A New Liquid Human Milk Fortifier and Linear Growth in Preterm Infants Breast milk fortification: Effect on gastric emptying Diet and Bone Mineral Content at Term in Premature Infants Effect of fortifying breast milk on gastric emptying. Moderate nutrient supplementation of mother's milk for preterm infants supports adequate bone mass and short-term growth: a randomized, controlled trial. Associations between prenatal and infancy weight gain and BMI, fat mass, and fat distribution in young adulthood: a prospective cohort study in males and females born very preterm. Randomized outcome trial of human milk fortification and developmental outcome in preterm infants. Target fortification of breast milk with fat, protein, and carbohydrates for preterm infants. Rickets in very-low-birth-weight infants born at Baragwanath Hospital. Growth of Very Low Birth Weight Infants on Varying Amounts of Human Milk Protein GRADE guidelines: 4. Rating the quality of evidence--study limitations (risk of bias). Effect of human milk fortification in appropriate for gestation and small for gestation preterm babies: a randomized controlled trial. Effects of human milk fortification on morbidity factors in very low birth weight infants. Human milk fortification and gastric emptying in the preterm neonate. Diet, growth, and bone mineralization in premature infants. Randomized trial of human milk cream as a supplement to standard fortification of an exclusive human milk-based diet in infants 750-1250 g birth weight. Growth and body composition of preterm infants: influence of nutrient fortification of mother's milk in hospital and breastfeeding post‐hospital discharge 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 Bone Mineralization and Mineral Homeostasis in Very Low‐Birth-Weight Infants Fed Either Human Milk or Fortified Human Milk Longitudinal Growth of Hospitalized Very Low Birth Weight Infants Promotion of Faster Weight Gain in Infants Born Small for Gestational Age: Is There an Adverse Effect on Later Blood Pressure? Postnatal malnutrition and growth retardation: an inevitable consequence of current recommendations in preterm infants? Bone mineralisation in premature infants cannot be predicted from serum alkaline phosphatase or serum phosphate Premature infants fed mothers' milk to 6 months corrected age demonstrate adequate growth and zinc status in the first year.
OBJECTIVES : To evaluate the growth , tolerance , and safety of a new ultraconcentrated liquid human milk fortifier ( LHMF ) design ed to provide optimal nutrients for preterm infants receiving human breast milk in a safe , nonpowder formulation . METHODS : Preterm infants with a body weight ≤1250 g fed expressed and /or donor breast milk were r and omized to receive a control powder human milk fortifier ( HMF ) or a new LHMF for 28 days . When added to breast milk , the LHMF provided ∼20 % more protein than the control HMF  . Weight , length , head circumference , and serum prealbumin , albumin , blood urea nitrogen , electrolytes , and blood gases were measured . The occurrence of sepsis , necrotizing enterocolitis , and serious adverse events were monitored . RESULTS : This multicenter , third party – blinded , r and omized controlled , prospect i ve study enrolled 150 infants . Achieved weight and linear growth rate were significantly higher in the LHMF versus control groups ( P = .04 and 0.03 , respectively ) . Among infants who adhered closely to the protocol , the LHMF had a significantly higher achieved weight , length , head circumference , and linear growth rate than the control HMF ( P = .004 , P = .003 , P = .04 , and P = .01 , respectively ) . There were no differences in measures of feeding tolerance or days to achieve full feeding volumes . Prealbumin , albumin , and blood urea nitrogen were higher in the LHMF group versus the control group ( all P < .05 ) . There was no difference in the incidence of confirmed sepsis or necrotizing enterocolitis . CONCLUSIONS : Use of a new LHMF in preterm infants instead of powder HMF is safe . Benefits of LHMF include improvements in growth and avoidance of the use of powder products in the NICU Aim . To determine whether a widely used fortifier affects gastric emptying in very low birth weight infants and whether the amount of fortifier added to breast milk makes a difference with regard to gastric emptying . Methods . The study hypothesis was tested in a balanced crossover design . Gastric emptying was determined in the same infant on the same day with each of the three test feedings ( unfortified breast milk , half-fortified breast milk , and fully fortified breast milk ) in r and om order . The antral cross-sectional area ( ACSA ) was measured by B-mode ultrasonography ( US ) and the feeding was given . The ACSA was determined again immediately after feeding was completed , and was then determined at 10-min intervals until the pre-feeding value was reached . Results . The average half-emptying time was 49 ± 23 min with breast milk , 54 ± 29 min with half-fortified breast milk , and 65 ± 36 min with fully fortified breast milk . The differences between feeding groups were not statistically significant . Conclusion . Fortification of breast milk does not play a clinical ly significant role in causing feeding intolerance in preterm babies when recommended concentrations of fortifier are used Premature infants are at risk of developing metabolic bone disease mainly because of low calcium and phosphorus intake . We have examined the effect of different mineral supplements on bone mineral content at term in 127 premature infants with gestational age < 32 wk in a double-blinded r and omized trial . We used either phosphate supplementation of human milk as recommended by the European Society of Pediatric Gastroenterology and Nutrition or fortified supplementation with protein , calcium , and phosphorus or preterm formula as recommended by the American Academy of Pediatrics . The intervention period was from 1 week old until 36 wk of gestational age , and the infants were fed approximately 200 mL·kg−1·d−1 . Bone mineral content was measured at term by dual-energy x-ray absorptiometry scan . Surprisingly , neither phosphate , fortifier , nor preterm formula supplementation had any significant effect on bone mineral content at term compared with infants fed their own mother 's milk only . There was a tendency to higher total bone mineral content in infants fed preterm formula compared with infants fed their own mother 's milk only ( p = 0.05 ) , but when the bone mineral content was corrected for the size of the infant , there was no difference ( p = 0.68 ) . Infants fed preterm formula had a significantly higher weight at term compared with infants fed their own mother 's milk only ( p = 0.02 ) , but did not differ significantly in length or head circumference . In a regression analysis , the amount of supplemented phosphorus was significantly associated with weight at term ( p = 0.008 ) . We conclude that when feeding 200 mL·kg−1·d−1 , mineral supplementation of human milk or use of preterm formula does not significantly improve bone mineralization outcome at term A study was performed to determine if the addition of a fortifier to expressed breast milk ( EBM ) affected gastric emptying in low birthweight infants . Using ultrasonography , the gastric emptying of EBM alone was compared with that containing a fortifier , in a blind , crossover study . Twenty two low birthweight infants were studied : median ( range ) gestation 31.5 weeks ( 28 - 37 ) ; birthweight 1495 g ( 1000 - 2480 g ) . The gastric antral cross-sectional area ( ACSA ) was measured by ultrasonography before each feed and then sequentially after its completion until the ACSA returned to its pre-feed value . The half emptying time was calculated as the time taken for the ACSA to decrease to half the maximum increment . The mean difference ( st and ard error ) between half emptying times for EBM alone and for EBM with added fortifier was not significant : 1.48 ( 4.9 ) minutes . These data show that fortifying breast milk does not affect gastric emptying and suggests that the practice is unlikely to affect feed tolerance in low birthweight infants Our objectives were 1 ) to determine whether moderate nutrient supplementation of mother 's milk ( MM ) for preterm infants , in the form of a new multinutrient fortifier ( MNF ) , would improve short-term growth and bone mineral content ( BMC ) when compared with supplementation with calcium and phosphorus alone ; and 2 ) to investigate whether moderate calcium and phosphorus intakes , in the form of calcium glycerophosphate ( CaGP ) , result ed in a BMC similar to that of term corrected infants . Twenty-five preterm infants fed MM were r and omly assigned to receive either MM+MNF or MM+CaGP . A third group of infants fed preterm formula ( PTF ) served as a comparison group . Whole-body BMC and lean and fat mass were determined by dual-energy X-ray absorptiometry ( DXA ) at full-term age . Nitrogen retention and calcium , phosphorus , and zinc intakes were determined by using mass balance techniques . Nitrogen retention was significantly lower in the MM+CaGP group than in the PTF group as were both weight and length gain ( weight gain : 16.6 + /- 1.6 , 14.2 + /- 2.0 , and 16.1 + /- 2.9 g x kg(-1 ) x d(-1 ) ; length gain : 1.1 + /- 0.2 , 0.9 + /- 0.2 , and 1.1 + /- 0.3 cm/wk for the MM+MNF , MM+CaGP , and PTF groups , respectively ) . Biochemical indexes of mineral status and bone turnover were normal . Conservative amounts of calcium and phosphorus , as CaGP , result ed in adequate BMC . Moderate amounts of protein , calcium , and phosphorus plus trace elements added to MM in the form of an MNF result ed in improved linear growth but did not provide any advantages to BMC when compared with supplementation with calcium and phosphorus alone BACKGROUND Increasing evidence indicates that adult body composition is associated with prenatal and infancy weight gain , but the relative importance of different time periods has not been eluci date d. OBJECTIVE The objective was to study the association between prenatal , early postnatal , and late infancy weight gain and body mass index ( BMI ) , fat mass , and fat distribution in young adulthood . DESIGN We included 403 men and women aged 19 y from a Dutch national prospect i ve follow-up study who were born at < 32 wk of gestation .  BMI , waist circumference , and waist-to-hip ratio SD scores and subscapular-to-triceps ratio , percentage body fat , fat mass , and fat-free mass at age 19 y were studied in relation to birth weight SD scores , weight gain from preterm birth until 3 mo postterm ( early postnatal weight gain ) , and weight gain from 3 mo until 1 y postterm ( late infancy weight gain ) . RESULTS Birth weight SD scores were positively associated with weight , height , BMI SD scores , and fat-free mass at age 19 y but not with fat mass , percentage body fat , or fat distribution . Early postnatal and late infancy weight gain were positively associated with adult height , weight , BMI , waist circumference SD scores , fat mass , fat-free mass , and percentage body fat but not with waist-to-hip ratio SD scores or subscapular-to-triceps ratio . CONCLUSIONS In infants born very preterm , weight gain before 32 wk of gestation is positively associated with adult body size but not with body composition and fat distribution . More early postnatal and , to a lesser extent , late infancy weight gain are associated with higher BMI SD scores and percentage body fat and more abdominal fat at age 19 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 OBJECTIVES Fortification of breast milk is an accepted practice for feeding very low birth weight infants , however , fixed dosage enhancement does not address variations in native breast milk . This could lead to deficiencies in calories and macronutrients . We therefore established the infrastructure for target fortification in breast milk by measuring and adjusting fat , protein , and carbohydrate content daily . We analyzed nutrient intake , growth , and safety variables . STUDY DESIGN Each 12-hour batch of breast milk was analyzed using near-infrared spectroscopy . Macronutrients were individually added to routine fortification to achieve final contents for fat ( 4.4 g ) , protein ( 3 g ) , and carbohydrates ( 8.8 g ) ( per 100 mL ) . Fully breast milk fed healthy very low birth weight infants ( < 32 weeks ) were fed the fortified breast milk for at least 3 weeks . Matched pair analysis of 20 infants fed routinely fortified breast milk was performed using birth weight , gestational age , and postnatal age . RESULTS All 650 pooled breast milk sample s required at least 1 macronutrient adjusted . On average , 0.3 ± 0.4 g of fat , 0.7 ± 0.2 g of protein , and 1.2 ± 0.2 g of carbohydrate were added . Biochemistry was normal in the 10 target fortified infants ( birth weight : 860 ± 309 g , 26.3 ± 1.6 weeks gestational age ) ; weight gain was 19.9 ± 2.7 g/kg/d ; and milk intake was 147 ± 5 mL/kg/d ( 131 ± 16 kcal/kg/d ) . Osmolality of fortified breast milk was 436 ± 13 mOsmol/kg . Matched pair analysis of infants indicated a higher milk intake ( 155 ± 5 mL/kg/d ) but similar weight gain ( 19.7 ± 3.3 g/kg/d ) . No adverse event was observed . The linear relationship between milk intake and weight gain observed in study babies but not seen in matched controls may be related to the variable composition of breast milk . CONCLUSIONS Daily target fortification can be safely implemented in clinical routine and may improve growth Disturbed mineral and bone metabolism has been reported to occur frequently in very-low-birth-weight infants fed breast-milk during the first 3 months of life . This study was design ed to assess the prevalence of disturbed mineral homeostasis in a breast-milk-fed very-low-birth-weight population at Baragwanath Hospital and to determine whether the addition of a preterm infant formula to the feeds would reduce this prevalence and increase the rate of weight gain .  Fifty-three neonates weighing less than 1 200 g at birth were monitored for weight gain , growth and biochemical and radiological evidence of metabolic bone disease at 2-weekly intervals during hospitalisation and for 18 weeks after discharge . The infants were r and omised at 2 weeks of age to receive either breast-milk only , or a combination of breast-milk and a premature formula containing 550 mg calcium and 300 mg phosphorus . All infants received 800 IU vitamin D daily from day 14 . Weight gain and growth were similar in both groups . Calcium and phosphorus intakes were higher in the mixed feeding group , but did not affect serum mineral levels . Radiological rickets was uncommon in both groups although periosteal reactions and osteopenia occurred frequently and with similar prevalences . Vitamin D deficiency was not found to be a problem . In conclusion , overt rickets is not a major problem in very-low-birth-weight infants born at Baragwanath Hospital , although biochemical abnormalities occur frequently . ( ABSTRACT TRUNCATED AT 250 WORDS ABSTRACT : In a double-blind , r and omized study , 28 healthy , growing very low birth wt , appropriate-for-gestational- age infants were fed human milk , preferably mother 's own , fortified daily with human milk protein and /or human milk fat . The infants entered the study when they were stable on complete enteral intakes of 170 ml/kgd ( mean ) age=19 d ) . The study lasted for a mean of 4 wk , Sample s from all the milks were collected daily , and intakes of protein , fat , carbohydrates , energy , and electrolytes were calculated weekly during the whole study period . Protein intakes ranged from 1.7 to 3.9 g/kg/d , and energy intakes from 100 to 150 kcal/kg/d . Wt and length gain in the nonprotein-enriched groups were 15.6 ± 2.7 g/kg/d ( mean ± SD ) and 0.88 ± 0.17 cm/wk ; the corresponding figures for the protein-enriched groups were 20.2 ± 2.1 g/ kg/d and 1.24 ± 0.14 cm/wk . There was a strong correlation between protein intake and growth in wt and length up to an intake of about 3 g/kg/d ; more protein did not result in increased growth . The same was true for energy intake , with a maximal growth rate at an intake of about 120 kcal/ kg/d . A protein intake of more than 3 g/kg/d result ed in a growth rate equal to or higher than the estimated intrauterine growth rate . Some infants fed mature banked human milk alone had a poor growth . Sodium intake was low , ranging from 1.5 to 2.6 mmol/kg/d . No correlation was found between sodium intake and growth rates In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias OBJECTIVE To study the effects of human milk fortification on short term growth and biochemical parameters in preterm very low birth weight ( VLBW ) appropriate for gestation ( AGA ) and small for gestation ( SGA ) babies . DESIGN Prospect i ve , r and omized controlled trial . SETTING Level III neonatal unit . SUBJECTS Preterm infants weighing < or = 1500 grams and < or = 34 weeks of gestation born between March 2001 to June 2002 . METHODS Babies ( n = 166 ) were r and omized in two groups either to get fortified human milk or exclusive human milk along with mineral and vitamin supplementation when feed volume reached 150 mL/Kg/day . Fortification was done with a powdered fortifier added in expressed breast milk and continued till the baby reached 2 Kg or full breast feeds . Primary outcome measures were Short-term growth ( daily weight , length and head circumference ( HC ) weekly ) till discharge or 2 Kg . RESULTS Fortification ( n = 85 , birth weight 1202 g , gestation 30.8 wk ) result ed in better growth in preterm VLBW babies as compared to control group ( n=81 , birth weight 1259 g , gestation 31.3 wk ) . Weight gain ( 15.1 and 12.9 g/kg/d , P < 0.001 ) , length ( 1.04 and 0.86 cm/week , P = 0.017 ) and HC ( 0.83 and 0.75 cm/week , P<0.001 ) increased significantly in fortified group . SGA babies showed significant improvements in weight ( 16 g/Kg/d and 12.9 g/kg/d , P = 0.002 ) and length ( 1.09 cm/week and 0.92 cm/week , P = 0.042 ) in fortified group ( n = 38 ) as compared to control group ( n = 29 ) . In AGA subgroup , there was significant increase ( P = 0.006 ) in length ( 1 cm vs 0.82 cm ) in fortified group but no difference in weight ( P = 0.12 ) or HC ( P=0.054 ) in fortified ( n=47 ) vs control ( n=52 ) group . Biochemical parameters were comparable , however feed intolerance was more in control group . CONCLUSION Preterm VLBW babies showed better growth with human milk fortification . The effect is significant in SGA ( weight and length)rather than AGA ( only length ) babies BACKGROUND The use of human milk as a sole source of nutrients for preterm infants has been the subject of debate in recent years . We studied the morbidity factors associated with hospitalization of very low birth weight ( VLBW ) infants fed human milk with and without fortification . PATIENTS AND METHODS One hundred VLBW infants were r and omly assigned to two groups with stratification for gestation and weight . The  control group ( n-50 ; mean birth weight 1239+/-186 g and mean gestation 29.3+/-2.1 wks ) was fed human milk only , and in the fortifier group ( n=50 ; mean birth weight 1245+/-191 g and mean gestation 29.5+/-2.1 wks ) , human milk was enriched with a fortifier after the babies reached a volume of 140 mL/kg/day by the enteral route . Weight was measured twice weekly , biochemical indices of nutritional and bone status and serum electrolytes were obtained weekly , and clinical evidence for sepsis , necrotizing enterocolitis and feeding intolerance was assessed regularly until infants were discharged . RESULTS Hospital stay was less than 45 days in the majority ( 94 % ) of the babies in the fortifier group , whereas the majority ( 66 % ) of the babies in the control group stayed for more than 45 days ( P<0.01 ) . Low serum phosphorus and raised alkaline phosphate levels were seen more frequently in the control group without fortification ( p<0.01 ) , as weel as hyponatremia ( P<0.01 ) , late metabolic acidosis of prematurity ( P<0.01 ) and culture-proven sepsis ( p<0.05 ) . There was no significant difference in the occurrence of necrotizing enterocolitis between the two groups ( P>0.05 ) . CONCLUSION Human milk fortification has beneficial effects on the growth of VLBW infants and decreases hospital stay and morbidity associated with prematurity and very low birth weight , with economic and psychological benefits for the parents Fortification of expressed breast milk ( EBM ) is widely recommended for preterm feeding . Fortification of EBM results in increased caloric density and osmolarity , both of which may retard gastric emptying . As gastric emptying is a major determinant of feed tolerance , we investigated the effect of fortification ( with Lactodex HMF ) of EBM on gastric emptying in preterm neonates . The half gastric emptying time was measured using real time ultrasonography in 25 consecutive preterm neonates first on EBM alone , then on EBM + Lactodex HMF . Each baby served as its own control . The students t-test was used for statistical analysis . The mean gestation age was 34.48 + /- 0.77 weeks . The mean birth weight was 1.92 + /- 0.14 kg . The mean half gastric emptying time at an age of 5.4 + /- 0.86 days on EBM was 24.00 + /- 5.00 min and 24.40 + /- 5.06 min on EBM + human milk fortifier ( HMF ) . The same at 2nd assessment ( 15.2 + /- 1.79 days ) , with EBM was 22.80 + /- 4.58 min vs. 23.60 + /- 4.89 min when given EBM + HMF . These differences were not statistically significant . Fortification of EBM with Lactodex HMF does not affect the gastric emptying in preterm neonates and therefore is unlikely to affect feed tolerance in them Energy , protein , and mineral requirements in premature infants are high , hence increasing the risk of poor growth and development of metabolic bone disease . This double-blind study included 127 consecutive premature infants with gestational age below 32 weeks . Both sick and healthy infants participated . Average duration of ventilator treatment : 2 days , CPAP treatment : 10 days ( range , 0 - 50d ) . Infants were r and omized to 3 groups from 1 week old to 37 weeks of gestational age and fed the following : a ) human milk ( their own mother 's milk or banked milk ) supplemented with phosphate , b ) human milk fortified with protein , calcium , and phosphate , or c ) unsupplemented mother 's milk or preterm formula . Infants r and omized to preterm formula were fed formula only if their own mother 's milk was not available , hence there were 2 subgroups of infants fed either unsupplemented human milk or preterm formula . Volume of intake was 191+/-14mL/kg/d ( mean + /- SD ) ; linear growth was measured weekly by knemometry ; head circumference was measured weekly ; and growth rate was calculated by linear regression for each infant . Bone mineralization and body composition were measured by DEXA-scan ( Hologic 1000/W ) at term . There was a tendency toward slower growth and less bone mineral content in infants fed unsupplemented human milk but , surprisingly , the difference was small and not significant OBJECTIVE To evaluate whether premature infants who received an exclusive human milk (HM)-based diet and a HM-derived cream supplement ( cream )  would have weight gain ( g/kg/d ) at least as good as infants receiving a st and ard feeding regimen ( control ) . STUDY DESIGN In a prospect i ve noninferiority , r and omized , unmasked study , infants with a birth weight 750 - 1250 g were r and omly assigned to the control or cream group . The control group received mother 's own milk or donor HM with donor HM-derived fortifier . The cream group received a HM-derived cream supplement if the energy density of the HM tested < 20 kcal/oz using a near infrared HM analyzer . Infants were continued on the protocol until 36 weeks postmenstrual age . Primary outcomes included growth velocities and amount of donor HM-derived fortifier used . The hypothesis of noninferiority was established if the lower bound of the one-sided 95 % CI for the difference in weight velocities exceeded -3 g/kg/day . RESULTS There were no differences between groups in baseline demographics for the 78 infants studied except racial distribution ( P = .02 ) . The cream group ( n = 39 ) had superior weight ( 14.0 ± 2.5 vs 12.4 ± 3.0 g/kg/d , P = .03 ) and length ( 1.03 ± 0.33 vs 0.83 ± 0.41 cm/wk , P = .02 ) velocity compared with the control group ( n = 39 ) . There were no significant differences in amount of fortifier used between study groups . The 1-sided 95 % lower bound of the CI for the difference in mean velocity ( cream-control ) was 0.38 g/kg/d . CONCLUSIONS Premature infants who received HM-derived cream to fortified HM had improved weight and length velocity compared with the control group . HM-derived cream should be considered an adjunctive supplement to an exclusive HM-based diet to improve growth rates in premature infants We examined the influence of multi‐nutrient fortification of mother 's milk ( MM + MNF ) compared to supplementation with calcium and phosphorus ( MM + CaGP ) alone in hospital ( in a r and omized trial ) , and of breastfeeding ( post‐MM ) compared to formula feeding ( post‐FF ) after hospital discharge with a descriptive analysis of growth and body composition to 1 y corrected age in preterm infants .  Anthropometry , nutrient intakes and whole body bone mineral content , lean and fat mass were determined at four time points in the first year after term corrected age . Body composition was determined with dual energy X‐ray absorptiometry . MM + MNF compared to MM + CaGP for preterm infants in the early neonatal period did not appear to influence growth or body composition in the first year . Growth in post‐MM and post‐FF groups was within the normal range of growth references derived from term infants fed mother 's milk . Post‐MM infants had lower whole body bone mineral content ( 132.3 ± 10.4 g ) at 6 months corrected age when compared to post‐FF infants ( 159.4 ± 14.1 g ) and greater percent fat mass to 12 months corrected age . These differences may result from the lower calcium , phosphorus and protein intakes in post‐MM compared to post‐FF infants . Our findings demonstrate that dietary practice s after hospital discharge likely have a greater impact on body composition in prematurely born infants than dietary practice s in hospital . Whether the observed differences in body composition between breastfed and formula‐fed preterm infants have any long‐term consequences requires further investigation 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 Abnormalities in bone mineral metabolism are frequently found in very low-birth-weight infants , especially if fed breast milk . To assess the efficacy of a breast-milk fortifier in the feeding of these very small infants , very low-birth-weight babies ( between 1,000 g-1,500 g at birth ) were r and omly assigned to one of two groups on day 4 of life . The fortified group received the fortifier mixed in equal proportions with their own mother 's milk , while the breast-milk group received only their own mother 's milk . All infants received an oral vitamin D supplement of 750 IU/day . The study was continued until the infants weighed 1,800 g , at which stage breast feeding was encouraged . Thirty infants in the breast-milk group and 29 in the fortified group completed the study . Infants in the fortified group had significantly lower alkaline phosphatase values , a greater bone mineral content ( BMC ) and BMC /bone width ratio , and lower urinary calcium excretion than the breast-milk group at a weight of 1,800 g. At follow-up study 3 months after delivery , when most of the infants in both groups had been breast fed for at least 6 weeks , the breast-milk group 's biochemical and BMC abnormalities were almost totally corrected and were now similar to those of the fortified group . Thus , the addition of the fortifier to breast milk during the first 4–6 weeks of life decreased the biochemical evidence of abnormal bone mineral homeostasis and increased BMC in very low-birth-weight infants . By 3 months of age , however , the breast-milk group had almost totally corrected its abnormalities Background . The interpretation of growth rates for very low birth weight infants is obscured by limited data , recent changes in perinatal care , and the uncertain effects of multiple therapies . Objectives . To develop contemporary postnatal growth curves for very low birth weight preterm infants and to relate growth velocity to birth weight , nutritional practice s , fetal growth status ( small- or appropriate-for-gestational-age ) , and major neonatal morbidities ( chronic lung disease , nosocomial infection or late-onset infection , severe intraventricular hemorrhage , and necrotizing enterocolitis ) . Design . Large , multicenter , prospect i ve cohort study . Methods . Growth was prospect ively assessed for 1660 infants with birth weights between 501 to 1500 g admitted by 24 hours of age to 1 of the 12 National Institute of Child Health and Human Development Neonatal Research Network centers between August 31 , 1994 and August 9 , 1995 . Infants were included if they survived > 7 days ( 168 hours ) and were free of major congenital anomalies .  Anthropometric measures ( body weight , length , head circumference , and midarm circumference ) were performed from birth until discharge , transfer , death , age 120 days , or a body weight of 2000 g. To obtain representative data , nutritional practice s were not altered by the study protocol . Results . Postnatal growth curves suitable for clinical and research use were constructed for body weight , length , head circumference , and midarm circumference . Once birth weight was regained , weight gain ( 14.4–16.1 g/kg/d ) approximated intrauterine rates . However , at hospital discharge , most infants born between 24 and 29 weeks of gestation had not achieved the median birth weight of the reference fetus at the same postmenstrual age . Gestational age , race , and gender had no effect on growth within 100-g birth weight strata . Appropriate-for-gestational age infants who survived to hospital discharge without developing chronic lung disease , severe intraventricular hemorrhage , necrotizing enterocolitis , or late onset-sepsis gained weight faster than comparable infants with those morbidities . More rapid weight gain was also associated with a shorter duration of parenteral nutrition providing at least 75 % of the total daily fluid volume , an earlier age at the initiation of enteral feedings , and an earlier age at achievement of full enteral feedings . Conclusions . These growth curves may be used to better underst and postnatal growth , to help identify infants developing illnesses affecting growth , and to aid in the design of future research . They should not be taken as optimal . R and omized clinical trials should be performed to evaluate whether different nutritional management practice s will permit birth weight to be regained earlier and result in more rapid growth , more appropriate body composition , and improved short- and long-term outcomes Background — Being born small for gestational age is associated with later risk factors for cardiovascular disease , such as high blood pressure . Promotion of postnatal growth has been proposed to ameliorate these effects . There is evidence in animals and infants born prematurely , however , that promotion of growth by increased postnatal nutrition increases rather than decreases later cardiovascular risk . We report the long-term impact of growth promotion in term infants born small for gestational age ( birth weight < 10th percentile ) . Methods and Results — Blood pressure was measured at 6 to 8 years in 153 of 299 ( 51 % ) of a cohort of children born small for gestational age and r and omly assigned at birth to receive either a  st and ard or a nutrient-enriched formula . The enriched formula contained 28 % more protein than st and ard formula and promoted weight gain . Diastolic and mean ( but not systolic ) blood pressure was significantly lower in children assigned to st and ard compared with nutrient-enriched formula ( unadjusted mean difference for diastolic blood pressure , −3.2 mm Hg ; 95 % CI , −5.8 to −0.5 ; P=0.02 ) independent of potential confounding factors ( adjusted difference , −3.5 mm Hg ; P=0.01 ) . In observational analyses , faster weight gain in infancy was associated with higher later blood pressure . Conclusions — In the present r and omized study targeted to investigate the effect of early nutrition on long-term cardiovascular health , we found that a nutrient-enriched diet increased later blood pressure . These findings support an adverse effect of relative “ overnutrition ” in infancy on long-term cardiovascular disease risk , have implication s for the early origins of cardiovascular disease hypothesis , and do not support the promotion of faster weight gain in infants born small for gestational age BACKGROUND Nutrient intakes meeting recommended dietary intakes ( RDIs ) take time to establish and once established are rarely maintained throughout hospital stay in preterm infants . A nutrient deficit , therefore , accrues . RDI are based on needs for maintenance and growth , with no provision to replace this deficit . We , therefore , hypothesized that postnatal malnutrition and growth retardation were inevitable in infants fed current RDI . METHODOLOGY Dietary intakes were prospect ively collected , by a single observer ( N.P. ) , on a daily basis in a group of preterm infants ( n = 105 ; birth weight < /=1750 g ; gestational age < /=34 weeks ) admitted to neonatal intensive care unit over a 6-month period . Actual was subtracted from recommended energy ( 120 kcal/kg/day ) and protein ( 3 g/kg/day ) intakes and nutritional deficits calculated . Infants were weighed on admission and throughout hospital stay . The data were analyzed using a combination of repeated measures analysis of variance and stepwise regression analysis . RESULTS Nutrient intakes meeting current RDIs were rarely achieved during early life . By the end of the first week , cumulative energy and protein deficits were 406 + /- 92 and 335 + /- 86 kcal/kg and 14 + /- 3 and 12 + /- 4 g/kg in infants < /=30 and those at > /=31 weeks . By the end of the fifth week , cumulative energy and protein deficits were 813 + /- 542 and 382 + /- 263 kcal/kg and 23 + /- 12 and 13 + /- 15 g/kg and the z scores were -1.14 + /-.6 and -.82 + /-.5 for infants at < /=30 and > /=31 weeks . Stepwise regression analysis indicated that variation in dietary intake accounted for 45 % of the variation in changes in z score . CONCLUSIONS Preterm infants inevitably accumulate a significant nutrient deficit in the first few weeks of life that will not be replaced when current RDIs are fed . This deficit can be directly related to subsequent postnatal growth retardation.postnatal growth retardation , preterm infants Background : The bone mineral content of premature infants at term is lower than in mature infants at the same postconceptional age . Serum alkaline phosphatase and serum phosphate are often used as indicators of bone mineralisation . Objective : To analyse the association between bone mineral content and serum alkaline phosphatase and serum phosphate . Methods :  Serum alkaline phosphatase and phosphate were measured at weekly intervals during admission in 108 premature infants of gestational age below 32 weeks ( mean ( SD ) gestational age 29 ( 2 ) weeks ; mean ( SD ) birth weight 1129 ( 279 ) g ) .  Bone mineral content was measured at term ( mean gestational age 41 weeks ) by dual energy x ray absorptiometry and corrected for body size . Results : Serum alkaline phosphatase was significantly negatively associated with serum phosphate ( p < 0.001 ) . Bone mineral content was not associated with mean serum alkaline phosphatase ( p = 0.8 ) , peak serum alkaline phosphatase ( p = 0.5 ) , or mean serum phosphate ( p = 0.2 ) at term . Conclusion : Routine measurements of  serum alkaline phosphatase and serum phosphate  are of no use in predicting bone mineralisation outcome in premature infants The objective of this investigation was to describe zinc status to 12 months corrected age in premature infants fed their mother 's milk in relation to nutritional management in hospital and post-hospital discharge . Twenty-five premature infants fed their mother 's milk in hospital were r and omized to receive either a multi-nutrient fortifier ( MNF ) , providing protein , calcium , phosphorus and zinc ( MM + MNF ) or calcium and phosphorus alone ( MM + CaGP ) .  Twelve preterm infants fed a preterm formula ( PTF ) served as a comparison group . At 35 weeks post-menstrual age zinc retention was determined using the stable isotope tracer 70Zn . After hospital discharge infants in MM + MNF and MM + CaGP were design ated to a mother 's milk-feeding group to 6 months corrected age ( Post-MM ) or formula feeding group ( Post-FF ) based on parental choice of feeding practice . Anthropometry was performed at term , three , 6 and 12 months corrected age . At 6 and 12 months corrected age a hair sample was obtained to determine hair zinc concentrations . Preterm infants receiving supplemental zinc in hospital , as MNF , had significantly greater zinc retention in hospital compared to MM + CaGP but not greater hair zinc concentrations at 6 or 12 months corrected age . Despite significantly lower zinc intakes to 6 months corrected age , Post-MM had significantly greater hair zinc concentrations at 6 months compared to PTF ( median[25 - 75th percentile ] : 146[106 - 190 ] versus 85[54 - 91 ] microg/g , P < 0.05 ) . Hair zinc in Post-FF ( 124[77 - 163 ] microg/g ) was lower than Post-MM , but this was not significant ( P = 0.09 ) . Only in Post-MM were hair zinc concentrations above the median of reference values from term born infants at 12 months corrected age . Mean values of weight , length and head circumference of the preterm infants in Post-MM , Post-FF and PTF groups were between the 3rd and 97th percentiles derived from WHO reference growth st and ards for mother 's milk-fed term infants . Our findings suggest that supplemental zinc either in hospital or post-hospital discharge does not appear to be required for preterm infants fed their mother 's milk
BACKGROUND Exclusively breast milk-fed preterm infants may accumulate nutrient deficits leading to extrauterine growth restriction .
Feeding preterm infants with multi-nutrient fortified human breast milk rather than unfortified breast milk may increase nutrient accretion and growth rates and may improve neurodevelopmental outcomes .
OBJECTIVES To determine whether multi-nutrient fortified human breast milk improves important outcomes ( including growth and development ) over unfortified breast milk for preterm infants without increasing the risk of adverse effects ( such as feed intolerance and necrotising enterocolitis ) .