Am Fam Physician. 2011 Jun 1;83(11):1344.
Background: Studies have suggested that pregnant women who increase their intake of n-3 long-chain polyunsaturated fatty acids, specifically docosahexaenoic acid (DHA) from fish and seafood, have a lower risk of maternal depression and improved neonatal development. Human studies have been inconclusive, mostly because of methodologic flaws; however, the nutritional supplement industry markets prenatal supplements with DHA, and some organizations recommend supplementation to improve brain function in the mother and infant. Makrides and colleagues designed the DHA to Optimize Mother Infant Outcome (DOMInO) trial to better quantify any benefits and identify any risks to mothers and infants receiving DHA supplementation.
The Study: This double-blind, multicenter, randomized controlled trial was conducted in five Australian medical centers. Women with singleton pregnancies earlier than 21 weeks of gestation were invited to participate. Women already taking DHA supplements, with a bleeding disorder in which tuna oil was contraindicated, taking anticoagulants, with a pregnancy complicated by a known fetal abnormality, or with documented drug or alcohol abuse were excluded. Groups were stratified by center and by parity (first versus subsequent birth) and randomized to take three capsules daily of 500 mg of fish oil concentrate or a similarly appearing vegetable oil capsule. The fish oil capsules provided 800 mg of DHA and 100 mg of eicosapentaenoic acid per day; these doses were estimated to be above the threshold associated with lower rates of maternal depression and improved infant development outcomes. The vegetable oil capsule was designed to match the fatty-acid profile of the average Australian diet. Women were instructed to take the supplements until delivery. Participants were contacted two weeks after enrollment and at 28 and 36 weeks of gestation to assess adverse effects and to encourage compliance. Adherence was measured by DHA concentrations in cord blood.
The primary outcome for mothers was a high level of postpartum depression, as suggested by a score of more than 12 on the Edinburgh Postnatal Depression Scale, which the women completed six weeks and six months after delivery. The primary childhood outcome was neurodevelopment at 18 months of age. Study psychologists administered the Cognitive and Language Composite Scales of the Bayley Scales of Infant and Toddler Development, Third Edition.
Results: The authors enrolled 1,197 women in the DHA group and 1,202 in the control group, and the study was powered to detect a 4.2 percent absolute reduction in depressive symptoms. Similarly, the offspring sample size, which required at least 572 children, was designed to detect a clinically meaningful difference of 4 points in developmental scores. All 96 preterm children were assessed and 630 full-term children were randomly chosen during the first year of life to be tested. The baseline characteristics of both groups were similar and the drop-out rate was less than 4 percent in all groups. Adverse effects were similar in each group except for an increased incidence of eructation in the DHA group.
There was no difference in maternal depression outcomes between the DHA and control groups, and there was no difference in mean cognitive scores between children in each group. Secondary analyses suggested decreased incidence of very early preterm births in the DHA group, but also increased postterm pregnancies requiring induction with or without cesarean delivery. Boys had no language development differences between groups, whereas girls exposed to DHA had lower mean language scores, an increased risk of language delay, and lower mean adaptive scores than girls in the control group.
Conclusion: The authors conclude that the results of the DOMInO trial do not support the routine use of DHA supplementation in pregnant women to reduce levels of postpartum depression or improve cognitive and language development in early childhood.
Makrides M, et al. Effect of DHA supplementation during pregnancy on maternal depression and neuro-development of young children: a randomized controlled trial. JAMA. October 20, 2010;304(15):1675–1683.
Copyright © 2011 by the American Academy of Family Physicians.
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