Fish Oil in Various Doses or Flax Oil in Pregnancy and Timing of Spontaneous
Delivery: A Randomized Controlled Trial
[Obstetrics: Preconception and Prenatal Care]
Knudsen, V K.; Hansen, H S.; Østerdal, M L.; Mikkelsen, T B.; Mu, H; Olsen,
S F.
Maternal Nutrition Group, Department of Epidemiology Research, Statens Serum
Institut, Copenhagen S, Denmark; the Department of Pharmacology, Danish
University of Pharmaceutical Sciences, Copenhagen, Denmark; and the
Biochemistry and Nutrition Group, BioCentrum-DTU, Technical University of
Denmark, Lyngby, Denmark
BJOG 2006;113:536543
ABSTRACT http://gateway.ut.ovid.com/gw1/ovidweb.cgi#toc#toc
Previous studies have suggested that a diet containing long-chain n-3 fatty
acids derived from fish oil may delay spontaneous delivery. The
investigators, in a randomized, controlled trial, addressed this hypothesis
and also sought to determine whether alpha-linolenic acid (ALA), in the form
of flax oil capsules, might have the same effect. Participants were 3098
women who reported a low intake of fish and who were randomized to receive
one of 5 doses (0.1, 0.3, 0.7, 1.4, or 2.8 g) of eicosapentaenoic acid and
docosahexaenoic acid daily, 2.2 g daily of ALA, or no treatment.
Supplementation began at 17 to 27 weeks gestation and continued until
delivery. The treatment groups were similar with respect to age, parity,
gestational age, fish consumption, body mass index, and smoking.
Analyzing singleton live-born pregnancies, no significant difference in
gestational length was found between control women and any of the treatment
groups whether comparing mean gestational ages or hazard rates of
spontaneous delivery. This held for both intention-to-treat analyses and
analyses based on the participants only. There were no apparent differences
in intake of any of the fatty acids between the treatment groups. The
difference in time to spontaneous delivery between pregnant women given the
highest dose of fish oil and control women was less than 1 day. A majority
of women in the treatment groups failed to continue taking their capsules up
to the time of delivery.
These findings may indicate that there is in fact no meaningful effect of
dietary n-3 fatty acids on the timing of spontaneous delivery. It also is
possible that there is a rapidly diminishing effect that depends on
continued supplementation.
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EDITORIAL COMMENT http://gateway.ut.ovid.com/gw1/ovidweb.cgi#toc#toc
(For some time, there has been interest in the potential for the n-3, or
omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid
(DHA), to prolong gestation and/or prevent preterm birth. Marine foods are a
rich source of both EPA and DHA, and Olsen and his colleagues observed that
birth weight and gestational age was higher in the Faroe Islands, which are
between Norway and Iceland and where the rate of consumption of marine food
is very high, than in Denmark, where it is lower (J Epidemiol Community
Health 1985;39:27). Pregnant Faroese women had higher omega-3/omega-6
erythrocyte ratios, and among Danish women, an increased ratio was
associated with longer gestation (Olsen SF, et al. Am J Obstet Gynecol
1991;164:1203). This association is plausible. As opposed to omega-6 fatty
acids, which are proinflammatory, omega-3 fatty acids are antiinflammatory
and suppress the production of inflammatory cytokines and prostaglandins E
and F. Thus, the overall intake of omega-3 fatty acids, and the proportion
of omega-3 to omega-6 fatty acids in the diet and in various tissue
compartments, might influence the onset of parturition.
However, the observational data to support that dietary omega-3 intake
influences the length of gestation is not all one-sided, because there are
studies that report no association (eg, Oken E, et al. Am J Epidemiol
2004;160:774). Whether omega-3 supplementation can prolong gestation or
prevent preterm birth has also been the subject of a fair number of
randomized studies. The first was conducted in 1938 and 1939 and reanalyzed
with an eye to gestational length some 50 years later (Olsen SF, Secher NJ.
Br J Nutr 1990;64:599). In this trial, over 5500 pregnant women were
randomly allocated to daily supplementation with halibut oil, vitamins, and
minerals or to no supplementation. Women allocated to supplementation were
20% less likely to deliver before 40 weeks, but no information was available
on preterm delivery, and neither infant birth weights nor perinatal
mortality differed between groups. The strongest experimental support for
the prevention of preterm birth with omega-3 fatty acids is the trial of
Olsen et al (BJOG 2000;107:382) in which 232 women with a history of preterm
birth were randomly allocated to a daily fish oil supplement containing 1300
mg of EPA and 900 mg DHA or matching placebo (olive oil). In this trial,
women allocated to fish oil had a significantly reduced risk of preterm
birth (37 weeks, 21% vs 33%) and early preterm birth (34 weeks,
