Epigenetic profiling of preterm birth: a dual-tissue methylation patterns using long-read sequencing.

Hospital-based case-control study using long-read sequencing to profile DNA methylation in matched maternal and neonatal samples.

“This hospital-based case–control study was conducted at the Women’s Wellness and Research Center (WWRC), Qatar, from September 2022 to December 2024.”

Singleton mother-infant pairs from preterm (<32 weeks) and full-term (37-42 weeks) deliveries with natural labor.

“The study included 22 singleton mother-infant pairs who had natural labor, comprising 15 preterm births (gestational age of less than 32 weeks) and seven full-term births (gestational age of 37-42 weeks) with normal birth weight.”

22 mother-infant pairs (15 preterm, 7 full-term).

“The study included 22 singleton mother-infant pairs who had natural labor, comprising 15 preterm births (gestational age of less than 32 weeks) and seven full-term births (gestational age of 37-42 weeks) with normal birth weight.”

Data collection occurred from September 2022 to December 2024.

“This hospital-based case–control study was conducted at the Women’s Wellness and Research Center (WWRC), Qatar, from September 2022 to December 2024.”

Identification of 1,151 differentially methylated regions and 25,336 differentially methylated loci across maternal and neonatal blood samples.

“A total of 1,151 significantly differentially methylated regions (DMRs) and 25,336 differentially methylated loci (DMLs) were identified across maternal and neonatal blood samples.”

Distinct hypermethylated and hypomethylated genes were identified in maternal blood (e.g., MED38, EXTL3) and neonatal cord blood (e.g., LOC401478, ALOX12).

“In maternal blood from PTB cases, the most significantly hypermethylated genes were MED38, PSMB11, and WNT7B, whereas EXTL3 and MMP9 were among the most hypomethylated.”

Enrichment analysis indicated that epigenetic alterations impact developmental, immune, and neuroendocrine pathways including Wnt signaling and oxytocin signaling.

“Enrichment analysis revealed that these epigenetic alterations impact critical developmental, immune, and neuroendocrine pathways, including Wnt signaling, calcium signaling, MAPK, oxytocin signaling, and neuroactive ligand-receptor interaction.”

The study did not perform RNA sequencing to directly correlate methylation changes with gene expression.

“RNA sequencing was not performed on maternal peripheral or cord blood samples in this study; hence, direct correlation between promoter-associated DMLs and gene expression was not assessed.”