胎盘和脐带血清中的炎性细胞因子与儿童18个月时的特定领域神经发育：母体维生素D状态的影响修饰作用

Placental and cord serum inflammatory cytokines and children's domain-specific neurodevelopment at 18 months:

effect modification by maternal vitamin D status
胎盘和脐带血清中的炎性细胞因子与儿童 18 个月时的特定领域神经发育：母体维生素 D 状态的影响修饰作用

Authors：Menglong Geng, Zhen Yu, Yafei Wang, Juan Tong, Hui Gao, Hong Gan, Jixing Zhou, Baolin Wang, Peng Ding, Shuangqin Yan, Kun Huang, Xiaoyan Wu, Fangbiao Tao
Source：Bmc Medicine
DOI: 10.1186/s12916-025-04096-w

Abstract
Background: Epidemiological studies that have simultaneously explored the effects of placental and cord blood inflammatory cytokine levels on neurodevelopment in offspring, as well as the role of maternal vitamin D in these associations, are lacking. To investigate the associations of placental and cord blood inflammatory cytokine levels with neurodevelopment in 18-month-old children, and the potential modification effect by maternal vitamin D.
Methods: Based on the Ma'anshan birth cohort, the current study involved 1241 mother-child pairs. The placental inflammatory cytokine mRNA expression levels, cord serum inflammatory cytokine concentrations, and maternal serum vitamin D concentrations were determined. Children's neurodevelopmental outcomes were defined as the Chinese version of the Ages and Stages Questionnaire (Third Edition) subdomain scores below the established cutoff scores. Generalized linear models were utilized to assess the effects of placental and cord serum inflammatory cytokines on neurodevelopmental outcomes and to examine the modification effects of maternal vitamin D.

Results: After adjusting for confounders, each one-unit increase in placental IL-6 (OR = 1.30, 95% CI: 1.09, 1.55, P-FDR = 0.024), IL-8 (OR = 1.25, 95% CI: 1.05, 1.49, P-FDR = 0.036), and IFN-γ level in the cord serum (OR = 1.74, 95% CI: 1.16, 2.61, P-FDR = 0.042) was associated with an increased risk of fine motor delay. Elevated levels of placental TNF-α (OR = 1.38, 95% CI: 1.12, 1.69, P-FDR = 0.012), IL-6 (OR = 1.29, 95% CI: 1.04, 1.61, P-FDR = 0.042), and IL-8 (OR = 1.31, 95% CI: 1.06, 1.62, P-FDR = 0.036) were associated with an increased risk of personal-social delay. Stratified analyses showed that lower maternal vitamin D levels (< 20 ng/mL) moderated the associations between inflammatory markers and delays in fine motor, gross motor, and personal-social subdomains.
Conclusions: Elevated levels of specific inflammatory cytokines in the placenta and umbilical cord blood were associated with developmental delays on a parental-reported screening tool. Maternal vitamin D status can modify the adverse effects of the intrauterine pro-inflammatory milieu on the neurodevelopment of children.
Keywords: Birth cohort; Cytokine; Neurodevelopment; Placenta; Umbilical cord blood; Vitamin D.

摘要
背景：目前还缺乏同时探讨胎盘和脐带血炎症细胞因子水平对后代神经发育的影响以及母体维生素 D 在这些关联中的作用的流行病学研究。目的：研究胎盘和脐带血炎性细胞因子水平与 18 个月大儿童神经发育的关系，以及母体维生素 D 的潜在调节作用。
方法：本研究以马鞍山出生队列为基础，涉及 1241 对母婴。研究测定了胎盘炎症细胞因子 mRNA 表达水平、脐带血清炎症细胞因子浓度和母体血清维生素 D 浓度。儿童的神经发育结果是指中文版年龄与阶段问卷（第三版）子域得分低于既定的临界值。利用广义线性模型评估胎盘和脐带血清炎症细胞因子对神经发育结果的影响，并研究母体维生素 D 的调节作用。
结果：调整混杂因素后，胎盘IL-6（OR = 1.30，95% CI：1.09，1.55，P-FDR = 0.024）、IL-8（OR = 1.25，95% CI：1.05，1.49，P-FDR = 0.036）和脐带血清中IFN-γ水平每增加一个单位，精细运动迟缓的风险就会增加（OR = 1.74，95% CI：1.16，2.61，P-FDR = 0.042）。胎盘TNF-α（OR = 1.38，95% CI：1.12，1.69，P-FDR = 0.012）、IL-6（OR = 1.29，95% CI：1.04，1.61，P-FDR = 0.042）和IL-8（OR = 1.31，95% CI：1.06，1.62，P-FDR = 0.036）水平升高与个人-社会发育迟缓风险增加有关。分层分析表明，较低的母体维生素D水平（< 20 ng/mL）缓和了炎症标志物与精细动作、粗大动作和个人-社会分领域延迟之间的关联。
结论：胎盘和脐带血中特定炎症细胞因子水平的升高与父母报告的筛查工具显示的发育迟缓有关。母亲的维生素 D 状态可改变宫内促炎环境对儿童神经发育的不良影响。
关键词：出生队列，细胞因子，神经发育，胎盘，脐带血，维生素D