Creasey Nicole, Schuurmans Isabel, Tsotsi Stella, Defina Serena, Baltramonaityte Vilte, Felix Janine F, Neumann Alexander, Page Christian M, Tollenaar Marieke, Bekkhus Mona, Walton Esther, Cecil Charlotte
Faculty of Education, PEDAL Research Centre, University of Cambridge, Cambridge, UK; Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Psychoneuroendocrinology. 2025 May;175:107388. doi: 10.1016/j.psyneuen.2025.107388. Epub 2025 Feb 12.
Recent work suggests that DNA methylation can be used as a proxy of fetal glucocorticoid exposure (MPS-GC), showing associations with maternal psychopathology during pregnancy. However, it is unknown whether the MPS-GC may act as a marker for broader prenatal stress and whether it partially mediates associations of prenatal stress with child internalizing and externalizing symptoms.
Using harmonized data from three prospective birth cohorts (N = 6086), we examined whether a cumulative measure of prenatal stress, and its individual stress domains, associate with the MPS-GC in cord blood at birth. Next, we examined (i) whether the MPS-GC at birth associates with child psychiatric symptoms, (ii) whether this association is moderated by postnatal stress, and (iii) whether the effect of prenatal stress on child psychiatric symptoms is partially mediated by the MPS-GC at birth.
Our meta-analysis revealed no significant associations between the MPS-GC at birth and prenatal stress or the individual stress domains. Moreover, the MPS-GC did not significantly associate with later child internalizing or externalizing symptoms, and there were no moderating effects of postnatal stress. Additionally, while prenatal stress significantly associated with child psychiatric symptoms, we found no partial mediation via the MPS-GC at birth.
We did not find support that the MPS-GC in cord blood reliably proxies prenatal stress, associates with child psychiatric risk, or partially mediates the associations between prenatal stress and psychiatric risk.
近期研究表明，DNA甲基化可作为胎儿糖皮质激素暴露（MPS-GC）的替代指标，显示出与孕期母亲精神病理学的关联。然而，尚不清楚MPS-GC是否可作为更广泛的产前应激指标，以及它是否部分介导了产前应激与儿童内化和外化症状之间的关联。
我们使用来自三个前瞻性出生队列（N = 6086）的协调数据，研究产前应激的累积测量及其各个应激领域是否与出生时脐带血中的MPS-GC相关。接下来，我们研究了（i）出生时的MPS-GC是否与儿童精神症状相关，（ii）这种关联是否受产后应激的调节，以及（iii）产前应激对儿童精神症状的影响是否部分由出生时的MPS-GC介导。
我们的荟萃分析显示，出生时的MPS-GC与产前应激或各个应激领域之间无显著关联。此外，MPS-GC与后期儿童内化或外化症状无显著关联，且产后应激无调节作用。此外，虽然产前应激与儿童精神症状显著相关，但我们未发现出生时的MPS-GC有部分中介作用。
我们没有找到证据支持脐带血中的MPS-GC能可靠地代表产前应激、与儿童精神风险相关或部分介导产前应激与精神风险之间的关联。
