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(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. (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. 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). 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. Buck Louis GM, Hediger ML, Bell EM, Kus CA, Sundaram R, McLain AC, et al. 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. Helland IB, Smith L, Saarem K, Saugstad OD, Drevon CA. A separate question queried if fish oil supplementation was taken more than one time per week during pregnancy. 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. 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. Multiple imputations were used to generate ten independent datasets when there were missing covariate values for ten or more mother-child pairs. The frequencies of domain failures by supplementation group are presented in Supplemental Table 1. Karr JE, Alexander JE, Winningham RG. Gamoh S, Hashimoto M, Hossain S, Masumura S. Chronic administration of docosahexaenoic acid improves the performance of radial arm maze task in aged rats. (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). Torres-Espinola FJ, Berglund SK, Garca-Valds LM, Segura MT, Jerez A, Campos D, et al. When examining plurality, both twin siblings were included in analyses (n= 2038) independent from the singleton children (n = 3807). Each of the ten imputed datasets were analyzed and the resultant data were then pooled to achieve complete analyses. 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. Developmental neurotoxicity of industrial chemicals. The 12 month questionnaire inquired about how many servings of fish were consumed per week during pregnancy. (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. A literature review. The site is secure. 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. 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. Neurodevelopmental outcomes of triplets or higher-order extremely low birth weight infants. J Dev Orig Health Dis. 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. (55) n-3 PUFA supplementation has been shown to improve synaptic plasticity, learning, and memory in matured rats. Kobayashi K. Role of catecholamine signaling in brain and nervous system functions: new insights from mouse molecular genetic study. (4, 51) n-3 PUFA deficiency has been related to the suppression of the biosynthesis of catecholamines, neurotransmitters that are essential for learning and memory function(52), in the offspring of rats. We also assessed the relationship among the mothers who indicated supplementing throughout both time points and ASQ fails. This study examines the associations between fish oil supplementation both before pregnancy and throughout pregnancy and subsequent child development. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Accessibility Boucher O, Burden MJ, Muckle G, Saint-Amour D, Ayotte P, Dewailly E, et al. Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments childrens IQ at 4 years of age. Similarly, a randomized clinical trial examining maternal fish oil supplementation and pregnancy outcomes failed to detect effects in twin pregnancies. (4, 5). Maternal consumption of a DHA-containing functional food benefits infant sleep patterning: an early neurodevelopmental measure. (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. (81) Our analyses examined twins in addition to singletons and independently. With regards to nutrition, taking fish oil supplementation was associated with also taking prenatal vitamins and consuming fish during pregnancy. Ikemoto A, Ohishi M, Sato Y, Hata N, Misawa Y, Fujii Y, et al. (45) Supplementation of n-3 PUFA has also been associated with heightened attention which in turn is linked with improved cognition. Effects of prenatal fish-oil and 5-methyltetrahydrofolate supplementation on cognitive development of children at 6.5 y of age. No interactions were observed at other time points. Lastly, both fish oil supplementation and child performance on the ASQ were assessed using maternal report which could potentially introduce bias. Campoy C, Escolano-Margarit MV, Ramos R, Parrilla-Roure M, Csbi G, Beyer J, et al. 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). Health information including parental body mass index (BMI), parity, and maternal smoking history was obtained from the baseline questionnaire. Methodology for establishing a population-based birth cohort focusing on couple fertility and childrens development, the Upstate KIDS Study. 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. Measuring socioeconomic status in studies of child development. 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. Compared to singletons, twins typically have a higher rate of neurodevelopmental deficits mainly due in part to factors such as low birth weight, smaller gestational age, higher maternal age and socioeconomic status. 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). Neurophysiologic and neurobehavioral evidence of beneficial effects of prenatal omega-3 fatty acid intake on memory function at school age. The elements of each questionnaire were scored as follows: yes = 10 points, sometimes = 5 points, not yet = 0 points. Weiser MJ, Butt CM, Mohajeri MH. Evidence from clinical trials. 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. Tuzun F, Kumral A, Ozbal S, Dilek M, Tugyan K, Duman N, et al. Chin-Lun Hung G, Hahn J, Alamiri B, Buka SL, Goldstein JM, Laird N, et al. The baseline questionnaire also collected information on how many days per week the mothers took prenatal vitamins. Controversial studies have warranted further prospective research to investigate the potential long-term effects of prenatal fish oil intake and child development (29)). The body of evidence supporting the beneficial fetal impacts of maternal fish oil supplementation is mounting. Wadhawan R, Oh W, Vohr BR, Wrage L, Das A, Bell EF, et al. 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. Odds ratio for risk of developmental delays by maternal fish oil supplementation status. 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 authors thank all the Upstate KIDS participants and staff for their important contributions. Yehuda S, Rabinovitz S, Mostofsky DI. Lassek WD, Gaulin SJ. On average, 23% of children failed each domain. Escolano-Margarit MV, Ramos R, Beyer J, Csbi G, Parrilla-Roure M, Cruz F, et al. 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. Maternal DHA and the development of attention in infancy and toddlerhood. To account for repeated ASQ measures of development, an infant-level random intercept was included in all models. Catena A, Muoz-Machicao JA, Torres-Espnola FJ, Martnez-Zaldvar C, Diaz-Piedra C, Gil A, et al. (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. All infants with birth certificates indicating conception by way of infertility treatment were recruited to participate in the study. government site. (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. Bobiski R, Mikulska M. The ins and outs of maternal-fetal fatty acid metabolism. (53) The role of n-3 PUFA on cognitive function in the developing as well as the aged brain has been previously demonstrated. Colombo J, Kannass KN, Shaddy DJ, Kundurthi S, Maikranz JM, Anderson CJ, et al. Gow RV, Hibbeln JR. Omega-3 fatty acid and nutrient deficits in adverse neurodevelopment and childhood behaviors. The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina. However, information on prenatal vitamins suggests the majority took them every day. 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. WHO. Mother-child pairs were excluded from this analysis if the maternal questionnaire, which captured self-reported exposure information, was not completed. Human placental transcriptome shows sexually dimorphic gene expression and responsiveness to maternal dietary n-3 long-chain polyunsaturated fatty acid intervention during pregnancy. 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. Independent of dietary intake, females typically have greater blood lipid concentrations of DHA than males. In utero exposure to omega-3 fatty acids is exclusively dependent on maternal nutrition. Sensitivity analyses included several independent models. Careers. (14) Suggested mechanisms include differences among rates of -oxidation, adipose tissue composition, and sex hormone function between the genders. Clandinin MT, Chappell JE, Leong S, Heim T, Swyer PR, Chance GW. (70, 80). Meldrum S, Dunstan JA, Foster JK, Simmer K, Prescott SL. Specifically, it is associated with a lower risk of failing the problem solving domain up to 3 years of age. Huffman SL, Harika RK, Eilander A, Osendarp SJ. (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. Ages & Stages Questionnaires [R], (ASQ-3 [TM]): A Parent-Completed Child-Monitoring System. (33) Participants were recruited from New York State livebirth registry and included mothers who gave birth between July 2008 and May 2010. 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. 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%). Released in 2009, the ASQ-3rd edition was used for screening from 18 through 36 months of age. 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. Concurrent validity of the parent-completed Ages and Stages Questionnaires, 2nd Ed. Bale TL, Baram TZ, Brown AS, Goldstein JM, Insel TR, McCarthy MM, et al. The frequencies and percentages of ASQ domain failures by supplementation group were obtained and presented for each of the seven specific stages of screening. 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. (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. Barker DJ, Clark PM. 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. (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). The hippocampus, frontal lobes, and basal ganglia of the brain, areas that are fundamental in higher-order cognition(42, 43), are all very receptive to DHA. When including both siblings in a set of twins a second random intercept was added to the models. Docosahexaenoic Acid and Cognition throughout the Lifespan. 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. The influence of long chain polyunsaturate supplementation on docosahexaenoic acid and arachidonic acid in baboon neonate central nervous system. Federal government websites often end in .gov or .mil. 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). Morse NL. Koletzko B, Larqu E, Demmelmair H. Placental transfer of long-chain polyunsaturated fatty acids (LC-PUFA). The parents engaged in different activities with their children and then responded to questions on the ASQ rating their childs skills. (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. Similar effects on problem solving were apparent in singleton, but not twin, children. (15) Preformed n-3 PUFA, directly obtained through diet, accumulates more readily than those derived from precursor acids due to enhanced bioavailability. The slow discovery of the importance of omega 3 essential fatty acids in human health. Secondary analyses were suggestive of a positive relationship between fish oil supplementation and personal-social and problem solving skills among female children only. Omega-3 polyunsaturated fatty acids and cognition throughout the lifespan: a review. Sedlmeier EM, Brunner S, Much D, Pagel P, Ulbrich SE, Meyer HH, et al. Socioeconomic disadvantage and neural development from infancy through early childhood. The longitudinal approach with multiple collected ASQ data points employed by the Upstate KIDS Study is a valuable design aspect. Maternal docosahexaenoic acid feeding protects against impairment of learning and memory and oxidative stress in prenatally stressed rats: possible role of neuronal mitochondria metabolism. (44) While the underlying mechanisms between n-3 PUFA and cognition remain unknown, several postulations exist. Cheatham CL, Colombo J, Carlson SE. Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Wilson RS, et al. Regardless of the means of conception, all multiple births were recruited. Kelly L, Grehan B, Chiesa AD, OMara SM, Downer E, Sahyoun G, et al. Maternal prenatal omega-3 fatty acid supplementation attenuates hyperoxia-induced apoptosis in the developing rat brain. (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. Suganuma H, Arai Y, Kitamura Y, Hayashi M, Okumura A, Shimizu T. Maternal docosahexaenoic acid-enriched diet prevents neonatal brain injury. (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). (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). Obesity: preventing and managing the global epidemic. Neurodevelopmental outcomes of preterm infants fed high-dose docosahexaenoic acid: a randomized controlled trial. Grandjean P, Landrigan PJ. HHS Vulnerability Disclosure, Help Additionally, nutritional data was captured on self-reported questionnaires. (10, 11) In response to increased fetal demands, maternal adipose deposits release stored fatty acids into the bloodstream at an enhanced rate during the final trimester, suggesting adequate n-3 PUFA intake is important in the time preceding conception as well as during pregnancy. (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). Randomized controlled trial of maternal omega-3 long-chain PUFA supplementation during pregnancy and early childhood development of attention, working memory, and inhibitory control. with the Bayley Scales of Infant Development II in a low-risk sample. All mothers provided written informed consent. Cowan N. Working Memory Underpins Cognitive Development, Learning, and Education. Maternal baseline characteristics by fish oil supplementation status. Both infants and the elderly are vulnerable populations with regard to many exposures. Gollenberg AL, Lynch CD, Jackson LW, McGuinness BM, Msall ME. The Furthermore, while intermittent interactions were also observed at 30 months with fine motor and overall fails, no other interactions were detected at additional time points. will also be available for a limited time. 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. Three randomized controlled trials of early long-chain polyunsaturated Fatty Acid supplementation on means-end problem solving in 9-month-olds. However, our analyses were strengthened by the notable sample size of greater than 4,800 mother-child pairs. (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. (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. Lorenz JM. 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. Yolton K, Khoury J, Xu Y, Succop P, Lanphear B, Bernert JT, et al. 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. Olsen SF, Secher NJ, Tabor A, Weber T, Walker JJ, Gluud C. Randomised clinical trials of fish oil supplementation in high risk pregnancies. Arterburn LM, Hall EB, Oken H. Distribution, interconversion, and dose response of n-3 fatty acids in humans. Although the evidence is inconsistent (29), prenatal fish oil supplementation has been associated with modest improvements in gross motor function. (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. (26, 27) Additionally, research indicates that the effects of DHA on the developing brain may be impacted by gender and genotype (21). A higher percentage of children in the no fish oil group tended to fail than the fish oil group. 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). While our study did not detect an effect on gross motor function, the ASQ may not be sensitive enough to capture these subtle variations. Stonehouse W. Does consumption of LC omega-3 PUFA enhance cognitive performance in healthy school-aged children and throughout adulthood? Dunstan JA, Simmer K, Dixon G, Prescott SL. Saccone G, Saccone I, Berghella V. Omega-3 long-chain polyunsaturated fatty acids and fish oil supplementation during pregnancy: which evidence? Prostaglandins Leukot Essent Fatty Acids. 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. Holman RT. 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. The same mothers were less likely to smoke during pregnancy when compared to those who did not consume fish oil supplements. McNamara RK, Carlson SE. Mothers were asked (yes/no) if they took fish oil (n-3 PUFA) more than once per week in the 12 months preceding pregnancy. Feng Z, Zou X, Jia H, Li X, Zhu Z, Liu X, et al. 8600 Rockville Pike (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. Luchtman DW, Song C. Cognitive enhancement by omega-3 fatty acids from child-hood to old age: findings from animal and clinical studies. The use of WHO BMI categories in place of the continuous BMI value did not have an impact on results (data not shown). The new PMC design is here! (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. In total, the analyses encompassed 4843 mother-child pairs with baseline characteristics displayed in Table 1. Hadders-Algra M. The neuromotor examination of the preschool child and its prognostic significance. Ghassabian A, Sundaram R, Bell E, Bello SC, Kus C, Yeung E. Gross Motor Milestones and Subsequent Development. 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). (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. This study aims to examine the association between maternal fish oil supplementation and subsequent child developmental capabilities up to 3 years of age. Sex differences in the relationship of dietary Fatty acids to cognitive measures in american children. (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. Schlotz W, Phillips DI. 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. Due to the potential differences in neurodevelopment, stratified analyses were conducted by gender and plurality. Early life programming and neurodevelopmental disorders. Fish Oil Trials In Pregnancy (FOTIP) Team. Clouard C, Souza AS, Gerrits WJ, Hovenier R, Lammers A, Bolhuis JE. 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. Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort 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. Fetal origins of mental health: evidence and mechanisms. Before 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. Imaging incorporation of circulating docosahexaenoic acid into the human brain using positron emission tomography. National Library of Medicine (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. No differences were observed for child gender. Maternal Obesity, Overweight and Gestational Diabetes Affect the Offspring Neurodevelopment at 6 and 18 Months of Age A Follow Up from the PREOBE Cohort. Relationship between long-chain polyunsaturated fatty acids at birth and motor function at 7 years of age. In total, 5034 mothers were recruited, including mothers of singletons, twins and higher order births. Generalized linear mixed models were used to estimate odds ratios (OR) while adjusting for covariates. (1, 2) Maternal nutrition has a substantial influence on offspring neurodevelopment during early life due to increased fetal metabolic requirements and neurologic vulnerabilities. When conducting primary analyses, one child was randomly selected from each twin pair and included with the eligible singletons (n = 4843). 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). Previous research warranted future studies including children of multiple gestations. Additionally, due to limited numbers, triplets and quadruplets were excluded (n = 128 children and n = 42 mothers). Lauritzen L, Hansen HS, Jrgensen MH, Michaelsen KF. 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. 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).