Maternal sleep disturbance during pregnancy and child intelligence quotient: A metabolome‐wide association study in the Shanghai Birth Cohort

BACKGROUND: The impact of maternal sleep disturbances during pregnancy on long-term neurodevelopment and the role of metabolites in this process are not well understood. In a prospective cohort study, we aimed to investigate the associations between maternal sleep disturbances during each trimester and child intelligence quotient (IQ) at the age of 4 years and to identify metabolites that might mediate these relationships. METHODS: This study included 1,870 mother-child pairs from the Shanghai Birth Cohort (SBC). Maternal sleep quality was assessed using the Pittsburgh sleep quality index (PSQI) questionnaire in the first and second trimesters, and a simplified version of the PSQI was used in the third trimester. Child IQ was evaluated at age 4 using the Wechsler Primary and Preschool Scale of Intelligence-Fourth Edition (WPPSI-IV). We conducted untargeted analyses of maternal serum metabolomics in the first trimester in 1,461 subjects. We employed multiple linear regression models to examine the associations between maternal sleep disturbances during each trimester and child IQ. Additionally, we utilized longitudinal latent class analysis (LLCA) to identify patterns of sleep quality changes throughout the three trimesters and employed multiple linear regression models to investigate how these sleep patterns across the entire pregnancy were associated with child IQ. We applied a 'meet-in-the-middle' approach to identify potential metabolites linking maternal sleep disturbances during early pregnancy with child IQ. RESULTS: Longer sleep latency was associated with lower child Full-Scale IQ (FSIQ) and verbal comprehension index (VCI) for the first trimester, while lower child fluid reasoning index (FRI) for the second trimester. Longer sleep latency throughout the pregnancy was associated with decreased FSIQ (β = -4.68; 95% CI: -8.32, -1.03), VCI (β = -6.38; 95% CI: -10.39, -2.37), and FRI (β = -4.29; 95% CI: -7.96, -0.63). We found that inositol, indoleacrylic acid, and 4-hydroxyquinoline emerged as potential biomarkers that play an intermediary role in the association between maternal sleep disturbances and child IQ. CONCLUSIONS: Sleep disturbance during pregnancy may be a risk factor for compromised IQ in preschool-aged offspring. Alterations in inositol and tryptophan metabolism might be the mediator for the link between maternal sleep disturbances and child IQ.