Effect of two doses of docosahexaenoic acid (DHA) in the diet of preterm infants on infant fatty acid status: results from the DINO trial. Effects of Bifidobacterium lactis Bb12 Supplementation on Body Weight, Fecal pH, Acetate, Lactate, Calprotectin, and IgA in Preterm Infants Lower Incidence of Necrotizing Enterocolitis in Infants Fed a Preterm Formula with Egg Phospholipids First year growth of preterm infants fed standard compared to marine oil n−3 supplemented formula Higher dose of docosahexaenoic acid in the neonatal period improves visual acuity of preterm infants: results of a randomized controlled trial. Visual-acuity development in healthy preterm infants: effect of marine-oil supplementation. Effect of long-chain n-3 fatty acid supplementation on visual acuity and growth of preterm infants with and without bronchopulmonary dysplasia. Effects of Bifidobacterium lactis Bb12 Supplementation on Intestinal Microbiota of Preterm Infants: a Double-Blind, Placebo-Controlled, Randomized Study Evaluation of a long-chain polyunsaturated fatty acid supplemented formula on growth, tolerance, and plasma lipids in preterm infants up to 48 weeks postconceptional age. The effect of supplementation of docosahexaenoic acid and arachidonic acid on visual acuity and neurodevelopment in larger preterm infants. Effect of Bifidobacterium lactis on the Incidence of Nosocomial Infections in Very-Low-Birth-Weight Infants: A Randomized Controlled Trial Dietary supplementation of long‐chain polyunsaturated fatty acids in preterm infants: effects on cerebral maturation Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial. Enteral feeding of premature infants with Lactobacillus GG. Supplementation of a bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants Effects of feeding premature infants with Lactobacillus GG on gut fermentation. The effect of a bifidobacter supplemented bovine milk on intestinal permeability of preterm infants. Growth and development of preterm infants fed infant formulas containing docosahexaenoic acid and arachidonic acid. The effect of a fructo-oligosaccharide supplemented formula on gut flora of preterm infants. Lack of effect of Lactobacillus on gastrointestinal bacterial colonization in premature infants Probiotics Feeding in Prevention of Urinary Tract Infection, Bacterial Sepsis and Necrotizing Enterocolitis in Preterm Infants Effects of probiotic and prebiotic on gastrointestinal motility in newborns. Prebiotic oligosaccharides reduce stool viscosity and accelerate gastrointestinal transport in preterm infants. Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study. Influence of feeding artificial-formula milks containing docosahexaenoic and arachidonic acids on the postnatal long-chain polyunsaturated fatty acid status of healthy preterm infants. Lack of effects of oral probiotics on growth and neurodevelopmental outcomes in preterm very low birth weight infants. Oral supplementation with probiotics in very-low-birth-weight preterm infants: a randomized, double-blind, placebo-controlled trial. Randomized, double-blind trial of long-chain polyunsaturated fatty acid supplementation with fish oil and borage oil in preterm infants. Prebiotics Improve Gastric Motility and Gastric Electrical Activity in Preterm Newborns A Randomized Placebo-controlled Comparison of 2 Prebiotic/Probiotic Combinations in Preterm Infants: Impact on Weight Gain, Intestinal Microbiota, and Fecal Short-chain Fatty Acids Neurodevelopmental outcomes of preterm infants fed high-dose docosahexaenoic acid: a randomized controlled trial. The effects of probiotics on feeding tolerance, bowel habits, and gastrointestinal motility in preterm newborns. Improved Cognitive Development Among Preterm Infants Attributable to Early Supplementation of Human Milk With Docosahexaenoic Acid and Arachidonic Acid
Formula supplemented with docosahexaenoic acid ( DHA ) improves retinal function of preterm infants but the optimal dose is unknown . In a r and omized controlled trial we examined the effect of increasing the DHA concentration of human milk and formula on circulating fatty acids of preterm infants . Infants born <33 weeks gestation were fed high-DHA milk ( 1 % total fat as DHA ) or st and ard-DHA milk ( 0.2 - 0.3 % DHA ) until reaching their estimated due date ( EDD ) . Milk arachidonic acid ( AA ) concentration was approximately 0.5 % for both groups . At EDD , erythrocyte membrane phospholipid DHA was elevated in the high-DHA group compared with st and ard-DHA ( mean+/-SD , high-DHA 6.8+/-1.2 , st and ard-DHA 5.2+/-0.7 , p<0.0005 ) but AA was lower ( high-DHA 14.9+/-1.3 , st and ard-DHA 16.0+/-1.2 , p<0.0005 ) . Feeding preterm infants human milk and formula with 1 % DHA raises but does not saturate erythrocyte phospholipids with DHA . Milk exceeding 1 % DHA may be required to increase DHA status to levels seen in term infants Preterm infants are prone to abnormal bacterial colonization of the intestine with ensuing adverse health effects . To examine whether the oral application of Bifidobacterium lactis Bb12 ( probiotic ) may improve selected indicators of health status in preterm infants , a double blind , placebo controlled r and omized clinical study was performed on 69 preterm infants ( < 37 gestation wk ) .  Weight gain was defined as the primary outcome measure . In antibiotic-treated infants , probiotic supplementation result ed in a higher body weight compared with placebo ( p < 0.001 ) . In the probiotic group , the fecal pH was significantly lower than in the placebo group . The fecal concentrations of acetate and lactate were 42 and 38 % higher , respectively , in the probiotic group than in the placebo group . Fecal calprotectin was lower in the probiotic group ( p = 0.041 ) , while fecal IgA was higher in this group compared with the placebo group ( p = 0.021 ) Necrotizing enterocolitis ( NEC ) causes approximately 4000 deaths/y and significant morbidity among U.S.-born preterm infants alone . Various combinations of inadequate tissue oxygenation , bacterial overgrowth , and enteral feeding with immaturity may cause the initial damage to intestinal mucosa that culminates in necrosis . Presently , there is not a way to predict the onset of the disease or to prevent its occurrence . As part of risk-benefit assessment , we compared disease in hospitalized preterm infants fed a commercial ( control ) preterm formula or an experimental formula with egg phospholipids  for a r and omized , double-masked , clinical study of diet and infant neurodevelopment . Infants fed the experimental formula developed significantly less stage II and III NEC compared with infants fed the control formula ( 2.9 versus 17.6 % , p < 0.05 ) , but had similar rates of bronchopulmonary dysplasia ( 23.4 versus 23.5 % ) , septicemia ( 26 versus 31 % ) , and retinopathy of prematurity ( 38 versus 40 % ) . Compared with the control formula , the experimental formula provided 7-fold more esterified choline , arachidonic acid ( AA , 0.4 % of total fatty acids ) , and docosahexaenoic acid ( 0.13 % ) . Phospholipids are constituents of mucosal membranes and intestinal surfactant , and their components , AA and choline , are substrates for intestinal vasodilatory and cytoprotective eicosanoids ( AA ) and the vasodilatory neurotransmitter , acetylcholine ( choline ) , respectively . One or more of these components of egg phospholipids may have enhanced one or more immature intestinal functions to lower the incidence of NEC in this study . Regardless of the potential mechanism , a larger r and omized trial design ed to test the effect of this egg phospholipid-containing formula on NEC seems warranted Very low birth weight ( VLBW ) infants ( 748–1390 g , n=65 ) were r and omly assigned to receive control or marine oil-supplemented formula when they achieved intakes > 454 kJ ( 110 kcal)/kg/d of a formula design ed for VLBW infants . Study formulas with or without marine oil were provided until 79 wk of postconceptional age ( PCA ) , first in a formula design ed for preterm infants followed by a formula design ed for term infants . Infants were studied at regular intervals through 92 wk PCA . Weight , length , and head circumference were determined by st and ardized prodedures and normalized to the National Center for Health Statistics figures for growth of infants born at term of the same age and gender . Mean normalized weight , weight-to-length , and head circumference were greatest at 48 wk and decreased thereafter . The decline in normalized weight was greater in infants fed the marine oil-supplemented formula . Beginning at 40 wk , marine oil-supplemented infants compared to controls had significantly poorer Z-scores for weight , length and head circumference . In addition , birth order ( negatively ) and maternal height ( positively ) influenced weight and length achievement in infancy as shown previously in infants born at term BACKGROUND Preterm infants have improved visual outcomes when fed a formula containing 0.2 - 0.4 % docosahexaenoic acid ( DHA ) compared with infants fed no DHA , but the optimal DHA dose is unknown . OBJECTIVE We assessed visual responses of preterm infants fed human milk ( HM ) and formula with a DHA concentration estimated to match the intrauterine accretion rate ( high-DHA group ) compared with infants fed HM and formula containing DHA at current concentrations . DESIGN A double-blind r and omized controlled trial studied preterm infants born at <33 wk gestation and fed HM or formula containing 1 % DHA ( high-DHA group ) or approximately 0.3 % DHA ( current practice ; control group ) until reaching their estimated due date ( EDD ) . Both groups received the same concentration of arachidonic acid . Sweep visual evoked potential ( VEP ) acuity and latency were assessed at 2 and 4 mo corrected age ( CA ) . Weight , length , and head circumference were assessed at EDD and at 2 and 4 mo CA . RESULTS At 2 mo CA , acuity of the high-DHA group did not differ from the control group [ high-DHA group ( x + /- SD ) : 5.6 + /- 2.4 cycles per degree ( cpd ) , n = 54 ; control group : 5.6 + /- 2.4 cpd , n = 61 ; P = 0.96 ] . By 4 mo CA , the high-DHA group exhibited an acuity that was 1.4 cpd higher than the control group ( high-DHA : 9.6 + /- 3.7 cpd , n = 44 ; control : 8.2 + /- 1.8 cpd ; n = 51 ; P = 0.025 ) . VEP latencies and anthropometric measurements were not different between the high-DHA and control groups . CONCLUSION The DHA requirement of preterm infants may be higher than currently provided by preterm formula or HM of Australian women Docosahexaenoic acid ( DHA ; 22:6n-3 ) is important for normal visual development . We hypothesized that preterm infants fed formulas with marine oil as a source of DHA  would have better visual acuity than infants fed formulas without marine oil  , as measured by the Teller Acuity Card procedure . Marine oil ( P < 0.001 ) and age ( P < 0.0001 ) influenced visual acuity , by repeated- measures analysis of variance ( ANOVA ) corrected for the effect of subject . Marine-oil-supplemented infants had better visual acuity than those fed st and ard formulas at 2 and 4 mo of age , by Fishers ' least-squares difference ( LSD ) . Acuity of both dietary groups improved through 6.5 mo of age , then plateaued . Through 4 mo of age , acuity was inversely related to oxygen supplementation ( log10 h ) and positively related to DHA status , by general-linear-models ( GLM ) analysis . After 4 mo of age , birth weight and gestational age were the only variables consistently related to visual acuity by GLM . We conclude that marine-oil-supplemented formula improved visual acuity of preterm infants through 4 mo of age by improving DHA status Healthy preterm infants fed formula with long-chain n-3 fatty acids ( n-3 LCFAs ) from marine oil have better early visual acuity but lower plasma phosphatidylcholine ( PC ) arachidonic acid ( AA ) and growth than infants fed formula containing  linolenic acid ( LLA ) as the sole n-3 fatty acid . This r and omized , double-blind trial was design ed to study the effects of a different source of n-3 LCFAs and a shorter feeding interval on visual acuity ( by Teller Acuity Card ) and growth of preterm infants ( n = 59 ; 747 - 1275 g birth wt ) , some of whom required long periods of supplemental oxygen and developed bronchopulmonary dysplasia ( BPD ) . Infants were studied at 0 , 2 , 4 , 6 , 9 , and 12 mo past term . Plasma PC AA , and normalized weight , length , and head circumference were not influenced by BPD or n-3 LCFAs except that n-3 LCFA-supplemented infants weighed less at 6 ( P<0.05 ) and 9 ( P<0.01 ) mo and had smaller head circumferences at 9 mo ( P<0.05 ) . Compared with control infants , however , those fed n-3 LCFAs had lower weight-for-length at 2 , 6 , 9 , and 12 mo ( P<0.0003 , P<0.0114 , P<0.0008 , and P<0.006 , respectively ) . n-3 LCFAs  improved early ( 2-mo ) but not later acuity among infants without BPD ( P<0.02 ) . Regardless of diet , infants with BPD had poorer grating acuity at 2 ( P<0.0002 ) and 4 ( P<0.04 ) mo but not thereafter ABSTRACT The gastrointestinal microbiota of preterm infants in a neonatal intensive care unit differs from that of term infants . In particular , the colonization of preterm infants by bifidobacteria is delayed . A double-blind , placebo-controlled , r and omized clinical study was performed on 69 preterm infants to investigate the role of Bifidobacterium lactis Bb12 supplementation in modifying the gut microbiota . Both culture-dependent and culture-independent approaches were used to study the gut microbiota . Bifidobacterial numbers , determined by fluorescence in situ hybridization , were significantly higher in the probiotic than in the placebo group ( log10 values per g of fecal wet weight : probiotic , 8.18 + 0.54 [ st and ard error of the mean ] ; placebo , 4.82 + 0.51 ; P < 0.001 ) . A similar trend for bifidobacterial numbers was also obtained with the culture-dependent method . The infants supplemented with Bb12 also had lower viable counts of Enterobacteriaceae ( log10 values of CFU per g of fecal wet weight : probiotic , 7.80 + 0.34 ; placebo , 9.03 + 0.35 ; P = 0.015 ) and Clostridium spp . ( probiotic , 4.89 + 0.30 ; placebo , 5.99 + 0.32 ; P = 0.014 ) than the infants in the placebo group . Supplementation of B. lactis Bb12 did not reduce the colonization by antibiotic-resistant organisms in the study population . However , the probiotic supplementation increased the cell counts of bifidobacteria and reduced the cell counts of enterobacteria and clostridia BACKGROUND The last trimester of pregnancy is a period of rapid accretion of long-chain polyunsaturated fatty acids , both in the central nervous system and the body as a whole . Human milk contains these fatty acids , whereas some preterm infant formulas do not . Infants fed formulas without these fatty acids have lower plasma and erythrocyte concentrations than infants fed human milk . Pre clinical and clinical studies have demonstrated that single-cell sources ( algal and fungal ) of long-chain polyunsaturated fatty acids are bioavailable . A balanced addition of fatty acids from these oils to preterm formula results in blood fatty acid concentrations in low birth weight infants comparable to those of infants fed human milk . METHODS In the present study the growth , acceptance ( overall incidence of discontinuation , reasons for discontinuation , overall incidence and type of individual adverse events ) , and plasma fatty acid concentrations were compared in three groups of infants fed a long-chain polyunsaturated fatty acid-supplemented preterm infant formula , an unsupplemented control formula , or human milk .  The study was prospect i ve , double-blind ( formula groups only ) , and r and omized ( formula groups only ) . Two hundred eighty-eight infants were enrolled ( supplemented formula group , n = 77 ; control formula group , n = 78 ; human milk group , n = 133 ) . RESULTS Anthropometric measurements at enrollment , at first day of full oral feeding , and at both 40 and 48 weeks postconceptional age did not differ between the formula groups , whereas the human milk-fed group initially grew at a lower rate . The incidence of severe adverse events was rare and not significantly different between formula groups . The groups fed either human milk or supplemented formula had long-chain polyunsaturated fatty acid concentrations higher than those in the control formula group . CONCLUSIONS The results of this study demonstrate the safety and efficacy of a preterm formula supplemented with long-chain polyunsaturated fatty acids from single-cell oils BACKGROUND Preterm infants may be born with deficits of both docosahexaenoic acid ( DHA ) and arachidonic acid ( AA ) , but studies on supplementation of DHA and AA for preterm infants are limited . METHODS Preterm infants with a gestational age between 30 and 37 weeks who met all the inclusion criteria were enrolled in this double blind , r and omized , comparative study . Infants over 2000 g body weight , over 32 weeks of gestation and in full feeding status would enter into the active intervention period of 6 months . Sixteen infants received Neoangelac Plus with AA and DHA supplementation .  Eleven infants received Neoangelac without AA and DHA supplementation . The babies had scheduled physical examinations and their cognitive development , visual acuity , and vital signs to be checked . Adverse events were also recorded . RESULTS The mean Mental Development Index ( MDI ) scores for the supplementation and non-supplementation groups were 96.1 + /- 8.6 and 91.7 + /- 10.4 respectively at 6 months and 98.7 + /- 8.0 and 90.5 + /- 6.9 respectively at 1 year . The mean Physical Development Index ( PDI ) scores of these two groups were 102.2 + /- 10.5 and 95.4 + /- 13.2 respectively at 6 months and 98.0 + /- 5.8 and 86.7 + /- 11.1 respectively at 1 year . By repeated measures ANOVA , significant differences existed between groups for MDI and PDI ( p = 0.020 and 0.008 ) . However , there were no differences in visual acuity , physical examination variables or vital signs between these two groups . No obvious adverse effects were observed during the study period . CONCLUSION These results showed possible benefits in the neurodevelopment of larger preterm infants given formula supplemented with DHA and AA Background : Nosocomial infections endanger preterm infants . Objective : The aim of the present controlled r and omized trial was to investigate whether Bifidobacterium lactis reduces the incidence of nosocomial infections in infants with very low birth weight ( VLBW ; < 1,500 g ) < 30 weeks of gestation . Patients and Methods : In a r and omized controlled trial , 183 VLBW infants < 30 weeks of gestation were stratified according to gestational age ( 23–26 and 27–29 weeks ) and early antibiotic therapy ( days 1–3 , yes or no ) and r and omly assigned to have their milk feedings supplemented with B. lactis ( 6 × 2.0 × 109 CFU/kg/day , 12 billion CFU/kg/day ) or placebo for the first 6 weeks of life . Primary outcome was the ‘ incidence density ’ of nosocomial infections defined as periods of elevated C-reactive protein ( > 10 mg/l ) from day 7 after initiation of milk feedings until the 42nd day of life ( number of nosocomial infections/total number of patient days ) . The main secondary outcome was necrotizing enterocolitis ( NEC ; ≧stage 2 ) . Results : There were 93 infants in the B. lactis group and 90 in the placebo group . There was no significant difference between the two groups with regard to the incidence density of nosocomial infections ( 0.021 vs. 0.016 ; p = 0.9 , χ2 test ) . There were 2 cases of NEC in the B. lactis group and 4 in the placebo group . None of the blood cultures grew B. lactis . Conclusion : In the present setting , B. lactis at a dosage of 6 × 2.0 × 109 CFU/kg/day ( 12 billion CFU/kg/day ) did not reduce the incidence density of nosocomial infections in VLBW infants . No adverse effect of B. lactis was observed Aim : To study the influence of dietary‐supplied long‐chain polyunsaturated fatty acids on structural brain maturation in preterm infants and to investigate parameters of functional brain development , relating them to structural maturation . Other studies have suggested that dietary supplementation of long‐chain polyunsaturated fatty acids in preterm infants may enhance their visual development . The influence on structural brain development has never been evaluated . Methods : In a prospect i ve , double‐blind study , 42 formula‐fed premature infants were r and omized to be fed either a st and ard preterm formula without long‐chain polyunsaturated fatty acids or an identical formula supplemented with docosahexaenoic acid ( 0.015 g/100 ml ) and arachidonic acid ( 0.031 g/100ml ) . Infants with significant cerebral damage , retinopathy , chronic disease or feeding problems were excluded . Follow‐up was focused on assessment of cerebral myelination by MRI . Psychomotor , mental and visual development was analysed and flash‐visual evoked potentials were recorded . Results : It was found that progress of myelination , mental and motor development and latencies of visual evoked potentials were not positively influenced by supplementation of long‐chain polyunsaturated fatty acids . At each test age , visual acuity was slightly better in the supplemented infants than in the non‐supplemented infants , but the difference never reached significance OBJECTIVES A r and omized , masked , controlled trial was conducted to assess effects of supplementing premature infant formulas with oils containing the long-chain polyunsaturated fatty acids , arachidonic acid ( AA ; 20:4 n6 ) , and docosahexaenoic acid ( DHA ; 22:6 n3 ) on growth , visual acuity , and multiple indices of development . METHODS Infants ( N = 470 ) with birth weights 750 to 1800 g were assigned within 72 hours of the first enteral feeding to 1 of 3 formula groups with or without long-chain polyunsaturated fatty acids : 1 ) control ( N = 144 ) , 2 ) AA+DHA from fish/fungal oil ( N = 140 ) , and 3 ) AA+DHA from egg-derived triglyceride (egg-TG)/fish oil ( N = 143 ) .  Infants were fed human milk and /or Similac Special Care with or without 0.42 % AA and 0.26 % DHA to term corrected age ( CA ) , then fed human milk or NeoSure with or without 0.42 % AA and 0.16 % DHA to 12 months ' CA . Infants fed exclusively human milk to term CA ( EHM-T ; N = 43 ) served as a reference . RESULTS Visual acuity measured by acuity cards at 2 , 4 , and 6 months ' CA was not different among groups . Visual acuity measured by swept-parameter visual-evoked potentials in a subgroup from 3 sites ( 45 control , 50 AA+DHA [ fish/fungal ] ; 39 AA+DHA [ egg-TG/fish ] ; and 23 EHM-T ) was better in both the AA+DHA ( fish/fungal ; least square [ LS ] means [ cycle/degree ] + /- st and ard error [ SE ; octaves ] 11.4 + /- 0.1 ) and AA+DHA ( egg-TG/fish ; 12.5 + /- 0.1 ) than control ( 8.4 + /- 0.1 ) and closer to that of the EHM-T group ( 16.0 + /- 0.2 ) at 6 months ' CA . Visual acuity improved from 4 to 6 months ' CA in all but the control group . Scores on the Fagan test of novelty preference were greater in AA+DHA ( egg-TG/fish ; LS means + /- SE , 59.4 + /- 7.7 ) than AA+DHA ( fish/fungal ; 57.0 + /- 7.5 ) and control ( 57.5 + /- 7.4 ) at 6 months ' CA , but not at 9 months ' CA . There were no differences in the Bayley Mental Development Index at 12 months ' CA . However , the Bayley motor development index was higher for AA+DHA ( fish/fungal ; LS means + /- SE , 90.6 + /- 4.4 ) than control ( 81.8 + /- 4.3 ) for infants < /=1250 g. When Spanish-speaking infants and twins were excluded from the analyses , the MacArthur Communicative Development Inventory revealed that control infants ( LS means + /- SE , 94.1 + /- 2.9 ) had lower vocabulary comprehension at 14 months ' CA than AA+DHA ( fish/fungal ) infants ( 100.6 + /- 2.9 ) or AA+DHA ( egg-TG/fish ) infants ( 102.2 + /- 2.8 ) . There were no consistent differences in weight , length , head circumference , or anthropometric gains . CONCLUSION These results showed a benefit of supplementing formulas for premature infants with AA and DHA from either a fish/fungal or an egg-TG/fish source from the time of first enteral feeding to 12 months ' CA The objectives of this study were to determine whether or not the probiotic Lactobacillus GG can colonise the immature bowel of premature infants and if so , does colonisation result in a reduction of the size of the bowel reservoir of nosocomial pathogens such as enterobacteriaceae , enterococci , yeasts or staphylococci , and does colonisation with Lactobacillus GG have any effect on the clinical progress and outcome . Twenty preterm infants with a gestational age of 33 weeks or less who were resident on a neonatal unit were studied from the initiation of milk feeds until discharge . The infants were r and omised to receive either milk feeds or milk feeds supplemented with Lactobacillus GG 10(8 ) colony forming units twice a day for two weeks . The clinical features of the two groups of infants were similar . Orally administered Lactobacillus GG was well tolerated and did colonise the bowel of premature infants . However , colonisation with Lactobacillus GG did not reduce the faecal reservoir of potential pathogens and there was no evidence that colonisation had any positive clinical benefit for this particular group of infants Background : The establishment of a balanced intestinal microflora which may protect against infection is desirable for the preterm infant . Objective : To investigate the effect of a preterm formula milk supplement consisting of oligosaccharides in similar proportions to human milk on the faecal flora and stool characteristics of preterm infants . Study design : To resemble the effect of human milk , an oligosaccharide mixture consisting of 90 % galacto-oligosaccharides and 10 % fructo-oligosaccharides was used to supplement a st and ard preterm formula at a concentration of 10 g/l . This supplemented formula was studied in 15 preterm infants , and the results were compared with those found in 15 infants fed a formula supplemented with maltodextrin as placebo .  A group fed fortified mother 's milk  was investigated as a reference group ( n = 12 ) . On four days during a 28 day feeding period ( 1 , 7 , 14 , and 28 ) , the faecal flora was investigated , and stool characteristics , growth , and possible side effects were recorded . Results : During the study period , the number of bifidobacteria in the group fed the oligosaccharide supplemented formula increased to the upper range of bifidobacteria counts in the reference group . The difference between the supplemented and non-supplemented groups was highly significant ( p = 0.0008 ) . The stool characteristics were also influenced by the supplement : the stool frequency after 28 days was significantly lower in the control group than in the oligosaccharide supplemented group ( p = 0.0079 ) and the reference group ( p < 0.0001 ) . Over the study period , the stool consistency in the control group became harder , but remained fairly stable in the other two groups . There was no effect of the different diets on the incidence of side effects ( crying , regurgitation , vomiting ) or on weight gain or length gain . Conclusion : Supplementing preterm formula with a mixture of galacto- and fructo-oligosaccharides at a concentration of 10 g/l stimulates the growth of bifidobacteria in the intestine and results in stool characteristics similar to those found in preterm infants fed human milk . Therefore prebiotic mixtures such as the one studied may help to improve intestinal tolerance to enteral feeding in preterm infants The study aim ed to find out whether gut colonisation of premature babies with a probiotic , Lactobacillus GG , modified enteric carbohydrate fermentation . Twenty preterm infants were r and omised to receive Lactobacillus GG 10(8 ) colony forming units twice a day for two weeks or to a control group . Faecal short chain fatty acids ( SCFAs ) , ethanol , and urinary 2,3-butanediol , were measured in parallel with microbiological studies . Lactobacillus GG colonised nine babies . From 1 - 28 days of age faecal SCFAs did not differ significantly from controls . Median and ranges were ( treated and controls , respectively ) : acetic acid : 173 ( trace-799 ) , 166 ( trace-700 ) ; propionic acid : 44 ( trace-169 ) , 37 ( 11 - 229 ) ; butyric acid : 31 ( 5 - 107 ) , 37 ( 2 - 118 ) mumol/g dry weight . Ethanol was detected in more faecal sample s from treated babies ( 65 % v 37 % ) , and at higher concentration ( 6.3 ( trace-40 ) v 3.3 ( 0.6 - 8.8 ; one 229 ) mumol/g ) . 2,3-Butanediol was found in 66 % of urine sample s from treated babies and 58 % from controls . On 83 % of these occasions Klebsiella sp , Enterobacter sp , or Serratia sp were cultured from faeces . Lactobacillus GG had no obvious adverse effects on nutritionally important SCFAs . The small increase in ethanol excretion is unlikely to have clinical significance BACKGROUND Preterm infants have increased intestinal permeability which can render them susceptible to infections from enterobacteriae . OBJECTIVES The primary objective was to investigate whether probiotic administration to preterm infants decreases intestinal permeability . Secondary outcomes studied were : somatic growth , tolerance , rates of sepsis and necrotizing enterocolitis . METHODS In a prospect i ve r and omized case-control study 41 stable preterm infants of 27 to 36 weeks gestation and 34 matched comparison infants consecutively admitted to the neonatal unit were studied . The study group received a preterm formula supplemented with Bifidobacter lactis ( 2 x 10(7 ) cfu/g of dry milk ) while the control group received the same formula but without supplementation .  Intestinal permeability was measured within two days of birth and then seven and thirty days later using the sugar absorption test . Additionally anthropometric parameters were recorded throughout the study as well as acceptance and tolerance of the formula . RESULTS All infants tolerated the study formula well . Median counts of stool bifidobacteria and lactulose/mannitol ratios at baseline were comparable . After 7 days of supplementation median bifidobacteria counts were significantly higher in the study group than in the control group ( p=0.0356 ) and they remained higher to the end of the study ( p at day 30=0.075 ) . The L/M ratio in the study group was significantly lower at day 30 of the study as compared to the control group ( p=0.003 ) . Head growth was significantly higher in the study group ( p=0.001 ) . CONCLUSIONS The administration of a bifidobacter supplemented infant formula decreases intestinal permeability of preterm infants and leads to increased head growth OBJECTIVES To evaluate safety and benefits of feeding preterm infants formulas containing docosahexaenoic acid ( DHA ) and arachidonic acid ( ARA )  until 92 weeks postmenstrual age ( PMA ) , with follow-up to 118 weeks PMA . STUDY DESIGN This double-blinded study of 361 preterm infants r and omized across three formula groups : ( 1 ) control , no supplementation ; ( 2 ) algal-DHA ( DHA from algal oil , ARA from fungal oil ) ; and ( 3 ) fish-DHA ( DHA from fish oil , ARA from fungal oil ) . Term infants breast-fed > or = 4 months ( n = 105 ) were a reference group . Outcomes included growth , tolerance , adverse events , and Bayley development scores . RESULTS Weight of the algal-DHA group was significantly greater than the control group from 66 to 118 weeks PMA and the fish-DHA group at 118 weeks PMA but did not differ from term infants at 118 weeks PMA . The algal-DHA group was significantly longer than the control group at 48 , 79 , and 92 weeks PMA and the fish-DHA group at 57 , 79 , and 92 weeks PMA but did not differ from term infants from 79 to 118 weeks PMA . Supplemented groups had higher Bayley mental and psychomotor development scores at 118 weeks PMA than did the control group . Supplementation did not increase morbidity or adverse events . CONCLUSIONS Feeding formulas with DHA and ARA from algal and fungal oils result ed in enhanced growth . Both supplemented formulas provided better developmental outcomes than unsupplemented formulas AIM The intestinal flora of breast-fed infants is generally dominated by bifidobacteria which have beneficial properties . Their presence is due to various components of breast milk , including prebiotic substances . This prospect i ve double-blind study compared the numbers of bifidobacteria in the stool flora of bottle-fed preterm infants r and omized to receive for 14 days either a formula with prebiotic fructo-oligosaccharides at a concentration of 0.4 g/dL or the same formula with maltodextrin as a placebo . METHODS Within 0 - 14 days after birth , 56 healthy bottle-fed infants were enrolled to receive either the prebiotic or placebo . Faecal sample s were taken at inclusion day and at study day 7 . The number of bifidobacteria in the stools , stool characteristics and somatic growth were recorded during the study . RESULTS In the group fed fructo-oligosaccharides , both the numbers of bifidobacteria in the stools and the proportion of infants colonized with them were significantly higher as compared to the placebo group ( p=0.032 and p=0.030 respectively ) . There was also a higher number of bacteroids in the fructo-oligosaccharide group as compared to the placebo ( p=0.029 ) . At the same time , reduction was noted in the numbers of Escherichia coli and enterococci . ( p=0.029 , and p=0.025 , respectively ) . Supplementation had also significant influence on stool frequency per day ( p=0.0080 ) . CONCLUSION An infant formula containing a small quantity of prebiotic oligosaccharides is well accepted and leads to rapid growth of bifidobacteria in the gut of bottle-fed preterm infants while decreasing the numbers of pathogenic microorganisms Studies were carried out on premature infants in the neonatal intensive care unit to determine the effect of feeding of lactobacilli on colonization of the gastrointestinal tract by antibiotic-resistant gram-negative enteric organisms . Thirty premature infants were matched by birth weight and gestational age , r and omized and fed double blind either lactobacilli-containing formula or non-lactobacilli-containing formula within 72 hours of delivery . The two study groups were screened weekly by culture for stool lactobacilli , for gram-negative bacteria and for antibiotic resistance of these bacteria .  Lactobacilli  were cultured from the stools of 13 of 15 patients receiving lactobacilli and from 3 of 15 patients not receiving lactobacilli ( P < 0.001 ) . Gram-negative enteric organisms were isolated during 40 of the 86 weeks ( 47 % ) of hospitalization for patients receiving lactobacilli and during 28 of 57 weeks ( 49 % ) for patients not receiving lactobacilli . There was no significant difference between the study groups in the number of resistant organisms or in the proportion of resistant organisms per gram-negative enteric isolates ( 4 of 40 vs. 0 of 28 ) . These results suggest that facultative gram-negative enteric bacterial colonization , with either total or aminoglycoside-resistant strains , is not decreased by oral feedings of Lactobacillus acidophilus in premature infants Background : It has been suggested that probiotics can reduce the overgrowth of pathogens in the bowels of preterm infants and contribute to the reduction of the incidence of nosocomial infections in neonatal intensive care units ( NICUs ) . The purpose of this study was to evaluate the effectiveness of Lactobacillus GG supplementation in reducing the incidence of urinary tract infections ( UTIs ) , bacterial sepsis and necrotizing enterocolitis ( NEC ) in preterm infants . Methods : A double-blind study was conducted in 12 Italian NICUs . Newborn infants with a gestational age <33 weeks or birthweight < 1,500 g were r and omized to receive st and ard milk feed supplemented with Lactobacillus GG ( Dicoflor ® , Dicofarm , Rome , Italy ) in a dose of 6 × 109 colony-forming units ( cfu ) once a day until discharge , starting with the first feed or placebo . Results : Five hundred eighty-five patients were studied . The probiotics group ( n = 295 ) and the placebo group ( n = 290 ) exhibited similar clinical characteristics . The duration  of Lactobacillus GG and placebo supplementation was 47.3 ± 26.0 and 48.2 ± 24.3 days , respectively . Although UTIs ( 3.4 vs. 5.8 % ) and NEC ( 1.4 vs. 2.7 % ) were found less frequently in the probiotic group compared to the control group , these differences were not significant . Bacterial sepsis was more frequent in the probiotics group ( 4.4 % , n = 11 ) than in the placebo group ( 3.8 % , n = 9 ) , but the difference was not significant . Conclusion : Seven days of Lactobacillus GG supplementation starting with the first feed is not effective in reducing the incidence of UTIs , NEC and sepsis in preterm infants . Further studies are required to confirm our results in lower birthweight population To fortify the biological role of milk formula has been suggested to use probiotics and prebiotics as functional components to mimic the effect of breast milk . The aim of this study was to evaluate the effects of prebiotic , probiotic added to a st and ard formula on gastrointestinal motility respect to placebo-formula .  Cutaneous electrogastrography ( EGG ) and ultrasound gastric emptying ( GE ) were performed in 49 preterm newborns . 17 newborns were exclusively breast-fed ; 32 were r and omly assigned to receive prebiotic-added formula ( 0.8 g/dl of a mixture from scGOS and lcFOS , ratio 9:1 ) ( 10 ) , a probiotic-added formula ( L. reuteri at dose of 1x10(8 ) colony forming units ( CFU ) per day ) ( 10 ) , a formula with placebo ( 12 ) for 30 days . No difference was seen in the nutritional parameters and no adverse events were reported . After the intervention period , the prebiotic , probiotic , and breast milk groups showed a higher percentage of EGG slow wave propagation and faster gastric half emptying time respect to placebo group ( ANOVAon ranks p<0.001 ; Dunn test vs control : prebiotic , probiotic and breast-milk vs placebo formula p<0.05 ; and ANOVA on ranks p=0.005 ; Dunn test vs control : prebiotic , probiotic and breast-milk vs placebo formula p<0.05 , respectively ) . Feeding preterm infants with a formula supplemented with prebiotics or probiotics may stimulate gastric emptying and improve maturation of the EGG activity mimicking the effect of breast milk AIM To investigate whether a mixture of prebiotic non-digestible oligosaccharides ( GosFos ; referring to galacto- and fructo-oligosaccharides ) would improve feeding tolerance in preterm infants on full enteral formula feeding . We hypothesized that GosFos would : ( 1 ) reduce stool viscosity and ( 2 ) accelerate gastrointestinal transport . METHODS In a placebo-controlled double-blind trial 20 preterm infants on full enteral nutrition ( gestational age 27 ( 24 - 31 ) weeks , postnatal age 42 ( 11 - 84 ) days , and weight at study entry 1570 ( 1080 - 2300 ) g were r and omly allocated to have their feedings supplemented with either GosFos ( 1 g/100 mL ) or placebo for 14 days . Stool viscosity was measured by high-pressure capillary rheometry . Gastrointestinal transport time was assessed as the time from feeding carmine red to its appearance in the diaper . The hypotheses were tested as a priori ordered hypotheses . Data are shown as median ( range ) . RESULTS Birth weight , gestational age , postnatal age , and weight at study entry did not differ between groups . GosFos significantly reduced both stool viscosity , as measured by extrusion force ( 32 ( 2 - 67 ) versus 158 ( 24 - 314 ) N ) , and gastrointestinal transit time ( 12 ( 4 - 33 ) versus 26 ( 5 - 52 ) h ) . No adverse effects were observed . CONCLUSION Formula supplementation with GosFos reduced stool viscosity and accelerated gastrointestinal transport . Further trials are required to investigate whether GosFos facilitates enteral feeding advancement and early enteral nutrition thereby eventually reducing the incidence of catheter-related nosocomial infections and improving long-term outcome BACKGROUND Colonization by C and ida species is the most important predictor of the development of invasive fungal disease in preterm neonates , and the enteric reservoir is a major site of colonization . We evaluated the effectiveness of an orally supplemented probiotic ( Lactobacillus casei subspecies rhamnosus ; Dicoflor [ Dicofarm spa ] ; 6 x 10(9 ) cfu/day ) in the prevention of gastrointestinal colonization by C and ida species in preterm , very low birth weight ( i.e. , < 1500-g ) neonates during their stay in a neonatal intensive care unit . METHODS Over a 12-month period , a prospect i ve , r and omized , blind , clinical trial that involved 80 preterm neonates with a very low birth weight was conducted in a large tertiary neonatal intensive care unit . During the first 3 days of life , the neonates were r and omly assigned to receive either an oral probiotic added to human ( maternal or pooled donors ' ) milk ( group A ) or human milk alone ( group B ) for 6 weeks or until discharge from the NICU , if the neonate was discharged before 6 weeks . On a weekly basis , specimens obtained from various sites ( i.e. , oropharyngeal , stool , gastric aspirate , and rectal specimens ) were collected from all patients for surveillance culture , to assess the occurrence and intensity of fungal colonization in the gastrointestinal tract . RESULTS The incidence of fungal enteric colonization ( with colonization defined as at least 1 positive culture result for specimens obtained from at least 1 site ) was significantly lower in group A than in group B ( 23.1 % vs. 48.8 % ; relative risk , 0.315 [ 95 % confidence interval , 0.120 - 0.826 ] ; P = .01 ) . The numbers of fungal isolates obtained from each neonate ( P = .005 ) and from each colonized patient ( P = .005 ) were also lower in group A than in group B. L. casei subspecies rhamnosus was more effective in the subgroup of neonates with a birth weight of 1001 - 1500 g. There were no changes in the relative proportions of the different C and ida strains . No adverse effects potentially associated with the probiotic were recorded . CONCLUSIONS Orally administered L. casei subspecies rhamnosus significantly reduces the incidence and the intensity of enteric colonization by C and ida species among very low birth weight neonates In view of the importance of long-chain polyunsaturated fatty acids ( LCP ) for growth and development of fetal and infant neural tissue , the influence of the dietary n-3 and n-6 LCP intake on the LCP status of forty-three preterm infants ( birth weight < 1800 g ) was studied . Thirty-one formula-fed infants were r and omly assigned to receive a conventional formula lacking LCP ( n 16 ) , or an 22:6n-3- and 20:4n-6-enriched formula ( n 15 ) ; twelve infants received their own mother 's breast milk .  Fatty acid compositions of plasma and erythrocyte ( RBC ) phospholipids ( PL ) were determined in umbilical venous blood , in weekly postnatal sample s until day 35 of life and , for the formula-fed infants , at 3 months of corrected age . Both in plasma ( P < 0.001 ) and RBC ( P < 0.01 ) PL , the changes with time until day 35 for 22:6n-3 and 20:4n-6 in the two groups of formula-fed infants were significantly different , with higher values , comparable with those of human-milk-fed infants , in the LCP-enriched-formula group . At 3 months of corrected age , differences between the two formula-fed groups were even more pronounced . In conclusion , adding 22:6n-3 and 20:4n-6 to artificial formulas in balanced ratios and in amounts similar to those found in preterm human milk raises both the 22:6n-3 and the 20:4n-6 status of formulated preterm infants to values found for human-milk-fed preterm infants . Additional studies are necessary to evaluate the potentially favourable effects of this combined addition on the neurodevelopmental outcome of preterm infants OBJECTIVE To evaluate growth and neurodevelopmental outcomes in preterm very low birth weight ( PVLBW ) infants treated with oral probiotics for the prevention of necrotizing enterocolitis ( NEC ) . STUDY DESIGN A prospect i ve follow-up study was performed in a cohort of PVLBW infants enrolled in a single center with a masked r and omized control trial to evaluate the efficacy of oral probiotics in preventing NEC . Growth measures included weight , length , and head circumference . Neurologic and sensory performance was evaluated with st and ard techniques . Psychometric parameters were measured used the Bayley Scales of Infant Development II ( BSID-II ) . The studies were performed at 3 years corrected age . The primary outcome was death or neurodevelopmental impairment . RESULTS Of the 367 subjects enrolled in trial , 301 ( 89.9 % ) were evaluated ( 153 in the probiotics group and 148 in the control group ) . There were no significant differences in growth or in any of the neurodevelopmental and sensory outcomes between the 2 groups . CONCLUSIONS Oral probiotics given to PVLBW infants at 1 week after birth to reduce the incidence of NEC did not affect growth and neurodevelopmental and sensory outcomes at 3 years corrected age BACKGROUND Although recent reports suggest that supplementation with probiotics may enhance intestinal function in premature infants , the mechanisms are unclear , and questions remain regarding the safety and efficacy of probiotics in extremely low-birth-weight infants . OBJECTIVE The objective was to evaluate the efficacy of probiotics on the digestive tolerance to enteral feeding in preterm infants born with a very low or extremely low birth weight . DESIGN In a bicentric , double-blind , r and omized controlled clinical trial that was stratified for center and birth weight , 45 infants received enteral probiotics ( Bifidobacterium longum BB536 and Lactobacillus rhamnosus GG ; BB536-LGG )  and 49 received placebo .  The primary endpoint was the percentage of infants receiving > 50 % of their nutritional needs via enteral feeding on the 14th day of life . A triangular test was used to perform sequential analysis . RESULTS The trial was discontinued after the fourth sequential analysis concluded a lack of effect . The primary endpoint was not significantly different between the probiotic ( 57.8 % ) and placebo ( 57.1 % ) groups ( P = 0.95 ) . However , in infants who weighed > 1000 g , probiotic supplementation was associated with a shortening in the time to reach full enteral feeding ( P = 0.04 ) . Other than colonization by the probiotic strains , no alteration in the composition of intestinal microbiota or changes in the fecal excretion of calprotectin was observed . No colonization by probiotic strains was detected in infants who weighed < or = 1000 g , presumably because of more frequent suspensions of enteral feeding , more courses of antibiotic treatment , or both . CONCLUSIONS Supplementation with BB536-LGG may not improve the gastrointestinal tolerance to enteral feeding in very-low-birth-weight infants but may improve gastrointestinal tolerance in infants weighing > 1000 g. This trial was registered at clinical trials.gov as NCT 00290576 OBJECTIVE To test the efficacy and safety of long-chain polyunsaturated fatty acid ( LCPUFA ) supplementation with gamma-linolenic acid , a precursor of arachidonic acid , and docosahexaenoic acid in preterm infants . STUDY DESIGN Preterm ( < 35 weeks , < or = 2000 g birth weight ) infants ( n=238 ) r and omly assigned to unsupplemented or LCPUFA-supplemented formula to 9 months after term . The main outcome measure was the Bayley Mental and Psychomotor Indexes ( MDI , PDI ) at 18 months after term . Safety outcome measures were anthropometry ( 9 and 18 months ) , feed tolerance , infection , and clinical complications . RESULTS There were no significant differences in neurodevelopment between groups overall . In preplanned subgroup analyses , LCPUFA-supplemented boys had significantly higher Bayley MDI than did control boys ( difference , 5.7 points ; 95 % CI , 0.3 to 11.1 ; P=.04 ) . LCPUFA-supplemented infants showed significantly greater weight gain ( difference , 310 g ; 95 % CI , 30 to 590 g ; P=.03 ) and length gain ( difference , 1.0 cm ; 95 % CI , 0.02 to 1.9 ; P=.05 ) between birth and 9 months , with greater effect in boys ( weight difference at 9 months , 510 g ; 95 % CI , 80 to 930 g ; P=.02 ; length difference at 18 months , 1.8 cm ; 95 % CI , 0.1 to 1.8 ; P=.03 ) . CONCLUSIONS This trial , using the strategy of providing gamma-linolenic acid as a source of arachidonic acid , showed efficacy for growth and for neurodevelopment in boys , with no adverse effects . These data have important implication s for LCPUFA-supplementation strategy in preterm infants The aim of this double-blind , r and omized , placebo-controlled study was to evaluate the effect of a prebiotic mixture on gastric motility in preterm newborns . After a feeding period of 15 days , gastric electrical activity was measured by electrogastrography , and the gastric emptying time was studied by ultrasound technique . No difference was seen in the daily increase of body weight , and no adverse events have been reported . The percentage of time in which propagation was detected in the electrogastrography signal was twice in newborns receiving formula with prebiotics  with respect to placebo , and the gastric half-emptying time was 30 % faster in the prebiotic group than the placebo group . Prebiotic oligosaccharides can modulate the electrical activity and the gastric emptying and may improve the intestinal tolerance of enteral feeding in preterm infants Objective : To compare the effect of 2 prebiotic/probiotic products on weight gain , stool microbiota , and stool short-chain fatty acid ( SCFA ) content of premature infants . Patients and Methods : This r and omized , blinded , placebo-controlled trial included 90 premature infants treated with either a dietary supplement containing 2 lactobacillus species plus fructooligosaccharides ( CUL , Culturelle , ConAgra , Omaha , NE ) , a supplement containing several species of lactobacilli and bifidobacteria plus fructooligosaccharides ( PBP  , ProBioPlus DDS , UAS Laboratories , Eden Prairie , MN ) , or placebo ( a dilute preparation of Pregestamil formula ) twice daily for 28 days or until discharge if earlier . The primary outcome was weight gain . Secondary outcomes were stool bacterial analysis by culture and 16S rDNA quantitative polymerase chain reaction and stool SCFA content measured by high performance liquid chromatography . Results : Both prebiotic/probiotic combinations contained more bacterial species than noted on the label . No significant effect on infant growth of either prebiotic/probiotic supplement was observed . By cultures , 64 % of infants receiving PBP became colonized with bifidobacteria , compared with 18 % of infants receiving CUL and 27 % of infants receiving placebo ( chi-square , P = 0.064 ) . No differences were noted between groups in colonization rates for lactobacilli , Gram-negative enteric bacteria , or staphylococci . By 16S rDNA polymerase chain reaction analysis , the bifidobacteria content in the stools of the infants receiving PBP was higher than in the infants receiving CUL or placebo ( Kruskal-Wallis , P = 0.011 ) . No significant differences in stool SCFA content were detected between groups . No adverse reactions were noted . Conclusions : Infants receiving PBP were more likely to become colonized with bifidobacteria . No significant differences in weight gain or stool SCFA content were detected CONTEXT Uncertainty exists about the benefit of dietary docosahexaenoic acid ( DHA ) on the  neurodevelopment of preterm infants . OBJECTIVE To determine the effect of meeting the estimated DHA requirement of preterm infants on neurodevelopment at 18 months ' corrected age . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind controlled trial enrolling infants born at less than 33 weeks ' gestation from April 2001 to October 2005 at 5 Australian tertiary hospitals , with follow-up to 18 months . INTERVENTION High-DHA ( approximately 1 % total fatty acids ) enteral feeds compared with st and ard DHA ( approximately 0.3 % total fatty acids ) from day 2 to 4 of life until term corrected age . MAIN OUTCOME MEASURES Bayley Mental Development Index ( MDI ) at 18 months ' corrected age . A priori subgroup analyses were conducted based on r and omization strata ( sex and birth weight < 1250 g vs > or = 1250 g ) . RESULTS Of the 657 infants enrolled , 93.5 % completed the 18-month follow-up . Bayley MDI scores did not differ between the high- and st and ard-DHA groups ( mean difference , 1.9 ; 95 % confidence interval [ CI ] , -1.0 to 4.7 ) . The MDI among girls fed the high-DHA diet was higher than girls fed st and ard DHA in unadjusted and adjusted analyses ( unadjusted mean difference , 4.7 ; 95 % CI , 0.5 - 8.8 ; adjusted mean difference , 4.5 ; 95 % CI , 0.5 - 8.5 ) . The MDI among boys did not differ between groups . For infants born weighing less than 1250 g , the MDI in the high-DHA group was higher than with st and ard DHA in the unadjusted comparison ( mean difference , 4.7 ; 95 % CI , 0.2 - 9.2 ) but did not reach statistical significance following adjustment for gestational age , sex , maternal education , and birth order ( mean difference , 3.8 ; 95 % CI , -0.5 to 8.0 ) . The MDI among infants born weighing at least 1250 g did not differ between groups . CONCLUSION A DHA dose of approximately 1 % total fatty acids in early life did not increase MDI scores of preterm infants overall born earlier than 33 weeks but did improve the MDI scores of girls . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12606000327583 OBJECTIVE To investigate the effect of dietary supplementation with a probiotic on feeding tolerance and gastrointestinal motility in healthy formula-fed preterm infants . STUDY DESIGN Thirty preterm newborns were enrolled ; 10 were exclusively breast-fed , and the remaining 20 were r and omly assigned in a double-blind manner to receive either Lactobacillus reuteri ATCC 55730 ( at dose of 1 x 10(8 ) colony forming units a day ) or placebo for 30 days . Clinical symptoms of gastrointestinal function ( regurgitation , vomiting , inconsolable crying , and evacuation ) and physiological variables ( gastric electrical activity and emptying ) were recorded before and after the dietary intervention . RESULTS Body weight gains per day were similar for the 3 groups , and no adverse events were recorded . Newborns receiving probiotics showed a significant decrease in regurgitation and mean daily crying time and a larger number of stools compared with those given placebo .  Gastric emptying rate was significantly increased , and fasting antral area was significantly reduced in both the newborns receiving L. reuteri and breast-fed newborns compared with placebo . CONCLUSIONS Our results suggest a useful role for L. reuteri supplementation in improving feeding tolerance and gut function in formula-fed preterm newborns OBJECTIVE . The objective of our study was to evaluate the effect of supplementation with docosahexaenoic acid and arachidonic acid for human milk-fed preterm infants . The primary end point was cognitive development at 6 months of age . METHODS . The study was a r and omized , double-blind , placebo-controlled study among 141 infants with birth weights of < 1500 g. The intervention with 32 mg of docosahexaenoic acid and 31 mg of arachidonic acid per 100 mL of human milk started 1 week after birth and lasted until discharge from the hospital ( on average , 9 weeks ) . Cognitive development was evaluated at 6 months of age by using the Ages and Stages Question naire and event-related potentials , a measure of brain correlates related to recognition memory . RESULTS . There was no difference in adverse events or growth between the 2 groups . At the 6-month follow-up evaluation , the intervention group performed better on the problem-solving subscore , compared with the control group ( 53.4 vs 49.5 points ) . There was also a nonsignificant higher total score ( 221 vs 215 points ) . The event-related potential data revealed that infants in the intervention group had significantly lower responses after the st and ard image , compared with the control group ( 8.6 vs 13.2 ) . There was no difference in responses to novel images . CONCLUSIONS . Supplementation with docosahexaenoic acid and arachidonic acid for very preterm infants fed human milk in the early neonatal period was associated with better recognition memory and higher problem-solving scores at 6 months
This paper summarizes the literature concerning the effects of administering ( 1 ) long-chain polyunsaturated fatty acids ( LCPUFA ) , ( 2 ) probiotics and /or ( 3 ) prebiotics to preterm infants .