Long-chain polyunsaturated fatty acids (LCPUFAs) are hypothesized to affect visual acuity development in infants. Randomized controlled trials (RCTs) have been conducted to assess whether supplementation of LCPUFAs of infant formulas affects infant visual acuity. This meta-analysis was conducted to evaluate whether LCPUFA supplementation of infant formulas improves infants’ visual acuity.
PubMed and PsycInfo were searched for RCTs assessing the efficacy of LCPUFA supplementation of infant formulas on infant visual acuity. RCTs assessing the effects of LCPUFA supplementation on visual acuity (by using either visual evoked potential or behavioral methods) in the first year of life were included in this meta-analysis. Our primary outcome was the mean difference in visual resolution acuity (measured in logarithm of minimum angle of resolution [logMAR]) between supplemented and unsupplemented infants. We also conducted secondary subgroup analyses and meta-regression examining the effects of LCPUFA dose and timing, preterm versus term birth status, and trial methodologic quality.
Nineteen studies involving 1949 infants were included. We demonstrated a significant benefit of LCPUFA supplementation on infants’ visual acuity at 2, 4, and 12 months of age when visual acuity was assessed by using visual evoked potential and at 2 months of age by using behavioral methods. There was significant heterogeneity between trials but no evidence of publication bias. Secondary analysis failed to show any moderating effects on the association between LCPUFA supplementation and visual acuity.
Current evidence suggests that LCPUFA supplementation of infant formulas improves infants’ visual acuity up to 12 months of age.
Comments
Why Any Analysis of Infant Formula Effects on Infant Visual Acuity Performed Before the Age of 7 Years is Not Likely Predictive
Qawasmi, et. al. conducted a meta-analysis of 16 randomized controlled trials (RCTs) assessing the effects of Long Chain Polyunsaturated Fatty Acid (LCPUFA) supplementation in infant formula on infant's visual acuity at 2, 4, and 12 months of age using visual evoked potential (VEP) and at 2 months of age by behavioral methods. This meta- analysis raises two fundamental issues: whether early assessment of visual acuity is valid (i.e., predictive of later visual function); and whether a meta-analysis of LCPUFA supplementation of infant formula on infant's visual acuity in the first year of life is informative. Without a clarification of these two issues, the conclusion of this meta-analysis could be misleading and the validity of any such analysis is questionable.
Ocular development is not completed until 7 to 9 years of age (1). Visual acuity develops slowly during the first 4 to 6 years of life, with wide variations in visual acuities often in the 20/200 range (logMAR 1.0) at birth improving to about 20/40 (logMAR 0.3) by 3 to 4 years of life (2, 3). Multiple infant formula supplementation studies have shown that early observations of visual measurements are not predictive of later visual function (4, 5). The development of fine degrees of visual acuity (visual acuity of 20/40 or better) needed for many tasks such as reading do not occur in infants or young children <3 years of age (2, 3). Thus, visual acuity is most meaningful when measured after 7 years of age, when the visual acuity measurement may be predictive of later visual function.
Additionally, even though Qawasmi, et. al. reported that LCPUFA supplements improved electrical brain activity following visual stimulation as assessed by VEP assessment in this age group, they did not discuss two basic questions: 1. whether the electrical differences observed in these studies are clinically meaningful; 2. whether the benefits reported have any long-term impact on actual visual acuity development. A doubling of the visual angle which is equivalent to a 0.3 logMAR difference is commonly considered to be clinically significant. When examining the studies listed in the review, the improvement was small (theoretically equivalent to 0.05 - 0.2 logMAR) and decreased over time. This indicates that LCPUFA supplementation might have a minimal transient statistical effect, but this effect can not be considered clinically significant. Up to date, no study has followed children for 7 years or longer. The only known studies with 2 - 6 year olds, demonstrated that DHA and ARA supplements had no effect on visual function in either term or preterm infants (4, 5).
For these reasons, the conclusion of this meta-analysis and other similar analyses could be misleading. It is not possible to determine whether supplementation will result in improved visual function in the absence of controlled clinical trials in which pediatric subjects are randomized to receive infant formula with or without supplementation and visual acuity is measured after the fine-resolving ability of the eye has developed.
Reference List
(1) Assaf AA. The sensitive period: transfer of fixation after occlusion for strabismic amblyopia. Br J Ophthalmol 1982;66:64-70.
(2) Pan Y, Tarczy-Hornoch K, Cotter SA, et al. Visual Aucity Norms in Preschool Children: The Multi-Ethnic Pediatric Eye Disease Study. Optom Vis Sci 2009 June; 86(6):607-612.
(3) Atkinson J, Braddick O, Pimm-Smith E. 'Preferential looking' for monocular and binocular acuity testing of infants. Br J Ophthalmol 1982; 66:264-268.
(4) Auestad N, Scott DT, Janowsky JS et al. Visual, cognitive, and language assessments at 39 months: a follow-up study of children fed formulas containing long-chain polyunsaturated fatty acids to 1 year of age. Pediatrics 2003;112:e177-e183.
(5) Singhal A, Morley R, Cole TJ et al. Infant nutrition and stereoacuity at age 4-6 y. Am J Clin Nutr 2007;85:152-159.
Conflict of Interest:
None declared
Questionable Impact of Fatty Acid Supplementation of Infant Formula
There was no comparison of the visual acuity associated with supplemented infant formula and the visual acuity obtained with breastfeeding, especially optimal breastfeeding, based on early initiation (within one hour of birth), exclusive breastfeeding for six months, and continued breastfeeding for two years or more. It might be that, on this dimension, supplemented formula is slightly better than un-supplemented formula, but far worse than breastfeeding.
The study showed that the efficacy of supplementation was not significantly associated with its dosage, with either of the two assessment methods that were used to detect visual acuity. Similarly, the timing of the start of supplementation and its duration apparently had no impact on the efficacy of the supplementation in improving visual acuity. These observations raise further questions about whether the supplementation produced substantial improvements in visual acuity.
The concluding discussion begins, "In this meta-analysis, we demonstrate a significant benefit of LCPUFA supplementation of infant formula on infant visual acuity at several stages of development." The closing paragraph repeats, "Overall, our meta-analysis demonstrates a significant benefit of LCPUFA supplementation to infant formula on infant visual acuity during the first year of life." These statements could mislead some readers. There might have been "significant" impacts in the purely statistical sense, but that is not the same as claiming there were substantial benefits for infants.
The claim, "Our meta-analysis provides strong evidence to support LCPUFA supplementation of infant formula to enhance visual development" was followed with discussion of several limitations to the study. Those, together with the issues raised here, raise hard question about whether this meta-analysis in fact provides strong support for supplementation.
An article by Qawasmi and colleagues in Pediatrics in June 2012 with a similar title and purpose was mentioned in this newer article only in passing. Its finding was, "Our meta-analysis demonstrated no significant effect of LCPUFA supplementation of formula on infant cognition." How is it that the polar opposite findings of these two similar studies were not discussed in this later article?
Also, the value of early assessments of visual acuity were questioned in a critique by John Columbo and Susan Carlson in an article published in Pediatrics at the same time as Qawasmi's earlier article. Why were these concerns not addressed in this more recent article from Qawasmi?
Aloha, George Kent
REFERENCES
Colombo, J., Carlson, S.E., 2012. Is the measure the message: the BSID and nutritional interventions. Pediatrics. 129(6), June. 1166-1167.
Qawasmi, A., Landeros-Weisenberger, A., Leckman, J.F., Bloch, M.H., 2012. Meta-analysis of long-chain polyunsaturated fatty acid supplementation of formula and infant cognition. Pediatrics.129(6) June.
Conflict of Interest:
None declared