A randomised double blind placebo controlled trial of fish oil in high risk pregnancy. Effects of a combination of evening primrose oil (gamma linolenic acid) and fish oil (eicosapentaenoic + docahexaenoic acid) versus magnesium, and versus placebo in preventing pre-eclampsia. Randomised controlled trial of effect of fish-oil supplementation on pregnancy duration. A randomized trial of docosahexaenoic acid supplementation during the third trimester of pregnancy. Randomised clinical trials of fish oil supplementation in high risk pregnancies. Fish Oil Trials In Pregnancy (FOTIP) Team.
To determine whether n-3 fatty acid (EPA/DCHA) prophylaxis is beneficial in high risk pregnancies.
                A randomised, double blind, placebo controlled trial.
                Antenatal clinic of St James's University Hospital, Leeds.
                Two hundred and thirty-three pregnant women at high risk of developing proteinuric or nonproteinuric pregnancy induced hypertension or asymmetrical intrauterine growth retardation.
                Active treatment was 2.7 g of MaxEpa daily (1.62 g of eicosapentaenoic acid and 1.08 g of docosahexaenoic acid). Placebo were matching air-filled capsules.
                Occurrence of proteinuric, nonproteinuric pregnancy induced hypertension or birthweight < 3rd centile.
                There was no difference in an intention to treat analysis between the placebo and active treatment groups for occurrence of proteinuric pregnancy induced hypertension (relative risk (RR) = 0.88; 95% CI 0.47-1.66), nonproteinuric pregnancy induced hypertension (RR = 0.89; 95% CI 0.48-1.64), birthweight < 3rd centile (RR = 0.89; 95% CI 0.48-1.64), or the duration of pregnancy (difference of mean durations = 0.1 days; 95% CI -4.8 to 4.9 days). Analyses stratified by use of tobacco, and analyses excluding known major protocol violators gave essentially identical results.
                There is no evidence from this study for any useful effect of fish oil supplementation for women at high risk of adverse outcomes from a pregnancy, but a small protective effect remains a possibility. In a placebo controlled, partially double-blinded, clinical trial, a combination of evening primrose oil and fish oil was compared to Magnesium Oxide, and to a Placebo in preventing Pre-Eclampsia of Pregnancy. All were given as nutritional supplements for six months to a group of primiparous and multiparous pregnant women. Some of these women had personal or family histories of hypertension (21%). Only those patients who received prenatal care at the Central Maternity Hospital for Luanda were included in the study. Compared to the Placebo group (29%), the group receiving the mixture of evening primrose oil and fish oil containing Gamma-linolenic acid (GLA), Eicosapentaenoic acid (EPA), and Docosahexaenoic acid (DHA) had a significantly lower incidence of edema (13%, p = 0.004). The group receiving Magnesium Oxide had statistically significant fewer subjects who developed hypertension of pregnancy. There were 3 cases of eclampsia, all in the Placebo group. The high birthweights and long duration of pregnancy in the Faroe Islands led us to suggest that a high intake of marine-fat-derived n-3 fatty acids might prolong pregnancy by shifting the balance of production of prostaglandins involved in parturition. We have compared the effects on pregnancy duration, birthweight, and birth length of a fish-oil supplement, a control olive-oil supplement, and no supplementation. 533 healthy Danish women in week 30 of pregnancy were randomly assigned in a ratio of 2/1/1 to fish oil (four 1 g Pikasol capsules [containing 2.7 g n-3 fatty acids] per day), olive oil (four 1 g capsules per day), or no supplement. The three groups differed in mean length of gestation (p = 0.006), which was highest in the fish-oil group and lowest in the olive-oil group; the result was similar when the analysis was restricted to women with an estimate of gestation length based on early ultrasound findings (443 women). Pregnancies in the fish-oil group were on average 4.0 (95% confidence interval 1.5-6.4) days longer than those in the olive-oil group; the difference in birthweight was 107 (1-214) g. The effect of supplementation on length of gestation was influenced by intake of fish and of fish oil: the difference between fish-oil and other groups was increased by a low fish intake at baseline. 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 labour. To hypothesize that higher intake of docosahexaenoic acid, an n-3 long chain polyunsaturated fatty acid, would increase duration of gestation and birth weight in US women.
                This was a randomized, double-blind, controlled, clinical trial. Subjects were enrolled in an ambulatory clinic where they received prenatal care. This was a population-based sample. Most subjects received government assistance for medical care and most were black (73%). Subjects were enrolled between the 24th and 28th week of pregnancy and consumed docosahexaenoic acid (33 or 133 mg) from eggs until parturition. Gestational age and birth weight were the main study outcomes. Infant length and head circumference, preterm birth, and low birth weight were secondary outcomes.
                Eighty-three percent of subjects completed the study (291 of 350 enrolled). No subject was discontinued for an adverse event. After controlling for important predefined risk factors and confounding variables, gestation increased by 6.0 +/- 2.3 days (P =.009) in the higher docosahexaenoic acid group. Birth weight, length, and head circumference increased, but did not reach statistical significance (P =.06-.18), although the increases could be clinically important indications of enhanced intrauterine growth. No safety concerns were raised by the study.
                Duration of gestation increased significantly when docosahexaenoic acid intake was increased during the last trimester of pregnancy. The increase in gestation was similar to that reported for interventions with much larger amounts of n-3 long chain polyunsaturated fatty acids. To test the postulated preventive effects of dietary n-3 fatty acids on pre-term delivery, intrauterine growth retardation, and pregnancy induced hypertension.
                In six multicentre trials, women with high risk pregnancies were randomly assigned to receive fish oil (Pikasol) or olive oil in identically-looking capsules from around 20 weeks (prophylactic trials) or 33 weeks (therapeutic trials) until delivery.
                Nineteen hospitals in Europe.
                Four prophylactic trials enrolled 232, 280, and 386 women who had experienced previous pre-term delivery, intrauterine growth retardation, or pregnancy induced hypertension respectively, and 579 with twin pregnancies. Two therapeutic trials enrolled 79 women with threatening pre-eclampsia and 63 with suspected intrauterine growth retardation.
                The fish oil provided 2.7 g and 6.1 g n-3 fatty acids/day in the prophylactic and therapeutic trials, respectively.
                Preterm delivery, intrauterine growth retardation, pregnancy induced hypertension.
                Fish oil reduced recurrence risk of pre-term delivery from 33% to 21% (odds ratio 0.54 (95% CI 0.30 to 0.98)) but did not affect recurrence risks for the other outcomes (OR 1.26; 0.74 to 2.12 and 0.98; 0.63 to 1.53, respectively). In twin pregnancies, the risks for all three outcomes were similar in the two intervention arms (95% CI for the three odds ratios were 0.73 to 1.40, 0.90 to 1.52, and 0.83 to 2.32, respectively). The therapeutic trials detected no significant effects on pre-defined outcomes. In the combined trials, fish oil delayed spontaneous delivery (proportional hazards ratio 1.22; 1.07 to 1.39, P = 0.002).
                Fish oil supplementation reduced the recurrence risk of pre-term delivery, but had no effect on pre-term delivery in twin pregnancies. Fish oil had no effect on intrauterine growth retardation and pregnancy induced hypertension, affecting neither recurrence risk nor risk in twin pregnancies.
There is not enough evidence to support the routine use of marine oil, or other prostaglandin precursor, supplements during pregnancy to reduce the risk of pre-eclampsia, preterm birth, low birthweight or small-for-gestational age.