To date, few methods have been proposed to predict women at high risk of preterm birth, and few are used clinically. However, even if pregnancies at risk for early preterm birth (EPB) could be identified, reliable prevention measures have been elusive, according the the authors of the current study published in 'EClinicalMedicine'.
A recent Cochrane Review concluded there is strong evidence that n-3 long chain polyunsaturated fatty acid supplementation, including docosahexaenoic acid (DHA), can reduce EPBs by nearly half; however, the optimal dose was never identified, the type of omega-3 supplementation was not tested and the analysis included both DHA and eicosapentaenoic acid (EPA) supplementation. This is a potential concern as low dietary intake of DHA is common in parts of the world that consume little or no seafood.
The authors of the current study therefore undertook the multicentre, double-blind, randomised, superiority trial to compare the early preterm birth (< 34 weeks) of women (recruited at 12 to 20 weeks gestation) given 1,000 mg of DHA to those given 200 mg - the amount in most prenatal supplements. They hypothesised that 1000 mg DHA per day would be superior to 200 mg.
Nearly 1,100 participants were enrolled (from academic medical centers in the US) and randomised to receive either 200 mg or 1000 mg of DHA daily. All participants received a bottle containing 200 mg DHA capsules and instructed to take one capsule daily. They were also assigned to take 2 additional capsules daily that contained either a mixture of corn and soybean oil or 400 mg of an algal source of DHA (Life's DHA-S oil, DSM Nutritional Products LLC, Switzerland).
Blood samples were collected at enrolment and again at delivery when umbilical cord blood was also taken. Gestational age at delivery, as well as weight, length and head circumference at delivery were also recorded.
This study, funded by the National Institutes of Health Child Health and Human Development (NICHD), is the first to compare these doses of DHA in their ability to prevent early preterm birth. The study found 1000 mg DHA was likely better than 200 mg DHA in reducing early preterm birth <34 weeks (posterior probability or pp = 0.91), especially for women with low DHA status at the time they were enrolled (pp = 0.93). The higher dose also resulted in fewer maternal and neonatal serious adverse events.
Specifically, 1.7% of women in the high dose group delivered early preterm compared to 2.4% in the standard dose group. Women in the high dose group with low DHA levels at study entry had the greatest reduction in early preterm birth (2% rate, compared to a 4.1% rate for those with low DHA levels on the standard dose). Among women who had high DHA levels at study entry, the rate of early preterm birth was low and did not differ by dose (1.4% vs. 1.1%).
The authors call for screening DHA levels in pregnancy and advise that pregnant women with low DHA status should consume a DHA supplement of 1000 mg per day.
The report states: "The most recent Cochrane Review supports implementation of DHA supplementation in pregnancy at a dose between 500 and 1000 mg per day. The exploratory results of the Australian ORIP trial and those of ADORE provide evidence that DHA supplementation needs to be higher than in current prenatal supplements for women with low DHA status. "
Mechanism of action
While the mechanism of preterm birth remains elusive and complex, the authors say biomarkers assessed prior to 20 weeks gestation suggest spontaneous preterm labor may be associated with stressors linked to inflammation.
The report states: "DHA is a precursor of docosanoids (resolvins, maresins) that are anti-inflammatory and that resolve and protect against inflammation, and both resolvin D1 and D2 from DHA and inflammatory mediators formed from the n-6 fatty acid, arachidonic acid, increase with spontaneous preterm birth. We observed fewer cases of spontaneous preterm birth, which are known to be driven by inflammatory mechanisms, in the high compared to the low DHA dose group.
"Because of this, we suggest that our finding of lower EPB with higher DHA supplementation could be due to a change in balance between n-3 and n-6 derived mediators to reduce or prevent the inflammatory process associated with labor."
Carlson. S. E., et al
"Higher dose docosahexaenoic acid supplementation during pregnancy and early preterm birth: A randomised, double-blind, adaptive-design superiority trial"