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(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. 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)). The 12 month questionnaire inquired about how many servings of fish were consumed per week during pregnancy. 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. Odds ratio for risk of developmental delays by maternal fish oil supplementation status. 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. 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. Cowan N. Working Memory Underpins Cognitive Development, Learning, and Education. (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). (46, 47) Nonetheless, these findings are contested (56). 2017 Aug; 8(4): 465473. The authors thank all the Upstate KIDS participants and staff for their important contributions. Prostaglandins Leukot Essent Fatty Acids. Neither did an interaction between supplementation and plurality reach statistical significance. National Library of Medicine and transmitted securely. (44) While the underlying mechanisms between n-3 PUFA and cognition remain unknown, several postulations exist. This study examines the associations between fish oil supplementation both before pregnancy and throughout pregnancy and subsequent child development. Corresponding author: Dr. Edwina H. Yeung, 6100 Executive Blvd, 7B03, Rockville, MD 20852, Tel: 301-435-6921, The publisher's final edited version of this article is available at, GUID:26F29032-8F60-4ADE-AB7F-D2F410C95D60, Fish oil, prenatal, child development, omega-3 fatty acids, problem solving. Sedlmeier EM, Brunner S, Much D, Pagel P, Ulbrich SE, Meyer HH, et al. (66) A study of the human placental transcriptome discovered that maternal n-3 PUFA supplementation during pregnancy is associated with more pronounced placental gene expression in females compared to males. Stonehouse W. Does consumption of LC omega-3 PUFA enhance cognitive performance in healthy school-aged children and throughout adulthood? Omega-3 fatty acids reverse age-related decreases in nuclear receptors and increase neurogenesis in old rats. Accessibility (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. The parents engaged in different activities with their children and then responded to questions on the ASQ rating their childs skills. 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. Grandjean P, Landrigan PJ. The Upstate KIDS Study is a population-based birth cohort in New York State (excluding the five New York City boroughs) originally designed to examine the impact of infertility treatment on child growth and development. Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial. Bakker EC, Hornstra G, Blanco CE, Vles JS. Neurodevelopmental outcomes of triplets or higher-order extremely low birth weight infants. Boucher O, Burden MJ, Muckle G, Saint-Amour D, Ayotte P, Dewailly E, et al. Role of omega-3 fatty acids in brain development and function: potential implications for the pathogenesis and prevention of psychopathology. An official website of the United States government. will also be available for a limited time. Controversial studies have warranted further prospective research to investigate the potential long-term effects of prenatal fish oil intake and child development (29)). Campoy C, Escolano-Margarit MV, Ramos R, Parrilla-Roure M, Csbi G, Beyer J, et al. Ghassabian A, Sundaram R, Bell E, Bello SC, Kus C, Yeung E. Gross Motor Milestones and Subsequent Development. 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. The permanence of the potential impacts of in utero exposures is one of the critical facets regarding fetal programming. (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. 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 ASQ-2nd edition was used to screen the children at 46, 8, and 12 months of age. 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. (4, 5). 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. WHO. Mother-child pairs were excluded from this analysis if the maternal questionnaire, which captured self-reported exposure information, was not completed. (55) n-3 PUFA supplementation has been shown to improve synaptic plasticity, learning, and memory in matured rats. 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. 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. At four months postpartum, mothers completed a self-administered questionnaire which inquired about their prior pregnancy with the participating child. Methodology for establishing a population-based birth cohort focusing on couple fertility and childrens development, the Upstate KIDS Study. The slow discovery of the importance of omega 3 essential fatty acids in human health. Gow RV, Hibbeln JR. Omega-3 fatty acid and nutrient deficits in adverse neurodevelopment and childhood behaviors. No differences were observed for child gender. Judge MP, Cong X, Harel O, Courville AB, Lammi-Keefe CJ. Imaging incorporation of circulating docosahexaenoic acid into the human brain using positron emission tomography. Fish Oil Trials In Pregnancy (FOTIP) Team. First, the accumulation of n-3 PUFA within the cell membranes may result in enhanced information processing speed which would thus lead to improved problem solving. Hadders-Algra M. The neuromotor examination of the preschool child and its prognostic significance. Although the evidence is inconsistent (29), prenatal fish oil supplementation has been associated with modest improvements in gross motor function. 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. The longitudinal approach with multiple collected ASQ data points employed by the Upstate KIDS Study is a valuable design aspect. 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. Karr JE, Alexander JE, Winningham RG. A separate question queried if fish oil supplementation was taken more than one time per week during pregnancy. Fetal undernutrition and disease in later life. (15) Preformed n-3 PUFA, directly obtained through diet, accumulates more readily than those derived from precursor acids due to enhanced bioavailability. Maternal docosahexaenoic acid feeding protects against impairment of learning and memory and oxidative stress in prenatally stressed rats: possible role of neuronal mitochondria metabolism. 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. (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. Chin-Lun Hung G, Hahn J, Alamiri B, Buka SL, Goldstein JM, Laird N, et al. To account for repeated ASQ measures of development, an infant-level random intercept was included in all models. Luchtman DW, Song C. Cognitive enhancement by omega-3 fatty acids from child-hood to old age: findings from animal and clinical studies. (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. The elements of each questionnaire were scored as follows: yes = 10 points, sometimes = 5 points, not yet = 0 points. (67) Similarly, animal research has suggested that fish oil supplementation during pregnancy results in improved social behavior; however, this finding did not take gender into account.(70). 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. The .gov means its official. Concurrent validity of the parent-completed Ages and Stages Questionnaires, 2nd Ed. Health information including parental body mass index (BMI), parity, and maternal smoking history was obtained from the baseline questionnaire. Neurophysiologic and neurobehavioral evidence of beneficial effects of prenatal omega-3 fatty acid intake on memory function at school age. 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. In total, 5034 mothers were recruited, including mothers of singletons, twins and higher order births. 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. Ikemoto A, Ohishi M, Sato Y, Hata N, Misawa Y, Fujii Y, et al. In utero exposure to omega-3 fatty acids is exclusively dependent on maternal nutrition. J Dev Orig Health Dis. (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. No notable differences in results were detected (i.e., problem solving OR adjusted for fish consumption: 0.57; 95% CI: 0.271.20). Torres-Espinola FJ, Berglund SK, Garca-Valds LM, Segura MT, Jerez A, Campos D, et al. official website and that any information you provide is encrypted Maternal fish oil supplementation in pregnancy: a 12 year follow-up of a randomised controlled trial. Previous studies have suggested that prenatal fish oil supplementation has positive impacts on child neurodevelopment later in life. Animal models suggest that maternal n-3 PUFA supplementation may be neuroprotective in regards to neonatal hypoxic-ischemic brain injury(22), hyperoxic injury(23), and prenatal stress-induced learning and memory deficits. (33) Participants were recruited from New York State livebirth registry and included mothers who gave birth between July 2008 and May 2010. Childs CE, Romeu-Nadal M, Burdge GC, Calder PC. While our study did not detect an effect on gross motor function, the ASQ may not be sensitive enough to capture these subtle variations. 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. Both infants and the elderly are vulnerable populations with regard to many exposures. Low-level prenatal exposure to nicotine and infant neurobehavior.

Diau GY, Hsieh AT, Sarkadi-Nagy EA, Wijendran V, Nathanielsz PW, Brenna JT. Yolton K, Khoury J, Xu Y, Succop P, Lanphear B, Bernert JT, et al. (75) Our study identified significant interactions with problem solving at 30 and 36 months and in utero supplementation status; however, this relationship may be attributed to more appreciable problem solving skills at older ages. 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). Colombo J, Kannass KN, Shaddy DJ, Kundurthi S, Maikranz JM, Anderson CJ, et al. Neurodevelopmental outcomes of preterm infants fed high-dose docosahexaenoic acid: a randomized controlled trial. (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. 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). 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. The use of WHO BMI categories in place of the continuous BMI value did not have an impact on results (data not shown). Cheatham CL, Colombo J, Carlson SE. Lassek WD, Gaulin SJ. (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). Escolano-Margarit MV, Ramos R, Beyer J, Csbi G, Parrilla-Roure M, Cruz F, et al. 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. The https:// ensures that you are connecting to the Mothers who took fish oil supplementation were more likely to be older, Non-Hispanic White, married, possess an advanced degree, have lower pre-pregnancy BMIs, use fertility treatment, and have private insurance. The Hauser RM. 8600 Rockville Pike Five developmental domains were assessed: fine motor, gross motor, communication, personal-social functioning, and problem solving. (45) Supplementation of n-3 PUFA has also been associated with heightened attention which in turn is linked with improved cognition. 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. (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. (14) Suggested mechanisms include differences among rates of -oxidation, adipose tissue composition, and sex hormone function between the genders.

In all of the models, the mother-child pairs who did not consume supplementation were the reference group. Essential fats: how do they affect growth and development of infants and young children in developing countries? Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; contracts #HHSN275201200005C, #HHSN267200700019C). When examining plurality, both twin siblings were included in analyses (n= 2038) independent from the singleton children (n = 3807). Mother-child pairs from the Upstate KIDS Study, a birth cohort consisting of children born between 2008 and 2010, were included.

Bethesda, MD 20894, Web Policies To our knowledge, no studies have examined the impact of prenatal n-3 PUFA supplementation on the neurodevelopment of twins. 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. Fetal origins of mental health: evidence and mechanisms. Maternal Fish Oil Supplementation Affects the Social Behavior, Brain Fatty Acid Profile, and Sickness Response of Piglets. This study aims to examine the association between maternal fish oil supplementation and subsequent child developmental capabilities up to 3 years of age. Interaction terms were tested for between fish oil supplementation during pregnancy and gender as well as supplementation and plurality. Morse NL. Domain specific fails were estimated in the same manner. Omega-3 polyunsaturated fatty acids and cognition throughout the lifespan: a review. With regards to nutrition, taking fish oil supplementation was associated with also taking prenatal vitamins and consuming fish during pregnancy. Careers. (70, 80). Makrides M, Gibson RA, McPhee AJ, Collins CT, Davis PG, Doyle LW, et al. 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 influence of long chain polyunsaturate supplementation on docosahexaenoic acid and arachidonic acid in baboon neonate central nervous system. Feng Z, Zou X, Jia H, Li X, Zhu Z, Liu X, et al. 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. (71, 72) When stratifying by plurality in our study, the beneficial association on problem solving was significant for singletons but not twins. Learn more When including both siblings in a set of twins a second random intercept was added to the models. Randomized controlled trial of maternal omega-3 long-chain PUFA supplementation during pregnancy and early childhood development of attention, working memory, and inhibitory control. (1, 2) Maternal nutrition has a substantial influence on offspring neurodevelopment during early life due to increased fetal metabolic requirements and neurologic vulnerabilities. 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. Tuzun F, Kumral A, Ozbal S, Dilek M, Tugyan K, Duman N, 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. Coletta JM, Bell SJ, Roman AS. 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. Socioeconomic disadvantage and neural development from infancy through early childhood. It is likely that the observed positive cognitive impacts of n-3 PUFA supplementation in aged populations occur through the same pathways as during the early stages of life. 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). (56) Aged rats fed a diet supplemented with n-3 PUFA had decreased hippocampal levels of lipid peroxide and improved learning abilities. Prenatal fish oil supplementation may be beneficial in regards to neurodevelopment. (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. 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. Makrides M, Gibson RA, McPhee AJ, Yelland L, Quinlivan J, Ryan P, et al. Federal government websites often end in .gov or .mil. On average, 23% of children failed each domain. Holman RT. However, information on prenatal vitamins suggests the majority took them every day. Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study.

All infants with birth certificates indicating conception by way of infertility treatment were recruited to participate in the study. 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. Gould JF, Makrides M, Colombo J, Smithers LG. Report of a WHO consultation. However, a consensus regarding n-3 PUFA supplementation and aforementioned benefits has not been reached. Suganuma H, Arai Y, Kitamura Y, Hayashi M, Okumura A, Shimizu T. Maternal docosahexaenoic acid-enriched diet prevents neonatal brain injury. The ASQ users guide for the Ages & Stages Questionnaire: a parent-completed, child-monitoring system. The frequencies and percentages of ASQ domain failures by supplementation group were obtained and presented for each of the seven specific stages of screening. (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. (34, 36). Buck Louis GM, Hediger ML, Bell EM, Kus CA, Sundaram R, McLain AC, et al. However, our analyses were strengthened by the notable sample size of greater than 4,800 mother-child pairs. The polyunsaturated fatty acids, EPA and DPA exert a protective effect in the hippocampus of the aged rat. (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. Koletzko B, Larqu E, Demmelmair H. Placental transfer of long-chain polyunsaturated fatty acids (LC-PUFA). 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). We were unable to detect a significant statistical interaction for supplementation during pregnancy and gender. In total, the analyses encompassed 4843 mother-child pairs with baseline characteristics displayed in Table 1. (53) The role of n-3 PUFA on cognitive function in the developing as well as the aged brain has been previously demonstrated. Evidence from clinical trials. Maternal baseline characteristics by fish oil supplementation status. Hibbeln JR, Davis JM, Steer C, Emmett P, Rogers I, Williams C, et al. (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.