MicroRNAs in Umbilical Cord Blood and Development in Full-Term Newborns: A Prospective Study

Abstract

Background: Exploring the epigenetic regulations, such as microRNA, in newborns holds significant promise for enhancing our ability to address and potentially prevent early-life developmental delays.

Objectives: Hence, this research seeks to investigate if the expression of miRNA in the umbilical cord blood of infants can forecast their developmental outcomes as they grow older.

Design and method: We enrolled 143 full-term newborns, delivered either via cesarean section (CS) or through natural spontaneous delivery (NSD). We then analyzed the profiles of specific miRNAs (miR-486-5p, miR-126-5p, miR-140-3p, miR-151a-3p, miR-142-5p, and miR-30e-5p) in the umbilical cord blood of these infants. Subsequently, we performed follow-up assessments using Bayley-III scores when the cohort reached 1 year of age. Furthermore, we conducted pathway-enrichment analyses on the target genes associated with these examined miRNAs.

Results: When comparing newborns delivered via cesarean section (CS) to those born via natural spontaneous delivery (NSD), we observed notable differences. Specifically, newborns through NSD displayed significantly higher ΔCt values for miR-486-5p, alongside lower ΔCt values for miR-126-5p and miR-151a-3p in their cord blood. At 1 year of age, cognitive development was significantly linked to the ΔCt values of miR-140-3p and miR-142-5p, while language development showed a significant association with the ΔCt values of miR-140-3p. Moreover, our pathway enrichment analyses revealed that the target genes of these miRNAs were consistently involved in the pathways related to neurons, such as axon guidance and the neurotrophin signaling pathway.

Conclusion: In summary, this study represents a pioneering effort in elucidating the potential connections between miRNA levels in cord blood and the health indicators and neurodevelopment of newborns at 1 year of age. Our findings underscore the significance of miRNA levels at birth in influencing mechanisms related to neurodevelopment.

Keywords: Epigenetics; cohort study; cord blood; development; pediatric.

Figure 1.

Differential miRNA expression profile (A: miR-486-5p; B: miR-126-5p; C: miR-151a-3p) between normal spontaneous delivery (NSD) and cesarean section (CS). The P values of comparisons were derived with a t test. * and ** denote P value < .05 and P value < .01, respectively.

Figure 2.

Results of pathway enrichment analysis and interactions among pathways of miR-151a-3p. We had the target genes of miR-151a-3p analyzed with ShinyGO to identify the significant pathways (FDR < 0.05). The top 20 most significant pathways (if applicable) enriched by the target genes were tabulated (the upper panel). N. of Genes denoted the number of the genes commonly shared by the input target genes and the member genes of specific KEGG pathway. Pathway network indicated frequent and close interactions among these significant pathways (the lower panel).