Loma Linda University Children's Hospital Colton, California, United States
Background: Preeclampsia (PE) is a pregnancy-specific hypertensive disease with multisystem involvement diagnosed at >20 weeks gestation in previously normotensive women. In the past 20 years, PE incidence has increased by 25% in the U.S. and is now the leading cause of maternal/infant morbidity and mortality. Neonatal comorbidities include acute and chronic sequelae even into adulthood (e.g., sepsis, RDS, BPD, NDD, mood disorders, and metabolic syndrome). These observed comorbidities may be due to fetal reprogramming, an epigenetic modification caused by PE. Cell-free fetal RNA (cffRNA), found in maternal blood, may be differentially expressed in preeclamptic mothers and can be used to assess potential biomarkers for disease severity correlation in PE and neonatal outcomes. Objective: In this study, our objective is to determine how preeclampsia alters global gene expression in fetal tissue and quantify changes in expression that correlate with disease severity, defined as time to delivery, and neonatal outcomes, including IUGR, HIE, RDS, TTN, BPD, apnea of prematurity, caffeine therapy, cytopenia, hypoglycemia, NDD). We will test this by assessing the differential expression of cffRNA in mothers with PE compared to normotensive controls. Design/Methods: We recruited 20 singleton preeclamptic mothers and 4 singleton normotensive mothers with term, uncomplicated pregnancies upon admission to the Loma Linda University Hospital Labor and Delivery unit. We collected 10 mL of whole blood into EDTA tubes using sterile phlebotomy techniques. Plasma was separated (centrifuged) and stored at –80 degrees C. RNA sequencing will then be performed with 75 base paired-end primers at a depth of 20 million bases by NORGEN. We will use R plus the DESeq2 package to identify differentially expressed genes (DEGs) that correlate with the pre-defined outcomes. Our work will evaluate associations between DEGs and disease severity to suggest a multi-omic foundation for future guidance on the optimum delivery interval for PE exposed fetuses.
