The role of m6A methylation in prenatal maternal psychological distress and birth outcome

Background: Prenatal maternal psychological distress (PMPD) is a known risk factor for adverse birth outcomes. N6-methyladenosine RNA (m6A) methylation is crucial in moderating RNA biology. This study aimed to evaluate the relationships between PMPD, birth outcomes, and placental m6A methylation.Methods: This was a prospective cohort study. PMPD exposure was assessed by questionnaires about prenatal stress, depression, and anxiety. Placental m6A methylation was measured using a colorimetric assay. The re-lationships between PMPD, m6A methylation, gestational age (GA), and birth weight (BW) were analyzed using structural equation models (SEMs). Maternal weight gain during pregnancy and infant sex were included as covariables. Results: The study included 209 mother-infant dyads. In an adjusted SEM, PMPD was associated with BW (B = -26.034; 95 % CI:-47.123,-4.868) and GA (B = - 0.603; 95 % CI:-1.102,-0.154). M6A methylation was associated with PMPD (B = 0.055; 95 % CI: 0.040,0.073) and BW (B = - 305.799; 95 % CI:-520.164,-86.460) but not GA. The effect of PMPD on BW was partially mediated by m6A methylation (B =-16.817; 95 % CI: -31.348,-4.638) and GA (B = - 12.280; 95 % CI:-23.612,-3.079). Maternal weight gain was associated with BW (B = 5.113; 95 % CI: 0.229,10.438). Limitations: The study sample size was small, and the specific mechanism of m6A methylation on birth outcomes needs to be further explored. Conclusions: In this study, PMPD exposure negatively affected BW and GA. Placental m6A methylation was associated with PMPD and BW and partially mediated the effect of PMPD on BW. Our findings highlight the importance of perinatal psychological evaluation and intervention.