Geng Menglong, Yu Zhen, Wang Yafei, Tong Juan, Gao Hui, Gan Hong, Zhou Jixing, Wang Baolin, Ding Peng, Yan Shuangqin, Huang Kun, Wu Xiaoyan, Tao Fangbiao
Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei, Anhui, 230032, China.
Anhui Provincial Key Laboratory of Environment and Population Health Across the Life Course, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui, 230032, China.
BMC Med. 2025 Apr 30;23(1):252. doi: 10.1186/s12916-025-04096-w.
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.
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.
After adjusting for confounders, each one-unit increase in placental IL-6 (OR = 1.30, 95% CI: 1.09, 1.55, P- = 0.024), IL-8 (OR = 1.25, 95% CI: 1.05, 1.49, P- = 0.036), and IFN-γ level in the cord serum (OR = 1.74, 95% CI: 1.16, 2.61, P- = 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- = 0.012), IL-6 (OR = 1.29, 95% CI: 1.04, 1.61, P- = 0.042), and IL-8 (OR = 1.31, 95% CI: 1.06, 1.62, P- = 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.
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.
目前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。为了研究胎盘和脐带血炎症细胞因子水平与18个月大儿童神经发育的关联，以及母体维生素D的潜在调节作用。
基于马鞍山出生队列，本研究纳入了1241对母婴。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。儿童神经发育结局定义为中文版《年龄与发育进程问卷》（第三版）低于既定临界值的子领域得分。采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局的影响，并检验母体维生素D的调节作用。
在调整混杂因素后，胎盘白细胞介素-6（IL-6）水平每升高一个单位（比值比[OR]=1.30，95%置信区间[CI]：1.09，1.55，P=0.024）、IL-8水平每升高一个单位（OR=1.25，95%CI：1.05，1.49，P=0.036）以及脐带血清中干扰素-γ（IFN-γ）水平每升高一个单位（OR=1.74，95%CI：1.16，2.61，P=0.042）与精细运动发育迟缓风险增加相关。胎盘肿瘤坏死因子-α（TNF-α）水平升高（OR=1.38，95%CI：1.12，1.69，P=0.012）、IL-6水平升高（OR=1.29，95%CI：1.04，1.61，P=0.042）以及IL-8水平升高（OR=1.31，95%CI：1.06，1.62，P=0.036）与个人-社交发育迟缓风险增加相关。分层分析显示，较低的母体维生素D水平（<20 ng/mL）会减弱炎症标志物与精细运动、大运动和个人-社交子领域发育迟缓之间的关联。
胎盘和脐带血中特定炎症细胞因子水平升高与家长报告的筛查工具上的发育迟缓相关。母体维生素D状态可改变宫内促炎环境对儿童神经发育的不良影响。
