Efficacy and safety of long-chain polyunsaturated fatty acid supplementation of infant-formula milk: a randomised trial

Background We tested whether addition of n-3 and n-6 longchain polyunsaturated fatty acids (LCPUFA) to infant-formula milk during the first 6 months promotes long-term cognitive and motor development, without adverse consequences. Methods We did a double-blind, randomised, controlled, efficacy and safety trial of formula with and without LCPUFAs, with an additional breastfed reference group, in four hospitals in two cities in the UK. The participants were 447 healthy full-term babies. 309 were fed formula (155 without LCPUFAs) and 138 were breastfed for at least 6 weeks. The main outcome measures were: Bayley Mental and Psychomotor Development Indices (MDI, PDI) at 18 months (primary efficacy outcome) and Knobloch, Passamanick, and Sherrards test at 9 months (secondary outcome). Principal safety outcomes were: infection, atopy, growth, and gastrointestinal tolerance. Findings Babies fed formula with and without LCPUFA did not differ in cognitive or motor development, growth, infection, atopy or tolerance. The mean (95% CI) MDI was 0•5 (-2•7 to 3•8) units and the PDI 0•6 (-1•8 to 3•0) units higher in the supplementation group. Formula-fed infants had similar developmental scores to the breastfed reference group after adjustment for higher social class and maternal education in the latter. Interpretation There was no evidence of a beneficial or adverse effect on cognitive and motor development or growth up to 18 months. Although no significant differences in safety outcomes were observed, we suggest such data should be collected in future LCPUFA trials. Our trial does not provide support for addition of LCPUFA to standard infant formula but we are now doing further follow-up of this cohort.