Breastfeeding and child cognitive development: new evidence from a large randomized trial. The Groningen LCPUFA Study: No Effect of Short-Term Postnatal Long-Chain Polyunsaturated Fatty Acids in Healthy Term Infants on Cardiovascular and Anthropometric Development at 9 Years Visual, cognitive, and language assessments at 39 months: a follow-up study of children fed formulas containing long-chain polyunsaturated fatty acids to 1 year of age. Effect of providing a formula supplemented with long-chain polyunsaturated fatty acids on immunity in full-term neonates. Breast feeding and cognitive development in childhood: a prospective birth cohort study. Dietary Long-Chain Polyunsaturated Fatty Acids Do Not Influence Growth of Term Infants: A Randomized Clinical Trial Long-Chain Polyunsaturated Fatty Acid Supplementation in Infancy Reduces Heart Rate and Positively Affects Distribution of Attention A randomized controlled trial of long-chain polyunsaturated fatty acid supplementation of formula in term infants after weaning at 6 wk of age. Visual maturation of term infants fed long-chain polyunsaturated fatty acid-supplemented or control formula for 12 mo. Effect of Dietary Omega-3 Fatty Acids on Retinal Function of Very-Low-Birth-Weight Neonates Infants fed formula with added long chain polyunsaturated fatty acids have reduced incidence of respiratory illnesses and diarrhea during the first year of life Effects of long-chain PUFA supplementation in infant formula on cognitive function in later childhood. Relationship between omega3 long-chain polyunsaturated fatty acid status during early infancy and neurodevelopmental status at 1 year of age. Growth and development in term infants fed long-chain polyunsaturated fatty acids: a double-masked, randomized, parallel, prospective, multivariate study. A novel infant formula milk with added long-chain polyunsaturated fatty acids from single-cell sources: a study of growth, satisfaction and health A Critical Appraisal of the Role of Dietary Long-Chain Polyunsaturated Fatty Acids on Neural Indices of Term Infants: A Randomized, Controlled Trial Safety of supplementing infant formula with long-chain polyunsaturated fatty acids and Bifidobacterium lactis in term infants: a randomised controlled trial. Breastfeeding Duration and Academic Achievement at 10 Years Formula Supplementation With Long-chain Polyunsaturated Fatty Acids: Are There Developmental Benefits? The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid. Long chain polyunsaturated fatty acid supplementation in infant formula and blood pressure in later childhood: follow up of a randomised controlled trial Impact of Breast Milk on Intelligence Quotient, Brain Size, and White Matter Development Visual Acuity, Erythrocyte Fatty Acid Composition, and Growth in Term Infants Fed Formulas with Long Chain Polyunsaturated Fatty Acids for One Year Effects of long-chain polyunsaturated fatty acid supplementation of infant formula on cognition and behaviour at 9 years of age. Are long-chain polyunsaturated fatty acids essential nutrients in infancy? Erythrocyte fatty acid composition in term infants fed human milk or a formula enriched with a low eicosapentanoic acid fish oil for 4 months Effect of formula supplemented with docosahexaenoic acid and gamma-linolenic acid on fatty acid status and visual acuity in term infants. Developmental quotient at 24 months and fatty acid composition of diet in early infancy: a follow up study Effects of high-dose fish oil supplementation during early infancy on neurodevelopment and language: a randomised controlled trial. Effect of Feeding a Formula Supplemented With Long-chain Polyunsaturated Fatty Acids for 14 Weeks Improves the Ex Vivo Response to a Mitogen and Reduces the Response to a Soy Protein in Infants at Low Risk for Allergy Visual Acuity and the Essentiality of Docosahexaenoic Acid and Arachidonic Acid in the Diet of Term Infants Red blood cell membrane fatty acid composition in infants fed formulas with different lipid profiles. Neurodevelopmental Quotient of Healthy Term Infants at 4 Months and Feeding Practice: The Role of Long-Chain Polyunsaturated Fatty Acids Long‐chain polyunsaturated fatty acids and neurological developmental outcome at 18 months in healthy term infants Effect of long-chain polyunsaturated fatty acids in infant formula on problem solving at 10 months of age Cognitive function in 18-month-old term infants of the DIAMOND study: a randomized, controlled clinical trial with multiple dietary levels of docosahexaenoic acid. Long-term effects of LCPUFA supplementation on childhood cognitive outcomes. Growth and development of term infants fed with milk with long-chain polyunsaturated fatty acid supplementation. Infant formula composition affects energetic efficiency for growth: the BeMIM study, a randomized controlled trial. Effect of dietary linoleic/alpha-linolenic acid ratio on growth and visual function of term infants. A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants. Docosahexaenoic acid supplementation and time at achievement of gross motor milestones in healthy infants: a randomized, prospective, double-blind, placebo-controlled trial. Formula with long-chain polyunsaturated fatty acids reduces incidence of allergy in early childhood. A randomized trial of DHA intake during infancy: school readiness and receptive vocabulary at 2-3.5 years of age. Efficacy and safety of long-chain polyunsaturated fatty acid supplementation of infant-formula milk: a randomised trial Influence of Breast‐Feeding on the Infant's Intellectual Development Visual Acuity and Fatty Acid Status of Term Infants Fed Human Milk and Formulas with and without Docosahexaenoate and Arachidonate from Egg Yolk Lecithin1 Visual acuity and cognitive outcomes at 4 years of age in a double-blind, randomized trial of long-chain polyunsaturated fatty acid-supplemented infant formula. Impact of Early Dietary Intake and Blood Lipid Composition of Long-Chain Polyunsaturated Fatty Acids on Later Visual Development The Groningen LCPUFA study: no effect of postnatal long-chain polyunsaturated fatty acids in healthy term infants on neurological condition at 9 years.
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 Conflicting evidence exists on the effect of long-chain polyunsaturated fatty acid ( LCPUFA ) formula supplementation on cardiovascular health in term infants . It is known that LCPUFA supplementation does not affect infant growth , but long term outcome data are not available . The current study investigates whether 2 mo LCPUFA formula supplementation affects cardiovascular and anthropometric development at 9 y. A prospect i ve , double-blind , r and omized trial was performed in healthy term infants : a st and ard formula control group ( CF , n = 169 ) and a LCPUFA-supplemented group [ LF , n = 145 ; 0.45 % ( by wt ) AA  and 0.30 % ( by wt ) docosahexaenoic acid ( DHA ) ] . A breastfed group ( BF ; n = 159 ) served as reference . At the age of 9 y , systolic and diastolic blood pressure , heart rate , head circumference , weight , and height were measured . Univariate and multivariate analyses were performed ; 63 to 79 % of children were assessed . None of the cardiovascular or anthropometric measurements differed between the formula groups . Breastfed children had a marginally lower heart rate than formula-fed children , in particular compared with children fed control formula . Blood pressure and parameters of growth including BMI of breast and formula-fed children did not differ . In conclusion , the study suggests that short-term LCPUFA supplementation does not influence cardiovascular and anthropometric development at 9 OBJECTIVE Docosahexaenoic acid ( DHA ) and arachidonic acid ( ARA ) are long-chain polyunsaturated fatty acids found in breast milk and recently added to infant formulas . Their importance in infant nutrition was recognized by the rapid accretion of these fatty acids in the brain during the first postnatal year , reports of enhanced intellectual development in breastfed children , and recognition of the physiologic importance of DHA in visual and neural systems from studies in animal models . These considerations led to clinical trials to evaluate whether infant formulas that are supplemented with DHA or both DHA and ARA would enhance visual and cognitive development or whether conversion of linoleic acid and alpha-linolenic acid , the essential fatty acid precursors of ARA and DHA , respectively , at the levels found in infant formulas is sufficient to support adequately visual and cognitive development . Visual and cognitive development were not different with supplementation in some studies , whereas other studies reported benefits of adding DHA or both DHA and ARA to formula . One of the first trials with term infants that were fed formula supplemented with DHA or both DHA and ARA evaluated growth , visual acuity ( Visual Evoked Potential ; Acuity Card Procedure ) , mental and motor development ( Bayley Scales of Infant Development ) , and early language development ( MacArthur Communicative Developmental Inventories ) . Growth , visual acuity , and mental and motor development were not different among the 3 formula groups or between the breastfed and formula-fed infants in the first year of life . At 14 months of age , infants who were fed the formula with DHA but no ARA had lower vocabulary production and comprehension scores than infants who were fed the unsupplemented control formula or who were breastfed , respectively . The present follow-up study evaluated IQ , receptive and expressive vocabulary , visual-motor function , and visual acuity of children from the original trial when they reached 39 months of age . METHODS Infants were r and omized within 1 week after birth and fed a control formula ( n = 65 ) , one containing DHA ( n = 65 ) , or one containing both ARA and DHA ( n = 66 ) to 1 year of age . A comparison group ( n = 80 ) was exclusively breastfed for at least 3 months after which the infants continued to be exclusively breastfed or were supplemented with and /or weaned to infant formula . At 39 months , st and ard tests of IQ ( Stanford Binet IQ ) , receptive vocabulary ( Peabody Picture Vocabulary Test-Revised ) , expressive vocabulary ( mean length of utterance ) , visual-motor function ( Beery Visual-Motor Index ) , and visual acuity ( Acuity Card Procedure ) were administered . Growth , red blood cell fatty acid levels , and morbidity also were evaluated . RESULTS Results were analyzed using analysis of variance or linear regression models . The regression model for IQ , receptive and expressive language , and the visual-motor index controlled for site , birth weight , sex , maternal education , maternal age , and the child 's age at testing . The regression model for  visual acuity  controlled for site only . A variable selection model also identified which of 22 potentially prognostic variables among different categories ( feeding groups , the child and family demographics , indicators of illness since birth , and environment ) were most influential for IQ and expressive vocabulary . A total of 157 ( 80 % ) of the 197 infants studied at 12 months participated in this follow-up study . Characteristics of the families were representative of US families with children up to 5 years of age , and there were no differences in the demographic or family characteristics among the r and omized formula groups . As expected , the formula and breastfed groups differed in ethnicity , marital status , parental education , and the prevalence of smoking . Sex , ethnicity , gestational age at birth , and birth weight for those who participated at 39 months did not differ from those who did not . The 12-month Bayley mental and motor scores and 14-month vocabulary scores of the children who participated also were were not different from those who did not . At 39 months , IQ , receptive and expressive language , visual-motor function , and visual acuity were not different among the 3 r and omized formula groups or between the breastfed and formula groups . The adjusted means for the control , ARA+DHA , DHA , and breastfed groups were as follows : IQ scores , 104 , 101 , 100 , 106 ; Peabody Picture Vocabulary Test , 99.2 , 97.2 , 95.1 , 97.4 ; mean length of utterance , 3.64 , 3.75 , 3.93 , 4.08 ; the visual-motor index , 2.26 , 2.24 , 2.05 , 2.40 ; and visual acuity ( cycles/degree ) , 30.4 , 27.9 , 27.5 , 28.6 , respectively . IQ was positively associated with female sex and maternal education and negatively associated with the number of siblings and exposure to cigarette smoking in utero and /or postnatally . Expressive language also was positively associated with maternal education and negatively associated with the average hours in child care per week and hospitalizations since birth but only when the breastfed group was included in the analysis . The associations between maternal education and child IQ scores are consistent with previous reports as are the associations between prenatal exposure to cigarette smoke and IQ and early language development . Approximately one third of the variance for IQ was explained by sex , maternal education , the number of siblings , and exposure to cigarette smoke . Growth achievement , red blood cell fatty acid levels , and morbidity did not differ among groups . CONCLUSIONS We reported previously that infants who were fed an unsupplemented formula or one with DHA or with both DHA and ARA through 12 months or were breastfed showed no differences in mental and motor development , but those who were fed DHA without ARA had lower vocabulary scores on a st and ardized , parent-report instrument at 14 months of age when compared with infants who were fed the unsupplemented formula or who were breastfed . When the infants were reassessed at 39 months using age-appropriate tests of receptive and expressive language as well as IQ , visual-motor function and visual acuity , no differences among the formula groups or between the formula and breastfed groups were found . The 14-month observation thus may have been a transient effect of DHA ( without ARA ) supplementation on early vocabulary development or may have occurred by chance . The absence of differences in growth achievement adds to the evidence that DHA with or without ARA supports normal growth in full-term infants . In conclusion , adding both DHA and ARA when supplementing infant formulas with long-chain polyunsaturated fatty acids supports visual and cognitive development through 39 months To determine the effect of feeding formula containing long-chain PUFA ( LCP ) on immune function , healthy term infants were r and omised at age 2 weeks to either a st and ard term formula ( Formula ; n 14 ) or the same formula supplemented with the LCP 20 : 4n-6 and 22 : 6n-3 ( Formula+LCP ; n 16 ) . Peripheral blood was collected at 2 and 6 weeks to measure immune cell response ( the rate of [3H]thymidine uptake and cytokine production after stimulation with phytohaemagglutinin ( PHA ) ) . Compared with cells from infants receiving only human milk ( HM ) , the rate of [3H]thymidine uptake in response to PHA , but not IL-2 production , was lower for Formula+LCP infants ( P < 0.05 ) . Compared with HM-fed infants , Formula-fed infants ( but not Formula+LCP infants ) produced more TNF-alpha ( unstimulated ) and had a fewer CD3+CD44 + cells before stimulation and fewer CD11c+ cells post-stimulation ( P < 0.05 ) . However , compared with Formula-fed infants , the Formula+LCP infants had an immune cell distribution ( higher percentage CD3+CD44 + and CD4+CD28 + cells ) and cytokine profile ( lower production of TNF-alpha post-stimulation ) that did not differ from HM infants . Additionally , it was found that feeding infants formula during the first 10 d of life influenced immune function . These infants had a higher percentage of CD3 + , CD4+CD28 + , and lower percentage of CD14 + cells and produced more TNF-alpha and interferon-gamma after PHA stimulation than HM-fed infants ( P < 0.05 ) . These results demonstrate that early diet influences both the presence of specific cell types and function of infant blood immune cells . Since many diseases have a strong immunological component , these immune changes may be of physiological importance to the developing infant The aim of this study was to examine prospect ively the relation between duration of breast feeding and cognitive outcomes . A cohort study of 2860 children enrolled before birth provided data from 2393 term infants of English-speaking mothers . Of these , complete infant feeding data in the first year of life and verbal cognitive IQ ( Peabody Picture Vocabulary Test - PPVT-R ) were available for 1450 children at 6 years , and a performance subtest ( Perceptual organisation WISC - Block Design ) for 1375 children at 8 years . Full breast feeding was categorised as none , > 0 to < 4 months , 4 - 6 months and > 6 months . Associations between breast-feeding duration and PPVT-R at 6 years and Block Design at 8 years were estimated before and after adjustment for gender , gestational age , maternal age , maternal education , parental smoking and the presence of older siblings . The early cessation of full breast feeding was associated with reduced verbal IQ and the performance subtest . In unadjusted analysis , mean st and ardised PPVT-R scores were 6.44 points greater ( P < 0.0001 ) in children fully breast fed for > 6 months compared with those never breast fed . After adjustment , mean PPVT-R scores were 3.56 points higher in children fully breast fed for > 6 months compared with those children never breast fed ( P = 0.003 ) . Similarly , Block Design scores were higher in those fully breast fed for > 6 months compared with those never breast fed in unadjusted ( P = 0.001 ) but not adjusted analyses ( P = 0.223 ) . Interactions between maternal education ( four levels ) and breast feeding demonstrated a positive association of maternal education on verbal IQ ( F = 2.64 ; P = 0.005 ) in children breast fed for longer but not on performance ( F = 0.74 ; P = 0.67 ) . The early introduction of milk other than breast milk was associated with reduced verbal IQ after adjustment for social and perinatal confounders . Although these effects were interacting with maternal education , they may act through undefined mechanisms in human milk Objective . To determine if dietary long-chain polyunsaturated fatty acids ( LCPUFA ) affect the growth of formula-fed infants relative to breastfed infants . Methods . A r and omized , double-blind trial of three formula-fed groups and a parallel reference group of breastfed infants was conducted . The three treatments were a placebo ( no LCPUFA ) , docosahexaenoic acid ( DHA ) supplemented , and DHA plus arachidonic acid supplemented formulas fed for 12 months . Infant weight , length , head circumference , and fatty acid status were assessed at 6 , 16 , 34 weeks , and 1 year of age . Anthropometrics were repeated at 2 years of age . Results . There were no differences between the r and omized formula groups for weight , length , or head circumference even after adjustment for gender , gestational age , and the actual age at assessment . Post hoc regressions demonstrated a small negative association between DHA status at 16 weeks of age and weight at 1 and 2 years . Conclusions . Dietary LCPUFA do not influence growth of healthy term infants to a clinical ly significant degree A double-blind , r and omized , controlled , parallel-group prospect i ve trial was conducted to determine whether a dose-response existed for four different levels of docosahexaenoic acid ( DHA ) supplementation on the cognitive performance of infants . A total of 122 term infants were fed one of four different formulas varying in their DHA composition ( 0.00 , 0.32 , 0.64 , and 0.96 % of total fatty acids as DHA ) from birth to 12 mo . The three DHA-supplemented formulas also contained 0.64 % of total fatty acids as arachidonic acid ( ARA , 20:4n-6 ) . Infants were tested at 4 , 6 , and 9 mo of age on a visual habituation protocol that yielded both behavioral and psychophysiological indices of attention . Infants in all DHA+ARA-supplemented conditions had lower heart rates than those in the unsupplemented condition ; there was no dose-response for this effect . The distribution of time that infants spent in different phases of attention ( a cognitive index derived from the convergence of behavioral and cardiac responses ) varied as a function of dosage . Infants supplemented at the two lower DHA doses spent proportionately more time engaged in active stimulus processing than infants fed the unsupplemented formula , whereas infants fed the highest dose were intermediate and did not differ from any other group BACKGROUND The critical period during which the dietary supply of long-chain polyunsaturated fatty acids ( LCPs ) may influence the maturation of cortical function in term infants is unknown . OBJECTIVE The aim of the present study was to determine the relative importance for maturation of the visual cortex of the dietary supply of LCPs during the first 6 wk of life compared with that during weeks 7 - 52 . DESIGN A r and omized controlled clinical trial of LCP supplementation in 65 healthy term infants who were weaned from breast-feeding at 6 wk of age was conducted to determine whether the dietary supply of LCPs after weaning influenced the maturation of visual acuity and stereoacuity . RESULTS Despite a dietary supply of LCPs from breast milk during the first 6 wk of life , infants who were weaned to formula that did not provide LCPs had significantly poorer visual acuity at 17 , 26 , and 52 wk of age and significantly poorer stereoacuity at 17 wk of age than did infants who were weaned to LCP-supplemented formula .  Better acuity and stereoacuity at 17 wk was correlated with higher concentrations of docosahexaenoic acid in plasma . Better acuity at 52 wk was correlated with higher concentrations of docosahexaenoic acid in plasma and red blood cells . No significant effects of diet on growth were found . CONCLUSION The results suggest that the critical period during which the dietary supply of LCPs can influence the maturation of cortical function extends beyond 6 wk of age BACKGROUND Several studies found a benefit of long-chain polyunsaturated fatty acid ( LCP ) supplementation for visual or mental development , but others found no benefit . Likely contributors to differences among studies are the amount of LCP supplementation , functional outcomes , and sample size . OBJECTIVE We evaluated LCP supplementation in amounts typical for human milk ( based on local and worldwide surveys ) in a large cohort of infants by using sweep visual evoked potential ( VEP ) acuity as the functional outcome . DESIGN The study was a double-masked , r and omized , controlled clinical trial in 103 term infants . By age 5 d , infants were r and omly assigned to receive either formula with no docosahexaenoic acid ( DHA ) or arachidonic acid ( ARA ) or formula supplemented with DHA and ARA as 0.36 % and 0.72 % , respectively , of total fatty acids .  Sweep VEP acuity was the primary outcome . R and om dot stereoacuity , blood lipid profile , growth , and tolerance were secondary outcomes . RESULTS VEP acuity in the LCP-supplemented group was significantly better than that in the control group at ages 6 , 17 , 26 , and 52 wk . Stereoacuity in the LCP-supplemented group was significantly better than that in the control group at age 17 wk but not at ages 39 and 52 wk . By ages 17 and 39 wk , the red blood cell DHA concentration in the LCP-supplemented group was more than double and more than triple , respectively , that in the control group . Growth of infants fed LCP-supplemented and control formulas did not differ significantly , and both diets were well tolerated . CONCLUSION LCP supplementation of term infant formula during the first year of life yields clear differences in visual function and in total red blood cell lipid composition 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 Background Long chain polyunsaturated fatty acids ( LCPUFAs ) may influence the immune system . Our objective was to compare the frequency of common illnesses in infants who received formula with or without added LCPUFAs .  Methods In this observational , multi-center , prospect i ve study , infants consumed formula with 17 mg DHA and 34 mg ARA/100 kcal ( n = 233 ) or with no added DHA or ARA ( n = 92 ) . Pediatricians recorded respiratory illnesses , otitis media , eczema , and diarrhea through 1 year of age . Results Infants who consumed formula with DHA/ARA  had lower incidence of bronchitis/bronchiolitis ( P = 0.004 ) , croup ( P = 0.044 ) , nasal congestion ( P = 0.001 ) , cough ( P = 0.014 ) , and diarrhea requiring medical attention ( P = 0.034 ) . The odds ratio ( OR ) of having at least one episode of bronchitis/bronchiolitis ( 0.41 , 95 % CI 0.24 , 0.70 ; P = 0.001 ) , croup ( 0.23 , 95 % CI 0.05 , 0.97 ; P = 0.045 ) , nasal congestion ( 0.37 , 95 % CI 0.20 , 0.66 ; P = 0.001 ) , cough ( 0.52 , 95 % CI 0.32 , 0.86 ; P = 0.011 ) , and diarrhea requiring medical attention ( 0.51 , 95 % CI 0.28 , 0.92 ; P = 0.026 ) was lower in infants fed DHA/ARA . The OR of an increased number of episodes of bronchitis/bronchiolitis , croup , nasal congestion , cough , and diarrhea , as well as the hazard ratio for shorter time to first episode of bronchitis/bronchiolitis , nasal congestion , cough , and diarrhea were also significantly lower in the DHA/ARA group . Conclusions In healthy infants , formula with DHA/ARA was associated with lower incidence of common respiratory symptoms and illnesses , as well as diarrhea BACKGROUND Evidence is accumulating that a dietary supply of long-chain polyunsaturated fatty acids ( LC-PUFAs ) enhances the development of attention and efficient information processing in infants . However , it is uncertain whether LC-PUFAs in infancy influence cognitive development in later childhood . OBJECTIVE The objective was to determine the effects of dietary LC-PUFAs in infancy on measures of cognitive function at age 6 y. DESIGN Infants were r and omly assigned to receive formula containing either docosahexaenoic acid and arachidonic acid or no LCPUFAs for a period of 4 mo . A reference breastfed group was also included . In a follow-up conducted at age 6 y , children received assessment s of intelligence quotient ( IQ ) , attention control ( Day-Night Test ) , and speed of processing on the Matching Familiar Figures Test ( MFFT ) . RESULTS At follow-up there were 71 children in the LC-PUFA group , 76 in the control group , and 88 in the breastfed group . The formula groups did not differ on measures of Full-Scale IQ ( LCPUFA mean = 98.0 ; control mean = 100.9 ) or attention control ( LCPUFA mean = 12.7 ; control mean = 12.8 ) . MFFT error scores were the same for both formula groups , but when making correct responses , the LC-PUFA group was significantly faster ( mean = 6.2 s ) than the control group [ mean = 7.8 s ; F(1 , 131 ) = 6.09 , P = 0.015 ] . CONCLUSIONS IQ scores of children who were fed a formula containing either LC-PUFAs or no LC-PUFAs did not differ at age 6 y. However , children who received LC-PUFAs were faster at processing information compared with children who received unsupplemented formula . Variation in the dietary supply of LC-PUFAs in the first months of life may have long-term consequences for the development of some cognitive functions in later childhood OBJECTIVE To determine the influence of alpha-linolenic acid ( ALA ; 18 : 3omega3 ) intake and , hence , the influence of plasma and /or erythrocyte phospholipid content of docosahexaenoic acid ( DHA ; 22 : 6omega3 ) during early infancy on neurodevelopmental outcome of term infants . METHODS The Bayley Scales of Infant Development ( second edition ) , the Clinical Adaptive Test/ Clinical Linguistic and Auditory Milestone Scale ( CAT/CLAMS ) and the Gross Motor Scale of the Revised Gesell Developmental Inventory were administered at a mean age of 12.26 + /- 0.94 months to 44 normal term infants enrolled in a study evaluating the effects of infant formulas differing only in ALA content ( 0.4 , 1.0 , 1.7 and 3.2 % of total fatty acids ) . RESULTS As reported previously [ Jensen et al. , Lipids 13 ( 1996 ) 107 ; J. Pediatr . 131 ( 1997 ) 200 ] , the group fed the formula with the lowest ALA content had the lowest mean plasma and erythrocyte phospholipid DHA contents at 4 months of age . This group also had the lowest mean score on every neurodevelopmental measure . The difference in mean gross motor developmental quotient of this group versus the group fed the formula with 1.0 % ALA but not of the other groups was statistically significant ( P < 0.05 ) . Across the groups , motor indices correlated positively with each other and with the plasma phospholipid DHA content at 4 months of age ( P=0.02 - 0.03 ) . The CLAMS developmental quotient correlated with the erythrocyte phospholipid content of 20 : 5omega3 ( P < 0.01 ) but not with DHA . CONCLUSIONS These statistically significant correlations suggest that the omega3 fatty acid status during early infancy may be important with respect to neurodevelopmental status at 1 year of age and highlight the need for further studies of this possibility OBJECTIVE To evaluate the effects of dietary intake of the long-chain polyunsaturated fatty acids , arachidonic acid ( AA ) , and docosahexaenoic acid ( DHA ) on multiple indices of infant growth and development . DESIGN A double-masked , r and omized , parallel trial was conducted with term infants fed formulas with or without AA+DHA for 1 year ( N = 239 ) . Reference groups of breastfed infants ( N = 165 ) weaned to formulas with and without AA+DHA  were also studied . Infants in the formula groups were r and omized at < /=9 days of age to a control formula with no AA or DHA ( n = 77 ) or 1 of 2 otherwise identical formulas containing AA+DHA ( AA , 0.46 % and DHA , 0.14 % of total fatty acids ) from either egg-derived triglyceride ( egg-DTG [ n=80 ] ) or fish oil and fungal oil ( fish/fungal [ n = 82 ] ) at levels similar to the average in breast milk sample s as measured in the reference group . All formulas contained 50 % of energy from fat with the essential dietary fatty acids , linoleic acid ( 20 % fatty acids ) and alpha-linolenic acid ( 2 % fatty acids ) . The main study outcomes were AA and DHA levels in plasma and red blood cells , and multiple measures of infant development at multiple ages from birth to 14 months : growth , visual acuity , information processing , general development , language , and temperament . RESULTS  AA and DHA levels in plasma and red cells were higher in AA+DHA-supplemented groups than in the control formula group and comparable to those in reference groups . No developmental test results distinguished these groups . Expected differences in family demographics associated with breastfeeding were found , but no advantages to breastfeeding on any of the developmental outcome demonstrated . CONCLUSIONS These findings do not support adding AA+DHA to formulas containing 10 % energy as linoleic acid and 1 % energy as alpha-linolenic acid to enhance growth , visual acuity , information processing , general development , language , or temperament in healthy , term infants during the first 14 months after birth.infant development , breast feeding , infant formula , long-chain polyunsaturated fatty acids , docosahexaenoic acid Objective : To evaluate the growth , feeding and health of babies fed a novel infant formula milk  with added long chain polyunsaturated fatty acids ( LCPs ) produced from single-cell sources , at concentrations similar to those found in mature breast milk . Design : R and omized double-blind control trial . Subjects : One-hundred and forty healthy , full-term infants of birth weight 2.5–4.5 kg born at the Maternity Department , East Glamorgan General Hospital , Wales , whose mothers had already decided to bottle feed . Interventions : Subjects were r and omized to two groups ; one ( control group ) to receive a st and ard formula milk and the other to receive the trial milk with added LCPs . Milks were supplied in a double-blind fashion and given for the first 12 weeks of life . Anthropometric measurements were made at recruitment , 3 months , 6 months and 1 y. Feeding diaries were completed at 6 weeks and 3 months , and a parental record was kept of any ill health suffered by the subjects during the first year of life . Results : Of 140 infants recruited , 31 did not complete the protocol . Small but statistically significant differences were found only in the subscapular skinfold thickness at 6 weeks and 3 months , that in the trial group being slightly higher , but unlikely to be of any clinical importance . No differences were found in the feeding patterns of the infants in the two groups . Stool patterns were similar , as were the frequencies of illness and allergy . Conclusions : This study supports the view that LCPs from single-cell sources do not have detrimental effects on the growth , feeding and general health of infants . Sponsorship : The research nurse and equipment used in this study were funded by Cow & Gate Nutricia ( UK ) Ltd . European Journal of Clinical Nutrition ( 2000 ) 54 , Objective . To determine whether dietary long-chain polyunsaturated fatty acids ( LCPUFA ) , such as docosahexaenoic acid ( DHA ) and arachidonic acid , affect visual evoked potential ( VEP ) acuity of formula-fed infants , relative to breastfed infants . A secondary objective was to assess the effect of LCPUFA on Bayley 's mental developmental index ( MDI ) and psychomotor developmental index ( PDI ) . Methods . Formula-fed infants were r and omly allocated , in a double-blind manner , to either a placebo ( no LCPUFA;n = 21 ) , DHA supplemented ( n = 23 ) , or DHA+arachidonic acid supplemented formula ( n = 24 ) . Infants were fed their assigned formula from the first week of life until 1 year of age . A parallel reference group of breastfed infants was recruited and followed ( n = 46 ) . Infant VEP acuity was assessed at 16 and 34 weeks , and Bayley 's MDI and PDI were assessed at 1 and 2 years of age . Results . There were no differences among the r and omized formula groups for VEP acuity at either 16 or 34 weeks of age . Breastfed infants had better VEP acuity at 34 weeks of age , but not at 16 weeks , compared with all formula-fed infants . Bayley 's MDI and PDI were similar in the 3 formula-fed groups at 1 and 2 years . Breastfed infants had higher MDI scores than formula-fed infants at 2 years of age even after adjusting for environmental variables . Conclusions . LCPUFA supplementation did not influence VEP acuity development in these well-nourished , formula-fed infants Probiotics and long-chain PUFA ( LC-PUFA ) may be beneficial supplements for infants who are not breast-fed . The aim of the present study is to evaluate the safety of an infant formula containing the LC-PUFA DHA and arachidonic acid ( AA ) and the probiotic Bifidobacterium lactis by comparing the growth rate of infants fed the supplemented and unsupplemented formulas . One hundred and forty-two healthy , term infants were enrolled in a single-centre , r and omised , double-blind , controlled , parallel-group trial , and allocated to receive either st and ard or probiotic and LC-PUFA-containing experimental formulas . The infants were fed with their assigned formulas for 7 months . The primary outcome ( weight gain ) and the secondary outcomes ( length , head circumference and formula tolerance ) were measured throughout the study . LC-PUFA status was assessed at 4 months of age and immune response to childhood vaccines was measured at 7 months of age . There was no significant difference in growth between the two groups . The 90 % CI for the difference in mean weight gain was - 0.08 , 3.1 g in the intention-to-treat population and 0.1 - 3.8 g in the per protocol population , which lay within the predefined boundaries of equivalence , - 3.9 - 3.9 . There were no significant differences in mean length and head circumference . DHA and AA concentrations were higher in infants in the experimental formula group compared with the control formula group . No influence of the supplements on the response to vaccines was observed . Growth characteristics of term infants fed the starter formula containing a probiotic and LC-PUFA were similar to st and ard formula-fed infants INTRODUCTION : The aim of this study was to examine the relationship between duration of breastfeeding  and educational outcomes . We hypothesized that longer periods of breastfeeding would predict better educational outcomes in middle childhood . METHODS : The Western Australian Pregnancy Cohort ( Raine ) Study used a cohort of 2900 women who were enrolled at 18 weeks ' gestation ; with 2868 live-born children were followed prospect ively . At ∼10 years of age , data from 1038 children were linked to st and ardized mathematics , reading , writing , and spelling scores . Associations between breastfeeding duration and educational outcomes were estimated by using linear models with adjustment for gender , family income , maternal factors , and early stimulation at home through reading . RESULTS : Ten-year-old children who were predominantly breastfed for 6 months or longer in infancy had higher academic scores than children who were breastfed for less than 6 months . The effect of breastfeeding on educational outcomes differed according to gender ; boys were particularly responsive ( in mathematics , spelling , reading , and writing ) to a longer duration of breastfeeding . CONCLUSIONS : Predominant breastfeeding for 6 months or longer was positively associated with academic achievement in children at 10 years of age . However , the effectiveness of breastfeeding differed according to gender ; the benefits were only evident for boys Objective . To evaluate the developmental outcomes of children who participated in an augmented r and omized clinical trial of supplementing a st and ard infant formula with long-chain polyunsaturated fatty acids . Design . R and omized clinical trial , augmented with a nonr and omized human milk comparison group . There were three r and omized formula groups : st and ard formula , st and ard formula containing docosahexaenoic acid ( DHA ) , and st and ard formula containing DHA and arachidonic acid . Setting . Three clinical sites serving diverse population s : Kansas City , MO ; Portl and , OR ; and Seattle , WA . Participants . A total of 274 healthy full-term infants were enrolled in the infant-feeding protocol ; of these , 197 ( 72 % ) participated in assessment s of developmental outcome . Formula Supplements . In the r and omized trial , one group received a st and ard formula , another group received a formula that had been supplemented with DHA from fish oil , and a third group received a formula supplemented with both DHA and arachidonic acid from an egg phospholipid . Outcome Measures . Mental and Motor Scales of the Bayley Scales of Infant Development at 12 months of age ; vocabulary and gesture communication scores from the MacArthur Communicative Development Inventories at 14 months of age . Results . There were no statistically significant differences for either the Bayley Mental Scale or the Bayley Motor Scale , neither when the analysis was restricted to the three r and omized formula groups nor when the analysis included all four groups . However , the DHA formula group had significantly lower scores on two of the MacArthur scales : the DHA group scored lower than the nonr and omized human milk comparison group on the Vocabulary Comprehension Scale , and the DHA group scored lower than the r and omized control formula group on the Vocabulary Production Scale . Moreover , additional analyses both in the formula groups and in the human milk comparison group found significant negative correlations between DHA levels and vocabulary outcomes . Conclusion . We believe that additional research should be undertaken before the introduction of these supplements into st and ard infant formulas BACKGROUND The range of human milk docosahexaenoic acid ( DHA ) concentrations worldwide is much broader than the range explored in r and omized clinical trials to date . OBJECTIVE The primary objective was to determine the effect of 4 amounts of DHA supplementation on the visual acuity of formula-fed infants at 12 mo of age . Secondary objectives were to evaluate visual acuity maturation , red blood cell fatty acids , tolerance , anthropometric measures , and adverse events . DESIGN This double-masked , r and omized trial was conducted at 2 sites ( Dallas and Kansas City ) . Three hundred forty-three healthy , term , formula-fed infants were enrolled at 1 - 9 d of age and were r and omly assigned to be fed 1 of the following 4 infant formulas containing equivalent nutrient amounts , except for long-chain polyunsaturated fatty acids : control ( 0 % DHA ) , 0.32 % DHA , 0.64 % DHA , or 0.96 % DHA ; DHA-supplemented formulas also provided 0.64 % arachidonic acid .  Visual acuity was measured by visual evoked potentials in 244 infants who completed the 12-mo primary outcome examination . RESULTS Infants fed control formula had significantly poorer visual evoked potential visual acuity at 12 mo of age than did infants who received any of the DHA-supplemented formulas ( P < 0.001 ) . There were no significant differences in visual evoked potential visual acuity between the 3 amounts of DHA supplementation for either site at any age tested . CONCLUSIONS DHA supplementation of infant formula at 0.32 % of total fatty acids improves visual acuity . Higher amounts of DHA supplementation were not associated with additional improvement of visual acuity . This trial was registered at clinical trials.gov as NCT00753818 Abstract Objective : To determine whether supplementation of infant formula milk with long chain polyunsaturated fatty acids ( LCPUFAs ) influences blood pressure  in later childhood . Design : Follow up of a multicentre , r and omised controlled trial . Setting : Four study centres in Europe . Participants : 147 formula fed children , with a reference group of 88 breastfed children . Intervention : In the original trial newborn infants were r and omised to be fed with a formula supplemented with LCPUFAs ( n=111 ) or a formula without LCPUFAs but otherwise nutritionally similar ( n=126 ) . In the present follow up study the blood pressure of the children at age 6 years was measured . Main outcome measures : Systolic , diastolic , and mean blood pressure . Results : 71 children in the  LCPUFA supplementation group ( 64 % of the original group ) and 76 children in the non-supplementation group ( 60 % ) were enrolled into the follow up study . The LCPUFA group had significantly lower mean blood pressure ( mean difference −3.0 mm Hg ( 95 % confidence interval −5.4 mm Hg to −0.5 mm Hg ) ) and diastolic blood pressure ( mean difference −3.6 mm Hg ( −6.5 mm Hg to −0.6 mm Hg ) ) than the non-supplementation group . The diastolic pressure of the breastfed children ( n=88 ( 63 % ) ) was significantly lower than that of the non-supplemented formula group but did not differ from the LCPUFA formula group . Conclusions : Dietary supplementation with LCPUFAs during infancy is associated with lower blood pressure in later childhood . Blood pressure tends to track from childhood into adult life , so early exposure to dietary LCPUFAs may reduce cardiovascular risk in adulthood . What is already known on this topic Breast milk contains long chain polyunsaturated fatty acids , and breastfed children have lower blood pressure than children fed with formula milk Blood pressure differences in childhood are known to carry through into adulthood Dietary omega 3 fatty acid supplementation can lower blood pressure in adults with hypertension What this paper adds Supplementation with long chain polyunsaturated fatty acids in infancy results in lower blood pressure later in Although observational findings linking breast milk to higher scores on cognitive tests may be confounded by factors associated with mothers ' choice to breastfeed , it has been suggested that one or more constituents of breast milk facilitate cognitive development , particularly in preterms . Because cognitive scores are related to head size , we hypothesized that breast milk mediates cognitive effects by affecting brain growth . We used detailed data from a r and omized feeding trial to calculate percentage of expressed maternal breast milk ( % EBM ) in the infant diet of 50 adolescents . MRI scans were obtained ( mean age = 15 y 9 mo ) , allowing volumes of total brain ( TBV ) and white and gray matter ( WMV , GMV ) to be calculated . In the total group , % EBM correlated significantly with verbal intelligence quotient ( VIQ ) ; in boys , with all IQ scores , TBV and WMV . VIQ was , in turn , correlated with WMV and , in boys only , additionally with TBV . No significant relationships were seen in girls or with gray matter . These data support the hypothesis that breast milk promotes brain development , particularly white matter growth . The selective effect in males accords with animal and human evidence regarding gender effects of early diet . Our data have important neurobiological and public health implication s and identify areas for future mechanistic study The CNS and the retina are enriched in long chain polyunsaturated ( LCP ) fatty acids , specifically docosahexaenoic acid ( DHA , 22:6n-3 ) and arachidonic acid ( AA , 20:4n-6 ) , which are present in human milk but not in most infant formulas . In the present study of 134 formula-fed and 63 breast-fed infants , we prospect ively evaluated whether providing a source of DHA and AA or DHA alone in formula would increase red blood cell ( RBC ) phospholipid levels of these fatty acids , enhance visual function , or affect growth during the first year .  Healthy term infants < 7 d old were r and omized to be fed formulas containing linoleic acid ( ≈10 % kcal ) and α-linolenic acid ( ≈1 % kcal ) plus ( 1 ) no added LCP fatty acids ( control formula ) , ( 2 ) DHA ( 0.12 wt% fatty acids ) and AA ( 0.43 wt% ) from egg yolk phospholipid ( AA + DHA formula ) , or ( 3 ) DHA ( 0.2 wt% ) from fish oil ( DHA formula ) . A breast-fed group was studied concurrently and permitted formula supplementation after 3 mo . Visual acuity was measured using both the acuity card procedure and a visual evoked potential method at 2 , 4 , 6 , 9 , and 12 mo . Infants fed the control formula had 10 - 40 % lower RBC levels of DHA and AA than infants in the breast-fed group . Infants fed the AA+ DHA formula had levels of both LCP within ≈10 % of the values for infants in the breast-fed group , and infants fed the DHA formula had 25 - 55 % higher DHA levels and 15 - 40 % lower AA levels . There were no differences in growth or in visual function during this 12-mo feeding study AIM Long-chain polyunsaturated fatty acid ( LCPUFA ) supplementation of infant formula may have a beneficial effect on cognitive development . This study aim ed to investigate the effect of LCPUFA formula supplementation primarily on cognition and secondarily on behaviour at age 9 years . Special attention was paid to the potentially modifying effect of maternal smoking during pregnancy . METHOD A double-blind , r and omized control study was performed in two groups of healthy infants born at term : one group , constituting the control group , received st and ard formula ( n=169 ) and another group received st and ard formula supplemented with LCPUFAs ( n=146 ) . A breastfed group ( n=159 ) served as an additional reference . At 9 years of age , 72 % of the children ( control group : n=123 ; 71 males , 52 females ; LCPUFA group : n=91 ; 42 males , 49 females ; breastfed group : n=127 , 64 males , 63 females ) underwent extensive cognitive and behavioural testing . RESULTS An interaction between infant nutrition and smoking during pregnancy was found . Among children exposed to smoking during pregnancy , LCPUFA supplementation was associated with higher mean verbal IQ scores ( p=0.007 ) and learning and memory ( p=0.006 ) . Among children not exposed to smoking during pregnancy , LCPUFA supplementation was associated with lower mean verbal memory scores ( p=0.003 ) . Executive function scores were significantly lower in the LCPUFA-supplemented group than in the control group ( p=0.001 ) . Breastfeeding was associated with better performance on IQ ( p=0.005 ) . INTERPRETATION No consistent beneficial effect of LCPUFA formula supplementation on cognitive development in term-born infants was found . The study confirmed that breastfeeding is associated with better cognition 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 Abstract When term infants are fed st and ard formula that does not contain long-chain polyunsaturated fatty acids ( LC-PUFA ) , they still show lower levels of docosahexaenoic acid ( DHA ) in red blood cell ( RBC ) phospholipids by several weeks or months postnatally . This study was design ed in order to evaluate a potential alternative for supplementing term infant formulas with DHA by adding a high-DHA/low-eicosapentanoic acid fish oil to levels similar to that in human milk ( 0.3 % ) . A total of 37 term infants were included in the study at 3 days of life .  DHA concentrations remained stable between inclusion and 4 months of life at around 8 % of the RBC phospholipids in the LC-PUFA enriched formula-fed group whereas it decreased significantly in the st and ard formula-fed group . In the human milk-fed group , RBC DHA concentrations at 4 months of age were significantly lower than that at birth and were significantly correlated with the duration of breast feeding ( r = 0.85 ; P = 0.0002 ) . A significant decrease of arachidonic acid between inclusion and 4 months of age was observed in the enriched formula-fed group and reached a mean value at 4 months , which was significantly lower than that observed in the human milk or st and ard formula-fed groups ( P < 0.0001 ) . Conclusion Supplementing term formulas with a high-docosahexaenoic acid/low-eicosapentanoic acid fish oil up to 4 months of age is efficient in improving docosahexaenoic acid status , however it increases the risk of impaired n-6 fatty acid status BACKGROUND Docosahexaenoic acid is present in high concentration in retina and does not influence visual development in preterm infants . It is still under discussion whether docosahexaenoic acid is important for visual development in term infants . METHODS Thirty-seven infants fed formula for a median of 14 days were r and omized at median age of 25 days to three formulas : a ) DHAGF : 0.3 wt% docosahexaenoic acid and 0.5 wt% gamma-linolenic acid ; b ) DHAF 0.3 wt% docosahexaenoic acid ; or c ) STF : st and ard formula without long-chain polyunsaturated fatty acids and  17 breast-fed infants were observed , using blood sample s and anthropometric measurements from 1 to 4 months of age . At 4 months , visual acuity was measured by swept steady-state visual evoked potential . A cross-sectional study on 25 breast-fed infants was carried out as a reference group for the analyses . RESULTS Infants fed the two docosahexaenoic acid-supplemented formula had relative docosahexaenoic acid concentrations in red blood cell phospholipids almost as high as those in breast-fed infants , whereas infants in the st and ard formula group had significantly lower levels . The addition of gamma-linolenic acid to the formula had a positive effect on red blood cell arachidonic acid levels , compared with levels obtained using fish oil only . Visual acuity was significantly different among all feeding groups ( analysis of variance ; p = 0.05 , means + /- st and ard deviation : breast-fed , 0.37+/-0.06 logMAR ; DHAF and DHAGF combined , 0.40+/-0.07 logMAR ; and st and ard formula 0.44+/-0.07 logMAR . However , there was no statistical difference among the formula groups . In a multiple regression analysis including all formula-fed infants , weight at delivery ( p = 0.002 ) , but not type of formula , was significantly associated with visual acuity at 4 months of age . CONCLUSIONS The addition of docosahexaenoic acid result ed in concentrations in red blood cells at similar levels as those in breast-fed infants , whereas the increase in visual acuity did not reach significance . The addition of gamma-linolenic acid result ed in higher arachidonic acid concentrations in red blood cells AIM A follow up study of developmental quotient ( DQ ) at 24 months of toddlers whose diets in early infancy differed in fatty acid composition , and in whom an association between diet and DQ was observed at 4 months . METHODS 81 toddlers were distributed among three groups according to early type of diet : st and ard infant formula ( SFo , n = 30 ) ; long chain polyunsaturated fatty acid ( LC-PUFA ) enriched formula ( LCPFo , n = 26 ) ; human milk ( HM , n = 25 ) . DQ at 24 months was assessed by Brunet-Lézine ’s psychomotor developmental test . A subgroup ( n = 20 ; SFo 8 ; LCPFo 6 ; HM 6 ) was tested for erythrocyte phosphatidylcholine and phosphatidylethanolamine . RESULTS No DQ differences were found by analysis of variance . Neither DQ nor erythrocyte docosahexaenoic acid at 4 months were predictors of DQ scores at 24 months . Phosphatidylcholine arachidonic and docosahexaenoic acid correlated positively , and phosphatidylcholine linoleic acid and phosphatidylethanolamine eicosapentaenoic acid negatively , with DQ . Multiple regression analysis including these variables explained 52 % of interindividual DQ variance . A strong association was found between the erythrocyte phosphatidylcholine arachidonic/linoleic acid ratio and DQ ( r= 0.75 ; p = 0.0001 ) . CONCLUSIONS The diet/DQ association found at 4 months was not predictive of DQ scores at 24 months . Irrespective of dietary or genetic factors , there appears to be a strong correlation between the LC-PUFA composition of the red cell membrane and higher neurodevelopmental performance n-3 Long-chain PUFA ( LC-PUFA ) intake during infancy is important for neurodevelopment ; however , previous studies of n-3 LC-PUFA supplementation have been inconclusive possibly due to an insufficient dose and limited methods of assessment . The present study aim ed to evaluate the effects of direct supplementation with high-dose fish oil ( FO ) on infant neurodevelopmental outcomes and language . In the present r and omised , double-blind , placebo-controlled trial , 420 healthy term infants were assigned to receive a DHA-enriched FO supplement ( containing at least 250 mg DHA/d and 60 mg EPA/d ) or a placebo ( olive oil ) from birth to 6 months . Assessment occurred at 18 months via the Bayley Scales of Infant and Toddler Development ( 3rd edition ; BSID-III ) and the Child Behavior Checklist . Language assessment occurred at 12 and 18 months via the Macarthur-Bates Communicative Development Inventory .  The FO group had significantly higher erythrocyte DHA ( P = 0·03 ) and plasma phospholipid DHA ( P = 0·01 ) levels at 6 months of age relative to placebo . In a small subset analysis ( about 40 % of the total population ) , children in the FO group had significantly higher percentile ranks of both later developing gestures at 12 and 18 months ( P = 0·007 ; P = 0·002 , respectively ) and the total number of gestures ( P = 0·023 ; P = 0·006 , respectively ) . There was no significant difference between the groups in the st and ard or composite scores of the BSID-III . The results suggest that improved postnatal n-3 LC-PUFA intake in the first 6 months of life using high-dose infant FO supplementation was not beneficial to global infant neurodevelopment . However , some indication of benefits to early communicative development was observed Background and Objective : Feeding long-chain polyunsaturated fatty acids ( LCP ) influences immunity in adults ; however , less is known about their effect during development . The aim of the study was to determine the effect of feeding LCP on immunity in healthy infants during the first 4 months of life . Patients and Methods : Formula-fed infants were r and omized at ≤14 days of age to st and ard term formula ( Formula ) or formula containing LCP ( Formula+LCP ) . Infants exclusively fed human milk ( HM ) were included for comparison . At 16 weeks of age , blood was collected and phenotypes , the ability to proliferate and produce cytokines ( interleukin [IL]-2 , IL-4 , IL-6 , IL-10 , IL-12 , interferon [IFN]-γ , tumor necrosis factor [TNF]-α , TGF-β ) after incubation with phytohemaglutinin ( PHA ) , β-lactoglobulin , or soy protein were measured . Results : Feeding LCP result ed in a higher than and more similar proliferation rate to PHA in HM-fed infants , possibly because of a greater TH1 type cytokine response and a higher percentage of antigen mature ( CD45RO+ ) cells ( P < 0.05 ) . The response to β-lactoglobulin did not differ among groups . After incubation with soy protein Formula+LCP , compared with Formula produced less IL-2 and more TNF-α and had a higher percentage of CD8 + and a lower percentage of CD20 + ( CD20+CD54 + ) cells poststimulation ( P < 0.05 ) . Both formula groups produced less IL-2 after PHA , had a lower percentage of CD80 + cells , and a higher percentage of CD54 + cells after incubation with food proteins ( P < 0.05 ) . Conclusions : Formula-fed infants , at low risk for allergy , respond differently to mitogen and food proteins ex vivo than those fed HM . Feeding LCP altered some of these differences in the direction that is hypothesized to confer immune benefits The need for a dietary supply of docosahexaenoic acid ( DHA ) and arachidonic aid ( AA ) in term infants was evaluated in a double-masked r and omized clinical trial of the effects of supplementation of term infant formula with DHA ( 0.35 % of total fatty acids ) or with DHA ( 0.36 % ) and AA(0.72 % ) on visual acuity development . One hundred and eight healthy term infants were enrolled in the study ; 79 were exclusively formula-fed from birth ( r and omized group ) and 29 were exclusively breast-fed ( gold st and ard group ) . Infants were evaluated at four time points during the first 12 mo of life for blood fatty acid composition , growth , sweep visual evoked potential(VEP ) acuity , and forced choice preferential looking acuity . Supplementation of term infant formula with DHA or with DHA and AA during the first 4 mo of life yields clear differences in total red blood cell ( RBC ) lipid composition . Supplementation of term infant formula with DHA or with DHA and AA also yields better sweep VEP acuity at 6 , 17 , and 52 wk of age but not at 26 wk of age , when acuity development reaches a plateau . The RBC lipid composition and sweep VEP acuity of supplemented infants was similar to that of human milk-fed infants , whereas the RBC lipid composition and sweep VEP acuity of unsupplemented infants was significantly different from human milk-fed infants . Differences in acuity among diet groups were too subtle to be detected by the forced choice preferential looking protocol . Infants in all diet groups had similar rates of growth and tolerated all diets well . Thus , early dietary intake of preformed DHA and AA appears necessary for optimal development of the brain and eye of the human infant BACKGROUND There is growing interest in the fatty acid composition of breast milk and substitute formulas used to replace or complement infant breastfeeding . AIM The aims of this study were to assess the impact of two follow-up infant formulas based on cow milk fat , vegetable oils and different docosahexaenoic ( DHA ) and arachidonic ( ARA ) acid content on red blood cell membrane fatty acid composition , and determine the percent saturated fatty acid ( SFA ) incorporation into the membrane . STUDY DESIGN This was a double-blind , r and omized , controlled , parallel-group clinical trial . Infants received treatment or control product for at least four months before the age of six months . The control group ( n=25 ) received st and ard infant formula ( FA ) and the treatment group ( n=24 ) received the same formula supplemented with higher DHA and ARA content ( FB ) . The reference group ( n=47 ) consisted of normal healthy exclusively breastfed infants . OUTCOME MEASURE Red blood cell membrane fatty acid composition was determined by capillary gas chromatography . RESULTS Ninety-six infants completed the study ( FA , 25 ; FB , 24 ; reference , 47 ) . Higher DHA content reflected higher DHA percentage in the red blood cell membrane . Breast milk and FB did not show any significant differences in DHA content . ARA percentage was higher in breastfed infants and palmitic acid percentage was higher in FB- compared with FA-fed infants . CONCLUSION DHA and palmitic acid percent distributions were higher in the red blood cell membrane of infants receiving FB . DHA percent distribution was not significantly different in FB-fed and breastfed infants . SFA percent distribution was not significantly different when comparing both formulas with breast milk ABSTRACT : A direct influence of dietary long-chain polyunsaturated fatty acids ( LC-PUFA ) on the developmental quotient ( DQ ) of the healthy term infant remains unexplored . To test this hypothesis , we design ed a prospect i ve study of three types of diet . Twentynine infants received a LC-PUFA-supplemented formula , 31 received a st and ard infant formula , and 30 infants were breastfed exclusively .  Neurodevelopmental response was measured by the Brunet-Lézine psychomotor development lest at 4 mo . The fatty acid status was also assessed among three diet subgroups ( 59 subjects ) at 4 mo . Formula-fed infants who received LC-PUFA supplementation scored significantly higher ( p < 0.01 ) on the Brunet-Lézine scale than infants who received the st and ard formula . Breast-fed infants also performed better than those fed the st and ard formula . Arachidonic acid and docosahexaenoic acid levels in circulating lipids and erythrocyte phospholipids were higher among breast-fed infants and among the group fed the arachidonic- and docosahexaenoic acid-supplemented formula . These findings are suggestive that formula supplementation with one or both of these fatty acids can benefit term infants in neurodevelopmental performance Aim : Previously , we found a beneficial effect of 2 mo supplementation of infant formula with long‐chain polyunsaturated fatty acids ( LC‐PUFA ) on neurological condition at 3 mo in healthy term infants . The aim of the present follow‐up study was to evaluate whether the effect on neurological condition persists until 18 mo . Methods : A prospect i ve , double‐blind , r and omized control study was conducted . Three groups were formed : a control ( CF ; n=169 ) , an LC‐PUFA‐supplemented ( LF ; n=146 ) and a breastfed ( BF ; n=159 ) group . Information on potential confounders was collected at enrolment . At the age of 18 mo , neurodevelopmental condition was assessed by the age‐specific neurological examination of Hempel and the Bayley scales . The Hempel assessment result ed in a clinical neurological diagnosis , a total optimality score and a score on the fluency of motility . The Bayley scales result ed in mental and psychomotor developmental indices . Attrition at 18 mo was 5.5 % and non‐selective . Multivariate regression analyses were carried out to evaluate the effect of type of feeding while adjusting for confounders . Results : None of the children had developed cerebral palsy and 23 ( CF : n=8 ; LF : n=10 ; BF : n=5 )  showed minor neurological dysfunction . The groups did not show statistically significant differences in clinical neurological condition , neurological optimality score , fluency score , and the psychomotor and mental development indices . Multivariate analysis confirmed that there was no effect of type of feeding on neurological condition BACKGROUND Long-chain polyunsaturated fatty acids ( LCPUFA ) are important for normal visual and brain development . Although present in human milk , LCPUFA have until recently been absent from artificial formulas , and infants may have limited ability to synthesis e LCPUFA . To determine the clinical significance of this relative deficiency of LCPUFA , we undertook a r and omised trial of the relation between LCPUFA supplementation and infant cognitive behaviour . METHODS 44 term infants had been r and omised to a formula supplemented with LCPUFA ( 21 ) or not supplemented with LCPUFA ( 23 ) , which they had taken from birth to age 4 months .  Infant cognitive behaviour was assessed at 10 months of age by a means-end problem-solving test -- the intentional execution of a sequence of steps to achieve a goal . The problem required three intermediate steps to achieve the final goal , uncovering and retrieving a hidden toy . FINDINGS Infants who received LCPUFA-supplemented formula had significantly more intentional solutions than infants who received the no-LCPUFA formula ( median 2.0 vs 0 , p=0.021 ) . Intention scores ( median 14.0 vs 11.5 [ maximum 18 ] ) were also increased in this group ( p=0.035 ) . INTERPRETATION These findings suggest that term infants may benefit from LCPUFA supplementation , and that the effects persist beyond the period of supplementation . Since higher problem-solving scores in infancy are related to higher childhood IQ scores , supplementation with LCPUFA may be important for the development of childhood intelligence BACKGROUND Studies investigating cognitive outcomes following docosahexaenoic acid ( DHA ) supplementation of infant formula yield conflicting results , perhaps due to inadequate dietary concentrations . AIM To determine the optimal DHA concentration in term formula to support cognitive maturation . DESIGN This was a double-masked , r and omized , controlled , prospect i ve trial . A total of 181 infants were enrolled at 1 - 9 days of age and assigned r and omly to receive one of four term infant formulas with one of four levels of docosahexaenoic acid : Control ( 0 % DHA ) , 0.32 % DHA , 0.64 % DHA , or 0.96 % DHA . All DHA-supplemented formulas contained 0.64 % arachidonic acid ( ARA ) .  Infants were fed the assigned formulas until 12 months of age . One hundred forty-one children completed the 12-month feeding trial and were eligible for this study .  Cognitive function was assessed in 131 children at 18 months of age using the Bayley Scales of Infant Development II ( BSID II ) . RESULTS There were no diet group differences on the Mental Development Index ( MDI ) , the Psychomotor Development Index ( PDI ) , or the Behavior Rating Scale ( BRS ) of the BSID II . However , when the scores of children who received any of the three DHA-supplemented formulas were combined and compared to control children , a significant difference emerged : the MDI scores of DHA-supplemented children were higher ( 104.1 v. 98.4 ; p=0.02 ) . CONCLUSIONS These results suggest that dietary supplementation of DHA during the first year of life leads to enhanced cognitive development at 18 months of age . DHA concentration of 0.32 % is adequate to improve cognitive function ; higher concentrations did not confer additional benefit BACKGROUND The effect of long-chain polyunsaturated fatty acid ( LCPUFA ) intake on cognitive development is controversial . Most r and omized trials have assessed cognition at 18 mo , although significant development of cognitive abilities ( early executive function ) emerge later . OBJECTIVE The objective was to evaluate cognition beyond 18 mo and longitudinal cognitive change from 18 mo to 6 y in children who were fed variable amounts of docosahexaenoic acid ( 0.32 % , 0.64 % , and 0.96 % of total fatty acids ) and arachidonic acid ( ARA ; 0.64 % ) compared with children who were not fed LCPUFA as infants . DESIGN Eighty-one children ( 19 placebo , 62 LCPUFA ) who participated in a double-blind , r and omized trial of LCPUFA supplementation as infants were re-enrolled at 18 mo and tested every 6 mo until 6 y on age-appropriate st and ardized and specific cognitive tests . RESULTS LCPUFA supplementation did not influence performance on st and ardized tests of language and performance at 18 mo ; however , significant positive effects were observed from 3 to 5 y on rule-learning and inhibition tasks , the Peabody Picture Vocabulary Test at 5 y , and the Weschler Primary Preschool Scales of Intelligence at 6 y. Effects of LCPUFAs were not found on tasks of spatial memory , simple inhibition , or advanced problem solving . CONCLUSIONS The data from this relatively small trial suggest that , although the effects of LCPUFAs may not always be evident on st and ardized developmental tasks at 18 mo , significant effects may emerge later on more specific or fine-grained tasks . The results imply that studies of nutrition and cognitive development should be powered to continue through early childhood . This parent trial was registered at clinical trials.gov as NCT00266825 Presently , there is growing interest in long-chain polyunsaturated fatty acids ( LCPUFAs ) , which are considered a major determinant of growth , visual and neural development , and long-term health.1 Two groups of LCPUFAs have received special interest : homologues of linoleic acid ( LA ) of the n-6 series , which are precursors of arachidonic acid ( AA ) , and homologues of α-linolenic acid ( ALA ) of the n-3 series , which are precursors of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) BACKGROUND & AIMS Protein source , macronutrient composition and content of long chain-polyunsaturated fatty acids ( LC-PUFA ) of infant formulae may influence infant growth . We aim ed to assess the effect of a modified infant formula on growth . METHODS In a r and omized , double-blind trial , 213 healthy term infants consumed  isoenergetic study formulae ( intervention formula - IF , control formula - CF ) from the first month of life until the age of 120 days . IF ( 1.89 g protein/100 kcal ) contained α-lactalbumin ( ALAB ) and LC-PUFA , while CF ( 2.30 g protein/100 kcal ) provided st and ard whey and no LC-PUFA . Anthropometry and dietary intake were regularly assessed . A venous blood sample was obtained on day 120 . RESULTS Both formulae were well-accepted without significant differences in health related observations . Weight gain was not statistically different between formula groups ( IF : 30.2 ± 6.3 vs. CF : 28.3 ± 6.5 g/day , mean ± SD , P = 0.06 ) . Length gain was higher in IF ( 0.11 ± 0.02 vs. 0.10 ± 0.02 cm/day , P = 0.02 ) . Energy intake from formula was higher in CF at 90 and 120 days ( IF : 509 ± 117 and 528 ± 123 vs. CF : 569 ± 152 and 617 ± 169 kcal/day , P < 0.01 ) . Protein intake in CF was significantly higher at each assessment . Growth per energy intake was higher in IF compared to CF for weight ( 6.45 ± 2.01 vs. 5.67 ± 2.21 g/100 kcal , P = 0.02 ) and length ( 0.23 ± 0.08 vs. 0.20 ± 0.08 mm/100 kcal , P = 0.04 ) . CONCLUSIONS The modified infant formula with reduced protein content with added ALAB and LC-PUFA , meets infant requirements of protein for adequate growth . The increased energetic efficiency of the new infant formula might result from improved protein composition by added ALAB . Apparently minor differences in composition can markedly affect energetic efficiency for growth . The study was registered at Clinical Trials.gov ( NCT01094080 ) OBJECTIVES To determine the effect of alpha-linolenic acid ( ALA ) intake ( or the dietary linoleic acid [LA]/ALA ratio ) on the growth and visual function of term infants . STUDY DESIGN Normal term infants were assigned r and omly and in masked fashion at birth to receive formulas with approximately 16 % of total fatty acids as LA and 0.4 % , 1.0 % , 1.7 % , or 3.2 % of fatty acids as ALA ( LA/ALA ratios of 44 , 18.2 , 9.7 , and 4.8 ) for the first 4 months of life . The fatty acid pattern of plasma phospholipids was determined shortly after birth and at approximately 21 , 60 , and 120 days of age . Anthropometric data were obtained at the same times and also at approximately 240 days of age . Transient visual evoked responses ( VERs ) were measured at approximately 120 and 240 days of age . For comparisons , anthropometric and VER data also were obtained in infants who were exclusively breast-fed for the first 4 months of life . RESULTS Infants who received the formula with 3.2 % ALA ( LA/ALA ratio , 4.8 ) had higher plasma concentrations of phospholipid docosahexaenoic acid ( DHA ) but lower concentrations of arachidonic acid at 21 , 60 , and 120 days of age . Mean weight of this group at 120 days of age was 760 gm less ( p < 0.05 ) than the mean weight of the group that received the formula with 0.4 % ALA ( LA/ALA ratio , 44 ) . Despite differences in plasma phospholipid DHA contents among groups , neither VER latency nor amplitude differed significantly among formula groups or between any formula group and age-matched , breast-fed infants . CONCLUSIONS The highest versus the lowest ALA intake ( or the lowest vs the highest LA/ALA ratio ) result ed in higher plasma phospholipid DHA content from 21 to 120 days of age but was not associated with improved visual function as assessed by transient VER . Moreover , mean body weight of infants who received the highest versus lowest ALA intake was less at 120 days ( p < 0.05 ) . These data suggest that the lower LA/ALA ratios currently recommended for infant formulas should not be adopted until the effect of such ratios on growth are evaluated more completely The effects of dietary docosahexaenoic acid ( DHA ) supply during infancy on later cognitive development of healthy term infants were evaluated in a r and omized clinical trial of infant formula milk supplemented with 0.35 % DHA or with 0.36 % DHA and 0.72 % arachidonic acid ( AA ) , or control formula which provided no DHA or AA .  Fifty-six 18-month-old children ( 26 male , 30 female ) who were enrolled in the trial within the first 5 days of life and fed the assigned diet to 17 weeks of age were tested using the Bayley Scales of Infant Development , 2nd edition ( BSID-II ) ( Bayley 1993 ) at the Retina Foundation of the Southwest , Dallas , TX . These children had also been assessed at 4 months and 12 months of age for blood fatty-acid composition , sweep visual evoked potential ( VEP ) acuity , and forced-choice preferential looking ( FPL ) acuity ( Birch et al. 1998 ) . Supplementation of infant formula with DHA+AA was associated with a mean increase of 7 points on the Mental Development Index ( MDI ) of the BSID-II . Both the cognitive and motor subscales of the MDI showed a significant developmental age advantage for DHA- and DHA+AA-supplemented groups over the control group . While a similar trend was found for the language subscale , it did not reach statistical significance . Neither the Psychomotor Development Index nor the Behavior Rating Scale of the BSID-II showed significant differences among diet groups , consistent with a specific advantage of DHA supplementation on mental development . Significant correlations between plasma and RBC-DHA at 4 months of age but not at 12 months of age and MDI at 18 months of age suggest that early dietary supply of DHA was a major dietary determinant of improved performance on the MDI BACKGROUND Docosahexaenoic acid ( DHA ) intake throughout the first year of life is associated with neurodevelopmental and neuropsychological benefits . Few studies have evaluated the role of DHA intakes on age at achievement of gross motor milestones . OBJECTIVE The objective was to assess the effects of DHA supplementation throughout the first year of life on the achievement of four gross motor milestones in healthy infants . DESIGN In this multicenter prospect i ve , r and omized , double-blind , placebo-controlled trial , 1160 healthy neonates were assigned to receive supplementation with either 20 mg liquid DHA ( n = 580 ) or placebo ( n = 580 ) orally once daily throughout the first year of life . The primary endpoint was the time at achievement of 4 gross motor milestones ( sitting without support , h and s- and -knees crawling , st and ing alone , and walking alone ) . All analyses were performed on an intention-to-treat basis . RESULTS The time to achievement of sitting without support was shorter ( P < 0.001 ) in infants who received DHA [ median : 26 wk ; interquartile range ( IQR ) : 24 - 29 wk ] than in those who received placebo ( 27 wk ; 26 - 31 wk ) . No significant difference between infants who received DHA or placebo was found for h and s- and -knees crawling [ 39 wk ( 34 - 44 wk ) compared with 40 wk ( 35 - 44 wk ) , respectively ] , st and ing alone [ 49 wk ( 43 - 55 wk ) compared with 49 wk ( 44 - 57 wk ) , respectively ] , and walking alone [ 55 wk ( 50 - 60 wk ) compared with 56 wk ( 52 - 61 wk ) , respectively ] . CONCLUSIONS Despite the 1-wk advance in sitting without support associated with DHA supplementation , no demonstrable persistent effects of DHA supplementation on later motor development milestones were found . Thus , the long-term clinical significance of the 1-wk change in sitting without support , if any , remains unknown . This trial is registered at ( clinical trials.gov ) as NCT00610922 BACKGROUND Allergy has sharply increased in affluent Western countries in the last 30 years . N-3 long-chain polyunsaturated fatty acids ( n-3 LCPUFAs ) may protect the immune system against development of allergy . METHODS We prospect ively categorized illnesses by body system in a subset of 91 children from the Kansas City cohort of the DIAMOND ( DHA Intake and Measurement of Neural Development ) study who had yearly medical records through 4 years of age . As infants , they were fed either a control formula without LCPUFA ( n = 19 ) or one of three formulas with LCPUFA from docosahexaenoic acid ( DHA ) and arachidonic acid ( ARA ) ( n = 72 ) . RESULTS Allergic illnesses in the first year were lower in the combined LCPUFA group compared to the control . LCPUFAs significantly delayed time to first allergic illness ( p = 0.04 ) and skin allergic illness ( p = 0.03 ) and result ed in a trend to reduced wheeze/asthma ( p = 0.1 ) . If the mother had no allergies , LCPUFAs reduced the risk of any allergic diseases ( HR = 0.24 , 95 % CI = 0.1 , 0.56 , p = 0.0.001 ) and skin allergic diseases ( HR = 0.35 , 95 % CI = 0.13 , 0.93 , p = 0.04 ) . In contrast , if the mother had allergies , LCPUFAs reduced wheezing/asthma ( HR = 0.26 , 95 % CI = 0.07 , 0.9 , p = 0.02 ) . CONCLUSIONS LCPUFA supplementation during infancy reduced the risk of skin and respiratory allergic diseases in childhood with effects influenced by maternal allergies BACKGROUND Studies investigating the effects of docosahexaenoic acid ( DHA ) in infant formula on language development yield conflicting results . No study to date has investigated the effects of DHA in infant formula on school readiness . AIM To determine the effects of different dietary concentrations of DHA provided during the first 12 months of life on language development and school readiness . DESIGN This was a double-masked , r and omized , controlled , prospect i ve trial . A total of 182 infants were enrolled at 1 - 9 days of age and assigned r and omly to receive infant formula with one of four levels of DHA : control ( 0 % DHA ) , 0.32 % DHA , 0.64 % DHA , or 0.96 % DHA . All formulas with DHA also contained 0.64 % arachidonic acid .  One hundred forty-one children completed the 12-month feeding trial and were eligible for this study . Consent was obtained from 131 participants .  School readiness was assessed at 2.5 years using the Bracken Basic Concept Scale-Revised ( BBCS-R ) and receptive vocabulary was assessed at 2 and 3.5 years using the Peabody Picture Vocabulary Test-Third Edition ( PPVT-III ) . RESULTS There were no diet group differences on any of the BBCS-R subscales . On the PPVT-III , the control group had higher raw scores and st and ard scores than both the 0.32 % and 0.96 % groups at 2 years of age . These differences were not evident at 3.5 years . CONCLUSIONS Dietary DHA during the first year of life did not enhance school readiness or language development . Children who consumed infant formula with 0.32 % and 0.96 % DHA showed lower receptive vocabulary scores than controls at 2 but not 3.5 years of age BACKGROUND We tested whether addition of n-3 and n-6 long-chain polyunsaturated fatty acids ( LCPUFA ) to infant-formula milk during the first 6 months promotes long-term cognitive and motor development , without adverse consequences . METHODS We did a double-blind , r and omised , controlled , efficacy and safety trial of formula with and without LCPUFAs , with an additional breastfed reference group , in four hospitals in two cities in the UK . The participants were 447 healthy full-term babies . 309 were fed formula ( 155 without LCPUFAs )  and 138 were breastfed for at least 6 weeks . The main outcome measures were : Bayley Mental and Psychomotor Development Indices ( MDI , PDI ) at 18 months ( primary efficacy outcome ) and Knobloch , Passamanick , and Sherrards test at 9 months ( secondary outcome ) . Principal safety outcomes were : infection , atopy , growth , and gastrointestinal tolerance . FINDINGS Babies fed formula with and without LCPUFA did not differ in cognitive or motor development , growth , infection , atopy or tolerance . The mean ( 95 % CI ) MDI was 0.5 ( -2.7 to 3.8 ) units and the PDI 0.6 ( -1.8 to 3.0 ) units higher in the supplementation group . Formula-fed infants had similar developmental scores to the breastfed reference group after adjustment for higher social class and maternal education in the latter . INTERPRETATION There was no evidence of a beneficial or adverse effect on cognitive and motor development or growth up to 18 months . Although no significant differences in safety outcomes were observed , we suggest such data should be collected in future LCPUFA trials . Our trial does not provide support for addition of LCPUFA to st and ard infant formula but we are now doing further follow-up of this cohort 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 Preterm infants fed formulas with docosahexaenoic acid ( DHA , 22:6n-3 ) during the interval equivalent to the last intrauterine trimester and beyond have higher circulating DHA and transiently higher visual acuity compared with infants fed formulas containing linolenic acid . In term infants several nonr and omized studies of infants receiving DHA from human milk suggest a relationship between DHA status and acuity , but the evidence for a cause- and -effect relationship is mixed . In the present study , term infants were r and omly assigned to a st and ard term formula ( n = 20 ) or the same formula with egg yolk lecithin to provide DHA ( 0.1 % ) and arachidonic acid(AA , 20:4n-6 , 0.43 % ) ( n = 19 ) at levels reported in milk of American women . A third group of infants was breast fed for ≥3 mo(n = 19 ) . Grating visual acuity ( Teller Acuity Card procedure ) and plasma and red blood cell ( RBC ) phosphatidylcholine ( PC ) and phosphatidylethanolamine ( PE ) DHA and AA were determined at corrected ages of 2 , 4 , 6 , 9 ( acuity only ) , and 12 mo past term = 40 wk postmenstrual age ( PMA ) . At 2 mo breast-fed infants and infants fed the supplemented formula had higher grating acuity than term infants fed st and ard formula . As in preterm infants , the increase was transient . Plasma PC DHA and AA and RBC PE AA increased by 2 mo in supplemented infants , but RBC PE DHA in supplemented infants was not higher than in controls until 4 mo and beyond . Despite normal intrauterine accumulation of DHA and AA , infants fed formula with 2 % linolenic acid and 0.1 % DHA had better 2-mo visual acuity than infants fed formula with 2 % linolenic acid BACKGROUND While there is a large body of data on the effects of long-chain polyunsaturated fatty acid supplementation of infant formula on visual and cognitive maturation during infancy , longterm visual and cognitive outcome data from r and omized trials are scarce . AIM To evaluate docosahexaenoic acid ( DHA ) and arachidonic acid (ARA)-supplementation of infant formula on visual and cognitive outcomes at 4 years of age . METHODS Fifty-two of 79 healthy term infants who were enrolled in a single-center , double-blind , r and omized clinical trial of DHA and ARA supplementation of infant formula were available for follow-up at 4 years of age . In addition , 32 breast-fed infants served as a " gold st and ard " . Outcome measures were visual acuity and the Wechsler Preschool and Primary Scale of Intelligence -- Revised . RESULTS At 4 years , the control formula group had poorer visual acuity than the breast-fed group ; the DHA- and DHA+ARA-supplemented groups did not differ significantly from the breast-fed group . The control formula and DHA-supplemented groups had Verbal IQ scores poorer than the breast-fed group . CONCLUSION DHA and ARA-supplementation of infant formula supports visual acuity and IQ maturation similar to that of breast-fed infants Background In contrast to human milk , current infant formulas in the United States do not contain ω3 and ω6 long-chain polyunsaturated fatty acids . This may lead to suboptimal blood lipid fatty acid profiles and to a measurable diminution of visual function in developing term infants . The need for docosahexaenoic acid and arachidonic acid supplementation in the infant diet was evaluated in a double-blind , r and omized clinical trial . Methods Healthy term infants were r and omized to diets of ( 1 ) commercial formula , ( 2 ) docosahexaenoic acid – enriched formula ( 0.35 % of total fatty acids ) , or ( 3 ) docosahexaenoic acid– ( 0.36 % ) and arachidonic acid– ( 0.72 % ) enriched formula .  Eighty-seven infants completed the 17-week nutritional trial , and 58 were observed until 52 weeks of life . A reference group was exclusively breast fed for at least 17 weeks ( n = 29 ) . Outcome measures included electroretinographic responses , visual evoked potentials , and blood fatty acid analysis in infants at birth and at 6 , 17 , and 52 weeks of age . Results Commercial formula-fed infants had 30 % to 50 % lower content of docosahexaenoic acid in total red blood cell lipids during the 17-week feeding trial compared with breast-fed infants . Significant differences persisted at the 1-year follow-up . Arachidonic acid content was consistently reduced in the commercial formula group by 15 % to 20 % . Infants fed long-chain polyunsaturated fatty acid – enriched formulas had docosahexaenoic acid and arachidonic acid blood lipid profiles resembling those of human milk-fed infants . Infants receiving this enriched formula had more mature electroretinographic responses than commercial formula-fed infants at 6 weeks of age . Human milk-fed and docosahexaenoic acid-enriched formula-fed infants had better visual acuity than commercial formula-fed infants at both 17 and 52 weeks of age . Early ( 17-week ) fatty acid profiles in blood lipids were correlated with later ( 52-week ) visual function development in study infants . Conclusions Results from this clinical trial demonstrate that long-chain polyunsaturated fatty acid supplementation of formula in term infants produces blood lipid fatty acid profiles that are similar to those observed in breast-fed infants . This supplementation leads to better visual function later in life ( i.e. , 1 year of age ) than that shown by infants fed commercial formula Long-chain PUFA ( LCPUFA ) supplementation of formula can have beneficial effects on neurodevelopmental outcome in early infancy , but uncertainty exists regarding effects after 6 months . The present study is the first to investigate whether consumption by term infants of formula containing LCPUFA for the first 2 months after birth improves neurological condition of these children at 9 years of age . A prospect i ve , double-blind , r and omised control study was performed in two groups of healthy term infants : a control group with st and ard formula ( n 169 ) and a LCPUFA-supplemented group ( LF ; n 146 ) . A breast-fed group ( BF ; n 159 ) served as a reference . At age 9 years , children were neurologically assessed according to Touwen , result ing in a Neurological Optimality Score and information on severity and type of minor neurological dysfunction ( MND ) . Information on potential confounders was collected at enrollment and follow-up . Multivariate analyses were carried out to evaluate the effect of nutrition while adjusting for confounders . Attrition ( 28 % ) was selective : drop-outs in the LF group were more often boys and had a significantly lower mental developmental index at 18 months . Neurological optimality and severity and type of MND at 9 years did not differ between the two formula groups . Children in the BF group showed significantly less often fine manipulative dysfunction than formula-fed children . In conclusion , LCPUFA supplementation of formula during the first 2 postnatal months in healthy term infants does not alter neurological function at school age . The study confirmed that breast-fed infants have a slightly better neurodevelopmental outcome than formula-fed infants
BACKGROUND The long chain polyunsaturated fatty acids ( LCPUFA ) docosahexaenoic acid ( DHA ) and arachidonic acid ( AA ) are considered essential for maturation of the developing brain , retina and other organs in newborn infants .
St and ard infant milk formulae are not supplemented with LCPUFA ; they contain only alpha-linolenic acid and linoleic acid , from which formula-fed infants must synthesis e their own DHA and AA , respectively .
Over the past few years , some manufacturers have added LCPUFA to formula milk and have marketed these products as providing an advantage for the overall development of full-term infants .
OBJECTIVES To assess whether supplementation of formula milk with LCPUFA is both safe and beneficial for full-term infants , while focusing on effects on visual function , neurodevelopment and physical growth .