BackgroundThe 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.MethodsThis 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.ResultsLonger 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.ConclusionsSleep 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.

中文翻译：

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孕期母亲睡眠障碍和儿童智商： 上海出生队列中的代谢组范围关联研究

背景孕期母亲睡眠障碍对长期神经发育的影响以及代谢物在此过程中的作用尚不清楚。在一项前瞻性队列研究中，我们旨在调查每个孕期母亲睡眠障碍与 4 岁儿童智商 （IQ） 之间的关联，并确定可能介导这些关系的代谢物。方法本研究纳入了来自上海出生队列 （SBC） 的 1,870 对母子。在孕早期和孕中期使用匹兹堡睡眠质量指数 （PSQI） 问卷评估产妇睡眠质量，在孕晚期使用 PSQI 的简化版本。使用 Wechsler 小学和学前智力量表 - 第四版 （WPPSI-IV） 在 4 岁时评估儿童智商。我们对 1,461 名受试者在妊娠早期的母体血清代谢组学进行了非靶向分析。我们采用多元线性回归模型来检查每个孕期母亲睡眠障碍与儿童智商之间的关联。此外，我们利用纵向潜在类别分析 （LLCA） 来确定整个孕期睡眠质量变化的模式，并采用多元线性回归模型来研究整个怀孕期间的这些睡眠模式与儿童智商的关系。我们应用了一种 “meet-in-the-middle” 方法来确定将怀孕早期产妇睡眠障碍与儿童智商联系起来的潜在代谢物。结果较长的睡眠潜伏期与妊娠早期儿童满量表 IQ （FSIQ） 和语言理解指数 （VCI） 较低相关，而妊娠中期儿童液体推理指数 （FRI） 较低。 整个怀孕期间睡眠潜伏期的延长与 FSIQ （β = -4.68;95% CI： -8.32， -1.03）、VCI （β = -6.38;95% CI： -10.39， -2.37） 和 FRI （β = -4.29;95% CI： -7.96， -0.63） 的降低有关。我们发现肌醇、吲哚丙烯酸和 4-羟基喹啉成为潜在的生物标志物，在母亲睡眠障碍与儿童智商之间的关联中起中介作用。结论妊娠期睡眠障碍可能是学龄前后代智商受损的危险因素。肌醇和色氨酸代谢的改变可能是母亲睡眠障碍与儿童智商之间联系的中介。