Babies born too early are at higher risk of poor health and some may not survive. Very few interventions have been shown to prevent preterm birth, so new findings that omega-3 fatty acid supplementation during pregnancy can help prevent babies being born too soon are very important for pregnant women, babies and the health professionals who care for them.
A team of researchers, led by A/Prof Middleton and Prof Makrides from the South Australian Institute of Health and Medical Research Institute, are studying long-chain omega-3 fats and their role in reducing the risk of premature births – particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) found in fatty fish and fish oil supplements. On World Prematurity Day in November last year, we published a Cochrane review that included 70 randomised trials with nearly 20,000 women overall.1
We found high-quality evidence that increasing the daily intake of omega-3 long chain fatty acids during pregnancy lowers the risk of:
- having a preterm baby (less than 37 weeks gestation) by 11 per cent
- having an early preterm baby (less than 34 weeks) by 42 per cent
The proposed action of omega-3 fatty acids is by reducing the potency of prostaglandins, which can trigger preterm birth.
An increase in gestational length and in prolonged pregnancy was seen with omega-3 supplementation. There was a possibly reduced risk of perinatal death and of neonatal care admission, a reduced risk of low birthweight babies and possibly a small increased risk of large for gestational age babies with omega-3 fatty acids.
Very few differences between antenatal omega-3 fatty acid supplementation and no supplementation were observed in children’s cognition, IQ, vision, other neurodevelopment and growth outcomes, language and behaviour, so we are uncertain of the effects of omega-3 fatty acid supplementation on these outcomes.
Most of the trials were conducted in high-income countries and included women mostly with singleton pregnancies, who were at either normal or high risk for poor pregnancy outcomes. The trials often used omega-3 supplements, though a few tested the effect of dietary changes, such as advice to eat more fish.
So while there is convincing evidence that omega-3 fatty acids can prevent preterm birth, we have a number of implementation challenges ahead. The first challenge has been to formulate some practical guidance for women and health professionals. On present evidence, we have suggested that the optimum dose of fish oil is a daily supplement containing between 500 and 1000 mg of long-chain omega-3 fats (containing at least 500 mg of DHA) starting at 12 weeks of pregnancy, for women with a singleton pregnancy. Currently available antenatal vitamin and mineral supplements usually contain less than 200 mg DHA+EPA, so they are not adequate on their own for preventing preterm birth.
Why not advise pregnant women to eat more fish?
Some women may want to do this, and this is encouraged. They would need to eat two to three serves a week of fatty fish, such as salmon, and this can be expensive and difficult for many women. Other pregnant women are concerned about heavy metal content in fish, but careful selection of species (for example, reducing shark and swordfish intake) addresses this concern. Others are concerned about sustainability of fish stocks, but some algal supplements are available. In fact, fish usually get their high omega-3 content from eating algae.
Table 1. Main results from ‘Omega-3 fatty acid addition in pregnancy’ Cochrane review.
|Outcome||RR||95% CI||No. of RCT||No. of women||% change*||GRADE|
|Preterm < 37 weeks||0.89||0.81 to 0.97||26||10,304||13 to 11||high|
|Preterm < 34 weeks||0.58||0.44 to 0.77||9||5204||4.6 to 2.7||high|
|Prolonged pregnancy > 42 weeks||1.61||1.11 to 2.33||6||5151||1.6 to 2.6||moderate|
|Perinatal death||0.75||0.54 to 1.03||10||7416||2 to 1.5||moderate|
|Low birthweight||0.90||0.82 to 0.99||15||8449||16 to 14||high|
|Large for gestational age||1.15||0.97 to 1.36||6||3722||12 to 13||moderate|
RR: risk ratio; CI: confidence interval; RCT: randomised controlled trial; *absolute
Can we optimise who should take omega-3 fatty acids in pregnancy?
There is emerging evidence that some women may benefit more than others from topping up their omega-3s. In a recent analysis from the Danish National Birth Cohort,2 women with low concentrations of omega-3 fatty acids in early–mid pregnancy had the highest risk of preterm birth, while women with high omega-3 status did not appear to have reduced risk of preterm birth. It may be that low omega-3 status is a risk factor for prematurity. Indeed, earlier work has suggested that omega-3 supplementation may benefit women with the lowest intakes of omega-3 fatty acids.3 Our research group has recently completed the ORIP randomised controlled trial of 5400 women who were supplemented with omega-3 fatty acids4 and through the use of innovative dried blood spot technology to measure omega-3 fatty acid status, we will be able to add to knowledge about women’s characteristics and differential responses to omega-3 fatty acid supplementation; including how to avoid any harm from prolonging pregnancy, for example.
It is now time to translate the evidence into action and we have begun the process of developing national clinical practice guidelines and an international statement. One of the challenges will be how health professionals and research translators (like us) can work together to implement nutrition solutions for preventing preterm birth, which calls for a ‘social prescribing’ approaches. We have begun to work with professional groups and hospitals to find and deliver the best strategies for using omega-3 fatty acids to prevent preterm birth – and to refine the strategies as we discover more about which women are likely to gain the most from omega-3 fatty acid supplementation.
- Middleton P, Gomersall JC, Gould JF, et al. Omega-3 fatty acid addition during pregnancy. Cochrane Database of Systematic Reviews. 2018,11:CD003402. doi: 10.1002/14651858.CD003402.pub3. Available at: www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003402.pub3/full
- Olsen SF, Halldorsson TI, Thorne-Lyman AL, et al. Plasma concentrations of long chain n-3 fatty acids in early and mid-pregnancy and risk of early preterm birth. EBioMedicine. 2018;35:325-33.
- Olsen SF, Osterdal ML, Salvig JD, et al. Duration of pregnancy in relation to fish oil supplementation and habitual fish intake: a randomised clinical trial with fish oil. Eur J Clin Nutr. 2007;61(8):976-85.
- Zhou J, Best K, Gibson R, et al. Study protocol for a randomised controlled trial evaluating the effect of prenatal omega-3 LCPUFA supplementation to reduce the incidence of preterm birth: the ORIP trial. BMJ Open. 2017;7(9):e018360.