Randomised controlled trial of effect of fish-oil supplementation on pregnancy duration. Randomised clinical trials of fish oil supplementation in high risk pregnancies. Fish Oil Trials In Pregnancy (FOTIP) Team. A randomised double blind placebo controlled trial of fish oil in high risk pregnancy. Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women. Nutritional factors and rest reduce pregnancy-induced hypertension and pre-eclampsia in positive roll-over test primigravidas. First year growth of preterm infants fed standard compared to marine oil n-3 supplemented formula. Growth and development of preterm infants fed infant formulas containing docosahexaenoic acid and arachidonic acid. 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. Randomized trial of administration of prostaglandin E2 gel for induction of labor in the morning or the evening.
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 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. 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. There have been indications that high intake of n-3 long-chain polyunsaturated fatty acids (PUFAs) during pregnancy may increase birth weight and gestational length. In addition, n-3 long-chain PUFAs may be important for the neurobiological development of the infants. High levels of docosahexaenoic acid (DHA, 22:6 n-3) are found in the gray matter of the cerebral cortex and in the retina, and it seems as if the availability of long-chain PUFAs may be limiting cerebral development. The fetus and the newborn are dependent on a high supply from their mothers, either via the placenta or via breast milk. We supplemented pregnant and lactating women with n-3 or n-6 long-chain PUFAs to evaluate the effect on birth weight, gestational length, and infant development.
                We performed a double-blind, randomized study recruiting 590 pregnant, healthy, nulli- or primiparous women (19-35 years old) in weeks 17 to 19 of pregnancy. The women were provided 10 mL of either cod liver oil or corn oil daily until 3 months after delivery.
                Primary outcomes were gestational length and birth weight. Electroencephalography (EEG) was done on the second day of life and at 3 months of age. Novelty preference (Fagan test) was used as an indicator of cognitive function at 6 and 9 months of age. The fatty acid pattern in umbilical plasma phospholipids and in breast milk was measured, and dietary assessments were performed, both on the mothers during pregnancy and on the infants at 3 months of age. The growth of the infants was followed up to 1 year of age.
                Three hundred forty-one mothers took part in the study until delivery. There were no significant differences in maternal body mass index before pregnancy and at birth, or parity between the 2 groups. Smoking habits and parental education were also similar in the 2 groups. The mean age of the mothers receiving cod liver oil was, by chance, 1 year higher than the age of the mothers receiving corn oil (28.6 [3.4] vs 27.6 [3.2] years). The maternal dietary intake in the 2 groups receiving cod liver oil or corn oil was similar, except for the supplementation. There were no differences in gestational length or birth weight between the cod liver oil group and the corn oil group (279.6 [9.2] vs 279.2 [9.3] days; 3609 [493] vs 3618 [527] g, respectively). Birth length, head circumference, and placental weight were also similar in the 2 groups. The concentrations of the n-3 fatty acids eicosapentaenoic acid (20:5 n-3), docosapentaenoic acid (22:5 n-3), and DHA in umbilical plasma phospholipids were higher in the cod liver oil group compared with the corn oil group (10.8 [7.6] vs 2.5 [1.8] microg/mL, 5.0 [2.6] vs 2.9 [1.3] microg/mL, 55.8 [20.6] vs 45.3 [12.8] microg/mL, respectively). Neonates with high concentration of DHA in umbilical plasma phospholipids (upper quartile) had longer gestational length than neonates with low concentration (lower quartile; 282.5 [8.5] vs 275.4 [9.3] days). No differences in EEG scores or Fagan scores were found, but neonates with mature EEG (N = 70) had a higher concentration of DHA in umbilical plasma phospholipids than neonates with immature EEG (N = 51) on the second day of life. Dietary information from 251 infants at 3 months of age was collected and 85% of these infants were exclusively breastfed, in addition to 12% who were partly breastfed. The breast milk of mothers supplemented with cod liver oil contained more n-3 long-chain PUFAs and less n-6 long-chain PUFAs than breast milk of mothers supplemented with corn oil. There were no significant differences in infant growth during the first year of life between the 2 groups.
                This study shows neither harmful nor beneficial effects of maternal supplementation of long-chain n-3 PUFAs regarding pregnancy outcome, cognitive development, or growth, as compared with supplementation with n-6 fatty acids. However, it confirms that DHA concentration may be related to gestational length and cerebral maturation of the newborn. The possibility of reducing pregnancy-induced hypertension and preeclampsia in primigravidas with low doses of nutritional factors and relative rest in the left lateral position was investigated in a randomized controlled, double-blind trial.
                Seventy-four normotensive women at 28-29 weeks' gestation, judged to be at risk of PIH or pre-eclampsia because they presented with a mean blood pressure of 80 mmHg or higher and a positive roll-over test, were studied. The treatment protocol was received by 37 women and the other 37 women received standard antenatal control until delivery.
                Twenty-nine (78.3%) women in the control group developed PIH and/or pre-eclampsia, as opposed to only 4 (10.8%) cases in the treatment group (P < 0.001). There were no adverse effects of treatment in mothers or in infants.
                This protocol reduces PIH and pre-eclampsia in primigravidas judged to be at risk of hypertension. Further studies are required to evaluate prostacyclin and prostaglandin E2 changes. Very low birth weight (VLBW) infants (748-1390 g, n = 65) were randomly assigned to receive control or marine oil-supplemented formula when they achieved intakes > 454 kJ (110 kcal)/kg/d of a formula designed for VLBW infants. Study formulas with or without marine oil were provided until 79 wk of postconceptional age (PCA), first in a formula designed for preterm infants followed by a formula designed for term infants. Infants were studied at regular intervals through 92 wk PCA. Weight, length, and head circumference were determined by standardized procedures and normalized to the National Center for Health Statistics figures for growth of infants born at term of the same age and gender. Mean normalized weight, weight-to-length, and head circumference were greatest at 48 wk and decreased thereafter. The decline in normalized weight was greater in infants fed the marine oil-supplemented formula. Beginning at 40 wk, marine oil-supplemented infants compared to controls had significantly poorer Z-scores for weight, length and head circumference. In addition, birth order (negatively) and maternal height (positively) influenced weight and length achievement in infancy as shown previously in infants born at term. To evaluate safety and benefits of feeding preterm infants formulas containing docosahexaenoic acid (DHA) and arachidonic acid (ARA) until 92 weeks postmenstrual age (PMA), with follow-up to 118 weeks PMA.
                This double-blinded study of 361 preterm infants randomized across three formula groups: (1) control, no supplementation; (2) algal-DHA (DHA from algal oil, ARA from fungal oil); and (3) fish-DHA (DHA from fish oil, ARA from fungal oil). Term infants breast-fed > or =4 months (n = 105) were a reference group. Outcomes included growth, tolerance, adverse events, and Bayley development scores.
                Weight of the algal-DHA group was significantly greater than the control group from 66 to 118 weeks PMA and the fish-DHA group at 118 weeks PMA but did not differ from term infants at 118 weeks PMA. The algal-DHA group was significantly longer than the control group at 48, 79, and 92 weeks PMA and the fish-DHA group at 57, 79, and 92 weeks PMA but did not differ from term infants from 79 to 118 weeks PMA. Supplemented groups had higher Bayley mental and psychomotor development scores at 118 weeks PMA than did the control group. Supplementation did not increase morbidity or adverse events.
                Feeding formulas with DHA and ARA from algal and fungal oils resulted in enhanced growth. Both supplemented formulas provided better developmental outcomes than unsupplemented formulas. 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. To compare the outcome of induction of labor and patient's preferences using a protocol with the first dose of prostaglandin E2 endocervical gel in the evening versus a protocol with the first dose in the morning.
                We performed a randomized trial comparing administration of prostaglandin E2 endocervical gel in the morning with administration of prostaglandin E2 gel in the evening, followed if necessary by a second dose being given after six hours if labor had not started or the cervix was still unripe. Formal induction of labor by amniotomy and oxytocin infusion was performed the morning after the initial prostaglandin E2 dose. Patients' preferences were assessed using a questionnaire that was completed after delivery.
                Tertiary care hospital in the Netherlands with 1,600 deliveries per year.
                One-hundred and twenty-six women with viable singleton pregnancies at term who had induction of labor with prostaglandins.
                Time of delivery (daytime, evening or night) and patient's satisfaction.
                Fifty-eight women were allocated for administration of gel in the morning, whereas 68 had their gel in the evening. Administration of gel in the evening did not significantly reduce delivery between 23.00 hours and 08.00 hours, although there was a reduction in delivery between 23.00 hours and 08.00 hours in nulliparae. None of the multiparous women delivered between 18.00 hours and 23.00 hours after induction of labor in the evening. The relative risk for delivery by vacuum or forceps was increased after allocation of gel in the evening (4.2; 95% confidence limits 1.4 to 13). Patients' preferences favored administration of gel in the morning.
                There was no benefit in starting induction of labor with prostaglandin E2 in the evening, compared with starting in the morning.
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.