Research Article| Volume 85, ISSUE 6, P311-316, December 2011

Post term dietary-induced changes in DHA and AA status relate to gains in weight, length, and head circumference in preterm infants

Published:October 13, 2011DOI:


      Preterms need supplementation with docosahexaenoic (DHA) and arachidonic (AA) acids to prevent steep postnatal declines.
      Associations between growth and erythrocyte (RBC) DHA and AA were studied in 139 preterms (51% male, gestational age 30.3±1.5 weeks, birth weight 1341±288 g) fed human milk with breast milk fortifier or preterm formula until term, followed by postdischarge formula (PDF; n=52, 0.4% DHA, 0.4% AA), term formula (TF; n=41, 0.2% DHA, 0.2% AA), or human milk (HM; n=46).
      At six months, PDF resulted in higher RBC-DHA than TF and HM, while RBC-AA was higher than TF, but similar to HM. There were no between-group differences in growth between term and six months. RHC-DHA related positively with gain in weight and length and negatively with gain in head circumference. RBC-AA related positively with gain in head circumference and negatively with gain in weight and length.
      In conclusion, PDF with higher DHA and AA than TF may promote postnatal growth of preterms.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Prostaglandins, Leukotrienes and Essential Fatty Acids
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Lauritzen L.
        • Hansen H.S.
        • Jorgensen M.H.
        • Michaelsen K.F.
        The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina.
        Prog. Lipid Res. 2001; 40: 1-94
        • Martinez M.
        • Mougan I.
        Fatty acid composition of human brain phospholipids during normal development.
        J. Neurochem. 1998; 71: 2528-2533
        • Fewtrell M.S.
        • Morley R.
        • Abbott R.A.
        • et al.
        Double-blind, randomized trial of long-chain polyunsaturated fatty acid supplementation in formula fed to preterm infants.
        Pediatrics. 2002; 110: 73-82
      1. Uauy R., Rojas C., Llanos A., Mena P. Dietary Essential Fatty Acids in Early Postnatal Life: Long-Term Outcomes. Nestlé Nutr. Workshop Ser. Pediatr. Program, 2005, 55: pp. 101–133.

        • Uauy W.
        • Mena P.
        Lipids and neurodevelopment.
        Nutr. Rev. 2001; 59: S34-S48
        • Clandinin M.T.
        • Chappell J.E.
        • Leong S.
        • Heim T.
        • Swyer P.R.
        • Chance G.W.
        Intrauterine fatty acid accretion in human brain: implications for fatty acid requirements.
        Early Hum. Dev. 1980; 4: 121-129
        • Carlson S.E.
        • Cooke R.J.
        • Rhodes P.G.
        • Peeples J.M.
        • Werkman S.H.
        • Tolley E.A.
        Long-term feeding of formulas high in linolenic acid and marine oil to very low birth weight infants: phospholipid fatty acids.
        Pediatr. Res. 1991; 30: 404-412
        • Makrides M.
        • Gibson R.A.
        • Udell T.
        • et al.
        Supplementation of infant formula with long-chain polyunsaturated fatty acids does not influence the growth of term infants.
        Am. J. Clin. Nutr. 2005; 81: 1094-1101
        • Simmer K.
        • Schulzke S.M.
        • Patole S.
        Longchain polyunsaturated fatty acid supplementation in preterm infants.
        Cochrane Database Syst. Rev. 2008; 23: CD000375
        • Simmer K.
        • Patole S.K.
        • Rao S.C.
        Longchain polyunsaturated fatty acid supplementation in infants born at term.
        Cochrane Database Syst. Rev. 2008; 23: CD000376
        • Makrides M.
        • Neumann M.A.
        • Byard R.W.
        Fatty acid composition of the brain, retina and erythrocytes in breast- and formula-fed infants.
        Am. J. Clin. Nutr. 1994; 60: 180-194
        • Farquharson J.
        • Jamieson E.C.
        • Abbasi K.A.
        • et al.
        Effect of diet on the fatty acid composition of the major phospholipids of infant cerebral cortex.
        Arch. Dis. Child. 1995; 72: 198-203
        • Carlson S.E.
        • Rhodes P.G.
        • Rao V.S.
        • Goldgar D.E.
        Effect of fish oil supplementation on the n-3 fatty acid content of red blood cell membranes in preterm infants.
        Pediatr. Res. 1987; 21: 507-510
        • Lapillonne A.
        • Picaud J.C.
        • Chirouze V.
        • et al.
        The use of low-EPA fish oil for long-chain polyunsaturated fatty acid supplementation of preterm infants.
        Pediatr. Res. 2000; 48: 835-841
        • Klein C.J.
        Nutrient requirements for preterm infants formulas.
        J. Nutr. 2002; 123: 1395S-1577S
        • Innis S.M.
        Essential fatty acid transfer and fetal development.
        Placenta. 2005; 26: S70-75
        • Brenna J.T.
        • Varamini B.
        • Jensen R.G.
        • Diersen-Schade D.A.
        • Boettcher J.A.
        • Arterburn L.M.
        Docosahexaenoic and arachidonic acid concentrations in human breast milk worldwide.
        Am. J. Clin. Nutr. 2007; 85: 1457-1464
        • Bokor S.
        • Koletzko B.
        • Decsi T.
        Systematic review of fatty acid composition of human milk from mothers of preterm compared to full-term infants.
        Ann. Nutr. Metab. 2007; 51: 550-556
        • van Goor S.A.
        • Dijck-Brouwer D.A.
        • Hadders-Algra M.
        • et al.
        Human milk arachidonic acid and docosahexaenoic acid contents increase following supplementation during pregnancy and lactation.
        Prostaglandins Leukot. Essent Fatty Acids. 2009; 80: 65-69
        • Muskiet F.A.J.
        • van Goor S.A.
        • Kuipers R.S.
        • et al.
        Long-chain polyunsaturated fatty acids in maternal and infant nutrition.
        Prostaglandins Leukot. Essent Fatty Acids. 2006; 75: 135-144
        • Koletzko B.
        • Lien E.
        • Agostoni C.
        • et al.
        The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus reccomendations.
        J. Perinatal. Med. 2008; 36: 5-14
        • van Goor S.A.
        • Smit E.N.
        • Schaafsma A.
        • Bijck-Brouwer D.A.
        • Muskiet F.A.
        Milk of women with lifetime consumption of the recommended daily intake of fish fatty acids should constitue the basis for the DHA contents of infant formula.
        J. Perinatal. Med. 2008; 36: 548-549
        • Koletzko B.
        • Agostoni C.
        • Carlson S.E.
        • et al.
        Long chain polyunsaturated fatty acids (LC-PUFA) and perinatal development.
        Acta Paediatr. 2001; 90: 460-464
        • Koletzko B.
        • Baker S.
        • Cleghorn G.
        • et al.
        Global standard for the composition of infant formula: recommendations of an ESPGHAN coordinated international expert group.
        J. Pediatr. Gastroenterol. Nutr. 2005; 41: 584-599
        • Agostoni C.
        • Buonocore G.
        • Carnielli V.P.
        • et al.
        Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition Committe on Nutrition.
        J. Pediatr. Gastroenterol. Nutr. 2010; 50: 85-91
        • Amesz E.M.
        • Schaafsma A.
        • Cranendonk A.
        • Lafeber H.N.
        Optimal growth and lower fat mass in preterm infants fed a protein-enriched postdischarge formula.
        J. Pediatr. Gastroenterol. Nutr. 2010; 50: 200-207
        • Niklasson A.
        • Ericson A.
        • Fryer J.G.
        • Karlberg J.
        • Lawrence C.
        • Karlberg P.
        An update of the Swedish reference standards for weight, length and head circumference at birth for given gestational age (1977–1981).
        Acta Paediatr. Scand. 1991; 80: 756-762
        • Fredriks A.M.
        • Buuren S.
        • van, Burgmeijer R.J.
        • et al.
        Continuing positive secular growth change in The Netherlands 1955–1997.
        Pediatr. Res. 2000; 47: 316-323
        • Muskiet F.A.
        • van Doormaal J.J.
        • Martini I.A.
        • Wolthers B.G.
        • van der Slik W.
        Capillary gas chromatographic profiling of total long-chain fatty acids and cholesterol in biological materials.
        J. Chromatogr. 1983; 278: 231-244
        • Woltil H.A.
        • van Beusekom C.M.
        • Schaafsma A.
        • Muskiet F.A.J.
        • Okken A.
        Long-chain polyunsaturated fatty acid status and early growth of low birth weight infants.
        Eur. J. Pediatr. 1998; 157: 146-152
        • Carlson S.E.
        • Werkman S.H.
        • Peeples J.M.
        • Cooke R.J.
        • Tolley E.A.
        Arachidonic acid status correlates with first year growth in preterm infants.
        Proc. Natl. Acad. Sci. USA. 1993; : 1073-1077
        • Nelson G.J.
        • Schmidt P.C.
        • Bartolini G.
        • et al.
        The effect of dietary arachidonic acid on plasma lipoprotein distributions, apoproteins, blood lipid levels, and tissue fatty acid composition in humans.
        Lipids. 1997; 32: 427-433
        • Kuipers R.S.
        • Luxwolda M.F.
        • Sango W.S.
        • Kwesigabo G.
        • Dijck-Brouwer D.A.J.
        • Muskiet F.A.
        Maternal DHA equilibrium during pregnancy and lactation is reached at an erythrocyte DHA content of 8 g/100 g fatty acids.
        J. Nutr. 2011; 141: 418-427
        • Kuipers R.S.
        • Luxwolda M.F.
        • Dijck-Brouwer D.A.J.
        • Muskiet F.A.J.
        Intrauterine, postpartum and adult relationships between arachidonc acid (AA) and docosahexaenoic acid (DHA).
        Prostaglandins Leukot. Essent Fatty Acids. 2011;
        • Crowther N.J.
        • Cameron N.
        • Trusler J.
        • Gray I.P.
        Association between poor glucose tolerance and rapid postnatal weight gain in seven-year-old children.
        Diabetologia. 1998; 41: 1163-1167
        • Iñiguez G.
        • Ong K.
        • Bazaes R.
        • et al.
        Longitudinal changes in insulin-like growth factor-1, insulin sensitivity and secretion from birth to age three years in small-for-gestational-age children.
        J. Clin. Endocrinol. Metab. 2006; 91: 4645-4649
        • Eriksson J.
        Commentary: early ‘catch-up’ growth is good for later health.
        Int. J. Epidemiol. 2001; 30: 1330-1331
        • Singhal A.
        • Lucas A.
        Early origins of cardiovascular disease: is there a unifying hypothesis?.
        Lancet. 2004; 363: 1642-1645
        • Singhal A.
        • Kennedy K.
        • Lanigan J.
        • et al.
        Nutrition in infancy and long–term risk of obesity: evidence from 2 randomized controlled trials.
        Am. J. Clin. Nutr. 2010; 92: 1133-1144
        • Monteiro P.O.A.
        • Victora C.G.
        Rapid growth in infancy and childhood and obesity in later life—a systematic review.
        Obes. Rev. 2005; 6: 143-154
        • Latal-Hajnal B.
        • Siebenthal K.
        • von, Kovari H.
        • Bucher H.U.
        • Largo R.H.
        Postnatal growth in very low birth weight infants: significant association with neurodevelopmental outcome.
        J. Pediatr. 2003; 143: 163-170
        • Brandt I.
        • Sticker E.J.
        • Lentze M.J.
        Catch up growth of head circumference of very low birth weight, small for gestational age preterm infants and mental development to adulthood.
        J. Pediatr. 2003; 142: 463-468
        • McCann J.C.
        • Ames B.N.
        Is docosahexaenoic acid, an n-3 long-chain polyunsaturated fatty acid, required for development of normal brain function? An overview of evidence from cognitive and behavioral tests in humans and animals.
        Am. J. Clin. Nutr. 2005; 85: 281-295