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Omega-3 fatty acid supplementation during pregnancy
Gal Dubnov-Raz MD MSC, Yaron Finkelstein MD, Gideon Koren MD FRCPC
Several pregnant patients have asked recently whether media reports of children’s intelligence quotients’ increasing with increased intake of essential fatty acids are meaningful enough to be worth the effort of supplementation. What advice should they be given?
Existing evidence from interventional studies is sparse and conflicting and should not lead to supplementation with polyunsaturated fatty acids.
Quelques patientes enceintes m’ont demandé récemment si les rapports médiatiques à l’effet que le quotient intellectuel des enfants augmentait avec un apport accru en acides gras essentiels étaient assez significatifs pour justifier de prendre un supplément. Quels conseils faut-il leur donner?
Les données scientifiques actuelles tirées d’études interventionnelles sont plutôt rares et contradictoires et ne sont pas suffisantes pour recommander un supplément d’acides gras essentiels.
Polyunsaturated fatty acids (PUFAs) of the ω-3 and ω-6 families are essential for a healthy diet. ω-3 PUFAs mainly include alpha-linolenic acid (ALA), which is derived from plants, and eicosapentenoic acid (EPA) and docosahexaenoic acid (DHA), which are found in fish oil. ω-6 PUFAs mainly include linoleic acid (LA) and arachidonic acid (AA), which are found in most vegetable oils, whole grain breads, eggs, and cereals. These fatty acids are essential components of the human brain and are required especially in the third trimester of pregnancy when brain growth is at its peak.1,2 As PUFAs from both families are metabolized by the same enzymes, the ratio between them is important.3,4 For example, increasing dietary intake of ω-3 fatty acids might reduce the levels of essential ω-6 products in fetuses.5,6 When ω-3 PUFAs without AA were given to preterm infants, slower growth was reported.7,8 One-year-old children given DHA alone had lower language scores than those given DHA with AA or than controls.9 Therefore, a primary concern of giving ω-3 supplements is the risk of reducing AA levels in growing fetuses and children. Yet ω-3 intake during pregnancy might still have benefits.
Possible benefits of ω-3 supplementation during pregnancy
Prenatal ω-3 intake and preeclampsia. A negative relationship between PUFAs and preeclamspia, or pregnancy-induced hypertension, has been suggested through observational studies,10 but not shown in interventional trials.10-12 Recently, ω-3 intake was even associated with hypertensive disorders during pregnancy.13
Prenatal ω-3 intake and length of gestation. Several studies have suggested that maternal supplementation with ω-3 PUFAs can increase pregnancy duration by 4 to 6 days,5,11,14 but other studies found no such effect.15,16 No decrease in the rate of preterm deliveries, a much more important end point, was found. Among women with previous preterm deliveries, however, a nearly 50% reduction in prematurity was found.17
Prenatal ω-3 intake and fetal size. While several studies have addressed the potential effects of ω-3 supplementation on birth size, most did not find any effect.18 One recent study on LA with ALA supplementation during pregnancy noted higher birth weights in offspring.5
Prenatal ω-3 intake and brain function of offspring. Both ω-3 and ω-6 PUFAs are essential to normal brain development and function.1,2 Yet trials of postnatal ω-3 supplementation have yielded conflicting results. Studies of prenatal supplementation and children’s cognitive function are few and are mostly observational. The only interventional study that assessed maternal ω-3 supplementation and intelligence showed that, at 4 years old, children whose mothers took ω-3 supplements during pregnancy and lactation had higher cognitive function.19 Maternal DHA intake (but not infant intake) positively correlated with children’s mental processing ability. Another study, on prenatal supplementation with fish oil and infants’ visual function found no effect.16 It should be noted that, although statistically significant differences existed in some studies, changes were small and probably of little clinical importance.
Supplementation with ω-3 for pregnant women might influence several obstetric and neonatal characteristics, but conflicting results from too few studies prevent us from drawing definitive conclusions. Much evidence is still missing, such as which types of ω-3 fatty acids are of benefit (ALA, EPA, or DHA) and at what dosage; whether AA should also be added and at what exact ω-6–to–ω-3 ratio; when supplements should be given; and what benefits to mothers, infants, or children should be expected. Until evidence accumulates, no recommendation should be made to encourage pregnant women to take ω-3 fatty acid supplements.
1. Larque E, Demmelmair H, Koletzko B. Perinatal supply and metabolism of long-chain polyunsaturated fatty acids. Importance for the early development of the nervous system. Ann NY Acad Sci 2002;967:299-310.
2. McCann JC, Ames B. 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 behavioural tests in humans and animals. Am J Clin Nutr 2005;82:281–95.
3. Dubnov G, Berry EM. Polyunsaturated fatty acids, insulin resistance, and atherosclerosis: is inflammation the connecting link? Metabol Synd Relat Disord 2004;2:124-8.
4. Dubnov G, Berry EM. Omega 6/omega 3 fatty acid ratio: the Israeli paradox. World Rev Nutr Diet 2003;92:81-91.
5. De Groot RH, Hornstra G, van Houwelingen AC, Roumen F. Effect of alpha-linolenic acid supplementation during pregnancy on maternal and neonatal polyunsaturated fatty acid status and pregnancy outcome. Am J Clin Nutr 2004;79:251-60.
6. Van Houwelingen AC, Sorensen JD, Hornstra G, Simonis MM, Boris J, Olsen SF, et al. Essential fatty acid status in neonates after fish-oil supplementation during late pregnancy. Br J Nutr 1995;74:723–31.
7. Carlson SE, Cooke RJ, Werkman SH, Tolley EA. First year growth of preterm infants fed standard compared to marine oil n-3 supplemented formula. Lipids 1992;27:901–7.
8. Ryan AS, Montalto MB, Groh-Wargo S, Mimouni F, Sentipal-Walerius J, Doyle J, et al. Effect of DHA-containing formula on growth of preterm infants to 59 weeks postmenstrual age. Am J Hum Biol 1999;11:457–67.
9. 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):e59.
10. Makrides M, Gibson RA. Long-chain polyunsaturated fatty acid requirements during pregnancy and lactation. Am J Clin Nutr 2000;71(1 Suppl):307S-11S
11. 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.
12. Onwude JL, Lilford RJ, Hjartardottir H, Staines A, Tuffnell D. A randomised double blind placebo controlled trial of fish oil in high risk pregnancy. Br J Obstet Gynaecol 1995;102:95–100.
13. Olafsdottir AS, Skuladottir GV, Thorsdottir I, Hauksson A, Thorgeirsdottir H, Steingrimsdottir L. Relationship between high consumption of marine fatty acids in early pregnancy and hypertensive disorders in pregnancy. Br J Obstet Gynaecol 2006;113:301-9.
14. Olsen SF, Sorensen JD, Secher NJ, Hedegaard M, Henriksen TB, Hansen HS, et al. Randomised controlled trial of effect of fish-oil supplementation on pregnancy duration. Lancet 1992;339:1003-7.
15. Helland IB, Saugstad OD, Smith L, Saarem K, Solvoll K, Ganes T, et al. Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women. Pediatrics 2001;108:e82.
16. Malcolm CA, McCulloch DL, Montgomery C, Shepherd A, Weaver LT. Maternal docosahexaenoic acid supplementation during pregnancy and visual evoked potential development in term infants: a double blind, prospective, randomised trial. Arch Dis Child Fetal Neonatal Ed 2003;88:F383-90.
17. Olsen SF, Secher NJ, Tabor A, Weber T, Walker JJ, Gluud C. Randomised clinical trials of fish oil supplementation in high risk pregnancies. Fish Oil Trials in Pregnancy (FOTIP) Team. Br J Obstet Gynaecol 2000;107:382–95.
18. Decsi T, Koletzko B. n-3 fatty acids and pregnancy outcomes. Curr Opin Clin Nutr Metab Care 2005;8:161-6.
19. Helland IB, Smith L, Saarem K, Saugstad OD, Drevon CA. Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children’s IQ at 4 years of age. Pediatrics 2003;111:e39-44.