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
Developmental Cognitive Neuroscience Lab (DCNL), Graduate Program in Pediatrics and Child Health-School of Medicine, Pontifical University Catholic of Rio Grande Do Sul (PUCRS), Porto Alegre, Brazil.
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.
Front Neurol. 2021 Apr 1;12:643576. doi: 10.3389/fneur.2021.643576. eCollection 2021.
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. 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. 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; = 0.014) and NT-3 (SMD = -0.31; 95% CI: -0.52, -0.09; = 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. 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.
通过对文献进行系统综述和荟萃分析，我们旨在比较足月儿和早产儿之间脑源性神经营养因子（BDNF）、神经生长因子（NGF）、神经营养素-3（NT-3）、神经营养素-4（NT-4）和胶质细胞源性神经营养因子（GDNF）的水平，并研究与效应大小估计值变异性相关的因素。分析在三个在线数据库MEDLINE Complete、PsycINFO和CINAHL中进行。采用随机效应模型计算早产儿与足月儿神经营养因子水平的标准化均数差（SMD），置信区间为95%（CI）。为了探索异质性来源，实施了meta回归模型。本荟萃分析纳入了16项研究。对1379例早产儿和1286例足月儿的合并样本进行了评估。我们发现，与足月儿相比，早产儿的BDNF（SMD = -0.32；95%CI：-0.59，-0.06；P = 0.014）和NT-3（SMD = -0.31；95%CI：-0.52，-0.09；P = 0.004）水平显著降低。两组之间NGF和NT-4水平未观察到显著差异。鉴于GDNF水平仅产生了两个效应大小，未进行荟萃分析模型。Meta回归模型显示，样本类型（胎盘组织、脑脊液、外周血和脐带血）是BDNF荟萃分析异质性的显著调节因素。未发现新生儿孕周、出生体重和临床合并症与效应大小之间存在显著关联。我们的研究结果表明，较低的BDNF和NT-3水平可能与早产有关。未来更大样本量的研究应调查早产儿神经营养因子失调导致的神经发育表现。
