Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial. Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age. Allergic disease in infants up to 2 years of age in relation to plasma omega-3 fatty acids and maternal fish oil supplementation in pregnancy and lactation. A Docosahexaenoic Acid-Functional Food During Pregnancy Benefits Infant Visual Acuity at Four but not Six Months of Age Effects of fish-oil and folate supplementation of pregnant women on maternal and fetal plasma concentrations of docosahexaenoic acid and eicosapentaenoic acid: a European randomized multicenter trial. Stereoacuity at age 3.5 y in children born full-term is associated with prenatal and postnatal dietary factors: a report from a population-based cohort study. Essential n-3 fatty acids in pregnant women and early visual acuity maturation in term infants. Maternal consumption of a docosahexaenoic acid-containing functional food during pregnancy: benefit for infant performance on problem-solving but not on recognition memory tasks at age 9 mo. Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women. Scotopic electroretinogram in term infants born of mothers supplemented with docosahexaenoic acid during pregnancy. Maternal supplementation with docosahexaenoic acid during pregnancy does not affect early visual development in the infant: a randomized controlled trial. Maternal fish and other seafood intakes during pregnancy and child neurodevelopment at age 4 years. Cognitive assessment of children at age 2½ years after maternal fish oil supplementation in pregnancy: a randomised controlled trial Supplementation of DHA but not DHA with arachidonic acid during pregnancy and lactation influences general movement quality in 12-week-old term infants. Supplementation of fish-oil and soy-oil during pregnancy and psychomotor development of infants. The Effects of Maternal Supplementation of Polyunsaturated Fatty Acids on Visual, Neurobehavioural, and Developmental Outcomes of the Child: A Systematic Review of the Randomized Trials Maternal consumption of a DHA-containing functional food benefits infant sleep patterning: an early neurodevelopmental measure. Effect of N-3 polyunsaturated fatty acid supplementation in pregnancy: the Nuheal trial. Maternal docosahexaenoic acid supplementation during pregnancy and visual evoked potential development in term infants: a double blind, prospective, randomised trial Prenatal DHA status and neurological outcome in children at age 5.5 years are positively associated. Effects of prenatal fish-oil and 5-methyltetrahydrofolate supplementation on cognitive development of children at 6.5 y of age. Those confounded vitamins: what can we learn from the differences between observational versus randomised trial evidence? Auditory- and visual-evoked potentials in Mexican infants are not affected by maternal supplementation with 400 mg/d docosahexaenoic acid in the second half of pregnancy. Effect of Supplementing Pregnant and Lactating Mothers With n-3 Very-Long-Chain Fatty Acids on Children's IQ and Body Mass Index at 7 Years of Age Neurodevelopmental outcomes of preterm infants fed high-dose docosahexaenoic acid: a randomized controlled trial.
CONTEXT Uncertainty about the benefits of dietary docosahexaenoic acid ( DHA ) for pregnant women and their children exists , despite international recommendations that pregnant women increase their DHA intakes . OBJECTIVE To determine whether increasing DHA during the last half of pregnancy will result in fewer women with high levels of depressive symptoms and enhance the neurodevelopmental outcome of their children . DESIGN , SETTING , AND PARTICIPANTS A double-blind , multicenter , r and omized controlled trial ( DHA to Optimize Mother Infant Outcome [ DOMInO ] trial ) in 5 Australian maternity hospitals of 2399 women who were less than 21 weeks ' gestation with singleton pregnancies and who were recruited between October 31 , 2005 , and January 11 , 2008 . Follow-up of children ( n = 726 ) was completed December 16 , 2009 . INTERVENTION Docosahexaenoic acid-rich fish oil capsules ( providing 800 mg/d of DHA ) or matched vegetable oil capsules without DHA from study entry to birth . MAIN OUTCOME MEASURES High levels of depressive symptoms in mothers as indicated by a score of more than 12 on the Edinburgh Postnatal Depression Scale at 6 weeks or 6 months postpartum . Cognitive and language development in children as assessed by the Bayley Scales of Infant and Toddler Development , Third Edition , at 18 months . RESULTS Of 2399 women enrolled , 96.7 % completed the trial . The percentage of women with high levels of depressive symptoms during the first 6 months postpartum did not differ between the DHA and control groups ( 9.67 % vs 11.19 % ; adjusted relative risk , 0.85 ; 95 % confidence interval [ CI ] , 0.70 - 1.02 ; P = .09 ) . Mean cognitive composite scores ( adjusted mean difference , 0.01 ; 95 % CI , -1.36 to 1.37 ; P = .99 ) and mean language composite scores ( adjusted mean difference , -1.42 ; 95 % CI , -3.07 to 0.22 ; P = .09 ) of children in the DHA group did not differ from children in the control group . CONCLUSION The use of DHA-rich fish oil capsules compared with vegetable oil capsules during pregnancy did not result in lower levels of postpartum depression in mothers or improved cognitive and language development in their offspring during early childhood . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000569606 OBJECTIVES Docosahexaenoic acid ( DHA ; 22:6 n-3 ) and arachidonic acid ( AA ; 20:4 n-6 ) are important for development of the central nervous system in mammals . There is a growth spurt in the human brain during the last trimester of pregnancy and the first postnatal months , with a large increase in the cerebral content of AA and DHA .  The fetus and the newborn infant depend on maternal supply of DHA and AA . Our hypothesis was that maternal intake of DHA during pregnancy and lactation is marginal and that high intake of this fatty acid would benefit the child . We examined the effect of supplementing pregnant and lactating women with very-long-chain n-3 polyunsaturated fatty acids ( PUFAs ; cod liver oil ) on mental development of the children , compared with maternal supplementation with long-chain n-6 PUFAs ( corn oil ) . METHODS The study was r and omized and double-blinded . Pregnant women were recruited in week 18 of pregnancy to take 10 mL of cod liver oil or corn oil until 3 months after delivery . The cod liver oil contained 1183 mg/10 mL DHA , 803 mg/10 mL eicosapentaenoic acid ( 20:5 n-3 ) , and a total of 2494 mg/10 mL summation operator n-3 PUFAs . The corn oil contained 4747 mg/10 mL linoleic acid ( 18:2 n-6 ) and 92 mg/10 mL alpha-linolenic acid ( 18:3 n-3 ) . The amount of fat-soluble vitamins was identical in the 2 oils ( 117 micro g/mL vitamin A , 1 micro g/mL vitamin D , and 1.4 mg/mL dl-alpha-tocopherol ) . A total of 590 pregnant women were recruited to the study , and 341 mothers took part in the study until giving birth . All infants of these women were scheduled for assessment of cognitive function at 6 and 9 months of age , and 262 complied with the request . As part of the protocol , 135 subjects from this population were invited for intelligence testing  with the Kaufman Assessment Battery for Children ( K-ABC ) at 4 years of age . Of the 135 invited children , 90 came for assessment . Six children did not complete the examination . The K-ABC is a measure of intelligence and achievement design ed for children aged 2.5 years through 12.5 years . This multisubtest battery comprises 4 scales : Sequential Processing , Simultaneous Processing , Achievement ( not used in the present study ) , and Nonverbal Abilities . The Sequential Processing and Simultaneous Processing scales are hypothesized to reflect the child 's style of problem solving and information processing . Scores from these 2 scales are combined to form a Mental Processing Composite , which serves as the measure of intelligence in the K-ABC . RESULTS We received dietary information from 76 infants ( 41 in the cod liver oil group and 35 in the corn oil group ) , documenting that all of them were breastfed at 3 months of age . Children who were born to mothers who had taken cod liver oil ( n = 48 ) during pregnancy and lactation scored higher on the Mental Processing Composite of the K-ABC at 4 years of age as compared with children whose mothers had taken  corn oil  ( n = 36 ; 106.4 [ 7.4 ] vs 102.3 [ 11.3 ] ) . The Mental Processing Composite score correlated significantly with head circumference at birth ( r = 0.23 ) , but no relation was found with birth weight or gestational length . The children 's mental processing scores at 4 years of age correlated significantly with maternal intake of DHA and eicosapentaenoic acid during pregnancy . In a multiple regression model , maternal intake of DHA during pregnancy was the only variable of statistical significance for the children 's mental processing scores at 4 years of age . CONCLUSION Maternal intake of very-long-chain n-3 PUFAs during pregnancy and lactation may be favorable for later mental development of children We have previously reported a protective effect of maternal omega-3 long-chain polyunsaturated fatty acids ( ω-3 LCPUFA ) supplementation in pregnancy and lactation on IgE-associated eczema and food allergy in the infant during the first year of life . Here we investigate whether the effects of the LCPUFA supplementation on IgE-associated diseases last up to 2 yr of age and assess the relationship between plasma proportions of ω-3 PUFAs and the frequency and severity of infant allergic disease . 145 pregnant women , at risk of having an allergic infant , were r and omized to daily supplementation with 1.6 g eicosapentaenoic acid ( EPA ) and 1.1 g docosahexaenoic acid ( DHA ) or placebo starting in the 25th gestational week and continuing through 3.5 months of breastfeeding . Clinical examinations , skin prick tests and analysis of maternal and infant plasma phospholipid fatty acids and infant specific IgE were performed . No difference in the prevalence of allergic symptoms was found between the intervention groups . The cumulative incidence of IgE-associated disease was lower in the ω-3-supplemented group ( 6/54 , 13 % ) compared with the placebo group ( 19/62 , 30 % , p=0.01 ) . Higher maternal and infant proportions of DHA and EPA were associated with lower prevalence of IgE associated disease ( p=0.01 - 0.05 ) in a dose-dependent manner . Higher maternal and infant proportions of DHA and EPA were found if the infants presented none , when compared with multiple allergic symptoms , ( p<0.05 ) regardless of sensitization . In summary , the ω-3 supplementation offered no obvious preventive effect on the prevalence of clinical symptoms of allergic disease , but the decrease in cumulative incidence of IgE-associated disease seen during the first year still remained until 2 yr of age . Furthermore , high proportions of DHA and EPA in maternal and infant plasma phospholipids were associated with less IgE-associated disease and a reduced severity of the allergic phenotype Within the visual system , docosahexaenoic acid ( DHA , 22:6n−3 ) is an important structural component for retinal photoreceptors and cortical gray matter . There is a marked decrease in neural DHA accumulation in the face of DHA deficiency . DHA is accumulated at an accelerated rate during pregnancy , especially in the third trimester . However , pregnant women in the US and Canada have dietary DHA intakes that are significantly below the optimal level . The main objective of this study was to determine whether a DHA-functional food during pregnancy would benefit infant visual acuity at four and six months of age measured behaviorally using the acuity card procedure ( ACP ) . In a r and omized , longitudinal , double-blinded , and placebo-controlled trial , 30 pregnant women received either the DHA-functional food ( n = 16 ) or the placebo ( n = 14 ) . There were significant main effects for visual acuity at four months of age ( P = 0.018 ) . The mean acuity scores were 3.8 ± 1.1 cycles/degree in the DHA group versus 3.2 ± 0.7 cycles/degree in the placebo group . At six months there were no group differences . Based on our results , we conclude that DHA supplemented during pregnancy plays a role in the maturation of the visual system BACKGROUND Pregnant women usually meet their increased energy needs but do not always meet their increased micronutrient requirements . The supply of both folic acid and docosahexaenoic acid ( DHA ) has been related to positive pregnancy and infant outcomes . OBJECTIVE We aim ed to assess whether fish-oil ( FO ) supplementation with or without folate from gestation week 22 to birth improves maternal and fetal n-3 long-chain polyunsaturated fatty acid ( n-3 LC-PUFA ) status . DESIGN We conducted a multicenter ( Germany , Hungary , and Spain ) , r and omized , double-blind , 2 x 2 factorial , placebo-controlled trial . From gestation week 22 until delivery , 311 pregnant women received daily a preparation with FO [ 0.5 g DHA and 0.15 g eicosapentaenoic acid ( EPA ) ] , 400 microg methyltetrahydrofolic acid ( MTHF ) , FO with MTHF , or placebo . Outcome measures included maternal and cord plasma DHA and EPA contents at gestation weeks 20 and 30 and at delivery , indicators of pregnancy outcome , and fetal development . RESULTS FO significantly ( P<0.001 ) increased maternal DHA and EPA ( % by wt ) , as shown by 3-factor repeated- measures ANOVA ( ie , MTHF , FO , and time ) with adjustment for maternal baseline DHA and EPA . In addition , FO significantly ( P<0.001 ) increased cord blood DHA ( % by wt ; 2-factor ANOVA ) . MTHF was significantly ( P=0.046 ) associated with increased maternal DHA ( % by wt ) . There was no FO x MTHF interaction for the time course of DHA or EPA ( P=0.927 and 0.893 ) . Pregnancy outcomes and fetal development did not differ significantly among the intervention groups . CONCLUSIONS FO supplementation from gestation week 22 until delivery improves fetal n-3 LC-PUFA status and attenuates depletion of maternal stores . MTHF may further enhance maternal n-3 LC-PUFA proportions BACKGROUND Observational studies suggested that breast-feeding benefits the visual development of preterm children , which has been attributed to the presence of docosahexaenoic acid ( DHA ) in breast milk but not most formula milks . R and omized studies showed that preterm children require a dietary supply of DHA in the first few weeks of life for optimal visual development , but it is unclear whether full-term children experience similar benefits from breast milk or DHA supplements . OBJECTIVE The objective of this study was to compare stereoacuity at age 3.5 y in healthy , full-term children who were breast-fed and in similar children who had not been breast-fed after adjustment for socioeconomic status and maternal diet . DESIGN Prospect ively collected data on maternal diet during pregnancy ( including intake of oily fish ) , the child 's diet , and the socioeconomic status of the family were examined . Stereoacuity at age 3.5 y was assessed . RESULTS Children who had been breast-fed for 4 mo were more likely to achieve high- grade stereopsis , or stereoscopic vision , than were children who had not been breast-fed ( adjusted odds ratio : 2.77 ; 95 % CI : 1.54 , 4.97 ) . The mother 's antenatal blood DHA content was associated with her intake of oily fish ( P < 0.0001 ) . Children whose mothers ate oily fish during pregnancy were also more likely to achieve high- grade stereopsis than were children whose mothers did not eat oily fish ( adjusted odds ratio : 1.57 ; 95 % CI : 1.00 , 2.45 ) . CONCLUSIONS The results of this study suggest that for full-term infants , breast-feeding is associated with enhanced stereopsis at age 3.5 y , as is a maternal DHA-rich antenatal diet , irrespective of later infant feeding practice BACKGROUND Docosahexaenoic acid ( DHA ) is important to neural development . Whether DHA intakes are low enough in some pregnant women to impair infant development is uncertain . OBJECTIVE We sought to determine whether DHA deficiency occurs in pregnant women and contributes to poor infant development . DESIGN Biochemical cutoffs , dietary intakes , or developmental scores indicative of DHA deficiency are not defined . Infant development has a distribution in which an individual 's potential development is unknown . This was a r and omized intervention to establish a distribution of developmental scores for infants of women with DHA intakes considered to be above requirements against which to compare the development of infants of mothers consuming their usual diet .  DHA ( 400 mg/d ; n = 67 ) or a placebo ( n = 68 ) was consumed by the women from 16 wk gestation until delivery . We determined maternal red blood cell ethanolamine phosphoglyceride fatty acids , dietary intakes at 16 and 36 wk gestation , and infant visual acuity at 60 d of age . RESULTS We described an approach to identify DHA deficiency when biochemical and functional markers of deficiency are unknown . In multivariate analyses , infant visual acuity was related to sex ( beta = 0.660 , SE = 0.93 , and odds ratio = 1.93 ) and maternal DHA intervention ( beta = 1.215 , SE = 1.64 , and odds ratio = 3.37 ) . More infant girls in the placebo than in the DHA intervention group had a visual acuity below average ( P = 0.048 ) . Maternal red blood cell ethanolamine phosphoglyceride docosatetraenoic acid was inversely related to visual acuity in boys ( rho = -0.37 , P < 0.05 ) and girls ( rho = -0.48 , P < 0.01 ) . CONCLUSIONS These studies suggest that some pregnant women in our study population were DHA-deficient BACKGROUND There are few studies reporting on docosahexaenoic acid ( DHA , 22:6n-3 ) supplementation during pregnancy and infant cognitive function . DHA supplementation in pregnancy and infant problem solving in the first year have not been investigated . OBJECTIVE We tested the hypothesis that infants born to women who consumed a DHA-containing functional food during pregnancy would demonstrate better problem-solving abilities and recognition memory than would infants born to women who consumed the placebo during pregnancy . DESIGN In a double-blind , placebo-controlled , r and omized trial , pregnant women consumed a DHA-containing functional food or a placebo from gestation week 24 until delivery . Study groups received DHA-containing cereal-based bars ( 300 mg DHA/92-kcal bar ; average consumption : 5 bars/wk ; n = 14 ) or cereal-based placebo bars ( n = 15 ) . The Infant Planning Test and Fagan Test of Infant Intelligence were administered to infants at age 9 mo . The problem-solving trial included a support step and a search step . The procedure was scored on the basis of the infant 's performance on each step and on the entire problem ( intention score and total intentional solutions ) . Scores were generated on the basis of the cumulative performance of the infant on 5 trials . RESULTS Treatment had significant effects on the performance of problem-solving tasks : total intention score ( P = 0.017 ) , total intentional solutions ( P = 0.011 ) , and number of intentional solutions on both cloth ( P = 0.008 ) and cover ( P = 0.004 ) steps . There were no significant differences between groups in any measure of Fagan Test of Infant Intelligence . CONCLUSION These data point to a benefit for problem solving but not for recognition memory at age 9 mo in infants of mothers who consumed a DHA-containing functional food during pregnancy OBJECTIVE There have been indications that high intake of n-3 long-chain polyunsaturated fatty acids ( PUFAs ) during pregnancy may increase birth weight and gestational length . In addition , n-3 long-chain PUFAs may be important for the neurobiological development of the infants . High levels of docosahexaenoic acid ( DHA , 22:6 n-3 ) are found in the gray matter of the cerebral cortex and in the retina , and it seems as if the availability of long-chain PUFAs may be limiting cerebral development . The fetus and the newborn are dependent on a high supply from their mothers , either via the placenta or via breast milk . We supplemented pregnant and lactating women with n-3 or n-6 long-chain PUFAs to evaluate the effect on birth weight , gestational length , and infant development . DESIGN We performed a double-blind , r and omized study recruiting 590 pregnant , healthy , nulli- or primiparous women ( 19 - 35 years old ) in weeks 17 to 19 of pregnancy . The women were provided 10 mL of either cod liver oil or corn oil daily until 3 months after delivery . MAIN OUTCOME MEASURES Primary outcomes were gestational length and birth weight . Electroencephalography ( EEG ) was done on the second day of life and at 3 months of age . Novelty preference ( Fagan test ) was used as an indicator of cognitive function at 6 and 9 months of age . The fatty acid pattern in umbilical plasma phospholipids and in breast milk was measured , and dietary assessment s were performed , both on the mothers during pregnancy and on the infants at 3 months of age . The growth of the infants was followed up to 1 year of age . RESULTS Three hundred forty-one mothers took part in the study until delivery . There were no significant differences in maternal body mass index before pregnancy and at birth , or parity between the 2 groups . Smoking habits and parental education were also similar in the 2 groups . The mean age of the mothers receiving cod liver oil was , by chance , 1 year higher than the age of the mothers receiving corn oil ( 28.6 [ 3.4 ] vs 27.6 [ 3.2 ] years ) . The maternal dietary intake in the 2 groups receiving cod liver oil or corn oil was similar , except for the supplementation . There were no differences in gestational length or birth weight between the cod liver oil group and the corn oil group ( 279.6 [ 9.2 ] vs 279.2 [ 9.3 ] days ; 3609 [ 493 ] vs 3618 [ 527 ] g , respectively ) . Birth length , head circumference , and placental weight were also similar in the 2 groups . The concentrations of the n-3 fatty acids eicosapentaenoic acid ( 20:5 n-3 ) , docosapentaenoic acid ( 22:5 n-3 ) , and DHA in umbilical plasma phospholipids were higher in the cod liver oil group compared with the corn oil group ( 10.8 [ 7.6 ] vs 2.5 [ 1.8 ] microg/mL , 5.0 [ 2.6 ] vs 2.9 [ 1.3 ] microg/mL , 55.8 [ 20.6 ] vs 45.3 [ 12.8 ] microg/mL , respectively ) . Neonates with high concentration of DHA in umbilical plasma phospholipids ( upper quartile ) had longer gestational length than neonates with low concentration ( lower quartile ; 282.5 [ 8.5 ] vs 275.4 [ 9.3 ] days ) . No differences in EEG scores or Fagan scores were found , but neonates with mature EEG ( N = 70 ) had a higher concentration of DHA in umbilical plasma phospholipids than neonates with immature EEG ( N = 51 ) on the second day of life . Dietary information from 251 infants at 3 months of age was collected and 85 % of these infants were exclusively breastfed , in addition to 12 % who were partly breastfed . The breast milk of mothers supplemented with cod liver oil contained more n-3 long-chain PUFAs and less n-6 long-chain PUFAs than breast milk of mothers supplemented with corn oil . There were no significant differences in infant growth during the first year of life between the 2 groups . CONCLUSIONS This study shows neither harmful nor beneficial effects of maternal supplementation of long-chain n-3 PUFAs regarding pregnancy outcome , cognitive development , or growth , as compared with supplementation with n-6 fatty acids . However , it confirms that DHA concentration may be related to gestational length and cerebral maturation of the newborn PURPOSE To test the hypothesis that the supplementation of the diets of pregnant women with a fish oil rich in docosahexaenoic acid ( DHA ) enhances retinal development in their healthy term infants , as measured during the early postnatal period by the electroretinogram ( ERG ) . METHODS One hundred pregnant women were r and omized to receive either a fish oil ( n = 50 ) or a placebo oleic acid dietary supplement ( n = 50 ) from 15 weeks of pregnancy until delivery . Total fatty acids in red blood cells ( RBCs ) and plasma were measured in mothers at 15 and 28 weeks of pregnancy and at delivery and in their infants in umbilical cord blood . Infant retinal development was assessed within the first week of life with full-field ERGs that included a scotopic blue intensity series ( n = 41 ) and a bright white flash ( 2.0 log cd-s/m(2 ) ; n = 44 ) . RESULTS Infants born of mothers who received supplements did not differ at birth in weight , gestational age , or any other st and ard variable . Infant DHA status at birth , as measured from umbilical cord blood , did not differ significantly between maternal supplementation groups . ERG implicit times , amplitudes , and parameters of the stimulus-response function did not differ significantly between infants in the maternal supplemented and placebo groups . There was , however , a relationship between infant DHA status and maturity of the retina at birth , regardless of maternal supplementation group . A measure of retinal sensitivity ( log sigma ) correlated significantly ( P < 0.005 ) with DHA status ( as a percentage of total fatty acid ; TFA ) in infant cord blood . Infants in the highest quartile for cord blood DHA had higher retinal sensitivity compared with infants in the lowest quartile . Infants in the highest quartile for plasma DHA , both as a percentage of TFA and concentration , were born at a significantly later gestational age than were infants in the lower quartiles . CONCLUSIONS These findings demonstrate an association between the DHA status of term infants and retinal sensitivity , suggesting an essential role of this long-chain polyunsaturated fatty acid ( LCPUFA ) in the development and function of the retina . However , maternal DHA status was not significantly associated with infant retinal sensitivity and no direct effect of maternal supplementation was observed BACKGROUND The docosahexaenoic acid ( DHA ) intake of pregnant women is lower than estimates of the DHA accretion by the fetus , and recommendations were made to increase the DHA intake of pregnant women . OBJECTIVE The objective of this study was to determine whether the supplementation of pregnant women with DHA improved the visual acuity of infants at 4 mo . DESIGN We conducted a blinded assessment of a subset of healthy , full-term infants born to women enrolled in a double-blind , r and omized controlled trial called the DHA for Maternal and Infant Outcomes ( DOMInO ) trial . Women were r and omly assigned to consume DHA-rich fish-oil capsules ( ≈800 mg DHA/d in the treatment group ) or vegetable oil capsules ( control group ) from midpregnancy to delivery . The primary outcome was the sweep visual evoked potential ( VEP ) acuity at 4 mo . The VEP latency at 4 mo was a secondary outcome . RESULTS Mean ( ±SD ) VEP acuity did not differ between treatment and control groups [ treatment group : 8.37 ± 2.11 cycles per degree ( cpd ) , n = 89 ; control group : 8.55 ± 1.86 cpd , n = 93 ; P = 0.55 ] . VEP latencies also did not differ between groups . Irrespective of the group , maternal smoking in pregnancy was independently associated with poorer VEP acuity in the infant . CONCLUSIONS DHA supplementation in women with singleton pregnancies does not enhance infant visual acuity in infants at 4 mo of age . Visual acuity in infancy is adversely associated with maternal smoking in pregnancy . This trial was registered at www.anzctr.org.au as ACTRN12606000327583 . The DOMInO trial was registered at www.anzctr.org.au as ACTRN12605000569606 OBJECTIVE To analyse the relationship between maternal intakes of fish and other seafood during pregnancy and child neurodevelopment at age 4 years . Although pregnant women are advised to limit seafood intakes because of possible neurotoxin contamination , several studies suggest that overall maternal seafood intakes are associated with improved child neurodevelopment , perhaps because of higher DHA intakes . DESIGN The study uses data from a prospect i ve birth cohort study . Maternal seafood intakes were assessed using a semi-quantitative FFQ administered shortly after delivery . Multivariate linear regression was used to estimate associations between seafood consumption and scores on the McCarthy Scales of Children 's Abilities ( MCSA ) . Analyses were stratified by breast-feeding duration as breast milk is a source of DHA during the postnatal phase of the brain growth spurt . SETTING Menorca , Spain , 1997 - 2001 . SUBJECTS Full-term children ( n 392 ) with data on maternal diet in pregnancy , breast-feeding duration and neurodevelopment at age 4 years . RESULTS Among children breast-fed for < 6 months , maternal fish intakes of > 2 - 3 times/week were associated with significantly higher scores on several MCSA subscales compared with intakes < or = 1 time/week . There was no association among children breast-fed for longer periods . Maternal intakes of other seafood ( shellfish/squid ) were , however , inversely associated with scores on several subscales , regardless of breast-feeding duration . CONCLUSIONS The study suggests that moderately high intakes of fish , but not other seafood , during pregnancy may be beneficial for neurodevelopment among children breast-fed for < 6 months . Further research in other population s with high seafood intakes and data on additional potential confounders are needed to confirm this finding Objective : To assess the effects of antenatal omega 3 long-chain polyunsaturated fatty acid ( n-3 LC PUFA ) on cognitive development in a cohort of children whose mothers received high-dose fish oil in pregnancy . Design : A double-blind r and omised placebo-controlled trial . Setting : Perth , Western Australia , Australia . Patients : 98 pregnant women received the supplementation from 20 weeks ’ gestation until delivery . Their infants ( n = 72 ) were assessed at age 2½ years . Interventions : Fish oil ( 2.2 g docosahexaenoic acid ( DHA ) and 1.1 g eicosapentaenoic acid (EPA)/day ) or olive oil from 20 weeks ’ gestation until delivery . Outcome measures : Effects on infant growth and developmental quotients ( Griffiths Mental Development Scales ) , receptive language ( Peabody Picture Vocabulary Test ) and behaviour ( Child Behaviour Checklist ) . Results : Children in  the fish oil-supplemented group ( n = 33 ) attained a significantly higher score for eye and h and coordination ( mean ( ( SD ) score 114 ( 10.2 ) ) than those in the placebo group ( n = 39 , mean score 108 ( SD 11.3 ) ; p = 0.021 , adjusted p = 0.008 ) . Eye and h and coordination scores correlated with n-3 PUFA levels in cord blood erythrocytes ( EPA : r = 0.320 , p = 0.007 ; DHA : r = 0.308 , p = 0.009 ) and inversely correlated with n-6 PUFA ( arachidonic acid 20:4n-6 : r = −0.331 , p = 0.005 ) . Growth measurements in the two groups were similar at age 2½ years . Conclusion : Maternal fish oil supplementation during pregnancy is safe for the fetus and infant , and may have potentially beneficial effects on the child ’s eye and h and coordination . Further studies are needed to determine the significance of this finding DHA and arachidonic acid ( AA ) are important for neurodevelopment . A traditional neonatal neurological examination and the evaluation of general movement quality are sensitive techniques for assessing neurodevelopment in young infants . Mildly abnormal general movements at 3 months have been associated with a non-optimal current brain condition . We investigated whether supplementation of DHA during pregnancy and lactation influences the infant 's brain development and whether additional AA modulates this effect . Healthy women were r and omly assigned to DHA ( 220 mg/d , n 42 ) , DHA+AA ( 220 mg each/d , n 41 ) or control ( n 36 ) , from about week 17 ( range 14 - 20 weeks ) of pregnancy until 12 weeks postpartum . The control and the DHA+AA groups had approximately comparable dietary DHA/AA ratios . The st and ardised neonatal neurological examination was carried out at 2 weeks . General movement quality was assessed at 2 and 12 weeks . Neither DHA alone nor DHA+AA influenced outcomes in the traditional examination . General movement quality of infants in the DHA group was lower than that of infants in the other two groups , especially at 12 weeks : 61 % of the infants in the DHA group showed mildly abnormal general movements compared with 31 % in the control group ( P = 0.008 ) and 34 % in the DHA+AA group ( P = 0.015 ) . We conclude that general movement quality at 12 weeks is sensitive to the maternal dietary DHA/AA balance Supplementation of docosahexaenoic acid ( DHA ) in infancy improves neuro-developmental outcomes , but there is limited information about the impact of supplementing pregnant mothers with DHA on the development of their infants . In a follow-up of a r and omized , double-blind controlled trial with 400 pregnant mothers , the effects of supplementation of fish-oil or soy-oil ( 4 g/day ) during the last trimester of pregnancy on psychomotor development and behaviour of infants at 10 months of age ( n=249 ) were assessed . The quality of psychosocial stimulation at home ( HOME ) and nutritional status of the subjects were also measured . There were no significant differences in the fish-oil group and soy-oil group in any of the developmental ( mean + /-SD mental development index : 102.5 + /- 8.0 vs. 101.5 + /- 7.8 , psychomotor development index : 101.7 + /- 10.0 vs. 100.5 + /- 10.1 ) or behavioural outcomes . It may , therefore , be concluded that supplementation of fish-oil during the last trimester of pregnancy does not have any added benefit over supplementation of soy-oil on the development or behaviour of infants in this population Polyunsaturated fatty acid ( PUFA ) use in pregnancy has been promoted as beneficial for visual and neurobehavioural development in the fetus . However , no systematic review of the r and omized trials has been conducted . The objective of this review was to evaluate potential advantages of this regiment by review ing all r and omized trials in pregnancy . Methods . Systematic review of r and omized controlled studies comparing cognitive and visual achievements among infants whose mothers were treated and untreated with PUFA during gestation . Results . Nine studies met the inclusion criteria , three focusing on  visual and six on neurobehavioural development . Due to differing outcome measurements in the infants , the studies could not be combined into a formal meta- analysis . Synthesizing the existing data , for both visual and neurobehavioural development , most studies could not show sustained benefits to infant cognition or visual development . Conclusion . At the present time a recommendation to change practice and supplement all expecting mothers with PUFA  to improve offspring vision or neurobehavioural function is not supported by existing evidence BACKGROUND Docosahexaenoic acid ( DHA ; 22:6n-3 ) is highly important during pregnancy for optimal development and functioning of fetal neural tissue . Infant ability to organize sleep and wake states following parturition is highly associated with later developmental outcomes . The impact of maternal DHA intake on sleep organization has not been previously investigated . AIMS To examine the effect of a DHA-containing functional food consumed during pregnancy on early neurobehavioral development as assessed by infant sleep patterning in the first 48 postnatal hours . STUDY DESIGN A longitudinal , r and omized , double-blinded , placebo-controlled design was used . SUBJECTS Women ( 18 - 35 y ) with no pregnancy complications consumed a cereal-based functional food ( 92 kcal ) containing 300 mg DHA an average of 5 d/week or placebo bars ( n=27 DHA , n=21 Placebo ) . The intervention began at 24 weeks gestation and continued until delivery ( 38 - 40 weeks ) . OUTCOME MEASURES Infant sleep/wake states were measured on postnatal days 1 ( D1 ) and 2 ( D2 ) using a pressure sensitive mattress recording respiration and body movements . RESULTS Using ANCOVA and controlling for ethnic variation , there were significant group differences in arousals in quiet sleep on D1 ( P=0.006 ) and D2 ( P=0.011 ) with fewer arousals in the DHA intervention group compared to the placebo group . Similarly , arousals in active sleep on D1 were significantly lower in the DHA-intervention group ( P=0.012 ) compared to the placebo group . CONCLUSIONS We conclude that increased prenatal supply of dietary DHA has a beneficial impact on infant sleep organization In this placebo controlled , r and omised , double blind trial , pregnant women received from the 20th week of gestation onwards either 500 mg docosahexaenoic acid ( DHA ) , 400 mg 5-methyl-tetra-hydro-folate ( 5-MTHF ) , or placebo , or a combination of 500 mg DHA and 400 mg 5-MTHF . The dietary supplements were well tolerated ; the dropout rates did not differ significantly in the active arms of the study ( 10 % to 19 % ) from that seen in the placebo group ( 13 % ) . DHA supplementation result ed in significant enhancement of the contribution of DHA to maternal , placental and venous cord blood lipids Aim : To test the hypothesis that maternal docosahexaenoic acid ( DHA ) supplementation during pregnancy enhances maturation of the visual evoked potential ( VEP ) in healthy term infants . Methods : One hundred women were supplemented with either fish oil capsules rich in DHA ( n = 50 ) or placebo capsules ( n = 50 ) from week 15 of pregnancy until delivery . Total fatty acids in red blood cells and plasma were measured at weeks 15 , 28 , and 40 of pregnancy and at delivery in umbilical cord blood . Infant visual pathway development was assessed using VEPs recorded to flash stimuli shortly after birth and to both flash and pattern-reversal stimuli at 50 and 66 weeks post-conceptional age ( PCA ) . Results : Maternal supplementation did not significantly elevate the level of DHA in umbilical cord blood . Moreover , there were no significant differences in any of the VEP measures observed between supplementation groups . However , maturity of the pattern-reversal VEP at 50 and 66 weeks PCA was associated with DHA status of the infants at birth . Infants with higher DHA status , both as a concentration and as a percentage of total fatty acids , showed shorter P100 peak latencies of the pattern-reversal VEP than those with lower DHA status . Conclusions : Maternal DHA supplementation during pregnancy did not enhance VEP maturation in healthy term infants . However , these results show an association between the DHA status of infants at term and early postnatal development of the pattern-reversal VEP , suggesting that DHA status itself may influence maturation of the central visual pathways Beneficial effects of perinatal DHA supply on later neurological development have been reported . We assessed the effects of maternal DHA supplementation on the neurological development of their children . Healthy pregnant women from Spain , Germany , and Hungary were r and omly assigned to a dietary supplement consisting of either fish oil ( FO ) ( 500 mg/d DHA + 150 mg/d EPA ) , 400 μg/d 5-methyltetrahydrofolate , both , or placebo from wk 20 of gestation until delivery . Fatty acids in plasma and erythrocyte phospholipids ( PL ) were determined in maternal blood at gestational wk 20 and 30 and in cord and maternal blood at delivery . Neurological development was assessed with the Hempel examination at the age of 4 y and the Touwen examination at 5.5 y. Minor neurological dysfunction , neurological optimality score ( NOS ) , and fluency score did not differ between groups at either age , but the odds of children with the maximal NOS score increased with every unit increment in cord blood DHA level at delivery in plasma PL ( 95 % CI : 1.094 - 2.262 ) , erythrocyte phosphatidylethanolamine ( 95 % CI : 1.091 - 2.417 ) , and erythrocyte phosphatidylcholine ( 95 % CI : 1.003 - 2.643 ) . We conclude that  higher DHA levels in cord blood may be related to a better neurological outcome at 5.5 y of age BACKGROUND The influence of prenatal long-chain polyunsaturated fatty acids ( LC-PUFAs ) and folate on neurologic development remains controversial . OBJECTIVE The objective was to assess the long-term effects of n-3 ( omega-3 ) LC-PUFA supplementation , 5-methyltetrahydrofolate ( 5-MTHF ) supplementation , or both in pregnant women on cognitive development of offspring at 6.5 y of age . DESIGN This was a follow-up study of the NUHEAL ( Nutraceuticals for a Healthier Life ) cohort . Healthy pregnant women in 3 European centers were r and omly assigned to 4 intervention groups . From the 20th week of pregnancy until delivery , they received a daily supplement of 500 mg docosahexaenoic acid ( DHA ) + 150 mg eicosapentaenoic acid [ fish oil ( FO ) ] , 400 μg 5-MTHF , or both or a placebo .  Infants received formula containing 0.5 % DHA and 0.4 % arachidonic acid ( AA ) if they were born to mothers receiving FO supplements or were virtually free of DHA and AA until the age of 6 mo if they belonged to the groups that were not supplemented with FO . Fatty acids and folate concentrations were determined in maternal blood at weeks 20 and 30 of pregnancy , at delivery , and in cord blood . Cognitive function was assessed at 6.5 y of age with the Kaufman Assessment Battery for Children ( K-ABC ) . RESULTS We observed no significant differences in K-ABC scores between intervention groups . Higher DHA in maternal erythrocytes at delivery was associated with a Mental Processing Composite Score higher than the 50th percentile in the offspring . CONCLUSION We observed no significant effect of supplementation on the cognitive function of children , but maternal DHA status may be related to later cognitive function in children . This trial was registered at clinical trials.gov as NCT01180933 Both these papers were published in The Lancet , both are thought to be method ologically sound , and both are widely cited , yet their conclusions are contradictory . In this example , in the r and omised trial vitamin C was part of a multivitamin supplement , whereas in the observa- tional study plasma concentrations of vitamin C were assessed . However , it is difficult to see why a combination of vitamin C with other vitamins should reduce its protective effects , if they were real . Furthermore , in the case of other antioxidant vitamins , notably vitamin E , results of single-factor trials and observational studies show a similar discordance to those seen in our figure for vitamin C. 2 - 4 Why did observational studies and r and omised controlled trials come up with different answers ? Several reasons have been proposed for the disparity between the results of observational epidemiological studies and trials . First , antioxidants might be useful only for primary prevention of cardiovascular disease , and not protective once atherosclerosis is established . 6 However , trials 4,7 found that antioxidants did not reduce cardio- vascular disease risk in participants who had no evidence of this disorder at r and omisation . Second , in many of the trials the choice of antioxidant regimen has been criticised . The evidence relating prenatal supplementation with DHA to offspring neurological development is limited . We investigated the effect of prenatal DHA supplementation on infant brainstem auditory-evoked responses and visual- evoked potentials in a double-blind , r and omized controlled trial in Cuernavaca , Mexico . Pregnant women were supplemented daily with 400 mg DHA or placebo from gestation wk 18 - 22 through delivery . DHA and placebo groups did not differ in maternal characteristics at r and omization or infant characteristics at birth . Brainstem auditory-evoked responses were measured at 1 and 3 mo in 749 and 664 infants , respectively , and visual-evoked potentials were measured at 3 and 6 mo in 679 and 817 infants , respectively . Left-right brainstem auditory-evoked potentials were moderately correlated ( range , 0.26 - 0.43 ; all P < 0.001 ) and left-right visual-evoked potentials were strongly correlated ( range , 0.79 - 0.94 ; all P < 0.001 ) within any assessment . Correlations across visits were modest to moderate ( range , 0.09 - 0.38 ; all P < 0.01 ) . The offspring of  DHA-supplemented women did not differ from those of control women with respect to any outcome measure ( all comparisons P > 0.10 ) . We conclude that DHA supplementation during pregnancy did not influence brainstem auditory-evoked responses at 1 and 3 mo or visual-evoked potentials at 3 and 6 mo OBJECTIVES . Arachidonic acid ( 20:4n-6 ) and docosahexaenoic acid ( 22:6n-3 ) are essential for brain growth and cognitive development . We have reported that supplementing pregnant and lactating women with n-3 very-long-chain polyunsaturated fatty acids promotes higher IQ scores at 4 years of age as compared with maternal supplementation with n-6 polyunsaturated fatty acids . In our present study , the children were examined at 7 years of age with the same cognitive tests as at 4 years of age . We also examined the relation between plasma fatty acid pattern and BMI in children , because an association between arachidonic acid and adipose tissue size has been suggested . METHODS . The study was r and omized and double-blinded . The mothers took 10 mL of cod liver oil or corn oil from week 18 of pregnancy until 3 months after delivery . Their children were tested with the Kaufman Assessment Battery for Children at 7 years of age , and their height and weight were measured . RESULTS . We did not find any significant differences in scores on the Kaufman Assessment Battery for Children test at 7 years of age between children whose mothers had taken cod liver oil ( n = 82 ) or corn oil ( n = 61 ) . We observed , however , that maternal plasma phospholipid concentrations of α-linolenic acid ( 18:3n-3 ) and docosahexaenoic acid during pregnancy were correlated to sequential processing at 7 years of age . We observed no correlation between fatty acid status at birth or during the first 3 months of life and BMI at 7 years of age . CONCLUSION . This study suggests that maternal concentration of n-3 very-long-chain polyunsaturated fatty acids during pregnancy might be of importance for later cognitive function , such as sequential processing , although we observed no significant effect of n-3 fatty acid intervention on global IQs . Neonatal fatty acid status had no influence on BMI at 7 years of age CONTEXT Uncertainty exists about the benefit of dietary docosahexaenoic acid ( DHA ) on the  neurodevelopment of preterm infants . OBJECTIVE To determine the effect of meeting the estimated DHA requirement of preterm infants on neurodevelopment at 18 months ' corrected age . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind controlled trial enrolling infants born at less than 33 weeks ' gestation from April 2001 to October 2005 at 5 Australian tertiary hospitals , with follow-up to 18 months . INTERVENTION High-DHA ( approximately 1 % total fatty acids ) enteral feeds compared with st and ard DHA ( approximately 0.3 % total fatty acids ) from day 2 to 4 of life until term corrected age . MAIN OUTCOME MEASURES Bayley Mental Development Index ( MDI ) at 18 months ' corrected age . A priori subgroup analyses were conducted based on r and omization strata ( sex and birth weight < 1250 g vs > or = 1250 g ) . RESULTS Of the 657 infants enrolled , 93.5 % completed the 18-month follow-up . Bayley MDI scores did not differ between the high- and st and ard-DHA groups ( mean difference , 1.9 ; 95 % confidence interval [ CI ] , -1.0 to 4.7 ) . The MDI among girls fed the high-DHA diet was higher than girls fed st and ard DHA in unadjusted and adjusted analyses ( unadjusted mean difference , 4.7 ; 95 % CI , 0.5 - 8.8 ; adjusted mean difference , 4.5 ; 95 % CI , 0.5 - 8.5 ) . The MDI among boys did not differ between groups . For infants born weighing less than 1250 g , the MDI in the high-DHA group was higher than with st and ard DHA in the unadjusted comparison ( mean difference , 4.7 ; 95 % CI , 0.2 - 9.2 ) but did not reach statistical significance following adjustment for gestational age , sex , maternal education , and birth order ( mean difference , 3.8 ; 95 % CI , -0.5 to 8.0 ) . The MDI among infants born weighing at least 1250 g did not differ between groups . CONCLUSION A DHA dose of approximately 1 % total fatty acids in early life did not increase MDI scores of preterm infants overall born earlier than 33 weeks but did improve the MDI scores of girls . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12606000327583
BACKGROUND Maternal fish consumption during pregnancy has been positively associated with cognitive and visual abilities in the offspring , leading to the hypothesis that maternal omega-3 ( n-3 ) long-chain PUFA ( LCPUFA ) supplementation improves children 's neurologic and visual development .
OBJECTIVE The objective was to evaluate the effect of maternal omega-3 LCPUFA supplementation in pregnancy on neurologic and visual development in the offspring .