Effect of two doses of docosahexaenoic acid (DHA) in the diet of preterm infants on infant fatty acid status: results from the DINO trial. Breastfeeding and child cognitive development: new evidence from a large randomized trial. Synthesis of long-chain polyunsaturated fatty acids in preterm newborns fed formula with long-chain polyunsaturated fatty acids. A randomized trial of visual attention of preterm infants fed docosahexaenoic acid until two months First year growth of preterm infants fed standard compared to marine oil n−3 supplemented formula Daily Enteral DHA Supplementation Alleviates Deficiency in Premature Infants 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. 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 Dietary Omega-3 Fatty Acids on Retinal Function of Very-Low-Birth-Weight Neonates Safety and efficacy of omega-3 fatty acids in the nutrition of very low birth weight infants: soy oil and marine oil supplementation of formula. Pre- and post-term growth in pre-term infants supplemented with higher-dose DHA: a randomised controlled trial. Body Composition in Preterm Infants Who Are Fed Long-Chain Polyunsaturated Fatty Acids: A Prospective, Randomized, Controlled Trial Dietary supplementation of long‐chain polyunsaturated fatty acids in preterm infants: effects on cerebral maturation Long-Chain Polyunsaturated Fatty Acids and Cognition in VLBW Infants at 8 years: an RCT Effects of different arachidonic acid supplementation on psychomotor development in very preterm infants; a randomized controlled trial Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial. Are long-chain polyunsaturated fatty acids essential nutrients in infancy? Growth and development of preterm infants fed infant formulas containing docosahexaenoic acid and arachidonic acid. A Multicenter Long-Term Safety and Efficacy Trial of Preterm Formula Supplemented with Long-Chain Polyunsaturated Fatty Acids Double-blind, randomized trial of long-chain polyunsaturated fatty acid supplementation in formula fed to preterm infants. The Use of Low-EPA Fish Oil for Long-Chain Polyunsaturated Fatty Acid Supplementation of Preterm Infants Neurodevelopmental outcomes at 7 years’ corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: a follow-up of a randomised controlled trial Long-Term Feeding of Formulas High in Linolenic Acid and Marine Oil to Very Low Birth Weight Infants: Phospholipid Fatty Acids 10-year Cognition in Preterms After Random Assignment to Fatty Acid Supplementation in Infancy Visual evoked potentials and dietary long chain polyunsaturated fatty acids in preterm infants. Assessment of the Efficacious Dose of Arachidonic and Docosahexaenoic Acids in Preterm Infant Formulas: Fatty Acid Composition of Erythrocyte Membrane Lipids Fatty acid profiles, antioxidant
status, and growth of preterm infants fed diets without or with
long-chain polyunsaturated fatty acids The 10-year follow-up of a randomised trial of long-chain polyunsaturated fatty acid supplementation in preterm infants: effects on growth and blood pressure Randomized, double-blind trial of long-chain polyunsaturated fatty acid supplementation with fish oil and borage oil in preterm infants. Retinal development in very-low-birth-weight infants fed diets differing in omega-3 fatty acids. Influence of Breast‐Feeding on the Infant's Intellectual Development Docosahexaenoic acid and arachidonic acid enhance growth with no adverse effects in preterm infants fed formula. Neurodevelopmental outcomes of preterm infants fed high-dose docosahexaenoic acid: a randomized controlled trial. 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 CONTEXT The evidence that breastfeeding improves cognitive development is based almost entirely on observational studies and is thus prone to confounding by subtle behavioral differences in the breastfeeding mother 's behavior or her interaction with the infant . OBJECTIVE To assess whether prolonged and exclusive breastfeeding improves children 's cognitive ability at age 6.5 years . DESIGN Cluster-r and omized trial , with enrollment from June 17 , 1996 , to December 31 , 1997 , and follow-up from December 21 , 2002 , to April 27 , 2005 . SETTING Thirty-one Belarussian maternity hospitals and their affiliated polyclinics . PARTICIPANTS A total of 17,046 healthy breastfeeding infants were enrolled , of whom 13,889 ( 81.5 % ) were followed up at age 6.5 years . INTERVENTION Breastfeeding promotion intervention modeled on the Baby-Friendly Hospital Initiative by the World Health Organization and UNICEF . MAIN OUTCOME MEASURES Subtest and IQ scores on the Wechsler Abbreviated Scales of Intelligence , and teacher evaluations of academic performance in reading , writing , mathematics , and other subjects . RESULTS The experimental intervention led to a large increase in exclusive breastfeeding at age 3 months ( 43.3 % for the experimental group vs 6.4 % for the control group ; P < .001 ) and a significantly higher prevalence of any breastfeeding at all ages up to and including 12 months . The experimental group had higher means on all of the Wechsler Abbreviated Scales of Intelligence measures , with cluster-adjusted mean differences ( 95 % confidence intervals ) of + 7.5 ( + 0.8 to + 14.3 ) for verbal IQ , + 2.9 ( -3.3 to + 9.1 ) for performance IQ , and + 5.9 ( -1.0 to + 12.8 ) for full-scale IQ . Teachers ' academic ratings were significantly higher in the experimental group for both reading and writing . CONCLUSION These results , based on the largest r and omized trial ever conducted in the area of human lactation , provide strong evidence that prolonged and exclusive breastfeeding improves children 's cognitive development . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N37687716 BACKGROUND Docosahexaenoic acid ( DHA ) and arachidonic acid ( AA ) are long-chain polyunsaturated fatty acids ( LCPs ) that play pivotal roles in growth and neurodevelopment . OBJECTIVE We aim ed to quantify the synthesis of LCPs in preterm infants fed infant formula containing LCPs . DESIGN Twenty-two preterm infants were r and omly assigned to either the no-LCP group ( fed formula without LCPs ; n = 11 ) or the LCP group ( fed formula with LCPs ; n = 11 ) . Dietary LCPs had higher (13)C content than did the endogenously synthesized LCPs , which were derived from linoleic and alpha-linolenic acids . The (13)C content of major selected plasma fatty acids was measured by using gas chromatography-isotope ratio mass spectrometry at birth and at age 1 , 3 , and 7 mo . Absolute LCP synthesis and the percentage of LCP synthesis relative to dietary intake were calculated . RESULTS Percentage AA synthesis was 67.2 + /- 7.8 % , 35.9 + /- 9.8 % , and 29.0 + /- 10.3 % , and that of DHA was 41.7 + /- 14.9 % , 10.5 + /- 8.1 % , and 7.4 + /- 6.2 % at 1 , 3 , and 7 mo old , respectively . Absolute AA synthesis was 26.7 + /- 4.2 , 14.4 + /- 3.9 , and 11.6 + /- 4.1 mg x kg(-1 ) x d(-1 ) and that of DHA was 12.6 + /- 4.5 , 3.2 + /- 2.5 , and 2.3 + /- 1.9 mg x kg(-1 ) . d(-1 ) at 1 , 3 , and 7 mo old , respectively . AA and DHA synthesis decreased significantly ( P < 0.01 ) with time , and AA synthesis was significantly ( P < 0.01 ) greater than DHA synthesis . CONCLUSIONS By this novel approach , we measured endogenous LCP synthesis in infants receiving dietary LCPs over long periods . By age 7 mo , LCP synthesis was dramatically lower in preterm infants fed LCPs This was a r and omized , double-blind trial to determine if a nutrient-enriched ( preterm ) formula supplemented with 0.2 % docosahexaenoic acid ( DHA , 22∶6n−3 ) from a low eicosapentaenoic acid ( 0.06 % ) source of marine oil would enhance visual novelty preference and attention of preterm infants . Both the st and ard and experimental formulas contained 3 % of total fatty acids as linolenic acid ( 18∶3n−3 ) and were fed from approximately three days of age to two months past term . After two months , both diet groups were fed a commercially-available term formula with linolenic acid as the only source of n−3 fatty acid . At 12 mo visual recognition memory ( novelty preference ) and visual attention ( number and duration of discrete looks ) were determined with the Fagan Test of Infant Intelligence . The DHA-supplemented group compared with the control group had more and shorter duration looks in comparisons of familiar and novel stimuli , confirming earlier evidence that DHA can increase information processing speed of preterm infants who otherwise are receiving good intakes of linolenic acid . Because supplementation was stopped at two months and the effects seen at 12 mon , this study demonstrates for the first time that a relatively short period of DHA supplementation can produce significant effects on later visual attention 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 Docosahexaenoic acid ( DHA ) is an essential fatty acid ( FA ) important for health and neurodevelopment . Premature infants are at risk of DHA deficiency and circulating levels directly correlate with health outcomes . Most supplementation strategies have focused on increasing DHA content in mother ’s milk or infant formula . However , extremely premature infants may not reach full feedings for weeks and commercially available parenteral lipid emulsions do not contain preformed DHA , so blood levels decline rapidly after birth . Our objective was to develop a DHA supplementation strategy to overcome these barriers . This double-blind , r and omized , controlled trial determined feasibility , tolerability and efficacy of daily enteral DHA supplementation ( 50 mg/day ) in addition to st and ard nutrition for preterm infants ( 24–34 weeks gestational age ) beginning in the first week of life .  Blood FA levels were analyzed at baseline , full feedings and near discharge in  DHA ( n = 31 ) or placebo supplemented ( n = 29 ) preterm infants . Term peers ( n = 30 ) were analyzed for comparison . Preterm infants had lower baseline DHA levels ( p < 0.0001 ) . Those receiving DHA had a progressive increase in circulating DHA over time ( from 3.33 to 4.09 wt% or 2.88 to 3.55 mol% , p < 0.0001 ) while placebo-supplemented infants ( receiving st and ard neonatal nutrition ) had no increase over time ( from 3.35 to 3.32 wt% or 2.91 to 2.87 mol% ) . Although levels increased with additional DHA supplementation , preterm infants still had lower blood DHA levels than term peers ( 4.97 wt% or 4.31 mol% ) at discharge ( p = 0.0002 ) . No differences in adverse events were observed between the groups . Overall , daily enteral DHA supplementation is feasible and alleviates deficiency in premature infants 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 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 ABSTRACT : Retinal function was assessed by electroretinogram in 32 neonates r and omly assigned to formulas of different ω-3 fatty acid content and in 10 infants fed human milk . All neonates had a birth weight of 1000 - 1500 g and were fed study diets from d 10 to 45 or discharge . Group A received formula containing predominantly 18:2 ω-6 . Group B received a balanced mix of 18:2 ω-6 and 18:3 ω- 3 . Group C was given a formula containing both essential fatty acids and supplemented with marine oil to provide 22:6 ω-3 content similar to that of human milk . The fatty acid composition of plasma and red blood cell ( RBC ) lipids were similar for all groups on entry but marked dietinduced differences were found after feeding the study diets . Group C was comparable to the human milk-fed group , but group A had lower 22:6 ω-3 and ω-3 long-chain polyunsaturated fatty acids ( LCPUFA ) in plasma and RBC membranes . Cone function was not affected by dietary essential fatty acids . Rod electroretinogram thresholds were significantly higher for group A relative to the human milk-fed group and group C and significantly correlated with RBC ω-3 LCPUFA ( r = -0.63 , p < 0.0001 ) ; 44 % of the variance could be explained by RBC and plasma ω-3 LCPUFA content . Rod electroretinogram amplitude was significantly lower for group A relative to the human milkfed group and group C and related to plasma 22:6 ω-3 ( r = 0.55 ) and total ω-3 LCPUFA ( r = 0.58 ) ( both p < 0.0001 ) ; 42 % of the variance was explained by plasma ω-3 LCPUFA , the ratio of ω-6/ω-3 LCPUFA in RBC , and gestational age at birth . Our results support an essential role for ω-3 fatty acids in retinal development Because formula-fed preterm infants may be at risk of omega 3 essential fatty acid deficiency , we tested experimental formulas supplemented with soy oil to provide alpha-linolenic acid or marine oil to provide preformed omega 3 long-chain polyunsaturated fatty acids at a level comparable to that of human milk . This report addresses the effect of feeding formula supplemented with soy oil or with soy and marine oils on growth , clinical tolerance , coagulation test results , changes in erythrocyte membrane fluidity , and plasma concentrations of vitamins A and E in very low birth weight infants from 30 to 57 weeks of postconceptional age . " Healthy " preterm infants were maternally selected to receive human milk or selected at r and om to receive commercial ready-to-feed  liquid formula  , which provided limited omega 3 fatty acid , or experimental formulas supplemented with soy oil or soy and marine oils . Results of this study indicate that formula enriched with soy oil or soy and marine oils containing preformed omega 3 long-chain polyunsaturated fatty acids does not induce abnormalities in growth , clotting function , erythrocyte membrane fluidity , or vitamin A or E levels in healthy very low birth weight preterm infants . Additional studies to evaluate safety in a representative preterm population are required The effect of the dietary n-3 long-chain PUFA , DHA ( 22 : 6n-3 ) , on the growth of pre-term infants is controversial . We tested the effect of higher-dose DHA ( approximately 1 % dietary fatty acids ) on the growth of pre-term infants to 18 months corrected age compared with st and ard feeding practice ( 0·2 - 0·3 % DHA ) in a r and omised controlled trial . Infants born < 33 weeks gestation ( n 657 ) were r and omly allocated to receive breast milk and /or formula with higher DHA or st and ard DHA according to a concealed schedule stratified for sex and birth-weight ( < 1250 and ≥ 1250 g ) . The dietary arachidonic acid content of both diets was constant at approximately 0·4 % total fatty acids . The intervention was from day 2 to 5 of life until the infant 's expected date of delivery ( EDD ) . Growth was assessed at EDD , and at 4 , 12 and 18 months corrected age . There was no effect of higher DHA on weight or head circumference at any age , but infants fed higher DHA were 0·7 cm ( 95 % CI 0·1 , 1·4 cm ; P = 0·02 ) longer at 18 months corrected age . There was an interaction effect between treatment and birth weight strata for weight ( P = 0·01 ) and length ( P = 0·04 ) . Higher DHA result ed in increased length in infants born weighing ≥ 1250 g at 4 months corrected age and in both weight and length at 12 and 18 months corrected age . Our data show that DHA up to 1 % total dietary fatty acids does not adversely affect growth The objective of this study was to evaluate growth and body composition of premature infants who were fed formulas with arachidonic acid ( ARA ; 20:4n6 ) and docosahexaenoic acid ( DHA ; 22:6n3 ) to 1 y of gestation-corrected age ( CA ) . Preterm infants ( 750–1800 g birth weight and <33 wk gestational age ) were assigned within 72 h of first enteral feeding to one of three formulas : control ( n = 22 ) , DHA+ARA from fish/fungal oil [ DHA+ARA(FF ) ; n = 20 ] , or DHA+ARA from egg/fish oil [ DHA+ARA(EF ) ; n = 18 ] . Human milk feeding was allowed on the basis of the mother 's choice . Infants were fed breast milk and /or preterm formulas with or without 0.26 % DHA and 0.42 % ARA to term CA followed by breast milk or postdischarge preterm formulas with or without 0.16 % DHA and 0.42 % ARA to 12 mo CA . Body composition was measured by dual-energy x-ray absorptiometry . There were no significant differences among the three study groups at any time point in weight , length , or head circumference . Bone mineral content and bone mineral density did not differ among groups . At 12 mo CA , infants who were fed DHA+ARA-supplemented formulas had significantly greater lean body mass ( p < 0.05 ) and significantly less fat mass ( p < 0.05 ) than infants who were fed the unsupplemented control formula . The DHA+ARA-supplemented formulas supported normal growth and bone mineralization in premature infants who were born at <33 wk gestation . Preterm formulas that had DHA+ARA at the levels and ratios in this study and were fed to 1 y CA led to increased lean body mass and reduced fat mass by 1 y of age 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 OBJECTIVE : To test the hypothesis that supplementation with the long chain polyunsaturated fatty acids docosahexaenoic acid ( DHA ) and arachidonic acid ( AA ) to very low birth weight ( VLBW ) infants would improve long-term cognitive functions and influence neuroanatomical volumes and cerebral cortex measured by MRI . METHODS : The current study is a follow-up of a r and omized , double-blinded , placebo-controlled study of supplementation with high-dose DHA ( 0.86 % ) and AA ( 0.91 % ) to 129 VLBW infants fed human milk . Ninety-eight children participated at 8 years follow-up and completed a broad battery of cognitive tests .  Eighty-one children had cerebral MRI scans of acceptable quality . RESULTS : There were no significant differences between the intervention group and the control group on any of the cognitive measures . Equally , MRI data on segmental brain volumes and cerebral cortex volume , area , and thickness suggested no overall group effect . CONCLUSIONS : This study is the first long-term follow-up of a r and omized controlled trial with supplementation of DHA and AA to human milk fed VLBW infants investigating both cognitive functions and brain macrostructure measured by MRI . No cognitive or neuroanatomical effects of the supplementation were detected at 8 years of age Background & aims Nutritional supplementation with polyunsaturated fatty acids is important in preterm infants neurodevelopment , but it is not known if the omega-6/omega-3 ratio affects this process . This study was design ed to determine the effects of a balanced contribution of arachidonic acid in very preterm newborns fed with formula milk . Methods This was a r and omized trial , in which newborns < 1500 g and /or < 32 weeks gestational age were assigned to one of two groups , based on the milk formula they would receive during the first year of life . Initially , 60 newborns entered the study , but ultimately , group A was composed of 24 newborns , who were given formula milk with an ω-6/ω-3 ratio of 2/1 , and Group B was composed of 21 newborns , given formula milk with an ω-6/ω-3 ratio of 1/1 . The infants were followed up for two years : growth , visual-evoked potentials , brainstem auditory-evoked potentials , and plasma fatty acids were periodically measured , and psychomotor development was assessed using the Brunet Lézine scale at 24 months corrected age . A control group , for comparison of Brunet Lézine score , was made up of 25 newborns from the SEN1500 project , who were fed exclusively with breast milk . Results At 12 months , arachidonic acid values were significantly higher in group A than in group B ( 6.95 ± 1.55 % vs. 4.55 ± 0.78 % ) , as were polyunsaturated fatty acids ( 41.02 ± 2.09 % vs. 38.08 ± 2.32 % ) achieved a higher average . Group A achieved a higher average Brunet Lézine score at 24 months than group B ( 99.9 ± 9 vs. 90.8 ± 11 , p = 0.028 ) . The Brunet Lézine results from group A were compared with the control group results , with very similar scores registered between the two groups ( 99.9 ± 9 vs. 100.5 ± 7 ) . There were no significant differences in growth or evoked potentials between the two formula groups . Conclusions Very preterm infants who received formula with an ω-6/ω-3 ratio of 2/1 had higher blood levels of essential fatty acids during the first year of life , and better psychomotor development , compared with very preterm newborns who consumed formula with an ω-6/ω-3 of 1/1 . Therefore , formula milk with an arachidonic acid quantity double that of docosahexaenoic acid should be considered for feeding very preterm infants . Trial registration Clinical Trials.gov Identifier NCT02503020 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 We investigated whether the disparity in neural maturation between breastfed and formula-fed term infants could be corrected by the addition of fish oil , a source of docosahexaenoic acid ( DHA , 22:6 omega 3 ) , to infant formula . Healthy , term infants were r and omised at birth to receive either a supplemented or placebo formula if their mothers had chosen to bottle feed . Breastfed term infants were enrolled as a reference group . Infant erythrocyte fatty acids and anthropometry were assessed on day 5 and at 6 , 16 , and 30 weeks of age . Visual evoked potential ( VEP ) acuity was determined at 16 and 30 weeks . VEP acuities of breastfed and supplemented-formula-fed infants were better than those of placebo-formula-fed infants at both 16 and 30 weeks of age ( p < 0.001 and p < 0.01 ) . Erythrocyte DHA in breastfed and supplemented-formula-fed infants was maintained near birth levels throughout the 30-week study period but fell in placebo-formula-fed infants ( p < 0.001 ) . Erythrocyte DHA was the only fatty acid that consistently correlated with VEP acuity in all infants at both ages tested . A continuous supply of DHA may be required to achieve optimum VEP acuity since infants breastfed for short periods ( < 16 weeks ) had slower development of VEP than infants receiving a continuous supply of DHA from either breastmilk or supplemented formula . Erythrocyte arachidonic acid ( 20:4 omega 6 ) in supplemented-formula-fed infants was reduced below that of infants fed breastmilk or placebo formula at 16 and 30 weeks ( p < 0.001 ) , although no adverse effects were noted , with growth of all infants being similar . DHA seems to be an essential nutrient for the optimum neural maturation of term infants as assessed by VEP acuity . Whether supplementation of formula-fed infants with DHA has long-term benefits remains to be eluci date 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 Background The tissue accretion of long-chain polyunsaturated fatty acids is compromised in infants born prematurely . Human milk contains long-chain polyunsaturated fatty acids , but most preterm infant formulas do not . The long-term effects of preterm formula supplemented with arachidonic acid and docosahexaenoic acid , in proportions typical of those in human milk , were therefore investigated . Methods In this double-blind , r and omized study , 288 preterm infants received experimental formula ( n = 77 ) , unsupplemented ( control ) formula ( n = 78 ) , or human milk ( n = 133 ) until 48 weeks postconceptional age ( PCA ) .  Term formula , without supplemental long-chain polyunsaturated fatty acids , was administered from 48 to 92 weeks PCA to formula-fed infants and to infants weaned from human milk .  Anthropometric and fatty acid data were assessed by using analysis of variance . Results At 92 weeks PCA , no statistically significant anthropometric measurement differences were found except for midarm circumference , which was smaller in human milk – fed infants than in those fed formula . Phospholipid concentrations were similar in the experimental and human milk – fed groups , and docosahexaenoic acid levels were significantly greater than in the control group . The types and incidences of adverse events were similar among the feeding groups . Conclusions The results of this study demonstrate the efficacy and long-term safety of preterm formula supplemented with long-chain polyunsaturated fatty acids OBJECTIVE We tested the hypothesis that balanced addition of long-chain polyunsaturated fatty acid ( LCPUFA ) to preterm formula during the first weeks of life would confer long-term neurodevelopmental advantage in a double-blind , r and omized , controlled trial of preterm formula with and without preformed LCPUFA . METHODS The participants were 195 formula-fed preterm infants ( birth weight < 1750 g , gestation < 37 weeks ) from 2 UK neonatal units and 88 breast milk-fed infants . Main outcome measures were Bayley Mental Developmental Index ( MDI ) and Psychomotor Developmental Index ( PDI ) at 18 months and Knobloch , Passamanick and Sherrard 's Developmental Screening Inventory at 9 months ' corrected age . Safety outcome measures were anthropometry at 9 and 18 months , tolerance , infection , necrotizing enterocolitis , and death . RESULTS There were no significant differences in developmental scores between r and omized groups , although infants who were fed LCPUFA-supplemented formula showed a nonsignificant 2.6-point ( 0.25 st and ard deviation ) advantage in MDI and PDI at 18 months , with a greater ( nonsignificant ) advantage ( MDI : 4.5 points ; PDI : 5.8 points ) in infants below 30 weeks ' gestation . LCPUFA-supplemented infants were shorter than control infants at 18 months ( difference in length st and ard deviation score : 0.44 ; 95 % confidence interval : 0.08 - 0.8 ) . No other significant short- or long-term differences in safety outcomes were observed . Breastfed infants had significantly higher developmental scores at 9 and 18 months than both formula groups and were significantly heavier and longer at 18 months than LCPUFA-supplemented but not control infants . CONCLUSIONS With the dose , duration , and preparation of LCPUFA used , efficacy was not demonstrated , although an advantage in later neurodevelopment can not be excluded by global tests of development up to 18 months , particularly in infants below 30 weeks ' gestation . The surprising effect of LCPUFA-supplemented formula on growth 18 months beyond the intervention period needs to be confirmed in other studies using similar supplementation strategies . Additional follow-up of this cohort is critical at an age when more specific tests of cognitive function are possible Because docosahexaenoic acid ( DHA ) may be an essential nutrient for the visual and early cognitive development of preterm infants , DHA enrichment of preterm formulas has been recommended . This r and omized trial was design ed to study the n-6 and n-3 fatty acid status of healthy preterm infants fed a formula enriched with a low eicosapentaenoic-fish oil until 4 mo corrected age compared with that of infants fed a st and ard formula .  A reference group of breast-fed infants was studied concurrently . The fatty acid content of red blood cell ( RBC ) phospholipid was assessed at enrollment , hospital discharge , expected term , and 3 and 6 mo postterm . The DHA content of RBC phospholipid was higher in infants fed the enriched versus the st and ard formula at hospital discharge , expected term , and 3 and 6 mo postterm . However , compared with infants fed the st and ard formula , infants fed the enriched formula had also higher RBC phospholipid eicosapentaenoic content ( 0.69 ± 0.15%versus 0.25 ± 0.12 % , p < 0.001 ) , and lower RBC phospholipid arachidonic acid content ( 15.1 ± 0.93%versus 18.8 ± 0.89%;p < 0.001 ) . We conclude that supplementing preterm infants with low-eicosapentaenoic fish oil is effective in improving DHA status , but results in worsening of n-6 fatty acid status . We speculate that preterm infants may require a dietary supply of arachidonic acid as well as DHA if the same fatty acid status as that of breast-fed infants is to be achieved Objective To determine if improvements in cognitive outcome detected at 18 months ’ corrected age ( CA ) in infants born <33 weeks ’ gestation receiving a high-docosahexaenoic acid ( DHA ) compared with st and ard-DHA diet were sustained in early childhood . Design Follow-up of a multicentre r and omised controlled trial . R and omisation was stratified for sex , birth weight ( < 1250 vs ≥1250 g ) and hospital . Setting Five Australian tertiary hospitals from 2008 to 2013 . Participants 626 of the 657 participants r and omised between 2001 and 2005 were eligible to participate .  Interventions High-DHA ( ≈1 % total fatty acids ) enteral feeds compared with st and ard-DHA ( ≈0.3 % total fatty acids ) from age 2–4 days until term CA . Primary outcome Full Scale IQ of the Wechsler Abbreviated Scale of Intelligence ( WASI ) at 7 years CA . Prespecified subgroup analyses based on the r and omisation strata ( sex , birth weight ) were conducted . Results 604 ( 92 % of the 657 originally r and omised ) consented to participate ( 291 high-DHA , 313 st and ard-DHA ) . To address missing data in the 604 consenting participants ( 22 for primary outcome ) , multiple imputation was performed . The Full Scale IQ was not significantly different between groups ( high-DHA 98.3 , SD 14.0 , st and ard-DHA 98.5 , SD 14.9 ; mean difference adjusted for sex , birthweight strata and hospital −0.3 , 95 % CI −2.9 to 2.2 ; p=0.79 ) . There were no significant differences in any secondary outcomes . In prespecified subgroup analyses , there was a significant sex by treatment interaction on measures of parent-reported executive function and behaviour . Scores were within the normal range but girls receiving the high-DHA diet scored significantly higher ( poorer outcome ) compared with girls receiving the st and ard-DHA diet . Conclusions Supplementing the diets of preterm infants with a DHA dose of approximately 1 % total fatty acids from days 2–4 until term CA showed no evidence of benefit at 7 years ’ CA . Trial registration number Australian New Zeal and Clinical Trials Registry : ACTRN12606000327583 ABSTRACT : Red blood cell ( RBC ) phospholipids of infants fed human milk compared with formula have more arachidonic acid ( AA ) and docosahexanoic acid ( DHA ) . The addition of low levels of marine oil to infant formula with 0.6 to 2.0 % α-linolenic acid ( LLA , 18:3n-3 ) prevented declines in DHA in formula-fed infants ; however , the feeding trials were short ( 4 to 6 wk ) , LLA concentrations were low compared with current formulas ( 3.0 to 5.0 % LLA ) , and the formulas were unstable . Trials with stable formulas were necessary to determine if dietary DHA could maintain phospholipid DHA after discharge from the hospital and , in fact , if it was necessary with higher intakes of LLA . The results of acute ( 4 wk ) and extended ( to 79 wk postconception ) feeding of such formulas on RBC and plasma phospholipid AA and DHA are reported here . Control formulas were identical to commercially available formulas . Experimental formulas differed only in the addition of small amounts of marine oil  . DHA in RBC and plasma phosphatidylethanolamine ( PE ) declined during four weeks of feeding but not if marine oil provided DHA ( 0.2 % or 0.4 % ) and plasma phospholipid AA ( g/100 g ) decreased with time and marine oil feeding . Extended feeding with marine oil accounted for half the DHA in RBC and plasma phosphatidylethanolamine at equilibrium ; however , RBC ( g/100 g ) and plasma AA ( g/100 g ; mg/L plasma ) decreased progressively until late infancy and were depressed further by marine oil . We conclude that 1 ) AA and DHA decline in RBC and plasma phospholipids of preterm infants when only their n-6 and n-3 fatty acid precursors are consumed ; and 2 ) marine oil can maintain cord concentrations of RBC phosphatidylethanolamine DHA but further reduces AA OBJECTIVE : To test the hypothesis that long-chain polyunsaturated fatty acid ( LCPUFA ) supplementation in infancy would improve cognition into later childhood ( after 9 years ) at both general and specific levels . METHODS : A comprehensive cognitive battery was completed by 107 formerly preterm infants ( mean age : 128 months ) . As infants , they had been assigned r and omly to receive LCPUFA-supplemented ( N = 50 ) or control ( N = 57 ) formula , between birth and 9 months ; the docosahexaenoic acid level ( DHA ) in the supplemented formulas was 0.5 % . In addition to r and omized comparisons , we planned supplementary analyses to examine the effects of both gender and feeding group ( those receiving some maternal breast milk versus those receiving none ) . RESULTS : There were no significant differences between r and omized diet groups on any cognitive measure . There was significant interaction between gender and supplementation ; girls only showed beneficial effects of LCPUFAs on literacy . Significant interaction also occurred between feeding group and supplementation ; increases of 0.7 SD in verbal IQ , full-scale IQ , and memory scores were found for the LCPUFA group , but only for infants who received only formula and no maternal breast milk . CONCLUSIONS : The results of this post–9-year cognitive follow-up study in a r and omized trial of LCPUFA-supplemented formula for preterm infants suggest no overall group effects but indicate that gender-specific and diet-specific effects may exist . The data provide some evidence that LCPUFAs are a key factor in the cognitive benefits of breast milk . Caution is advised in data interpretation because of the small groups used The influence of dietary long chain polyunsaturated fatty acid ( LCP ) supply , and especially of docosahexaenoic acid ( DHA ) , on evoked potential maturation , was studied in 58 healthy preterm infants using flash visual evoked potentials ( VEPs ) , flash electroretinography ( ERG ) , and brainstem acoustic evoked potentials ( BAEPs )  at 52 weeks of postconceptional age . At the same time , the fatty acid composition of red blood cell membranes was examined . The infants were fed on breast milk ( n = 12 ) , a preterm formula supplemented with LCP ( PF-LCP ) ( n = 21 ) , or a traditional preterm formula ( PF ) ( n = 25 ) . In the breast milk and PF-LCP groups the morphology and latencies of the waves that reflect the visual projecting system were similar ; in the PF group the morphology was quite different and the wave latencies were significantly longer . This could mean that the maturation pattern of VEPs in preterm infants who did not receive LCP was slower . Moreover , a higher level of erythrocyte LCP , especially DHA , was found in breast milk and PF-LCP groups compared with the PF group . ERG and BAEP recordings were the same in all three groups . These results suggest that a well balanced LCP supplement in preterm formulas can positively influence the maturation of visual evoked potentials in preterm infants when breast milk is not available The nutritional requirements of preterm infants for the long chain polyunsaturated essential fatty acids , arachidonic acid ( AA ) and docosahexaenoic acid ( DHA ) , have not been clearly defined . The present study evaluated preterm infants of less than 2.3 kg birth weight fed a commercial formula ( Preemie SMA ® ) devoid of AA and DHA  and compared this control group with similar infant groups fed one of three formulas containing a range of 0.32 to 1.1 % AA and 0.24 to 0.76 % DHA . An analogous group of infants fed their mothers ' breast milk and a breast milk fortifier  ( when indicated ) was also studied . Erythrocyte membrane phospholipids were isolated from blood sample s collected at 12 d of age and after a further 4 wk of feeding . Infants fed the formula without AA and DHA showed a reduction in AA level in erythrocyte phosphatidylcholine , and a reduced level of DHA in phosphatidylethanolamine in comparison with infants fed breast milk or infant formula containing AA and DHA . Supplementing infant formula with increasing levels of AA and DHA produced a clear dose response in the levels of AA and DHA found in erythrocyte membrane phospholipids . From comparison of membrane phospholipid fatty acid composition it appears that a formula level of 0.32 - 1.1 % AA and 0.24 - 0.76 % DHA provides sufficient levels of these fatty acids to achieve a similar fatty acid composition to that of infants fed human milk for most of the lipid fractions examined Summary .Long-chain polyunsaturated fatty acids ( LCP ) are considered conditionally essential nutrients for the infant born prematurely , and attempts are being made to match fatty acid profiles of formula and breast fed infants . In this double-blind , r and omized study we investigated the effects of a formula enriched with both n-6 and n-3 LCP on plasma fatty acid profiles , antioxidant status and growth of premature infants . 29 infants received either a formula devoid of LCP or a LCP supplemented formula ( 0.5 g/100 g fat linoleic acid metabolites , 0.8 g/100 g fat α-linolenic acid metabolites ) . 17 breast fed infants served as a control group . At study entry as well as two and four weeks later , plasma and urine sample s were collected , growth data obtained and food tolerance was documented . At the end of the four week study period , plasma docosahexaenoic acid ( DHA ) levels of supplemented infants were significantly higher than those of unsupplemented infants and similar to those of infants fed human milk . Plasma n-6 LCP concentrations including arachidonic acid ( AA ) were similar between groups . The plasma α-tocopherol levels of breast fed and supplemented infants were similar and tended to be lower than in infants fed the formula devoid of LCP . Urinary malondialdehyde ( MDA ) excretion of formula fed infants was significantly higher compared to infants fed human milk , but did not differ between the two formula groups . Parameters of growth and milk tolerance did not differ between groups . Our results demonstrate that plasma LCP levels similar to those of breast fed infants can be achieved with the LCP supplemented formula used in this trial , without evidence of adverse effects of the LCP enrichment Objective To test the hypothesis that consumption of infant formulas containing long-chain polyunsaturated fatty acids ( LCPUFAs ) by preterm infants would favourably influence growth , body composition and blood pressure ( BP )  at age 10 years . Methods This was a follow-up study of a preterm cohort ( < 35 weeks and birth weight < 2000 g ) r and omly assigned to unsupplemented or LCPUFA-supplemented formulas to 9 months post term . The setting was a research clinic at Yorkhill Hospital for Sick Children , Glasgow , UK . A total of 107 children aged 9–11 years who participated in the original r and omised controlled trial ( 45 % follow-up ) took part . Main outcome measures were : ( 1 ) anthropometry , ( 2 ) body composition and ( 3 ) BP . Results There were no differences in growth or BP between r and omised groups for the whole cohort . However , girls who had received LCPUFA-supplemented formula were heavier ( 42.20 ( SD 9.61 ) vs 36.94 ( 9.46 ) kg , p=0.05 ) , had greater skin fold thicknesses ( biceps 10.7 ( 3.3 ) vs 8.5 ( 3.6 ) mm , p=0.03 ; suprailiac 16.7 ( 8.2 ) vs 12.0 ( 7.5 ) mm , p=0.03 ) and higher BP ( mean 82.2 ( 8.4 ) vs 78.1 ( 6.2 ) mm Hg , p=0.04 : systolic 111.4 ( 10.1 ) vs 105.9 ( 9.0 ) mm Hg , p=0.04 : diastolic 64.8 ( 8.4 ) vs 61.1 ( 5.4 ) mm Hg , p=0.05 ) . Differences in weight SD score ( 0.85 ( 95 % CI 0.13 to 1.58 ) , p=0.02 ) , Ln sum of skin fold thicknesses ( 0.27 ( 0.02 to 0.52 ) , p=0.04 ) and BP ( mean 4.6 mm Hg ( 0.43 to 8.84 ) , p=0.03 ; systolic 6.1 ( 0.45 to 11.7 ) , p=0.04 ) remained after adjustment for prer and omisation confounders . Differences in BP were not significant following adjustment for current weight . Conclusions Girls born preterm and r and omised to LCPUFA-supplemented formula showed increased weight , adiposity and BP at 9–11 years , which might have adverse consequences for later health . No effects were seen in boys . Long-term follow-up of other LCPUFA supplementation trials is required to further investigate this finding 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 Full-field electroretinograms ( ERGs ) were obtained from very-low-birth-weight ( VLBW ) neonates to determine whether omega-3 ( omega-3 ) fatty acids are essential for normal human retinal development . Eighty-one infants born at 30.4 ( st and ard deviation , + /- 1.5 ) wk gestation were , within 10 d of birth , either enrolled to receive mother 's milk ( naturally containing both omega-6 and omega-3 essential fatty acids ) or  r and omized to receive one of the infant formulas . Corn oil-based Formula A contained mainly linoleic acid ( 18:2 omega-6 ) and was low in all omega-3 fatty acids . Soy oil-based Formula B contained ample alpha-linolenic acid ( 18:3 omega-3 ) but no long-chain omega-3 . Formula C , supplemented with both alpha-linolenic acid and marine oils , was comparable to human milk in long-chain omega-3 . Full-field ERGs were obtained in the special care nursery from infants aged 36 and 57 wk postconception . Ten healthy preterm infants born at 35 wk gestation were tested at 36 wk postconception . Significant differences were found among groups in rod ERG function . Post hoc comparisons showed that infants fed Formula A had significantly higher rod thresholds than infants receiving long-chain omega-3 ( human milk , Formula C , and intrauterine ) . Infants receiving Formula B had intermediate thresholds that were significantly higher than those of infants receiving intrauterine nutrition . Analysis of the leading edge of the a-wave showed that b-wave differences originated at the photoreceptor level . Differences were not present in infants at 57 wk postconception . No significant differences among groups were found in cone b-waves at 36 or 57 wk postconception . Oscillatory potentials had significantly longer implicit times at 57 wk postconception in infants fed Formula A than in infants receiving human milk . These findings suggest that retinal function varies with the dietary supply of omega-3 fatty acids in VLBW infants Summary : The objective of this study was to analyze the effects of breast-feeding on the intellectual development of the infant , controlling for possible confounding factors . A prospect i ve study of cohorts was carried out in a group of 229 healthy infants , studied from birth to 2 years of age . The infants were divided into two groups : group 1,99 infants who were bottle-fed ; and group 0 , 130 who were breast-fed .  All other characteristics in both groups were similar . Psychomotor development was measured between 18 and 29 months using the Bayley scales . Lower results on the Index of Mental Development were associated with bottle-fed infants , lower-middle and lower social class , elementary education of the mother , temper tantrums , and having siblings . Lower results on the Index of Motor Development were associated only with lower and lower-middle social class OBJECTIVE To determine if docosahexaenoic acid ( DHA ) and arachidonic acid ( ARA ) supplementation influences growth or visual acuity of formula-fed premature infants . STUDY DESIGN Double-blind , multi-center study of 194 premature infants given preterm formula with no DHA or ARA ( control ) , 0.15 % energy DHA , or 0.14 % DHA + 0.27 % ARA from single-cell triglycerides for at least 28 days and then fed term formula ( no DHA or ARA ) to 57 weeks postmenstrual age ( PMA ) , with 90 breast-fed term infants as reference . RESULTS Infants fed DHA+ARA formula  gained weight significantly faster ( post-hoc analysis ) during preterm formula feeding than control infants ( 34.7 vs. 30.7 g/d ) and had weights and weight : length ratios not different from term breast-fed infants at 48 and 57 weeks PMA . Infants fed control or DHA formula had lower body weights than term infants . Red blood cell phosphatidylethanolamine ARA was significantly correlated to weight gain during preterm formula feeding and to weight and length at 40 , 48 , and 57 weeks PMA ( r = 0.19 to 0.24 , P = .004-.02 ) . Providing DHA or DHA+ARA during the preterm period had no effect on subsequent visual acuity or incidence of adverse events . CONCLUSIONS Feeding DHA+ARA from single-cell triglycerides enhances weight gain in formula-fed premature infants with no evidence of adverse effects 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 . 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
BACKGROUND Controversy exists over whether longchain polyunsaturated fatty acids ( LCPUFA ) are essential nutrients for preterm infants because they may not be able to synthesis e sufficient amounts of LCPUFA to meet the needs of the developing brain and retina .
OBJECTIVES To assess whether supplementation of formula milk with LCPUFA is safe and of benefit to preterm infants .
The main areas of interest were the effects of supplementation on the visual function , development and growth of preterm infants .