Placental epigenetic age: Associations with prenatal maternal psychosocial adversities and preschool emotional and behavioral problems

Background: The link between prenatal psychosocial adversity and offspring behavioral problems is wellestablished; however, the underlying pathways are still being explored. Methods: Data was a random sample from the Shanghai Maternal-Child Pairs Cohort including women enrolled at early pregnancy and followed children 3-6 years old. The current study comprised 82 mother-offspring dyads based on the availability of placental DNA methylation. A cumulative number of maternal psychosocial adversities was the primary exposure, including socioeconomic, mental conditions, behavioral lifestyle, and physical disorders. Individual adversity components were analyzed as secondary exposures. Placental epigenetic age acceleration (EAA) derived from the difference between epigenetic age and gestational age at birth. Emotional and behavioral problems for preschool children were assessed by the Strengths and Difficulties Questionnaire. Results: Mothers who faced two to four psychosocial adversities, or at least five adversities, exhibited 1.51 weeks (95 % CI: 0.66-2.36) and 1.67 weeks (95 % CI: 0.87-2.47) of EAA, respectively, compared to those without or one adversity. Maternal prenatal high-level stress, depression symptoms, occupational hazards, poor sleep quality, GDM were associated with placental EAA. Placental EAA was positively associated with preschool greater emotional and behavioral problems, especially in boys. The mediated proportion of EAA was 13.8 %, 21.3 % for the association of psychosocial adversities with total difficulties and internalizing problems. Conclusion: Prenatal maternal psychosocial adversities would accelerate placental epigenetic age, which would increase preschool emotional and behavioral problems.