Chen Hong, Shao Li-Zhen, Wang Ying-Xiong, Han Zhi-Jie, Wang Yong-Heng, Li Xia, Chen Jing-Yu, Liu Tai-Hang
Department of Bioinformatics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.
Joint International Research Laboratory of Reproduction and Development, Chongqing Medical University, Chongqing 400016, China.
Mediators Inflamm. 2024 Dec 26;2024:6349687. doi: 10.1155/mi/6349687. eCollection 2024.
The tolerance and dynamic regulation of the maternal immune system during pregnancy are pivotal for ensuring fetal health. Immune cell subsets play a complex and crucial role in this process, closely linked to the neonatal health status. Despite recognizing the significance of dysregulation in the quantity and activity of immune cells in neonatal disease occurrence, their specific roles remain elusive, resulting in a dearth of clinically viable interventions for immune-mediated neonatal diseases. Employing two-sample Mendelian randomization (MR) methodology, this study systematically investigated 446 leukocyte features ( = 500,675), including leukocyte subsets, absolute cell (AC) counts, and morphological parameters (MP) and their correlation with seven adverse fetal outcomes ( = 1,100,458), encompassing fetal growth restriction (FGR), preterm birth (PTB), neonatal jaundice (NNJ), digestive system disorders of fetus and newborn (DSDFN), hemorrhagic and hematological disorders of fetus and newborn (HDFN), respiratory distress of newborn (RDN), and transitory disorders of metabolism specific to fetus and newborn (TDMSFN). The results unveiled significant causal relationships between 301 leukocyte subsets and these seven adverse fetal outcomes, with 259, 245, 15, 44, 11, 32, and 68 pairs of notable associations for each adverse outcome, respectively. Furthermore, the study highlighted potential pathogenic mechanisms underlying the mutual influence among neonatal diseases. MR results indicated FGR as a robustly correlated risk factor for PTB and NNJ and showed a reciprocal causal relationship between NNJ and FGR. PTB exhibited a positive correlation with HDFN. This study provided profound insights into the intricate regulatory mechanisms of leukocyte subsets in neonatal diseases, paving the way for new avenues in the diagnosis and treatment of associated disorders.
孕期母体免疫系统的耐受性和动态调节对于确保胎儿健康至关重要。免疫细胞亚群在此过程中发挥着复杂而关键的作用，与新生儿健康状况密切相关。尽管认识到免疫细胞数量和活性失调在新生儿疾病发生中的重要性，但其具体作用仍不明确，导致针对免疫介导的新生儿疾病缺乏临床可行的干预措施。本研究采用两样本孟德尔随机化（MR）方法，系统研究了446个白细胞特征（n = 500,675），包括白细胞亚群、绝对细胞（AC）计数和形态学参数（MP），以及它们与七种不良胎儿结局（n = 1,100,458）的相关性，这些不良结局包括胎儿生长受限（FGR）、早产（PTB）、新生儿黄疸（NNJ）、胎儿和新生儿消化系统疾病（DSDFN）、胎儿和新生儿出血及血液系统疾病（HDFN）、新生儿呼吸窘迫（RDN）以及胎儿和新生儿特有的短暂代谢紊乱（TDMSFN）。结果揭示了301个白细胞亚群与这七种不良胎儿结局之间存在显著的因果关系，每种不良结局分别有259、245、15、44、11、32和68对显著关联。此外，该研究突出了新生儿疾病之间相互影响的潜在致病机制。MR结果表明FGR是PTB和NNJ的一个强相关危险因素，并显示NNJ与FGR之间存在相互因果关系。PTB与HDFN呈正相关。本研究为新生儿疾病中白细胞亚群的复杂调节机制提供了深刻见解，为相关疾病的诊断和治疗开辟了新途径。
