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 relationships 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.

Associations between maternal prenatal depression and neonatal behavior and brain function - Evidence from the functional near-infrared spectroscopy.

BACKGROUND: Maternal prenatal depression is a significant public health issue associated with mental disorders of offspring. This study aimed to determine if maternal prenatal depressive symptoms are associated with changes in neonatal behaviors and brain function at the resting state. METHODS: A total of 204 pregnant women were recruited during the third trimester and were evaluated by Edinburgh Postpartum Depression Scale (EPDS). The mother-infant pairs were divided into the depressed group (n = 75) and control group (n = 129) based on the EPDS, using a cut-off value of 10. Cortisol levels in the cord blood and maternal blood collected on admission for delivery were measured. On day three of life, all study newborns were evaluated by the Neonatal Behavior Assessment Scale (NBAS) and 165 infants were evaluated by resting-state functional near-infrared spectroscopy (rs-fNIRS). To minimize the influences of potential bias on the rs-fNIRS results, we used a binary logistic regression model to carry out propensity score matching between the depressed group and the control group. Rs-fNIRS data from 21 pairs of propensity score-matched newborns were used for analysis. The associations between maternal EPDS scores, neonatal NBAS scores, and cortisol levels were analyzed using linear regressions and the mediation analysis models. RESULTS: Compared to the control group, the newborns in the depressed group had lower scores in the social-interaction and autonomic system dimensions of NBAS (P < 0.01). Maternal and umbilical cord plasma cortisol levels in the depressed group were higher (P < 0.01) than in the control group. However, only umbilical cord plasma cortisol played a negative mediating role in the relationship between maternal EPDS and NBAS in the social-interaction and autonomic system (ß med = -0.054 [-0.115,-0.018] and -0.052 [-0.105,-0.019]. Proportional mediation was 13.57 % and 12.33 for social-interaction and autonomic systems, respectively. The newborns in the depressed group showed decreases in the strength of rs-fNIRS functional connections, primarily the connectivity of the left frontal-parietal and temporal-parietal regions. However, infants in the depressed and control groups showed no differences in topological characteristics of the brain network, including standardized clustering coefficient, characteristic path length, small-world property, global efficiency, and local efficiency (P > 0.05). The social-interaction Z-scores had positive correlations with functional connectivity strength of left prefrontal cortex-left parietal lobe (r = 0.57, p < 0.01)，prefrontal cortex-left parietal lobe - left temporal lobe (r = 0.593, p < 0.01) and left parietal lobe - left temporal lobe (r = 0.498, p < 0.01). Autonomic system Z-scores were also significantly positive correlation with prefrontal cortex-left parietal lobe (r = 0.509, p < 0.01)，prefrontal cortex-left parietal lobe - left temporal lobe (r = 0.464, p < 0.01), left parietal lobe - left temporal lobe (r = 0.381, p < 0.05), and right temporal lobe and left temporal lobe (r = 0.310, p < 0.05). CONCLUSION: This study shows that maternal prenatal depression may affect the development of neonatal social-interaction and autonomic system and the strength of neonatal brain functional connectivity. The fetal cortisol may play a role in behavioral development in infants exposed to maternal prenatal depression. Our findings highlight the importance of prenatal screening for maternal depression and early postnatal behavioral evaluation that provide the opportunity for early diagnosis and intervention to improve neurodevelopmental outcomes.