title: Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. The initial maternal cost of providing 100 mL of human milk for very low birth weight infants in the neonatal intensive care unit. Costs of necrotizing enterocolitis and cost-effectiveness of exclusively human milk-based products in feeding extremely premature infants. Positive Effect of Human Milk Feeding during NICU Hospitalization on 24 Month Neurodevelopment of Very Low Birth Weight Infants: An Italian Cohort Study Randomized Trial of Donor Human Milk Versus Preterm Formula as Substitutes for Mothers' Own Milk in the Feeding of Extremely Premature Infants Breast milk and neonatal necrotising enterocolitis Cost Savings of Human Milk as a Strategy to Reduce the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants
abstract: 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 OBJECTIVES Human milk ( HM ) feeding is associated with lower incidence and severity of costly prematurity-specific morbidities compared to formula feeding in very low birth weight ( VLBW ; < 1,500 g ) infants . However , the costs of providing HM are not routinely reimbursed by payers and can be a significant barrier for mothers . This study determined the initial maternal cost of providing 100 mL of HM for VLBW infants during the early neonatal intensive care unit ( NICU ) stay . METHODS This secondary analysis examined data from 111 mothers who provided HM for their VLBW infants during the early NICU stay . These data were collected during a multisite , r and omized clinical trial where milk output and time spent pumping were recorded for every pumping session ( n = 13,273 ) . The cost analysis examined the cost of the breast pump rental , pump kit  , and  maternal opportunity cost  ( an estimate of the cost of maternal time ) . RESULTS Mean daily milk output and time spent pumping were 558.2 mL ( SD = 320.7 ; range = 0 - 2,024 ) and 98.7 minutes ( SD = 38.6 ; range = 0 - 295 ) , respectively . The mean cost of providing 100 mL of HM  varied from $ 2.60 to $ 6.18 when maternal opportunity cost was included and from $ 0.95 to $ 1.55 when it was excluded . The cost per 100 mL of HM  declined with every additional day of pumping and was most sensitive to the costs of the breast pump rental and pump kit . CONCLUSIONS These findings indicate that HM is reasonably inexpensive to provide and that the maternal cost of providing milk is mitigated by increasing milk output over the early NICU stay 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 The aim of this study was to determine the effect of human milk feeding during NICU hospitalization on neurodevelopment at 24 months of corrected age in very low birth weight infants . A cohort of 316 very low birth weight newborns ( weight ≤ 1500 g ) was prospect ively enrolled in a follow-up program on admission to the Neonatal Intensive Care Unit of S. Orsola Hospital , Bologna , Italy , from January 2005 to June 2011 . Neurodevelopment was evaluated at 24 months corrected age using the Griffiths Mental Development Scale . The effect of human milk nutrition on neurodevelopment was first investigated using a multiple linear regression model , to adjust for the effects of gestational age , small for gestational age , complications at birth and during hospitalization , growth restriction at discharge and socio-economic status . Path analysis was then used to refine the multiple regression model , taking into account the relationships among predictors and their temporal sequence . Human milk feeding during NICU hospitalization and higher socio-economic status were associated with better neurodevelopment at 24 months in both models . In the path analysis model intraventricular hemorrhage — periventricular leukomalacia and growth restriction at discharge proved to be directly and independently associated with poorer neurodevelopment . Gestational age and growth restriction at birth had indirect significant effects on neurodevelopment , which were mediated by complications that occurred at birth and during hospitalization , growth restriction at discharge and type of feeding . In conclusion , our findings suggest that mother ’s human milk feeding during hospitalization can be encouraged because it may improve neurodevelopment at 24 months corrected age Objective . Compared with preterm formula ( PF ) , mother 's milk ( MM ) is associated with lower rates of late-onset sepsis ( LOS ) and necrotizing enterocolitis ( NEC ) among premature infants . Because not all mothers of premature infants produce sufficient milk to supply their infants throughout hospitalization , we reasoned that pasteurized donor human milk ( DM ) would be a suitable alternative . Methods . Extremely premature infants ( < 30 weeks of gestation ) whose mothers intended to breastfeed were assigned r and omly to receive either pasteurized DM or PF if the supply of their own MM became insufficient during the study ( birth to 90 days of age or hospital discharge ) . Infection-related events ( LOS , NEC , meningitis , presumed sepsis , or urinary tract infection ) that occurred after the attainment of a milk intake of 50 mL/kg , dietary intake , growth , skin-to-skin contact , and duration of hospital stay were compared . The primary analysis compared groups DM and PF on an intent-to-treat basis . If no differences were noted , then these groups were combined and compared with the reference group , group MM . If differences were noted , then the subsequent analyses compared each group with group MM . Results . Of 243 infants , 70 ( 29 % ) received only MM ; group DM included 81 infants and group PF included 92 infants . Because of poor weight gain , 17 infants ( 21 % ) , all in group DM , were switched to PF . There were no differences in birth weight , gestational age , multiple births , and age at attainment of feeding of 50 mL/kg among groups . There were no differences between group DM and group PF in LOS and /or NEC , other infection-related events , hospital stay , or number of deaths . Group DM received a greater intake of milk and more nutritional supplements but had a slower rate of weight gain , compared with group PF . Compared with groups DM and PF , group MM had fewer episodes of LOS and /or NEC and total infection-related events and a shorter duration of hospital stay . Group MM also had fewer Gram-negative organisms isolated from blood cultures than did the other groups . Conclusions . In this r and omized , blinded trial of feeding of extremely premature infants , we found that , as a substitute for MM , DM offered little observed short-term advantage over PF for feeding extremely premature infants . Advantages to an exclusive diet of MM were observed in terms of fewer infection-related events and shorter hospital stays In a prospect i ve multicentre study on 926 preterm infants formally assigned to their early diet , necrotising enterocolitis developed in 51 ( 5.5 % ) .  Mortality was 26 % in stringently confirmed cases . In exclusively  formula-fed  babies confirmed disease was 6 - 10 times more common than in those fed breast milk alone and 3 times more common than in those who received formula plus breast milk . Pasteurised donor milk seemed to be as protective as raw maternal milk . Among babies born at more than 30 weeks ' gestation confirmed necrotising enterocolitis was rare in those whose diet included breast milk ; it was 20 times more common in those fed formula only . Other risk factors included very low  gestational age , respiratory disease , umbilical artery catheterisation , and polycythaemia . In formula-fed but not breast-milk-fed infants , delayed enteral feeding was associated with a lower frequency of necrotising enterocolitis . With the fall in the use of breast milk in British neonatal units , exclusive formula feeding could account for an estimated 500 extra cases of necrotising enterocolitis each year . About 100 of these infants would die Background : Necrotizing enterocolitis ( NEC ) is a costly morbidity in very low birth weight ( VLBW ; < 1,500 g birth weight ) infants that increases hospital length of stay and requires expensive treatments . Objectives : To evaluate the cost of NEC as a function of dose and exposure period of human milk ( HM ) feedings received by VLBW infants during the neonatal intensive care unit ( NICU ) hospitalization and determine the drivers of differences in NICU hospitalization costs for infants with and without NEC . Methods : This study included 291 VLBW infants enrolled in an NIH-funded prospect i ve observational cohort study between February 2008 and July 2012 . We examined the incidence of NEC , NICU hospitalization cost , and cost of individual re sources used during the NICU hospitalization . Results : Twenty-nine ( 10.0 % ) infants developed NEC . The average total NICU hospitalization cost ( in 2012 USD ) was USD 180,163 for infants with NEC and USD 134,494 for infants without NEC ( p = 0.024 ) . NEC was associated with a marginal increase in costs of USD 43,818 , after controlling for demographic characteristics , risk of NEC , and average daily dose of HM during days 1 - 14 ( p < 0.001 ) . Each additional ml/kg/day of HM during days 1 - 14 decreased non-NEC-related NICU costs by USD 534 ( p < 0.001 ) . Conclusions : Avoidance of formula and use of exclusive HM feedings during the first 14 days of life is an effective strategy to reduce the risk of NEC and result ing NICU costs in VLBW infants . Hospitals investing in initiatives to feed exclusive HM during the first 14 days of life could substantially reduce NEC-related NICU hospitalization costs
target: It is likely that donor milk provides short-term cost savings by reducing the incidence of NEC .
background: BACKGROUND Necrotizing enterocolitis ( NEC ) is a costly gastrointestinal disorder that mainly affects preterm and low-birth-weight infants and can lead to considerable morbidity and mortality .
  Mother 's own milk is protective against NEC but is not always available .
  In such cases , donor human milk has also been shown to be protective ( although to a lesser extent ) compared with formula milk , but it is more expensive .
  This systematic review aim ed at evaluating the cost of donor milk , the cost of treating NEC , and the cost-effectiveness of exclusive donor milk versus formula milk feeding to reduce the short-term health and treatment costs of NEC .