n-3 Polyunsaturated Fatty Acids and Foetal Growth

  • Gudrun V. SkuladottirEmail author


Pregnancy is a period in a woman’s life when good nutrition is exceptionally important, for both the growing foetus and the health of the mother. Several studies have reported that marine n-3 polyunsaturated fatty acids (PUFA) are one of the macronutrients required for optimal perinatal development and growth. The n-3 PUFA docosahexaenoic acid (DHA, 22:6n-3) plays an important role in foetal development. The placenta transports DHA specifically and in concentrated amounts from the mother’s blood to the foetus. DHA is incorporated into cell membranes of the central nervous system and retina of the foetus, where it increases fluidity of the membranes and participates in various cell functions. Studies indicate that dietary intake of preformed DHA is necessary, because the synthesis of DHA in the human body is not sufficient to meet physiological needs. It has been suggested that maternal red blood cells (RBC) act as a reservoir of DHA. Maternal dietary n-3 PUFA is therefore the most important determinant of n-3 PUFA availability to the growing foetus, since maternal dietary n-3 PUFA intake is assumed to reflect the maternal n-3 PUFA status of RBC lipids. Foetal growth during the first 10 weeks of pregnancy has been shown to be a major determinant of birth weight, and the neonate’s brain experiences a tremendous increase in growth during late gestation and early postnatal life. Moreover, it is indicated that n-3 PUFA could be one of the factors programming the later health of the growing individual. A recent study reported an association between maternal diet and lifestyle during pregnancy and foetal growth. Mothers who consumed a diet classified as the ‘Western diet’ (mainly red meat and little fish), and who smoked, were more likely to give birth to a baby that was small for gestational age. Optimal outcome of pregnancy has been related to improved health of the offspring later in life. The foetus’ birth weight and the risk of hypertension and cardiovascular disease in adult life are dependent on the mother’s nutrition and lifestyle during intrauterine life. The responsibility of women of reproductive age and during the pregnancy is therefore great, since they have to consume fish oil and/or seafood in order to have a reservoir of n-3 PUFA. In this chapter, an attempt is made to give an overview of the maternal status of blood DHA during pregnancy, intrauterine DHA sources, and their association with foetal growth.


Foetal Growth High Birth Weight PUFA Intake PUFA Status Maternal Adipose Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Arachidonic acid (20:4n-6)


α-Linolenic acid (18:3n-3)


Docosahexaenoic acid (22:6n-3)


Docosapentaenoic acid (22:5n-3)


Eicosapentaenoic acid (20:5n-3)


Linoleic acid (LA, 18:2n-6)




Polyunsaturated fatty acids


Red blood cells


  1. Agostoni C, Riva E, Giovannini M, Pinto F, Colombo C, Risé P, Galli C, Marangoni F. Maternal smoking habits are associated with differences in infants’ long-chain polyunsaturated fatty acids in whole blood: a case-control study. Arch Dis Child. 2008;93:414–8.PubMedCrossRefGoogle Scholar
  2. Arterburn LM, Hall EB, Oken H. Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr. 2006;83 Suppl:1467S–76S.PubMedGoogle Scholar
  3. Azain MJ. Role of fatty acids in adipocyte growth and development. J Anim Sci. 2004;82:916–24.PubMedGoogle Scholar
  4. Bukowski R, Smith GC, Malone FD, Ball RH, Nyberg DA, Comstock CH, Hankins GD, Berkowitz RL, Gross SJ, Dugoff L, Craigo SD, Timor-Tritsch IE, Carr SR, Wolfe HM, D’Alton ME. Fetal growth in early pregnancy and risk of delivering low birth weight infant: prospective cohort study. BMJ. 2007;334:836–40.PubMedCrossRefGoogle Scholar
  5. Burdge GC, Wootton SA. Conversation of alpha-linolenic acid to eicosapentaenoic docosapentaenoic and docosahexaenoic acids in young women. Br J Nutr. 2002;88:411–20.PubMedCrossRefGoogle Scholar
  6. Carlson SE. Docosahexaenoic acid supplementation in pregnancy and lactation. Am J Clin Nutr. 2009;89 Suppl:678S–84S.PubMedCrossRefGoogle Scholar
  7. Cleland LG, James MJ, Neumann MA, D’Angelo M, Gibson RA. Linoleate inhibits EPA incorporation from dietary fish-oil supplements in human subjects. Am J Clin Nutr. 1992;55:395–9.PubMedGoogle Scholar
  8. Dirix CE, Kester AD, Hornstra G. Associations between neonatal birth dimensions and maternal essential and trans fatty acid contents during pregnancy and at delivery. Br J Nutr. 2009;101:399–407.PubMedCrossRefGoogle Scholar
  9. Dobbing J, Sands J. Quantitative growth and development of human brain. Arch Dis Child. 1973;48:757–67.PubMedCrossRefGoogle Scholar
  10. Drouillet P, Forhan A, De Lauzon-Guillain B, Thiébaugeorges O, Goua V, Magnin G, Schweitzer M, Kaminski M, Ducimetière P, Charles MA. Maternal fatty acid intake and fetal growth: evidence for an association in overweight women. The ‘EDEN mother-child’ cohort (study of pre- and early postnatal determinants of the child’s development and health). Br J Nutr. 2009;101:583–91.PubMedCrossRefGoogle Scholar
  11. Dunstan JA, Mori TA, Barden A, Beilin LJ, Holt PG, Calder PC, Taylor AL, Prescott SL. Effects of n-3 polyunsaturated fatty acid supplementation in pregnancy on maternal and fetal erythrocyte fatty acid composition. Eur J Clin Nutr. 2004;58:429–37.PubMedCrossRefGoogle Scholar
  12. Freeman MP. Omega-3 fatty acids and perinatal depression: a review of the literature and recommendations for future research. Prostglandins Leukot Essent Fatty Acids. 2006;75:291–7.CrossRefGoogle Scholar
  13. Ghebremeskel K, Min Y, Crawford MA, Nam JH, Kim A, Koo JN, Suzuki H. Blood fatty acid composition of pregnant and nonpregnant Korean women: red cells may act as a reservoir of arachidonic acid and docosahexaenoic acid for utilization by the developing fetus. Lipids. 2000;35:567–74.PubMedCrossRefGoogle Scholar
  14. Gunnarsdottir I, Birgisdottir BE, Benediktsson R, Gudnason V, Thorsdottir I. Relationship between size at birth and hypertension in a genetically homogeneous population of high birth weight. J Hypertens. 2002;20:623–8.PubMedCrossRefGoogle Scholar
  15. Haggarty P, Allstaff S, Hoad G, Ashton J, Abramovich DR. Placental nutrient transfer capacity and fetal growth. Placenta. 2002;23:86–92.PubMedCrossRefGoogle Scholar
  16. Hauner H, Vollhardt C, Schneider KTM, Zimmermann A, Schuster T, Amann-Gassner U. The impact of nutritional fatty acids during pregnancy and lactation on early human adipose tissue development. Rationale and design of the INFAT study. Ann Nutr Metab. 2009;54:97–103.PubMedCrossRefGoogle Scholar
  17. Helland IB, Saugstad OD, Smith L, Saarem K, Solvoll K, Ganes T, Drevon CA. Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women. Pediatrics. 2001;108:e82.PubMedCrossRefGoogle Scholar
  18. Herrera E, Ortega H, Alvino G, Giovannini N, Amusquivar E, Cetin I. Relationship between plasma fatty acid profile and antioxidant vitamins during normal pregnancy. Eur J Clin Nutr. 2004;58:1231–8.PubMedCrossRefGoogle Scholar
  19. Hornstra G, Al MDM, Houwelingen AC van, Foreman-van Drongelen MMHP. Essential fatty acids in pregnancy and early human development. Eur J Obstet Gynecol Reprod Biol. 1995;61:57–62.PubMedCrossRefGoogle Scholar
  20. Innis SM. Dietary (n-3) fatty acids and brain development. J Nutr. 2007;137:855–9.PubMedGoogle Scholar
  21. Jaddoe VW, Troe EJ, Hofman A, Mackenbach JP, Moll HA, Steegers EA, Witteman JC. Active and passive maternal smoking during pregnancy and the risks of low birthweight and preterm birth: the Generation R study. Paediatr Perinat Epidemiol. 2008;22:162–71.PubMedCrossRefGoogle Scholar
  22. Katan MB, Deslypere JP, van Birgelen AP, Penders M, Zegwaard M. Kinetics of the incorporation of dietary fatty acids into serum cholesteryl esters, erythrocyte membranes, and adipose tissue: an 18-month controlled study. J Lipid Res. 1997;38:2012–22.PubMedGoogle Scholar
  23. Knudsen VK, Orozova-Bekkevold IM, Mikkelsen TB, Wolff S, Olsen SF. Major dietary patterns in pregnancy and fetal growth. Eur J Clin Nutr. 2008;62:463–70.PubMedCrossRefGoogle Scholar
  24. Koletzko B, Lien E, Agostoni C, Böhles H, Campoy C, Cetin I, Decsi T, Dudenhausen JW, Dupont C, Forsyth S, Hoesli I, Holzgreve W, Lapillonne A, Putet G, Secher NJ, Symonds M, Szajewska H, Willatts P, Uauy R. The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations. J Perinat Med. 2008;36:5–14.PubMedCrossRefGoogle Scholar
  25. Krauss-Etschmann S, Shadid R, Campoy C, Hoster E, Demmelmair H, Jiménez M, Gil A, Rivero M, Veszprémi B, Decsi T, Koletzko BV. Effects of fish-oil and folate supplementation of pregnant women on maternal and fetal plasma concentrations of docosahexaenoic acid and eicosapentaenoic acid: a European randomized multicenter trial. Am J Clin Nutr. 2007;85:1392–400.PubMedGoogle Scholar
  26. Kris-Etherton PM, Taylor DS, Yu-Poth S, Huth P, Moriarty K, Fishell V, Hargrove RL, Zhao G, Etherton TD. Polyunsaturated fatty acids in the food chain in the United States. Am J Clin Nutr. 2000;71:179S–88S.PubMedGoogle Scholar
  27. Lakin V, Haggarty P, Abramovich DR, Ashton J, Moffat CF, McNeill G, Danielian PJ, Grubb D. Dietary intake and tissue concentration of fatty acids in omnivore, vegetarian and diabetic pregnancy. Prostaglandins Leukot Essent Fatty Acids. 1998;59:209–20.PubMedCrossRefGoogle Scholar
  28. Lapillonne A, Jensen CL. Reevaluation of the DHA requirement for the premature infant. Prostaglandins Leukot Essent Fatty Acids. 2009;81:143–50.PubMedCrossRefGoogle Scholar
  29. Leaf AA, Leighfield MJ, Costeloe KL, Crawford MA. Long chain polyunsaturated fatty acids and fetal growth. Early Hum Dev. 1992;30:183–91.PubMedCrossRefGoogle Scholar
  30. Magnusardottir AR, Steingrimsdottir L, Thorgeirsdottir H, Gunnlaugsson G, Skuladottir GV. Docosahexaenoic acid in red blood cells of women of reproductive age is positively associated with oral contraceptive use and physical activity. Prostaglandins Leukot Essent Fatty Acids. 2009a;80:27–32.Google Scholar
  31. Magnusardottir AR, Steingrimsdottir L, Thorgeirsdottir H, Hauksson A, Skuladottir GV. Red blood cell n-3 polyunsaturated fatty acids in first trimester of pregnancy are inversely associated with placental weight. Acta Obstet Gynecol Scand. 2009b;88:91–7.PubMedCrossRefGoogle Scholar
  32. Martinez M. Tissue levels of polyunsaturated fatty acids during early human development. J Pediatr. 1992;120 Suppl:S129–38.PubMedCrossRefGoogle Scholar
  33. Nakamura MT, Cho HP, Xu J, Tang Z, Clarke SD. Metabolism and functions of highly unsaturated fatty acids: an update. Lipids 2001;36:961–4.PubMedCrossRefGoogle Scholar
  34. Olafsdottir AS, Magnusardottir AR, Thorgeirsdottir H, Hauksson A, Skuladottir GV, Steingrimsdottir L. Relationship between dietary intake of cod liver oil in early pregnancy and birthweight. BJOG. 2005;112:424–9.PubMedCrossRefGoogle Scholar
  35. Olsen SF, Secher NJ. Low consumption of seafood in early pregnancy as a risk factor for preterm delivery: prospective cohort study. BMJ. 2002;324:447.PubMedCrossRefGoogle Scholar
  36. Olsen SF, Grandjean P, Weihe P, Viderø T. Frequency of seafood intake in pregnancy as a determinant of birth weight: evidence for a dose dependent relationship. J Epidemiol Community Health. 1993;47:436–40.PubMedCrossRefGoogle Scholar
  37. Olsen SF, Hansen HS, Sandstrom B, Jensen B. Erythrocyte levels compared with reported dietary intake of marine n-3 fatty acids in pregnant women. Br J Nutr. 1995;73:387–95.PubMedCrossRefGoogle Scholar
  38. Olsen SF, Secher NJ, Tabor A, Weber T, Walker JJ, Gluud C. Randomised clinical trials of fish oil supplementation in high risk pregnancies. BJOG. 2000;107:382–95.PubMedCrossRefGoogle Scholar
  39. Olsen SF, Østerdal ML, Salvig JD, Weber T, Tabor A, Secher NJ. Duration of pregnancy in relation to fish oil supplementation and habitual fish intake: a randomised clinical trial with fish oil. Eur J Clin Nutr. 2007;61:976–85.PubMedCrossRefGoogle Scholar
  40. Olsen SF, Østerdal ML, Salvig JD, Mortensen LM, Rytter D, Secher NJ, Henriksen TB. Fish oil intake compared with olive oil intake in late pregnancy and asthma in the offspring: 16 y of registry-based follow-up from a randomized controlled trial. Am J Clin Nutr. 2008;88:167–75.PubMedGoogle Scholar
  41. Otto SJ, Houwelingen AC, Hornstra G. The effect of supplementation with docosahexaenoic and arachidonic acid derived from single cell oils on plasma and erythrocyte fatty acids of pregnant women in the second trimester. Prostaglandins Leukot Essent Fatty Acids. 2000;63:323–8.PubMedCrossRefGoogle Scholar
  42. Rapoport SI, Rao JS, Igarashi M. Brain metabolism of nutritionally essential polyunsaturated fatty acids depends on both the diet and the liver. Prostaglandins Leukot Essent Fatty Acids. 2007;77:251–61.PubMedCrossRefGoogle Scholar
  43. Reddy S, Sanders TA, Obeid O. The influence of maternal vegetarian diet on essential fatty acid status of the newborn. Eur J Clin Nutr. 1994;48:358–68.PubMedGoogle Scholar
  44. Rump P, Hornstra G. The n-3 and n-6 polyunsaturated fatty acid composition of plasma phospholipids in pregnant women and their infants. Relationship with maternal linoleic acid intake. Clin Chem Lab Med. 2002;40:32–9.CrossRefGoogle Scholar
  45. Rump P, Mensink RP, Kester ADM, Hornstra G. Essential fatty acid composition of plasma phospholipids and birth weight: a study in term neonates. Am J Clin Nutr. 2001;73:797–806.PubMedGoogle Scholar
  46. Ruyle M, Connor WE, Anderson GJ, Lowensohn RI. Placental transfer of essential fatty acids in humans: venous-arterial difference for docosahexaenoic acid in fetal umbilical erythrocytes. Proc Natl Acad Sci USA. 1990;87:7902–6.PubMedCrossRefGoogle Scholar
  47. Sanders TA. Polyunsaturated fatty acids in the food chain in Europe. Am J Clin Nutr. 2000;71 Suppl:176S–8S.PubMedGoogle Scholar
  48. Schiefermeier M, Yavin E. n-3 Deficient and docosahexaenoic acid-enriched diets during critical periods of the developing prenatal rat brain. J Lipid Res. 2002;43:124–31.PubMedGoogle Scholar
  49. Simopoulos AP. Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr. 1991;54:438–63.PubMedGoogle Scholar
  50. Simopoulos AP. Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases. Biomed Pharmacother. 2006;60:502–7.PubMedCrossRefGoogle Scholar
  51. Smuts CM, Huang M, Mundy D, Plasse T, Major S, Carlson SE. A randomized trial of docosahexaenoic acid supplementation during the third trimester of pregnancy. Obstet Gynecol. 2003;101:469–79.PubMedCrossRefGoogle Scholar
  52. Sprecher H, Luthria DL, Mohammed BS, Baykousheva SP. Reevaluation of the pathways for the biosynthesis of polyunsaturated fatty acids. J. Lipid Res. 1995;36:2471–7.PubMedGoogle Scholar
  53. Van Duyne CM, Havel RJ. Plasma unesterified fatty acid concentration in fetal and neonatal life. Proc Soc Exp Biol Med. 1959;102:599–602.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Physiology, Faculty of Medicine, School of Health SciencesUniversity of IcelandReykjavikIceland

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