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. Despite limitations from the observational nature of our study design, we found that reported maternal fish oil supplementation, both before and during pregnancy, was protective against failing the problem solving domain of the ASQ with the association persisting until three years of age. Lauritzen L, Hansen HS, Jrgensen MH, Michaelsen KF. Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial.
(65) Therefore, fish oil supplementation, typically free from contaminants found in fish and seafood, may be a valuable alternative source of n-3 PUFA. This study examines the associations between fish oil supplementation both before pregnancy and throughout pregnancy and subsequent child development. The authors thank all the Upstate KIDS participants and staff for their important contributions. Tuzun F, Kumral A, Ozbal S, Dilek M, Tugyan K, Duman N, et al. (44) While the underlying mechanisms between n-3 PUFA and cognition remain unknown, several postulations exist. Luchtman DW, Song C. Cognitive enhancement by omega-3 fatty acids from child-hood to old age: findings from animal and clinical studies. (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. Boucher O, Burden MJ, Muckle G, Saint-Amour D, Ayotte P, Dewailly E, et al. Fetal undernutrition and disease in later life.
Recommended for use from infancy through early childhood, the Ages and Stages Questionnaire (ASQ) is a validated parent-completed screening tool designed for early assessment of developmental delays.
The body of evidence supporting the beneficial fetal impacts of maternal fish oil supplementation is mounting. and transmitted securely. (8, 14), Associations between maternal supplementation and lower risks of failing the personal-social and problem solving domains of the ASQ were significant among female, but not male, children, suggesting potential gender modification.
Socioeconomic disadvantage and neural development from infancy through early childhood. (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. Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments childrens IQ at 4 years of age. The new PMC design is here! Essential fats: how do they affect growth and development of infants and young children in developing countries? Weiser MJ, Butt CM, Mohajeri MH.
(14) Suggested mechanisms include differences among rates of -oxidation, adipose tissue composition, and sex hormone function between the genders. Holman RT.
Grandjean P, Landrigan PJ. A recent randomized controlled trial did not find any evidence supporting the long-term beneficial impacts of prenatal fish oil supplementation on child attention (48). Similarly, a randomized clinical trial examining maternal fish oil supplementation and pregnancy outcomes failed to detect effects in twin pregnancies. (15) Preformed n-3 PUFA, directly obtained through diet, accumulates more readily than those derived from precursor acids due to enhanced bioavailability. Takeuchi T, Fukumoto Y, Harada E. Influence of a dietary n-3 fatty acid deficiency on the cerebral catecholamine contents, EEG and learning ability in rat. (26, 27) Additionally, research indicates that the effects of DHA on the developing brain may be impacted by gender and genotype (21). Although the evidence is inconsistent (29), prenatal fish oil supplementation has been associated with modest improvements in gross motor function. 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. The elements of each questionnaire were scored as follows: yes = 10 points, sometimes = 5 points, not yet = 0 points. Lastly, both fish oil supplementation and child performance on the ASQ were assessed using maternal report which could potentially introduce bias.
(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.
The influence of long chain polyunsaturate supplementation on docosahexaenoic acid and arachidonic acid in baboon neonate central nervous system. (53) The role of n-3 PUFA on cognitive function in the developing as well as the aged brain has been previously demonstrated.
Given that pregnant women are advised to increase n-3 PUFA intake to aid fetal brain development while concurrently restricting fish and seafood consumption, our findings demonstrate the potential value of fish oil supplementation as an alternate source of n-3 PUFA during pregnancy. Hauser RM. Gould JF, Makrides M, Colombo J, Smithers LG. Low-level prenatal exposure to nicotine and infant neurobehavior.
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. Five developmental domains were assessed: fine motor, gross motor, communication, personal-social and problem solving.
Judge MP, Cong X, Harel O, Courville AB, Lammi-Keefe CJ. Multiple imputation for nonresponse in surveys. (68) A randomized double-blind controlled trial described a correlation between postnatal DHA supplementation in preterm infants and Bayley Mental Development Index (MDI) scores at 18 months corrected age among females only. In total, 5034 mothers were recruited, including mothers of singletons, twins and higher order births. 
In model 2, fish oil supplementation before pregnancy was additionally related to a decreased risk of failing the communication and personal-social domains although the associations were borderline significant (p<0.10). Specifically, it is associated with a lower risk of failing the problem solving domain up to 3 years of age. Maternal prenatal omega-3 fatty acid supplementation attenuates hyperoxia-induced apoptosis in the developing rat brain.
Barker DJ, Clark PM. 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.
Role of omega-3 fatty acids in brain development and function: potential implications for the pathogenesis and prevention of psychopathology. Released in 2009, the ASQ-3rd edition was used for screening from 18 through 36 months of age. Prenatal DHA status and neurological outcome in children at age 5.5 years are positively associated. Maternal consumption of a DHA-containing functional food benefits infant sleep patterning: an early neurodevelopmental measure. The site is secure. Gil A, Gil F. Fish, a Mediterranean source of n-3 PUFA: benefits do not justify limiting consumption. The https:// ensures that you are connecting to the Fish oil contains omega-3 fatty acids, which play a vital role in fetal growth and development. (33) Participants were recruited from New York State livebirth registry and included mothers who gave birth between July 2008 and May 2010. 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). 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. Additionally, nutritional data was captured on self-reported questionnaires. with the Bayley Scales of Infant Development II in a low-risk sample. A separate question queried if fish oil supplementation was taken more than one time per week during pregnancy. The ASQ-2nd edition was used to screen the children at 46, 8, and 12 months of age. Obesity: preventing and managing the global epidemic.
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. (70, 80). 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. 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. This study faced some limitations. 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. Muldoon MF, Ryan CM, Yao JK, Conklin SM, Manuck SB. Before No differences were observed for child gender. In addition, we investigate any divergences in these impacts among singletons and twins. No notable differences in results were detected (i.e., problem solving OR adjusted for fish consumption: 0.57; 95% CI: 0.271.20). (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. No interactions were observed at other time points. However, our analyses were strengthened by the notable sample size of greater than 4,800 mother-child pairs. At four months postpartum, mothers completed a self-administered questionnaire which inquired about their prior pregnancy with the participating child. Accessibility With regards to nutrition, taking fish oil supplementation was associated with also taking prenatal vitamins and consuming fish during pregnancy.
Schlotz W, Phillips DI. When including both siblings in a set of twins a second random intercept was added to the models. Interaction terms were tested for between fish oil supplementation during pregnancy and gender as well as supplementation and plurality. Cognitive assessment of children at age 2(1/2) years after maternal fish oil supplementation in pregnancy: a randomised controlled trial.
(1, 2) Maternal nutrition has a substantial influence on offspring neurodevelopment during early life due to increased fetal metabolic requirements and neurologic vulnerabilities. Multiple imputations were used to generate ten independent datasets when there were missing covariate values for ten or more mother-child pairs.
(62) In developing countries, access to food sources rich in n-3 PUFA is limited due to geographic as well as economic challenges. Maternal fish oil supplementation in pregnancy: a 12 year follow-up of a randomised controlled trial.
A literature review. Maternal Obesity, Overweight and Gestational Diabetes Affect the Offspring Neurodevelopment at 6 and 18 Months of Age A Follow Up from the PREOBE Cohort.
(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. Benefits of docosahexaenoic acid, folic acid, vitamin D and iodine on foetal and infant brain development and function following maternal supplementation during pregnancy and lactation. (46, 47) Nonetheless, these findings are contested (56).
The baseline questionnaire also collected information on how many days per week the mothers took prenatal vitamins. Bakker EC, Hornstra G, Blanco CE, Vles JS. The .gov means its official. Each of the ten imputed datasets were analyzed and the resultant data were then pooled to achieve complete analyses. 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. Future research needs to focus on clearing up discrepancies in the literature, establishing optimal dosages, identifying the ideal timing and duration of supplementation, the persistence of subsequent health outcomes, gender interactions, and impacts on children of multiple births. 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. WHO. 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). The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina. Feng Z, Zou X, Jia H, Li X, Zhu Z, Liu X, et al. Concurrent validity of the parent-completed Ages and Stages Questionnaires, 2nd Ed. Hibbeln JR, Davis JM, Steer C, Emmett P, Rogers I, Williams C, et al. Dyall SC, Michael GJ, Michael-Titus AT. Omega-3 polyunsaturated fatty acids and cognition throughout the lifespan: a review. 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. Neurophysiologic and neurobehavioral evidence of beneficial effects of prenatal omega-3 fatty acid intake on memory function at school age.
will also be available for a limited time. (60, 61) The American food industry has become much more reliant on processed foods which are often void of n-3 due to the desire for increased shelf life.
(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. Meldrum S, Dunstan JA, Foster JK, Simmer K, Prescott SL. Sedlmeier EM, Brunner S, Much D, Pagel P, Ulbrich SE, Meyer HH, et al.
Maternal baseline characteristics by fish oil supplementation status. Randomized controlled trial of maternal omega-3 long-chain PUFA supplementation during pregnancy and early childhood development of attention, working memory, and inhibitory control. Ikemoto A, Ohishi M, Sato Y, Hata N, Misawa Y, Fujii Y, et al. The 12 month questionnaire inquired about how many servings of fish were consumed per week during pregnancy. Early life programming and neurodevelopmental disorders. FOIA The same mothers were less likely to smoke during pregnancy when compared to those who did not consume fish oil supplements.
Arterburn LM, Hall EB, Oken H. Distribution, interconversion, and dose response of n-3 fatty acids in humans. 8600 Rockville Pike (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). (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. Vital records in combination with self-reported information (where missing) provided demographic data on maternal age, race/ethnicity, educational achievement, marital status, and health insurance status. 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. Three randomized controlled trials of early long-chain polyunsaturated Fatty Acid supplementation on means-end problem solving in 9-month-olds. To our knowledge, no studies have examined the impact of prenatal n-3 PUFA supplementation on the neurodevelopment of twins.
National Library of Medicine Yolton K, Khoury J, Xu Y, Succop P, Lanphear B, Bernert JT, et al. Confounders were selected a priori based on previously described associations with the exposure and child developmental deficits (e.g., educational achievement(38), income(39), and maternal smoking during pregnancy(40)).
Maternal DHA and the development of attention in infancy and toddlerhood. On average, 23% of children failed each domain. Animal models show that the learning deficits associated with shortages of n-3 PUFA during this critical prenatal period are challenging to reverse(77) and reduce brain plasticity and performance in adulthood. government site.
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. It is widely accepted that the intrauterine environment not only plays a pivotal role in fetal development but has the potential to cause lasting health effects in offspring. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease.
Similar effects on problem solving were apparent in singleton, but not twin, children. A higher percentage of children in the no fish oil group tended to fail than the fish oil group. 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. J Dev Orig Health Dis. Due to the potential differences in neurodevelopment, stratified analyses were conducted by gender and plurality. (2830) The mixed results may be attributed, in part, to high attrition rates, lack of statistical power, diverse study designs, and varying time points for outcome assessment. For the analyses, fish consumption was treated as a dichotomous covariate (0 servings of fish eaten per week or > 0 servings of fish eaten per week) due to few mothers eating multiple servings per week. 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). Health information including parental body mass index (BMI), parity, and maternal smoking history was obtained from the baseline questionnaire. Dunstan JA, Simmer K, Dixon G, Prescott SL. Colombo J, Kannass KN, Shaddy DJ, Kundurthi S, Maikranz JM, Anderson CJ, et al. Gamoh S, Hashimoto M, Hossain S, Masumura S. Chronic administration of docosahexaenoic acid improves the performance of radial arm maze task in aged rats. Prostaglandins Leukot Essent Fatty Acids. 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). When conducting primary analyses, one child was randomly selected from each twin pair and included with the eligible singletons (n = 4843). Report of a WHO consultation. The longitudinal approach with multiple collected ASQ data points employed by the Upstate KIDS Study is a valuable design aspect.
Nutritional factors such as prenatal vitamin usage and fish consumption were adjusted for in a third model. (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). Similarly, associations were primarily among singletons. (73) Due to the inclusion of the aforementioned covariates in our analyses, it is possible that the positive effect of fish oil supplementation was not apparent. Five developmental domains were assessed: fine motor, gross motor, communication, personal-social functioning, and problem solving.
Makrides M, Gibson RA, McPhee AJ, Yelland L, Quinlivan J, Ryan P, et al. Diau GY, Hsieh AT, Sarkadi-Nagy EA, Wijendran V, Nathanielsz PW, Brenna JT. Umhau JC, Zhou W, Carson RE, Rapoport SI, Polozova A, Demar J, et al. Gender interaction was not statistically significant although stratified results indicated stronger associations among girls. Docosahexaenoic Acid and Cognition throughout the Lifespan. (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.
The use of WHO BMI categories in place of the continuous BMI value did not have an impact on results (data not shown). Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study. Stonehouse W. Does consumption of LC omega-3 PUFA enhance cognitive performance in healthy school-aged children and throughout adulthood? Omega-3 Fatty acids and pregnancy. Campoy C, Escolano-Margarit MV, Ramos R, Parrilla-Roure M, Csbi G, Beyer J, et al.
All mothers provided written informed consent. 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. Federal government websites often end in .gov or .mil.
Both infants and the elderly are vulnerable populations with regard to many exposures.
Omega-3 fatty acids reverse age-related decreases in nuclear receptors and increase neurogenesis in old rats. 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. (45) Supplementation of n-3 PUFA has also been associated with heightened attention which in turn is linked with improved cognition. (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.
Ronalds GA, De Stavola BL, Leon DA. Fish Oil Trials In Pregnancy (FOTIP) Team. 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. Methodology for establishing a population-based birth cohort focusing on couple fertility and childrens development, the Upstate KIDS Study. (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.
HHS Vulnerability Disclosure, Help To examine the impact of exposure duration, we separated the mothers who consumed fish oil supplementation exclusively before pregnancy from the mothers who supplemented solely during pregnancy. At multiple time points, from 4 months to 3 years of age, child development was reported by the parents on the Ages and Stages Questionnaire (ASQ). The frequencies of domain failures by supplementation group are presented in Supplemental Table 1. 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. Escolano-Margarit MV, Ramos R, Beyer J, Csbi G, Parrilla-Roure M, Cruz F, et al. All infants with birth certificates indicating conception by way of infertility treatment were recruited to participate in the study.
Bethesda, MD 20894, Web Policies Helland IB, Smith L, Saarem K, Saugstad OD, Drevon CA.
(34, 36) The items from each domain were then summed with total scores ranging from 0 to 300 (60 points for each domain). Suganuma H, Arai Y, Kitamura Y, Hayashi M, Okumura A, Shimizu T. Maternal docosahexaenoic acid-enriched diet prevents neonatal brain injury. We were unable to detect a significant statistical interaction for supplementation during pregnancy and gender. Self-reported prenatal fish oil supplementation data was available for 5,845 children (3807 singletons and 2038 twins). Cowan N. Working Memory Underpins Cognitive Development, Learning, and Education. Secondary analyses were suggestive of a positive relationship between fish oil supplementation and personal-social and problem solving skills among female children only. Neither did an interaction between supplementation and plurality reach statistical significance.
Phillips MA, Childs CE, Calder PC, Rogers PJ. Childs CE, Romeu-Nadal M, Burdge GC, Calder PC.
(12) DHA and EPA enter fetal circulation through simple diffusion across the placenta driven by a concentration gradient. (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. N-3 fatty acids and cognitive and visual acuity development: methodologic and conceptual considerations. The outcomes were treated as binary variables (pass/fail) due to the original design of the tool which intends the ASQ to be used as an initial screening test accompanied by follow-up assessment in situations where a child fails any domain or there is parental concern (36). The sociodemographic, nutritional, and infant characteristics of mother-child pairs relative to fish oil supplementation status were compared using the chi-squared test and independent sample t tests. (81) Our analyses examined twins in addition to singletons and independently. 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.
The Kobayashi K. Role of catecholamine signaling in brain and nervous system functions: new insights from mouse molecular genetic study. Intrauterine fatty acid accretion rates in human brain: implications for fatty acid requirements. The permanence of the potential impacts of in utero exposures is one of the critical facets regarding fetal programming.
(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. Relationship between long-chain polyunsaturated fatty acids at birth and motor function at 7 years of age. Previous research warranted future studies including children of multiple gestations. Mother-child pairs from the Upstate KIDS Study, a birth cohort consisting of children born between 2008 and 2010, were included. The literature as a whole is lacking consistent epidemiological evidence with numerous studies failing to observe child impacts stemming from in utero n-3 PUFA exposure.
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