High-dose docosahexaenoic acid supplementation during pregnancy and early preterm birth: a randomized, double-blind, adaptive design superiority trial
Several meta-analyses have concluded that n-3 fatty acids, including docosahexaenoic acid (DHA), reduce preterm birth (EPB, <34 weeks), but the amount of DHA needed is unknown. We hypothesized that 1000 mg of DHA per day would be better than 200 mg, the amount in most prenatal supplements.
DOI: https : //doi.org/10.1016/j.eclinm.2021.100905
Commentary
This study was a randomized, multicenter, double-blind, adaptive design, superiority trial and was conducted at three medical centers in the United States. Women with singleton pregnancies and 12-20 weeks gestation were eligible, and randomization was generated in blocks of four per site in SAS®.
Results of the study were as follows: 1,100 participants were enrolled between June 8, 2016 and March 13, 2020; if participants had a low DHA status at enrollment, participants with a high enrollment DHA status did not perceive a dose effect. Higher doses were associated with fewer serious adverse events, leading to the conclusion that clinicians can consider prescribing 1000 mg of DHA daily during pregnancy to reduce EPB in women with low DHA status if they can screen for DHA.
However, the ITT analysis reported in this study may underestimate the true benefit of DHA in reducing EPB because not all women were fully compliant with their assigned capsule intake.
Also, due to lower than expected EPB, the EPB rate in the U.S. at the time this study was designed and conducted was 3.4%, compared to 7% for non-black and black women. The most recent data shows 2.3% and 4.9% respectively, which is stated to reflect the fact that many US women are consuming low-dose supplements of DHA during pregnancy.
