Landmark Study – Long-chain omega-3 fats reduce the risk of premature birth

Preterm birth (less than 37 weeks gestation) is the most important factor in the survival and long-term neurodevelopment of the newborn.^1,2 Premature birth before 37 weeks is directly responsible for 85 percent of all complications in early life³ and is the leading cause of death in children under 5 years of age.⁴ Early preterm babies (those born before 34 weeks) are especially at risk. They often require long periods in intensive care and may develop lifelong health problems involving the lungs, gut and immune system together with neurodevelopmental vision, hearing behavior, learning and communication difficulties.

Cost of early preterm birth

Apart from the significant emotional and financial costs to the family, early preterm birth (ePTB) is a major economic cost to society. According to Carlson et al⁵, the rate of ePTB has decreased little since 1990. The researchers reported that docosahexaenoic acid (DHA) supplementation is a ‘potential high yield, low risk strategy to reduce early preterm delivery in the U.S. by up to 75 percent’. Kar et al⁶ noting the limitations of current risk-based approaches to reducing the incidence of preterm birth identified the need to focus on a population-based approach to risk reduction, especially for ePTB. The intervention needed to be accessible, inexpensive, acceptable to women and have minimal side effects.⁷

Prevalence of preterm birth

The magnitude and importance of the problem is reflected by the rate of preterm birth of 11.4 percent in the United States in 2014 with early preterm birth accounting for approximately 3 percent of births.⁸ Approximately 15 million babies are born prematurely worldwide each year⁹.

Diet

The influence of diet on pregnancy outcome was highlighted in a 1985 paper¹⁰ where scientists reported that women, living in the Faroe Islands where diets are typically high in omega-3 rich seafood, had longer pregnancies and babies born with higher birth weights than those born in mainland Denmark. The long-chain omega-3 fats from marine sources such as fish and algae were thought to be responsible for the longer pregnancies.

In 2015, Kar et al¹¹ undertook a systematic review to assess the effects of omega-3 fatty acids on early pregnancy birth and any preterm birth. They found a 58 percent reduction in early preterm delivery rates and a 17 percent reduction in any preterm deliveries, concluding that omega-3 fatty acids are safe and effective in reducing the risk of early and preterm delivery.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are long-chain omega-3 fatty acids that are readily available as nutritional supplements, although there are recommendations for 200 – 300 mg DHA per day during pregnancy¹², there is yet to be a dose recommendation in pregnancy to support a reduction in the risk of preterm birth¹³.

Landmark Cochrane Review

Cochrane Reviews are internationally recognized as the ‘gold standard’ for bringing together evidence and have been conducted evaluating the benefits of long-chain omega-3 fats in pregnancy by Makrides et al, in 2006¹⁴ and by Middleton et al, in 2018¹⁵. The 2018 review assessed all published, randomized controlled trials investigating the effects of long-chain omega-3 fats during pregnancy on the outcomes of mothers and babies. The quality of the research was taken into account. All forms and doses of supplementation in pregnancy were analyzed. The researchers analyzed 70 trials, mostly conducted in high income countries, involving 19,787 women mainly with singleton pregnancies. As a result of the findings, the authors have provided long-chain omega 3 fatty acid recommendations.

The 2018 Cochrane Review found high-quality evidence that supplementation with long-chain omega-3 fats during pregnancy reduced the risk of having a premature baby (less than 37 weeks) by 11 percent (25 trials:10,184 participants) and reduced the risk of ePTB (less than 34 weeks) by 42 percent (9 trials: 5,204 participants) compared with no long-chain omega-3 supplementation.

The researchers also found a reduced risk of delivering a low birth weight baby (15 trials: 8,449 participants). In light of these findings, the authors concluded that a dose of 500-1,000 mgs of long-chain omega-3 fats, DHA and EPA, daily with a minimum addition of 500 mg of DHA per day was the most effective.

Some studies assessed the growth and neurological development of children after birth, finding very few outcomes different between the children of women who received supplements and those who did not.

In summary, the 2018 Cochrane Review findings and author recommendations:

1.  Supplementation with long-chain omega-3 fats (DHA and EPA) during pregnancy lowers the risk of having a premature baby, especially in singleton pregnancies.

2.  Supplementation with long-chain omega-3 fats (DHA and EPA) during pregnancy reduces the risk of having a small baby.

3.  The best available evidence suggests that the most effective dose is 500 – 1,000 mg of long-chain omega-3s daily where at least 500 mg is from DHA.

4.  There is uncertainty about the longer-term benefit on the growth and development of children after birth with omega-3 supplementation during pregnancy.

Questions that need to be studied further include the minimum effective dose of long-chain omega-3 fats, what is the optimal combination, and which women will benefit most from supplementation with long chain omega-3 fats.

To further explore the role of DHA in reducing the risk of ePTB, the ADORE trial¹⁶ is investigating the benefits of receiving two daily capsules of algal oil (800 mg DHA) in addition to a prenatal supplement containing 200 mg DHA. As inflammation is a well-known cause of pre-term labor the authors postulate that DHA may be effective because of its anti-inflammatory properties.

Although the Cochrane Review found no apparent benefit on the growth and development of children after birth, Kannass et al in 2009¹⁷ showed that infants born to mothers with higher blood levels of DHA at delivery had advanced levels of attention span well into their second year of life. Further evidence of the correlation between the mother’s DHA status in pregnancy and the problem-solving skills of the newborn healthy infant was provided by a 2018 Norwegian study, which showed that the mother’s DHA status in pregnancy was positively associated with the infant’s problem-solving skills at 12 months, even after allowing for confounding factors such as maternal education.

Along with the 2018 Cochrane Review, the authors concluded that the results reinforced the importance of the women having a satisfactory DHA intake from their diet or other DHA rich sources.

As evidenced by the 2018 Cochrane Review and the papers cited above, an optimal intake of long-chain omega-3 fatty acids containing DHA is essential to ensure a healthy pregnancy by supporting optimal maternal and arguably infant health and development.

The WHO recommends an intake of 200-300 mg per day of DHA, but this recent evidence now supports the recommendation that pregnant women with a singleton pregnancy consume a daily supplement containing 500 – 1,000 mg of long-chain omega-3 fats (DHA and EPA), with a minimum of 500 mg DHA, daily to reduce their risk of having a premature baby.

1. Harper, M., Thom, E., Klebanoff, M.A., Thorp Jr, J., Sorokin, Y., Varner, M.W., Wapner, R.J., Caritis, S.N., Iams, J.D., Carpenter, M.W. and Peaceman, A.M., 2010. Omega-3 fatty acid supplementation to prevent recurrent preterm birth: a randomized controlled trial. Obstetrics and gynecology, 115(2 0 1), p.234.
2. RCOG. Tocolysis for Women in Preterm Birth Royal College of Obstetricians and Gynaecologists - Greentop guideline no 1b. London; 2011.
3. Thornton, S., 2008. Preterm Birth: Causes, Consequences and Prevention. The Obstetrician & Gynaecologist, 10(4), pp. 280-280.
4. Liu, L., Oza, S., Hogan, D., Chu, Y., Perin, J., Zhu, J., Lawn, J.E., Cousens, S., Mathers, C. and Black, R.E., 2016. Global, regional, and national causes of under-5 mortality in 2000–15: an updated systematic analysis with implications for the Sustainable Development Goals. The Lancet, 388(10063), pp.3027-3035.
5. Carlson, S.E., Gajewski, B.J., Valentine, C.J., Rogers, L.K., Weiner, C.P., DeFranco, E.A. and Buhimschi, C.S., 2017. Assessment of DHA on reducing early preterm birth: the ADORE randomized controlled trial protocol. BMC pregnancy and childbirth, 17(1), p.62.
6. Kar, S., Wong, M., Rogozinska, E. and Thangaratinam, S., 2016. 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, 198, pp.40-46.
7. Carlson, S.E., Gajewski, B.J., Valentine, C.J., Rogers, L.K., Weiner, C.P., DeFranco, E.A. and Buhimschi, C.S., 2017. Assessment of DHA on reducing early preterm birth: the ADORE randomized controlled trial protocol. BMC pregnancy and childbirth, 17(1), p.62.
8. Hamilton, B.E., Martin, J.A., Osterman, M.J., Curtin, S.C. and Mathews, T.J., 2015. Births: final data for 2014.
9. World Health Organisation.Preterm birth: Key facts, 2018. Accessed from http://www.who.int/en/news-room/fact-sheets/detail/preterm-birth
10. Olsen, S.F. and Joensen, H.D., 1985. High liveborn birth weights in the Faroes: a comparison between birth weights in the Faroes and in Denmark. Journal of Epidemiology & Community Health, 39(1), pp.27-32.
11. Kar, S., Wong, M., Rogozinska, E. and Thangaratinam, S., 2016. 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, 198, pp.40-46.
12. FAO Food and Nutrition Paper 91, fats and fatty Acids in Human Nutrition. Report of an Expert Consultation 2008. http://www.fao.org/3/a-i1953e.pdf accessed November 7th 2018.
13. ibid
14. Makrides, M., Duley, L. and Olsen, S.F., 2006. Marine oil, and other prostaglandin precursor, supplementation for pregnancy uncomplicated by pre‐eclampsia or intrauterine growth restriction. Cochrane database of systematic reviews, (3).
15. Middlleton et al., 2018. Cochrane Review
16. Carlson, S.E., Gajewski, B.J., Valentine, C.J., Rogers, L.K., Weiner, C.P., DeFranco, E.A. and Buhimschi, C.S., 2017. Assessment of DHA on reducing early preterm birth: the ADORE randomized controlled trial protocol. BMC pregnancy and childbirth, 17(1), p.62.
17. Kannass, K.N., Colombo, J. and Carlson, S.E., 2009. Maternal DHA levels and toddler free-play attention. Developmental neuropsychology, 34(2), pp.159-174.