Randomised clinical trials of fish oil supplementation in high risk pregnancies

Abstract

Objective To test the postulated preventive effects of dietary n-3 fatty acids on pre-term delivery, intrauterine growth retardation, and pregnancy induced hypertension.Design 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. Setting Nineteen hospitals in Europe.Samples Four prophylactic trials enrolled 232,280, and 386 women who had experienced previous preterm 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.Interventions The fish oil provided 2.7 g and 6.1 g n-3 fatty aciddday in the prophylactic and therapeutic trials, respectively. Main outcome measures Preterm delivery, intrauterine growth retardation, pregnancy induced hypertension.Results 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).Conclusions 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.

Duration of pregnancy in relation to fish oil supplementation and habitual fish intake: a randomised clinical trial with fish oil

“…Subjects and design of study The overall design was that of a multicentre, randomised, clinical intervention study (Olsen et al, 2000). It was hospital based with centres in Denmark, Scotland, Sweden, England, Russia, Italy, Belgium, Holland, and Norway, and approved by each local ethical committee.…”

“…Restricted blockwise computer-generated randomisation (1:1, individual-based) was employed within strata defined by cross tabulating clinical centres against the six original (Olsen et al, 2000) clinical groups (trials A-F). Within each stratum, the size of the first block was always four, after which block sizes of four, six, and eight occurred in random order.…”

“…The hypothesis has been supported by some (Olsen et al, 1992;Olsen et al, 2000;Smuts et al, 2003) but not all (Bulstra-Ramakers et al, 1995;Onwude et al, 1995;Helland et al, 2001;Knudsen et al, 2006) randomised controlled trials (Olsen 2004;Makrides et al, 2006;Szajewska et al, 2006), and by some (Olsen et al, 1991;Olsen and Secher 2002) but, again, far from all (Olsen 1994;Olsen et al, 1995;Bjerregaard and Hansen 1996;Oken et al, 2004;Rogers et al, 2004;Thorsdottir et al, 2004) observational studies. Two recent meta-analyses of controlled trials concluded that fish oil probably prolongs pregnancy, but that the size of this effect, estimated from the pooled analyses, is most probably too small to be of any clinical significance (Makrides et al, 2006;Szajewska et al, 2006).…”

“…None of the other published trials addressed this issue however, probably because baseline data on diet were unavailable. We, therefore, made a reanalysis of data from a large multicentre European trial where such data were available for a large proportion of the women, but had not been used in the primary report as they were not part of the prior hypotheses (Olsen et al, 2000).…”

Effect of placental function on fatty acid requirements during pregnancy

“…The fatty acid composition of the maternal diet during pregnancy is thought to affect a number of pregnancy outcomes including the rate of growth in utero (Carlson et al, 1992;Smuts et al, 2003) and the length of gestation (Olsen et al, 2000;Olsen & Secher, 2002), but the outcomes most often studied in relation to LCPUFA in early life are visual and intellectual development, largely as a result of the observation that tissues such as the brain and retina require a high concentration of DHA to function properly (Innis, 1991). Although the brain of the newborn has a relatively high concentration of DHA, the absolute accretion during in utero life is small.…”