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    Objectives: Through a systematic review and meta-analysis of the literature we aimed to compare the levels of BDNF, NGF, NT-3, NT-4, and GDNF between human term and preterm infants, and investigate factors implicated in the variability of effect size estimates. Methods: The analysis was performed in three online databases, MEDLINE Complete, PsycINFO, and CINAHL. A random effects model was used to calculate the standardized mean difference (SMD) of neurotrophic factor levels in preterm infants vs. term within a 95% confidence interval (CI). To explore sources of heterogeneity meta-regression models were implemented. Results: Sixteen studies were included in this meta-analysis. A combined sample of 1,379 preterm and 1,286 term newborns were evaluated. We identified significant lower BDNF (SMD = -0.32; 95% CI: -0.59, -0.06; p = 0.014) and NT-3 (SMD = -0.31; 95% CI: -0.52, -0.09; p = 0.004) levels in preterm compared to term infants. No significant difference was observed in NGF and NT-4 levels between groups. Given that only two effect sizes were generated for GDNF levels, no meta-analytical model was performed. Meta-regression models revealed sample type (placental tissue, cerebrospinal fluid, peripheral blood, and umbilical cord blood) as a significant moderator of heterogeneity for BDNF meta-analysis. No significant associations were found for gestational week, birth weight, and clinical comorbidity of newborns with effect sizes. Conclusions: Our findings indicated that lower BDNF and NT-3 levels may be associated with preterm birth. Future studies with larger samples sizes should investigate neurodevelopmental manifestations resulting from neurotrophic factor dysregulation among preterm infants. Copyright © 2021 Krey, Stocchero, Creutzberg, Heberle, Tractenberg, Xiang, Wei, Kluwe-Schiavon and Viola.


    Francieli Cristina Krey, Bruna Alvim Stocchero, Kerstin Camile Creutzberg, Bernardo Aguzzoli Heberle, Saulo Gantes Tractenberg, Li Xiang, Wei Wei, Bruno Kluwe-Schiavon, Thiago Wendt Viola. Neurotrophic Factor Levels in Preterm Infants: A Systematic Review and Meta-Analysis. Frontiers in neurology. 2021;12:643576

    PMID: 33868149

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