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Effect of long-chain polyunsaturated fatty acid supplementation of preterm infants on disease risk and neurodevelopment: a systematic review of randomized controlled trials ^1,2,3

¹ From the Child Health Research Institute, Child, Youth and Women's Health Service, North Adelaide, Australia and the Department of Paediatrics, University of Adelaide, Adelaide, Australia (LGS, RAG, and MM); the Child Health Research Institute at Flinders, Flinders Medical Centre, Bedford Park, Australia (LGS and MM); the School of Agriculture, Food and Wine, University of Adelaide, Adelaide, Australia (RAG); and the Neonatal Medicine, Child, Youth and Women's Health Service, North Adelaide, Australia (AM)

Background: Supplementation of preterm formulas with long-chain polyunsaturated fatty acids (LCPUFAs) is based on their effectiveness to increase blood status and improve visual outcomes. Dispute remains over their efficacy on global development.

Objective: The objective was to compare the effects of LCPUFA-supplemented with those of control formulas on neurodevelopment and diseases associated with prematurity.

Design: We systematically reviewed randomized controlled trials involving preterm infants that tested LCPUFA-supplemented formulas. The weighted mean differences (WMDs) in neurodevelopmental scores and relative risk (RR) of disease were calculated to compare infants fed LCPUFA-supplemented formula with those fed control formula.

Results: No clear differences in Bayley Scales of Infant Development (BSID) scores were observed between groups. Mental development of LCPUFA-supplemented infants was 3.4 points higher than that of control infants with BSID version II (WMD: 3.44; 95% CI: 0.56, 6.31; P = 0.02; n = 879), although it was driven by 2 trials with large effect sizes and wide CIs. Psychomotor development was lower in supplemented infants tested with BSID version I (WMD: –7.99; 95% CI: –14.00, –1.99; P = 0.009; n = 87); however, it was limited by small sample sizes. No differences in the RR of sepsis (1.08; 95% CI: 0.79, 1.46; P = 0.63; n = 1333) or in the RR of necrotizing enterocolitis (1.13; 95% CI: 0.62, 2.04; P = 0.69; n = 1333) were found. Similarly, the risks of retinopathy of prematurity, intraventricular hemorrhage, and bronchopulmonary dysplasia were not different between groups, but data were limited by small sample sizes and trials with an increased risk of bias.

Conclusions: LCPUFA-supplemented formula does not alter the risk of NEC or sepsis. Further work is needed to determine the extent of benefit of LCPUFA-supplemented formula on the mental development of preterm infants.