Long-chain polyunsaturated fatty acid (LCPUFA) supplementation on neurodevelopmental outcomes in preterm or low birth weight (LBW) infants is controversial. This study aims to evaluate the effects of early LCPUFA supplementation on short- and long-term neurodevelopmental outcomes in preterm or LBW infants. This study was previously registered (CRD42024503566). We searched MEDLINE, Embase, PsycInfo, ClinicalTrials.gov and Cochrane Database through January 2024. Randomised clinical trials (RCTs) or follow-up studies comparing early LCPUFA supplementation to placebo or no supplementation in preterm or LBW infants were included. Outcomes assessed included long-term (>= 5 years) and short-term (< 5 years) measures, such as IQ, neurodevelopmental impairment (NDI), mental development index (MDI) and psychomotor development index (PDI). A random-effects model was used to pool outcome data. Thirteen RCTs involving 3360 participants were analysed. Due to imprecision, it was unclear whether LCPUFA supplementation had a beneficial or harmful effect on long-term IQ (SMD, 0.00; 95% CI, -0.32 to 0.33; I2 = 63%; very low certainty) or on the risk of NDI (RR, 0.77; 95% CI, 0.55-1.08; low certainty), as the confidence intervals allow for potentially clinically meaningful effects. LCPUFA supplementation may reduce the risk of intellectual disability (RR, 0.58; 95% CI, 0.36-0.93; moderate certainty). The evidence did not clearly show short-term neurodevelopmental benefits. Evidence quality varied from moderate to very low. LCPUFA supplementation may not improve most neurodevelopmental outcomes, but could reduce the risk of intellectual disability in preterm or LBW infants. Further studies with long-term follow-up are recommended.
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