RNA-Sequencing of Umbilical Cord Blood to Investigate Spontaneous Preterm Birth: A Pilot Study

Objective  To analyze the transcriptomic gene expression of umbilical cord blood leukocytes using RNA-sequencing from preterm birth (PTB) and term birth (TB). Study Design  Eight women with spontaneous PTB (sPTB) and eight women with unlabored TB were enrolled prospectively. The sPTB and TB cohorts were matched for maternal age, race, mode of delivery, and fetal sex. Cord blood RNA was extracted and a globin depletion protocol was applied, then sequenced on the Illumina HiSeq 4000. Raw read counts were analyzed with DESeq2 to test for gene expression differences between sPTB and TB. Results  148 genes had significant differential expression ( q  < 0.01). Cell cycle/metabolism gene expression was significantly higher and immune/inflammatory signaling gene expression significantly lower in the sPTB cohort compared with term. In African American (AA) infants, 18 genes specific to cell signaling, neutrophil activity, and major histocompatibility complex type 1 had lower expression in preterm compared with term cohort; the opposite pattern was seen in non-Hispanic Whites (NHWs). Conclusion  Compared with term, preterm fetuses have higher cell cycle/metabolism gene expression, suggesting metabolic focus on growth and development. Immune function gene expression in this pilot study is lower in the sPTB group compared with term and differs in AA compared with NHW infants.