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).

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.

Objective

To compare postdischarge growth, adiposity and metabolic outcomes of appropriate for gestational age (AGA) versus small for gestational age (SGA) premature infants fed an exclusive human milk (HM)-based diet in the neonatal intensive care unit.

Method

Premature infants (birth weight ≤1250 g) fed an exclusive HM-based diet were examined at 12–15 months corrected gestational age (CGA) (visit 1) for anthropometrics, serum glucose and non-fasting insulin, and at 18–22 months CGA (visit 2) for body composition by dual-energy X-ray absorptiometry.

Results

Of 51 children, 33 were AGA and 18 were SGA at birth. The SGA group had weight gain (g/day) equal to AGA group during the follow-up period. SGA had a significantly greater body mass index (BMI) z-score gain from visit 1 to visit 2 (0.25±1.10 vs −0.21±0.84, p=0.02) reflecting catch-up growth. There were no significant differences in total fat mass (FM) and trunk FM between groups. SGA had significantly lower insulin level (5.0±3.7 vs 17.3±15.1 µU/mL, p=0.02) and homeostatic model of assessment-insulin resistance (1.1±0.9 vs 4.3±4.1, p=0.02). Although regional trunk FM correlated with insulin levels in SGA (r=0.893, p=0.04), they had lower insulin level compared with AGA and no difference in adiposity.

Conclusions

SGA premature infants who received an exclusive HM-based diet exhibited greater catch-up growth without increased adiposity or elevated insulin resistance compared with AGA at 2 years of age. An exclusive HM-based diet may improve long-term body composition and metabolic outcomes of premature infants with ≤1250 g birth weight, specifically SGA.

Background

Mother's own milk (MOM) is protective against gut microbiota alterations associated with necrotizing enterocolitis (NEC) and feeding intolerance among preterm infants. It is unclear whether this benefit is preserved with donor milk (DM) feeding.

Objective

We aimed to compare microbiota development, growth, and feeding tolerance in very-low-birth-weight (VLBW) infants fed an exclusively human milk diet of primarily MOM or DM.

Methods

One hundred and twenty-five VLBW infants born at Texas Children's Hospital were enrolled and grouped into cohorts based on percentage of MOM and DM in enteral feeds. Feeds were fortified with DM-derived fortifier per unit protocol. Weekly stool samples were collected for 6 wk for microbiota analysis [16S ribosomal RNA (rRNA) sequencing]. A research nurse obtained weekly anthropometrics. Clinical outcomes were compared via Wilcoxon's rank-sum test and Fisher's exact test, as well as multivariate analysis.

Results

The DM cohort (n = 43) received on average 14% mothers’ milk compared with 91% for the MOM cohort (n = 74). Diversity of gut microbiota across all time points (n = 546) combined was increased in MOM infants (P < 0.001). By 4 and 6 wk of life, microbiota in MOM infants contained increased abundance of Bifidobacterium (P = 0.02) and Bacteroides (P = 0.04), whereas DM-fed infants had increased abundance of Staphylococcus (P = 0.02). MOM-fed infants experienced a 60% reduction in feeding intolerance (P = 0.03 by multivariate analysis) compared with DM-fed infants. MOM-fed infants had greater weight gain than DM-fed infants.

Conclusions

Compared with DM-fed infants, MOM-fed infants have increased gut microbial community diversity at the phylum and genus levels by 4 and 6 wk of life, as well as better feeding tolerance. MOM-fed infants had superior growth. The incidence of NEC and other gastrointestinal morbidity is low among VLBW infants fed an exclusively human milk diet including DM-derived fortifier.

Objective

Human milk administration in the early peritransplant period would lower intestinal inflammation after bone marrow transplant (BMT).

Methods

Children 0–5 years undergoing BMT received either a ready-to-feed human milk preparation designed for these children (Prolacta Bioscience, Duarte, CA) or standard formula. Babies breastfeeding at the time of BMT were also enrolled on the human milk arm. Human milk was administered from day −3 until day +14 after BMT. Metagenomic shotgun sequencing and metabolomics of stool, plasma cytokines, and regenerating islet-derived 3α (REG3α) levels were measured at enrollment and day +14. Human leukocyte antigen-DR isotype (HLA-DR), CD38, and CD69 expression on T cells were evaluated at day +21.

Results

Forty-six children were enrolled, 32 received human milk (donor milk n = 23, breastfeeding babies n = 9), and 14 were controls who received standard feeds supervised by a BMT dietician. Twenty-four patients received at least 60% of goal human milk and were evaluable. Plasma interleukin (IL)-8 (p = 0.04), IL-10 (p = 0.02), and REG3α (p = 0.03) were decreased in the human milk cohort. Peripheral blood CD69+ CD8+ T cells were higher in controls (p = 0.01). Species abundance of Adenovirus (p = 0.00034), Escherichia coli (p = 0.0017), Cryptosporidium parvum (p = 0.0006), Dialister invisus (p = 0.01), and Pseudomonas aeruginosa (p = 0.05) from stool was higher in controls. Stool alanine, tyrosine, methionine, and the ratio of fecal alanine to choline and phosphocholine were higher in controls (p < 0.05). No difference was observed in stool propionate and butyrate levels as measures of short-chain fatty acids between the two cohorts.

Conclusions

Administration of human milk resulted in decreased markers of intestinal inflammation and could be a valuable adjunct for patients after BMT.

The guidelines are a compendium of multidisciplinary collaboration between members of the newborn Center at Texas Children's Hospital and Baylor College of Medicine. These guidelines provide beside clinicians with a practical up-to-date and evidence-based reference for patient care.

Objective

Articles previously published by Sullivan et al. and Cristofalo et al. were reanalyzed using the proportion of cow milk-based nutrition received to determine whether that affected clinical outcomes during hospitalization for infants birth weight 500–1250 g. Abrams et al. showed in the same cohort incidences of necrotizing enterocolitis (NEC), NEC requiring surgery and sepsis increased proportionally to the amount of dietary cow milk.

Methods

The data from the two studies conducted under essentially the same protocol were combined yielding a cohort of 260 infants receiving a diet ranging from 0% to 100% cow milk. Data analysis utilized negative binomial regression which mitigates differences between subjects in terms of their time on study by incorporating that number into the statistical model. The percent of cow milk-based nutrition was the only predictor investigated.

Results

For all outcomes the larger the amount of cow's milk in the diet the greater the number of days of that intervention required. A trend toward statistical significance was seen for ventilator days; however, only parenteral nutrition (PN) days and days to full feeds achieved statistical significance.

Conclusions

Incorporation of any cow milk-based nutrition into the diet of extremely premature infants correlates with more days on PN and a longer time to achieve full feeds. There was a nonstatistically significant trend toward increased ventilator days. These represent additional clinical consequences of the use of any cow milk-based protein in feeding EP 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.

Objective

Donor milk is the best option when mother’s own milk is unavailable. Heat treatments are applied to ensure donor milk safety. The effects of heat treatments on milk gangliosides—bioactive compounds with beneficial antibacterial, anti-inflammatory, and prebiotic roles—have not been studied.

Methods

The most abundant gangliosides in non-homogenized human milk were characterized and quantified by liquid chromatography–mass spectrometry (LC–MS)/MS before and after pasteurization treatments mimicking industrial conditions (63 °C/30 min, 72 °C/15 s, 127 °C/5 s, and 140 °C/6 s). Ganglioside stability over a 3-month period was assessed following the storage at 4 and 23 °C.

Results

Independent of the heat treatment applied, gangliosides were stable after 3 months of storage at 4 or 23 °C, with only minor variations in individual ganglioside structures.

Conclusion

These findings will help to define the ideal processing and storage conditions for donor milk to maximize the preservation of the structure of bioactive compounds to enhance the health of fragile newborns. Moreover, these results highlight the need for, and provide a basis for, a standardized language enabling biological and food companies, regulatory agencies, and other food stakeholders to both annotate and compute the ways in which production, processing, and storage conditions alter or maintain the nutritive, bioactive, and organoleptic properties of ingredients and foods, as well as the qualitative effects these foods and ingredients may have on conferring phenotype in the consuming organism.

Objective

An exclusive human milk diet (EHM) fortified with human milk‐based fortifier decreases necrotizing enterocolitis (NEC) compared to maternal milk supplemented with preterm formula and bovine fortifier (PTF). Growth has been less with EHM and also maternal milk supplemented with donor human milk and bovine fortifier (HMBF). The objective was to evaluate the effect of a standardized feeding protocol on the growth of infants ≤1250 g birth weight supported with EHM and HMBF. The effect on the incidence of NEC was also evaluated.

Methods

A retrospective study of growth before and after implementation of a feeding protocol for infants who received either EHM or HMBF. Primary outcomes were weight, length, and head circumference gain velocities from birth to discharge. The incidence of NEC was also recorded.

Results

Analysis of covariance for 379 total infants showed that earlier day of life for fortification to 24 Kcal/oz was associated with increased weight gain (p = 0.0166) and length gain (p = 0.0064). Implementation of the feeding protocol was associated with increased head circumference gain (p = 0.006). EHM was associated with decreased incidence of NEC (p = 0.0302).

Conclusions

Implementation of a standardized feeding protocol including earlier fortification of maternal milk was associated with improved growth for infants receiving human milk feedings. EHM significantly decreased NEC. Earlier fortification had no effect on NEC.

Background

When human milk is unavailable, banked milk is recommended for feeding premature infants. Milk banks use processes to eliminate pathogens; however, variability among methods exists. Research aim: The aim of this study was to compare the macronutrient (protein, carbohydrate, fat, energy), immune-protective protein, and human milk oligosaccharide (HMO) content of human milk from three independent milk banks that use pasteurization (Holder vs. vat techniques) or retort sterilization.

Methods

Randomly acquired human milk samples from three different milk banks ( n = 3 from each bank) were analyzed for macronutrient concentrations using a Fourier transform mid-infrared spectroscopy human milk analyzer. The concentrations of IgA, IgM, IgG, lactoferrin, lysozyme, α-lactalbumin, α antitrypsin, casein, and HMO were analyzed by mass spectrometry.

Results

The concentrations of protein and fat were significantly ( p < .05) less in the retort sterilized compared with the Holder and vat pasteurized samples, respectively. The concentrations of all immune-modulating proteins were significantly ( p < .05) less in the retort sterilized samples compared with vat and/or Holder pasteurized samples. The total HMO concentration and HMOs containing fucose, sialic acid, and nonfucosylated neutral sugars were significantly ( p < .05) less in retort sterilized compared with Holder pasteurized samples.

Conclusion

Random milk samples that had undergone retort sterilization had significantly less immune-protective proteins and total and specific HMOs compared with samples that had undergone Holder and vat pasteurization. These data suggest that further analysis of the effect of retort sterilization on human milk components is needed prior to widespread adoption of this process.