Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. Does fortification of pasteurized donor human milk increase the incidence of necrotizing enterocolitis among preterm neonates? A randomized controlled trial Growth of Very Low Birth Weight Infants on Varying Amounts of Human Milk Protein Costs of necrotizing enterocolitis and cost-effectiveness of exclusively human milk-based products in feeding extremely premature infants. Effect of human milk fortification in appropriate for gestation and small for gestation preterm babies: a randomized controlled trial. Early human milk feeding is associated with a lower risk of necrotizing enterocolitis in very low birth weight infants An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milk-based products. An exclusive human milk-based diet in extremely premature infants reduces the probability of remaining on total parenteral nutrition: a reanalysis of the data A comparison of 2 intravenous lipid emulsions: interim analysis of a randomized controlled trial. Fortified human milk in the small for gestational age neonate Growth and morbidity of extremely preterm infants after early full enteral nutrition Effect of Donor Milk on Severe Infections and Mortality in Very Low-Birth-Weight Infants: The Early Nutrition Study Randomized Clinical Trial. Nutrient enrichment of human milk with human and bovine milk-based fortifiers for infants born weighing <1250 g: a randomized clinical trial.
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 r and omized trial of formula vs human milk . STUDY DESIGN Multicenter r and omized 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 Abstract Objective : To compare the effect of fortified pasteurized donor human milk ( PDHM ) versus unfortified PDHM on the incidence of necrotizing enterocolitis ( NEC ) and immediate outcome among preterm neonates . Methods : This r and omized controlled trial ( RCT ) conducted in a tertiary care teaching hospital , south India included 80 healthy preterm neonates r and omized to two groups ( Group A and B ) . Neonates in Group A and B were fed with fortified PDHM and unfortified PDHM , respectively . Neonates in both groups were managed uniformly as per st and ard NICU protocol . The primary outcome was the incidence of NEC and the secondary outcomes included severity of NEC , incidence of sepsis , mortality , duration of hospital stay , number of days to reach full enteral feeds and weight gain . Neonates were followed up for 28 days or discharge whichever was earlier . Results : The baseline maternal and neonatal characteristics in both groups were comparable . There was no increase in incidence of NEC in fortified PDHM group compared to unfortified PDHM group ( 2.5 versus 7.5 % , p = .31 ) . Severity of NEC , incidence of sepsis , mortality , duration of hospital stay , number of days to reach full enteral feeds and weight gain were also similar in both groups . Conclusions : St and ard fortification of PDHM does not increase the incidence of NEC among preterm neonates ABSTRACT : In a double-blind , r and omized study , 28 healthy , growing very low birth wt , appropriate-for-gestational- age infants were fed human milk , preferably mother 's own , fortified daily with human milk protein and /or human milk fat . The infants entered the study when they were stable on complete enteral intakes of 170 ml/kgd ( mean ) age=19 d ) . The study lasted for a mean of 4 wk , Sample s from all the milks were collected daily , and intakes of protein , fat , carbohydrates , energy , and electrolytes were calculated weekly during the whole study period . Protein intakes ranged from 1.7 to 3.9 g/kg/d , and energy intakes from 100 to 150 kcal/kg/d . Wt and length gain in the nonprotein-enriched groups were 15.6 ± 2.7 g/kg/d ( mean ± SD ) and 0.88 ± 0.17 cm/wk ; the corresponding figures for the protein-enriched groups were 20.2 ± 2.1 g/ kg/d and 1.24 ± 0.14 cm/wk . There was a strong correlation between protein intake and growth in wt and length up to an intake of about 3 g/kg/d ; more protein did not result in increased growth . The same was true for energy intake , with a maximal growth rate at an intake of about 120 kcal/ kg/d . A protein intake of more than 3 g/kg/d result ed in a growth rate equal to or higher than the estimated intrauterine growth rate . Some infants fed mature banked human milk alone had a poor growth . Sodium intake was low , ranging from 1.5 to 2.6 mmol/kg/d . No correlation was found between sodium intake and growth rates OBJECTIVE This study evaluated the cost-effectiveness of a 100 % human milk-based diet composed of mother 's milk fortified with a donor human milk-based human milk fortifier ( HMF ) versus mother 's milk fortified with bovine milk-based HMF to initiate enteral nutrition among extremely premature infants in the neonatal intensive care unit ( NICU ) . METHODS A net expected costs calculator was developed to compare the total NICU costs among extremely premature infants who were fed either a bovine milk-based HMF-fortified diet or a 100 % human milk-based diet  , based on the previously observed risks of overall necrotizing enterocolitis ( NEC ) and surgical NEC in a r and omized controlled study that compared outcomes of these two feeding strategies among 207 very low birth weight infants . The average NICU costs for an extremely premature infant without NEC and the incremental costs due to medical and surgical NEC were derived from a separate analysis of hospital discharges in the state of California in 2007 . The sensitivity of cost-effectiveness results to the risks and costs of NEC and to prices of milk supplements was studied . RESULTS The adjusted incremental costs of medical NEC and surgical NEC over and above the average costs incurred for extremely premature infants without NEC , in 2011 US$ , were $ 74,004 ( 95 % confidence interval , $ 47,051-$100,957 ) and $ 198,040 ( 95 % confidence interval , $ 159,261-$236,819 ) per infant , respectively . Extremely premature infants fed with 100 % human-milk based products had lower expected NICU length of stay and total expected costs of hospitalization , result ing in net direct savings of 3.9 NICU days and $ 8,167.17 ( 95 % confidence interval , $ 4,405-$11,930 ) per extremely premature infant ( p < 0.0001 ) . Costs savings from the donor HMF strategy were sensitive to price and quantity of donor HMF , percentage reduction in risk of overall NEC and surgical NEC achieved , and incremental costs of surgical NEC . CONCLUSIONS Compared with feeding extremely premature infants with mother 's milk fortified with bovine milk-based supplements , a 100 % human milk-based diet that includes mother 's milk fortified with donor human milk-based HMF may result in potential net savings on medical care re sources by preventing NEC OBJECTIVE To study the effects of human milk fortification on short term growth and biochemical parameters in preterm very low birth weight ( VLBW ) appropriate for gestation ( AGA ) and small for gestation ( SGA ) babies . DESIGN Prospect i ve , r and omized controlled trial . SETTING Level III neonatal unit . SUBJECTS Preterm infants weighing < or = 1500 grams and < or = 34 weeks of gestation born between March 2001 to June 2002 . METHODS Babies ( n = 166 ) were r and omized in two groups either to get fortified human milk or exclusive human milk along with mineral and vitamin supplementation when feed volume reached 150 mL/Kg/day . Fortification was done with a powdered fortifier added in expressed breast milk and continued till the baby reached 2 Kg or full breast feeds . Primary outcome measures were Short-term growth ( daily weight , length and head circumference ( HC ) weekly ) till discharge or 2 Kg . RESULTS Fortification ( n = 85 , birth weight 1202 g , gestation 30.8 wk ) result ed in better growth in preterm VLBW babies as compared to control group ( n=81 , birth weight 1259 g , gestation 31.3 wk ) . Weight gain ( 15.1 and 12.9 g/kg/d , P < 0.001 ) , length ( 1.04 and 0.86 cm/week , P = 0.017 ) and HC ( 0.83 and 0.75 cm/week , P<0.001 ) increased significantly in fortified group . SGA babies showed significant improvements in weight ( 16 g/Kg/d and 12.9 g/kg/d , P = 0.002 ) and length ( 1.09 cm/week and 0.92 cm/week , P = 0.042 ) in fortified group ( n = 38 ) as compared to control group ( n = 29 ) . In AGA subgroup , there was significant increase ( P = 0.006 ) in length ( 1 cm vs 0.82 cm ) in fortified group but no difference in weight ( P = 0.12 ) or HC ( P=0.054 ) in fortified ( n=47 ) vs control ( n=52 ) group . Biochemical parameters were comparable , however feed intolerance was more in control group . CONCLUSION Preterm VLBW babies showed better growth with human milk fortification . The effect is significant in SGA ( weight and length)rather than AGA ( only length ) babies Background : Necrotizing enterocolitis ( NEC ) is a frequent cause of mortality and morbidity in very low birth weight ( VLBW ) infants .  Human milk ( HM ) feeding has been associated with lower risk of NEC . However , mothers of VLBW infants often experience insufficient milk production , result ing in mixed feedings of HM and formula . Moreover , medical complications often limit the volume of feeding they can be given . Objective : To determine if high proportions of ( 50 % or greater ) HM enteral feeding within the first 14 days of life are protective against NEC . Method : This was a prospect i ve cohort study of VLBW infants who were grouped according to the HM proportion of enteral feeding in the first 14 days : < 50 % ( low human milk , LHM , n=46 ) and ⩾50 % ( high human milk , HHM , n=156 ) . The outcome of interest was development of NEC ( Bell stage 2 or 3 ) . Logistic regression was used to estimate odds ratios ( OR ) and 95 % confidence intervals ( CI ) and to assess potential confounding due to perinatal risk factors . Result : Two hundred and two infants were studied . Confirmed NEC occurred in 5/46 ( 10.6 % ) of the LHM group , as compared with 5/156 ( 3.2 % ) of the HHM . Gestational age was the only perinatal factor associated with risk of NEC . After adjustment for gestational age , HHM was associated with a lower risk of NEC ( ( OR=0.17 , 95 % CI : 0.04 to 0.68 ) , P=0.01 ) . Conclusion : Enteral feeding containing at least 50 % HM in the first 14 days of life was associated with a sixfold decrease in the odds of NEC OBJECTIVE To evaluate the health benefits of an exclusively human milk-based diet compared with a diet of both human milk and bovine milk-based products in extremely premature infants . STUDY DESIGN Infants fed their own mothers ' milk were r and omized to 1 of 3 study groups . Groups HM100 and HM40 received pasteurized donor human milk-based human milk fortifier when the enteral intake was 100 and 40 mL/kg/d , respectively , and both groups received pasteurized donor human milk if no mother 's milk was available . Group BOV received bovine milk-based human milk fortifier when the enteral intake was 100 mL/kg/d and preterm formula if no mother 's milk was available . Outcomes included duration of parenteral nutrition , morbidity , and growth . RESULTS The 3 groups ( total n = 207 infants ) had similar baseline demographic variables , duration of parenteral nutrition , rates of late-onset sepsis , and growth . The groups receiving an exclusively human milk diet had significantly lower rates of necrotizing enterocolitis ( NEC ; P = .02 ) and NEC requiring surgical intervention ( P = .007 ) . CONCLUSIONS For extremely premature infants , an exclusively human milk-based diet is associated with significantly lower rates of NEC and surgical NEC when compared with a mother 's milk-based diet that also includes bovine milk-based products 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 r and omized 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 . Trial registration This study was registered at http://www . clinical trials.gov reg . # OBJECTIVE To assess the safety and efficacy of a fish oil-based intravenous fat emulsion ( FIFE ) in reducing the incidence of cholestasis in neonates compared with the traditional soybean oil-based intravenous fat emulsion ( SIFE ) . METHODS A double-blind r and omized controlled trial was conducted . Nineteen neonates were enrolled ( 10 SIFE ; 9 FIFE ) . Nutrition assessment s and laboratory studies were serially obtained for the duration of PN support or until 6 months ' corrected gestational age . Neurodevelopmental outcomes were assessed at 6 and 24 months ' corrected age . RESULTS There were no differences between groups in demographic characteristics , with an overall median age of 2 days , gestational age of 36 weeks , and birth weight of 2410 g. There were no differences between groups in baseline laboratory values other than alkaline phosphatase ( lower in the FIFE group ) or in the duration of parenteral nutrition ( PN ) , amount of enteral intake , or the number of operative procedures . The incidence of cholestasis among enrolled patients was significantly lower than expected , result ing in early study termination and an inability to assess for differences in the incidence of cholestasis . The FIFE was associated with no increased risk of growth impairment , coagulopathy , infectious complications , hypertriglyceridemia , or adverse neurodevelopmental outcomes . No patient developed essential fatty acid deficiency . CONCLUSION The FIFE at 1 g/kg/d was well tolerated in the neonates recruited for this study . Given the necessary early termination of this study , a follow-up trial with revised eligibility criteria is necessary to determine whether the provision of FIFE decreases the incidence of PN-cholestasis compared with the traditional SIFE Objective To assess the nutritional advantage of fortified human milk in the small for gestational age neonate . Methods Term asymmetric small for gestational age babies were r and omly assigned to either the study group or the control group . The babies in the study group received fortified EBM , ( more proteins , calories , vitamins and minerals ) whereas babies in the control group received EBM only . Babies were followed up weekly for a period of 28 ± 2 days for physical growth ( weight , length and OFC ) . Biochemical markers of nutritional status ( Blood urea , serum calcium , phosphorus , alkaline phosphatase , serum electrolytes and serum protein ) were done initially and then on Day 28 ± 2 . Results The weight gain in the study group ( 38.77 ± 7.43 g/day ) was significantly better than in the control group ( 28.71 ± 3.18 g/day ) . The length and OFC gain in the study group ( 1.14 ± 0.33 cm/week and 0.62 ± 0.07 cms/week , respectively ) were significantly better than in the control group ( 0.87 ± 0.17 cm/week and 0.49 ± 0.07 cm/week respectively ) . The biochemical markers of nutrition , however , were not significantly different in the two groups . Conclusion Fortified breast milk results in improved physical growth in the term asymmetric small for gestational age neonate Objectives To evaluate feasibility and consequences of accelerated feeding advancement on short-term outcomes in extremely low gestational age neonates ( ELGANs ) who stayed in our institution for > 28 days . Methods Retrospective single-centre cohort analysis covering the years 2011–2013 . Data are presented as median ( IQR ) . Results Infants ' ( n=77 ) birth weight was 745 ( 640 to 960 ) g and gestational age at birth 26.7 ( 25.1 to 27.4 ) weeks .  Full enteral feeds were attained by postnatal day 7 ( 5 to 11 ) . Weight gain from birth to discharge was 14.3 ( 13.3 to 16.1 ) g/kg/day , change in SD score for weight −0.03 ( −0.55 to 0.46 ) and 0.09 ( −0.78 and 0.82 ) for head circumference . Rates of necrotising enterocolitis and spontaneous intestinal perforation in all ELGANs admitted during the study period were 3.1 % and 9.4 % , respectively . Conclusions This cohort of ELGANs showed good weight gain and head growth after early full enteral nutrition . The impact of this feeding practice on neonatal morbidity and long-term outcome remains to be tested in adequately powered r and omised trials IMPORTANCE Infections and necrotizing enterocolitis , major causes of mortality and morbidity in preterm infants , are reduced in infants fed their own mother 's milk when compared with formula . When own mother 's milk is not available , human donor milk is considered a good alternative , albeit an expensive one . However , most infants at modern neonatal intensive care units are predominantly fed with own mother 's milk . The benefits of add-on donor milk over formula are not clear . OBJECTIVE To determine whether providing donor milk instead of formula as supplemental feeding whenever own mother 's milk is insufficiently available during the first 10 days of life reduces the incidence of serious infection , necrotizing enterocolitis , and mortality . DESIGN , SETTING S , AND PARTICIPANTS The Early Nutrition Study was a multicenter , double-blind r and omized clinical trial in very low-birth-weight infants ( birth weight < 1500 g ) admitted to 1 of 6 neonatal intensive care units in the Netherl and s from March 30 , 2012 , through August 17 , 2014 . Intent-to-treat analysis was performed . INTERVENTIONS Infants received pasteurized donor milk or preterm formula during the first 10 days of life if own mother 's milk was not ( sufficiently ) available . MAIN OUTCOMES AND MEASURES The primary end point was cumulative occurrence of serious infection ( sepsis or meningitis ) , necrotizing enterocolitis , or mortality during the first 60 days of life . RESULTS A total of 930 infants were screened for inclusion ; 557 were excluded , result ing in 373 infants ( 183 receiving donor milk and 190 receiving formula )  who were evaluated by intent-to-treat analysis ( median birth weight , 1066 g ; mean gestational age , 28.4 weeks ) . Own mother 's milk comprised 89.1 % and 84.5 % of total mean intake during the intervention period for the donor milk and formula groups , respectively . The incidence of the combined outcome was not different ( 85 [ 44.7 % ] [ formula ] vs 77 [ 42.1 % ] [ donor milk ] ; mean difference , 2.6 % ; 95 % CI , -12.7 % to 7.4 % ) . The adjusted hazard ratio was 0.87 ( 95 % CI , 0.63 - 1.19 ; P = .37 ) . CONCLUSIONS AND RELEVANCE In the current study , pasteurized donor milk and preterm formula as supplemental feeding during the first 10 days of life yielded similar short-term outcomes in very low-birth-weight infants regarding safety and efficacy when own mother 's milk availability was insufficient . Future studies investigating longer duration of use of human donor milk on short-term and long-term outcomes are necessary . TRIAL REGISTRATION trialregister.nl Identifier : NTR3225 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 r and omized 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 r and omized 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 r and omized ( 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 ( 48.4 % HMBF , 49.2 % BMBF , adjusted P = 0.76 ) , 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 . This trial was registered at clinical trials.gov as NCT02137473
BACKGROUND Preterm infants who are fed breast milk in comparison to infant formula have decreased morbidity such as necrotizing enterocolitis .
Multi-nutrient fortifiers used to increase the nutritional content of the breast milk are commonly derived from bovine milk .
Human milk-derived multi-nutrient fortifier is now available , but it is not clear if it improves outcomes in preterm infants fed with breast milk .
OBJECTIVES To determine whether the fortification of breast milk feeds with human milk-derived fortifier in preterm infants reduces mortality , morbidity , and promotes growth and development compared to bovine milk-derived fortifier .