Long-chain omega-3 fatty acids and optimization of cognitive performance. First, exposure data on maternal fish oil consumption was captured on the maternal baseline questionnaire as a dichotomous variable (once or more per week), limiting our ability to distinguish specific dose or the exact frequency of supplementation. Cowan N. Working Memory Underpins Cognitive Development, Learning, and Education. Cheatham CL, Colombo J, Carlson SE. Gould JF, Makrides M, Colombo J, Smithers LG. (33) Additionally, to further investigate temporal relationships, an interaction term between the time of the ASQ and fish oil supplementation status was tested in all models. Torres-Espinola FJ, Berglund SK, Garca-Valds LM, Segura MT, Jerez A, Campos D, et al.
Additionally, females have a greater capacity to convert ALA into EPA and DHA than males. Prostaglandins Leukot Essent Fatty Acids. (78) With a half-life in the human brain of approximately two and a half years, DHA content remains for a substantial amount of time. Maternal docosahexaenoic acid feeding protects against impairment of learning and memory and oxidative stress in prenatally stressed rats: possible role of neuronal mitochondria metabolism. The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina. Evidence from clinical trials. Grandjean P, Landrigan PJ. and transmitted securely. (49) Previous research demonstrates that motor development may be indicative of later in life cognitive skills(50); therefore, it is possible that problem solving enhancements may be mediated by heightened gross motor abilities. Dunstan JA, Simmer K, Dixon G, Prescott SL. Low-level prenatal exposure to nicotine and infant neurobehavior. The authors thank all the Upstate KIDS participants and staff for their important contributions. The https:// ensures that you are connecting to the Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial. Helland IB, Smith L, Saarem K, Saugstad OD, Drevon CA. about navigating our updated article layout. Prenatal DHA status and neurological outcome in children at age 5.5 years are positively associated. Stonehouse W. Does consumption of LC omega-3 PUFA enhance cognitive performance in healthy school-aged children and throughout adulthood? In total, 5034 mothers were recruited, including mothers of singletons, twins and higher order births.
Furthermore, our findings suggest that female children experienced the greatest benefit from maternal supplementation with lower risks of personal-social and problem solving deficits significantly correlated to prenatal fish oil exposure. The .gov means its official. Due to the potential differences in neurodevelopment, stratified analyses were conducted by gender and plurality. Gil A, Gil F. Fish, a Mediterranean source of n-3 PUFA: benefits do not justify limiting consumption. Neurophysiologic and neurobehavioral evidence of beneficial effects of prenatal omega-3 fatty acid intake on memory function at school age. Cognitive assessment of children at age 2(1/2) years after maternal fish oil supplementation in pregnancy: a randomised controlled trial. Similarly, a randomized clinical trial examining maternal fish oil supplementation and pregnancy outcomes failed to detect effects in twin pregnancies. In the unadjusted analyses (Model 1), supplementation at both time points was significantly associated with a lower risk of failing multiple ASQ domains (Table 2). (56) Aged rats fed a diet supplemented with n-3 PUFA had decreased hippocampal levels of lipid peroxide and improved learning abilities. Similarly, associations were primarily among singletons. When examining plurality, both twin siblings were included in analyses (n= 2038) independent from the singleton children (n = 3807). (4) Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the two most biologically active n-3 PUFAs(8), are nutrients vital for optimal growth and development during the fetal and early postnatal stages of life. When testing an interaction term between the time of the ASQ and supplementation status, some evidence suggested an interaction with the problem solving domain when the children were older (30 and 36 months); however, sporadic interactions were also observed at the 30-month time point with the fine motor domain and overall fails (data not shown). In utero exposure to omega-3 fatty acids is exclusively dependent on maternal nutrition.
Hibbeln JR, Davis JM, Steer C, Emmett P, Rogers I, Williams C, et al. Supporting the criticality of the in utero exposure time point, prenatal n-3 PUFA deficiencies have been strongly linked with decrements in cognitive function and neurodevelopment. The use of WHO BMI categories in place of the continuous BMI value did not have an impact on results (data not shown). Long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) are essential lipids involved in neurologic functions including: maintaining membrane fluidity(6), myelination(7), gene expression, signal transduction, and neural growth. The body of evidence supporting the beneficial fetal impacts of maternal fish oil supplementation is mounting. Clouard C, Souza AS, Gerrits WJ, Hovenier R, Lammers A, Bolhuis JE. Bethesda, MD 20894, Web Policies The cognitive cost of being a twin: evidence from comparisons within families in the Aberdeen children of the 1950s cohort study. A literature review. Suganuma H, Arai Y, Kitamura Y, Hayashi M, Okumura A, Shimizu T. Maternal docosahexaenoic acid-enriched diet prevents neonatal brain injury.
Hauser RM. Buck Louis GM, Hediger ML, Bell EM, Kus CA, Sundaram R, McLain AC, et al. After adjustment for sociodemographic and maternal lifestyle factors (Model 2), the risk of failing the problem solving domain remained significantly lower among those who supplemented with fish oil before pregnancy (OR 0.40, 95% CI: 0.18 0.89) and during pregnancy (OR 0.43, 95% CI: 0.22 0.83). Tuzun F, Kumral A, Ozbal S, Dilek M, Tugyan K, Duman N, et al. 
(62) With the transition of corn and grain based livestock feeds, animals have become n-3 deficient and thus, our meat sources lack n-3 PUFA as well. Phillips MA, Childs CE, Calder PC, Rogers PJ. No Effect of Omega-3 Fatty Acid Supplementation on Cognition and Mood in Individuals with Cognitive Impairment and Probable Alzheimers Disease: A Randomised Controlled Trial. Relationship between long-chain polyunsaturated fatty acids at birth and motor function at 7 years of age. Second, the ASQ is a validated screening instrument but not a diagnostic tool; therefore, results may not be appropriate for direct comparison with outcomes from diagnostic developmental assessment tools. Singletons who were not conceived through infertility treatments were frequency matched on geographic residence and recruited at a ratio of 3:1 to those infants who were exposed to infertility treatment. All analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC).
(3) Specifically, prenatal omega-3 fatty acid deficiencies have been linked to adverse impacts on brain development with potential effects evident throughout many life stages. Ages & Stages Questionnaires [R], (ASQ-3 [TM]): A Parent-Completed Child-Monitoring System. Neurodevelopmental outcomes of twins. (62) In developing countries, access to food sources rich in n-3 PUFA is limited due to geographic as well as economic challenges. However, because many of the mothers were likely to supplement during both timeframes, precision was reduced and the findings did not reach statistical significance in models among mothers who only supplemented prior to pregnancy (4%) or only during pregnancy (8%) after excluding those who supplemented both before and during (7%). No interactions were observed at other time points.
When conducting primary analyses, one child was randomly selected from each twin pair and included with the eligible singletons (n = 4843). Measuring socioeconomic status in studies of child development. This study aims to examine the association between maternal fish oil supplementation and subsequent child developmental capabilities up to 3 years of age. The ASQ-2nd edition was used to screen the children at 46, 8, and 12 months of age. A lower risk of failing the problem solving domain persisted in a third model which was further adjusted for prenatal vitamin usage and fish consumption (supplementation before pregnancy OR 0.40, 95% CI: 0.18 0.90 and during pregnancy OR 0.43, 95% CI: 0.22 0.84). Gender interaction was not statistically significant although stratified results indicated stronger associations among girls. Willatts P, Forsyth JS, DiModugno MK, Varma S, Colvin M. Effect of long-chain polyunsaturated fatty acids in infant formula on problem solving at 10 months of age. The five domains were viewed as independent hypotheses since in clinical practice they are informative of distinct and tailored interventions and no corrections for multiple comparisons were made; therefore, p < 0.05 was considered significant. Jacobson JL, Jacobson SW, Muckle G, Kaplan-Estrin M, Ayotte P, Dewailly E. Beneficial effects of a polyunsaturated fatty acid on infant development: evidence from the inuit of arctic Quebec. (31) Additionally, multiples are known to be at increased risk of neurodevelopmental delays due to the elevated likelihood of adverse health outcomes such as low birth weight.(32). Folate and long-chain polyunsaturated fatty acid supplementation during pregnancy has long-term effects on the attention system of 8.5-y-old offspring: a randomized controlled trial. Domain specific fails were estimated in the same manner. Karr JE, Alexander JE, Winningham RG. Umhau JC, Zhou W, Carson RE, Rapoport SI, Polozova A, Demar J, et al. In situations where less than ten pairs were missing specific covariate information, the data was imputed using the mean observed response from the existing dataset (e.g., insurance and smoking).(41). official website and that any information you provide is encrypted Lorenz JM. The Institutional Review Boards (IRB) at the New York State Department of Health and the University at Albany approved the study and under a reliance agreement served as the IRBs designated by the National Institutes of Health. Omega-3 Fatty acids and pregnancy. Five developmental domains were assessed: fine motor, gross motor, communication, personal-social functioning, and problem solving. Weiser MJ, Butt CM, Mohajeri MH.
National Library of Medicine Muldoon MF, Ryan CM, Yao JK, Conklin SM, Manuck SB. Methodology for establishing a population-based birth cohort focusing on couple fertility and childrens development, the Upstate KIDS Study. Escolano-Margarit MV, Ramos R, Beyer J, Csbi G, Parrilla-Roure M, Cruz F, et al. The influence of long chain polyunsaturate supplementation on docosahexaenoic acid and arachidonic acid in baboon neonate central nervous system. (55) n-3 PUFA supplementation has been shown to improve synaptic plasticity, learning, and memory in matured rats. Mother-child pairs were excluded from this analysis if the maternal questionnaire, which captured self-reported exposure information, was not completed. Socioeconomic disadvantage and neural development from infancy through early childhood. Omega-3 fatty acids reverse age-related decreases in nuclear receptors and increase neurogenesis in old rats. (57) In humans, increased fish consumption and n-3 PUFA intake has been associated with a decreased risk of developing Alzheimers disease (58), although this association is not unanimously supported (59). Uauy R, Mena P, Wegher B, Nieto S, Salem N. Long chain polyunsaturated fatty acid formation in neonates: effect of gestational age and intrauterine growth. Huffman SL, Harika RK, Eilander A, Osendarp SJ. (14) Suggested mechanisms include differences among rates of -oxidation, adipose tissue composition, and sex hormone function between the genders. Maternal DHA and the development of attention in infancy and toddlerhood. Self-reported prenatal fish oil supplementation data was available for 5,845 children (3807 singletons and 2038 twins). Intrauterine fatty acid accretion rates in human brain: implications for fatty acid requirements. WHO. Also, a significant protective association with the problem solving domain was observed for singletons (OR 0.39, 95% CI: 0.19 0.82) but not twins (OR 0.77, 95% CI: 0.33 1.78). Bhatia HS, Agrawal R, Sharma S, Huo YX, Ying Z, Gomez-Pinilla F. Omega-3 fatty acid deficiency during brain maturation reduces neuronal and behavioral plasticity in adulthood. (63) Moreover, pregnant women have been advised to limit seafood consumption to reduce fetal exposure to chemical pollutants commonly present such as polychlorinated biphenyls (PCBs) and methylmercury(18, 64), both of which are known neurotoxicants that cross the placenta. An official website of the United States government. Randomized controlled trial of maternal omega-3 long-chain PUFA supplementation during pregnancy and early childhood development of attention, working memory, and inhibitory control. (46, 47) Nonetheless, these findings are contested (56). Gamoh S, Hashimoto M, Hossain S, Masumura S. Chronic administration of docosahexaenoic acid improves the performance of radial arm maze task in aged rats. 
McFadyen M, Farquharson J, Cockburn F. Maternal and umbilical cord erythrocyte omega-3 and omega-6 fatty acids and haemorheology in singleton and twin pregnancies. 8600 Rockville Pike Another potential explanation is that DHA promotes neurite growth within the hippocampus and accumulates rapidly in the fetal brain at the same time as critical myelination and synaptogenesis. with the Bayley Scales of Infant Development II in a low-risk sample. Fish Oil Trials In Pregnancy (FOTIP) Team. Due to the inconsistencies of the interactions, our study does not present strong evidence regarding the temporality of the neurologic associations. (54) Models in geriatric animals suggest that fish oil supplementation may play a neuroprotective role in aging by increasing neurogenesis in the hippocampus and reversing changes in retinoid receptors. Additionally, the sample size of twins was smaller than that of singletons. Primary analyses showed that the risk of failing the ASQ problem solving domain was significantly lower among children of women who took fish oil before pregnancy (OR 0.40, 95% CI: 0.18 0.89) and during pregnancy (OR 0.43, 95% CI: 0.22 0.83). Concurrent validity of the parent-completed Ages and Stages Questionnaires, 2nd Ed. Catena A, Muoz-Machicao JA, Torres-Espnola FJ, Martnez-Zaldvar C, Diaz-Piedra C, Gil A, et al. (1, 2) Maternal nutrition has a substantial influence on offspring neurodevelopment during early life due to increased fetal metabolic requirements and neurologic vulnerabilities. Multiple imputation for nonresponse in surveys. However, in gender stratified analyses, the risk of failing both the problem solving (OR 0.17, 95% CI: 0.03 0.95) and the personal-social (OR 0.33, 95% CI: 0.12 0.95) domains were significantly lower among girls whose mothers used fish oil supplementation but not in boys (OR 0.64; 95% CI: 0.301.36), when adjusted for sociodemographic factors. (15) Therefore, fetal intake is largely dependent on maternal nutrition(16), with the richest sources of DHA and EPA naturally present in seafood and fish. The polyunsaturated fatty acids, EPA and DPA exert a protective effect in the hippocampus of the aged rat. No differences were observed for child gender. Additionally, nutritional data was captured on self-reported questionnaires. Previous research warranted future studies including children of multiple gestations.
Maternal Fish Oil Supplementation Affects the Social Behavior, Brain Fatty Acid Profile, and Sickness Response of Piglets. will also be available for a limited time. (69) Using National Health and Nutritional Examination Survey (NHANES) data, a study found the positive relationship between n-3 fatty acid intake and cognition to be twice as strong for school-aged females when compared to males. (8) Due to maternal dietary limitations and environmental health concerns, fish oil supplementation may be consumed as a substantial source of n-3 PUFA during pregnancy(17). 1Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 2Department of Pediatrics, New York University School of Medicine, New York, New York, USA, 3Biostatistics and Bioinformatics Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD. Omega-3 polyunsaturated fatty acids and cognition throughout the lifespan: a review. Maternal consumption of a DHA-containing functional food benefits infant sleep patterning: an early neurodevelopmental measure. (33) Participants were recruited from New York State livebirth registry and included mothers who gave birth between July 2008 and May 2010. Reversibility of n-3 fatty acid deficiency-induced alterations of learning behavior in the rat: level of n-6 fatty acids as another critical factor. The frequencies of domain failures by supplementation group are presented in Supplemental Table 1. Essential fats: how do they affect growth and development of infants and young children in developing countries? Specifically, it is associated with a lower risk of failing the problem solving domain up to 3 years of age. Yolton K, Khoury J, Xu Y, Succop P, Lanphear B, Bernert JT, et al.
At 4 months postpartum, mothers indicated (yes/no) if they had regularly consumed (> 1 time per week) numerous vitamins and dietary supplements (e.g., multivitamins, iron) throughout pregnancy. 
Campoy C, Escolano-Margarit MV, Ramos R, Parrilla-Roure M, Csbi G, Beyer J, et al. The potential for fetal insufficiencies of n-3 PUFA during critical windows of development is of concern due to the transition of many to Westernized diets high in saturated fats and low in polyunsaturated fatty acids, specifically n-3 PUFA. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Maternal baseline characteristics by fish oil supplementation status. It has been demonstrated that while singleton newborns have higher mean erythrocyte DHA concentrations than their mothers at the time of birth, twins have lower levels suggesting fetal insufficiencies. (71, 72) When stratifying by plurality in our study, the beneficial association on problem solving was significant for singletons but not twins. Luchtman DW, Song C. Cognitive enhancement by omega-3 fatty acids from child-hood to old age: findings from animal and clinical studies. To evaluate the associations between fish oil supplementation (before and during pregnancy) and any fail on the ASQ domains, generalized linear mixed models with a logit link function were used to estimate 95% confidence intervals (CI) and odds ratios (OR). However, a consensus regarding n-3 PUFA supplementation and aforementioned benefits has not been reached. In our analyses, regular prenatal vitamin consumption was defined as having taken the vitamins seven days per week due to the high frequency of adherence, 75% of mothers reported taking the vitamins every day. (24) Several randomized controlled trials of fish oil during pregnancy have described beneficial associations among maternal supplementation and child outcomes such as: hand and eye coordination(17), problem solving skills(25), and neurologic development. Chin-Lun Hung G, Hahn J, Alamiri B, Buka SL, Goldstein JM, Laird N, et al. Report of a WHO consultation. (4) While many studies have focused on the impact of n-3 PUFA on the development of brain regions such as the frontal lobe in school-aged children, our study shows that the beneficial association is present early in life, specifically in children 3 years and younger. Five developmental domains were assessed: fine motor, gross motor, communication, personal-social and problem solving.
(53) The role of n-3 PUFA on cognitive function in the developing as well as the aged brain has been previously demonstrated. This study faced some limitations. (34, 36) The items from each domain were then summed with total scores ranging from 0 to 300 (60 points for each domain). Bobiski R, Mikulska M. The ins and outs of maternal-fetal fatty acid metabolism. We also assessed the relationship among the mothers who indicated supplementing throughout both time points and ASQ fails. Released in 2009, the ASQ-3rd edition was used for screening from 18 through 36 months of age. The same mothers were less likely to smoke during pregnancy when compared to those who did not consume fish oil supplements. To our knowledge, no studies have examined the impact of prenatal n-3 PUFA supplementation on the neurodevelopment of twins. The elements of each questionnaire were scored as follows: yes = 10 points, sometimes = 5 points, not yet = 0 points. The longitudinal approach with multiple collected ASQ data points employed by the Upstate KIDS Study is a valuable design aspect. Due to many missing values, we ran analyses, adjusted for both sociodemographic and nutritional factors, for only those mother-child pairs with prenatal fish consumption data (n=2412) to compare with the analyses of the entire dataset which included imputed values. In addition, we investigate any divergences in these impacts among singletons and twins. On average, 23% of children failed each domain. Baseline data on maternal usage (yes/no) of rare supplements during pregnancy (echinacea, ginkgo biloba, kava kava, and St. Johns wort) were combined due to rarity when we evaluated their association with the ASQ outcomes. Saccone G, Saccone I, Berghella V. Omega-3 long-chain polyunsaturated fatty acids and fish oil supplementation during pregnancy: which evidence?
Feng Z, Zou X, Jia H, Li X, Zhu Z, Liu X, et al. Odds ratio for risk of developmental delays by maternal fish oil supplementation status. The new PMC design is here! Colombo J, Kannass KN, Shaddy DJ, Kundurthi S, Maikranz JM, Anderson CJ, et al. Previous studies have suggested that prenatal fish oil supplementation has positive impacts on child neurodevelopment later in life. Secondary analyses were suggestive of a positive relationship between fish oil supplementation and personal-social and problem solving skills among female children only. (53, 54) An autopsy study found that term infants had appreciably higher DHA contents in the frontal cortex than those infants who were in the second trimester(76), demonstrating the elevated requirement of n-3 PUFA during the final trimester of gestation. Docosahexaenoic Acid and Cognition throughout the Lifespan. The number of mothers who took rare supplements (e.g., St. Johns Wort, Echinacea) during pregnancy was very low (n=31); therefore, we were unable to detect any association with ASQ scores. Human placental transcriptome shows sexually dimorphic gene expression and responsiveness to maternal dietary n-3 long-chain polyunsaturated fatty acid intervention during pregnancy. Fails for each domain are defined as scores two standard deviations below the average score for the childs age which was derived from a US normative sample. (9) Perinatal brain maturation reaches its peak growth rate during the third trimester of gestation(6), requiring rapid DHA accretion into retinal and neural tissues. (15) Preformed n-3 PUFA, directly obtained through diet, accumulates more readily than those derived from precursor acids due to enhanced bioavailability. The authors assert that all procedures contributing to this work comply with the ethical standards approved by the New York State Department of Health and the University of Albany Institutional Review Board (NYSDOH IRB #07-097; UAlbany #08-179) serving as the IRB designated by the National Institutes of Health for this study under a reliance agreement. (13) In the adult liver, DHA is metabolically converted from alpha-linolenic acid (ALA); however, de novo synthesis is inefficient in humans(14) and elevated perinatal requirements cannot be met solely via endogenous formation. (81) Our analyses examined twins in addition to singletons and independently. Essential fatty acids and the brain: from infancy to aging. Barker DJ, Clark PM. Sensitivity analyses included several independent models. Kobayashi K. Role of catecholamine signaling in brain and nervous system functions: new insights from mouse molecular genetic study. A separate question queried if fish oil supplementation was taken more than one time per week during pregnancy. Gould JF, Smithers LG, Makrides M. The effect of maternal omega-3 (n-3) LCPUFA supplementation during pregnancy on early childhood cognitive and visual development: a systematic review and meta-analysis of randomized controlled trials. Both infants and the elderly are vulnerable populations with regard to many exposures. Neurodevelopmental outcomes of triplets or higher-order extremely low birth weight infants. (18) Observational studies have found that cord blood n-3 PUFA concentrations are associated with improved language, cognitive, visual motor(19) and memory skills(20) among children aged 11 months through 12 years suggesting that prenatal n-3 PUFA intake is of importance with effects potentially spanning many years (21). The studys design of oversampling based on infertility treatment and multiples was accounted for by the use of sampling weights, which were derived from New York state birth certificate data, in the analyses. At four months postpartum, mothers completed a self-administered questionnaire which inquired about their prior pregnancy with the participating child. Drover J, Hoffman DR, Castaeda YS, Morale SE, Birch EE. (79) While we cannot rule out postnatal n-3 PUFA exposures in our current study (e.g., infant formulas supplemented with DHA (80)), research suggests that the positive impacts of this prenatal exposure may be long-lasting, even after continuous supplementation has ceased. Lauritzen L, Brambilla P, Mazzocchi A, Harslf LB, Ciappolino V, Agostoni C. DHA Effects in Brain Development and Function. (74) A recent prospective cohort identified a temporary increase in child neurodevelopment followed by an accelerated decline in these skills among children born to obese mothers, suggesting a dynamic temporal association. (66) In early life, females begin storing DHA in adipose deposits in order to support the growth and development of future offspring(54, 67); therefore, higher quantities of the nutrient are required. Makrides M, Gibson RA, McPhee AJ, Collins CT, Davis PG, Doyle LW, et al. McNamara RK, Carlson SE. Developmental neurotoxicity of industrial chemicals. This study examines the associations between fish oil supplementation both before pregnancy and throughout pregnancy and subsequent child development. The site is secure. sharing sensitive information, make sure youre on a federal To account for repeated ASQ measures of development, an infant-level random intercept was included in all models.