Effect of Long-Chain Polyunsaturated Fatty Acids in Infant Formula on Cognitive Function Beyond Infancy: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Abstract

Background: Supplementation of infant formula with long-chain polyunsaturated fatty acids (LCPUFA) is now standard practice, but clear evidence from randomised controlled trials (RCT) of functional benefits is lacking. Methods: We performed a systematic review and meta-analysis of published and unpublished data from RCTs that compared infant formula with and without LCPUFA. We determined the effect of LCPUFA-supplementation on standardised assessments of cognitive function after the age of 2·5 years. We used fixed-effects meta-analyses to compare mean differences in intelligence scores, for participants born at term and preterm. This study is registered with PROSPERO. Findings: We included eight RCTs that randomised participants between 1982 and 2004. The age at the last available cognitive test ranged from 3·3 to 16 years. The pooled mean difference in IQ score from four trials in term-born children was consistent with a lower IQ score in LCPUFA-supplemented compared with unsupplemented groups: pooled mean difference -2·87 points (95% CI -5·74,-0·01). Two trials in preterm-born children found no detectable difference in IQ score between groups: pooled mean difference -1·88 (-6·04, 2·29). Overall study quality was low, partly due to high losses to follow-up. Interpretation: We found no evidence of benefit and weak evidence that LCPUFA-supplementation reduced IQ score in term-born children, though at borderline significance. These findings are relevant to regulators of infant formula when considering whether any evidence of benefit outweighs the potential disadvantages for cognitive function. Funding: Economic and Social Research Council UBEL DTP studentship. Declaration of Interest: M. Verfurden, S. Dib and Dr. Gilbert and Dr. Jerrim declare no competing interests. Dr. Fewtrell was involved in data analysis and publication of randomised trials of LCPUFA-supplemented infant formulas funded by grants from Numico Res BV and Heinz UK. The companies also provided the infant formulas for the studies. She was also involved in follow-up studies (including cognitive outcome) of children and adolescents from randomised trials of LCPUFA-supplemented formulas, with funding from the Medical Research Council and European Union (FP6-FOOD-2005-007036). She has been a member of Infant Nutrition Working Group at EFSA (European Food Safety Authority) since 2013.