Rapid Review Alert February 1, 2013
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ADVANCES
 In EPA & DHA Research
Abstract (as published in Am J Clin Nutr)

Background: Maternal fish consumption during pregnancy has been positively associated with cognitive and visual abilities in the offspring, leading to the hypothesis that maternal omega-3 (n-3) long-chain PUFA (LCPUFA) supplementation improves children’s neurologic and visual development.

Objective: The objective was to evaluate the effect of maternal omega-3 LCPUFA supplementation in pregnancy on neurologic and visual development in the offspring.

Design: Five electronic databases were searched. Human randomized controlled trials that supplemented the maternal diet with omega-3 LCPUFAs during pregnancy, or pregnancy and lactation, and that assessed either neurologic or visual development of the offspring were included. Trial quality was assessed, and the results of eligible trials were compared in meta-analyses.

Results: Eleven RCTs involving 5272 participants were included in the review. Most trials had methodologic limitations. No differences in standardized psychometric test scores for cognitive, language, or motor development were observed between the LCPUFA-supplemented and control groups, except for cognitive scores in 2–5-y-old children, in whom supplementation resulted in higher Developmental Standard Scores (mean difference: 3.92; 95% CI: 0.77, 7.08; n = 156; P = 0.01). However, this effect was from 2 trials with a high risk of bias. Because of the variety of visual assessments and age ranges, it was not possible to combine studies with visual outcomes in a meta-analysis, although 6 of the 8 assessments in 5 trials reported no difference between the supplemented and control groups.

Authors’ Conclusion: The evidence does not conclusively support or refute that omega-3 LCPUFA supplementation in pregnancy improves cognitive or visual development.
Rapid Review Alert
baby face
O-3s During Pregnancy on Early Cognitive and Visual Development

Review of:
Gould JF Smithers LG and Makrides M (Epub ahead of print 2013 Jan 30). The effect of maternal omega-3 (n-3) LCPUFA supplementation during pregnancy on early childhood cognitive and visual development: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr doi: 10.3945/ajcn.112.045781.


GOED Take-Aways

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 and lactation. Many organizations and government agencies recommend long-chain omega-3 supplementation for pregnant and lactating women, including:
  • ISSFAL (International Society for the Study of Fatty Acids and Lipids): at least 200 mg/day DHA
  • EFSA (European Food Safety Authority): 100-200mg/day DHA for pregnant women in addition to the general recommendation of 250mg/day EPA + DHA
  • ANSES (French Agency for Food, Environmental and Occupational Health and Safety)(formerly AFSSA; Agence Francais de Securite Santaire des Ailments): 500 mg/day EPA + DHA per day with at least 250mg from DHA
  • Joint FAO/WHO Expert Consultation on Fats and Fatty Acids in Human Nutrition: 300mg/day EPA + DHA of which at least 200mg should be DHA
  • Perinatal Lipid Intake Working Group: at least 200 mg/day DHA
  • Australia New Zealand National Health and Medical Research Council: 110 – 115mg EPA + DHA +DPA per day 
The following Article 14 Health Claims, based on scientific assessments from the European Food Safety Authority (EFSA), are authorized for use in the EU.
  • Docosahexaenoic acid (DHA) intake contributes to the normal visual development of infants up to 12 months of age.
  • Docosahexaenoic acid (DHA) maternal intake contributes to the normal development of the eye of the foetus and breastfed infants.
  • Docosahexaenoic acid (DHA) maternal intake contributes to the normal brain development of the foetus and breastfed infants.

What Else Should You Know? 

  • Most of the trials included in the analyses had relatively small sample sizes and were powered to detect relatively large differences rather than the modest effects that might be expected from a nutritional intervention. The rigorous Cochrane inclusion criteria allowed only 7 (of 312) studies to be included (IQ).
  • Most trials were of poor quality and did not clearly report the process for generation of the randomization sequence or concealment of allocation to allow a risk of bias judgment.
  • Attrition was high (up to 86%) in most trials, and there was selective loss from the treatment group in two trials which may also introduce systematic bias.
  • Few trials conducted intention-to-treat analyses, and many trials had post-randomization exclusions that could have introduced systematic bias by disrupting the randomization schedule.
  • Many of the trials conducted multiple comparisons on small samples without correction to avoid a Type I error.
  • Not all known data were available from the study authors for inclusion in the review. Only two of the seven studies provided additional unpublished data which would be necessary for an in depth statistical investigation.
  • Supplementation took place during pregnancy and lactation in some trials, which made it difficult to determine the period during which supplementation is effective.
  • One of the other purposes of maternal supplementation during pregnancy is for replenishing maternal stores of DHA, which this paper did not address.
  • Most of the mental development, motor development, and language indices the study investigated trended towards a benefit from DHA. Unfortunately, there were generally only one or two small studies, which means more studies are needed for a meta-analysis to be useful.
  • One meta-analysis of cognitive development found a benefit in 2-5 year old children (P=0.01).
  • The conclusions indicate there are no benefits for visual development, but a meta-analysis on visual development studies was not conducted. Instead, the authors reviewed a couple of studies but their "review" did not include the studies EFSA relied on to establish the visual development claims.
  • While the tone of the paper seems downbeat regarding cognitive effects, the actual Forrest plots are much more positive than that, with only a few areas where no benefit for DHA supplementation could be seen.
  • DHA supplementation of mothers varied widely from 240 mg to 3300 mg per day, and in one study it was taken “ad libitum”!
  • This study did not look at increased gestation length as an outcome measure.  A recent review by Larqué et al., 2012 concluded that prenatal DHA supplementation enhanced the length of gestation by an average of two days and increased the weight of the baby by 50 g.
  • A similar 2005 meta-analysis conducted by Cohen et al. was also based on seven studies but came up with much more positive results, concluding that increasing maternal DHA intake by 100 mg/day increases child IQ by an estimated 0.13 points.
  • It would be helpful if the authors had included the list of excluded studies, with reason for exclusion.  There are other studies that seem as though they should have met their inclusion criteria.

Suggested Citation

Global Organization for EPA and DHA Omega-3s (2013). Omega-3s During Pregnancy on Early Cognitive and Visual Development [Peer commentary on the paper “The effect of maternal omega-3 (n-3) LCPUFA supplementation during pregnancy on early childhood cognitive and visual development: a systematic review and meta-analysis of randomized controlled trials” by Gould JF, Smithers LG and Makrides M (Epub ahead of print 2013 Jan 30). Am J Clin Nutr doi: 10.3945/ajcn.112.045781.].

References

Cohen JT Bellinger DC Connor WE and Shaywitz BA (2005). A quantitative analysis of prenatal intake of n-3 polyunsaturated fatty acids and cognitive development. Am J Prev Med 29:366-374.
 
Larqué E Gil-Sánchez A Prieto-Sánchez MT and Koletzko B (2012). Omega 3 fatty acids, gestation and pregnancy outcomes. Br J Nutr 107:S77-S84.
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