Omega Fatty Acids and Pregnancy: Research Review

Omega 3 and omega 6 fatty acids are important classes of dietary fats. Omega 3 fatty acids, like EPA and DHA, are well known for their anti-inflammatory properties and have been found to help lower the risk of pregnancy complications. Omega 6 fatty acids aren’t inherently bad, but without a healthy intake of omega 3 fatty acids, could promote inflammation.

Fish oil or omega 3 supplements are commonly part of a fertility routine. Within the body, omega 3 fatty acids have anti-inflammatory and immune-modulating effects. They also help to counterbalance the inflammatory activities of omega 6 fatty acids.

Physiology

Both omega 3 and omega 6 fatty acids are essential components of phospholipids present in all tissues. They both synthesize lipids, support normal cell function as well as fetal development¹. The precursors of the omega 3 and omega 6 pathway are both essential fatty acids (your body can not synthesize them) and must be obtained through your diet². The figure below summarizes how omega 3 (EPA and DHA) can help reduce maternal inflammation/ oxidative stress³.

During pregnancy, they directly act on placenta to increase antioxidant production that will counteract the effects of reactive oxygen species (ROS). Resolvins and protectins (products of DHA and EPA metabolism) can reduce placental PGE2 (the prostaglandin associated with partition) and reduce placental inflammation. Altogether, these effects can reduce the risk of pregnancy losses or obstetrical complications.   

High leptin levels have been shown to disrupt folliculogenesis (maturation of follicle leading to the production of a fertilizable egg)¹⁸. This translates into “poor” embryo quality and ultimately higher chances for pregnancy failure¹⁹.

On the other hand, in nonoverweight PCOS women, lower leptin serum levels put them at higher risk for lower fertilization rate as the follicle maturation requires physiologic levels of leptin²⁰. Interestingly, leptin levels are negatively associated with EPA and DHA levels²¹. Further, studies find that a diet rich in Fish can significantly lower leptin levels²². Lastly, a large meta-analysis showed that omega 3 supplementation significantly reduced leptin levels²³.

Published clinical data

In fertility, an increased omega 3 intake prior to conception was shown to positively impact embryo morphology in a study on women undergoing IVF cycle⁴. Omega 3 appear to promote vascular development in the endometrium as seen by an in vitro study⁵.

Many other studies showed that a higher omega 3 intake:

• can reduce the risk of miscarriage⁶.
• increase uterine blood flow⁷.
• increase the length of pregnancy and reduce preterm birth^8-10.
• reduce placental inflammation when taking during the first trimester and through the pregnancy¹¹.

EPA and DHA are precursors to several mediators triggering anti-inflammatory¹² and anti-oxidative actions^13-14 and have been shown to play key roles in preventing pregnancy complications associated with excessive systemic and placental inflammation¹⁵.

In the above-mentioned review¹⁰, the authors reported that fish oil intake especially docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA):

• reduce by 42% the risk of early preterm births (<34 weeks)!
• reduce by 11% the risk of preterm births (<37 weeks).
• reduce by 25% the risk for perinatal deaths.
• reduce by 11% the risk for low birth weight babies.

Knowing that labor is a pro-inflammatory process, maintaining a balance between omega 3 and omega 6 levels is crucial to allow a normal gestation length¹⁶. Further, DHA may be crucial to support fetal brain development¹⁷.

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References

1. Innis SM,Essential fatty acid transfer and fetal development. Placenta 26 (2005). S70–S75.
2. Sprecher H,D.Luthria,B.Mohammed,S.Baykousheva,Reevaluation of the pathways for the biosynthes is of polyunsaturated fatty acids,J.LipidRes.36 (1995)2471–2477.
3. Leghi GE, Muhlhausler BS. The effect of n-3 LCPUFA supplementation on oxidative stress and inflammation in the placenta and maternal plasma during pregnancy. Prostaglandins Leukot Essent Fatty Acids. 2016 Oct; 113:33-39.
4. Hammiche F, Vujkovic M, Wijburg W, de Vries JH, Macklon NS, Laven JS, Steegers-Theunissen RP. Increased preconception omega-3 polyunsaturated fatty acid intake improves embryo morphology.
5. Johnsen GM, Basak S, Weedon-Fekjær MS, Staff AC, Duttaroy AK. Docosahexaenoic acid stimulates tube formation in first trimester trophoblast cells, HTR8/SVneo. Placenta. 2011 Sep;32(9):626-32.
6. Di Cintio E, Parazzini F, Chatenoud L, Surace M, Benzi G, Zanconato G, La Vecchia C. Dietary factors and risk of spontaneous abortion. Eur J Obstet Gynecol Reprod Biol. 2001 Mar;95(1):132-6.
7. Lazzarin N, Vaquero E, Exacoustos C, Bertonotti E, Romanini ME, Arduini D. Low-dose aspirin and omega-3 fatty acids improve uterine artery blood flow velocity in women with recurrent miscarriage due to impaired uterine perfusion. Fertil Steril. 2009 Jul;92(1):296-300.
8. Olsen SF, Sørensen JD, Secher NJ, Hedegaard M, Henriksen TB, Hansen HS, Grant A. Randomised controlled trial of effect of fish-oil supplementation on pregnancy duration. Lancet. 1992 Apr 25;339(8800):1003-7.
9. Kar S, Wong M, Rogozinska E, Thangaratinam S. Effects of omega-3 fatty acids in prevention of early preterm delivery: a systematic review and meta-analysis of randomized studies. Eur J Obstet Gynecol Reprod Biol. 2016 Mar; 198:40-46.
10. Middleton P, Gomersall JC, Gould JF, Shepherd E, Olsen SF, Makrides M. Omega-3 fatty acid addition during pregnancy. Cochrane Database Syst Rev. 2018 Nov 15;11:CD003402
11. Haghiac M, Yang XH, Presley L, Smith S, Dettelback S, Minium J, Belury MA,Catalano PM, Hauguel-de Mouzon S. Dietary Omega-3 Fatty Acid Supplementation Reduces Inflammation in Obese Pregnant Women: A Randomized Double-Blind Controlled Clinical Trial. PLoS One. 2015 Sep 4;10(9): e0137309.
12. Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol. 2008 May;8(5):349-61.
13. Ambrozova G, Pekarova M, Lojek A. Effect of polyunsaturated fatty acids on the reactive oxygen and nitrogen species production by raw 264.7 macrophages. Eur J Nutr. 2010 Apr;49(3):133-9.
14. Komatsu W, Ishihara K, Murata M, Saito H, Shinohara K. Docosahexaenoic acid suppresses nitric oxide production and inducible nitric oxide synthase expression in interferon-gamma plus lipopolysaccharide-stimulated murine macrophages by inhibiting the oxidative stress. Free Radic Biol Med. 2003 Apr 15;34(8):1006-16.
15. Keelan JA, Mas E, D’Vaz N, Dunstan JA, Li S, Barden AE, Mark PJ, Waddell BJ, Prescott SL, Mori TA. Effects of maternal n-3 fatty acid supplementation on placental cytokines, pro-resolving lipid mediators and their precursors. Reproduction. 2015 Feb;149(2):171-8.
16. Zhou J, Best K, Gibson R, McPhee A, Yelland L, Quinlivan J, et al. Study protocol for a randomized controlled trial evaluating the effect of prenatal omega-3 LCPUFA supplementation to reduce the incidence of preterm birth: the ORIP trial. BMJ Open 2017;7(9): e018360.
17. Shulkin M, Pimpin L, Bellinger D, Kranz S, Fawzi W, Duggan C, et al. n-3 fatty acid supplementation in mothers, preterm Infants, and term Infants and childhood psychomotor and visual development: a systematic review and meta-analysis. Journal of Nutrition 2018;148(3): 409–18.