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

To evaluate whether premature infants who received an exclusive human milk (HM)-based diet and a HM-derived cream supplement (cream) would have weight gain (g/kg/d) at least as good as infants receiving a standard feeding regimen (control).

Study design

In a prospective noninferiority, randomized, unmasked study, infants with a birth weight 750-1250 g were randomly assigned to the control or cream group. The control group received mother's own milk or donor HM with donor HM-derived fortifier. The cream group received a HM-derived cream supplement if the energy density of the HM tested <20 kcal/oz using a near infrared HM analyzer. Infants were continued on the protocol until 36 weeks postmenstrual age. Primary outcomes included growth velocities and amount of donor HM-derived fortifier used. The hypothesis of noninferiority was established if the lower bound of the one-sided 95% CI for the difference in weight velocities exceeded −3 g/kg/day.

Results

There were no differences between groups in baseline demographics for the 78 infants studied except racial distribution ( P = .02). The cream group (n = 39) had superior weight (14.0 ± 2.5 vs 12.4 ± 3.0 g/kg/d, P = .03) and length (1.03 ± 0.33 vs 0.83 ± 0.41 cm/wk, P = .02) velocity compared with the control group (n = 39). There were no significant differences in amount of fortifier used between study groups. The 1-sided 95% lower bound of the CI for the difference in mean velocity (cream-control) was 0.38 g/kg/d.

Conclusions

Premature infants who received HM-derived cream to fortified HM had improved weight and length velocity compared with the control group. HM-derived cream should be considered an adjunctive supplement to an exclusive HM-based diet to improve growth rates in premature infants.

Background

Provision of human milk has important implications for the health and outcomes of extremely preterm (EP) infants. This study evaluated the effects of an exclusive human milk diet on the health of EP infants during their stay in the neonatal intensive care unit.

Methods

EP infants <1,250 g birth weight received a diet consisting of either human milk fortified with a human milk protein-based fortifier (HM) (n=167) or a diet containing variable amounts of milk containing cow milk-based protein (CM) (n=93). Principal outcomes were mortality, necrotizing enterocolitis (NEC), growth, and duration of parenteral nutrition (PN).

Results

Mortality (2% versus 8%, p=0.004) and NEC (5% versus 17%, p=0.002) differed significantly between the HM and CM groups, respectively. For every 10% increase in the volume of milk containing CM, the risk of sepsis increased by 17.9% (p<0.001). Growth rates were similar between groups. The duration of PN was 8 days less in the subgroup of infants receiving a diet containing <10% CM versus ≥10% CM (p<0.02).

Conclusions

An exclusive human milk diet, devoid of CM-containing products, was associated with lower mortality and morbidity in EP infants without compromising growth and should be considered as an approach to nutritional care of these infants.

Objective:

This study tested the hypothesis that feeding an exclusively human milk (EHM) diet to premature infants reduces the incidence of necrotizing enterocolitis (NEC) associated with enteral feeding.

Study Design:

An observational study for infants born at less than 33 weeks of gestational age was performed in a single neonatal intensive care unit. An EHM diet prospectively eliminated bovine-based artificial milk, including bovine-based fortifier, through 33 weeks postmenstrual age (PMA). The clinical data from a 2.5-year interval of the EHM diet were compared with data from the previous 6.5 years for similar infants who received bovine-based milk products before 33 weeks PMA.

Results:

In the EHM diet cohort, 148 of 162 infants (91%) received EHM through 33 weeks PMA. In order to achieve an EHM diet, 140 of 162 infants (86%) received their own mother's milk, and 98 of 162 infants (60%) received donor human milk. The EHM cohort was also fed a human milk-based fortifier to truly eliminate bovine products. The distribution of NEC onset in the EHM cohort was significantly different from that in the control cohort for the day of onset (p=0.042) and the PMA at onset (p=0.011). In the control cohort, NEC onset after Day 7 of life occurred in 15 of 443 infants (3.4%), significantly more than in the EHM cohort where NEC occurred in two of 199 infants (1%) (p=0.009).

Conclusions:

Changing to an EHM milk diet through 33 weeks PMA reduced the incidence of NEC associated with enteral feeding.

Synopsis

Premature infants are a heterogeneous group with widely differing needs for nutrition and immune protection with risk of growth failure, developmental delays, necrotizing enterocolitis, and late-onset sepsis increasing with decreasing gestational age and birth weight. Human milk from women delivering prematurely has more protein and higher levels of many bioactive molecules compared to milk from women delivering at term.

Human milk must be fortified for small premature infants to achieve adequate growth. Mother’s own milk improves growth and neurodevelopment and decreases the risk of necrotizing enterocolitis and late-onset sepsis and should therefore be the primary enteral diet of premature infants. Donor milk is a valuable resource for premature infants whose mothers are unable to provide an adequate supply of milk, but presents significant challenges including the need for pasteurization, nutritional and biochemical deficiencies and a limited supply.

Background

Despite current nutritional strategies, premature infants remain at high risk for extrauterine growth restriction. The use of an exclusive human milk-based diet is associated with decreased incidence of necrotizing enterocolitis (NEC), but concerns exist about infants achieving adequate growth. The objective of this study was to evaluate growth velocities and incidence of extrauterine growth restriction in infants ≤ 1250 grams (g) birth weight (BW) receiving an exclusive human milk-based diet with early and rapid advancement of fortification using a donor human milk derived fortifier.

Methods

In a single center, prospective observational cohort study, preterm infants weighing ≤ 1250 g BW were fed an exclusive human milk-based diet until 34 weeks postmenstrual age. Human milk fortification with donor human milk derived fortifier was started at 60 mL/kg/d and advanced to provide 6 to 8 additional kilocalories per ounce (or 0.21 to 0.28 kilocalories per gram). Data for growth were compared to historical growth standards and previous human milk-fed cohorts.

Results

We consecutively evaluated 104 infants with mean gestational age of 27.6 ± 2.0 weeks and BW of 913 ± 181 g (mean ± standard deviation). Weight gain was 24.8 ± 5.4 g/kg/day with length 0.99 ± 0.23 cm/week and head circumference 0.72 ± 0.14 cm/week. There were 3 medical NEC cases and 1 surgical NEC case. 22 infants (21%) were small for gestational age at birth. Overall, 45 infants (43%) had extrauterine growth restriction. Weight velocity was affected by day of fortification (p = 0.005) and day of full feeds (p = 0.02). Our cohort had significantly greater growth in weight and length compared to previous entirely human milk-fed cohorts.

Conclusions

A feeding protocol for infants ≤ 1250 g BW providing an exclusive human milk-based diet with early and rapid advancement of fortification leads to growth meeting targeted standards with a low rate of extrauterine growth restriction. Consistent nutritional policies using this approach may be considered for this population.

Objective

To compare the duration of parenteral nutrition, growth, and morbidity in extremely premature infants fed exclusive diets of either bovine milk–based preterm formula (BOV) or donor human milk and human milk-based human milk fortifier (HUM), in a randomized trial of formula vs human milk.

Study design

Multicenter randomized controlled trial. The authors studied extremely preterm infants whose mothers did not provide their milk. Infants were fed either BOV or an exclusive human milk diet of pasteurized donor human milk and HUM. The major outcome was duration of parenteral nutrition. Secondary outcomes were growth, respiratory support, and necrotizing enterocolitis (NEC).

Results

Birth weight (983 vs 996 g) and gestational age (27.5 vs 27.7 wk), in BOV and HUM, respectively, were similar. There was a significant difference in median parenteral nutrition days: 36 vs 27, in BOV vs HUM, respectively ( P = .04). The incidence of NEC in BOV was 21% (5 cases) vs 3% in HUM (1 case), P = .08; surgical NEC was significantly higher in BOV (4 cases) than HUM (0 cases), P = .04.

Conclusions

In extremely preterm infants given exclusive diets of preterm formula vs human milk, there was a significantly greater duration of parenteral nutrition and higher rate of surgical NEC in infants receiving preterm formula. This trial supports the use of an exclusive human milk diet to nourish extremely preterm infants in the neonatal intensive care unit.

Objective

To study the incidence of sepsis and neonatal intensive care unit (NICU) costs as a function of the human milk (HM) dose received during the first 28 days post birth for very low birth weight (VLBW) infants.

Study Design

Prospective cohort study of 175 VLBW infants. The average daily dose of HM (ADDHM) was calculated from daily nutritional data for the 28 days post birth (ADDHM-Days 1-28). Other covariates associated with sepsis were used to create a propensity score, combining multiple risk factors into a single metric.

Results

The mean gestational age and birth weight were 28.1±2.4 weeks and 1087±252 g, respectively. The mean ADDHM-Days 1–28 was 54±39 ml kg_1 day_1 (range 0–135). Binary logistic regression analysis controlling for propensity score revealed that increasing ADDHM-Days 1–28 was associated with lower odds of sepsis (odds ratio 0.981, 95% confidence interval 0.967–0.995,P.0.008). Increasing ADDHM-Days 1–28 was associated with significantly lower NICU costs.

Conclusion

A dose–response relationship was demonstrated between ADDHM-Days 1–28 and a reduction in the odds of sepsis and associated NICU costs after controlling for propensity score. For every HM dose increase of 10 ml kg_1 day_1, the odds of sepsis decreased by 19%. NICU costs were lowest in the VLBW infants who received the highest ADDHM-Days 1–28.

Synopsis

Premature infants are a heterogeneous group with widely differing needs for nutrition and immune protection with risk of growth failure, developmental delays, necrotizing enterocolitis, and late-onset sepsis increasing with decreasing gestational age and birth weight. Human milk from women delivering prematurely has more protein and higher levels of many bioactive molecules compared to milk from women delivering at term.

Human milk must be fortified for small premature infants to achieve adequate growth. Mother’s own milk improves growth and neurodevelopment and decreases the risk of necrotizing enterocolitis and late-onset sepsis and should therefore be the primary enteral diet of premature infants.

Donor milk is a valuable resource for premature infants whose mothers are unable to provide an adequate supply of milk, but presents significant challenges including the need for pasteurization, nutritional and biochemical deficiencies and a limited supply.

Breastfeeding and human milk are the normative standards for infant feeding and nutrition. Given the documented short- and long-term medical and neurodevelopmental advantages of breastfeeding, infant nutrition should be considered a public health issue and not only a lifestyle choice. The American Academy of Pediatrics reaffirms its recommendation of exclusive breastfeeding for about 6 months, followed by continued breastfeeding as complementary foods are introduced, with continuation of breastfeeding for 1 year or longer as mutually desired by mother and infant. Medical contraindications to breastfeeding are rare. Infant growth should be monitored with the World Health Organization (WHO) Growth Curve Standards to avoid mislabeling infants as underweight or failing to thrive. Hospital routines to encourage and support the initiation and sustaining of exclusive breastfeeding should be based on the American Academy of Pediatrics-endorsed WHO/UNICEF “Ten Steps to Successful Breastfeeding.” National strategies supported by the US Surgeon General’s Call to Action, the Centers for Disease Control and Prevention, and The Joint Commission are involved to facilitate breastfeeding practices in US hospitals and communities. Pediatricians play a critical role in their practices and communities as advocates of breastfeeding and thus should be knowledgeable about the health risks of not breastfeeding, the economic benefits to society of breastfeeding, and the techniques for managing and supporting the breastfeeding dyad. The “Business Case for Breastfeeding” details how mothers can maintain lactation in the workplace and the benefits to employers who facilitate this practice. Pediatrics 2012;129:e827–e841

Background

We have previously shown that an exclusively human milk-based diet is beneficial for extremely premature infants who are at risk for necrotizing enterocolitis (NEC). However, no significant difference in the other primary study endpoint, the length of time on total parenteral nutrition (TPN), was found. The current analysis re-evaluates these data from a different statistical perspective considering the probability or likelihood of needing TPN on any given day rather than the number of days on TPN. This study consisted of 207 premature infants randomized into three groups: one group receiving a control diet of human milk, formula and bovine-based fortifier (“control diet”), and the other two groups receiving only human milk and human milk-based fortifier starting at different times in the enteral feeding process (at feeding volumes of 40 or 100 mL/kg/day; “HM40” and “HM100”, respectively). The counting process Cox proportional hazards survival model was used to determine the likelihood of needing TPN in each group.

Results

The two groups on the completely human-based diet had an 11-14 % reduction in the likelihood of needing nutrition via TPN when compared to infants on the control diet (p = 0.0001 and p = 0.001, respectively for the HM40 and HM100 groups, respectively). This was even more pronounced if the initial period of TPN was excluded (p < 0.0001 for both the HM40 and HM100 groups).

Conclusions

A completely human milk-based diet significantly reduces the likelihood of TPN use for extremely premature infants when compared to a diet including cow-based products. This likelihood may be reduced even further when the human milk fortifier is initiated earlier in the feeding process.