Background

Maternal depression and anxiety during pregnancy may enhance fetal exposure to glucocorticoids (GCs) and harm neurodevelopment. We tested whether a novel cross-tissue polyepigenetic biomarker indicative of in utero exposure to GC is associated with mental and behavioral disorders and their severity in children, possibly mediating the associations between maternal prenatal depressive and anxiety symptoms and these child outcomes.

Methods

Children (n = 814) from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study were followed-up from birth to age 7.1–10.7 years. A weighted polyepigenetic GC exposure score was calculated based on the methylation profile of 24 CpGs from umbilical cord blood. Child diagnosis of mental and behavioral disorder (n = 99) and its severity, defined as the number of days the child had received treatment (all 99 had received outpatient treatment and 8 had been additionally in inpatient treatment) for mental or behavioral disorder as the primary diagnosis, came from the Care Register for Health Care. Mothers (n = 408) reported on child total behavior problems at child's age of 2.3–5.8 years and their own depressive and anxiety symptoms during pregnancy (n = 583).

Results

The fetal polyepigenetic GC exposure score at birth was not associated with child hazard of mental and behavioral disorder (HR = 0.82, 95% CI 0.54; 1.24, p = 0.35) or total behavior problems (unstandardized beta = −0.10, 95% CI -0.31; 0.10, p = 0.33). However, for one standard deviation decrease in the polyepigenetic score, the child had spent 2.94 (95%CI 1.59; 5.45, p < 0.001) more days in inpatient or outpatient treatment with any mental and behavioral disorder as the primary diagnosis. Criteria for mediation tests were not met.

Conclusions

These findings suggest that fetal polyepigenetic GC exposure score at birth was not associated with any mental or behavioral disorder diagnosis or mother-rated total behavior problems, but it may contribute to identifying children at birth who are at risk for more severe mental or behavioral disorders.

中文翻译：

---

出生和儿童精神和行为障碍时的多表观遗传糖皮质激素暴露评分

背景

怀孕期间母亲的抑郁和焦虑可能会增加胎儿对糖皮质激素 (GC) 的暴露并损害神经发育。我们测试了一种指示子宫内接触 GC的新型跨组织多表观遗传生物标志物是否与儿童的精神和行为障碍及其严重程度相关，可能介导母亲产前抑郁和焦虑症状与这些儿童结局之间的关联。

方法

对来自先兆子痫和宫内生长受限 (PREDO) 研究的儿童 (n = 814) 进行了从出生到 7.1-10.7 岁的随访。基于来自脐带血的 24 个 CpG 的甲基化谱计算加权的多表观遗传 GC 暴露评分。儿童精神和行为障碍诊断 (n = 99) 及其严重程度，定义为儿童接受精神或行为障碍治疗的天数（所有 99 人接受门诊治疗，8 人额外住院治疗）初步诊断，来自医疗保健护理登记册。母亲（n = 408）报告了孩子在 2.3-5.8 岁时的总体行为问题以及她们自己在怀孕期间的抑郁和焦虑症状（n = 583）。

结果

出生时胎儿多表观遗传 GC 暴露评分与儿童精神和行为障碍风险（HR = 0.82, 95% CI 0.54; 1.24, p = 0.35）或总体行为问题（非标准化 β = -0.10, 95% CI - 0.31；0.10，p = 0.33）。然而，对于多表观遗传评分降低一个标准差，该儿童以任何精神和行为障碍为主要诊断的住院或门诊治疗多花 2.94 天（95%CI 1.59；5.45，p < 0.001）天。未达到调解测试的标准。

结论

这些发现表明，出生时胎儿多表观遗传 GC 暴露评分与任何精神或行为障碍诊断或母亲评定的总体行为问题无关，但它可能有助于识别出生时有更严重精神或行为障碍风险的儿童。