Sullivan, T.R.Yelland, L.N.Gibson, R.A.Thakkar, S.K.Huang, F.Best, K.P.Devaraj, S.Zolezzi, I.S.Makrides, M.2023-10-232023-10-232023BMJ Open, 2023; 13(9):e076507-1-e076507-82044-60552044-6055https://hdl.handle.net/2440/139739Background: 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.en© 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.HumansPremature BirthFatty Acids, Omega-3Fatty AcidsCapsulesPregnancyDietary SupplementsInfant, NewbornAustraliaFemaleHumansPremature BirthFatty Acids, Omega-3Fatty AcidsCapsulesPregnancyDietary SupplementsInfant, NewbornAustraliaFemaleJournal article10.1136/bmjopen-2023-0765072023-10-19656556Sullivan, T.R. [0000-0002-6930-5406]Yelland, L.N. [0000-0003-3803-8728]Gibson, R.A. [0000-0002-8750-525X]Best, K.P. [0000-0002-7653-5074]Makrides, M. [0000-0003-3832-541X]