Thank you for your Motherisk Update on -3 fatty acid supplementation during pregnancy.1 I agree that the essential fatty acids linoleic acid, -linolenic acid, docosahexaenoic acid (DHA), eicosapentenoic acid, and arachidonic acid are all essential components of the human brain and are all required for normal brain development and function.

It is important to remember the effects of -3 fatty acids on cell and cell membrane function. Docosahexaenoic acid has "significant effects on photoreceptor membranes and neurotransmitters involved in the signal transduction process; rhodopsin activation, rod and cone development, neuronal dendritic connectivity, and functional maturation of the central nervous system."2

I also agree that -3 fatty acids benefit preeclampsia, or pregnancy-induced hypertension, in observational studies. Reference 10,3 however, is used in the article for both observational and interventional trials. Which is it?

Second, reference 114 is used in the article to indicate that this interventional trial does not support benefit in preventing preeclampsia, when the opposite is true. This article showed improvement in gestational age (primary outcome) by about 6 days, which was statistically significant. It also showed improvement of birth weight (primary outcome), length, and head circumference (secondary outcomes), but these improvements were not statistically significant. Preeclampsia was not discussed beyond being listed in Table 3 of the article. Those taking high levels of DHA (interventional group) had a relative risk reduction of about 50% for developing preeclampsia and the number needed to treat to prevent 1 case of preeclampsia was 30, which certainly favours some benefit. Please explain.

The recent study5 that shows potential harm from -3 fatty acids and fish consumption is done in a community that traditionally has a high fish intake and might have an unaccounted confounder. Background levels of methylmercury were not taken in this population—a major concern in similar populations.6 It is recognized that hypertension has been induced by chronic ingestion of methylmercury among rats.7 Human exposure is a relatively new area of medicine and information is exploding at this time. The reason for the adverse outcome of the study might relate to toxicity, a point not mentioned in the article.

Third, I am disturbed by the conclusion of the article that no recommendations should be made to encourage women to take -3 fatty acid supplements. It has been estimated that the brain alone accumulates 67 mg DHA daily in the third trimester.8 Canada was the first country to recommend fatty acid intake, and international guidelines have been making recommendations since 1999. The International Society for the Study of Fatty Acids and Lipids, a scientific society, recommends adequate intakes of 4.44 g of linoleic acid and 2.22 g of -linolenic acid, with 0.22 g of DHA and 0.22 g of eicosapentenoic acid for adults and 0.3 g of DHA daily for pregnant women.9 Two excellent studies in Canada have shown that women rarely achieve these intakes and that more than 80% do not meet these requirements.10,11 If Canadian women are deficient in DHA, if women are choosing to limit seafood intake in pregnancy because of public health warnings about toxicant exposure,12 and if DHA is absolutely required for fetal brain development as the article correctly states, where do the authors propose that pregnant women obtain these required nutrients other than through supplementation? Public health recommendations have been discussed in other articles on this important topic.13

Finally, it would be appreciated if all sources of funding (including industry support) to the individual authors and the Motherisk program, as well as potential conflicts of interest, were fully disclosed in the article as is standard protocol with medical journals.