Randomised trial of early diet in preterm babies and later intelligence quotient Comparative Growth and Biochemical Response of Very Low Birthweight Infants Fed Own Mother's Milk, a Premature Infant Formula, or One of Two Standard Formulas Randomized diet in the neonatal period and growth performance until 7.5-8 y of age in preterm children. Improving head growth in very preterm infants – a randomised controlled trial I: neonatal outcomes Early macronutrient intake and overweight at five years of age Randomized trial of enteral protein and energy supplementation in infants less than or equal to 1250 g at birth Randomized trial of high nutrient density formula versus standard formula in chronic lung disease Growth in relation to protein intake of low birth weight infants. Early diet in preterm babies and developmental status at 18 months Short-term growth and substrate use in very-low-birth-weight infants fed formulas with different energy contents. Diet and growth in the premature infant. The effect of different dietary intakes of ash-electrolyte and protein on weight gain and linear growth. Nutritional Efficacy of Preterm Formula With a Partially Hydrolyzed Protein Source: A Randomized Pilot Study Nutrient accretion in preterm infants fed formula with different protein:energy ratios. Factors influencing body composition of premature infants at term-adjusted age. Two different low birth weight formulae compared. Feeding studies in low-birth-weight infants. I. Relationships of dietary protein, fat, and electrolyte to rates of weight gain, clinical courses, and serum chemical concentrations. Nutrition in infancy and long-term risk of obesity: evidence from 2 randomized controlled trials. Late effects of early dietary protein intake on low-birth-weight infants. Controlled trial of new formulae for feeding low birth weight infants. Milk protein quantity and quality in low-birth-weight infants. IV. Effects on tyrosine and phenylalanine in plasma and urine. Protein quality and quantity in preterm infants receiving the same energy intake. Clinical effects of two different levels of protein intake on low-birth-weight infants. Effect of varying protein intake on energy balance, protein balance and estimated weight gain composition in premature infants. Evaluation of a Mathematical Model for Predicting the Relationship between Protein and Energy Intakes of Low-Birth-Weight Infants and the Rate and Composition of Weight Gain National Institute of Child Health and Human Development A COMPARATIVE STUDY OF VARYING PROTEIN INTAKE IN LOW BIRTHWEIGHT INFANT FEEDING Calciuria and aminoaciduria in very low birth weight infants fed a high-mineral premature formula with varying levels of protein. Energy expenditure, energy balance, and composition of weight gain in low birth weight infants fed diets of different protein and energy content. Clinical trial of special premature formula for low-birth-weight infants. Effect of protein/energy ratio on growth and behavior of premature infants: preliminary findings. Randomized, Multicenter Trial of Two Different Formulas for Very Early Enteral Feeding Advancement in Extremely-Low-Birth-Weight Infants Milk protein quantity and quality in low-birth-weight infants: II. Effects on selected aliphatic amino acids in plasma and urine.
abstract Objectives : To determine whether perinatal nutrition influences cognitive function at 7 1/2 - 8 years in children born preterm . Design : R and omised , blinded nutritional intervention trial . Blinded follow up at 7 1/2 - 8 years . Setting : Intervention phase in two neonatal units ; follow up in a clinic or school setting . Subjects : 424 preterm infants who weighed under 1850 g at birth ; 360 of those who survived were tested at 7 1/2 - 8 years . Interventions : St and ard infant formula versus nutrient enriched preterm formula r and omly assigned as sole diet ( trial A ) or supplements to maternal milk ( trial B ) fed for a mean of 1 month . Main outcome measures : Intelligence quotient ( IQ ) at 7 1/2 - 8 years with abbreviated Weschler intelligence scale for children ( revised ) . Results : There was a major sex difference in the impact of diet . At 7 1/2 - 8 years boys previously fed st and ard versus preterm formula as sole diet had a 12.2 point disadvantage ( 95 % confidence interval 3.7 to 20.6 ; P<0.01 ) in verbal IQ . In those with highest intakes of trial diets corresponding figures were 9.5 point disadvantage and 14.4 point disadvantage in overall IQ ( 1.2 to 17.7 ; P<0.05 ) and verbal IQ ( 5.7 to 23.2 ; P<0.01 ) . Consequently , more infants fed term formula had low verbal IQ ( < 85 ) : 31 % versus 14 % for both sexes ( P=0.02 ) and 47 % versus 13 % in boys P=0.009 ) . There was a higher incidence of cerebral palsy in those fed term formula ; exclusion of such children did not alter the findings . Conclusions : Preterm infants are vulnerable to suboptimal early nutrition in terms of their cognitive performance — notably , language based skills — at 7 1/2 - 8 years , when cognitive scores are highly predictive of adult ones . Our data on cerebral palsy generate a new hypothesis that suboptimal nutritional management during a critical or plastic early period of rapid brain growth could impair functional compensation in those sustaining an earlier brain insult . Cognitive function , notably in males , may be permanently impaired by suboptimal neonatal nutrition Summary : Very low birthweight ( VLBW ) infants weighing < 1,600 g at birth were fed their own mother 's milk ( OMM ) or r and omly assigned to receive one of three formulas : a “ humanized ” formula ( SF ) , a partially modified casein-predominant cow 's milk formula ( CF ) , or a premature formula ( PF ) . All infants were fed at 120 kcal/kg/day where possible , PF infants had significantly greater weight increments ( 28.0 g/day ) than those on OMM ( 19.4 g/day ) , SF ( 18.9 g/day ) , and CF ( 18.2 g/day ) . Those on PF also had greater increments of length , head circumference , and skinfold thickness than those on the other two formulas and greater length increments than those on OMM . Dynamic skinfold measurements suggested that no infants accumulated excessive amounts of interstitial fluid . Infants on the two st and ard formulas had significantly greater base deficits , whereas those on CF also had higher urea values . Those on OMM had lower phosphate and higher alkaline phosphatase values than the other groups . Thus VLBW infants fed a premature formula had better growth and fewer biochemical problems than those on st and ard formulas , whereas supplementation of OMM may be necessary to ensure optimal growth and bone mineralization 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 Background : Infants born very preterm are at an increased risk of poor growth in the post-natal period . Poor brain growth in this critical period may result from inadequate nutrition , and has long-term effects on neurodevelopmental outcome . Aims : To examine the feasibility of providing macronutrients at amounts above current recommendations ( hyperalimentation ) to improve nutrition and head growth in preterm infants . Methods : 142 infants < 29 weeks ' gestation were r and omised to hyperalimented or st and ard parenteral and enteral nutrition .  Growth was monitored from birth to 36 weeks ' postmenstrual age ( PMA ) . The primary outcome measure was occipitofrontal circumference ( OFC ) at 36 weeks ' PMA . Results : 55 infants in the intervention group and 59 infants in the control group survived to 36 weeks ' PMA . 11 ( 16 % ) infants in the intervention group and 13 ( 18 % ) infants in the control group were small for gestational age ( SGA ) . There was no statistically significant difference between the two groups in the primary outcome measure or other growth variables . Babies in the intervention group received significantly more energy and protein , but 80 % were still in a cumulative protein/energy deficit at the end of 4 weeks . 20 ( 24 % , p = 0.008 ) of those in deficit at 4 weeks had an OFC of more than 2 SD below the mean at 36 weeks ' PMA , as opposed to none of those not in deficit . Conclusion : Cumulative energy/protein deficit is predictive of poor head growth , but the delivery of adequate intakes remains a challenge in the preterm OBJECTIVE : To examine the influence of the macronutrient intake in early life on the development of  overweight in children . DESIGN AND SUBJECTS : An ongoing longitudinal study including 147 r and omized healthy children followed up from birth . MEASUREMENTS : Anthropometric parameters were measured at birth , 1 and 5 y of age . Dietary habits at the age of 1 and 5 were assessed by age-adjusted food-frequency question naires and 24 h recalls .  Parents ’ body mass index ( BMI ) was also recorded . RESULTS :  Parental overweight was observed for 51 % children . The prevalence of overweight at the age of 5 y was higher in children with than without parental overweight ( 37.3 % vs 8.3 % , P<0.0001 ) . Five-year old overweight children had a higher percentage intake of proteins at the age of 1 y than non overweight children ( 22 % vs 20 % , P=0.024 ) and lower intake of carbohydrates ( 44 % vs 47 % , P=0.031 ) . Multiple logistic analysis confirmed that protein intake at 1 y of age was associated with overweight at 5 y ( P=0.05 ) . In children born from overweight mothers , prevalence of overweight at the age of 5 y tended to be higher in bottle-fed than in breast-fed ones ( 62.5 % vs 23.3 % , P=0.08 ) . CONCLUSION : Parental overweight is a major risk factor for childhood overweight in the first years of life , but an early high protein intake may also influence the development of adiposity Objective : To determine if enteral protein and energy supplementation would significantly improve weight gain as compared with energy supplementation alone in ⩽1250 g infants . Study Design : Inclusion criteria were birth weight ( BW ) ⩽1250 g , postnatal age ⩾14 days , diet of ⩾75 % enteral nutrition ( fortified human milk or formula ) and either failure to regain BW or weight gain<15 g kg−1 per days . Infants were r and omized to a multinutrient supplement that provided increased protein and energy ( P/E ) intake or energy alone ( medium chain triglyceride oil , MCT ) . Growth rates were compared at the end of the 4-week study period . Result : Of 30 eligible infants , 23 were enrolled , 12 received MCT ( BW=862±252 g , mean±s.d . ) and 11 received P/E ( BW=879±241 g ) . Significantly higher protein intake  ( P/E=3.5±0.3 g kg−1 per day , MCT=3.0±0.5 g kg−1 per day ) and better growth  ( P/E=17.0±2.4 g kg−1 per day , MCT=11.5±4.8 g kg−1 per day ) were observed in the P/E group . Conclusion : These data are consistent with the importance of providing additional daily protein intake to achieve increased postnatal growth in very low birth weight infants experiencing slow growth To test the hypothesis that the nutrient intake and growth of infants with chronic lung disease would be improved by providing nutrients in more concentrated form , and that the lower volume would improve respiratory status , 60 preterm infants requiring supplemental oxygen at 28 days of age were r and omly assigned a low‐density ( 24 kcal/oz ) formula fed at 180 ml/kg/day , or a high‐density ( 30 kcal/oz ) formula at 145 ml/kg/day . There was no difference in growth , respiratory outcome , oedema or diuretic requirement between dietary groups . Infants fed the high nutrient density formula had significantly greater total energy ( 143 vs 134 kcal/kg/day ) and protein ( 3.9 vs 3.6g/kg/day ) intakes , largely because the low‐density formula group did not achieve the design ated 180 ml/kg/day . In conclusion , use of a high‐density formula in infants with chronic lung disease did not improve growth or respiratory outcome , despite a small increase in total energy and protein intake 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 424 preterm infants were r and omly assigned a st and ard " term " formula or a nutrient-enriched " preterm " formula as sole diets ( trial A ) or as supplements to mother 's own expressed milk ( trial B ) for a median of 4 weeks postnatally . 18 months post term , blind evaluation of 377 survivors showed that those previously fed preterm rather than term formula had major developmental advantages , more so in motor than mental function ; the advantages , in both mental and motor scores , were especially striking in small-for-gestational-age infants and in males . For motor development index in trial A , this advantage was 15 points ; in infants born small for gestation , it was 23 points ( nearly 1.5 SD ) . Moderate developmental impairment ( developmental index less than 85 ) , notably motor impairment , was considerably more common in the group fed term formula . Infants fed preterm formula also had a small benefit in social maturity quotient . Thus , a short period of early dietary manipulation in preterm infants had major consequences for later development , which suggests that the first weeks may be critical for nutrition BACKGROUND Currently available preterm formulas with energy contents of 3350 kJ ( 800 kcal)/L promote weight and length gain at rates at or above intrauterine growth rates but disproportionately increase total body fat . OBJECTIVE The objective of this study was to determine whether fat accretion in formula-fed , very-low-birth-weight ( VLBW ) infants could be decreased and net protein gain maintained by reducing energy intakes from 502 kJ ( 80 kcal)*kg(-)(1)*d(-)(1 ) [ normal-energy ( NE ) formula ] to 419 kJ ( 100 kcal)*kg(-)(1)*d(-)(1 ) [ low-energy ( LE ) formula ] while providing similar protein intakes ( 3.3 g*kg(-)(1)*d(-)(1 ) ) . DESIGN The study was a r and omized , controlled trial enrolling 20 appropriate-for-gestational-age ( AGA ) and 16 small-for-gestational-age ( SGA ) VLBW infants ( mean birth weight : 1.1 kg ; mean gestational age : 31 wk ) ;  energy expenditure and nutrient balance were measured at 4 wk of age and anthropometric measurements were made when infants weighed 2 kg . RESULTS The percentage of fat in newly formed tissue was significantly lower in AGA infants fed the LE formula ( n = 9 ) than in those fed the NE formula ( n = 10 ) ( 9 % compared with 23 % ; analysis of variance , P = 0.001 ) . Energy expenditure was higher in AGA infants fed the NE formula than in those fed the LE formula . Skinfold thickness was markedly lower in AGA infants fed the LE formula than in those fed the NE formula , result ing in a lower estimated percentage body fat ( 8.0 + /- 1.9 % and 10.8 + /- 3.5 % , respectively ; P < 0.05 ) . Three of 6 SGA infants fed the LE formula were excluded during the study because of poor weight gain . CONCLUSIONS Body composition can easily be altered by changing the energy intakes of formula-fed VLBW infants . Energy intakes in these infants should be > 419 kJ ( 100 kcal)*kg(-)(1)*d(-)(1 ) Growth rates were determined from measurements of weight and length ( crown-heel and tibia ) on 29 premature infants ( birth weight range 920 to 1,510 grams ) who were fed 4 isocaloric formulas differing in ash and protein content . An unweighted means analysis showed that raising the protein content significantly increased all 3 rates of growth . Raising the ash content increased only weight , and this effect was limited to the neonatal period . These findings , supported by data from other workers , suggest that the increase in weight produced by ash in small , premature infants is not true growth . Increase in length is the best single measure of growth Background Decreased nitrogen levels , calcium intestinal absorption rates , and plasma amino acid imbalances were reported for preterm infants who were fed partially hydrolyzed preterm formulas . In this pilot study , we evaluated a new formula with modified nitrogen and calcium sources . Methods During their second week of life , 16 preterm infants were r and omly assigned to one of two groups : 9 were fed the  new partially hydrolyzed formula and 7 were fed a conventional formula . Nutrient balance was performed at the end of the first month of life . Amino acid concentrations and anthropometric parameters were measured at theoretical term . Results Birth weight and gestational age ( mean ± SD ) were similar in the two groups ( 28.9 ± 7.0 weeks and 1183 ± 242 g vs. 27.7 ± 1.0 weeks and 1139 ± 162 g ) . Median nitrogen absorption rates ( 85 % vs. 89%;P = 0.03 ) and biological values ( 59 % vs. 69%;P = 0.13 ) were lower for infants who were fed the new formula than for those fed the conventional formula . After correction for difference in nitrogen intake , there was no significant difference in nitrogen retained between the two groups ( P = 0.11 ) . Plasma amino acid concentrations were also similar in the two groups . Median calcium absorption tended to be higher in the new-formula group than in the conventional-formula group ( 54 % vs. 45 % , P = 0.19 ) . At theoretical term , infants fed the conventional formula were heavier than infants fed the new formula ( 3559 ± 362 g vs. 3193 ± 384 g , P = 0.04 ) . Conclusions Because nitrogen content is 10 % higher in hydrolyzed-protein formula than in entire-protein formula , appropriate nitrogen retention , plasma amino acid profile , and mineral use can be achieved with the new partially hydrolyzed formula . Further studies with larger groups are needed to evaluate the effect on growth 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 We investigated the influence of body size at birth , feeding of mother 's milk versus formula , or st and ard-term formula versus energy- or nutrient-enriched formula on the growth and whole body bone mineral content ( BMC ) , lean and fat mass ( using dual-energy X-ray absorptiometry ) of low-birth-weight ( LBW ) infants to term-adjusted age . LBW infants who were appropriate for gestational age were lighter and shorter than term-born infants ( n = 46 ) but had a higher percent fat mass ( 19 - 28 % vs. 15 + /- 7 % ) . For LBW infants fed st and ard formula or mother 's milk after hospital discharge , the mean BMC expressed either as a function of weight ( 17 + /- 2 , 19 + /- 2 vs. 20 + /- 2 g/kg ) or length ( 1.1 + /- 0.2 , 1.1 + /- 0.2 vs. 1.5 + /- 0.2 g/cm ) was more than 1 SD below term infant values . However , infants fed a nutrient-enriched formula from hospital discharge had BMC within 1 SD below term infants . Infants who were born small , compared to appropriate for gestational age , compared to infants of similar birth weight had lower percent body fat ( 16 + /- 6 vs. 19 + /- 5 ) and lower BMC ( 47 + /- 3 vs. 62 + /- 5 g ) at term age . Both size at birth and diet influence patterns of growth and body composition in early life in very-low-birth-weight ( VLBW ) infants . The long-term significance of these variable growth patterns in VLBW infants in early life requires further investigation The performance of two different , commercially available , low birth weight formulae feeds was compared in preterm infants . The aim of the study was to determine the effect of compositional differences on tolerance , stool frequency and consistency , fat balance and weight gain .  Inborn infants with birth weight less than 1500 g were r and omised at birth to receive Prematil or Osterprem . Thirty infants received more than 900 ml/kg per week of design ated formula alone during a total of 70 weeks of study . Three day fat balance was performed on 23 infants . Osterprem contains 40 % more fat than Prematil . The composition of this fat is different in that Osterprem contains no medium chain triglycerides ( MCT ) compared to 30 % in Prematil . Clinical evaluation demonstrated that Osterprem is associated with a significantly higher mean energy intake compared to Prematil ( 3442 and 3127 kJ/kg per week ) but mean weight gain is not significantly different ( 123 and 112 g/kg per week ) . Mean stool frequency is higher on Osterprem ( 20.5 and 14.5 stool/week ) and the consistency of stools firmer . This is attributable to a higher mean fat output ( 2.3 and 0.9 g/kg per day ) secondary to the higher fat content of the feed and lower mean absorption ( 71.6 and 83.5 % ) . Both feeds are well tolerated . The study also confirms that absorption of unsaturated fatty acids is inversely proportional to chain length The relationship of gain in weight to variable intakes of dietary protein has been evaluated in 442 low-birth-weight ( LBW ) infants .  Isocaloric formulas made with proprietary milk mixtures composed of cow's-milk protein , corn oil , and Dextri-maltose were adjusted so that intakes of protein of 6 , 4 , 3 , and 2 Gm . per kilogram per day , respectively , were fed to infants selected on a r and om basis . The specific formulas fed to individual infants were not known to any physician or nurse until the feeding experiment had been completed . The minimal intake of protein which was associated with consistently high rates of gain in weight ( RGW ) was 4 Gm . per kilogram per day . In addition , observations in respect to two different dietary intakes of fat and minerals were made in a limited number of infants . Within the range of variation in the daily intake of either fat or minerals there were no effects on gain in weight among the infants studied . Other metabolic evaluations , such as those of serum protein and calcium , blood-urea , and hemoglobin are detailed in the text BACKGROUND Growth acceleration as a consequence of relative overnutrition in infancy has been suggested to increase the risk of later obesity . However , few studies have investigated this association by using an experimental study design . OBJECTIVE We investigated the effect of early growth promotion on later body composition in 2 studies of infants born small for gestational age ( weight < 10th percentile in study 1 and < 20th percentile in study 2 ) . DESIGN We review ed a subset of children ( n = 153 of 299 in study 1 and 90 of 246 in study 2 ) r and omly assigned at birth to receive either a  control formula or a nutrient-enriched formula  ( which contained 28 - 43 % more protein and 6 - 12 % more energy than the control formula ) at 5 - 8 y of age . Fat mass was measured by using bioelectric impedance analysis in study 1 and deuterium dilution in study 2 . RESULTS Fat mass was lower in children assigned to receive the control formula than in children assigned to receive the nutrient-enriched formula in both trials [ mean ( 95 % CI ) difference for fat mass after adjustment for sex : study 1 : -38 % ( -67 % , -10 % ) , P = 0.009 ; study 2 : -18 % ( -36 % , -0.3 % ) , P = 0.04 ] . In nonr and omized analyses , faster weight gain in infancy was associated with greater fat mass in childhood . CONCLUSIONS In 2 prospect i ve r and omized trials , we showed that a nutrient-enriched diet in infancy increased fat mass later in childhood . These experimental data support a causal link between faster early weight gain and a later risk of obesity , have important implication s for the management of infants born small for gestational age , and suggest that the primary prevention of obesity could begin in infancy A follow-up study was carried out on 304 infants of birth weight below 2,000 gm . While in the prematurenursery these infants were r and omly assigned to either a 2 % or a 4 % protein diet in amounts to provide either 3.0–3.6 or 6.0–7.2 gm/kg/day of protein . Approximately 80 % of the infants were recalled for pediatric , psychometric , and ophthalmologic evaluation at 3 and 5–7 years of age . The incidence of medical , surgical , and neurologic sequelae was approximately equal in both diet groups . However , in the group which had received the 4 % protein diet , a significantly increased incidence of low IQ scores was found in infants of birth weight below 1,300 gm and a significantly increased incidence of strabismus in infants of birth weight below 1,700 gm . These data suggest that intakes of cow 's milk protein in excess of 6 gm/kg/day should not be used for low-birth-weight infants Over a 13-month period 85 babies were r and omly allocated to one of three groups at birth . Babies in Group A were fed SMA Low Birth Weight , Group B Prematalac and Group C Preaptamil . A fourth group , the control group was fed expressed breast milk ( EBM ) . The babies were studied when they were on full enteral feeds until weight was greater than 2.0 kg . Weight gain was greatest in Group B compared to the other three groups but there was no significant difference in gain of length or occipito-frontal circumference . The babies in Group B had a lower volume of feeds and lower energy intake than the other groups but had a significantly higher sodium intake which was reflected in higher mean sodium levels . This may have accounted for the increased weight gain . There was no significant difference in serum calcium , osmolality , total protein or haematocrit 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 Fifteen low-birth-weight appropriate for gestational age infants , weighing 1.3 to 1.6 kg , were assigned to three isocaloric formulas differing in the quantity and form of nitrogen delivered . A balance study was done between 21 and 30 days after birth . Nitrogen retention expressed as milligram per kilogram per 100 kcal of metabolizable energy was greater with the 60:40 whey/casein and with the casein hydrolysate preparations than with the 20:80 whey/casein formula , which provided the same amount of energy ( 150 kcal/kg/day ) but smaller quantities of protein ( 3.5 g/kg/day ) than the two others ( 4.3 g/kg/day and 4.4 g/kg/day ) . Weight gain until discharge from the hospital and increment of height and head circumference over a three-month period showed an advantage of the two formulas providing higher intakes of protein . This study suggests that with high-energy intakes , protein quality does not affect nitrogen retention and growth unless the quantity of protein ingested falls below a critical level A controlled clinical trial was carried out to evaluate the effects of two different levels of protein intake on 304 infants with birth weights below 2,000 grams ; the diets contained either 3.0 to 3.6 or 6.0 to 7.2 Gm . per kilogram per day of protein . The infants fed the higher intake had more fever , lethargy , and poor nipple feeding , but they had higher plasma protein levels and less edema than infants fed the lower intake OBJECTIVE We studied the effect of varying only protein intake on energy balance , protein balance and estimated weight gain composition in premature infants fed either a formula with a protein content of 2.0 g/100 ml ( F2 ) or a protein content of 1.5 g/100 ml ( F1.5 ) . DESIGN Premature infants were r and omly allocated to receive F1.5 or F2 .  Weight gain composition was estimated from protein and energy balances . Energy expenditure was measured with doubly labelled water . PATIENTS F1.5 , n = 8 ; gestational age 32 + /- 3 weeks , birth weight 1716 + /- 560 g. F2 , n = 8 ; gestational age 32 + /- 3 weeks , birth weight 1544 + /- 488 g. RESULTS Infants fed F2 showed a significantly higher protein accretion ( P = 0.003 ) and weight gain ( P = 0.011 ) when compared to the infants fed F1.5 . There were no differences in the energy balance . The estimated weight gain composition was different between both groups . CONCLUSION The F2 fed infants had an estimated weight gain composition comparable to the reported intrauterine values , while the F1.5 fed infants showed a weight gain composition more comparable to the reported values of the full term infant . The impact of nutrient composition in premature infant formulas on body composition and growth is discussed ABSTRACT : A model for predicting the relationship between protein and energy intakes of low-birth-weight ( LBW ) infants and the rate and composition of weight gain is described . It is based on linear multiple regression equations summarizing the rates of weight gain , nitrogen retention , and energy retention of 101 previously studied LBW infants fed protein intakes ranging from 2.25 to 3.9 g kg-1 d-1 and concomitant energy intakes ranging from 115 to 147 kcal kg-1 d-1 plus current theory concerning nutrient retention and body composition . To test the validity of the model , three combinations of protein and energy intake predicted by the model to result in specific rates and compositions of weight gain were fed to 44 LBW infants , and the observed rates of weight gain , protein accretion , and fat accretion were compared with the rates predicted by the model . Differences in these and other outcome variables between two of the groups , the intakes of which differed only in energy , also were compared to provide additional insight into the effect of concomitant energy intake on protein utilization . Across groups , actual outcomes correlated closely with predicted outcomes , supporting the validity of the model for the total population . However , outcomes of individual infants deviated as much as 30 % from predicted outcomes ; the magnitude of the deviation was independent of birth weight , gestational age , or size for gestational age . In addition , the mean rate of protein accretion of the group fed the highest protein/energy ratio was significantly less than predicted . The higher mean urinary nitrogen excretion as well as blood urea nitrogen and plasma amino acid concentrations of this group versus the group that received a similar protein intake with a higher energy intake suggest that the higher energy intake improved nitrogen utilization . In toto , the data support the concept that the rate and composition of weight gain of LBW infants can be manipulated by intake ; however , for individual infants , the extent of manipulation seems to be dependent on as-yet-unidentified inherent biologic variables The National Institute of Child Health and Human Development conducts and supports research on all stages of human development from preconception to adulthood in order to better underst and the health of children , youths , adults , families , and communities . Health and human development information is made easily available on the site with a simple A to Z list , along with clinical trials and health education campaign information . Links to clinical trials , news releases , publications , and related web sites are also available , as well as information on research being conducted at present and supported by the National Institute of Child Health and Human Development Svenningsen , N.W. , Lindroth , M. and Lindquist , B. ( Department of Paediatrics , University of Lund , Sweden ) . A comparative study of varying protein intake in low birthweight infant feeding . Acta Paediatr Sc and . Suppl . 296 : 28 , 1982 . — In a prospect i ve longitudinal study of 48 very low birthweight and preterm infants with mean birthweight 1 385±343 and gestational age 30.8±2.9 w 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 slightly higher in the infants fed formula 1 and 2 . There were no group differences in S‐albumin whereas B‐urea‐N and B‐base deficit were significantly increased in the formula fed infants in comparison to infants fed human milk . After the study period until around 15 weeks of age the slope in weight gain remained slightly higher for formula fed infants . However , the gain in body length and head 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 To assess the influence of protein intake on renal excretion of calcium and amino acids and on bone mineralization in preterm infants , we r and omly selected within weight group strata 27 infants who weighed < 1500 gm at birth ( nine per group ) to be fed a high-mineral ( calcium , 940 mg/L ; phosphorus , 470 mg/L ) premature formula with one of the following protein contents : formula A , 3.0 gm/100 kcal ; formula B , 2.7 gm/100 kcal ; and formula C , 2.2 gm/100 kcal . Mean ( + /- SD ) daily weight gain was greater in infants receiving the higher protein intakes for the first 30 days ( formula A , 24.8 + /- 5.1 gm ; formula B , 20.5 + /- 3.8 gm ; formula C , 16.2 + /- 5.9 gm ( analysis of variance : p < 0.01 ; C < A , p < 0.05 ) ) . Bone mineral content did not differ at any time point , and all groups had a high prevalence of generalized aminoaciduria ( 4 weeks : formula A , 56 % ; formula B , 71 % ; formula C , 75 % ) . Urinary calcium corrected for creatinine ( in milligrams per milligram ) increased as protein content decreased ( 2 weeks : formula A , 0.16 + /- 0.10 ; formula B , 0.20 + /- 013 ; formula C , 0.44 + /- 0.33 ( C > A , C > B , p < 0.05 ) ; 4 weeks : formula A , 0.23 + /- 0.15 ; formula B,0.34 + /- 0.47 ; formula C , 0.49 + /- 0.22 ( C > A , p < 0.01 ) . We conclude that the high mineral content and other components of premature formulas result in a higher growth rate and may increase protein requirements . Failure to meet protein requirements may result in underutilization of absorbed calcium and increased renal excretion of calcium . In preterm infants , higher protein intake probably supports rather than jeopardizes bone mineral accretion , and reduces rather then increases calciuria The effect of energy and protein intakes on energy expenditure , energy balance , and amount and relative rate of both protein and fat deposition in new tissue was investigated in 19 low birth weight infants whose mean protein and energy intakes , respectively , were 2.24 g/kg/d and 113 kcal/kg/d ( formula A , n = 8) , 3.6 g/kg/d and 115 kcal/kg/d ( formula B , n = 5 ) , and 3.5 g/kg/d and 149 kcal/kg/d ( formula C , n = 6 ) . The higher energy intake ( formula C ) but not the higher protein intake ( formula B ) result ed in greater energy expenditure . Both the higher protein ( formula B vs formula A ) and higher energy intakes ( formula C vs formula B ) result ed in greater weight gain secondary , in group B , to a greater absolute rate of protein deposition and , in group C , to a greater absolute rate of fat deposition . The relative composition of the new tissue deposited reflected the proportional intakes of protein and energy . The numerical value of the protein/fat ratio ( g/g ) of the new tissue deposited by infants fed formulas A and C , the protein contents of which were low relative to energy contents , were similar and significantly lower than the numerical value of the protein/fat ratio of the new tissue deposited by infants fed formula B , which had a higher protein content relative to energy content . These findings suggest that the composition of weight gain is related to both the absolute amounts and the proportions of dietary protein and energy ; thus , both must be considered in formulation of nutritional regimens for LBW infants Feeding 25 low birth weight infants during a one month period either with special premature formula or with st and ard formula result ed in better weight gain , nutritional efficacy , fat absorption , and lower frequency of metabolic acidosis in the special premature formula group . Various biochemical indices demonstrated excellent protein and mineral metabolization of this formula , which seem appropriate for the infants studied ( 1,000 - 1,750 g birth weight ) . Both formulae were well tolerated without any untoward effects Premature infants weighing less than 1550 gm at birth were r and omly assigned to receive one of three formulas identical in composition except for protein content ( 2.2 , 2.7 , and 3.2 gm.100 kcal-1 ) to determine the effects on growth , protein nutritional status , and behavior . Data collected for 2 weeks from the time of achieving an enteral energy intake of 100 kcal.kg-1.day-1 included measurements of weight , length , head circumference , and skin-fold thickness , and concentrations of plasma amino acids , serum total protein , prealbumin , retinol-binding protein , and urea nitrogen . In a subset of infants , behavior was assessed at the end of the feeding study with the Neonatal Behavior Assessment Scale . Except for the concentrations of plasma amino acids , there were no significant differences in growth or in other biochemical measurements among the three groups , but there were significant differences in the orientation , habituation , and stability clusters of the behavior assessment . Further , there were significant correlations between the plasma amino acid values and the behavioral clusters . These preliminary data suggest a relationship between protein intake in the neonatal period and behavioral outcome at the end of the feeding period in the absence of differences in growth and gross markers of protein nutritional status . The behavioral items noted to differ among the groups may indicate later cognitive outcome ; detailed studies about behavioral responses to neonatal dietary intakes and later outcome seem indicated Background In extremely-low-birth-weight ( ELBW ) infants , formula feeding is required if human milk is not available . The tolerance of a new ` high ' lactose ( 55 g/L ) , low protein , low phosphate , hydrolyzed protein formula ( HLF ) for early enteral feeding advancement of ELBW infants was compared with that of a low lactose ( 1 g/L ) hydrolyzed protein formula ( LLF ) . Methods In a r and omized multicenter trial , 99 ELBW infants were fed according to a st and ardized protocol beginning at 48 hours of age with 12 ml/kg daily increments . Primary outcome was the cumulative milk feeding volume ( CFV ) from days 3 to 14 . The authors hypothesized that feeding HLF as a supplement to human milk would increase the CFV at least by 20 % in at least 60 % of matched pairs compared with LLF . A secondary issue was to investigate whether human milk would increase the CFV compared with formula . Results The CFV was 720 mL/kg ( range , 0–962 mL/kg ) with HLF and 613 mL/kg ( range , 3–1,283 mL/kg ) with LLF feeding . There was no 20 % difference . On day 14 , the median feeding volume was 103 mL/kg . The CFV was 533 mL/kg ( range , 0–962 mL/kg ) in infants who received less than 10 % of human milk and 832 mL/kg ( range , 74–1,283 mL/kg ) in infants who received more than 10 % . Necrotizing enterocolitis ( Bell stage ≥2 ) occurred only with LLF feeding ( n = 5;P < 0.05 ) . Conclusions The study failed to find the hypothesized 20 % advantage of the new HLF . The observed advantage of human milk supports the hypothesis that it should be the first diet in ELBW infants ; however , this hypothesis still must be confirmed in a controlled , r and omized trial 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 The ideal quantity of dietary protein for formula-fed low birth weight infants is still a matter of debate .
Protein intake must be sufficient to achieve normal growth without negative effects such as acidosis , uremia , and elevated levels of circulating amino acids .
OBJECTIVES To determine whether higher ( ≥ 3.0 g/kg/d ) versus lower ( < 3.0 g/kg/d ) protein intake during the initial hospital stay of formula-fed preterm infants or low birth weight infants ( < 2.5 kilograms ) results in improved growth and neurodevelopmental outcomes without evidence of short- and long-term morbidity .
To examine the following distinctions in protein intake .
1 .
Low protein intake if the amount was less than 3.0 g/kg/d .
2 .
3 .
2 .
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4 .