The Fish Oil to Reduce Tobacco Use iN Expectant Mothers (FORTUNE) Feasibility Trial

Am J Obstet Gynecol MFM. 2022 Aug 7:100707. doi: 10.1016/j.ajogmf.2022.100707. Online ahead of print.

ABSTRACT

BACKGROUND: Three small clinical trials have suggested that supplementation with long chain n-3 polyunsaturated fatty acids (LCPUFA: eicosapentaenoic acid and docosahexaenoic acid) found in fish oils may reduce nicotine cravings and at higher doses reduce cigarette consumption. Pregnant women who smoke have fewer pharmacological options to aide them with smoking cessation. Although n-3 LCPUFA supplementation has been studied in pregnancy few studies have evaluated doses 4 grams/day or higher and no prior studies have selectively enrolled pregnant women who smoke. High dose n-3 LCPUFAs may aid cessation but could be poorly tolerated in pregnant women who smoke due to gastrointestinal side effects.

OBJECTIVE: We conducted a feasibility trial to determine the tolerability of high dose n-3 LCPUFA supplementation in pregnant women who smoked. We hypothesized that n-3 LCPUFA doses of 4.2 grams a day would be well tolerated as compared to an olive oil placebo. We assessed RBC phospholipid membrane concentrations at baseline and end-of-therapy (4-weeks) and piloted outcomes for a future efficacy trial of n-3 LCPUFA supplementation for smoking cessation in pregnancy.

STUDY DESIGN: We recruited 28 pregnant women between the gestational ages of 6 and 36 weeks who reported daily cigarette smoking and were motivated to quit to participate in a double-blind placebo-controlled randomized feasibility trial of 4.2 grams per day of n-3 LCPUFA supplementation. Participants reported cigarettes per day (CPD), completed the Fagerström Test for Cigarette Dependence (FTCD), and provided blood, urine, and exhaled carbon monoxide (CO) samples. We used repeated measured ANOVA to pilot analyses for changes in CPD and FTCD.

RESULTS: At baseline, RBC membrane eicosapentaenoic acid concentrations were negatively correlated with CPD (r = -0.44, P = 0.04). By 4-weeks, circulating n-3 LCPUFA levels increased by 18% in the n-3 LCPUFA supplementation arm compared to a decrease of 3% in the placebo arm. Occurrence of gastrointestinal side effects such as burping, heartburn, diarrhea, abdominal pain or nausea did not differ statistically between study arms. At 4-weeks, participants allocated to the n-3 LCPUFA arm reported a median of 3 CPD (IQR 1, 8) compared to 7 CPD (IQR 1, 14) in the placebo arm, which was not statistically significant (P =0.99). Participants allocated to the n-3 LCPUFA arm had a decrease of 1 (IQR 0,1) on the FTCD score compared to 0 (IQR 0, 0) for placebo (P = 0.46).

CONCLUSIONS: High dose n-3 LCPUFAs may be tolerated in pregnant women who smoke however there was a high level of participant dropout with more participants allocated to the fish oil arm becoming lost to follow up. These results will inform the design of a future large scale RCT to test the impact of fish oil supplements for smoking cessation in pregnancy.

PMID:35948268 | DOI:10.1016/j.ajogmf.2022.100707