Costs of necrotizing enterocolitis and cost-effectiveness of exclusively human milk-based products in feeding extremely premature infants. Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. Cost Savings of Human Milk as a Strategy to Reduce the Incidence 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. Randomized Trial of Donor Human Milk Versus Preterm Formula as Substitutes for Mothers' Own Milk in the Feeding of Extremely Premature Infants Early human milk feeding is associated with a lower risk of necrotizing enterocolitis in very low birth weight infants Necrotizing enterocolitis - classification and two initial steps towards prevention.
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 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 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 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 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 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 The premature infant suffers from immaturity of all organ systems , one of them being the gastrointestinal tract . When the infant is born , the immature gastrointestinal tract is exposed to milk and simultaneously colonized by high densities of bacteria . The combination of milk , microbiota and an immature gut , leaves the infant vulnerable to developing the dreaded intestinal emergency necrotizing enterocolitis ( NEC ) . NEC is often very aggressive and no cure exists , which means that prevention is an utmost important topic to research ers , physicians , parents - and infants . Despite immense research during the last decades , no specific test to determine if an infant suffers from NEC exists . Most neonatal units use Bell 's staging criteria , which are based on clinical and radiographic findings , as a diagnostic tool ; however the diagnosis given according to Bell 's stages has not been vali date d. In study I , we aim ed to determine the validity of the NEC diagnosis given at discharge . An expert panel consisting of a neonatologist , a paediatric surgeon and a paediatric radiologist served as the golden st and ard . We found that the diagnosis given at discharge had a poor validity which significantly affected the reported incidence of NEC in the neonatal department at Rigshospitalet , Denmark . The validity of the NEC diagnosis was worse than the validity of most other paediatric diagnoses that had been investigated . In studies II and III , we aim ed to explore possible means of NEC prevention . The role of nutrition in NEC development is well established with mother 's milk as the best option to avoid NEC in the preterm infant . Maternal milk is , however , most often not available in sufficient amounts during the first days of life , and preterm infant formula or human donor milk is used in its absence . Studies in preterm piglets showed that bovine colostrum equally to human donor milk protected against NEC compared to infant formula . Furthermore , bovine colostrum was superior to human donor milk in stimulating gut immunity and digestive functions . Hence , in study II we aim ed to design a pilot study of bovine colostrum used as a supplement to maternal milk in the first days of life and to determine if the study was feasible . In the paper , we present the protocol and the results of the first two phases of the Precolos study in which 12 infants were included and received pasteurized , spray-dried and reconstituted bovine colostrum during the first days of life as the first infants in the world . We found that the infants tolerated bovine colostrum without clinical adverse effects , but we also observed a transient hypertyrosinemia on day seven of life in five infants . The results were evaluated by a safety management board which encouraged us to continue the pilot study with the last phase , which was a r and omized controlled trial of 20 + 20 infants comparing supplementation with bovine colostrum to supplementation with st and ard nutrition . The r and omized trial has just finished recruitment . At last , we wanted to shed light on a possible microbiological angle of NEC prevention . Dysbiosis and bacterial translocation are believed to play a crucial role in the development of NEC as intestinal pneumatosis , which occurs when bacteria produce gas inside the intestinal wall , is a pathognomonic radiographic finding . In a quality improvement study from the US published in 2014 , NEC incidence was significantly reduced after the implementation of several quality improvement interventions . St and ardized weekly exchange of nasogastric feeding tubes was suggested as one of the potential NEC-reducing interventions . In the neonatal unit at Rigshospitalet , Denmark , preterm infants are fed 8 - 12 times daily through a resident nasogastric feeding tube which is exposed to body temperature , contains milk residuals from the last meal and is h and led by both parents and personnel . Since bacterial pollution of milk given through the nasogastric feeding tube might be NEC-inducing , we aim ed in study III to determine the bacterial load given to the infants when feeding them through a tube . We collected 92 used nasogastric feeding tubes and flushed them with one ml saline each to imitate a meal given through them . Eighty-nine percent of the tubes contaminated the meals with more than 1000 colony-forming units of bacteria and fifty-five percent contaminated the meals with the possible pathogens Enterobacteriaceae or Staphylococcus aureus . The concentration of bacteria in the saline flushed through the tubes was as high as 109 colony-forming units per ml ; however , neither the risk of contamination nor the concentration of bacteria in the flush was associated with the duration of use . Implementation of st and ardized weekly exchange of feeding tubes would therefore not prevent the contamination of meals . In conclusion , the studies included in this thesis serve as a base for future studies investigating the prevention of NEC . We found a poor validity of the NEC diagnosis given at discharge . This should be kept in mind when conducting epidemiological studies of NEC and especially when conducting interventional trials with NEC as an outcome . If the findings of the r and omized part of the Precolos study indicate a positive effect of bovine colostrum and do not give rise to concerns regarding feasibility , safety or tolerability , a large-scale r and omized controlled study with NEC as the primary outcome will be planned . Based on the high concentrations of bacteria found in the nasogastric feeding tubes , a r and omized controlled trial investigating whether the frequency of feeding tube exchange affects the early colonization has been commenced in the neonatal department at Rigshospitalet . Hopefully , the results of these studies will bring us closer to preventing NEC in the future
It is likely that donor milk provides short-term cost savings by reducing the incidence of NEC .
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 .