Maternal Supplementation With Very-Long-Chain n-3 Fatty Acids During Pregnancy and Lactation Augments Children’s IQ at 4 Years of Age

American Academy of Pediatrics (AAP) - Tập 111 Số 1 - Trang e39-e44 - 2003
Ingrid B. Helland1,2, Lars Smith3, Kristin Saarem4, Ola Didrik Saugstad1, Christian A. Drevon2
1Department of Pediatric Research
2Institute for Nutrition Research
3Institute of Psychology, University of Oslo, Oslo, Norway
4Peter Möller, avd Orkla, ASA, Oslo, Norway

Tóm tắt

Objectives. Docosahexaenoic acid (DHA; 22:6 n-3) and arachidonic acid (AA; 20:4 n-6) are important for development of the central nervous system in mammals. There is a growth spurt in the human brain during the last trimester of pregnancy and the first postnatal months, with a large increase in the cerebral content of AA and DHA. The fetus and the newborn infant depend on maternal supply of DHA and AA. Our hypothesis was that maternal intake of DHA during pregnancy and lactation is marginal and that high intake of this fatty acid would benefit the child. We examined the effect of supplementing pregnant and lactating women with very-long-chain n-3 polyunsaturated fatty acids (PUFAs; cod liver oil) on mental development of the children, compared with maternal supplementation with long-chain n-6 PUFAs (corn oil). Methods. The study was randomized and double-blinded. Pregnant women were recruited in week 18 of pregnancy to take 10 mL of cod liver oil or corn oil until 3 months after delivery. The cod liver oil contained 1183 mg/10 mL DHA, 803 mg/10 mL eicosapentaenoic acid (20:5 n-3), and a total of 2494 mg/10 mL ∑ n-3 PUFAs. The corn oil contained 4747 mg/10 mL linoleic acid (18:2 n-6) and 92 mg/10 mL α-linolenic acid (18:3 n-3). The amount of fat-soluble vitamins was identical in the 2 oils (117 μg/mL vitamin A, 1 μg/mL vitamin D, and 1.4 mg/mL dl-α-tocopherol). A total of 590 pregnant women were recruited to the study, and 341 mothers took part in the study until giving birth. All infants of these women were scheduled for assessment of cognitive function at 6 and 9 months of age, and 262 complied with the request. As part of the protocol, 135 subjects from this population were invited for intelligence testing with the Kaufman Assessment Battery for Children (K-ABC) at 4 years of age. Of the 135 invited children, 90 came for assessment. Six children did not complete the examination. The K-ABC is a measure of intelligence and achievement designed for children aged 2.5 years through 12.5 years. This multisubtest battery comprises 4 scales: Sequential Processing, Simultaneous Processing, Achievement (not used in the present study), and Nonverbal Abilities. The Sequential Processing and Simultaneous Processing scales are hypothesized to reflect the child’s style of problem solving and information processing. Scores from these 2 scales are combined to form a Mental Processing Composite, which serves as the measure of intelligence in the K-ABC. Results. We received dietary information from 76 infants (41 in the cod liver oil group and 35 in the corn oil group), documenting that all of them were breastfed at 3 months of age. Children who were born to mothers who had taken cod liver oil (n = 48) during pregnancy and lactation scored higher on the Mental Processing Composite of the K-ABC at 4 years of age as compared with children whose mothers had taken corn oil (n = 36; 106.4 [7.4] vs 102.3 [11.3]). The Mental Processing Composite score correlated significantly with head circumference at birth (r = 0.23), but no relation was found with birth weight or gestational length. The children’s mental processing scores at 4 years of age correlated significantly with maternal intake of DHA and eicosapentaenoic acid during pregnancy. In a multiple regression model, maternal intake of DHA during pregnancy was the only variable of statistical significance for the children’s mental processing scores at 4 years of age. Conclusion. Maternal intake of very-long-chain n-3 PUFAs during pregnancy and lactation may be favorable for later mental development of children.

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Tài liệu tham khảo

Crawford MA, Hassam AG, Williams G. Essential fatty acids and fetal brain growth. Lancet.1976;1:452–453

Neuringer M, Connor WE, Van Petten C, Barstad L. Dietary omega-3 fatty acid deficiency and visual loss in infant rhesus monkeys. J Clin Invest.1984;73:272–276

Clandinin MT, Chappell JE, Leong S, Heim T, Swyer PR, Chance GW.Intrauterine fatty acid accretion rates in human brain: implications for fatty acid requirements. Early Hum Dev.1980;4:121–129

Carlson SE, Rhodes PG, Ferguson MG. Docosahexaenoic acid status of preterm infants at birth and following feeding with human milk or formula. Am J Clin Nutr.1986;44:798–804

Hoffman DR, Uauy R. Essentiality of dietary omega 3 fatty acids for premature infants: plasma and red blood cell fatty acid composition. Lipids.1992;27:886–895

Makrides M, Neumann M, Simmer K, Pater J, Gibson R. Are long-chain polyunsaturated fatty acids essential nutrients in infancy?Lancet.1995;345:1463–1468

Al MD, Hornstra G, van der Schouw YT, Bulstra-Ramakers MT, Huisjes HJ. Biochemical EFA status of mothers and their neonates after normal pregnancy. Early Hum Dev.1990;24:239–248

Farquharson J, Cockburn F, Patrick WA, Jamieson EC, Logan RW. Infant cerebral cortex phospholipid fatty-acid composition and diet. Lancet.1992;340:810–813

Makrides M, Neumann MA, Byard RW, Simmer K, Gibson RA. Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants. Am J Clin Nutr.1994;60:189–194

Innis SM, Kuhnlein HV. Long-chain n-3 fatty acids in breast milk of Inuit women consuming traditional foods. Early Hum Dev.1988;18:185–189

Harris WS, Connor WE, Lindsey S. Will dietary omega-3 fatty acids change the composition of human milk?Am J Clin Nutr.1984;40:780–785

Helland IB, Saarem K, Saugstad OD, Drevon CA. Fatty acid composition in maternal milk and plasma during supplementation with cod liver oil. Eur J Clin Nutr.1998;52:839–845

Lucas A, Morley R, Cole TJ, Lister G, Leeson-Payne C. Breast milk and subsequent intelligence quotient in children born preterm. Lancet.1992;339:261–264

Rogan WJ, Gladen BC. Breast-feeding and cognitive development. Early Hum Dev.1993;31:181–193

Lucas A, Morley R, Cole TJ, Gore SM. A randomised multicentre study of human milk versus formula and later development in preterm infants. Arch Dis Child Fetal Neonatal Ed.1994;70:F141–F146

Anderson JW, Johnstone BM, Remley DT. Breast-feeding and cognitive development: a meta-analysis. Am J Clin Nutr.1999;70:525–535

Angelsen NK, Vik T, Jacobsen G, Bakketeig LS. Breast feeding and cognitive development at age 1 and 5 years. Arch Dis Child.2001;85:183–188

Agostoni C, Trojan S, Bellu R, Riva E, Giovannini M. Neurodevelopmental quotient of healthy term infants at 4 months and feeding practice: the role of long-chain polyunsaturated fatty acids. Pediatr Res.1995;38:262–266

Carlson SE, Ford AJ, Werkman SH, Peeples JM, Koo WW. Visual acuity and fatty acid status of term infants fed human milk and formulas with and without docosahexaenoate and arachidonate from egg yolk lecithin. Pediatr Res.1996;39:882–888

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. Lancet.1998;352:688–691

Birch EE, Hoffman DR, Uauy R, Birch DG, Prestidge C. Visual acuity and the essentiality of docosahexaenoic acid and arachidonic acid in the diet of term infants. Pediatr Res.1998;44:201–209

Birch EE, Garfield S, Hoffman DR, Uauy R, Birch DG. A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants. Dev Med Child Neurol.2000;42:174–181

Horby Jorgensen M, Holmer G, Lund P, Hernell O, Michaelsen KF. Effect of formula supplemented with docosahexaenoic acid and gamma-linolenic acid on fatty acid status and visual acuity in term infants. J Pediatr Gastroenterol Nutr.1998;26:412–421

Lucas A, Stafford M, Morley R, et al. Efficacy and safety of long-chain polyunsaturated fatty acid supplementation of infant-formula milk: a randomised trial. Lancet.1999;354:1948–1954

Makrides M, Neumann MA, Simmer K, Gibson RA. A critical appraisal of the role of dietary long-chain polyunsaturated fatty acids on neural indices of term infants: a randomized, controlled trial. Pediatrics.2000;105:32–38

Auestad N, Halter R, Hall RT, et al. Growth and development in term infants fed long-chain polyunsaturated fatty acids: a double-masked, randomized, parallel, prospective, multivariate study. Pediatrics.2001;108:372–381

Scott DT, Janowsky JS, Carroll RE, Taylor JA, Auestad N, Montalto MB. Formula supplementation with long-chain polyunsaturated fatty acids: are there developmental benefits?Pediatrics.1998;102(5). Available at: www.pediatrics.org/cgi/content/full/102/5/e59

Uauy RD, Birch DG, Birch EE, Tyson JE, Hoffman DR. Effect of dietary omega-3 fatty acids on retinal function of very-low-birth-weight neonates. Pediatr Res.1990;28:485–492

Carlson SE, Werkman SH, Rhodes PG, Tolley EA. Visual-acuity development in healthy preterm infants: effect of marine-oil supplementation. Am J Clin Nutr.1993;58:35–42

O’Connor DL, Hall R, Adamkin D, et al. Growth and development in preterm infants fed long-chain polyunsaturated fatty acids: a prospective, randomized controlled trial. Pediatrics.2001;108:359–371

Helland IB, Saugstad OD, Smith L, et al. Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women. Pediatrics.2001;108(5). Available at: www.pediatrics.org/cgi/content/full/108/5/e82

Kaufman AS, Kaufman NL. Kaufman Assessment Battery for Children. Circle Pines, MN: American Guidance Service; 1983

Clark RM, Roche ME. Gas chromatographic procedure for measuring total lipid in breast milk. J Pediatr Gastroenterol Nutr.1990;10:271–272

Nes M, Frost Andersen L, Solvoll K, et al. Accuracy of a quantitative food frequency questionnaire applied in elderly Norwegian women. Eur J Clin Nutr.1992;46:809–821

Solvoll K, Lund-Larsen K, Søyland E, Sandstad B, Drevon CA. A quantitative food frequency questionnaire evaluated in a group of dermatologic outpatients. Scand J Nutr.1993;37:150–155

Andersen LF, Solvoll K, Drevon CA. Very-long-chain n-3 fatty acids as biomarkers for intake of fish and n-3 fatty acid concentrates. Am J Clin Nutr.1996;64:305–311

Connor WE, Lowensohn R, Hatcher L. Increased docosahexaenoic acid levels in human newborn infants by administration of sardines and fish oil during pregnancy. Lipids.1996;31(suppl):S183–S187

Williams C, Birch EE, Emmett PM, Northstone K. Stereoacuity at age 3.5 y in children born full-term is associated with prenatal and postnatal dietary factors: a report from a population-based cohort study. Am J Clin Nutr.2001;73:316–322

Wienerroither H, Steiner H, Tomaselli J, Lobendanz M, Thun-Hohenstein L. Intrauterine blood flow and long-term intellectual, neurologic, and social development. Obstet Gynecol.2001;97:449–453

Markestad T, Vik T, Ahlsten G, et al. Small-for-gestational-age (SGA) infants born at term: growth and development during the first year of life. Acta Obstet Gynecol Scand Suppl.1997;165:93–101

Low JA, Handley-Derry MH, Burke SO, et al. Association of intrauterine fetal growth retardation and learning deficits at age 9 to 11 years. Am J Obstet Gynecol.1992;167:1499–1505

Larroque B, Bertrais S, Czernichow P, Leger J. School difficulties in 20-year-olds who were born small for gestational age at term in a regional cohort study. Pediatrics.2001;108:111–115

Sells CJ, Robinson NM, Brown Z, Knopp RH. Long-term developmental follow-up of infants of diabetic mothers. J Pediatr.1994;125:S9–S17

Hornstra G, Al MD, van Houwelingen AC, Foreman-van Drongelen MM. Essential fatty acids in pregnancy and early human development. Eur J Obstet Gynecol Reprod Biol.1995;61:57–62

Drevon CA. Omega-3 Fatty Acids. Metabolism and Biological Effects. Basel, Switzerland: Birkhäuser; 1993

Forsyth JS, Carlson SE. Long-chain polyunsaturated fatty acids in infant nutrition: effects on infant development. Curr Opin Clin Nutr Metab Care.2001;4:123–126