Brain-Derived Neurotrophic Factor Levels in Cord Blood from Growth Restricted Fetuses with Doppler Alteration Compared to Adequate for Gestational Age Fetuses

Abstract

Background and Objectives: Fetal growth restriction (FGR) is a severe obstetric disease characterized by a low fetal size entailing a set of undesired consequences. For instance, previous studies have noticed a worrisome association between FGR with an abnormal neurodevelopment. However, the precise link between FGR and neurodevelopmental alterations are not yet fully understood yet. Brain-derived neurotrophic factor (BDNF) is a critical neurotrophin strongly implicated in neurodevelopmental and other neurological processes. In addition, serum levels of BDNF appears to be an interesting indicator of pathological pregnancies, being correlated with the neonatal brain levels. Therefore, the aim of this study is to analyze the blood levels of BDNF in the cord blood from fetuses with FGR in comparison to those with weight appropriate for gestational age (AGA). Materials and Methods: In this study, 130 subjects were recruited: 91 in group A (AGA fetuses); 39 in group B (16 FGR fetuses with exclusively middle cerebral artery (MCA) pulsatility index (PI) < 5th percentile and 23 with umbilical artery (UA) PI > 95th percentile). Serum levels of BDNF were determined through ELISA reactions in these groups. Results: Our results show a significant decrease in cord blood levels of BDNF in FGR and more prominently in those with UA PI >95th percentile in comparison to AGA. FGR fetuses with exclusively decreased MCA PI below the 5th percentile also show reduced levels of BDNF than AGA, although this difference was not statistically significant. Conclusions: Overall, our study reports a potential pathophysiological link between reduced levels of BDNF and neurodevelopmental alterations in fetuses with FGR. However, further studies should be conducted in those FGR subjects with MCA PI < 5th percentile in order to understand the possible implications of BDNF in this group.

Blood Biomarkers in the Fetally Growth Restricted and Small for Gestational Age Neonate: Associations with Brain Injury

“…Therefore, findings discussed here require further exploration for validation. Results for BDNF are conflicting [26,41]. Although the findings for IGFBP-1 and later time points for MMP-9 are relatively consistent [27,28,43], there is little overlap in the timepoints assessed and the study populations are all from the Extremely Low Gestational Age Newborns (ELGAN) study.…”

“…Eight studies have examined growth and development markers in FGR, but few have considered the same biomarkers (see Table 2; [26][27][28][39][40][41][42][43]). Three studies examined the levels of Galectins 1 and 3 [39], Netrins 1 and 4 [40] neurogranin, and BDNF [26] and found no differences between FGR and AGA neonates.…”

“…There have been attempts to standardize the definition of FGR [6]. Unfortunately, none of the articles included here conformed to this definition although some used aspects of it [29, 41, 42, 52‒54, 56, 58]. Although only two studies report their cohorts as SGA or SFD [56, 57], many studies have described the cohort as FGR but use a definition of birth weight <10th percentile for GA (online supplementary Table 1; for all online suppl.…”

“…Differences in GA were observed between studies and groups within studies (online suppl. Table 1) [26,29,41,52,54,57,58]. For example, Yue et al [26] investigated a number of biomarkers of interest; however, the median GA for FGR and non-FGR neonates was significantly different (29.9 weeks and 27.3 weeks, respectively).…”

“…A further limitation is the relatively small cohort size in some studies (online suppl. Table 1) [29,39,41,42,51,53,56,58]. Without adequate power in such a heterogeneous population, it is difficult to draw definitive conclusions from reported results.…”