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: To evaluate the association between an exclusive human milk diet (EHMD) and motor function impairment at three years of corrected age among infants born before 32 weeks of gestation.

Methods: We conducted a retrospective study between 2018 and 2021. We assigned to the EHMD group infants who received an EHMD for ≥75% of the days between the first day of diet fortification and 33 6/7 weeks postmenstrual age. We used inverse propensity scores to balance potential confounders and developed a mixed-effects logistic regression model to assess the association.

Results: After adjusting for demographics and morbidities, an EHMD was associated with a reduced risk of motor function impairment, with an odds ratio of 0.74 (95% CI: 0.56-0.98, p = 0.036).

Conclusions: An EHMD is associated with a decrease in the odds of early childhood motor function impairment among infants born before 32 weeks of gestation.

Background

Preterm neonates ≤1000g have high nutrient demands and faltering growth is common, demonstrated by declines in z-scores for weight, length, and head circumference (HC) during their initial hospital stay.

In October 2023, a standardised nutrition bundle was introduced in our NICU which included enhancement of NICU dietitian hours, employment of nutrition allied health assistants, standardised enteral feeding protocol and introduction of exclusive human milk diet (EHMD) for neonates≤1000g with an aim to improve growth outcomes.EHMD consisted of human milk fortified with human milk derived fortifier (Humavant, Prolacta Bioscience) until 34 weeks corrected gestational age.

Methods

Prospective cohort study with historical controls of inborn infants ≤1000g. Primary outcome was change in anthropometric z-scores from birth to 36 weeks corrected gestational age (CGA). Mean (SD) are shown.

Results

• The baseline characteristics of both groups were similar.
• EHMD group demonstrated a smaller decline in weight and HC z-scores from birth to 36 weeks CGA (Table 1).
• EHMD group also achieved:
  • earlier commencement of fortification [10.4 (5.7) vs 20.8 (11.2) days, p<0.01]
  • earlier attainment of enteral feeds of 150 mL/kg/day [12.7 (5.6) vs 20.2 (10.4) days, p<0.01]
  • reduced duration of parenteral nutrition [12.8 (5.8) vs 20.3 (11.2) p<0.05].

Background

In October 2023, a standardised nutrition quality improvement bundle was implemented, which included:

1. Exclusive human milk diet (EHMD) for preterm infants ≤1000g. Enhancement of NICU dietitian hours
2. Nutrition allied health assistants to assist with accurate weighing and labelling of fortifiers and preparation of feeds
3. Standardised enteral feeding protocol for all infants.

EHMD consisted of mother's own milk (MOM) or pasteurised donor human milk (PDHM) fortified with human milk derived fortifier (Humavant, Prolacta Bioscience) from birth until 34 weeks corrected gestational age (CGA).

Methods

• This is a prospective cohort study with historical controls prior to the introduction ofthe nutritional bundle. Historical controls received cow's milk based fortifier.
• The growth trajectory in the first 6 weeks of life was compared between inborn infants ≤1000g born after October 2023 (intervention group) and those born between January and June 2023 (historical controls).
• Weights and head circumference was measured weekly for all neonates.
• Mean (SD) values of weight and head circumference (HC) were compared at weekly intervals from birth (i.e birth, day 7, 14, 21, 28, 35, and 42)

Results

• There were 21 and 18 neonates in EHMD and control groups, respectively.
• In EHMD group, all neonates survived and there were no occurrence of necrotising enterocolitis (NEC). In the control group, there were 2 (11%) deaths due to late onset sepsis, and 2 (11%) proven NEC.
• Mean weights at all time points were higher in the EHMD group compared to the control (Figure 1)
• Mean head circumference was higher from day of life 21 to day of life 42 in the EHMD group compared to the control (Figure 2)
• Mean weight (±SD)in EHMD increased by 620 (±222) g by day 42 compared to the control group 469 (±154)g (p 0.017)
• Mean HC (±SD) in EHMD increased by 3.54 (±2.57) cm by day 42 compared to the control group 2.46 (±1.26) cm (p 0.11)

Background

In October 2023, we introduced a standardised nutrition bundle that included implementation of exclusive human milk diet (EHMD, mother’s milk ± donor milk and a human milk-based fortifier, Humavant [Prolacta Bioscience]) for extremely low birth weight infants (ELBW) <1000g at birth until 34 weeks corrected gestational age (CGA). In this interim analysis, we compared weight z-score changes from birth to 34 weeks CGA pre and post-implementation of EHMD.

Methods

Post-implementation phase consisted of all inborn ELBW infants born between October 2023 to March 2024. Pre-implementation phase was from January to June 2023. Decline in weight-for-age z-score from birth to 34 weeks CGA was used to define malnutrition: mild (0.8-1.2 SD), moderate (>1.2-2.0 SD), and severe (>2.0 SD).

Results

At 34 weeks corrected gestational age (CGA), the incidence of malnutrition was significantly lower in the study group, decreasing from 88% in the control group to 39%. The study group also demonstrated a notable reduction in the severity of malnutrition. Moreover, there were no reported cases of necrotising enterocolitis (NEC) in the study group, in contrast to an 11% incidence observed in the control group.

Necrotizing enterocolitis (NEC) is common in preterm infants, especially infants less than 32 weeks gestation. Mortality from NEC is 7% and occurs in 1 out of 1000 preterm infants. Studies have shown the efficacy of an exclusive milk from mother diet in decreasing rates of NEC and associated mortality.

Purpose: 

To evaluate the effectiveness of an existing exclusive human milk diet (EHMD) protocol on the incidence of NEC in extremely premature infants. EHMD, for the purposes of this project is defined as breast milk of mother, with or without human milk-based fortifier.

Methods: 

A single-center retrospective quasi-experimental study. The sample included 201 infants born less than 32 weeks gestation, weighing less than 1250 grams, small for gestational age (SGA) and with low Apgar scores. Outcomes measured included incidences of NEC, mortality, and co-morbidities in infants pre- and postinitiation of an EHMD protocol.

Results: 

Just 4.8% of the EHMD group had a NEC diagnosis compared to 10.5% of the bovine-based (BOV) group. There was a 1% mortality rate of the EHMD group as compared to 6% in the BOV group. The EHMD group had a statistically significant greater weight gain during hospitalization as compared to infants fed BOV (P = < .05).

Human milk provides bioactive compounds such as milk fat globules (MFGs), which promote brain development, modulate the immune system, and hold antimicrobial properties. To ensure microbiological safety, donor milk banks apply heat treatments. This study compares the effects of heat treatments and homogenization on MFG's physicochemical properties, bioactivity, and bioavailability. Vat pasteurization (Vat-PT), retort (RTR), and ultra-high temperature (UHT) were performed with or without homogenization. UHT, RTR, and homogenization increased the colloidal dispersion of globules, as indicated by increased zeta potential. The RTR treatment completely inactivated xanthine oxidase activity (a marker of MFG bioactivity), whereas UHT reduced its activity by 93%. Interestingly, Vat-PT resulted in less damage, with 28% activity retention. Sialic acid, an important compound for brain health, was unaffected by processing. Importantly, homogenization increased the in vitro lipolysis of MFG, suggesting that this treatment could increase the digestibility of MFG. In terms of color, homogenization led to higher L* values, indicating increased whiteness due to finer dispersion of the fat and casein micelles (and thus greater light scattering), whereas UHT and RTR increased b* values associated with Maillard reactions. This study highlights the nuanced effects of processing conditions on MFG properties, emphasizing the retention of native characteristics in Vat-PT-treated human milk.

Conclusion: This study elucidates the intricate influence of processing conditions on the properties of MFG. The Vat-PT method notably preserves most of the native characteristics observed in unprocessed human milk MFG. Regarding the lipolysis characteristics, homogenization increased the in vitro lipolysis of MFG, suggesting that this treatment could increase the digestibility of MFG. The findings from the present study provide an increased understanding of processing techniques’ effects on milk fat globules and milk fat globule membranes, which could be translated into clinical human milk research for alternative human milk processing techniques and their impact on infant health.

An exclusive human milk diet (EHMD) and standardized feeding protocols are two critical methods for safely feeding very low birth weight (VLBW) infants. Our institution initiated a standardized feeding protocol for all VLBW infants in 2018. In this protocol, a human milk fat modular was used only reactively when an infant had poor weight gain, fluid restriction, or hypoglycemia. As part of our NICU quality improvement program, internal utilization review data revealed a potential opportunity to improve growth and reduce costs. While maintaining the EHMD, a simple feeding guideline process change could provide cost savings without sacrificing caloric density or growth. We examined this process change in pre-post cohorts of VLBW infants.

Methods: Our revised feeding protocol, established in October 2021, called for a human milk fat modular (Prolact CR) to be added to all infant feeding when parenteral nutrition (PN) and lipids were discontinued. The human milk fat modular concentration is 4 mL per 100 mL feed, providing approximately an additional 2 kcal/oz. We tracked data to compare (1) the use of the human milk fat modular, (2) the use of the human milk +8 fortifier, (3) overall growth before and after feeding protocol changes, and (4) cost differences between protocols. Results: Thirty-six VLBW infants were followed prospectively upon the introduction of the revised feeding protocol. In the revised era, the need for human milk +8 fortifier decreased from 43% to 14%. The decrease in the cost of a more costly fortifier provided a cost savings of USD 2967.78 on average per infant. Overall growth improved from birth to discharge, with severe malnutrition declining from 3.3% to 2.7% and moderate malnutrition declining from 37% to 8%.

Conclusions: With the proactive use of a human milk fat modular in a standardized feeding protocol, our VLBW infants showed improved growth, lower malnutrition rates, and decreased use of higher caloric fortifiers.

Abstract

This meta-analysis assessed short-term outcomes after using human milk-derived fortifiers (HMFs) compared with bovine milk fortifiers (BMFs) in preterm infants fed an exclusive human milk (HM) diet, either mother's own milk (MOM) or donor human milk (DHM). We searched PubMed, Embase, Google Scholar, CENTRAL and CINHAL between January 2015 and August 2023 for studies reporting outcomes in infants with ≤28 weeks gestation and/or birthweight ≤ 1500 g on an exclusive human milk diet fortified with HMF versus BMF.

The primary outcomes were death and NEC (stage ≥ 2). Four studies with a total of 681 infants were included. Mortality was significantly lower in infants fed with an HM-HMFs diet (four studies, 681 infants; RR = 0.50, 95% CI = 0.26-0.94; p = 0.03; I2 = 0%), NEC was similar between the two groups (four studies, 681 infants; RR = 0.48, 95% CI = 0.20-1.17; p = 0.11; I2= 39%). BPD was higher in the HM-BMFs group (four studies, 663 infants; RR = 0.83, 95% CI = 0.69-1.000; p = 0.05, I2 = 0%), although not statistically significant. No differences were found for sepsis (RR = 0.97, 95% CI = 0.66-1.42; p = 0.96; I2 = 26%) or combined ROP (four studies, 671 infants; RR = 0.64, 95% CI = 0.53-1.07; p = 0.28; I2 = 69%).

An HM-HMFs diet could possibly be associated with decreased mortality with no association with NEC, BPD, sepsis, or ROP. This meta-analysis was limited by the small number of studies included. However, the results should not be refuted for this reason as they provide an impetus for subsequent clinical trials to assess the observed associations.

Conclusion

Our data associates bovine milk-derived fortifiers with a possibly increased risk of death, which makes a reversal possibly necessary. However, the introduction of bovine milk fortifiers cannot yet be judged due to the lack of sufficiently powered clinical trials and the lack of relevant information about the long-term outcomes in terms of neurodevelopment. Although BPD itself is a disease for life and is associated with poorer neurodevelopmental outcomes, we need neurodevelopmental follow-up data from all survivors to definitely address the question of if the use of an exclusive human milk diet from MOM and/or pooled DM is warranted due to the unique nutritional and immunological benefits from human breast milk which can reduce the relevant outcomes of an extremely low gestational period. The results should not be refuted for formal reasons but should be taken as the need to further define the effects of a human milk diet (MOM and/or pooled DM) supplemented with human milk fortifiers.

Background: Implementation of exclusive human milk (EHM) feeding defined as mother's own milk or donor human milk fortified with human milk-derived fortifiers can place an economic burden on institutions.

Methods: Retrospective study of very low birth weight (VLBW) infants before and after the implementation of EHM feedings. Neonatal demographics and clinical outcomes including necrotizing enterocolitis, severe retinopathy of prematurity, bronchopulmonary dysplasia, late-onset sepsis, days on parenteral nutrition (PN), and length-of-stay were collected. The net cost to the institution was estimated using published data.

Results: Sixty-four infants in the pre-EHM period and 57 infants in the post-EHM period were enrolled. Net product acquisition cost in 2020 and 2021 was $884,823. The EHM feeding guideline led to a reduction in the mean length of stay and mean days of PN use by 6.3 and 6.8 days per infant, respectively. This led to a cost saving of $1,813,444 ($31,815 per infant). No significant difference in incidence of short-term morbidities was observed. Combining the cost avoidance from clinical outcomes, the estimated financial impact over 2 years excluding insurance reimbursement was an estimated $ 913,840 ($16,032 per infant).

Conclusion: Implementation of EHM-based feeding in VLBW infants is a cost-effective option for neonatal intensive care units that can result in reduced length of stay and days on PN without adversely impacting short-term morbidities.

Objectives: Enteral nutrition with unfortified human milk during the first 2 postnatal weeks often leads to cumulative protein and energy deficits among preterm infants. Fortified human milk administered soon after birth could increase fat-free mass (FFM) and improve growth in these infants.

Methods: This was a masked, randomized trial. Starting on feeding day 2, extremely preterm infants 28 weeks or younger fed maternal or donor milk were randomized to receive either a diet fortified with a human-based product (intervention group) or a standard, unfortified diet (control group). This practice continued until the feeding day when a standard bovine-based fortifier was ordered. Caregivers were masked. The primary outcome was FFM-for-age z score at 36 weeks of postmenstrual age (PMA).

Results: A total of 150 infants were randomized between 2020 and 2022. The mean birth weight was 795±250 g, and the median gestational age was 26 weeks. Eleven infants died during the observation period. The primary outcome was assessed in 105 infants (70%). FFM-for-age z scores did not differ between groups. Length gain velocities from birth to 36 weeks PMA were higher in the intervention group. Declines in head circumference-for-age z score from birth to 36 weeks' PMA were less pronounced in the intervention group.

Conclusions: In infants born extremely preterm, human milk diets fortified soon after birth do not increase FFM accretion at 36 weeks' PMA, but they may increase length gain velocity and reduce declines in head circumference-for-age z scores from birth to 36 weeks' PMA.