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Fetal DHA inadequacy and the impact on child neurodevelopment: a follow-up of a randomised trial of maternal DHA supplementation in pregnancy

  • Kelly A. Mulder (a1), Rajavel Elango (a1) (a2) and Sheila M. Innis (a1)

DHA is an important component of neural lipids accumulating in neural tissue during development. Inadequate DHA in gestation may compromise infant development, but it is unknown whether there are lasting effects. We sought to determine whether the observed effects of fetal DHA inadequacy on infant development persist into early childhood. This follow-up study assessed children (5–6 years) whose mothers received 400 mg/d DHA or a placebo during pregnancy. Child neurodevelopment was assessed with several age-appropriate tests including the Kaufman Assessment Battery for Children. A risk-reduction model was used whereby the odds that a child from the maternal placebo group would fail to achieve a test score in the top quartile was calculated. The association of maternal DHA intake and status in gestation with child test scores, as well as with child DHA intake and status, was also determined. No differences were detected in children (n 98) from the maternal placebo and DHA groups achieving a high neurodevelopment test score (P>0·05). However, maternal DHA status was positively related to child performance on some tests including language and short-term memory. Furthermore, child DHA intake and status were related to the mother’s intake and status in gestation. The neurodevelopment effects of fetal DHA inadequacy may have been lost or masked by other variables in the children. Although we provide evidence that maternal DHA status is related to child cognitive performance, the association of maternal and child DHA intake and status limits the interpretation of whether DHA before or after birth is important.

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* Corresponding author: R. Elango, email
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1. Lamptey MS & Walker BL (1976) A possible essential role for dietary linolenic acid in the development of the young rat. J Nutr 106, 8693.
2. Farquharson J, Jamieson EC, Abbasi KA, et al. (1995) Effect of diet on the fatty acid composition of the major phospholipids of infant cerebral cortex. Arch Dis Child 72, 198203.
3. Neuringer M, Connor WE, Van Petten C, et al. (1984) Dietary omega-3 fatty acid deficiency and visual loss in infant rhesus monkeys. J Clin Invest 73, 272276.
4. Reisbick S, Neuringer M, Gohl E, et al. (1997) Visual attention in infant monkeys: effects of dietary fatty acids and age. Dev Psychol 33, 387395.
5. Judge MP, Harel O & Lammi-Keefe CJ (2007) A docosahexaenoic acid-functional food during pregnancy benefits infant visual acuity at four but not six months of age. Lipids 42, 117122.
6. Helland IB, Smith L, Saarem K, et al. (2003) Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children’s IQ at 4 years of age. Pediatrics 111, e39e44.
7. Dunstan JA, Simmer K, Dixon G, et al. (2008) Cognitive assessment of children at age 2(1/2) years after maternal fish oil supplementation in pregnancy: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 93, 4550.
8. Helland IB, Saugstad OD, Smith L, et al. (2001) Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women. Pediatrics 108, E82.
9. Makrides M, Gibson RA, McPhee AJ, et al. (2010) Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial. JAMA 304, 16751683.
10. Smithers LG, Gibson RA & Makrides M (2011) Maternal supplementation with docosahexaenoic acid during pregnancy does not affect early visual development in the infant: a randomized controlled trial. Am J Clin Nutr 93, 12931299.
11. Gould JF, Treyvaud K, Yelland LN, et al. (2017) Seven-year follow-up of children born to women in a randomized trial of prenatal DHA supplementation. JAMA 317, 11731175.
12. Makrides M, Gould JF, Gawlik NR, et al. (2014) Four-year follow-up of children born to women in a randomized trial of prenatal DHA supplementation. JAMA 311, 18021804.
13. Agostoni C, Trojan S, Bellu R, et al. (1995) Neurodevelopmental quotient of healthy term infants at 4 months and feeding practice: the role of long-chain polyunsaturated fatty acids. Pediatr Res 38, 262266.
14. Birch EE, Garfield S, Castaneda Y, et al. (2007) Visual acuity and cognitive outcomes at 4 years of age in a double-blind, randomized trial of long-chain polyunsaturated fatty acid-supplemented infant formula. Early Hum Dev 83, 279284.
15. Hoffman DR, Birch EE, Castaneda YS, et al. (2003) Visual function in breast-fed term infants weaned to formula with or without long-chain polyunsaturates at 4 to 6 months: a randomized clinical trial. J Pediatr 142, 669677.
16. Colombo J, Carlson SE, Cheatham CL, et al. (2011) Long-chain polyunsaturated fatty acid supplementation in infancy reduces heart rate and positively affects distribution of attention. Pediatr Res 70, 406410.
17. Drover JR, Hoffman DR, Castaneda YS, et al. (2011) Cognitive function in 18-month-old term infants of the DIAMOND study: a randomized, controlled clinical trial with multiple dietary levels of docosahexaenoic acid. Early Hum Dev 87, 223230.
18. Carlson SE, Werkman SH, Rhodes PG, et al. (1993) Visual-acuity development in healthy preterm infants: effect of marine-oil supplementation. Am J Clin Nutr 58, 3542.
19. Osterhues A, Ali NS & Michels KB (2013) The role of folic acid fortification in neural tube defects: a review. Crit Rev Food Sci Nutr 53, 11801190.
20. Cao XY, Jiang XM, Dou ZH, et al. (1994) Timing of vulnerability of the brain to iodine deficiency in endemic cretinism. N Engl J Med 331, 17391744.
21. Innis SM (2003) Perinatal biochemistry and physiology of long-chain polyunsaturated fatty acids. J Pediatr 143, S1S8.
22. Martinez M (1992) Tissue levels of polyunsaturated fatty acids during early human development. J Pediatr 120, S129S138.
23. Coti Bertrand P, O’Kusky JR & Innis SM (2006) Maternal dietary (n-3) fatty acid deficiency alters neurogenesis in the embryonic rat brain. J Nutr 136, 15701575.
24. Chalon S (2006) Omega-3 fatty acids and monoamine neurotransmission. Prostaglandins Leukot Essent Fatty Acids 75, 259269.
25. Dekaban AS (1978) Changes in brain weights during the span of human life: relation of brain weights to body heights and body weights. Ann Neurol 4, 345356.
26. Levitt P (2003) Structural and functional maturation of the developing primate brain. J Pediatr 143, S35S45.
27. Dalton A, Wolmarans P, Witthuhn RC, et al. (2009) A randomised control trial in schoolchildren showed improvement in cognitive function after consuming a bread spread, containing fish flour from a marine source. Prostaglandins Leukot Essent Fatty Acids 80, 143149.
28. Ryan AS & Nelson EB (2008) Assessing the effect of docosahexaenoic acid on cognitive functions in healthy, preschool children: a randomized, placebo-controlled, double-blind study. Clin Pediatr 47, 355362.
29. Sinn N, Cooper P & O’Dea K (2011) Fish oil supplementation, learning and behaviour in Indigenous Australian children from a remote community school: a pilot feasibility study. Aust N Z J Public Health 35, 493494.
30. Richardson AJ, Burton JR, Sewell RP, et al. (2012) Docosahexaenoic acid for reading, cognition and behavior in children aged 7-9 years: a randomized, controlled trial (the DOLAB Study). PLOS ONE 7, e43909.
31. Kirby A, Woodward A, Jackson S, et al. (2010) A double-blind, placebo-controlled study investigating the effects of omega-3 supplementation in children aged 8-10 years from a mainstream school population. Res Dev Disabil 31, 718730.
32. Baym CL, Khan NA, Monti JM, et al. (2014) Dietary lipids are differentially associated with hippocampal-dependent relational memory in prepubescent children. Am J Clin Nutr 99, 10261032.
33. McNamara RK, Able J, Jandacek R, et al. (2010) Docosahexaenoic acid supplementation increases prefrontal cortex activation during sustained attention in healthy boys: a placebo-controlled, dose-ranging, functional magnetic resonance imaging study. Am J Clin Nutr 91, 10601067.
34. Mulder KA, King DJ & Innis SM (2014) Omega-3 fatty acid deficiency in infants before birth identified using a randomized trial of maternal DHA supplementation in pregnancy. PLOS ONE 9, e83764.
35. Brown L (1997) Test of Nonverbal Intelligence, vol. 3. Austin TX: Pro Ed.
36. Liou YA, King DJ, Zibrik D, et al. (2007) Decreasing linoleic acid with constant alpha-linolenic acid in dietary fats increases (n-3) eicosapentaenoic acid in plasma phospholipids in healthy men. J Nutr 137, 945952.
37. Kaufman AS & Kaufman NL (2004) Kaufman Assessment Battery for Children, vol. 2. San Antonio, TX: Pearson Education.
38. Dunn LM & Dunn DM (2007) Peabody Picture Vocabulary Test, vol. 4. San Antonio, TX: Pearson Education.
39. Beery KE, Buktenica NA & Beery NA (2004) The Beery-Buktenica Developmental Test of Visual Motor Integration (VMI), vol. 5. Minneapolis, MN: NCS Pearson Inc.
40. Leark RA GL, Kindschi CL, Dupuy TR, et al. (2007) Test of Variables of Attention. Los Alamitos, CA: The TOVA Company.
41. Brion MJ, Ness AR, Rogers I, et al. (2010) Maternal macronutrient and energy intakes in pregnancy and offspring intake at 10 y: exploring parental comparisons and prenatal effects. Am J Clin Nutr 91, 748756.
42. Oliveria SA, Ellison RC, Moore LL, et al. (1992) Parent-child relationships in nutrient intake: the Framingham Children’s Study. Am J Clin Nutr 56, 593598.
43. Deroma L, Valent F, Parpinel M, et al. (2013) Comparison of seafood consumption in a group of Italian mother–child pairs. J Health Popul Nutr 31, 455461.
44. Zuercher JL, Wagstaff DA & Kranz S (2011) Associations of food group and nutrient intake, diet quality, and meal sizes between adults and children in the same household: a cross-sectional analysis of U.S. households. Nutr J 10, 131.
45. Gould JF, Makrides M, Colombo J, et al. (2014) Randomized controlled trial of maternal omega-3 long-chain PUFA supplementation during pregnancy and early childhood development of attention, working memory, and inhibitory control. Am J Clin Nutr 99, 851859.
46. Helland IB, Smith L, Blomen B, et al. (2008) Effect of supplementing pregnant and lactating mothers with n-3 very-long-chain fatty acids on children’s IQ and body mass index at 7 years of age. Pediatrics 122, e472e479.
47. Escolano-Margarit MV, Ramos R, Beyer J, et al. (2011) Prenatal DHA status and neurological outcome in children at age 5.5 years are positively associated. J Nutr 141, 12161223.
48. Makrides M, Neumann MA, Byard RW, et al. (1994) Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants. Am J Clin Nutr 60, 189194.
49. Xie L & Innis SM (2008) Genetic variants of the FADS1 FADS2 gene cluster are associated with altered (n-6) and (n-3) essential fatty acids in plasma and erythrocyte phospholipids in women during pregnancy and in breast milk during lactation. J Nutr 138, 22222228.
50. Koletzko B, Lattka E, Zeilinger S, et al. (2011) Genetic variants of the fatty acid desaturase gene cluster predict amounts of red blood cell docosahexaenoic and other polyunsaturated fatty acids in pregnant women: findings from the Avon Longitudinal Study of Parents and Children. Am J Clin Nutr 93, 211219.
51. Martinez M & Mougan I (1998) Fatty acid composition of human brain phospholipids during normal development. J Neurochem 71, 25282533.
52. Tau GZ & Peterson BS (2010) Normal development of brain circuits. Neuropsychopharmacology 35, 147168.
53. Keim SA & Branum AM (2015) Dietary intake of polyunsaturated fatty acids and fish among US children 12–60 months of age. Matern Child Nutr 11, 987998.
54. van der Wurff IS, Bakker EC, Hornstra G, et al. (2016) Association between prenatal and current exposure to selected LCPUFAs and school performance at age 7. Prostaglandins Leukot Essent Fatty Acids 108, 2229.
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