Randomised clinical trials of fish oil supplementation in high risk pregnancies


  • For a list of all members of the Fish Oil Trials In Pregnancy (FOTIP) Team see page 393

Correspondence: Dr S. F. Olsen (email: sfo@ssi.dk), Maternal Nutrition Group, Danish Epidemiology Science Centre, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark

Correspondence: Professor N. J. Secher (email: njsecher@dadlnet.dk), Perinatal Epidemiological Research Unit, Department of Obstetrics and Gynaecology, Aarhus University Hospital, DK-8200 Aarhus N, Denmark.


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 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.

Interventions The fish oil provided 2.7 g and 6.1 g n-3 fatty acids/day 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.