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).

Problem:

Extremely low-birth-weight (ELBW) infants require fortification of human milk (HM) to prevent growth failure. Bovine milk-based fortifiers (BOV-f) may be associated with feeding intolerance and necrotizing enterocolitis. Evidence suggests that an exclusive HM diet (EHMD) using HM-based fortifier (HM-f) may improve these outcomes.

Method:

Implementation included establishing EHMD feeding protocol and growth monitoring. We compared infants receiving HM with BOV-f (n = 49) with infants receiving an EHMD (n = 15). The primary outcome was a reduction of no oral intake days due to feeding intolerance.

Results:

The EHMD cohort had a more advanced GA (28 vs 26 weeks; P = .03), more males (66.7% vs 42.9%; P = .02), and higher incidence of SGA (40.0% vs 18.4%; P = .16) compared with the HM-f group. The EHMD cohort had fewer days with no oral intake (2 vs 5; P < .005), which is insignificant when adjusted for small for gestational age (SGA) (P = .26). The EHMD cohort vs. the HM-f cohort had a significant decrease in weight and length z-scores from birth to discharge (-1.09 vs -0.26 [P = .002]; -1.76 vs -0.83 [P = .02]). Inadequate weight gain persisted after adjustment for SGA. Interventions were performed to increase caloric intake and institute milk preparation changes.

Conclusion:

EHMD improved feeding tolerance in our ELBW infants. Observed growth failure might be skewed by SGA prevalence. We highlight that implementation of EHMD requires close growth assessment, especially for SGA infants.

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.

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.

Objective:

To determine whether weight gain velocity (g/kg/day) 30 days after the initiation of feeds after cardiac surgery and other clinical outcomes improve in infants with single ventricle physiology fed an exclusive human milk diet compared with a mixed human and bovine diet.

Study design:

In this multicenter, randomized, single blinded, controlled trial, term neonates 7 days of age or younger with single ventricle physiology and anticipated cardiac surgical palliation within 30 days of birth were enrolled at 10 US centers. Both groups received human milk if fed preoperatively. During the 30 days after feeds were started postoperatively, infants in the intervention group received human milk fortified once enteral intake reached 60 mL/kg/day with a human milk-based fortifier designed for term neonates. The control group received standard fortification with formula once enteral intake reached 100 mL/kg/day. Perioperative feeding and parenteral nutrition study algorithms were followed.

Results:

We enrolled 107 neonates (exclusive human milk = 55, control = 52). Baseline demographics and characteristics were similar between the groups. The median weight gain velocity at study completion was higher in exclusive human milk vs control group (12 g/day [IQR, 5-18 g/day] vs 8 g/day [IQR, 0.4-14 g/day], respectively; P = .03). Other growth measures were similar between groups. Necrotizing enterocolitis of all Bell stages was higher in the control group (15.4 % vs 3.6%, respectively; P = .04). The incidence of other major morbidities, surgical complications, length of hospital stay, and hospital mortality were similar between the groups.

Conclusions:

Neonates with single ventricle physiology have improved short-term growth and decreased risk of NEC when receiving an exclusive human milk diet after stage 1 surgical palliation.

An exclusive human milk diet (EHMD) has been shown to reduce health complications of prematurity in infants born weighing ≤1250 g compared with cow milk–based diets. Accordingly, the number of available human milk (HM)-based nutritional products continues to increase. Newly available products, and those reportedly soon to enter the market, include homogenized donor HM and homogenized HM–based fortifiers.

Existing literature demonstrating the benefits of an EHMD, however, is limited to non-homogenized HM-based products. Herein, we summarize existing evidence on the impact of homogenization on HM, with a particular focus on changes to the macromolecular structure of the milk fat globule and the subsequent impact on digestion kinetics. We use these published data to create a conceptual framework for the potential implications of homogenized HM-based nutritional products on preterm infant health. Importantly, we underscore that the safety and efficacy of homogenized HM-based products warrant investigation.

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

Background

Several studies have confirmed the benefits of an exclusive human milk diet for premature infants; however, a donor human milk-based fortifier has not been available in Japan.

Case Presentation

A donor human milk-based fortifier was recently used for the first time ever in Japan, given in conjunction with mother’s own milk to three premature infants. Details of these three infant case studies are reported here. These infants received the donor human milk-based fortifier as part of a rescue nutritional intervention due to poor weight gain in the presence of meconium ileus and perforation. Infants demonstrated good tolerance and weight gain while receiving the exclusive human milk diet.

Conclusion

This is the first report of infants receiving an exclusive human milk diet in Japan, consisting of mother’s own milk with a donor human milk-based fortifier for additional calories and nutrients. Infants demonstrated good tolerance and experienced improved weight gain while receiving the product.

Background

An exclusive human milk diet (EHM) including fortification with a human milk-based fortifier has been shown to decrease the occurrence of necrotizing enterocolitis (NEC) but growth velocity may be less for infants receiving EHM compared to a bovine diet.

Objective

The objective of this study was to determine if growth is improved by earlier fortification of breast milk for preterm infants supported with a human milk based fortifier.

Study design

A multi-center retrospective cohort study of the outcomes of infants of 500– 1250 g birth weight whose breast milk feedings were fortified at >60 mL/kg/day (late) versus <60 mL/kg/day (early) of enteral feeding volume.

Results

Median±IQR range for gestational age (27.6±3.4 vs 27.0±2.9 weeks, p = 0.03) and chronic lung disease (CLD: 42.6 vs 27.6%, p = 0.008) were higher, and weight gain (12.9±2.6 vs 13.3±2.6 g/kg/day, p = 0.03) was lower in the late (N = 102) vs the early (N = 292) group. Adjusted multiple linear regression analysis found that early fortification was associated with improved growth velocity for weight (p = 0.007) and head circumference (HC) (p = 0.021) and less negative changes in z-scores for weight (p = 0.022) and HC (p = 0.046) from birth to discharge. Adjusted multiple logistic regression found that early fortification was associated with decreased occurrence of CLD (p = 0.004). No other outcomes, including NEC, were associated with early versus late fortification.

Conclusion

The study results suggested that early HM fortification appears to positively affect growth for infants whose human milk feedings are fortified with a human milk based fortifier without adverse effects. The incidence of CLD was also reduced in the early fortification group.