Predictors of compliance with higher dose omega-3 fatty acid supplementation during pregnancy and implications for the risk of prematurity: exploratory analysis of the ORIP randomised trial

Thomas R. Sullivan, Lisa N. Yelland, Robert A. Gibson, Sagar K. Thakkar, Fang Huang, Karen P. Best, Surabhi Devaraj, Irma Silva Zolezzi, Maria Makrides

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Background Intention-to-treat analyses of the Omega-3 to Reduce the Incidence of Prematurity (ORIP) trial found that omega-3 (n-3) fatty acid supplementation reduces the risk of prematurity in the subgroup of women with a singleton pregnancy and low n-3 status early in pregnancy, but not overall. However, results may have been influenced by less-than-optimal compliance. Objectives To identify predictors of compliance with n-3 supplementation and determine treatment effects among compliers. Design Exploratory analyses of a multicentre-blinded randomised trial. Setting 6 tertiary care centres in Australia. Participants 5328 singleton pregnancies. Interventions Daily capsules containing 900 mg n-3 long-chain polyunsaturated fatty acids or vegetable oil, consumed from before 20 weeks gestation until 34 weeks gestation. Outcome measures Early preterm (<34 weeks gestation) and preterm birth (<37 weeks gestation). Women were considered compliant if they reported missing less than a third of their allocated capsules in the previous week during a mid-pregnancy appointment. Results Among 2654 singleton pregnancies in the n-3 intervention group, 1727 (65%) were deemed compliant with supplementation. Maternal characteristics associated with compliance included age, years of full-time education, consuming alcohol but not smoking in the 3 months leading up to pregnancy, fewer previous births and taking dietary supplements at enrolment. Based on complier average causal effects, n-3 supplementation reduced the risk of preterm birth in compliers (relative risk=0.76; 95% CI 0.60 to 0.97), but not early preterm birth (relative risk=0.80; 95% CI 0.44 to 1.46). Consistent with intention-to-treat analyses, the lack of an overall effect on early preterm birth in compliers appeared to be due to beneficial effects in women with low n-3 status at enrolment but not women with replete status. Conclusions Results in compliers were similar to those from intention-to-treat analyses, suggesting that non-compliance was not a major factor in explaining outcomes from the ORIP trial. Trial registration number ACTRN12613001142729.

Original languageEnglish
Article numbere076507
JournalBMJ open
Issue number9
Publication statusPublished or Issued - 22 Sept 2023


  • Randomized Controlled Trial

ASJC Scopus subject areas

  • Medicine(all)

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