Assessing Omega-3 Fatty Acid Supplementation During Pregnancy and Lactation to Optimize Maternal Mental Health and Childhood Cognitive Development

Chelsea M Klemens; Kataneh Salari; Ellen L Mozurkewich


Clin Lipidology. 2012;7(1):93-109. 

In This Article

Intervention Studies of Long-chain PUFA Supplementation & Maternal Depression

Despite observational studies linking relative DHA deficiency in pregnancy and lactation with perinatal depression, results of intervention studies of omega-3 fatty acid supplementation have been mixed, with a few positive studies, but many not showing clear evidence of benefits.[43] Recently, Jans and colleagues conducted a meta-analysis of seven double blind, randomized controlled trials with a total of 612 participants that evaluated the effect of omega-3 fatty acids for prevention or treatment of depression in pregnancy and postpartum. The included studies involved comparison of oils containing differing combinations of DHA and EPA with placebo during pregnancy.[43] In their aggregate analysis of these trials, the authors did not demonstrate any benefits of omega-3 fatty acid supplementation during pregnancy for prevention or treatment of perinatal depression.[43] The trials included in this analysis included four in which participants were healthy, and three trials in which participants were suffering from major depressive disorder at baseline.[43] In contrast to the studies that aimed to prevent depression, the authors did find some evidence for effectiveness in the three studies that employed omega-3 fatty acid supplementation among subjects who were depressed at trial entry rather than among subjects who were healthy at baseline.[43]

Subsequent to these findings was the publication of a recent large multicenter study by Makrides et al.[44] This study randomized 2399 women in five Australian maternity hospitals to receive either 800 mg daily of DHA or placebo from study entry in the second trimester of pregnancy until delivery.[44] Participants were healthy women who were not selected based on depressive symptoms or predisposition to depression.[44] The primary outcome of the study was Edinburgh Postnatal Depression Scale Score (EPDS) at 6 weeks and 6 months postpartum.[44] The authors did not find any difference in the proportion of mothers reporting significant depressive symptoms (EPDS >12) or new diagnosis of depression.[44] Among women with depressive symptoms at trial entry, significant depressive symptoms at 6 months postpartum did not differ between groups.[44] The individual studies reviewed by Jans, as well as the more recent Makrides trial are summarized in Table 1 .[44–51]

There are several potential reasons that this study might have not shown effectiveness for the omega-3 fatty acid supplementation intervention. First, the supplementation was carried only through birth of the infant, and not until 6 weeks and 6 months postpartum when the outcome was assessed.[44] Second, it is possible that the selection of DHA rather than EPA as the study intervention led to the negative result. Alternatively, it is possible that the ratio of EPA:DHA may be of the greatest importance in the regulation of mood. This may explain why most of the extant trials of fish oil supplementation during pregnancy have shown no effect on mood disorders, in that most of these trials used DHA-predominant oils, or fish oils with a low EPA:DHA ratio ( Table 1 ). Two systematic reviews of studies concerning EPA and DHA for treating depression and other mood disorders in mixed pregnant and nonpregnant subjects have suggested that EPA, but not DHA, is effective in treating this disorder.[52,53] Indeed, Martins noted that trials in which fish oil contained at least 50% EPA were more likely to show benefits than trials in which the studied fish oils were DHA-predominant.[53] Martins noted that trials utilizing nearly pure EPA were most likely to show benefits.[53] However, no studies directly comparing these two fatty acids in pregnant patients are currently available. A double-blind, randomized pilot trial comparing EPA-rich fish oil with DHA-rich fish oil and with placebo in pregnant women selected based on risk for depression is currently underway.[54]


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