The effect of omega-3 supplementation on pregnancy outcomes by smoking status

Abstract

BACKGROUND Smoking during pregnancy is associated with adverse maternal and neonatal outcomes such as preterm delivery, intrauterine growth restriction, stillbirth, and low birth weight. Since smoking causes oxidative stress, some have suggested using antioxidants to counteract the effects of oxidative stress. Smokers have lower serum levels of omega-3 fatty acids, an important antioxidant, and thus, investigating whether omega-3 supplementation in smokers reduces adverse maternal and neonatal outcomes represents an important area of research. OBJECTIVE To investigate whether the antioxidant effect of omega-3 fatty acid supplementation on the incidence of adverse pregnancy outcomes differs between smokers and nonsmokers. STUDY DESIGN Secondary analysis of a multicenter randomized controlled trial of omega-3 supplementation for preterm delivery prevention in women with a singleton pregnancy and a history of a prior singleton spontaneous preterm delivery. Subjects were randomized to begin omega-3 or placebo prior to 22 weeks which was continued until delivery. All women received 17 alpha-hydroxyprogesterone caproate intramuscularly weekly beginning between 16 to 20 weeks of gestation and continued until 36 weeks of gestation or delivery, whichever occurred first. The primary outcome was spontaneous preterm delivery. Secondary outcomes were indicated preterm delivery, any preterm delivery (spontaneous and indicated), pregnancy-associated hypertension (gestational hypertension and preeclampsia), a neonatal composite (retinopathy of prematurity, intraventricular hemorrhage grade III or IV, patent ductus arteriosus, necrotizing enterocolitis, sepsis, respiratory morbidity, or perinatal death), low birth weight (<2500 grams), small for gestational age (less than the 10th percentile), and neonatal intensive care unit or intermediate nursery admission. The study population was stratified into smokers and nonsmokers, and the incidence of each outcome was compared by omega-3 supplementation versus placebo in each subgroup. Zelen tests were performed to test for homogeneity of effect in smokers and nonsmokers. RESULTS Of 851 subjects included in the analysis, 136 (16%) smoked. Baseline characteristics between omega-3 and placebo groups did not differ in smokers or nonsmokers. Omega-3 supplementation was associated with a lower risk of spontaneous preterm delivery in smokers (RR 0.56, 95% CI 0.36–0.87) but not in nonsmokers (RR 1.04, 95% CI 0.84–1.29); p-value for interaction = 0.013. Low birth weight was also less frequent in smokers receiving omega-3 supplementation (RR 0.57, 95% CI 0.36–0.90) compared to nonsmokers (RR 0.93, 95% CI 0.71–1.24); p-value for interaction = 0.047. The effect on other secondary outcomes did not differ significantly between smokers and nonsmokers. CONCLUSION Omega-3 supplementation in smokers may have a protective effect against recurrent spontaneous preterm delivery and low birth weight.

Oxidative stress-induced miR-27a targets the redox gene nuclear factor erythroid 2-related factor 2 in diabetic embryopathy

“…Experiments in animal models have clearly shown that oxidative stress is responsible for maternal diabetes-induced NTDs 1, 7, 11, 56–61 and congenital heart defects 62, 63 , and clinical research has demonstrated that oxidative stress is involved in various adverse pregnancy outcomes 64, 65 . For example, oxidative stress induced by tobacco smoke is associated with preterm delivery, intrauterine growth restriction, stillbirth, low birth weight, aberrant placental metabolism, syncytial knot formation, and multiple markers of oxidative damage 66, 67 . A case-control study showed that maternal oxidative stress may be an important contributor to preterm birth, regardless of subtype and timing of exposure during pregnancy 68 .…”

Omega-3 Long-Chain Polyunsaturated Fatty Acids and Preeclampsia: Trials Say “No,” but Is It the Final Word?

“…There were no notable differences between groups. However, the trial was not designed with this specific effect in mind, hence lacking the power to detect it confidently [ 65 ]. Nevertheless, this secondary analysis may become an example for future study designs because smoking affects pregnant women in non-obvious ways.…”

The Role Played by Salicylic Acid and Omega 3 in the Placental Vascular Resistance Mechanism: A Pilot Study

“…In this case, omega-3 supplementation was associated with lower risk of spontaneous preterm birth in smokers (RR=0.56; 95% CI; 0.36-0.87) than in nonsmokers (RR=1.04; 95% CI; 0.84-1.29). In addition, low birth weight was less often diagnosed in babies born from smokers subjected to omega-3 supplementation (RR=0.57, 95% CI 0.36-0.90) than in babies born from nonsmokers (RR=0.93; 95% CI; 0.71-1.24) [29].…”