Randomized diet in the neonatal period and growth performance until 7.5-8 y of age in preterm children. Adequacy of expressed breast milk for early gwoth of preterm 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. Growth in relation to protein intake of low birth weight infants. Effect of Human Milk or Formula on Gastric Function and Fat Digestion in the Premature Infant1 Early diet in preterm babies and developmental status in infancy. Growth and biochemical response of preterm infants fed human milk or modified infant formula. Nutrient accretion in preterm infants fed formula with different protein:energy ratios. A PLANNED PROSPECTIVE EVALUATION OF THE ANTI‐INFECTIVE PROPERTY OF VARYING QUANTITIES OF EXPRESSED HUMAN MILK 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 A randomised multicentre study of human milk versus formula and later development in preterm infants. Milk protein quantity and quality in low-birth-weight infants. IV. Effects on tyrosine and phenylalanine in plasma and urine. The value of human milk in the prevention of infection in the high-risk low-birth-weight infant. Nutrient balance, energy utilization, and composition of weight gain in very-low-birth-weight infants fed pooled human milk or a preterm formula. Milk protein quantity and quality in low-birth-weight infants: II. Effects on selected aliphatic amino acids in plasma and urine.
BACKGROUND Preterm children are at high risk of poor growth performance . In 2 r and omized trials , preterm infants fed preterm formula grew better in the neonatal period than those fed banked donor breast milk or st and ard term formula . OBJECTIVE Our objective was to test the hypothesis that for preterm infants , the neonatal period is a critical one for programming growth performance and that early diet influences long-term growth . DESIGN A total of 926 preterm infants were recruited into 2 parallel , r and omized trials of neonatal diet . In trial 1 , infants were fed either banked donor breast milk or preterm formula whereas in trial 2 , infants were fed either st and ard term formula or preterm formula . Within each trial , the allocated milk was the sole diet for some infants ( study A ) , whereas for others it was a supplement to maternal breast milk , given when not enough expressed breast milk was available ( study B ) . We followed up 781 of 833 survivors ( 94 % ) to age 7.5 - 8 y. Trained assessors obtained anthropometric measurements according to a st and ard protocol . RESULTS Despite significantly better neonatal growth performance in infants fed preterm formula ( compared with either banked donor breast milk or st and ard formula ) , early diet had no influence on weight , height , head circumference , or skinfold thicknesses at 9 or 18 mo postterm or at age 7.5 - 8 y. CONCLUSIONS These findings suggest that the preterm period is not a critical window for nutritional programming of growth , which contrasts with evidence from these trials showing that early diet influences later neurodevelopment 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 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 In a prospect i ve longitudinal study of 48 very low birth weight and preterm infants with mean birth weight 1385 + /- 343 g and gestational age 30.8 + /- 2.9 weeks an assessment was made of the impact of varying the protein intake in the postnatal period from the 3rd to 7th week of life . The infants were r and omly allocated to one of three dietary groups with isocaloric energy supply but different protein content , i.e. human milk ( 1.6 g/100 kcal ) , formula 1 ( 2.3 g/100 kcal ) and formula 2 ( 3.0 g/100 kcal ) . In the human milk group 12 of 18 infants were fed their own mother 's breastmilk . During the study period the mean weight gain was slight higher in the infants fed formula . There were no group differences in S-albumin but B-urea-N and B-base deficit were significantly higher in formula-fed infants compared to infants fed human milk . After the study period that lasted to about 20 weeks of age the slope in weight gain remained slightly higher for formula fed infants , whereas the gain in body length and hear circumference was equal in all three groups . After around 8 months of age there was no difference in any growth parameter . Neurodevelopmental examinations showed no group differences during the follow-up period to 2 years of age . With few exceptions breastmilk-preferably from their own mothers-was adequate for both early and longterm growth and development of the very low birth weight infants in this population The effect of diet , human milk or formula , on gastric function ( lipase and pepsin activity , pH , and volume ) and intragastric digestion of fat was assessed in 28 appropriate for gestational age preterm infants ( gestational age , 28.9 ± 1.4 , 29.1 ± 0.9 , 29.5 ± 0.6 wk ; birth weight , 1.00 ± 0.14 to 1.18 ± 0.07 kg ) . The infants were fed either human milk ( n = 11 ) , SMA Super Preemie formula ( n = 9 ) , or Similac , Special Care formula ( n = 8) . Fasting and postpr and ial activity of digestive enzymes , pH , and gastric volume ( measured before or during 50 min after gavage feeding ) did not differ as a function of diet among the three groups of infants . Gastric lipase output , 23.1 ± 5.1 , 28.3± 6.6 , and 22.5 ± 6.4 ( U/kg of body weight ) in human milk- , SMA SP- , or Similac SC-fed infants was comparable to the gastric lipase output of healthy adults fed a high fat diet ( 22.6 ± 3.0 ) . Pepsin output was , however , significantly lower ( 597 ± 77 , 743 ± 97 , and 639± 142 U/kg of body weight ) in human milk- , SMA SP- , and Similac SC-fed infants ) than in healthy adults ( 3352 ± 753 U/kg ) . The hydrolysis of dietary fat was 1.7 - 2.5-fold higher ( p < 0.01 ) in human milk-fed infants than in infants fed either formula . We conclude that differences in type of feeding , i.e. different fatty acid profiles(long chain or medium chain triglycerides ) , different emulsions ( natural or artificial ) , and different fat particle sizes do not affect the level of activity of gastric enzymes . However , the triglyceride within milk fat globules appears to be more accessible to gastric lipase than that within formula fat particles . We suggest that the contribution of gastric lipase to overall fat digestion might be greater in the newborn ( a period of pancreatic insufficiency ) than in the adult 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 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 BACKGROUND Although st and ard formulas for preterm infants promote intrauterine rates of weight gain , fat deposition in preterm infants fed these formulas has been reported to be considerably higher than that in the fetus . We hypothesized that a preterm infant formula with a higher protein : energy ( P : E ) ratio would promote accretion rates of fat , fat-free mass , and minerals closer to those of the fetus . METHODS As part of a larger study to determine whether accretion rates of fat and fat-free mass closer to those of the fetus can be achieved with a higher P : E ratio , we present a descriptive analysis of 72-h nutrient balance studies performed on a subset ( n = 15/30 ) of the infants r and omly assigned to be fed formula with a P : E ratio of either 3.2 g/100 kcal or 2.6 g/100 kcal . RESULTS Despite the higher intake and net absorption of nitrogen by infants fed the higher P : E formula , there was no statistically significant difference in net nitrogen retention between groups . There also were no statistically significant differences between groups in digestible energy , metabolizable energy , energy expenditure , or energy storage . Thus , partitioning of stored energy as protein and fat did not differ between groups . The retention of calcium , phosphorus , sodium , potassium , copper , and zinc also did not differ between groups , and nitrogen intake did not affect mineral retention . CONCLUSIONS In this study , formula for preterm infants with a P : E ratio of 3.2 g/100 kcal vs. 2.6 g/100 kcal provided no apparent benefit in terms of the proportion of fat to lean tissue accretion as determined from nutrient balance data ABSTRACT . This paper comprises 261 low birth weight infants who were divided into four groups with different feeding schedules . Group I – expressed human milk for all the feeds ; Group II – human milk for half the feeds and the nursery formula for the rest ; Group III – colostrum , 20 ml three times a day along with the nursery formula ; and Group IV – control – only the nursery formula . The groups were matched by means of a r and omised block design for identifiable factors which could predispose to the occurrence of infection . Infections were found to be significantly less in the groups which received human milk ( p < 0.001 ) 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 Whether breast milk influences later neurodevelopment  has been explored in non-r and omised studies , potentially confounded by social and demographic differences between feed groups . Here in a strictly r and omised prospect i ve multicentre trial , Bayley psychomotor and mental development indices ( PDI and MDI ) were assessed at 18 months postterm in survivors of 502 preterm infants assigned to receive , during their early weeks , mature donor breast milk or a preterm formula .  These diets were compared as sole enteral feeds or as supplements to the mother 's expressed breast milk . No differences in outcome at 18 months were seen between the two diet groups despite the low nutrient content of donor milk in relation to the preterm formula and to the estimated needs of preterm infants . These results contrast with those reported from our parallel two centre study that compared infants r and omly assigned a st and ard term formula or the preterm formula during their early weeks ; those fed st and ard formula , now regarded as nutritionally insufficient for preterm infants , were substantially disadvantaged in PDI and MDI at 18 months post-term . It is shown here that infants from that study fed solely on st and ard formula had significantly lower developmental scores at 18 months than those fed on donor breast milk in the present study ; yet the st and ard formula had a higher nutrient content than the donor milk . Thus , donor milk feeding was associated with advantages for later development that may have offset any potentially deleterious effects of its low nutrient content for preterm infants . As these outcome advantages were not confounded by the social and educational biases usually associated with mothers ' choice to breast feed , our data add significant support to the view that breast milk promotes neurodevelopment Well , appropriate-for-gestational age , low-birth-weight infants were divided into three gestational age groups and assigned r and omly within each age group to one of five feeding regimens : pooled human milk ( BM ) ; formula 1 ( F1 ) = 1.5 gm/dl protein , 60 parts bovine whey proteins : 40 parts bovine caseins ; F2 = 3.0 gm/dl , 60:40 ; F3 = 1.5 gm/dl , 18:82 ; F4 = 3.0 gm/dl , 18:82 . Plasma and urine concentrations of tyrosine and phenylalanine were far higher in the infants fed F1 to F4 , especially F2 and F4 , than in the infants fed BM . These findings offer further evidence for the limited capacity of the low-birth-weight infant to catabolize tyrosine . Infants fed F3 had significantly higher plasma tyrosine concentrations than infants fed F1 , and those fed F4 had higher concentrations than those fed F2 . Thus , increased plasma tyrosine concentrations in low-birth-weight infants are related directly both to the quantity and to the quality of the protein in their diets A controlled prospect i ve study was undertaken of 62 high-risk low-birth-weight infants to evaluate the effect of expressed human milk on the prevention of infection . One half received EHM and the remaining half were administered the nursery formula . There was no statistically significant difference in the predisposing factors in the two groups . Infections , however , were much fewer in babies who received EHM ( Growth , protein , and energy balances were studied in two groups of very-low-birth-weight premature infants fed pooled pasteurized human milk ( HM ) or a preterm formula ( PF ) .  Each infant was studied at 33 and 36 weeks gestational age with a combined technique of nutrient balance and indirect calorimetry measurement . Weight and length gains were higher with PF than with HM , but head circumference growth was similar with both milks . Although the volume of milk given was lower , energy intake was higher with PF than with HM in both studies ( 126 to 130 vs 103 to 109 kcal/kg/day ) . Percentage of energy absorbed was better with PF than with HM ( 94 % vs 84 % ) at 33 weeks , and similar ( 95 % ) with both milks at 36 weeks . Energy expenditure , which had increased from 33 weeks to 36 weeks , was higher with PF than with HM ( 57 to 63 vs 46 to 52 kcal/kg/day ) during both studies . Energy retention accounted for about 50 % of energy absorbed with both milks , but was higher with PF than with HM ( 60 vs 40 to 50 kcal/kg/day ) in both studies , and result ed in fat accretion well above that seen during intrauterine growth for both milks in both studies . Protein intake was higher with PF than with HM ( 3.1 vs 2.4 gm/kg/day ) in both studies , giving a protein accretion similar to the intrauterine accretion with PF ( 2.2 gm/kg/day ) , but lower with HM . Our results suggest that the nutritional value of pooled pasteurized human milk for VLBW infants should be reconsidered , especially because of its low protein content , and that energy density of preterm formulas must be question ed in view of elevated fat deposition The optimal quantity and quality of protein for low-birth-weight infants is undefined . In this study , 106 well , appropriate-for-gestational-age , low-birth-weight infants weighing 2,100 gm or less were divided into three gestational age groups and assigned r and omly within each age group to one of five feeding regimens : pooled human milk ; formula 1 ( protein content , 1.5 gm/100 ml- 60 parts bovine whey proteins to 40 parts bovine caseins ) ; formula 2 ( 3.0 gm/100 ml , 60:40 ) ; formula 3 ( 1.5 gm/100 ml , 18:82 ) ; and formula 4 ( 3.0 gm/100 ml , 18:82 ) . The concentrations of the free amino aicds in the plasma and urine of these infants were determined . The plasma concentrations of free amino acids were generally far greater in the infants fed the 3.0-gm/100 ml protein diets than they were in the infants fed pooled human milk . The plasma concentrations of free amino acids of the infants fed the 1.5-gm/100 ml protein diets were intermediate . In general , the concentrations of the free amino acids in the plasma of the infants fed the 3.0-gm/100 ml casein-predominant formula ( F4 ) were furthest from those fed pooled human milk . Glutamate showed the highest plasma amino acid concentrations in infants fed the 3.0-gm/100 ml casein-predominant formula ( F4 ) were furthest from those fed pooled human milk . Glutamate showed the highest plasma amino acid concentrations in infants fed both the high- and low-protein casein-predominant formulas . This was true despite the fact that the intake of glutamate on the high-protein , whey-predominant formula was twice that on the low-protein , casein-predominant formula . The differences between groups in the essential amino acids in plasma were generally greater than those of the nonessential amino acids . The concentrations of amino acids in the urine tended to parallel those of the plasma
BACKGROUND When sufficient maternal breast milk is not available , the alternative sources of enteral nutrition for preterm or low birth weight infants are donor breast milk or artificial formula milk .
Feeding preterm or low birth weight infants with formula milk might increase nutrient input and growth rates .
However , since feeding with formula milk may be associated with a higher incidence of feeding intolerance and necrotising enterocolitis , this may adversely affect growth and development .
OBJECTIVES To determine the effect of formula milk compared with donor human breast milk on growth and development in preterm or low birth weight infants .