Journal of Autism and Developmental Disorders

, Volume 47, Issue 11, pp 3358–3369 | Cite as

Effect of Omega-3 and -6 Supplementation on Language in Preterm Toddlers Exhibiting Autism Spectrum Disorder Symptoms

  • Kelly W. Sheppard
  • Kelly M. Boone
  • Barbara Gracious
  • Mark A. Klebanoff
  • Lynette K. Rogers
  • Joseph Rausch
  • Christopher Bartlett
  • Daniel L. Coury
  • Sarah A. Keim
Original Paper


Delayed language development may be an early indicator of autism spectrum disorder (ASD). Early intervention is critical for children with ASD, and the present study presents pilot data on a clinical trial of omega-3 and -6 fatty acid supplementation and language development, a secondary trial outcome, in children at risk for ASD. We randomized 31 children to receive an omega-3 and -6 supplement or a placebo for 3 months, and measured their language abilities at baseline and after supplementation. Gesture use, but not word production, increased for children in the treatment group more than children in the placebo group. These results suggest possible effectiveness of omega-3 and -6 supplementation for language development in children at risk for ASD.


Children born preterm Autism spectrum disorder Language development MacArthur Bates communicative development inventory Omega-3 fatty acids Omega-6 fatty acids 



We would like to thank the families who participated in the study and Yvette Bean, Kendra Heck, Chenali Jayadeva, Julia Less, and Kamma Smith of Nationwide Children’s Hospital for data collection and administrative support.


This study was funded by The Marci and Bill Ingram Fund for Autism Spectrum Disorders Research (no grant number), Cures Within Reach (no grant number), the National Center for Advancing Translational Sciences/NIH (UL1TR001070), and internal support from the Research Institute at Nationwide Children’s Hospital.


The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. Nordic Naturals provided the investigational product, and Welsh, Holme, & Clark Co., Inc. provided canola oil at no cost. Neither the study sponsors nor product providers had a role in the study design.

Author Contributions

KWS ran the statistical analyses, interpreted the results, and drafted and revised the manuscript; KMB participated in study design, oversaw data collection, participated in analyses, and revised the manuscript; JR participated in study conception and design, oversaw statistical analyses, and revised the manuscript; SAK, BG, MAK, LKR, CB, and DLC conceived of and designed the study, had overall oversight of the project, participated in statistical analyses and interpretation of data, and revised the manuscript.

Compliance with Ethical Standards

Conflict of interest

All authors declare that they have no conflicts of interest.

Ethical Approval

All procedures performed in this study were in accordance with institutional ethical standards and with the 1964 Helsinki declaration and its later amendments.

Informed Consent

Written informed consent (parental permission for the children) was obtained from all individual participants included in this study.

Supplementary material

10803_2017_3249_MOESM1_ESM.pdf (122 kb)
Supplementary material 1 (PDF 121 KB)


  1. Ahmad, A., Moriguchi, T., & Salem, N. (2002a). Decrease in neuron size in docosahexaenoic acid-deficient brain. Pediatric Neurology, 26, 210–218.CrossRefPubMedGoogle Scholar
  2. Ahmad, A., Murthy, M., Moriguchi, T., Salem, N., & Greiner, R. S. (2002b). A decrease in cell size accompanies a loss of docosahexaenoate in the rat hippocampus. Nutritional Neuroscience, 5, 103–113. doi: 10.1080/10284150290018973.CrossRefPubMedGoogle Scholar
  3. Aid, S., Vancassel, S., Poumes-Ballihaut, C., Chalon, S., Guesnet, P., & Lavialle, M. (2003). Effect of a diet-induced n-3 PUFA depletion on cholinergic parameters in the rat hippocampus. Journal of Lipid Research, 44, 1545–1551. doi: 10.1194/jlr.M300079-JLR200.CrossRefPubMedGoogle Scholar
  4. Pan, B.A., Rowe, M. L., Spier, E., & Tamis-Lemonda, C. (2004). Measuring productive vocabulary of toddlers in low-income families: Concurrent and predictive validity of three sources of data. Journal of Child Language, 31, 587–608. doi: 10.1017/s0305000904006270.CrossRefPubMedGoogle Scholar
  5. Amminger, G. P., Berger, G. E., Schafer, M. R., Klier, C., Friedrich, M. H., & Feucht, M. (2007). Omega-3 fatty acids supplementation in children with autism: A double-blind randomized, placebo-controlled pilot study. Biological Psychiatry, 61, 551–553. doi: 10.1016/j.biopsych.2006.05.007.CrossRefPubMedGoogle Scholar
  6. Arriaga, R. I., Fenson, L., Cronan, T., Pethick, S. J. (2008). Scores on the MacArthur Communicative Development Inventory of children from lowand middle-income families. Applied Psycholinguistics, 19, 209 doi: 10.1017/s0142716400010043.CrossRefGoogle Scholar
  7. Auestad, N., et al. (2001). Growth and development in term infants fed long-chain polyunsaturated fatty acids: A double-masked, randomized, parallel, prospective, multivariate study. Pediatrics, 108, 372–381. doi: 10.1542/peds.108.2.372.CrossRefPubMedGoogle Scholar
  8. Barden, A. E., Mas, E., & Mori, T. A. (2016). n-3 Fatty acid supplementation and proresolving mediators of inflammation. Current Opinion in Lipidology, 27, 26–32. doi: 10.1097/MOL.0000000000000262.CrossRefPubMedGoogle Scholar
  9. Bent, S., et al. (2014). Internet-based, randomized, controlled trial of omega-3 fatty acids for hyperactivity in autism. Journal of the American Academy of Child and Adolescent Psychiatry, 53, 658–666. doi: 10.1016/j.jaac.2014.01.018.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Bliss, T.V.P., & Collingridge, G. L. (1993). A synaptic model of memory: Long-term potentiation in the hippocampus. Nature, 361, 31–39.CrossRefPubMedGoogle Scholar
  11. Bourre, J. M., et al. (1989). The effects of dietary alpha-linolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons and performance of learning tasks in rats. Journal of Nutrition, 119, 1880–1892.PubMedGoogle Scholar
  12. Bourre, J.M., et al. (1993). Function of dietary polyunsaturated fatty acids in nervous system. Prostaglandins, Leukotrienes and Essential Fatty Acids, 48, 5–15.CrossRefGoogle Scholar
  13. Bowen, K. J., Harris, W. S., & Kris-Etherton, P. M. (2016). Omega-3 fatty acids and cardiovascular disease: Are there benefits? Current Treatment Options in Cardiovascular Medicine, 18, 69. doi: 10.1007/s11936-016-0487-1.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Breckenridge, W. C., Morgan, I. G., Zanetta, J. P., & Vincendon, G. (1973). Adult rat brain synaptic vesicles II. Lipid composition. Biochimica et Biophysica Acta, 320, 681–686.CrossRefPubMedGoogle Scholar
  15. Bruckner, C., Yoder, P., Stone, W., & Saylor, M. (2007). Construct validity of the MCDI-I receptive vocabulary scale can be improved: Differential item functioning between toddlers with autism spectrum disorders and typically-developing infants. Journal of Speech Language and Hearing Research, 50, 1631–1638.CrossRefGoogle Scholar
  16. Catalan, J., Moriguchi, T., Slotnick, B., Murthy, M., Greiner, R. S., & Salem, N. (2002). Cognitive deficits in docosahexaenoic acid-deficient rats. Behavioral Neuroscience, 116, 1022–1031. doi: 10.1037/0735-7044.116.6.1022.CrossRefPubMedGoogle Scholar
  17. Cattani, A., Bonifacio, S., Fertz, M., Iverson, J. M., Zocconi, E., & Caselli, M. C. (2010). Communicative and linguistic development in preterm children: a longitudinal study from 12 to 24 months. International Journal of Language & Communication Disorders, 45, 162–173. doi: 10.3109/13682820902818870.CrossRefGoogle Scholar
  18. Chalon, S., et al. (1998). Dietary fish oil affects monoaminergic neurotransmission and behavior in rats. Journal of Nutrition, 128, 2512–2519.PubMedGoogle Scholar
  19. Clandinin, M. T., et al. (2005). Growth and development of preterm infants fed infant formulas containing docosahexaenoic acid and arachidonic acid. The Journal of pediatrics, 146, 461–468. doi: 10.1016/j.jpeds.2004.11.030.CrossRefPubMedGoogle Scholar
  20. Clandinin, M. T., Cheema, S., Field, J., Garg, M. L., Venkatraman, J., & Clandinin, T. R. (1991). Dietary fat: Exogenous determination of membrane structure and cell function. FASEB Journal, 5, 2761–2769.PubMedGoogle Scholar
  21. Coderre, E. L., Chernenok, M., Gordon, B., & Ledoux, K. (2017). Linguistic and non-linguistic semantic processing in individuals with autism spectrum disorders: An ERP study. Journal of Autism and Developmental Disorders. doi: 10.1007/s10803-016-2985-0.PubMedGoogle Scholar
  22. Dale, P. S. (1991). The validity of a parent report measure of vocabulary and syntax at 24 months. Journal of Speech and Hearing Research, 34, 565–571.CrossRefPubMedGoogle Scholar
  23. Delion, S., Chalon, S., Herault, J., Guilloteau, D., Besnard, J.-C., & Durand, G. (1994). Chronic dietary alpha-linolenic acid deficiency alters dopaminergic and serotoninergic neurotransmission in rats. Journal of Nutrition, 124, 2466–2476.PubMedGoogle Scholar
  24. du Bois, T. M., Deng, C., Bell, W., & Huang, X. F. (2006). Fatty acids differentially affect serotonin receptor and transporter binding in the rat brain. Neuroscience, 139, 1397–1403. doi: 10.1016/j.neuroscience.2006.02.068.CrossRefPubMedGoogle Scholar
  25. Dyall, S. C., & Michael-Titus, A. T. (2008). Neurological benefits of omega-3 fatty acids. Neuromolecular Medicine, 10, 219–235. doi: 10.1007/s12017-008-8036-z.CrossRefPubMedGoogle Scholar
  26. Fang, Y. J., Zhou, M. H., Gao, X. F., Gu, H., & Mei, Y. A. (2011). Arachidonic acid modulates Na+ currents by non-metabolic and metabolic pathways in rat cerebellar granule cells. The Biochemical Journal, 438, 203–215. doi: 10.1042/BJ20110569.CrossRefPubMedGoogle Scholar
  27. Farvid, M. S., et al. (2014). Dietary linoleic acid and risk of coronary heart disease: A systematic review and meta-analysis of prospective cohort studies. Circulation, 130, 1568–1578. doi: 10.1161/CIRCULATIONAHA.114.010236.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Fenson, L., Pethick, S. J., Renda, C., Cox, J. L. (2000). Short-form versions of the MacArthur communicative development inventories. Applied Psycholinguistics, 21, 95–116.CrossRefGoogle Scholar
  29. Fewtrell, M. S., et al. (2004). Randomized, double-blind trial of long-chain polyunsaturated fatty acid supplementation with fish oil and borage oil in preterm infants. The Journal of Pediatrics, 144, 471–479. doi: 10.1016/j.jpeds.2004.01.034.CrossRefPubMedGoogle Scholar
  30. Foster-Cohen, S., Edgin, J. O., Champion, P. R., & Woodward, L. J. (2007). Early delayed language development in very preterm infants: Evidence from the MacArthur-Bates CDI. Journal of Child Language, 34, 655. doi: 10.1017/s0305000907008070.CrossRefPubMedGoogle Scholar
  31. Frank, M. C., Braginsky, M., Yurovsky, D., Marchman, V.A. (2016). Wordbank: An open repository for developmental vocabulary data. Journal of Child Language, 1–18. doi: 10.1017/S0305000916000209.
  32. Garton, A. F. (1985). The production of this and that by young children. First Language, 6, 29–39.CrossRefGoogle Scholar
  33. Gibson, R. A., Neumann, M. A., Lien, E. L., Boyd, K. A., & Tu, W. C. (2013). Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids. Prostaglandins Leukotrienes and Essential Fatty Acids, 88, 139–146. doi: 10.1016/j.plefa.2012.04.003.CrossRefGoogle Scholar
  34. Gordon, R. G., & Watson, L. R. (2015). Brief report: Gestures in children at risk for autism spectrum disorders. Journal of Autism and Developmental Disorders, 45, 2267–2273. doi: 10.1007/s10803-015-2390-0.CrossRefPubMedGoogle Scholar
  35. Groen, W. B., Zwiers, M. P., van der Gaag, R. J., & Buitelaar, J. K. (2008). The phenotype and neural correlates of language in autism: An integrative review. Neuroscience and Biobehavioral Reviews, 32, 1416–1425. doi: 10.1016/j.neubiorev.2008.05.008.CrossRefPubMedGoogle Scholar
  36. Harnack, K., Andersen, G., & Somoza, V. (2009). Quantitation of alpha-linolenic acid elongation to eicosapentaenoic and docosahexaenoic acid as affected by the ratio of n6/n3 fatty acids. Nutrition Metabolism, 6, 8. doi: 10.1186/1743-7075-6-8.CrossRefPubMedPubMedCentralGoogle Scholar
  37. Harris, W. S. (2006). The omega-6/omega-3 ratio and cardiovascular disease risk: Uses and abuses. Current Atherosclerosis Reports, 8, 453–459.CrossRefPubMedGoogle Scholar
  38. Henriksen, C., et al. (2008). Improved cognitive development among preterm infants attributable to early supplementation of human milk with docosahexaenoic acid and arachidonic acid. Pediatrics, 121, 1137–1145. doi: 10.1542/peds.2007-1511.CrossRefPubMedGoogle Scholar
  39. Ikemoto, A., Kobayashi, T., Watanabe, S., & Okuyama, H. (1997). Membrane fatty acid modifications of PC12 cells by arachidonate or docosahexaenoate affect neurite outgrowth but not norepinephrine release. Neurochemical Research, 22, 671–678.CrossRefPubMedGoogle Scholar
  40. Innis, S. M. (2014). Omega-3 fatty acid biochemistry: Perspectives from human nutrition. Military Medicine, 179, 82–87. doi: 10.7205/MILMED-D-14-00147.CrossRefPubMedGoogle Scholar
  41. Johnson, M., Fransson, G., Ostlund, S., Areskoug, B., & Gillberg, C. (2016). Omega 3/6 fatty acids for reading in children: A randomized, double-blind, placebo-controlled trial in 9-year-old mainstream schoolchildren in Sweden. Journal of Child Psychology and Psychiatry and Allied Disciplines. doi: 10.1111/jcpp.12614.Google Scholar
  42. Johnson, S., Hollis, C., Kochhar, P., Hennessey, E., Wolke, D., & Marlow, N. (2010). Autism spectrum disorders in extremely preterm children. Journal of Pediatrics, 156, 525–531.CrossRefPubMedGoogle Scholar
  43. Jucaite, A., Fernell, E., Halldin, C., Forssberg, H., & Farde, L. (2005). Reduced midbrain dopamine transporter binding in male adolescents with attention-deficit/hyperactivity disorder: Association between striatal dopamine markers and motor hyperactivity. Biological Psychiatry, 57, 229–238. doi: 10.1016/j.biopsych.2004.11.009.CrossRefPubMedGoogle Scholar
  44. Jumpsen, J., Lien, E. L., Goh, Y. K., & Clandinin, M. T. (1997a). During neuronal and glial cell development diet n-6 to n-3 fatty acid ratio alters the fatty acid composition of phosphatidylinositol and phosphatidylserine. Biochimica et Biophysica Acta, 1347, 40–50.CrossRefPubMedGoogle Scholar
  45. Jumpsen, J., Lien, E. L., Goh, Y. K., & Clandinin, M. T. (1997b). Small changes of dietary (n-6) and (n-3)/fatty acid content ratio alter phosphatidylethanolamine and phosphatidylcholine fatty acid composition during development of neuronal and glial cells in rats. Journal of Nutrition, 127, 724–731.PubMedGoogle Scholar
  46. Kato, K., Uruno, K., Saito, K., & Kato, H. (1991). Both arachidonic acid and 1-oleoyl-2-acetyl glycerol in low magnesium solution induce long-term potentiation in hippocampal CA1 neurons in vitro. Brain Research, 563, 94–100.CrossRefPubMedGoogle Scholar
  47. Keim, S. A., et al. (under review). Omega-3 and -6 fatty acid supplementation may benefit autism symptoms based on parent report in preterm toddlers. The Journal of Nutrition.Google Scholar
  48. Koletzko, B., et al. (2008). The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: Review of current knowledge and consensus recommendations. Journal of Perinatal Medicine, 36, 5–14. doi: 10.1515/JPM.2008.001.PubMedGoogle Scholar
  49. Kris-Etherton, P., Fleming, J., & Harris, W. S. (2010). The debate about n-6 polyunsaturated fatty acid recommendations for cardiovascular health. Journal of the American Dietetic Association, 110, 201–204. doi: 10.1016/j.jada.2009.12.006.CrossRefPubMedGoogle Scholar
  50. Kuzniewicz, M. W., Wi, S., Qian, Y., Walsh, E. M., Armstrong, M. A., & Croen, L. A. (2014). Prevalence and neonatal factors associated with autism spectrum disorders in preterm infants. The Journal of Pediatrics, 164, 20–25. doi: 10.1016/j.jpeds.2013.09.021.CrossRefPubMedGoogle Scholar
  51. Lapillonne, A., & Moltu, S. J. (2016). Long-chain polyunsaturated fatty acids and clinical outcomes of preterm infants. Annals of Nutrition and Metabolism, 69(Suppl 1), 35–44. doi: 10.1159/000448265.PubMedGoogle Scholar
  52. Lauritzen, L., Jorgensen, M. H., Olsen, S. F., Straarup, E. M., & Michaelsen, K. F. (2005). Maternal fish oil supplementation in lactation: Effect on developmental outcome in breast-fed infants. Reproduction Nutrition Development, 45, 535–547. doi: 10.1051/rnd:2005044.CrossRefGoogle Scholar
  53. LeBarton, E. S., Goldin-Meadow, S., & Raudenbush, S. (2015). Experimentally-induced Increases in Early gesture lead to increases in spoken vocabulary. Journal of Cognition and Development, 16, 199–220. doi: 10.1080/15248372.2013.858041.CrossRefPubMedGoogle Scholar
  54. LeBarton, E. S., & Iverson, J. M. (2016). Gesture development in toddlers with an older sibling with autism. International Journal of Language & Communication Disorders, 51, 18–30. doi: 10.1111/1460-6984.12180.CrossRefGoogle Scholar
  55. Lee, J.M., Lee, H., Kang, S., Park, W. J. (2016). Fatty acid desaturases, polyunsaturated fatty acid regulation, and biotechnological advances. Nutrients, 8, 23. doi: 10.3390/nu8010023.CrossRefPubMedCentralGoogle Scholar
  56. Lynch, M. A., & Voss, K. L. (1994). Membrane arachidonic acid concentration correlates with age and induction of long-term potentiation in the dentate gyrus in the rat. European Journal of Neuroscience, 6, 1008–1014.CrossRefPubMedGoogle Scholar
  57. Mankad, D., et al. (2015). A randomized, placebo controlled trial of omega-3 fatty acids in the treatment of young children with autism. Molecular Autism, 6, 18. doi: 10.1186/s13229-015-0010-7.CrossRefPubMedPubMedCentralGoogle Scholar
  58. Martinez, M. (1992). Tissue levels of polyunsaturated fatty acids during early human development. Journal of Pediatrics, 120, S129–S138.CrossRefPubMedGoogle Scholar
  59. Martinez, M., & Mougan, I. (1998). Fatty acid composition of human brain phospholipids during normal development. Journal of Neurochemistry, 71, 2528–2533.CrossRefPubMedGoogle Scholar
  60. McNamara, R. K., et al. (2007). Selective deficits in the omega-3 fatty acid docosahexaenoic acid in the postmortem orbitofrontal cortex of patients with major depressive disorder. Biological Psychiatry, 62, 17–24. doi: 10.1016/j.biopsych.2006.08.026.CrossRefPubMedGoogle Scholar
  61. McNamara, R. K. (2010). DHA deficiency and prefrontal cortex neuropathology in recurrent affective disorders. The Journal of Nutrition, 140, 864–868. doi: 10.3945/jn.109.113233.CrossRefPubMedPubMedCentralGoogle Scholar
  62. McNamara, R. K., Jandacek, R., Rider, T., Tso, P., Dwivedi, Y., & Pandey, G. N. (2010). Selective deficits in erythrocyte docosahexaenoic acid composition in adult patients with bipolar disorder and major depressive disorder. Journal of Affective Disorders, 126, 303–311. doi: 10.1016/j.jad.2010.03.015.CrossRefPubMedPubMedCentralGoogle Scholar
  63. McNamara, R. K., & Liu, Y. (2011). Reduced expression of fatty acid biosynthesis genes in the prefrontal cortex of patients with major depressive disorder. Journal of Affective Disorders, 129, 359–363. doi: 10.1016/j.jad.2010.08.021.CrossRefPubMedGoogle Scholar
  64. Meldrum, S. J., D’Vaz, N., Simmer, K., Dunstan, J. A., Hird, K., & Prescott, S. L. (2012). Effects of high-dose fish oil supplementation during early infancy on neurodevelopment and language: A randomised controlled trial. The British Journal of Nutrition, 108, 1443–1454. doi: 10.1017/S0007114511006878.CrossRefPubMedGoogle Scholar
  65. Mody, M., et al. (2017). Communication deficits and the motor system: exploring patterns of associations in autism spectrum disorder (ASD). Journal of Autism and Developmental Disorders, 47, 155–162. doi: 10.1007/s10803-016-2934-y.CrossRefPubMedGoogle Scholar
  66. Moriguchi, T., Greiner, R. S., & Salem, N. (2000). Behavioral deficits associated with dietary induction of decreased brain docosahexaenoic acid concentration. Journal of Neurochemistry, 75, 2563–2573.CrossRefPubMedGoogle Scholar
  67. Mundy, P., Sigman, M., Ungerer, J., & Sherman, T. (1987). Nonverbal communnication and play correlates of language development in autistic children. Journal of Autism and Developmental Disorders, 17, 349–364.CrossRefPubMedGoogle Scholar
  68. Nakamura, M. T., & Nara, T. Y. (2004). Structure, function, and dietary regulation of delta6, delta5, and delta9 desaturases. Annual Review of Nutrition, 24, 345–376. doi: 10.1146/annurev.nutr.24.121803.063211.CrossRefPubMedGoogle Scholar
  69. Ozcaliskan, S., Adamson, L. B., & Dimitrova, N. (2016). Early deictic but not other gestures predict later vocabulary in both typical development and autism. Autism, 20, 754–763. doi: 10.1177/1362361315605921.CrossRefPubMedGoogle Scholar
  70. Parlade, M. V., & Iverson, J. M. (2015). The development of coordinated communication in infants at heightened risk for autism spectrum disorder. Journal of Autism and Developmental Disorders, 45, 2218–2234. doi: 10.1007/s10803-015-2391-z.CrossRefPubMedPubMedCentralGoogle Scholar
  71. Parletta, N., Niyonsenga, T., Duff, J. (2016). Omega-3 and omega-6 polyunsaturated fatty acid levels and correlations with symptoms in children with attention deficit hyperactivity disorder, autistic spectrum disorder and typically developing controls. PLoS ONE. doi: 10.4226/78/572fdf0edfb74.PubMedPubMedCentralGoogle Scholar
  72. Patrick, R. P., & Ames, B. N. (2015). Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: Relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior. The FASEB Journal, 29, 2207–2222. doi: 10.1096/fj.14-268342.CrossRefPubMedGoogle Scholar
  73. Pritchard, M. A., et al. (2016). Autism in toddlers born very preterm. Pediatrics, 137, e20151949. doi: 10.1542/peds.2015-1949.CrossRefPubMedGoogle Scholar
  74. Rescorla, L. (1991). Identifying expressive language delay at two. Topics in Language Disorders, 11, 14–20.CrossRefGoogle Scholar
  75. Richardson, A. J., & Montgomery, P. (2005). The Oxford-Durham study: A randomized, controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder. Pediatrics, 115, 1360–1366. doi: 10.1542/peds.2004-2164.CrossRefPubMedGoogle Scholar
  76. Ring, E.D., Fenson, L. (2000). The correspondence between parent report and child performance for receptive and expressive vocabulary beyond infancy. First Language, 20, 141–159.CrossRefGoogle Scholar
  77. Sansavini, A., et al. (2011). Longitudinal trajectories of gestural and linguistic abilities in very preterm infants in the second year of life. Neuropsychologia, 49, 3677–3688. doi: 10.1016/j.neuropsychologia.2011.09.023.CrossRefPubMedGoogle Scholar
  78. Schaechter, J. D., & Benowitz, L. I. (1993). Activation of protein kinase C by arachidonic acid selectively enhances the phosphorylation of GAP-43 in nerve terminal membranes. The Journal of Neuroscience, 13, 4361–4371.PubMedGoogle Scholar
  79. Schneider, M. R., DelBello, M. P., McNamara, R. K., Strakowski, S. M., & Adler, C. M. (2012). Neuroprogression in bipolar disorder. Bipolar Disorders, 14, 356–374. doi: 10.1111/j.1399-5618.2012.01024.x.CrossRefPubMedGoogle Scholar
  80. Scott, D. T., Janowsky, J. S., Carroll, R. E., Taylor, J. A., Auestad, N., & Montalto, M. B. (1998). Formula supplementation with long-chain polyunsaturated fatty acids: Are there developmental benefits? Pediatrics, 102, e59–e59. doi: 10.1542/peds.102.5.e59.CrossRefPubMedGoogle Scholar
  81. Serhan, C. N., & Savill, J. (2005). Resolution of inflammation: The beginning programs the end. Nature Immunology, 6, 1191–1197. doi: 10.1038/ni1276.CrossRefPubMedGoogle Scholar
  82. Sheppard, K. W., & Cheatham, C. L. (2017). Executive functions and the omega-6-to-omega-3 fatty acid ratio: A cross-sectional study. The American Journal of Clinical Nutrition, 105, 32–41. doi: 10.3945/ajcn.116.141390.CrossRefPubMedGoogle Scholar
  83. Simmer, K., Schulzke, S., Patole, S. K. (2008). Longchain polyunsaturated fatty acid supplementation in preterm infants (Review). The Cochrane Library, 1, 1–57.Google Scholar
  84. Spencer, T. J., et al. (2007). Further evidence of dopamine transporter dysregulation in ADHD: A controlled PET imaging study using altropane. Biological Psychiatry, 62, 1059–1061. doi: 10.1016/j.biopsych.2006.12.008.CrossRefPubMedPubMedCentralGoogle Scholar
  85. Spittle, A. J., et al. (2017). Neurobehaviour at term-equivalent age and neurodevelopmental outcomes at 2 years in infants born moderate-to-late preterm. Developmental Medicine and Child Neurology, 59, 207–215. doi: 10.1111/dmcn.13297.CrossRefPubMedGoogle Scholar
  86. Verhaeghe, L., Dereu, M., Warreyn, P., De Groote, I., Vanhaesebrouck, P., & Roeyers, H. (2016). Extremely preterm born children at very high risk for developing autism spectrum disorder. Child Psychiatry and Human Development, 47, 729–739. doi: 10.1007/s10578-015-0606-3.CrossRefPubMedGoogle Scholar
  87. Voigt, R. G., et al. (2014). Dietary docosahexaenoic acid supplementation in children with autism. Journal of Pediatric Gastroenterology and Nutrition, 58, 715–722. doi: 10.1097/MPG.0000000000000260.PubMedGoogle Scholar
  88. Wainwright, P. E., Jalali, E., Mutsaers, M., Bell, R., & Cvitkovic, S. (1999). An imbalance of dietary essential fatty acids retards behavioral development in mice. Physiology and Behavior, 66, 833–839.CrossRefPubMedGoogle Scholar
  89. Wainwright, P. E., Xing, H.-C., Mutsaers, L., McCutcheon, D., & Kyle, D. (1997). Arachidonic acid offsests the effects of mouse brain and behavior of a diet with low (n−6):(n−3) ratio and very high levels of docosahexaenoic acid. Journal of Nutrition, 127, 184–193.PubMedGoogle Scholar
  90. Weiser, M. J., Wynalda, K., Salem, N. Jr., Butt, C. M. (2015). Dietary DHA during development affects depression-like behaviors and biomarkers that emerge after puberty in adolescent rats. Journal of Lipid Research, 56, 151–166. doi: 10.1194/jlr.M055558.CrossRefPubMedPubMedCentralGoogle Scholar
  91. Willatts, P., Forsyth, J. S. (2000). The role of long-chain polyunsaturated fatty acids in infant cognitive development. Prostaglandins Leukotrienes and Essential Fatty Acids, 63, 95–100.CrossRefGoogle Scholar
  92. Willett, W., et al. (1985). Reproducibility and validity of a semiquantitative food frequency questionnaire. American Journal of Epidemiology, 122, 51–65.CrossRefPubMedGoogle Scholar
  93. Winkens, B., van Breukelen, G. J., Schouten, H. J., & Berger, M. P. (2007). Randomized clinical trials with a pre- and a post-treatment measurement: Repeated measures versus ANCOVA models. Contemporary Clinical Trials, 28, 713–719. doi: 10.1016/j.cct.2007.04.002.CrossRefPubMedGoogle Scholar
  94. Zimmer, L., Delpal, S., Guilloteau, D., Aioun, J., Durand, G., & Chalon, S. (2000). Chronic n-3 polyunsaturated fatty acid deficiency alters dopamine vesicle density in the rat frontal cortex. Neuroscience Letters, 284, 25–28.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Kelly W. Sheppard
    • 1
    • 6
  • Kelly M. Boone
    • 1
  • Barbara Gracious
    • 2
    • 7
  • Mark A. Klebanoff
    • 3
    • 6
  • Lynette K. Rogers
    • 3
    • 6
  • Joseph Rausch
    • 1
  • Christopher Bartlett
    • 4
    • 6
  • Daniel L. Coury
    • 1
    • 5
  • Sarah A. Keim
    • 1
    • 6
  1. 1.Center for Biobehavioral HealthThe Research Institute at Nationwide Children’s HospitalColumbusUSA
  2. 2.Center for Innovation in Pediatric PracticeThe Research Institute at Nationwide Children’s HospitalColumbusUSA
  3. 3.Center for Perinatal ResearchThe Research Institute at Nationwide Children’s HospitalColumbusUSA
  4. 4.Battelle Center for Mathematical MedicineThe Research Institute at Nationwide Children’s HospitalColumbusUSA
  5. 5.Nationwide Children’s HospitalColumbusUSA
  6. 6.Department of Pediatrics, College of MedicineThe Ohio State UniversityColumbusUSA
  7. 7.Department of Psychiatry and Behavioral Health, College of MedicineThe Ohio State UniversityColumbusUSA

Personalised recommendations