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.

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

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

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.

Objective

To describe the results of utilizing a human milk-based human milk fortifier (HMHMF) as rescue therapy to meet nutritional requirements in very low birth weight and preterm infants demonstrating feeding intolerance to bovine-based human milk fortifier (BHMF) in the Canadian Neonatal Intensive Care Unit (NICU) setting.

Methods

At two Level III NICUs in Winnipeg, MB, Canada, a rescue protocol was implemented to provide HMHMF for infants demonstrating intolerance to BHMF. To qualify for rescue, infants were required to experience two episodes of significant gastrointestinal (GI) symptoms associated with fortification with BHMF. A case series report was conducted retrospectively examining the success of rescue therapy, growth rates, protein, and calorie intakes before and after initiation of HMHMF in seven infants.

Results

Seven infants (birth weight 723 ± 247 g, gestation 25.3 ± 3.4 weeks) were treated with rescue fortification with HMHMF. All infants were transitioned off parenteral nutrition (PN) without relapse of GI symptoms. Growth rate, protein, and calorie intakes improved with the use of HMHMF.

Conclusions

Very low birth weight and preterm infants with GI intolerance to BHMF were successfully rescued with use of HMHMF. Improvements in growth were achieved without need for supplementation with PN through achievement of sufficient enteral calorie and protein intakes.

Human milk is the preferred diet for preterm infants as it protects against a multitude of NICU challenges, specifically necrotizing enterocolitis. Infants who receive greater than 50% of mother’s own milk (MOM) in the 2 weeks after birth have a significantly decreased risk of NEC. An additional factor in the recent declining rates of NEC is the increased utilization of donor human milk (DHM). This creates a bridge until MOM is readily available, thus decreasing the exposure to cow milk protein. Preterm infants are susceptible to NEC due to the immaturity of their gastrointestinal and immune systems. An exclusive human milk diet compensates for these immature systems in many ways such as lowering gastric pH, enhancing intestinal motility, decreasing epithelial permeability, and altering the composition of bacterial flora. Ideally, preterm infants should be fed human milk and avoid bovine protein. A diet consisting of human milk-based human milk fortifier is one way to provide the additional nutritional supplements necessary for adequate growth while receiving the protective benefits of a human milk diet.

Objective

Infants may benefit from early nutritional intervention to decrease hospital stay. To evaluate the effects of adding a human milk (HM)-derived cream (Cream) product to a standard feeding regimen in preterm infants.

Methods

In a prospective multicenter randomized study, infants with birth weights 750–1,250 g were assigned to a Control or Cream group. The Control group received a standard feeding regimen consisting of mother's own milk or donor HM with donor HM-derived fortifier. The Cream group received the standard feeding regimen along with an additional HM-derived cream supplement when the HM they received was <20 kcal/oz. Primary outcomes of this secondary analysis included comorbidities, length of stay (LOS), and postmenstrual age (PMA) at discharge.

Results

We enrolled 75 infants (Control n = 37, Cream n = 38) with gestational age 27.7 ± 1.8 weeks and birth weight 973 ± 145 g (mean ± SD). After adjusting for gestational age, birth weight, and presence of bronchopulmonary dysplasia (BPD), the Cream group had a decreased PMA at discharge (39.9 ± 4.8 versus 38.2 ± 2.7 weeks, p = 0.03) and LOS (86 ± 39 versus 74 ± 22 days, p = 0.05). For 21 infants with BPD, these values trended toward significance for PMA at discharge (44.2 ± 6.1 versus 41.3 ± 2.7 weeks, p = 0.08) and LOS (121 ± 49 versus 104 ± 23 days, p = 0.08).

Conclusions

Very preterm infants who received an HM-derived cream supplement were discharged earlier. Infants with BPD may have benefited the most.

Objective

The aim of this study was to compare outcomes of infants pre and post initiation of a feeding protocol providing an exclusive human milk–based diet (HUM).

Methods

In a multicenter retrospective cohort study, infants with a birth weight <1,250 g who received a bovine-based diet (BOV) of mother's own milk fortified with bovine fortifier and/or preterm formula were compared to infants who received a newly introduced HUM feeding protocol. Infants were excluded if they had major congenital anomalies or died in the first 12 hours of life. Data were collected 2–3 years prior to and after introduction of an exclusive HUM diet. Primary outcomes were necrotizing enterocolitis (NEC) and mortality. Secondary outcomes included late-onset sepsis, retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD).

Results

A total of 1,587 infants were included from four centers in Texas, Illinois, Florida, and California. There were no differences in baseline demographics or growth of infants. The HUM group had significantly lower incidence of proven NEC (16.7% versus 6.9%, p < 0.00001), mortality (17.2% versus 13.6%, p = 0.04), late-onset sepsis (30.3% versus 19.0%, p < 0.00001), ROP (9% versus 5.2%, p = 0.003), and BPD (56.3% versus 47.7%, p = 0.0015) compared with the BOV group.

Conclusions

Extremely premature infants who received an exclusive HUM diet had a significantly lower incidence of NEC and mortality. The HUM group also had a reduction in late-onset sepsis, BPD, and ROP. This multicenter study further emphasizes the many benefits of an exclusive HUM diet, and demonstrates multiple improved outcomes after implementation of such a feeding protocol.

Objective

Human milk is the best form of nutrition for preterm infants and has been associated with a lower incidence of necrotizing enterocolitis (NEC). Infants that develop NEC have a higher incidence of feeding intolerance and longer hospitalizations. The combination of a donor milk bank and donor milk-derived fortifier has changed feeding practices in neonatal intensive care units (NICU). The purpose of this study is to assess the benefits and cost of an exclusive human milk (EHM) diet in very low birth weight (VLBW) infants in a community level III NICU.

Study Design

This is a retrospective study including preterm infants ⩽28 weeks and/or VLBW (⩽1500 g) who were enrolled from March 2009 until March 2014. Infants were grouped as follows: group H (entirely human milk based, born March 2012 to 2014), group B (bovine-based fortifier and maternal milk, born March 2009 to 2012), group M (mixed combination of maternal milk, bovine-based fortifier and formula, born March 2009 to 2012) and group F (formula fed infants, born March 2009 to 2012). Baseline characteristics among the four groups were similar.

Result

The study included 293 infants between gestational ages 23 to 34 weeks and birth weights between 490 and 1700 g. Feeding intolerance occurred less often (P<0.0001), number of days to full feeds was lower (P<0.001), incidence of NEC was lower (P<0.011), and total hospitalization costs were lower by up to $106,968 per infant (P<0.004) in those fed an EHM diet compared with the other groups. Average weight gain per day was similar among the four groups (18.5 to 20.6 g per day).

Conclusions

Implementing an EHM diet in our VLBW infants has led to a significant decrease in the incidence of NEC. Other benefits of this diet include: decreased feeding intolerance, shorter time to full feeds, shorter length of stay, and lower hospital and physician charges for extremely premature and VLBW infants.