Placental miRNA expression profiles are associated with measures of infant neurobehavioral outcomes

Abstract

Background: A growing body of research suggests that the intrauterine environment influences fetal neurodevelopment by altering the functional placental epigenome. A number of microRNAs (miRNAs) are expressed in the placenta, may be sensitive to dysregulation by environmental exposures, and are associated with adverse pregnancy outcomes. Our study aimed to identify the relationships between placental miRNA expression and newborn neurobehavior.

Methods: We examined the association between the expression of miR-16, miR-21, miR-93, miR-135b, miR-146a, and miR-182 in total RNA from the placentas of 86 term infants as measured by quantitative real-time PCR and newborn neurobehavioral outcomes as assessed using the NICU Network Neurobehavioral Scales (NNNS).

Results: Bivariate analysis revealed that placental miR-16 expression is negatively associated with attention score (P = 0.006), whereas expressions of both miR-146a and miR-182 are positively associated with quality of movement score (P = 0.016 and P = 0.016, respectively). Controlling for potential confounders, high miR-16 expression is significantly associated with reduced attention score (P = 0.04), and high miR-146a and miR-182 expressions are significantly associated with increased quality of movement score (P = 0.04 and P = 0.01, respectively).

Conclusion: These results suggest that placental miRNA expression is associated with early neurobehavioral outcomes and miRNAs in the placenta may contribute to the developmental origins of infant neurobehavior.

Figure 1

Distribution of infant NNNS score (y-axis) by primary term human placenta miRNA expression quartiles (x-axis). Black bar indicates mean NNNS score within each quartile. (A) Placental miR-16 expression is negatively associated with attention score (p=0.046), (B) Placental miR-146a expression is positively associated with quality of movement score (p=0.022), and (C) Placental miR-182 expression is positively associated with quality of movement score (p=0.027)

Figure 2

Distribution of infant NNNS score (y-axis) by high-low miRNA expression groups (x-axis). Black bar indicates mean NNNS score within each group (A) Placental miR-16 expression is negatively associated with attention score (p=0.006), (B) Placental miR-146a expression is positively associated with quality of movement score (p=0.016), and (C) Placental miR-182 expression is positively associated with quality of movement score (p=0.016).