Inflammatory Biomarkers and Neurotrophic Factors in Preterm Newborns as Predictors of Motor Development: A Systematic Review

<b>Background/Objectives:</b> Preterm newborns (NBs) are at increased risk of motor developmental impairments. Evidence on inflammatory and neurotrophic biomarkers measured in the neonatal period as predictors of motor outcomes is scarce and heterogeneous. This systematic review synthesised data on inflammatory biomarkers and neurotrophic factors in Preterm NB as predictors of motor development (MD) up to 24 months of corrected age. <b>Methods:</b> MEDLINE, SciELO, Web of Science and Embase were searched for longitudinal observational studies of Preterm NB (World Health Organization definition) that measured one or more inflammatory biomarkers and/or neurotrophic factors in blood, urine or saliva and applied validated neurodevelopmental scales up to 24 months. Non-original reports, populations outside scope and studies with incomplete data were excluded. Methodological quality of primary studies was assessed with the Newcastle-Ottawa Scale (NOS). The protocol was registered in PROSPERO (CRD42022365839). <b>Results:</b> Of 1475 records, eight studies met the eligibility criteria. Higher neonatal concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) were generally associated with poorer motor performance, although null findings occurred in some cohorts. One study assessing neurotrophic factors reported elevated urinary brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) among infants with below-expected MD. <b>Conclusions:</b> Inflammatory biomarkers show promise as early indicators of adverse MD in Preterm NB, but heterogeneity in populations, biospecimens, sampling windows, assays and outcome scales limits comparability and precludes definition of risk thresholds. Larger, standardised cohorts are needed to clarify the prognostic value of inflammatory and neurotrophic biomarkers and to inform early risk stratification.