Omega-3 Fatty Acids and Pregnancy
Omega-3 Fatty Acids and Pregnancy
By Jerry Cott, PhD
The relative dearth of omega-3 (n-3) fatty acids in a typical American diet may have an effect on several diseases and conditions. Six of 10 prospective cohort studies have reported an inverse relationship between fish intake and cardiovascular disease mortality.1 Depletion of n-3 fatty acids, particularly docosahexaenoic acid (DHA), may be important in the etiology of depression, aggression, schizophrenia, and other mental and neurological disorders.2 Insufficient intake of n-3 fatty acids also may be a risk factor in preterm birth.
Olsen et al suggested that the type of fatty acids in the diet may influence the length of gestation.3 In the Faeroe Islands, women deliver their babies after the customary 40 weeks of gestation while a high percentage of women in other parts of Denmark go into labor almost a week earlier. The difference was thought to be a result of the marine diet eaten on the Faeroes. Olsen et al hypothesized that a high intake of marine-derived n-3 fatty acids might prolong pregnancy by shifting the balance of production of prostaglandins involved in parturition. Prostacyclin, an omega-3-derived eicosanoid, is a vasodilator and smooth muscle relaxer, so it would be expected to work in the opposite way to the omega-6-derived thromboxane, a vasoconstrictor.4
In a clinical trial, these same investigators tested the effects of a fish oil supplement on pregnancy duration, birthweight, and birth length.5 Five hundred thirty-three healthy Danish women in week 30 of pregnancy were randomized to four 1 g capsules/d of a fish oil supplement (Pikasol, containing 2.7 g n-3 fatty acids), four 1 g olive oil capsules/d (control), or no supplementation. At the end of this study, the mean length of gestation differed by ANOVA (P = 0.006). Gestation was longest in the fish oil group and lowest in the olive oil group. The result was similar when the analysis was limited to the 443 women who underwent early ultrasound estimates of gestational age. Pregnancies in the fish oil group averaged 4.0 days longer (95% CI 1.5-6.4) than those in the olive oil group and the birthweight was 107 g (range 1-214 g) higher. The difference between the fish oil group and the other groups was increased by a low fish intake at baseline. Thus, fish oil supplementation in the third trimester seems to prolong pregnancy without detrimental effects on the growth of the fetus or on the course of labor.
Although a difference of four days in term deliveries may be of little clinical significance, fish oil may be helpful in preventing recurrent preterm birth. In the Fish Oil Trials In Pregnancy (FOTIP) study, Olsen et al examined the preventive effects of dietary n-3 fatty acids on preterm delivery and several other outcomes.6 Four prophylactic trials included 232 women with a previous preterm delivery who were randomized to 2.7 g/d n-3 fatty acids or olive oil placebo, starting from about 20 weeks. Fish oil reduced the risk of preterm delivery from 33.3% to 21.3% (odds ratio 0.54, 95% CI 0.30-0.98).
Pregnancy-Induced Hypertension and Intrauterine Growth Retardation
In preeclampsia, a disturbance in thromboxane and prostacyclin biosynthesis has been observed. Sorensen et al studied whether fish oil supplementation in late pregnancy interferes with maternal and fetal production of the omega-6-derived thromboxane A2 and prostacyclin I2.7 Forty-seven women in the 13th week of pregnancy were randomly assigned to receive fish oil (Pikasol), olive oil, or no supplementation. At the 37th week, the mean concentrations of the EPA-derived metabolites, thromboxane B3, and prostacyclin I3, were two to three times higher (P < 0.001) in the fish oil group compared with combined control groups. There were no significant effects of fish oil on the prostacyclin I2 metabolite. In umbilical cord blood, the mean concentration of thromboxane B2 was significantly lower in the group receiving fish oil (P = 0.03) compared to other groups. The authors concluded that fish oil was metabolized to the eicosanoids thromboxane A3 and prostacyclin I3 in pregnant women. Thus, there are theoretical reasons why fish oil may help to prevent or treat pregnancy-induced hypertension (PIH) or intrauterine growth retardation (IUGR).
In supplementation trials, however, fish oil supplementation does not reduce the risk of PIH or IUGR. In a double-blind trial, 223 pregnant women at high risk for developing PIH or IUGR were randomized to 2.7 g/d fish oil (MaxEpa, containing1.62 g of eicosapentaenoic acid [EPA] and 1.08 g of DHA) or placebo (a matching air-filled capsule).8 In an intention-to-treat analysis, there was no difference between the placebo and active treatment groups for occurrence of proteinuric PIH, nonproteinuric PIH, birthweight < 3rd percentile, or the duration of pregnancy. There was no evidence from this study for a useful effect of fish oil supplementation.
The FOTIP study tested the preventive effects of dietary n-3 fatty acids on preterm delivery, IUGR, and PIH.6 In six multicenter trials, women with high-risk pregnancies were randomly assigned to receive fish oil (2.7 g/d n-3 fatty acids in the prophylactic trials and 6.1 g/d n-3 fatty acids in the therapeutic trials) or olive oil from about 20 weeks (prophylactic trials) or 33 weeks (therapeutic trials) before delivery. Four prophylactic trials enrolled a total of 232 women with a previous preterm delivery, 280 women with IUGR, 386 women with PIH, and 579 women with twin pregnancies. Two therapeutic trials enrolled a total of 79 women with preeclampsia and 63 with suspected IUGR. In women with a previous preterm birth, fish oil reduced the risk of preterm birth but did not affect recurrence risks for the other outcomes. In twin pregnancies, there were no differences between groups in any outcome. The therapeutic trials detected no significant differences between groups in predefined outcomes. In the combined trials, fish oil delayed spontaneous delivery (proportional hazards ratio 1.22; P = 0.002). Thus, fish oil supplementation reduced the risk of preterm delivery in women with a previous preterm birth, but had no effect on preterm delivery of twins. Fish oil had no effect on IUGR or PIH.
In Western societies, most people eat more solid fats (rich in saturated fatty acids) and less soft fats (rich in polyunsaturated fatty acids) than they did a century or two ago. In addition, people now eat different types of polyunsaturated fats than they did previously. Today, the average diet contains an excess of corn, soy, or other plant food oils that are rich in omega-6 fatty acids, but low in omega-3 fatty acids (found in fish and flaxseed oil). Interestingly, a vegetarian diet may exacerbate this problem because vegetarians have lower intakes of n-3 fatty acids than omnivores.9 Vegetarians may want to consider adding flaxseed to their diets. The alpha-linolenic acid (ALA) from flaxseed is converted to EPA and DHA in the body.
Reddy et al examined the effect of a maternal vegetarian diet on pregnancy outcomes and essential fatty acid status of the newborn.10 Dietary intake and the fatty acid composition of plasma phospholipids were determined in a group of 24 South Asian vegetarian and 24 white omnivore non-pregnant premenopausal women. Umbilical cords and cord blood were collected at delivery from another group of 48 South Asian vegetarian women and 98 white omnivores from the same catchment area along with details of antenatal history and the outcome of pregnancy. The fatty acid composition of the cord blood and phospholipids in cord plasma were analyzed in a subset of 32 pairs of subjects, who were matched for maternal age, gestational age, parity, and sex of infant. Intakes of linoleic acid (LA) expressed as a proportion of the dietary energy and the ratio of LA to ALA were higher in the vegetarian women, and EPA and DHA were absent from their diets. (See Table 1.) Compared with omnivores, vegetarians had a higher concentration and proportion of LA and lower concentration and proportion of EPA and DHA in plasma phospholipids, plasma free fatty acid, and total plasma lipids. The proportion of DHA was lower (P > 0.001) but that of docosapentaenoic acid was greater (P < 0.001) in the cord blood of vegetarians compared to omnivores.
Table 1: Expressions of omega-3 fatty acids |
|
Fatty Acid |
Expression (# carbons:# double bonds, location of first double bond) |
linoleic acid (LA) | 18:2n-6 |
arachidonic acid (AA) | 20:4n-6 |
docosapentaenoic acid | 22:5n-6 |
alpha-linolenic acid (ALA) | 18:3n-3 |
eicosapentaenoic acid (EPA) | 20:5n-3 |
docosahexaenoic acid (DHA) | 22:6n-3 |
The duration of gestation was 5.6 days shorter, and birth weight, head circumference, and length were lower in the infants born to South Asian vegetarians even after adjusting for maternal height, duration of gestation, parity, gender of infants, and smoking habits. Multivariate analysis did not reveal any relationship between the proportions of DHA in plasma or cord artery phospholipids and the infants’ birthweight or head circumference. This study showed that vegetarians give birth to infants with less DHA in their plasma and cord artery phospholipids, but this did not appear to be independently related to pregnancy outcome.
Depletion of maternal omega-3 fatty acids has been noted during pregnancy.11 The physiology of pregnancy involves the mobilization of polyunsaturated fatty acids from maternal stores to the fetus, and supplementation with essential fatty acids may ensure adequate supplies for the needs of both mother and fetus.12,13 Hornstra et al demonstrated that maternal essential fatty acids, especially DHA, progressively decrease during pregnancy.14 Since breast milk has relatively high concentrations of DHA and EPA,15 decreased levels of DHA in plasma and erythrocytes may remain low for some time postpartum, particularly in lactating women, and may contribute to postpartum depression.2 The World Health Organization recommends that DHA and EPA be added to infant formulas. European infant formulas routinely are fortified with these fatty acids, but to date the FDA has not allowed the addition of either DHA or EPA to infant formulas sold in the United States. These n-3 fatty acids are necessary for optimal development of the fetal and neonatal visual and nervous systems.12,16
Pregnant women who wish to supplement their diet with omega-3 fatty acids have several choices. One option is to eat three servings of fish a week (more than three servings is not recommended for pregnant women because of possible mercury contamination of fish). Another option is to take an n-3 dietary supplement every day (the Danish studies were based on a daily dose of 4 g of fish oil containing a total of 2.4 g of n-3 fatty acids). Fish oil supplements would not be expected to contain mercury, which does not concentrate in fat; however, polychlorinated biphenyls (PCBs) do accumulate in fat. For that reason, flaxseed oil may be a better choice than either of the above. It may be beneficial for lactating women to continue omega-3 supplementation for as long as they breastfeed, or if not breast-feeding to use an infant formula fortified with n-3 fatty acids.
Dr. Cott is Scientific Director and Chief Science Officer at Scientific Herbal Products, Inc. in College Park, MD.
References
1. Albert CM, et al. Fish consumption and risk of sudden cardiac death. JAMA 1998;279:23-28.
2. Cott J. Omega-3 fatty acids and psychiatric disorders. Altern Ther Women’s Health 1999;1:97-101.
3. Olsen SF, et al. Gestational age in relation to marine n-3 fatty acids in maternal erythrocytes: A study of women in the Faroe Islands and Denmark. Am J Obstet Gynecol 1991;164(5 Pt 1):1203-1209.
4. Mills JL, et al. Prostacyclin and thromboxane changes predating clinical onset of preeclampsia: A multicenter prospective study. JAMA 1999;282:356-362.
5. Olsen SF, et al. Randomised controlled trial of effect of fish-oil supplementation on pregnancy duration. Lancet 1992;339:1003-1007.
6. Olsen SF, et al. Randomised clinical trials of fish oil supplementation in high risk pregnancies. Fish Oil Trials In Pregnancy (FOTIP) Team. BJOG 2000;107:382-395.
7. Sorensen JD, et al. Effects of fish oil supplementation in the third trimester of pregnancy on prostacyclin and thromboxane production. Am J Obstet Gynecol 1993;168(3 Pt 1):915-922.
8. Onwude JL, et al. A randomised double blind placebo controlled trial of fish oil in high risk pregnancy. Br J Obstet Gynaecol 1995;102:95-100.
9. Sanders TA. Essential fatty acid requirements of vegetarians in pregnancy, lactation, and infancy. Am J Clin Nutr 1999;70(3 Suppl):555S-559S.
10. Reddy S, et al. The influence of maternal vegetarian diet on essential fatty acid status of the newborn. Eur J Clin Nutr 1994;48:358-368.
11. Otto SJ, et al. Maternal and neonatal essential fatty acid status in phospholipids: An international comparative study. Eur J Clin Nutr 1997;51:232-242.
12. Holman RT, et al. Deficiency of essential fatty acids and membrane fluidity during pregnancy and lactation. Proc Natl Acad Sci U S A 1991;88:4835-4839.
13. Al MD, et al. Maternal essential fatty acid patterns during normal pregnancy and their relationship to the neonatal essential fatty acid status. Br J Nutr 1995;74:55-68.
14. Hornstra G, et al. Essential fatty acids in pregnancy and early human development. Eur J Obstet Gynecol Reprod Biol 1995;61:57-62.
15. Salem N. Omega-3 fatty acids: Molecular and biochemical aspects. In: Spiller GA, Scala J. New Protective Roles for Selected Nutrients. New York: Alan E. Liss, Inc.: 1989: 109-228.
16. Hornstra G. Essential fatty acids in mothers and their neonates. Am J Clin Nutr 2000;71(5 suppl):126S-129S.
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