METHODS: Our study was embedded in a prospective pregnancy cohort (Generation R; n = 3,598 mother-child dyads). We constructed a comprehensive prenatal infection score comprising common infections for each trimester of pregnancy. Child total, internalizing, and externalizing problems were assessed repeatedly using the parent-rated Child Behavioral Checklist (average age: 1.5, 3, 6, 10, and 14 years). Linear mixed-effects models were run adjusting for a range of confounders, including child polygenic scores for psychopathology, maternal chronic illness, birth complications, and infections during childhood. We also investigated trimester-specific effects and child sex as a potential moderator.
RESULTS: Prenatal exposure to infections was associated with higher child total, internalizing, and externalizing problems, showing temporally persistent effects, even after adjusting for important genetic and environmental confounders. We found no evidence that prenatal infections were associated with changes in child psychiatric symptoms over time. Moreover, in our trimester-specific analysis, we did not find evidence of significant timing effects of prenatal infection on child psychiatric symptoms. No interactions with child sex were identified.
CONCLUSIONS: Our research adds to evidence that common prenatal infections may be a risk factor for psychiatric symptoms in children. We also extend previous findings by showing that these associations are present early on, and that rather than changing over time, they persist into adolescence. However, unmeasured confounding may still explain in part these associations. In the future, employing more advanced causal inference designs will be crucial to establishing the degree to which these effects are causal.
方法:我们的研究被纳入了一个前瞻性妊娠队列(R代;n=3,598个母子二元组)。我们构建了一个全面的产前感染评分,包括妊娠每三个月的常见感染。儿童总数,内化,使用父母评估的儿童行为清单(平均年龄:1.5,3,6,10和14岁)反复评估外部问题。线性混合效应模型对一系列混杂因素进行了调整,包括儿童多基因精神病理学评分,孕产妇慢性病,出生并发症,和童年时的感染。我们还调查了特定于三个月的影响和儿童性别作为潜在的调节因素。
结果:产前接触感染与较高的儿童总数相关,内化,把问题外化,显示暂时持续的影响,即使在调整了重要的遗传和环境混杂因素之后。我们没有发现任何证据表明,随着时间的推移,产前感染与儿童精神症状的变化有关。此外,在我们三个月的具体分析中,我们没有发现产前感染对儿童精神症状有显著时间效应的证据.没有发现与儿童性的相互作用。
结论:我们的研究增加了证据,表明常见的产前感染可能是儿童精神症状的危险因素。我们还通过显示这些关联在早期就存在来扩展以前的发现,而不是随着时间的推移而改变,他们坚持到青春期。然而,无法测量的混杂因素仍可能部分解释这些关联。在未来,采用更先进的因果推理设计将是至关重要的,以确定这些影响是因果的程度。