing enterocolitis (NEC) (p = 0.004).

Conclusion

SGA PT fed a HUM diet had significantly decreased incidence of NEC, surgical NEC, and late-onset sepsis. Due to concerns about growth in a HUM diet, it is reassuring SGA infants fed the HUM diet had similar growth to CMD diet with trends toward improvement

Objective

An increasingly common practice is to feed preterm infants a base diet comprising only human milk (HM), usually fortified with a cow's milk (CM)-derived fortifier (CMDF). We evaluated the safety of CMDF in a diet of 100% mother's own milk (MOM) against a HM-derived fortifier (HMDF). To date, this has received little research attention.

Study Design

We reanalyzed a 12-center randomized trial, originally comparing exclusive HM feeding, including MOM, donor milk (DM), and HMDF, versus a CM exposed group fed MOM, preterm formula (PTF), and CMDF1. However, for the current study, we performed a subgroup analysis (n = 114) selecting only infants receiving 100% MOM base diet plus fortification, and fed no DM or PTF. This allowed for an isolated comparison of fortifier type: CMDF versus HMDF to evaluate the primary outcomes: necrotizing enterocolitis (NEC) and a severe morbidity index of NEC surgery or death; and several secondary outcomes.

Results

CMDF and HMDF groups had similar baseline characteristics. CMDF was associated with higher risk of NEC; relative risk (RR) 4.2 (p = 0.038), NEC surgery or death (RR 5.1, p = 0.014); and reduced head circumference gain (p = 0.04).

Conclusions

In neonates fed, as currently recommended with a MOM-based diet, the safety of CMDF when compared to HMDF has been little researched. We conclude that available evidence points to an increase in adverse outcomes with CMDF, including NEC and severe morbidity comprising NEC surgery or death.

Objective

Substantial losses of nutrients may occur during tube (gavage) feeding of fortified human milk. Our objective was to compare the losses of key macronutrients and minerals based on method of fortification and gavage feeding method.

Methods

We used clinically available gavage feeding systems and measured pre- and post-feeding (end-point) nutrient content of calcium (Ca), phosphorus (Phos), protein, and fat. Comparisons were made between continuous, gravity bolus, and 30-minute infusion pump feeding systems, as well as human milk fortified with donor human milk-based and bovine milk-based human milk fortifier using an in vitro model.

Results

Feeding method was significantly associated with fat and Ca losses, with increased losses in continuous feeds. Fat losses in continuous feeds were substantial, with 40 ± 3 % of initial fat lost during the feeding process. After correction for feeding method, human milk fortified with donor milk-based fortifier was associated with significantly less loss of Ca (8 ± 4% vs. 28 ± 4%, p< 0.001), Phos (3 ± 4% vs. 24 ± 4%, p < 0.001), and fat (17 ± 2% vs. 25 ± 2%, p = 0.001) than human milk fortified with a bovine milk-based fortifier (Mean ± SEM).

Objectives: Small infants require adequate enteral nutrition to achieve continuous growth. Therefore, breast milk should be supplemented with fortifier. In addition to the cost-efficient fortifiers produced from bovine milk, an expensive fortifier derived from human milk has been available. We compared, whether preterm infants benefit from human fortifier supplementation and whether the higher purchase costs are economically viable for hospitals.

Methods: Preterm infants of <32+0 gestational week and <1000 g birth weight, were enrolled. The newborns were nourished with human milk. Supplementation with human fortifier or bovine fortifier was initiated once oral milk intake reached 100 mL/kg BW/d. Standardized documentation of body weight, respiratory situation, Intraventricular Hemorrhage (IVH), Periventricular Leukomalacia (PVL), Necrotizing Enterocolitis (NEC) and Retinopathy of Prematurity (ROP) and duration of the in-hospital stay was undertaken at day of life 7, 14, 21, 35 and 42. For each individual the revenue was calculated.

Results: Between 01/2019 and 12/2020, 23 children were enrolled. 10 preterms received human and 13 bovine fortifier. 2 infants developed BPD and one required ligature for a Patent Ductus Arteriosus Botalli (PDA) in the children who were supplemented with human milk-based fortifier. Three children in the group fed the bovine fortifier developed BPD, PVL was documented in one, ROP in 2, higher-grade NEC in one and ductus ligature was required by two children. Stool-calprotectin values measured on study days 35 and 42 were significant lower in infants given human fortifier. Nevertheless, the in-hospital stay was shorter in the human fortifier group (median of 75.5 days) than in the bovine fortifier (median of 80 days) group.

Total revenue gain was +39854.20 € (+5958.20 € per patient) in patients fed the human fortifier versus +20573.42 €(-346.00 € per patient) in individuals who received bovine fortifier. The costs for human fortifier supplementation were in total € 41005.00. Bovine fortifier was less expensive (total cost: € 250.00).

Conclusion: Fortifiers produced from human milk entail higher therapeutic costs but are offset by shorter in-hospital stays and fewer morbidities among preterm infants. Preterm infants tolerate human milk-based fortifiers significantly better than bovine-based fortifiers.

Background

Our level III neonatal intensive care unit (NICU) implemented the use of an exclusive human milk diet (EHD) and sought to determine its effect on the severe co-morbidities of preterm infants as well as the potential cost-savings due to the anticipated reduction in these co-morbidities.

Methods

A retrospective cohort study was completed to determine if an EHD statistically decreased the rate of co-morbidities including length of stay (LOS), days on total parental nutrition (TPN), rates of late onset sepsis, necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), and severe retinopathy of prematurity (ROP).

Results

An EHD significantly decreased the odds of severe ROP (adjusted odds-ratio (aOR)=0.349; 95%CI [0.156, 0.739]; p=0.008) and late onset sepsis (aOR=0.323; 95%CI [0.123, 0.768]; p=0.014). Analysis of cost-effectiveness of an EHD relative to a BSD based on the incremental costs of these co-morbidities determined the net loss in direct hospital costs per patient were estimated to be $420 in 2016 US dollars; however, given the long-term health-care costs and non-pecuniary damages from the co-morbidities of severe ROP and sepsis this net loss appears negligible.

Conclusion

This study found that an EHD significantly decreased the odds of severe ROP and late onset sepsis; though not significant, there was a positive trend in decreasing cases of medical NEC; our surgical NEC rates dropped to 0. The benefits of human milk are vital, and the costs are nominal.

Recently we published a meta-analyses of morbidity seen with the use of cow’s milk derived fortifier (CMDF) rather than human milk derived fortifier (HMDF) in very low birthweight (VLBW) infants. Here, we further analyse these data to estimate the annual population risk of CMDF-related major morbidity in the United States and Canada. The outcome used was a mortality/morbidity index which was positive if the infants had one or more of death, necrotising enterocolitis, sepsis retinopathy of prematurity or bronchopulmonary dysplasia. Using the risk difference (RD) between the CMDF and HMDF groups we estimated, provisionally, that 4150 additional VLBW infants in the United States and Canada each year, or an additional infant approximately every 2 hours, may be expected to develop a positive mortality/morbidity index in relation to being fed CMDF – over and above the number of infants with a positive index if fed HMDF. We provide an in-depth discussion of the limitations of our estimate. This analysis provides preliminary evidence of the magnitude of population risk of major neonatal morbidity with use of CMDF versus HMDF in VLBW infants in current practice.

Objective

An increasingly common practice is to feed preterm infants a base diet comprising only human milk (HM), usually fortified with a cow's milk (CM)-derived fortifier (CMDF). We evaluated the safety of CMDF in a diet of 100% mother's own milk (MOM) against a HM-derived fortifier (HMDF). To date, this has received little research attention.

Methods

We reanalyzed a 12-center randomized trial, originally comparing exclusive HM feeding, including MOM, donor milk (DM), and HMDF, versus a CM exposed group fed MOM, preterm formula (PTF), and CMDF1. However, for the current study, we performed a subgroup analysis (n = 114) selecting only infants receiving 100% MOM base diet plus fortification, and fed no DM or PTF. This allowed for an isolated comparison of fortifier type: CMDF versus HMDF to evaluate the primary outcomes: necrotizing enterocolitis (NEC) and a severe morbidity index of NEC surgery or death; and several secondary outcomes.

Results

CMDF and HMDF groups had similar baseline characteristics. CMDF was associated with higher risk of NEC; relative risk (RR) 4.2 (p = 0.038), NEC surgery or death (RR 5.1, p = 0.014); and reduced head circumference gain (p = 0.04).

Conclusions

In neonates fed, as currently recommended with a MOM-based diet, the safety of CMDF when compared to HMDF has been little researched. We conclude that available evidence points to an increase in adverse outcomes with CMDF, including NEC and severe morbidity comprising NEC surgery or death.

Objectives

Human milk-based fortifiers have shown a protective effect on major complications for very low birth weight newborns. The current study aimed to estimate the cost-effectiveness of an exclusive human milk diet (EHMD) compared to the current approach using cow’s milk-based fortifiers in very low birth weight newborns.

Methods

A decision tree model using the health states of necrotising enterocolitis (NEC), sepsis, NEC + sepsis and no complication was used to calculate the cost-effectiveness of an EHMD. For each health state, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (RoP) and neurodevelopmental problems were included as possible complications; additionally, short-bowel syndrome (SBS) was included as a complication for surgical treatment of NEC. The model was stratified into birth weight categories. Costs for inpatient treatment and long-term consequences were considered from a third party payer perspective for the reference year 2017. Deterministic and probabilistic sensitivity analyses were performed, including a societal perspective, discounting rate and all input parameter-values.

Results

In the base case, the EHMD was estimated to be cost-effective compared to the current nutrition for very low birth weight newborns with an incremental cost-effectiveness ratio (ICER) of €28,325 per Life-Year-Gained (LYG). From a societal perspective, the ICER is €27,494/LYG using a friction cost approach and €16,112/LYG using a human capital approach. Deterministic sensitivity analyses demonstrated that the estimate was robust against changes in the input parameters and probabilistic sensitivity analysis suggested that the probability EHMD was cost-effective at a threshold of €45,790/LYG was 94.8 percent.

Conclusion

Adopting EHMD as the standard approach to nutrition is a cost-effective intervention for very low birth weight newborns in Germany.

Background

The University of Virginia neonatal intensive care unit is a 51-bed unit with approximately 600 to 700 admissions per year. Despite evidenced-based clinical care, necrotizing enterocolitis (NEC) and feeding intolerance remained problematic.

Purpose

In September 2016, the neonatal intensive care unit implemented an exclusive human milk diet (EHMD) for infants born 1250 g or less with the goal of reducing NEC, feeding intolerance, parenteral nutrition use, and late-onset sepsis. Length of stay, bronchopulmonary dysplasia (BPD), and retinopathy of prematurity were also evaluated.

Methods

A work group developed systems for charging and documenting products used in an EHMD. Outcomes were compared with a control group of similar infants born prior to the availability of the EHMD.

Results

Infants who received an EHMD had significantly fewer late-onset sepsis evaluations (P = .0027) and less BPD (P = .018). While not statistically significant, less surgical NEC was also demonstrated (4 cases vs 1 case, which was 57% of total NEC cases vs 14.3%) while maintaining desirable weight gain and meeting financial goals.

Human milk provides not only ideal nutrition for infant development but also immunologic factors to protect from infection and inflammation. For the newborn preterm infant, the natural delivery of milk is not attainable, and instead pumped maternal milk, donor human milk, and human milk fortification are mainstays of clinical care. Current research demonstrates a decreased risk of necrotizing enterocolitis with maternal milk and donor human milk when individually compared to formula and with a complete human milk diet of maternal milk supplemented with donor human milk. The incidence of severe retinopathy of prematurity is decreased with an exclusive human milk diet, and this decrease is more pronounced with human milk-based compared to bovine milk-based human milk fortifier. The incidence of other morbidities such as late-onset sepsis and bronchopulmonary dysplasia is decreased with higher dose of human milk though significant differences are not apparent in exclusive human milk diet studies.

Background

An 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.

Methods

We 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.

Results

An 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.

Conclusions

An 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.

Background

For preterm infants, human milk (HM) has to be fortified to cover their enhanced nutritional requirements and establish adequate growth. Most HM fortifiers are based on bovine protein sources (BMF). An HM fortifier based on human protein sources (HMF) has become available in the last few years. The aim of this study is to investigate the impact of an HMF versus BMF on growth in extremely low birth weight (ELBW, <1000 g) infants.

Methods

This was a retrospective, controlled, multicenter cohort study in infants with a birthweight below 1000 g. The HMF group received an exclusive HM diet up to 32+0 weeks of gestation and was changed to BMF afterwards. The BMF group received HM+BMF from fortifier introduction up to 37+0 weeks.

Results

192 extremely low birth weight (ELBW)-infants were included (HMF n = 96, BMF n = 96) in the study. After the introduction of fortification, growth velocity up to 32+0 weeks was significantly lower in the HMF group (16.5 g/kg/day) in comparison to the BMF group (18.9 g/kg/day, p = 0.009) whereas all other growth parameters did not differ from birth up to 37+0 weeks. Necrotizing enterocolitis (NEC) incidence was 10% in the HMF and 8% in the BMF group.

Conclusion

Results from this study do not support the superiority of HFM over BMF in ELBW infants.

Background

Human milk-based fortifiers (HMBFs) are being adopted in neonatal care to enrich the nutrients in human milk for very low birth weight (VLBW) infants despite being costly and there being limited efficacy data. No randomized clinical trial has evaluated the use of HMBF compared with bovine milk–based fortifiers (BMBFs) in the absence of formula feeding.

Objective

To determine if HMBF compared with BMBF for routine nutrient enrichment of human milk improves feeding tolerance, reduces morbidity, reduces fecal calprotectin (a measure of gut inflammation), and supports the growth of infants <1250 g.

Design

In this blinded randomized clinical trial, infants born weighing <1250 g were recruited from neonatal units in Ontario, Canada between August 2014 and November 2015. The infants were fed mother's milk and donor milk as required. Fortification commenced at 100 mL/kg per day of HMBF (0.81 kcal/mL) or BMBF (0.72 kcal/mL) and advanced at 140 mL/kg per day to 0.88 and 0.78 kcal/mL, respectively. The primary outcome was percentage of infants with a feeding interruption for ≥12 h or a >50% reduction in feeding volume. Secondary outcomes included a dichotomous mortality and morbidity index (i.e., affirmative for any one of death, late-onset sepsis, necrotizing enterocolitis, chronic lung disease, or severe retinopathy of prematurity), fecal calprotectin, and growth.

Results

Of 232 eligible infants, 127 (54.7%) were randomized (n = 64 HMBF, n = 63 BMBF). Mean ± SD birth weight and gestational age of infants were 888 ± 201 g and 27.7 ± 2.5 wk, respectively. No statistically significant differences were identified in feeding interruptions [17/64 HMBF, 20/61 BMBF; unadjusted risk difference: −6.2% (95% CI: −22.2%, 9.8%)]. There was no statistically significant difference in the mortality and morbidity index (35.9% HMBF, 49.2% BMBF, adjusted P = 0.07), changes in fecal calprotectin, or growth z scores.

Conclusions

Among infants born weighing <1250 g and exclusively fed human milk, the use of HMBF did not improve feeding tolerance or reduce mortality and morbidity compared with BMBF.