Rapid Review Alert October 29, 2010
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 In EPA & DHA Research
Abstract Details

Objective: To determine whether DHA-rich fish oil supplementation during the last half of pregnancy will 1) result in fewer women with high levels of depressive symptoms and 2) enhance the neurodevelopmental outcome of their children.

Experimental Design: In a double-blind, multicenter, randomized controlled trial, 2399 women who were less than 21 weeks' gestation with singleton pregnancies were assigned to receive (from study entry to birth) either 100mg EPA + 800mg DHA per day or placebo.

Outcome Measurements: 1) high levels of depressive symptoms in mothers as indicated by a score of more than 12 on the Edinburgh Postnatal Depression Scale (EPDS) at 6 weeks or 6 months postpartum; 2) cognitive and language development in children as assessed by the Bayley Scales of Infant and Toddler Development 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 treatment and control groups. The mean composite scores of children in the treatment group did not differ from children in the control group.  

Authors' Conclusions: The use of DHA-rich fish oil capsules compared with vegetable oil capsules during pregnancy did not result in 1) lower levels of postpartum depression in mothers or 2) improved cognitive and language development in their offspring during early childhood. 
Rapid Review Alert
Sudden cardiac death
Recent JAMA Article Misrepresented by Media

Review of:
Makrides M Gibson RA McPhee AJ Yelland L Quinlivan J Ryan P and the DOMInO Investigative Team (2010). Effect of DHA Supplementation During Pregnancy on Maternal Depression and Neurodevelopment of Young Children. JAMA 304:1675-1683. 

What You Need To Know

The benefits of DHA for a healthy pregnancy are well established and the results of the present research do not change the large body of scientific evidence in support of DHA supplementation during pregnancy. Many organizations and government agencies recommend DHA supplementation for pregnant women, including:  

  • ISSFAL (International Society for the Study of Fatty Acids and Lipids): at least 200 mg/day
  • March of Dimes: 200 mg/day
  • EFSA (European Food Safety Agency): 100-200mg DHA for pregnant women in addition to the general recommendation of 250mg per day  of EPA + DHA
  • AFSSA (Agence Francais de Securite Santaire des Ailments): 250 mg/day
  • FAO/WHO Expert Consultation: at least 200 mg/day
  • Perinatal Lipid Intake Working Group: at least 200 mg/day
  • Australia New Zealand National Health and Medical Research Council: 110 – 115mg/day 

Study Limitations
  • DHA status of women at beginning of pregnancy, as well as when evaluated for depression, was unknown.
  • No food intake records were collected during pregnancy to determine baseline DHA intake in the placebo group.
  • There was no assessment of dietary intake of omega-3 fatty acids after birth. Infants may have received DHA from infant formula and women may have received DHA from their diet or from supplements after delivery; therefore, the results of cognitive development at 18 months may have been confounded.
  • DHA status of 18 month olds at time of neurocognitive evaluation was unknown.
  • As quoted directly from the article-A limitation of the depression aspect of our study is that we did not verify high EPDS scores with a clinical diagnosis of depression as part of the trial protocol. It is possible that the lower than expected rate of women with high levels of depressive symptoms in the control group is explained by the Hawthorn effect, in which simply participating in a trial with increased contact with researchers helped to prevent depressive symptoms.
  • The sample size of women with severe depression was relatively small and unrepresentative of the norm. Typically, it is ~16% versus ~11% in this study.
  • The supplementation period was relatively short.
  • The Bayley Scales of Infant and Toddler Development are increasingly viewed as a tool for establishing a diagnosis of serious cognitive dysfunction. They are not thought to be sensitive enough or sufficiently focused to assess high level cognitive abilities. More recent and sensitive tests could have given very different results.
  • The treatment group received very low levels of EPA (100mg/day).
    • A previous study demonstrated an anti-depressant benefit of higher levels of EPA in women during pregnancy (Su et al., 2008). While the study designs were different, it does suggest that higher levels of EPA, with the DHA, may have been beneficial during pregnancy.
    • Earlier this month, prior to the publication of Makrides article in JAMA, the results of a systematic review assessing the possible association between omega-3 polyunsaturated fatty acid supplementation and intake in the perinatal period and the risk of maternal perinatal depression was published in the Journal of Maternal-Fetal and Neonatal Medicine (Wojcicki et al, 2010). The authors of that review concluded that future randomized clinical trials to investigate the role of omega-3 polyunsaturated fatty acid supplementation and risk for maternal perinatal depression should begin supplementation early in pregnancy and use a dosage closer to 2g of EPA + DHA.
    • Peet et al., 2002 reported a dosage of 1g/day of EPA was effective in treating depression. While that study was not specific to pregnant women, the results suggest a benefit of higher levels of EPA for the treatment of depression.  

Noteworthy, Yet Underreported 

  • The study corroborated the safety of fish oil during pregnancy.
  • Significantly fewer offspring of mothers receiving treatment had delayed cognitive development scores compared to toddlers born to mothers receiving placebo.  
  • Compared to placebo-treated women, those supplemented with DHA-rich fish oil
    • had a significantly lower incidence of preterm birth at less than 34 weeks’ gestation (2.25% versus 1.09%).
    • gave birth to significantly fewer low birth weight (<2500g) babies. Mean birth weight was 68g heavier in the treatment group versus placebo.
    • gave birth to significantly fewer babies requiring admission to a neonatal intensive care unit.
  • During the study, there was a trend (p<0.07) towards more new cases of depression in the placebo group (61) versus the treatment group (47).  

Suggested Citation

Global Organization for EPA and DHA Omega-3s (2010). Recent JAMA Article Misrepresented by Media [Peer commentary on the paper “Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children” by Makrides M Gibson RA McPhee AJ Yelland L Quinlivan J Ryan P and the DOMInO Investigative Team. JAMA 304:1675-1683]. 


Peet M and Horrobin DF (2002). A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Arch Gen Psychiatry. 59:913-919.
Su KP Huang SY Chiu TH Huang KC Huang CL Chang HC and Pariante CM (2008). Omega-3 fatty acids for major depressive disorder during pregnancy: results from a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 69:644-651.
Wojcicki JM and Heyman MB (2010 Oct 7 Epub ahead of print). Maternal omega-3 fatty acid supplementation and risk for perinatal maternal depression. J Matern Fetal Neonatal Med. DOI: 10.3109/14767058.2010.521873 
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