Promoter Methylation Changes in the Placental DIO3 and CRH Genes Are Involved in the Second Trimester Maternal Depression Induced Preterm Birth and Small for Gestational Age Birth

Abstract

Background Recent studies suggest that the incidence of preterm birth and SGA birth related to maternal depression, but the mechanism is unclear. The aim of this study was to explore the placental epigenetic changes involved in maternal depression induced preterm birth and small for gestational age birth. Methods Three hundred forty-five pregnant women were enrolled in this cohort study. Maternal depression in the second and third trimesters was assessed using a self-rating depression scale (SDS). We selected placental samples from pregnant women with depression and an equivalent number for samples from pregnant women without depression. Methylation of the promoter regions of the placental DIO3 and CRH genes was determined using next generation sequencing based on bisulfite sequencing PCR (NGS-BSP). Results There were 97 (28.1%) and 95 (27.5%) pregnant women who had depression in the second trimester and third trimester, respectively. The risk factors of preterm birth were older maternal age (RR = 1.43, 95%CI = 1.01–2.03), uterine infection (RR = 129.31, 95%CI = 2.16-7725.55), and maternal depression in the second trimester (RR = 79.97, 95%CI = 3.57-1792.56). The risk factors of SGA birth were low maternal BMI (RR = 0.71, 95%CI = 0.54ཞ0.92), hypertensive disorder complicating pregnancy (HDCP, RR = 4.7, 95%CI = 1.18ཞ18.72), and maternal depression in the second trimester (RR = 3.71, 95%CI = 1.31ཞ12.16). Pregnant women with depression had higher placental methylation of CRH and DIO3 genes, and there was a correlation between placental methylation of CRH and DIO3 genes. Conclusion Our study suggested that the changes in the promoter region of the placental DIO3 and CRH genes were involved in maternal depression in the second trimester induced preterm birth and small for gestational age birth.