Makrides M, Gibson RA, McPhee AJ, Yelland L, Quinlivan J, Ryan P; DOMInO Investigative Team. (2010) JAMA 304(15) 1675-83.
CONTEXT: Uncertainty about the benefits of dietary docosahexaenoic acid (DHA) for pregnant women and their children exists, despite international recommendations that pregnant women increase their DHA intakes.
OBJECTIVE: To determine whether increasing DHA during the last half of pregnancy will result in fewer women with high levels of depressive symptoms and enhance the neurodevelopmental outcome of their children.
DESIGN, SETTING, AND PARTICIPANTS: A double-blind, multicenter, randomized controlled trial (DHA to Optimize Mother Infant Outcome (DOMInO trial) in 5 Australian maternity hospitals of 2399 women who were less than 21 weeks' gestation with singleton pregnancies and who were recruited between October 31, 2005, and January 11, 2008. Follow-up of children (n = 726) was completed December 16, 2009.
INTERVENTION: Docosahexaenoic acid-rich fish oil capsules (providing 800 mg/d of DHA) or matched vegetable oil capsules without DHA from study entry to birth.
MAIN OUTCOME MEASURES: High levels of depressive symptoms in mothers as indicated by a score of more than 12 on the Edinburgh Postnatal Depression Scale at 6 weeks or 6 months postpartum. Cognitive and language development in children as assessed by the Bayley Scales of Infant and Toddler Development, Third Edition, at 18 months.
RESULTS: Of 2399 women enrolled, 96.7% completed the trial. The percentage of women with high levels of depressive symptoms during the first 6 months postpartum did not differ between the DHA and control groups (9.67% vs 11.19%; adjusted relative risk, 0.85; 95% confidence interval (CI), 0.70-1.02; P = .09). Mean cognitive composite scores (adjusted mean difference, 0.01; 95% CI, -1.36 to 1.37; P = .99) and mean language composite scores (adjusted mean difference, -1.42; 95% CI, -3.07 to 0.22; P = .09) of children in the DHA group did not differ from children in the control group.
CONCLUSION: The use of DHA-rich fish oil capsules compared with vegetable oil capsules during pregnancy did not result in lower levels of postpartum depression in mothers or improved cognitive and language development in their offspring during early childhood.
TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12605000569606.
The DOMInO Trial, supported by the Australian government, is the largest clinical trial to date investigating the effects of supplementation with long-chain omega-3 in pregnancy
In keeping with academic practice, the abstract reports only the 'primary outcomes'. These were not met, leading to the negative 'headline' results
Rates of post-natal depression were lower in mothers receiving DHA vs placebo (9.67 % vs 11.15 %), although this difference did not reach 'statistical significance' (Relative risk 0.85, p < 0.09).
Notably, rates were much lower in BOTH groups than in the general Australian population (15-16%) – i.e. there was a very large ‘placebo effect’.
Also of importance is that the supplement used provided very little EPA. While DHA is crucial for early brain development (hence important in pregnancy), clinical trials of depression in adults have shown that EPA, not DHA, appears more effective in reducing depressive symptoms. See
At 18 months, average cognitive and language development scores did not differ significantly between the two groups of children. This might be expected, as nutrients can only ever help those whose status is sub-optimal (which is unlikely to be the whole population).
As a secondary outcome, the researchers therefore looked at the proportion of infants who failed to meet normal developmental milestones, and found that:
Other significant benefits for general health from DHA supplementation (pre-specified as 'secondary outcomes') included:
Supplementation was not associated with any serious adverse events – for either mother or baby; and infants of DHA-supplemented mothers showed better general health.
Results from the DOMInO Trial show significant expected cost savings to the Australian government if all mothers-to-be received supplementation with DHA-rich omega-3 during the last half pregnancy (and these savings only take into account immediate benefits). See: