Abnormal Placental DNA Methylation Variation in Spontaneous Preterm Birth

Objective: Preterm birth (PTB) has become a major public health concern as the leading cause of neonatal death, but little is understood about its etiology. Children born preterm are also at increased risk of long-term consequences such as neurodevelopmental disorders, adulthood hypertension and diabetes. Recent studies have indicated that DNA methylation may be involved in the occurrence of PTB as well as related adverse outcomes. The latest Infinium EPIC BeadChip extends the coverage of the genome and provides a better tool to help investigate the involvement of DNA methylation in these conditions.

Methods: We conducted this case-control study in three Women and Children's hospitals in South China, and enrolled 32 spontaneous preterm births and 16 term births. We assessed placental DNA methylation profiling of these participants with the Infinium EPIC BeadChip. We identified PTB and gestational age (GA)-associated CpG sites with limma regression model, and applied to identify PTB-associated regions. We performed gene ontology analysis to further interpret functional enrichment of the identified differentially methylated genes in PTB.

Results: We identified a total of 8 differentially methylated positions (DMPs) that were significantly associated with PTB (FDR < 0.1) and a total of 15 DMPs that were associated with GA (FDR < 0.1). In the regional analysis, one differentially methylated region in the gene overlapped with PTB-associated CpG site. The differentially methylated CpG sites in PTB were mapped to the genes involving in biological processes mainly regarding neurodevelopment, regulation of inflammation and metabolism.

Conclusion: Our findings suggested that preterm placenta have distinct DNA methylation alterations, and these alteration patterns established at birth provide insight into the long-term consequences of preterm birth.