Omega-3 Supplementation May Help Reduce the Effect of Smoking on Preterm Birth

Smoking during pregnancy is a well-known risk factor associated with adverse pregnancy outcomes such as increased risk of spontaneous preterm delivery.[1] Despite these risks and others, 8% of pregnant women in the United States still smoke during pregnancy.[2] Smoking can lead to peroxidation of unsaturated fatty acids and increase oxidative stress. Moreover, women who smoke have lower levels of serum omega-3 fatty acids.[3] A recent study[4] has found that omega-3 supplementation during pregnancy in smokers has a protective effect against recurrent spontaneous preterm delivery and low birth weight.

Investigators from the University of Alabama at Birmingham enrolled pregnant women between the 16th to 20th week of gestation who had previously experienced a spontaneous preterm birth (20-36 weeks). All women were given alpha-hydroxyprogesterone caproate weekly for the prevention of recurrent spontaneous preterm birth. The patients were randomized to a 2000 mg/day omega-3 fatty acid supplement containing 1200 mg eicosapentaenoic acid (EPA) and 800 mg docosahexaenoic acid (DHA) or placebo capsules.  They received this supplement until week 36 of gestation or delivery. For this analysis, the women were further divided into smokers and non-smokers. There were 852 patients that had their smoking status determined.

This study found that 16% of their study subjects reported that they smoked during pregnancy. Importantly, in smokers omega-3 supplementation caused a 44% reduction in spontaneous preterm birth (30% vs. 53%); however, there was no effect in non-smokers (34% in the omega-3 group vs. 32% in the placebo group). Smokers who received the omega-3 fatty acid supplement had a 43% reduction in delivering low birth weight infants (28% vs. 50%); but again no significant change in delivery of a low birth weight infant in non-smokers (21% in the omega-3 supplemented group vs. 23% in the placebo group).

Thus, among this population of women, who had a previous preterm delivery, omega-3 supplementation at 2000 mg/day from early pregnancy to 36 weeks gestation had a significant effect to reduce recurrence of preterm delivery in smokers, but not in non-smokers. In addition, supplementation in smokers, but not non-smokers, also reduced the risk of delivering a low birth weight baby.

It is important to note that this study was a secondary data analysis of the largest U.S. trial of omega-3 fatty acid supplementation on the prevention of recurrent preterm delivery. In the original report[5] of that study, the authors concluded that omega-3 fatty acid supplementation did not reduce the risk of recurrent preterm delivery (Relative Risk = 0.91). However, no analysis was done to separate the effects of supplementation in smokers vs. non-smokers. Also, the study population was concurrently treated with a drug (alpha-hydroxyprogesterone caproate) to reduce the risk of preterm birth.  A recent systematic review and meta-analysis found a 58% reduction in preterm birth as a result of omega-3 supplementation in first-time mothers who were not on any other treatment to prevent preterm delivery.6 The authors of the current analysis4 proposed that the improved pregnancy outcomes in smokers could be due to the antioxidant effects of omega-3 fatty acids, which may have been beneficial in combating the oxidative stress associated with cigarette toxins. This notion would be consistent with previous findings by others who reported that vitamin C and vitamin E supplementation reduced the risk of preterm birth among mothers who smoked during pregnancy.7

Sources:

[1] Simpson WJ. A preliminary report on cigarette smoking and the incidence of prematurity. American Journal of Obstetrics and Gynecology 1957: 73; 807-15.
[2] Curtin SC, Matthews TJ. Smoking prevalence and cessation before and during pregnancy: data from the birth certificate, 2014. National Vital Statistics Report 2016: 65; 1-14.
[3] Simon JA, Fong J, Bemert JT, Browner WS. Relation of smoking and alcohol consumption to serum fatty acids. American Journal of Epidemiology 1996: 144: 325-34.
[4] Kuper SG, Abramovici AR, Jack VC, Harper LM, Biggio JR, Tita AT. The effect of omega-3 supplementation on pregnancy outcomes by smoking status. American Journal of Obstetrics and Gynecology 2017; 217: 476 e1-6.
[5] Harper M, Thorn E, Klebanoff MA, et al. Omega-3 fatty acid supplementation to prevent recurrent preterm birth: a randomized controlled trial. Obstetrics and Gynecology 2010; 115: 234-42.

6 Kar S, Wong M, Rogozinska E, Thangaratinam S. Effects of omega-3 fatty acids in prevention of early preterm delivery: a systematic review and meta-analysis of randomized studies. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2016; 198:40–6.

7Abramovici A, Gandley RE, Clifton RG et al. Prenatal vitamin C and E supplementation in smokers is associated with reduced placental abruption and preterm birth: a secondary analysis. BJOG 2015; 122:1740-7.