title: Human Milk Feedings and Infection Among Very Low Birth Weight Infants Persistent Beneficial Effects of Breast Milk Ingested in the Neonatal Intensive Care Unit on Outcomes of Extremely Low Birth Weight Infants at 30 Months of Age Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. Randomized outcome trial of human milk fortification and developmental outcome in preterm infants. Adequacy of expressed breast milk for early gwoth of preterm infants. Pasteurization of Mother’s Own Milk for Preterm Infants Does Not Reduce the Incidence of Late-Onset Sepsis An exclusively human milk diet reduces necrotizing enterocolitis. The influence of early postnatal nutrition on retinopathy of prematurity in extremely low birth weight infants. Growth and Development of Premature Infants Fed Predominantly Human Milk, Predominantly Premature Infant Formula, or a Combination of Human Milk and Premature Formula Multicentre trial on feeding low birthweight infants: effects of diet on early growth. EFFECT OF BREASTMILK CONSUMPTION ON NEURODEVELOPMENTAL OUTCOMES AT 6 AND 12 MONTHS OF AGE IN VLBW INFANTS Early human milk feeding is associated with a lower risk of necrotizing enterocolitis in very low birth weight infants Impact of Early Human Milk on Sepsis and Health Care Costs 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. Early diet in preterm babies and developmental status in infancy. Influence of own mother's milk on bronchopulmonary dysplasia and costs The effect of maternal milk on neonatal morbidity of very low-birth-weight infants. Growth and biochemical response of preterm infants fed human milk or modified infant formula. PARTIAL SUPPLEMENTATION WITH EXPRESSED BREAST-MILK FOR PREVENTION OF INFECTION IN LOW-BIRTH-WEIGHT INFANTS 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 Enteral feeding regimens and necrotising enterocolitis in preterm infants: a multicentre case–control study The nuts and bolts of PROSPERO: an international prospective register of systematic reviews Effect of Donor Milk on Severe Infections and Mortality in Very Low-Birth-Weight Infants: The Early Nutrition Study Randomized Clinical Trial. Cost Savings of Human Milk as a Strategy to Reduce the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants RANDOMISED CONTROLLED TRIAL OF EFFECT OF RAW AND HOLDER PASTEURISED HUMAN MILK AND OF FORMULA SUPPLEMENTS ON INCIDENCE OF NEONATAL INFECTION Beneficial Effects of Breast Milk in the Neonatal Intensive Care Unit on the Developmental Outcome of Extremely Low Birth Weight Infants at 18 Months of Age
abstract: BACKGROUND Preterm infants are immunologically immature at birth . Previous studies have demonstrated that human milk protects against infection in full-term infants , but there are few studies of its effect for preterm infants . OBJECTIVE To examine the effect of human milk feedings on infection incidence among very low birth weight ( VLBW ) infants during their initial hospitalization . STUDY DESIGN The sample consisted of 212 consecutive VLBW infants admitted to the Georgetown University Medical Center neonatal intensive care unit ( NICU ) during 1992 - 1993 and surviving to receive enteral feeding .  Type of feeding ( human milk vs formula ) , presence of infection and sepsis/meningitis ( clinical signs and positive cultures for pathogenic organisms ) , and potential confounding variables were abstract ed from medical records . Multiple logistic regression was used to control for confounders . RESULTS The incidence of infection ( human milk [ 29.3 % ] vs formula [ 47.2 % ] ) and sepsis/meningitis ( human milk [ 19.5 % ] vs formula [ 32.6 % ] ) differed significantly by type of feeding . Major risk factors for infection were similar in both groups . Human milk feeding was independently correlated with a reduced odds of infection ( odds ratio [ OR ] = 0.43 ; 95 % confidence interval [ CI ] : 0.23 - 0.81 ) , controlling for gestational age , 5-minute Apgar score , mechanical ventilation days , and days without enteral feedings ; and was independently correlated with a reduced odds of sepsis/meningitis ( OR = 0.47 , 95 % CI:0.23 - 0 . 95 ) , controlling for gestational age , mechanical ventilation days , and days without enteral feedings . CONCLUSIONS The incidence of any infection and sepsis/meningitis are significantly reduced in  human milk-fed VLBW infants compared with exclusively formula-fed VLBW infants BACKGROUND . We previously reported beneficial effects of breast milk ingestion by infants with extremely low birth weight in the NICU on developmental outcomes at 18 months ’ corrected age . The objective of this study was to determine whether these effects of breast milk in infants with extremely low birth weight persisted at 30 months ’ corrected age . METHODS . Nutrition data , including enteral and parenteral feeds , were prospect ively collected , and 30 months ’ corrected age follow-up assessment s were completed on 773 infants with extremely low birth weight who participated in the National Institute of Child Health and Human Development Neonatal Research Network Glutamine Trial . A total of 593 ingested some breast milk during the neonatal hospitalization , and 180 ingested none . Neonatal feeding characteristics and morbidities and 30-month interim history , neurodevelopmental outcomes , and growth parameters were analyzed . Children were divided into quintiles of breast milk volume to evaluate the effects of volume of human milk ingested during the NICU hospitalization . RESULTS . At 30 months , increased ingestion of breast milk was associated with higher Bayley Mental Developmental Index scores , higher Bayley behavior score percentiles for emotional regulation , and fewer rehospitalizations between discharge and 30 months . There were no differences in growth parameters or cerebral palsy . For every 10 mL/kg per day increase in breast milk , the Mental Developmental Index increased by 0.59 points , the Psychomotor Developmental Index by 0.56 points , and the total behavior percentile score by 0.99 points , and the risk of rehospitalization between discharge and 30 months decreased by 5 % . CONCLUSIONS . Beneficial effects of ingestion of breast milk in the NICU persist at 30 months ’ corrected age in this vulnerable extremely low birth weight population . Continued efforts must be made to offer breast milk to all extremely low birth weight infants both in the NICU and after discharge 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 Despite potential benefits , human milk may fail to meet preterm infants ' nutrient requirements . We tested the hypothesis that fortified breast milk , fed alone or with preterm formula , would improve neurodevelopment and growth at 18-mo follow-up without adverse short-term clinical or biochemical consequences . Two hundred seventy-five preterm infants from two medical centers ( birth weight < 1850 g ; mean gestation 29.8 + /- 2.7 wk ) whose mothers chose to provide breast milk were r and omly assigned to receive for a mean of 39 d a multinutrient fortifier or control supplement containing phosphate and vitamins . Breast milk comprised 47.6 % and 46.4 % of enteral intake in fortified and control groups , respectively ; preterm formula supplements were used when insufficient breast milk was available . Overall , there were no significant growth advantages with fortification ; although , when breast milk exceeded 50 % of intake , fortification promoted faster weight gain ( an advantage of 1.6 g.kg-1.d-1 ; 95 % CI : 0.1 , 3.1 ; P < 0.05 ) . Compared with control infants , the fortified group showed 1 ) higher plasma urea from week 2 ( P = 0.04 ) , 2 ) higher plasma calcium ( mean 2.34 + /- 0.01 compared with 2.27 + /- 0.02 mmol/L ; P = 0.003 ) , 3 ) a greater rise in alkaline phosphatase by week 6 ( P = 0.04 ) , 4 ) more clinical infections ( suspected plus proven ; 43 % compared with 31 % , P = 0.04 ) , 5 ) a nonsignificantly increased incidence of necrotizing enterocolitis ( 5.8 % compared with 2.2 % , P = 0.12 ) , and 6 ) higher white cell and platelet counts . Developmental scores at 18 mo were slightly but not significantly higher in the fortified group . This study confirmed that breast milk fortifiers can improve short-term growth ( when breast milk intakes are high ) ; but beneficial effects on long-term development remained unproven . Future research is required to evaluate potential adverse consequences and explore more optimal fortification strategies Poor weight gain observed in preterm infants who were fed expressed breast milk compared with those fed a cows ' milk formular  prompted a detailed study of early postnatal growth in preterm infants fed these two milks . 68 infants were divided into two categories by gestational age at birth ( i ) 28 - 32 weeks ( n=28 ) , ( ii ) 33 - 36 weeks ( n=40 ) . They were r and omly allocated to a feed of expressed breast milk or a milk formula ( Ostermilk 1 ) . Rates of weight gain , linear growth , and head circumference growth were evaluated over two periods : birth-1 month , 1 - 2 months . The younger group who were fed breast milk showed slower overall growth rates over the first month than those fed formula . In the second month , and for the older infants over both of the 2-monthly periods , growth rates were similar in the two feeding regimens . It is concluded that expressed breast milk is inadequate for the growth of very immature preterm infants during early postnatal life Background : Feeding preterm infants human  milk has a beneficial effect on the risk of late-onset sepsis ( LOS ) . Due to lack of microbiological st and ards , practice s such as pasteurization of mother ’s own milk differ widely among neonatal intensive care units worldwide . Objectives : To investigate whether pasteurization of mother ’s own milk for very-low-birth-weight ( VLBW ) infants influences the incidence and severity of infection-related outcomes . Methods : In this r and omized controlled trial , preterm infants ( gestational age < 32 weeks and /or birth weight < 1,500 g ) received either raw or pasteurized mother ’s own milk during the first 8 weeks of life . The primary outcome was the incidence of proven LOS . A dose-response relation was verified , i.e. the dependence of the risk of sepsis on the actual and cumulative quantities of mother ’s own milk . Results : This study included 303 VLBW infants ( mean birth weight : 1,276 g ; mean gestational age : 29 weeks ) whose baseline and nutritional characteristics were similar . The incidence of laboratory-confirmed sepsis was not statistically different in infants fed raw milk compared to infants who received pasteurized milk : 22/151 ( 0.15 , CI : 0.08–0.20 ) and 31/152 ( 0.20 , CI : 0.14–0.27 ) , respectively ( RR : 0.71 ; 95 % CI : 0.43–1.17 ) . A significant dose-response relation was observed between the adjusted quantity of enteral feeding and the risk of LOS , regardless of the type of feeding . Conclusion : For preterm infants , pasteurization of mother ’s own milk shows a trend towards an increase in infectious morbidity , although no statistical significance was reached . Practice s should focus on collection , storage and labeling procedures to ensure the safety and quality of expressed milk 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 prospect ively 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 BACKGROUND Retinopathy of prematurity(ROP ) is the most common serious ophthalmic disease in preterm infants .  Human milk may provide a protective effect for ROP ; however , beneficial effects of human milk preclude r and omized trials . Therefore , we conducted a retrospective analysis comparing early postnatal nutrition with ROP development . OBJECTIVE Evaluate relationship between early postnatal nutriture and ROP surgery . DESIGN / METHODS Nutrition data was collected for inborn AGA infants , BW 700 - 1000 g.  ROP surgery was the primary outcome variable . A single pediatric ophthalmologist supervised examinations . All infants received triweekly IM vitamin A as chronic lung disease prophylaxis ( Tyson : NEJM , 1999 ) . RESULTS  BW and gestational age were 867+/-85 g and 26.3+/-1.2 weeks ( n=77 , mean+/-1SD ) . ROP surgery infants(n=11 ) received more parenteral nutrition , 1648 mL , and less human milk , 13.8 mL/kg-day , and vitamin E , 1.4 mg/kg-day , during the second postnatal week . Human milk was a negative predictor for ROP surgery , odds ratio=0.94 . Both groups met vitamin A recommendations ; however , 74 % was administered via IM injections . Neither group met vitamin E recommendations . CONCLUSIONS Human milk feeding , parenteral nutrition volume and vitamin E intake were predictors for ROP surgery .  IM vitamin A injections provided the majority of vitamin A ; vitamin E administration was insufficient . Improving human milk feeding rates and vitamin dosing options may affect ROP surgery rates Background In a recent meta- analysis , human milk feeding of low birth-weight ( LBW ) infants was associated with a 5.2 point improvement in IQ tests . However , in the studies in this meta- analysis , feeding regimens were used ( unfortified human milk , term formula ) that no longer represent recommended practice . Objective To compare the growth , in-hospital feeding tolerance , morbidity , and development ( cognitive , motor , visual , and language ) of LBW infants fed different amounts of human milk until term chronologic age ( CA ) with those of LBW infants fed nutrient-enriched formulas from first enteral feeding . Methods The data in this study were collected in a previous r and omized controlled trial assessing the benefit of supplementing nutrient-enriched formulas for LBW infants with arachidonic acid and docosahexaenoic acid .  Infants ( n = 463 , birth weight , 750–1,800 g ) were enrolled from nurseries located in Chile , the United Kingdom , and the United States . If human milk was fed before hospital discharge , it was fortified ( 3,050–3,300 kJ/L , 22–24 kcal/oz ) . As infants were weaned from human milk , they were fed nutrient-enriched formula with or without arachidonic and docosahexaenoic acids ( 3,300 kJ/L before term , 3,050 kJ/L thereafter ) until 12 months CA . Formula fed infants were given nutrient-enriched formula with or without added arachidonic and docosahexaenoic acids ( 3,300 kJ/L to term , 3,050 kJ/L thereafter ) until 12 months CA . For the purpose s of this evaluation , infants were categorized into four mutually exclusive feeding groups : 1 ) predominantly human milk fed until term CA ( PHM-T , n = 43 ) ; 2 ) ≥ 50 % energy from human milk before hospital discharge ( ≥ 50 % HM , n = 98 ) ; 3 ) < 50 % of energy from human milk before hospital discharge ( < 50 % HM , n = 203 ) ; or 4 ) predominantly formula fed until term CA ( PFF-T , n = 119 ) . Results PFF-T infants weighed approximately 500 g more at term CA than did PHM-T infants . This absolute difference persisted until 6 months CA . PFF-T infants were also longer ( 1.0–1.5 cm ) and had larger head circumferences ( 0.3–1.1 cm ) than both PHM-T and ≥ 50 % HM infants at term CA . There was a positive association between duration of human milk feeding and the Bayley Mental Index at 12 months CA ( P = 0.032 full and P = 0.073 reduced , statistical models ) after controlling for the confounding variables of home environment and maternal intelligence . Infants with chronic lung disease fed ≥ 50 % HM until term CA ( n = 22 ) had a mean Bayley Motor Index about 11 points higher at 12 months CA compared with infants PFF-T ( n = 24 , P = 0.033 full model ) . Conclusion Our data suggest that , despite a slower early growth rate , human milk fed LBW infants have development at least comparable to that of infants fed nutrient-enriched formula . Exploratory analysis suggests that some subgroups of  human milk fed LBW infants may have enhanced development , although this needs to be confirmed in future studies A large multicentre study on the short and long term clinical and developmental outcome of infants r and omised to different diets is being undertaken . This report represents an interim analysis of the early postnatal growth performance of an unselected population of 194 preterm infants ( gestation , mean ( SD ) 31 . 0 ( 2 . 9 ) weeks ; birthweight , mean ( SD ) 1364 ( 294 ) g ) , both ill and well , examined in two ( of four ) parallel trials . One trial compared banked breast milk with a new preterm formula ( primary trial ) ; the other compared these diets as supplements to maternal milk ( supplement trial ) . A major dietary effect on the number of days taken to regain birthweight and subsequent gains in weight , length , and head circumference was observed in the primary trial . Infants fed banked breast milk  and weighing less than 1200 g at birth took a calculated additional three weeks to reach 2000 g compared with those fed on the preterm formula . A significant influence of diet on body proportions was seen in the relation between body weight , head circumference , and length . Similar though smaller differences in growth patterns were seen in the supplement trial . By the time they reach 2000 g , infants of birthweights 1200 to 1849 g fed on banked breast milk and infants below 1200 g fed on either banked breast milk or maternal milk supplemented ( as necessary ) with banked breast milk , fulfilled stringent criteria for failure to thrive ( weight less than 2 SD below the mean for age ) . Only infants fed the preterm formula as their sole diet had maintained their birth centile by discharge from hospital . The misleading nature of comparisons between extrauterine and intrauterine steady state weight gains is emphasised PURPOSE To determine the influence of breastmilk consumption , as a dose response , in very low-birth-weight ( VLBW ) infants ( < 1,500 g ) on neurodevelopmental outcomes at 6 and 12 months corrected age , and to determine the influence of selected sociodemographic and infant variables on neurodevelopmental outcomes . SUBJECTSVLBW infants ( n = 148 ) who were fed mother 's milk or formula by parental choice . DESIGN Prospect i ve cohort with longitudinal follow-up at 6 and 12 months corrected age . METHODS Self-administered question naires given to mothers at study entry , before discharge , and at 3- , 6- , and 12-month follow-up visits . During hospitalization , mothers recorded the 24-hour volume of expressed milk once per week . At each follow-up visit , the volume of a  single feeding was assessed by pre- and postbreastfeeding test weights of infants measured on an electronic scale accurate to 1.0 g. The amount of breastfeeding was also assessed by feeding records and mother 's report . MAIN OUTCOME MEASURES The Bayley Scales of Infant Development ( 2nd Edition ) , the Mental Development Index ( MDI ) , and the Psychomotor Development Index ( PDI ) . PRINCIPAL RESULTS After controlling for specific sociodemographic and infant variables , this study of VLBW infants showed no statistically significant effect of predominantly breastfeeding compared with predominantly formula feeding on neurodevelopmental outcomes to 12 months corrected age . The most significant predictor of MDI scores at 6 and 12 months corrected age was birth weight , in which higher birth weights predicted higher MDI scores . CONCLUSIONS Despite the lack of statistically significant differences , the findings suggest a small but consistent advantage in developmental scores in infants who were fed their mother 's milk compared with those who were predominantly formula fed . Supporting parents to breastfeed preterm infants may maximize the potential advantages of early nutrition in the neurodevelopmental outcome of VLBW infants 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 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 : Prospect i ve cohort study of 175 VLBW infants . The average daily dose of HM ( ADDHM ) was calculated from daily nutritional data for the first 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 . Result : 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 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 Few data from r and omised prospect i ve studies address whether early diet influences later neurodevelopment in man . As part of a larger multicentre trial , 502 low birthweight infants were assigned r and omly , for a median of 30 days , to receive a preterm formula or unfortified donor breast milk as sole diets or as supplements to their mothers ' expressed milk . Surviving infants were assessed at nine months after their expected date of delivery without knowledge of their feeding regimen . The mean developmental quotient was 0.25 st and ard deviations lower in those fed donor breast milk rather than preterm formula . In infants fed their mother 's expressed milk , however , the disadvantage of receiving banked milk compared with preterm formula as a supplement , was greater when the supplement was over half the total intake , and approached five points , representing 0.5 st and ard deviations for developmental quotient . Infants fed donor breast milk were at particular disadvantage following fetal growth retardation , with developmental quotients 5.3 points lower . We suggest that the diet used for low birthweight babies over a brief , but perhaps critical , postnatal period has developmental consequences that persist into infancy ; infants who are small for gestational age are especially vulnerable to suboptimal postnatal nutrition Background Human milk from the infant 's mother ( own mother 's milk ; OMM ) feedings reduces the risk of several morbidities in very low birthweight ( VLBW ) infants , but limited data exist regarding its impact on bronchopulmonary dysplasia ( BPD ) . Objective To prospect ively study the impact of OMM received in the neonatal intensive care unit ( NICU ) on the risk of BPD and associated costs . Design / methods A 5-year prospect i ve cohort study of the impact of OMM dose on growth , morbidity and NICU costs in VLBW infants .  OMM dose was the proportion of enteral intake that consisted of OMM from birth to 36 weeks postmenstrual age ( PMA ) or discharge , whichever occurred first . BPD was defined as the receipt of oxygen and /or positive pressure ventilation at 36 weeks PMA . NICU costs included hospital and physician costs . Results The cohort consisted of 254 VLBW infants with mean birth weight 1027±257 g and gestational age 27.8±2.5 weeks . Multivariable logistic regression demonstrated a 9.5 % reduction in the odds of BPD for every 10 % increase in OMM dose ( OR 0.905 ( 0.824 to 0.995 ) ) . After controlling for demographic and clinical factors , BPD was associated with an increase of US$ 41 929 in NICU costs . Conclusions Increased dose of OMM feedings from birth to 36 weeks PMA was associated with a reduction in the odds of BPD in VLBW infants .  Thus , high-dose OMM feeding may be an inexpensive , effective strategy to help reduce the risk of this costly multifactorial morbidity OBJECTIVE To examine the dose effect of maternal milk on  neonatal morbidity of very low-birth-weight ( < 1.5 kg ) infants . DESIGN Prospect i ve observational study . SETTING An urban tertiary care neonatal intensive care unit and follow-up clinic . POPULATION One hundred nineteen singleton very low-birth-weight infants admitted from January 1 , 1997 , to February 14 , 1999 ( mean birth weight , 1056 g ; mean gestational age , 28 weeks ; 57 % male ; and 43 % white ) . METHODS A comparison of the effect on neonatal outcomes of daily grade d doses ( 1 - 24 , 25 - 49 , and > or = 50 mL/kg of body weight ) of maternal milk through week 4 of life vs a reference group receiving no maternal milk . MAIN OUTCOME MEASURES Neonatal outcomes examined included rates of sepsis after age 5 days , retinopathy of prematurity , chronic lung disease , necrotizing enterocolitis , jaundice , duration of ventilator dependence , and length of hospital stay . RESULTS Seventy-nine infants ( 66 % ) received maternal milk , of whom 32 received at least 50 mL/kg per day through week 4 of life . Poisson regression analysis adjusting for birth weight , sex , and ethnicity revealed that the mean number of episodes of sepsis for infants receiving at least 50 mL/kg per day was lower by a factor of 0.27 ( 95 % confidence interval , 0.08 - 0.95 ) compared with infants receiving no maternal milk . There was no effect of maternal milk on other neonatal outcomes . CONCLUSIONS A daily threshold amount of at least 50 mL/kg of maternal milk through week 4 of life is needed to decrease the rate of sepsis in very low-birth-weight infants , but maternal milk does not affect other neonatal morbidities My colleagues and I compared the biochemical status and rates of growth of three groups of preterm infants : one group was fed  milk obtained early from mothers of preterm infants ;  one group received  milk produced during the mature stage of lactation by mothers of term infants ; and one group received a whey-based infant formula . Sixty healthy preterm infants with birth weights of 1600 g or less were r and omly assigned to one of the three feedings groups . The 20 infants in each group were followed until they reached a weight of 1800 g. The mean ( + /- S.E.M. ) number of days required to regain birth weight was similar for infants receiving the formula ( 10.3 + /- 0.8 ) and those receiving milk from mothers of preterm infants ( 11.4 + /- 0.8 ) ; both were significantly less than the number ( 18.8 + /- 1.7 ) for infants receiving milk from mothers of term infants ( P less than 0.001 ) . Subsequent rates of weight gain were greater for the groups receiving formula ( 27.0 + /- 0.8 g per day ) and milk from mothers of preterm infants ( 23.7 + /- 1.1 ) than for the group receiving milk from mothers of term infants ( 15.8 + /- 0.8 ) ( P less than 0.001 ) . Similarly , the average increments in crown-to-heel length and in the head circumference were significantly greater for the groups given formula and milk from mothers of preterm infants ( P less than 0.005 and P less than 0.001 , respectively ) . These data indicate that feeding with either milk from mothers of preterm infants or a whey-based infant formula results in more appropriate growth in preterm infants than feeding with milk from mothers of term infants In a prospect i ve controlled study the anti-infective properties of breast-milk were evaluated in 70 high-risk low-birth-weight infants . 32 babies ( group I ) were given fresh expressed breast-milk during the day and milk formula at night .  38 infants ( group II ) received only milk formula and served as controls . The two groups were matched for other factors that could influence the occurrence of infection . The incidence of infections was significantly less ( p < 0.01 ) in babies who received breast-milk 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 : Most preterm infants who develop necrotising enterocolitis ( NEC )  have received enteral feeds . Uncertainty exists about which aspects of the feeding regimen affect the risk of NEC . Aim : To examine associations between various enteral feeding practice s and the development of  NEC  in preterm infants . Methods : Multicentre case – control study . 53 preterm infants with NEC were enrolled together with a gestational age frequency-matched control without NEC from a r and omly selected neonatal unit . Clinical and feeding data were extracted and compared between the groups . Results : Significantly fewer cases than controls had received human breast milk ( 75 % vs 91 % ; OR 0.32 , 95 % CI 0.11 to 0.98 ) . The day on which enteral feeding was started did not differ significantly ( mean ( SD ) days after birth : cases 2.9 ( 2.8 ) and controls 2.8 ( 1.8 ) ) . The mean ( SD ) duration of trophic feeding ( < 1 ml/kg/h ) was significantly shorter in the cases ( 3.3 ( 3.1 ) days ) than controls ( 6.2 ( 6.7 ) days ) ( mean difference ( MD ) −2.9 , 95 % CI −4.9 to −0.9 ) days . Cases were fully fed significantly earlier than controls ( mean ( SD ) days after birth : cases 9.9 ( 4.2 ) and controls 14.3 ( 9.8 ) ; MD −4.4 , 95 % CI −7.3 to −1.5 ) . Conclusions : These data suggest that the duration of trophic feeding and rate of advancement of feed volumes may be modifiable risk factors for NEC in preterm infants . Further r and omised controlled trials are warranted to assess the effect of different rates of feed advancement on the incidence of NEC , as well as other outcomes Background Following publication of the PRISMA statement , the UK Centre for Review s and Dissemination ( CRD ) at the University of York in Engl and began to develop an international prospect i ve register of systematic review s with health-related outcomes . The objectives were to reduce unplanned duplication of review s and provide transparency in the review process , with the aim of minimizing reporting bias . Methods An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality . This article describes the development of the register , now called PROSPERO , and the process of registration . Results PROSPERO offers free registration and free public access to a unique prospect i ve register of systematic review s across all areas of health from all around the world . The dedicated web-based interface is electronically search able and available to all prospect i ve registrants . At the moment , inclusion in PROSPERO is restricted to systematic review s of the effects of interventions and strategies to prevent , diagnose , treat , and monitor health conditions , for which there is a health-related outcome .Ideally , registration should take place before the research ers have started formal screening against inclusion criteria but review s are eligible as long as they have not progressed beyond the point of completing data extraction .The required data set captures the key attributes of review design as well as the administrative details necessary for registration .Su bmi tted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register , rejected , or returned to the applicant for clarification . The public records include an audit trail of major changes to planned methods , details of when the review has been completed , and links to result ing publications when provided by the authors . Conclusions There has been international support and an enthusiastic response to the principle of prospect i ve registration of protocol s for systematic review s and to the development of PROSPERO .In October 2011 , PROSPERO contained 200 records of systematic review s being undertaken in 26 countries around the world on a diverse range of interventions 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 : 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 Supplementary formula feeds inhibited the protective effect of expressed raw and pasteurised human milk in 226 high-risk neonates in a r and omised controlled trial . The infection rate in the group given pasteurised human milk and formula ( 33 % ) was significantly higher than the rates in the groups given raw human milk ( 10.5 % ) , pasteurised human milk ( 14.3 % ) , and raw human milk and formula ( 16 % ) . This accords with the impressions that some of the association of infection with artificial feeding is partly attributable to the lack of the protective effect of human milk . Heating expressed human milk to 62.5 degrees C for 30 min significantly reduces its protective effect OBJECTIVE . Beneficial effects of breast milk on cognitive skills and behavior ratings have been demonstrated previously in term and very low birth weight infants . Extremely low birth weight infants are known to be at increased risk for developmental and behavior morbidities . The benefits of breast milk that is ingested in the NICU by extremely low birth weight infants on development and behavior have not been evaluated previously . METHODS . Nutrition data including enteral and parenteral feeds were collected prospect ively , and follow-up assessment s of 1035 extremely low birth weight infants at 18 months ’ corrected age were completed at 15 sites that were participants in the National Institute of Child Health and Human Development Neonatal Research Network Glutamine Trial between October 14 , 1999 , and June 25 , 2001 .  Total volume of  breast milk feeds  ( mL/kg per day ) during hospitalization was calculated . Neonatal characteristics and morbidities , interim history , and neurodevelopmental and growth outcomes at 18 to 22 months ’ corrected age were assessed . RESULTS . There were 775 ( 74.9 % ) infants in the breast milk and 260 ( 25.1 % ) infants in the no breast milk group . Infants in the breast milk group were similar to those in the no breast milk group in every neonatal characteristic and morbidity , including number of days of hospitalization . Mean age of first day of breast milk for the breast milk infants was 9.3 ± 9 days . Infants in the breast milk group began to ingest non – breast milk formula  later ( 22.8 vs 7.3 days ) compared with the non – breast milk group . Age at achieving full enteral feeds was similar between the breast milk and non – breast milk groups ( 29.0 ± 18 vs 27.4 ± 15 ) . Energy intakes of 107.5 kg/day and 105.9 kg/day during the hospitalization did not differ between the breast milk and non – breast milk groups , respectively . At discharge , 30.6 % of infants in the breast milk group still were receiving breast milk . Mothers in the breast milk group were significantly more likely to be white ( 42 % vs 27 % ) , be married ( 50 % vs 30 % ) , have a college degree ( 22 % vs 6 % ) , and have private health insurance ( 34 % vs 18 % ) compared with the no breast milk group . Mothers who were black , had a low household income ( ≤$20000 ) , or had higher parity were less likely to provide breast milk feeds . The analysis of outcomes between the any human milk and no human milk groups were adjusted for maternal age , maternal education , marital status , race/ethnicity , and the other st and ard covariates . Children in the breast milk group were more likely to have a Bayley Mental Development Index ≥85 , higher mean Bayley Psychomotor Development Index , and higher Bayley Behavior Rating Scale percentile scores for orientation/engagement , motor regulation , and total score . There were no differences in the rates of moderate to severe cerebral palsy or blindness or hearing impairment between the 2 study groups . There were no differences in the mean weight ( 10.4 kg vs 10.4 kg ) , length ( 80.5 cm vs 80.5 cm ) , or head circumference ( 46.8 cm vs 46.6 cm ) for the breast milk and no breast milk groups , respectively , at 18 months . Multivariate analyses , adjusting for confounders , confirmed a significant independent association of breast milk on all 4 primary outcomes : the mean Bayley ( Mental Development Index , Psychomotor Development Index , Behavior Rating Scale , and incidence of rehospitalization ) . For every 10-mL/kg per day increase in breast milk ingestion , the Mental Development Index increased by 0.53 points , the Psychomotor Development Index increased by 0.63 points , the Behavior Rating Scale percentile score increased by 0.82 points , and the likelihood of rehospitalization decreased by 6 % . In an effort to identify a threshold effect of breast milk on Bayley Mental Development Index and Psychomotor Development Index scores and Behavior Rating Scale percentile scores , the mean volume of breast milk per kilogram per day during the hospitalization was calculated , and infants in the breast milk group were divided into quintiles of breast milk ingestion adjusted for confounders . Overall , the differences across the feeding quintiles of Mental Development Index and Psychomotor Development Index were significant . There was a 14.0 % difference in Behavior Rating Scale scores between the lowest and highest quintiles . For the outcomes ( Mental Development Index , Psychomotor Development Index , Behavior Rating Scale , and Rehospitalization < 1 year ) , only the values for the > 80th percentile quintile of breast milk feeding were significantly different from the no breast milk values . In our adjusted regression analyses , every 10 mL/kg per day breast milk contributed 0.53 points to the Bayley Mental Development Index ; therefore , the impact of breast milk ingestion during the hospitalization for infants in the highest quintile ( 110 mL/kg per day ) on the Bayley Mental Development Index would be 10 × 0.53 , or 5.3 points . CONCLUSIONS . An increase of 5 points potentially would optimize outcomes and decrease costs by decreasing the number of very low birth weight children who require special education services . The societal implication s of a 5-point potential difference ( one third of an SD ) in IQ are substantial . The potential long-term benefit of receiving breast milk in the NICU for extremely low birth weight infants may be to optimize cognitive potential and reduce the need for early intervention and special education services
target: HM provided a clear protective effect against NEC , with an approximate 4 % reduction in incidence .
  HM also provided a possible reduction in LOS , severe ROP and severe NEC .
  Particularly for NEC , any volume of HM is better than EPTF , and the higher the dose the greater the protection .
  Evidence regarding pasteurisation is inconclusive , but it appears to have no effect on some outcomes .
  Improving the intake of mother ’s own milk ( MOM ) and /or donor HM results in small improvements in morbidity in this population
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