背景:关于与母亲产前抑郁(AD)相关的代谢改变的证据有限,以及它们作为潜在生物标志物的作用,改善AD和不良儿童出生的预测,神经发育,和心理健康的结果仍有待探索。
方法:在331个母子二元组的队列中,我们研究了AD(孕期住院诊断史和/或流行病学研究中心抑郁量表评分≥20分)与孕期分析的95项代谢指标之间的关联3次.我们测试了AD相关的代谢指标是否增加了AD中解释其危险因素的方差,在孩子出生时,神经发育,和精神健康结果超过AD。我们在416个母子双体的队列中复制了这一发现。
结果:弹性网络回归确定了15种代谢指标,它们共同解释了AD中25%(p<0.0001)的方差,包括氨基酸和脂肪酸,葡萄糖,炎症,和脂质。这些代谢指标增加了AD中解释的变异超过其危险因素(32.3%,p<0.0001vs.12.6%,p=0.004),和儿童胎龄(9.0%,p<0.0001vs.0.7%,p=0.34),出生体重(9.0%,p=0.03vs.0.7%,p=0.33),2.3-5.7岁的发展里程碑(21.0%,p=0.002vs.11.6%,p<0.001)和13.1-16.8岁的任何精神或行为障碍(25.2%,p=0.03vs.5.0%,p=0.11)超过AD,孩子的性别和年龄。这些发现在独立队列中重复。
结论:AD与15种代谢指标的改变有关,它们共同改善了对AD危险因素的预测,和出生,AD患儿的神经发育和心理健康结果。这些代谢指标可能成为识别风险母亲和儿童的生物标志物,以进行个性化干预。
BACKGROUND: Evidence regarding metabolic alterations associated with maternal antenatal depression (AD) is limited, and their role as potential biomarkers improving the prediction of AD and adverse child birth, neurodevelopmental, and mental health outcomes remains unexplored.
METHODS: In a cohort of 331 mother-child dyads, we studied associations between AD (history of medical register diagnoses and/or Center of Epidemiological Studies Depression Scale score during pregnancy≥20) and 95 metabolic measures analyzed three times during pregnancy. We tested whether the AD-related metabolic measures increased variance explained in AD over its risk factors, and in child birth, neurodevelopmental, and mental health outcomes over AD. We replicated the findings in a cohort of 416 mother-child dyads.
RESULTS: Elastic net regression identified 15 metabolic measures that collectively explained 25% (p<0.0001) of variance in AD, including amino and fatty acids, glucose, inflammation, and lipids. These metabolic measures increased the variance explained in AD over its risk factors (32.3%,p<0.0001 vs. 12.6%,p=0.004), and in child gestational age (9.0%,p<0.0001 vs. 0.7%, p=0.34), birth weight(9.0%,p=0.03 vs. 0.7%, p=0.33), developmental milestones at the age of 2.3-5.7 years(21.0%,p=0.002 vs. 11.6%,p<0.001) and any mental or behavioral disorder by the age of 13.1-16.8 years(25.2%,p=0.03 vs. 5.0%,p=0.11) over AD, child sex and age. These findings replicated in the independent cohort.
CONCLUSIONS: AD is associated with alterations in 15 metabolic measures, which collectively improve the prediction of AD over its risk factors, and birth, neurodevelopmental and mental health outcomes of the child over AD. These metabolic measures may become biomarkers identifying at-risk mothers and children for personalized interventions.