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.

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.
Competing Interests: Competing interests: RAG has received supplies from Croda UK, prepared supplies for a trial for Efamol/Wassen UK and holds a patent (WO2013/10 40 25 A1) on stabilising and analysing fatty acids in a biologic sample stored on solid media, owned by Adelaide Research and Innovation, the University of Adelaide, and licensed to Xerion. SKT, FH, SD and ISZ are employees of Société des Produits Nestlé (SPN). MM has received supplies from Croda UK, and prepared supplies for a trial for Efamol/Wassen UK. The other authors do not have any competing interests.
(© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)