Neurodevelopmental and functional outcomes of extremely low birth weight infants in the National Institute of Child Health and Human Development Neonatal Research Network, 1993-1994. Lower Proportion of CD45R0+ Cells and Deficient Interleukin-10 Production by Formula-Fed Infants, Compared With Human-Fed, Is Corrected With Supplementation of Long-Chain Polyunsaturated Fatty Acids Preterm infant formula supplementation with alpha linolenic acid and docosahexaenoic acid. Lower Incidence of Necrotizing Enterocolitis in Infants Fed a Preterm Formula with Egg Phospholipids Influence of formulas with borage oil or borage oil plus fish oil on the arachidonic acid status in premature infants 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. A functional magnetic resonance imaging study of language processing and its cognitive correlates in prematurely born children. 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 Effect of Supplementation of Preterm Formula With Long Chain Polyunsaturated Fatty Acids on Mineral Balance in Preterm Infants Early neurological and neurophysiological development of the preterm infant and polyunsaturated fatty acids supply Fatty acid balance studies in preterm infants fed formula milk containing long‐chain polyunsaturated fatty acids (LCP) II Children born weighing less than 1701 g: visual and cognitive outcomes at 11–14 years Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial. Influence of Long Chain Unsaturated Fatty Acids in Formula Feeds on Lipid Peroxidation and Antioxidants in Preterm Infants Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. The Use of Low-EPA Fish Oil for Long-Chain Polyunsaturated Fatty Acid Supplementation of Preterm Infants Visual evoked potentials and dietary long chain polyunsaturated fatty acids in preterm infants. Influence of feeding artificial-formula milks containing docosahexaenoic and arachidonic acids on the postnatal long-chain polyunsaturated fatty acid status of healthy preterm infants. Assessment of the Efficacious Dose of Arachidonic and Docosahexaenoic Acids in Preterm Infant Formulas: Fatty Acid Composition of Erythrocyte Membrane Lipids Dietary essential fatty acid supply and visual acuity development. Fatty acid absorption in preterms on formulas with and without long-chain polyunsaturated fatty acids and in terms on formulas without these added Fatty acid profiles, antioxidant
status, and growth of preterm infants fed diets without or with
long-chain polyunsaturated fatty acids Prevalence, Stability, and Predictors of Clinically Significant Behavior Problems in Low Birth Weight Children at 3, 5, and 8 Years of Age Randomized, double-blind trial of long-chain polyunsaturated fatty acid supplementation with fish oil and borage oil in preterm infants. The effect of N-6 and N-3 polyunsaturated fatty acids on hemostasis, blood lipids and blood pressure. Assessment of feeding different amounts of arachidonic and docosahexaenoic acids in preterm infant formulas on the fatty acid content of lipoprotein lipids Retinal development in very-low-birth-weight infants fed diets differing in omega-3 fatty acids. Docosahexaenoic acid and arachidonic acid enhance growth with no adverse effects in preterm infants fed formula. Prostanoid Formation during Feeding of a Preterm Formula with Long-Chain Polyunsaturated Fatty Acids in Healthy Preterm Infants during the First Weeks of Life
OBJECTIVES The purpose s of this study were to report the neurodevelopmental , neurosensory , and functional outcomes of 1151 extremely low birth weight ( 401 - 1000 g ) survivors cared for in the 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network , and to identify medical , social , and environmental factors associated with these outcomes . STUDY DESIGN A multicenter cohort study in which surviving extremely low birth weight infants born in 1993 and 1994 underwent neurodevelopmental , neurosensory , and functional assessment  at 18 to 22 months ' corrected age . Data regarding pregnancy and neonatal outcome were collected prospect ively . Socioeconomic status and a detailed interim medical history were obtained at the time of the assessment . Logistic regression models were used to identify maternal and neonatal risk factors for poor neurodevelopmental outcome . RESULTS Of the 1480 infants alive at 18 months of age , 1151 ( 78 % ) were evaluated . Study characteristics included a mean birth weight of 796 + /- 135 g , mean gestation ( best obstetric date s ) 26 + /- 2 weeks , and 47 % male . Birth weight distributions of infants included 15 infants at 401 to 500 g ; 94 at 501 to 600 g ; 208 at 601 to 700 g ; 237 at 701 to 800 g ; 290 at 801 to 900 g ; and 307 at 901 to 1000 g. Twenty-five percent of the children had an abnormal neurologic examination , 37 % had a Bayley II Mental Developmental Index < 70 , 29 % had a Psychomotor Developmental Index < 70 , 9 % had vision impairment , and 11 % had hearing impairment . Neurologic , developmental , neurosensory , and functional morbidities increased with decreasing birth weight . Factors significantly associated with increased neurodevelopmental morbidity included chronic lung disease , grade s 3 to 4 intraventricular hemorrhage/periventricular leukomalacia , steroids for chronic lung disease , necrotizing enterocolitis , and male gender . Factors significantly associated with decreased morbidity included increased birth weight , female gender , higher maternal education , and white race . CONCLUSION ELBW infants are at significant risk of neurologic abnormalities , developmental delays , and functional delays at 18 to 22 months ' corrected age Background The immune consequences of adding 20:4n-6 and 22:6n-3 fatty acids to preterm infant formula are not known . Methods The effect of feeding preterm infants ( 14–42 days of age ) human milk ( Human Milk group ) , infant formula ( Formula group )  , or formula with added long-chain polyunsaturated fatty acids 20:4n-6 and 22:6n-3 ( Formula + LCP group ) on isolated peripheral blood lymphocytes ( by flow cytometry ) and lipid composition ( by gas – liquid chromatography ) was determined . Lymphocytes were stimulated in vitro with phytohemagglutinin to measure soluble interleukin (sIL)-2R and IL-10 production ( by enzyme-linked immunosorbent assay ) . Results With age , the percentage of CD3+CD4 + T cells and the percentage of CD20 + cells increased in the Human Milk and Formula + LCP groups ( P < 0.05 ) , but not in the unsupplemented Formula group . Compared with the Formula group , CD4 + cells from the Formula + LCP and Human Milk groups expressed more CD45R0 ( antigen mature ) and less CD45RA ( antigen naive ) at 42 days of age ( P < 0.05 ) . At 42 days , IL-10 production was lower ( P < 0.05 ) in cells of the Formula group than in cells of the Human Milk group . Production of IL-10 by the cells of the Formula + LCP group was not different from that produced by the Human Milk group cells . An age-related decrease ( P < 0.05 ) in sIL-2R production by Formula + LCP lymphocytes was observed , but sIL-2R production at 42 days in the Formula + LCP group did not differ significantly from that in the Human Milk group . Compared with Formula alone , adding LCP to formula result ed in a lower C18:2n-6 and higher C20:4n-6 content in lymphocyte phospholipids ( P < 0.05 ) . Conclusions Adding LCP to a preterm infant formula result ed in lymphocyte population s , phospholipid composition , cytokine production , and antigen maturity that are more consistent with that in human milk – fed infants . This may affect the ability of the infant to respond to immune challenges OBJECTIVES To investigate if supplementation of preterm infant formula  with a high docosahexaenoic acid/eicosapentaenoic acid ( DHA/EPA ) ratio together with alpha-linolenic acid ( ALA ) was able to maintain plasma and red blood cell DHA levels similar to that obtained with breast milk feeding without altering n-6 fatty acid status . DESIGN AND SUBJECTS Preterm infants of mothers who elected not to breast feed ( n=13 ) were assigned to ALA- and DHA-enriched formula ( DHA group : DHA/EPA=5/l ) . Infants fed breast milk ( n=25 ) constituted a reference group ( BM group ) . Anthropometric and fatty acid parameters ( plasma phospholipids , cholesterol esters , triglycerides and red blood cell phosphatidylethanolamine , PL , CE , TG , RBC-PE , respectively ) were obtained after 2 days ( D2 ) and 15 days ( D15 ) of enteral feeding and at the 37th week ( W37 ) of post-conception age and 1 month later ( W37 + 30 ) in the DHA group . Mean DHA intake ranged between 16.5+/-1.6 and 17.9+/-2.9 mg/kg/day between D2 and W37 + 30 . RESULTS At W37 , infant weights , heights , and head circumferences were similar in DHA and BM groups . PL DHA was maintained in the DHA group at the same level as in the BM group and the same for DHA in PE at W37 . In RBC-PE and at W37 , AA status was the same in both groups . In PL , AA levels remained very stable throughout the study ; however , in the DHA group AA levels in PL remained in the range observed with st and ard formulas . CONCLUSION The combined 18:3 n-3 and DHA supplementation of infant formula with DHA/EPA ratio 5/l is compatible with growth and n-3 fatty acid metabolism similar to that of preterm infants fed human milk 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 Several studies have reported that feeding γ-linolenic acid ( GLA ) has result ed in no increase in arachidonic acid ( AA ) in newborns . This result was ascribed to the eicosapentaenoic acid (EPA)-rich fish oil used in these formulas . Docosahexaenoic acid ( DHA ) sources with only minor amounts of EPA are now available , thus the addition of GLA to infant formulas might be considered an alternative to AA supplementation . Sixty-six premature infants were r and omized to feeding one of four formulas [ ST : no GLA , no long-chain polyunsaturated fatty acids ; BO : 0.6 % GLA ( borage oil ) ; BO + FOLOW : 0.6 % GLA , 0.3 % DHA , 0.06 % EPA ; BO + FOHIGH : 0.6 % GLA , 0.3 % DHA , 0.2 % EPA ] or human milk ( HM , nonr and omized ) for 4 wk . Anthropometric measures and blood sample s were obtained at study entry and after 14 and 28 d. There were no significant differences between groups in anthropometric measures , tocopherol , and retinol status at any of the studied time points . The AA content of plasma phospholipids was similar between groups at study start and decreased significantly until day 28 in all formulafed groups , but not in the breast-fed infants [ ST : 6.6±0.2 % , BO : 6.9±0.3 % , BO + FOLOW : 6.9±0.4 % , BO + FOHIGH : 6.7±0.2 % , HM : 8.6±0.5 % , where values are reported as mean ±st and ard error ; all formulas significantly different ( P≤0.05 ) from HM ] . There was no significant influence  of GLA or fish oil addition to the diet . GLA had only a very limited effect on AA status which was too small to obtain satisfactory concentrations ( concentrations similar to breast-fed babies ) under the circumstances tested . The effect of GLA on AA is independent of the EPA and DHA content in the diet within the dose ranges studied 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 OBJECTIVE Abnormalities in brain structure , cognition , and behavior have been described in children born prematurely . However , no direct in vivo evidence has yet demonstrated abnormal neural processing in these children . Our aim was to compare brain activity associated with phonologic and semantic processing of language between term and preterm children using functional magnetic resonance imaging ( fMRI ) . METHODS fMRI scans were acquired during a passive language comprehension task in 26 preterm children at 8 years of age and in 13 term community control children who were comparable in age , sex , maternal education , and minority status . IQ was assessed using a st and ard measure of intelligence . RESULTS The pattern of brain activity identified in a semantic processing task in the preterm children closely resembled the pattern of brain activity identified in a phonologic processing task in term controls . The greater this resemblance in the preterm children , the lower their verbal comprehension IQ scores and the poorer their language comprehension during the scanning task . CONCLUSIONS Preterm children with the poorest language comprehension seemed not to fully engage normal semantic processing pathways in a language comprehension task . These children instead engaged pathways that normal term children used to process meaningless phonologic sounds . Aberrant processing of semantic content in these preterm children may account in part for their lower verbal IQ scores 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 Background Incorporation of long chain polyunsaturated fatty acids ( LCP ) into formulas may interfere with mineral metabolism . We investigate mineral balance in preterm infants who were fed a formula with LCP .  Methods Infants were r and omized in a double-blind manner , 20 infants in each group , to receive a formula with LCP ( F+LCP ) or without LCP ( F ) for 30 days . Plasma levels ( at the beginning and after 30 days ) and nutritional balance ( after 1 week ) for Ca , P , Mg , Zn , and Cu were obtained for all infants . Results Groups were similar regarding birth weight , gestational age , weight , and corrected age at study start . During the 30-day study period , the groups had comparable milk intake and reached similar and satisfactory weight gains and longitudinal growth . Within each group , there was no change in plasma mineral concentrations over the course of the study , and there were no differences at each time point between groups . All values were within the normal range for age . No differences in mineral balance were detected between the F and F+LCP groups , with both groups demonstrating comparable intake , net retention , and fecal losses of each mineral . Conclusions Adding a content of LCP blend similar to that of human milk to a preterm formula caused no disturbance in Ca , P , Mg , Zn , or Cu nutritional balance OBJECTIVES To compare the early neurological maturation of premature newborns ( PT ) fed breast milk ( BM ) or a formula containing only 18-carbon polyunsaturated fatty acids ( PUFA ) (  A ) or enriched with long chain ( LC ) PUFA ( B ) . METHODS PT enrolled the 2nd day of enteral feeding ( D0 ) were fed BM  ( n = 15 ; 4 dropped out ) or r and omly assigned to A ( n = 11 ; 2 ) or B ( n = 14 ; 1 ) for at least 30 days ( D30 ) . Auditory and visual evoked potentials ( EPs ) and nerve conduction velocity ( NCV ) and plasma and red blood cell ( RBC ) phospholipid composition were determined at D0 and D30 . No difference was found between groups for the D0-D30 changes in EP parameters . The maturation of motor NCV was slower in the B group than in the two other groups . In plasma , the changes were higher in B than in the BM and A groups for linoleic acid ( P < 0.05 ) , in BM versus B group for arachidonic acid ( P < 0.02 ) . In RBC , formula groups displayed higher linoleic acid level than the BM group ( P < 0.05 ) . No difference was found between groups for the changes in arachidonic and docosahexaenoic acids . CONCLUSIONS A balanced supply of n-6 and n-3 PUFA without addition of LC-PUFA allowed an adequate early maturation of the central nerve system . The effects of LC-PUFA on the maturation of NCV remain to be confirmed A milk formula ( Prematil‐LCP ) containing long‐chain polyunsaturated fatty acids ( LCP ) and with a fatty acid profile closely resembling breast milk has recently been introduced for preterm infants . A double‐blind r and omized controlled trial was performed comparing fatty acid absorption from Prematil‐LCP ( n= 10 ) and st and ard Prematil ( n= 10 ) . Formula‐fed preterm infants underwent 3 d fat balances ( once full enteral feeds were established ) along with a parallel human milk fed group ( n= 11 ) . Plasma sample s were taken on the last day . Median total fat excretion ( absorption , % ) was 2.34 g kg ( 82.0 ) , 2.64 g kg ( 82.9 ) and 1.65 g kg ( 87.8 ) with Prematil , Prematil‐LCP and human milk feeding , respectively . This reflected differences in the excretion and absorption of long‐chain saturated fatty acids . All groups excreted detectable LCP . LCP disappearance was higher in infants fed human milk than in those fed Prematil‐LCP , particularly for n‐6 LCP ( p < 0:01 ) . Nevertheless , excreted LCP equated to < 30 % dietary intake , with Prematil‐LCP feeding . Plasma lipid fatty acid composition reflected differences in dietary LCP intake Background and objective : Few studies of low birthweight children have explored the relationship between later visual morbidity and neuropsychological function . This study evaluated these outcomes using a geographically defined cohort . Methods : Prospect i ve study of retinopathy of prematurity ( ROP ) in infants born weighing < 1701 g , undertaken in 1985–7 . 254 of the survivors consented to ophthalmic examination at 10–13 years . Four children were severely disabled and could not complete the tests . 198 of the remaining agreed to  neuropsychological assessment  at 11–14 years ( British Ability Scales II ( BAS ) , Movement Assessment Battery ( ABC ) , Neale Analysis of Reading Ability ) . Results : At 10–13 years , 99/198 children had an adverse ophthalmic outcome ( AOO ) ( reduced acuity n = 48 , myopia n = 40 , strabismus n = 36 , colour defect n = 2 , field defect n = 1 ) . There were no significant differences between children with AOO and those with a normal ophthalmic outcome with regard to sex , gestation , birth weight , neonatal cranial scan appearances and social class . 106/198 had ROP ; 98 had mild ROP with no increased risk of AOO in later childhood . All eight children with severe ROP had an AOO in later childhood . Children with an AOO performed worse on the BAS , ABC and reading ability tests . Conclusions : At age 10–13 , 50 % of children born < 1701 g have an AOO . These children are not simply those with earlier gestations , lower birth weight or ROP . Children with AOO have a worse neuropsychological outcome . The next step is to determine whether there are visual interventions which can improve ophthalmic outcome and whether a better neuropsychological outcome follows 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 influence of long chain polyunsaturated fatty acids ( LCP ) in formula feeds on lipid peroxidation and antioxidants was studied in 35 healthy preterm infants ( gestational age 30 - 35 wk ) during the first 6 postnatal weeks . Infants received a preterm formula supplemented with n-3 LCP ( LCP group , n = 13 ) , or st and ard preterm formula ( NO-LCP group , n = 15 ) ; 7 infants fed human milk  served as a reference group . With LCP supplementation , erythrocyte C22:6n-3 levels were stable ; without supplementation , the levels declined ( difference p < 0.001 ) . LCP supplementation did not decrease vitamin E or C levels , or increase lipid peroxidation products ( thiobarbituric acid-reactive substances ) in plasma . In erythrocytes , LCP supplementation did not markedly influence the reduced/oxidized glutathione ratio ; however , the susceptibility to H2O2-induced oxidative stress was reduced . Our results suggest that healthy preterm infants are able to cope with any extra peroxidative stress produced by n-3 LCP supplementation . However , these findings might not be generally applicable to other formulas containing LCP supplements CONTEXT Neonatal infections are frequent complications of extremely low-birth-weight ( ELBW ) infants receiving intensive care . OBJECTIVE To determine if neonatal infections in ELBW infants are associated with increased risks of adverse neurodevelopmental and growth sequelae in early childhood . DESIGN , SETTING , AND PARTICIPANTS Infants weighing 401 to 1000 g at birth ( born in 1993 - 2001 ) were enrolled in a prospect ively collected very low-birth-weight registry at academic medical centers participating in the National Institute of Child Health and Human Development Neonatal Research Network .  Neurodevelopmental and growth outcomes were assessed at a comprehensive follow-up visit at 18 to 22 months of corrected gestational age and compared by infection group . Eighty percent of survivors completed the follow-up visit and 6093 infants were studied . Registry data were used to classify infants by type of infection : uninfected ( n = 2161 ) , clinical infection alone ( n = 1538 ) , sepsis ( n = 1922 ) , sepsis and necrotizing enterocolitis ( n = 279 ) , or meningitis with or without sepsis ( n = 193 ) . MAIN OUTCOME MEASURES Cognitive and neuromotor development , neurologic status , vision and hearing , and growth ( weight , length , and head circumference ) were assessed at follow-up . RESULTS The majority of ELBW survivors ( 65 % ) had at least 1 infection during their hospitalization after birth . Compared with uninfected infants , those in each of the 4 infection groups were significantly more likely to have adverse neurodevelopmental outcomes at follow-up , including cerebral palsy ( range of significant odds ratios [ ORs ] , 1.4 - 1.7 ) , low Bayley Scales of Infant Development II scores on the mental development index ( ORs , 1.3 - 1.6 ) and psychomotor development index ( ORs , 1.5 - 2.4 ) , and vision impairment ( ORs , 1.3 - 2.2 ) . Infection in the neonatal period was also associated with impaired head growth , a known predictor of poor neurodevelopmental outcome . CONCLUSIONS This large cohort study suggests that neonatal infections among ELBW infants are associated with poor neurodevelopmental and growth outcomes in early childhood . Additional studies are needed to eluci date the pathogenesis of brain injury in infants with infection so that novel interventions to improve these outcomes can be explored 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 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 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 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 The influence of dietary omega-3 fatty acid supply on visual acuity development was evaluated in very low birth weight ( VLBW ) infants using visual-evoked potential ( VEP ) and forced-choice preferential-looking ( FPL ) procedures at 36 and 57 wk postconception . The VLBW infants born at 27 - 33 wk postconception were r and omized to one of three diet groups : corn oil , which provided solely linoleic acid ; soy oil , which provided linoleic and alpha-linolenic acids ; or soy/marine oil ; which was similar to the soy oil formula but also provided preformed long chain omega-3 fatty acids . The VLBW infants in the soy/marine oil group had higher omega-3 levels in erythrocyte membranes and better VEP and FPL acuities at 36 and 57 wk than infants in the corn oil group . The soy oil group had intermediate omega-3 levels in erythrocyte membranes and significantly poorer VEP acuity at 57 wk compared with the soy/marine oil group . Only the soy/marine oil group had acuities comparable to the " gold st and ards " of VLBW infants fed human milk and preterm infants who were born and tested at 35 - 36 wk postconception . In addition , VEP and FPL acuity were poorer in a nonr and omized group of formula-fed full-term infants than in breast-fed full-term infants . The results suggest that dietary omega-3 fatty acid supply may play an important role in early human visual development Background / objective : Long chain polyunsaturated fatty acids have beneficial effects in preterm neurophysiological development and are semi-essential . Their levels and variation in plasma and red cells in term and preterms are better known than their intestinal absorption . In this paper the absorption of supplemented arachidonic acid ( AA ) and docosahexaenoic acid ( DHA ) is evaluated in a preterm group . Design : Four newborn r and omized groups were studied . Group T comprised 11 terms on regular formula . Preterms : group P ( n=9 ) was on a classic preterm formula . Intervention : groups PA ( n=9 ) and PB ( n=13 ) were on the same formula but PB contained AA and DHA in similar proportion to breast milk . At 20 days a 3 day metabolic balance was taken for Ca , Pi , Mg , total fat and individual fatty acids ( C8–C24 , saturated unsaturated ) . Results : Calcium absorption was ( mean±s.d . ) 51±13 % in terms . In preterms it was respectively 45±18 , 38±11 and 37±21 % . Total fat absorption was 92.0±8.0 % in terms , and from 95.0±2.0 to 91.0±8.0 % in preterms . Absorption of 8:0 , 10:0 and 12:0 showed a very high and constant rate despite significant intake differences ( 715–33 mg/kg/day ) . Linoleic acid and α-linolenic acid were absorbed in the three groups at around 94 % regardless of a greater LA intake in group P. Details of absorption ( mg/kg/day ) were : for AA , intake 17±7 , fecal excretion 5±4 , net retention 12±5 ( 75.0±18 % ) ; for DHA , intake 10±3 , fecal excretion 3±2 , net retention 6±4 ( 62.3±30 % ) . Conclusion : Intestinal absorption of fatty acids is high and is comparable in terms and preterms as regards the studied acids . Longer acids were less well absorbed . The supplemented amounts of AA and DHA  were less well absorbed and probably not impairing calcium absorption . Sponsorship : University of Alicante , University of Miguel Hernández . European Journal of Clinical Nutrition ( 2001 ) 55 , 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 Objectives . To examine the prevalence , stability , and predictors of clinical ly significant behavior problems in 869 preterm low birth weight ( LBW ) infants at 3 , 5 , and 8 years of age . Methods . A prospect i ve cohort study was conducted . Clinical ly significant behavior problems were assessed using dichotomized total problem Child Behavior Checklist scores in LBW children at ages 3 , 5 , and 8 years . Baseline sociodemographic and obstetric data were collected . Maternal General Health Question naire performed at 40 weeks ' gestation was dichotomized at a score of 12 to give a measure of maternal psychological distress . Prevalence and stability of behavior problems at ages 3 , 5 , and 8 were determined and potential predictors of behavior problems at age 3 , 5 , and 8 were examined using multiple logistic regression . Results . Prevalence of behavior problems remained at ∼20 % at 3 , 5 , and 8 years . Stability of behavior problems between different ages was ∼50 % . Significant behavior problems at ages 3 , 5 , and 8 were predicted by maternal psychological distress at 40 weeks ( odds ratio [ OR ] : 1.59 ; 95 % confidence interval [ CI ] : 1.21–2.09 ) , maternal cigarette smoking during pregnancy ( OR : 1.57 ; 95 % CI : 1.20–2.04 ) , Hispanic ethnicity ( OR : 2.00 ; 95 % CI : 1.24–3.24 ) , and maternal age ( OR : 0.97 ; 95 % CI : 0.94–0.99 ) . Conclusions . This sample had double the prevalence of behavior problems expected in the general child population . These problems showed stability over time . Cigarette smoking in pregnancy , maternal psychological distress at 40 weeks ' gestation , maternal age , and Hispanic ethnicity all were significant predictors of the development of behavior problems from ages 3 to 8 . These findings have implication s for health policies on smoking and postnatal depression 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 Diverging results from studies of marine oil supplementation to western diets initiated the undertaking of a double-blind crossover study , with administration to healthy volunteers for 4 weeks of either 10 g of fish oil or 10 g of vegetable oil . Each oil containing approx . 40 % of n-3 and n-6 polyunsaturated fatty acids ( PUFA ) respectively . During the n-3 PUFA period , systolic blood pressure , plasma total lipids , triglycerides and VLDL concentrations fell significantly whereas plasma antithrombin-III ( AT-III ) rose . Cutaneous bleeding time increased significantly . In contrast only AT-III rose during the n-6 PUFA feeding , however , more marked than during the n-3 oil period . It is concluded that a n-3 PUFA oil supplement to the western diet exerts an effect that generally is considered as beneficial in terms of the risk of developing cardiovascular diseases . It is in this respect superior to that of n-6 PUFA , stressing the necessity of a more differentiated approach to advice on dietary PUFA enrichment than presently is exerted This study evaluated preterm infants of less than 2.3 kg birth weight fed commercial formula ( Preemie SMA ® ) devoid of arachidonic acid ( AA ) and docosahexaenoic acid ( DHA ) and compared this control group with similar infant groups fed one of three formulas containing a range of 0.32—1.1 % AA and 0.24—0.75 % DHA  in the fat component of the formula . An analogous group of infants fed on their mothers ' breast milk and a breast milk fortifier  was also studied . Individual lipoprotein fractions were isolated from blood sample s collected at 12 d of age and after a further 4 wk of feeding . The fatty acid content of individual lipid components , isolated from each lipoprotein fraction was quantitatively determined in order to identify change in marker pools of essential fatty acid . The high density lipoproteins ( HDL ) and low density lipoproteins ( LDL ) phospholipid and cholesterol ester fractions contain most of the AA and DHA found in the lipoprotein fractions ( total of 0.49 % and 0.35 % , respectively ) . Infants fed a formula without AA and DHA showed a reduction in AA level in the phospholipid fraction of all lipoproteins and in the HDL and LDL cholesterol ester fraction . A reduced level of DHA was also observed primarily in the lipoprotein phospholipid fraction 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 level of AA found in the HDL and LDL phospholipid fraction . From comparison of the fatty acid levels present in the lipoproteins it appears that a formula level of 0.49 % AA and 0.35 % DHA provides sufficient levels of these fatty acids to achieve a similar fatty acid content to that of infants fed breast milk for the major lipoprotein fractions examined . □ Diet , fatty acid , infant , 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 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 The objective of this study was to evaluate the effect of conventional and long-chain polyunsaturated fatty acids (LCP)-enriched preterm formula on prostanoid formation in preterm infants during their first weeks of life . In a prospect i ve , r and omized , double-blind study , healthy infants received either formula enriched with LCP ( n = 10 ) , st and ard preterm formula(n = 10 ) , or ( expressed ) breast milk ( n = 10 ) . Urine was sample d , and anthropometric measurements were taken at study entry and after the study period of 3 wk . In vivo formation of prostagl and in E2 , thromboxane A2 , and prostacyclin was evaluated by measuring the urinary excretion of the respective index metabolites by gas chromatography-mass spectrometry . There were no significant differences in urinary prostanoid excretion and anthropometric data between the groups at the end of the study period . We conclude that neither conventional formula nor supplementation of a preterm formula with LCP for a period of 3 wk substantially influence prostanoid formation in healthy preterm infants
BACKGROUND Supplementation of preterm formulas with long-chain polyunsaturated fatty acids ( LCPUFAs ) is based on their effectiveness to increase blood status and improve visual outcomes .
Dispute remains over their efficacy on global development .
OBJECTIVE The objective was to compare the effects of LCPUFA-supplemented with those of control formulas on  neurodevelopment and diseases associated with prematurity .