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).

Objective

The objective of this multi-center study was to compare, in infants ≤1250 g birth weight (BW) with neurodevelopmental assessment at 18–22 months of corrected age (CA), whether their neurodevelopmental outcomes differed based on exposure to an exclusive human milk-based (HUM) or to a bovine milk-based fortifier and/or preterm formula (BOV).

Study Design

Retrospective multi-center cohort study of infants undergoing neurodevelopmental assessment as to whether HUM or BOV exposure related to differences in outcomes of infants at 18–22 months CA, using the Bayley Scales of Infant Development III (BSID-III). BSID-III cognitive, language, and motor scores were adjusted for BW, sex, study site, and necrotizing enterocolitis.

Results

252 infants from 6 centers were included. BSID-III cognitive scores were higher in the HUM group (96.5 ± 15.1 vs 89.6 ± 14.1, adjusted p = 0.0001). Mean BSID-III language scores were 85.5 ± 15.0 in HUM and 82.2 ± 14.1 in BOV (adjusted p = 0.09). Mean BSID-III motor scores were 92.9 ± 11.7 in HUM and 91.4 ± 14.6 in BOV (adjusted p = 0.32).

Conclusion

In this cohort of infants undergoing neurodevelopmental assessment, infants receiving HUM diet had significantly higher cognitive BSID-III scores at 18–22 months CA. Further investigation is needed of this potential for HUM to positively influence infant cognitive outcomes.

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

Compare the incidence of severe (grade III/IV) intraventricular hemorrhage (IVH) and/or periventricular leukomalacia (PVL) between two groups of ELBW infants based on diet until 34 weeks corrected gestational age (CGA): (1) Exclusive human milk (EHM)—mother’s own and/or pasteurized donor human milk, human milk-derived fortifier, and oral care with colostrum/human milk vs. (2) non-EHM—bovine formula or mother’s own milk with bovine-derived fortifier.

Study design

Retrospective observational study of two groups of ELBW infants based on diet until 34 weeks CGA.

Result

There were n = 306 infants, 127 EHM and 179 non-EHM. Demographics and morbidities were similar except higher antenatal steroids and NEC in EHM group. The rate of severe IVH/PVL was lower in EHM compared to non-EHM group (7 vs. 18%, p < 0.006).

Conclusion

EHM diet had an independent neuroprotective effect and was associated with decreased incidence of severe IVH/PVL, supporting the need of EHM in ELBW infants.

Background:

Very low birthweight (VLBW) preterm infants fed mothers own milk (MOM) need nutritional supplementation, tra-ditionally achieved with cow's milk (CM) derived fortifier CMDF) and preterm formula (PTF) if MOM is insufficient. CM products have been associated with diverse major morbidities. The current recommendation is to preferentially replace PTF with donor milk (DM) to produce a 100% human milk (HM) base diet, usually forti-fied with CMDF.

Objective:

To identify whether CMDF, even when fed with a 100% HM base diet, is related to an increased risk of major morbidities.

Methods:

We identified a randomized trial with an all-HM base diet, comparing CMDF with a fortifier derived from human milk (HMDF), and two additional studies of this design were generated from raw data as subgroup analyses of a randomized con-trolled trial and a quasi-experimental study. Using these studies, we calculated the impact of CMDF on major morbidities of death, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), sepsis, bronchopulmonary dysplasia (BPD) and patent ductus arteriosus (PDA).

Results:

Each study individually provided support for an increase in major morbidities with CMDF. Meta-analyses of pooled data showed that compared to HMDF, the CMDF group had large in-creases in NEC (RR=3.3; P=0.001), ROP (RR=2.2; P=0.007), PDA (RR=1.6; P=0.009), interruption of feeding (RR=3.4; P=0.001) and a positive mortality/morbidity index based on one or more of death, NEC, sepsis, ROP and BPD (RR=1.4; P=0.006).

Conclusions:

Despite the increased use of HM in modern neonatal care as a base diet, we found a greater risk of critical morbidities with CMDF compared with HMDF. This burden of morbidity provides evidence that the benefits of an HM base diet, might be, in part, counteracted by multiple adverse outcomes relating to the use of CMDF.

Background

An exclusive human milk (EHM) diet in extremely low birth weight (ELBW) infants (birth weight ≤1,000 g) is linked to an increased likelihood of extrauterine growth restriction (EUGR, weight <10% at discharge). Past studies associated EUGR with worse neurodevelopmental (ND) outcomes; however, its impact when an EHM diet is used is unknown.

Objective

Determine whether EUGR adversely affects 2-year ND outcomes of ELBW infants fed an EHM diet. Secondary aims were to compare short-term morbidities and growth through 2 years corrected age (CA).

Methods

Prospective cohort study of ELBW infants fed an EHM diet until 34 weeks corrected gestational age and assessed at 2 years CA. ND outcomes between EUGR and non-EUGR infants were compared using the Bayley Scales of Infant Development 3rd Ed (BSID-III).

Results

Eighty-one ELBW infants survived, 44 were seen for follow-up, and 16 (36%) were EUGR. Baseline characteristics and Neonatal Intensive Care Unit (NICU) morbidities were similar. There were no statistically significant differences (median [25–75%]) between EUGR and non-EUGR groups in cognition, (90 [80–99] versus 95 [90–104]), language (84 [68–105] versus 89 [75–100]), or motor composite scores (87 [74–96] versus 91 [88–96]). Weight z-scores during NICU stay dropped in both groups, more pronounced for the EUGR infants. There was no difference in linear or head growth.

Conclusion

In our institution, ND outcomes at 2 years CA for ELBW infants fed an EHM diet were similar regardless of EUGR status. This suggests a neuroprotective effect of EHM diet in the ELBW population, despite weight gain velocity during NICU stay.

Background

Long-term outcomes of preterm infants fed an exclusive human milk-based (EHM) diet using a donor human milk-based fortifier are not well defined.

Methods

Infants ≤1,250 g birth weight (BW) were studied prospectively at two outpatient visits: 12–15 and 18–22 months corrected age (CA). Dual-energy X-ray absorptiometry and Bayley Scales of Infant and Toddler Development III (BSID-III) were performed at 18–22 months CA.

Results

In this pilot study, 51 preterm infants (gestational age 27.8 ± 2.6 weeks and BW 893 ± 204 g) were evaluated. While anthropometric z-scores were significantly lower at discharge compared with birth, z-scores returned to birth levels by 12–15 months CA (length and head circumference [HC]) and 18–22 months CA (weight). Body composition at 2 years of age was similar to term-matched controls. Inpatient growth was significantly correlated with bone density, lean mass (LM), and fat-free mass at 18–22 months CA. Increased mother's own milk (MOM) was significantly correlated with decreased fat mass indices. BSID-III showed that 0% of cognitive composite scores were <70.

Conclusions

In addition to returning to BW, length, and HC z-scores by 2 years of age, body composition analysis revealed that increase in body size was appropriate as reflected by LM and bone density similar to matched term controls without an increase in fat mass. No child had severe cognitive developmental delay using a cutoff score of 70. Inpatient growth and increased receipt of MOM correlated with favorable growth and body composition outcomes. Positive outcomes as shown in this study to confirm postdischarge safety of an EHM diet during hospitalization.

Background

Postnatal growth failure (PGF) in very low birthweight (VLBW) infants is a result of factors such as prematurity, acute illness and suboptimal nutritional support. Before this project began, 84% of appropriately grown VLBW infants in our neonatal intensive care unit experienced PGF. The aims of this quality improvement project were to reduce the percentage of infants discharged with PGF to less than 50% within 2 years and to maintain a rate of PGF under 50%.

Methods

All inborn VLBW infants were eligible for this study. Infants with congenital anomalies were excluded. We determined key drivers for optimal nutrition and identified potentially better practices (process measures) based on a review of the literature, which included more rapid initiation of starter total parenteral nutrition (TPN), aggressive use and advancement of regular TPN, and fortification of human milk when the volume of intake reached 80 mL/kg/day. Three Plan-Do-Study-Act (PDSA) cycles were tested.

Results

Time to initiation of starter TPN was significantly reduced from 5.5 hours to under 3 hours. Regular TPN provided the goals for amino acids and lipids at increased frequency after the first two PDSA cycles. The proportion of infants whose milk was fortified at 80 mL/kg/day increased after the third PDSA cycle.

Conclusions

We found a sustained decrease in the percentage of infants discharged with PGF from 84% at baseline to fewer than 50% beginning in 2010–2011 through 2016, with 23.1% of infants experiencing PGF in 2016. We have achieved improved nutritional support for VLBW infants using the model for improvement.

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.

Objective

To estimate associations of exclusive human milk (EHM) feedings with growth and neurodevelopment through 18 months corrected age (CA) in extremely low birth weight (ELBW) infants.

Study Design

ELBW infants admitted from July 2011 to June 2013 who survived were reviewed. Infants managed from July 2011 to June 2012 were fed with bovine milk-based fortifiers and formula (BOV). Beginning in July 2012, initial feedings used a human milk-based fortifier to provide EHM feedings. Infants were grouped on the basis of feeding regimen. Primary outcomes were the Bayley-III cognitive scores at 6, 12, and 18 months and growth.

Results

Infants (n = 85; 46% received EHM) were born at 26 ± 1.9 weeks (p = 0.92 between groups) weighing 776 ± 139 g (p = 0.67 between groups). Cognitive domain scores were similar at 6 months (BOV: 96 ± 7; EHM: 95 ± 14; p = 0.70), 12 months (BOV: 97 ± 10; EHM: 98 ± 9; p = 0.86), and 18 months (BOV: 97 ± 16; EHM: 98 ± 14; p = 0.71) CA. Growth velocity prior to discharge (BOV: 12.1 ± 5.2 g/kg/day; EHM: 13.1 ± 4.0 g/kg/day; p = 0.33) and subsequent growth was similar between groups.

Conclusion

EHM feedings appear to support similar growth and neurodevelopment in ELBW infants as compared with feedings containing primarily bovine milk-based products.