Clayborne Zahra M, Zou Runyu, Gilman Stephen E, Khandaker Golam M, Fell Deshayne B, Colman Ian, El Marroun Hanan
School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Department of Child and Adolescent Psychiatry, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Brain Behav Immun. 2023 Nov;114:165-172. doi: 10.1016/j.bbi.2023.08.017. Epub 2023 Aug 20.
Maternal immune activation is a potential mechanism underlying associations between maternal stress during pregnancy and offspring mental health problems. This study examined associations between prenatal maternal stress, maternal inflammation during pregnancy, and children's internalizing and externalizing symptoms from 3 to 10 years of age, and whether maternal inflammation mediated the associations between prenatal maternal stress and children's internalizing and externalizing symptoms.
This study comprised 4,902 mother-child dyads in the Generation R study. Prenatal maternal stress was assessed using self-reported data collected during pregnancy and analyzed as a latent variable consisting of four stress domains. Maternal inflammation during pregnancy was assessed using serum concentrations of C-reactive protein (CRP) measured at a median of 13.5 weeks' gestation. Child internalizing and externalizing symptoms were assessed using the Child Behavior Checklist (CBCL) by maternal report at ages 3 years, 5 years, and 10 years; paternal-reported CBCL data were also available at 3 years and 10 years.
Prenatal maternal stress was associated with maternal-reported internalizing and externalizing symptoms of the child at 3, 5, and 10 years of age, and with paternal-reported internalizing and externalizing symptoms at 3 and 10 years. Prenatal maternal stress was associated with maternal CRP concentrations prior to, but not after, covariate adjustment. Maternal CRP concentrations during pregnancy were associated with paternal-reported internalizing symptoms of offspring at 10 years of age prior to, but not after, covariate adjustment. There was no evidence that CRP concentrations mediated the associations between prenatal maternal stress and children's internalizing or externalizing symptoms.
Maternal stress during pregnancy is associated with higher levels of internalizing and externalizing symptoms in children, but this association is not because of differences in maternal immune activation linked to maternal stress. Replication of these findings in other cohorts is required; examination of other biomarkers or variation in immune activity during pregnancy would also benefit from further exploration.
母体免疫激活是孕期母体应激与后代心理健康问题之间关联的潜在机制。本研究考察了产前母体应激、孕期母体炎症与儿童3至10岁时内化和外化症状之间的关联，以及母体炎症是否介导了产前母体应激与儿童内化和外化症状之间的关联。
本研究纳入了“R世代”研究中的4902对母婴。产前母体应激通过孕期收集的自我报告数据进行评估，并作为一个由四个应激领域组成的潜在变量进行分析。孕期母体炎症通过在妊娠13.5周中位数时测量的血清C反应蛋白（CRP）浓度进行评估。儿童内化和外化症状通过母亲报告，使用儿童行为检查表（CBCL）在3岁、5岁和10岁时进行评估；父亲报告的CBCL数据在3岁和10岁时也可获得。
产前母体应激与母亲报告的儿童在3岁、5岁和10岁时的内化和外化症状相关，与父亲报告的儿童在3岁和10岁时的内化和外化症状相关。产前母体应激与协变量调整前但不是调整后的母体CRP浓度相关。孕期母体CRP浓度与协变量调整前但不是调整后的父亲报告的后代在10岁时的内化症状相关。没有证据表明CRP浓度介导了产前母体应激与儿童内化或外化症状之间的关联。
孕期母体应激与儿童更高水平的内化和外化症状相关，但这种关联并非由于与母体应激相关的母体免疫激活差异。这些发现需要在其他队列中进行重复验证；对其他生物标志物或孕期免疫活动变化的研究也将受益于进一步探索。
