Associations of maternal prenatal emotional symptoms with neurodevelopment of children and the neonatal meconium microbiota: A prospective cohort study

Abstract

Background: Maternal emotional symptoms during pregnancy increase the risk of neurodevelopmental problems in offspring, and microbiota have been shown to be a potential mechanism underlying the link. However, the associations among maternal prenatal emotional symptoms, the meconium microbiota, and offspring neurodevelopment have yet to be fully elucidated. The aim of this prospective cohort study was to assess the relationship between maternal prenatal emotional symptoms and neurodevelopment of the child at 24 months of age, and to investigate the potential role of the neonatal meconium microbiota in the relationship.

Methods: A total of 410 mother-child pairs (152 women in the Symptoms group vs. 258 women in the No-symptoms group) were recruited from the ongoing Shanghai Maternal-Child Pairs Cohort. This study included a subgroup of women who were assessed for maternal anxiety and depressive symptoms at 32-36 weeks of gestation. Neonatal meconium samples were collected after birth for 16 S sequencing. Children's neurodevelopment was measured using the Ages and Stages Questionnaire, Third Edition (ASQ-3) and Strengths and Difficulties Questionnaire (SDQ) at 24 months postnatally (n = 287).

Results: Compared with the No-symptoms group, children in the Symptoms group had a higher degree of hyperactivity and total difficulties at 24 months of age. Increases in alpha diversity, distinct overall composition, enriched relative abundance of Proteobacteria, and different predicted microbial functions were observed in the meconium of neonates exposed to maternal prenatal emotional symptoms. The neonatal gut microbiota alpha diversity and relative abundance of genera from the Proteobacteria phylum and Lactobacillus were negatively correlated with children's degree of prosocial behavior, tendency toward hyperactivity, and poor fine motor development. In addition, mediating effects of neonatal meconium microbial richness and the relative abundance of Lactobacillus were observed between maternal emotional symptoms and children's prosocial behavior.

Conclusions: Maternal prenatal emotional symptoms are associated with alterations in the offspring meconium microbiota and children's neurodevelopment at 24 months of age, and the microbial richness indices and Lactobacillus may play a mediating role. Future research is needed to identify and understand the biological pathways and metabolisms linking the relationships among maternal emotional symptoms, meconium microbiota, and neurodevelopment of children.

Keywords: Child neurodevelopment; Cohort study; Maternal emotional symptoms; Meconium microbiota.