AUTHOR=Krey Francieli Cristina , Stocchero Bruna Alvim , Creutzberg Kerstin Camile , Heberle Bernardo Aguzzoli , Tractenberg Saulo Gantes , Xiang Li , Wei Wei , Kluwe-Schiavon Bruno , Viola Thiago Wendt 

TITLE=Neurotrophic Factor Levels in Preterm Infants: A Systematic Review and Meta-Analysis

JOURNAL=Frontiers in Neurology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.643576

DOI=10.3389/fneur.2021.643576

ISSN=1664-2295

ABSTRACT=<p><bold>Objectives:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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; <italic>p</italic> = 0.014) and NT-3 (SMD = −0.31; 95% CI: −0.52, −0.09; <italic>p</italic> = 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.</p><p><bold>Conclusions:</bold> 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.</p>