Cheng Jian, Dong Xiao, Yang Yang, Qin Xiaohan, Zhou Xing, Fu Yongcheng, Wang Jingyue, Wang Yuanyuan, Zhang Da
Center for Rare Diseases, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Department of Endocrinology, Genetics and Metabolism, Fuzhou Children's Hospital of Fujian Medical University, Fuzhou, 350000, China.
BMC Pregnancy Childbirth. 2025 Sep 1;25(1):915. doi: 10.1186/s12884-025-07860-1.
Adverse events during pregnancy are implicated in increasing the risk of congenital malformations in offspring. Current research does not fully encompass the spectrum of adverse events nor the mechanisms by which they affect fetal development.
A two-sample and two-step Mendelian randomization (MR) study was conducted to assess the association between adverse events during pregnancy and congenital malformations in offspring, and to investigate the mediating role of circulating metabolites in linking these adverse events to congenital malformations.
Maternal bleeding during pregnancy was associated with an increased risk of congenital ichthyosis and a decreased risk of congenital hydrocephalus. Anemia during pregnancy showed a significant correlation with an increased risk of atrioventricular septal defects. Placenta previa and placental abruption were associated with a decreased risk of congenital hydrocephalus and an increased risk of congenital malformation of the breast. Premature birth was associated with an increased risk of complex heart defects. Fetal malposition correlated with a decreased risk of cleft lip. Urogenital infection during pregnancy was linked to an increased risk of congenital malformation of cardiac chambers and connection. Glycine may mediate approximately 1.1% of the effect of premature birth on the risk of complex heart defects.
MR was employed to elucidate the mediating role of circulating metabolites in the impact of these adverse events on congenital malformations, providing new insights into their causal relationships. However, the underlying mechanisms remain unclear, necessitating further research and clinical trials to elucidate these relationships.
孕期不良事件与后代先天性畸形风险增加有关。目前的研究并未完全涵盖不良事件的范围及其影响胎儿发育的机制。
进行了一项两样本两步孟德尔随机化（MR）研究，以评估孕期不良事件与后代先天性畸形之间的关联，并研究循环代谢物在将这些不良事件与先天性畸形联系起来的中介作用。
孕期母体出血与先天性鱼鳞病风险增加及先天性脑积水风险降低有关。孕期贫血与房室间隔缺损风险增加显著相关。前置胎盘和胎盘早剥与先天性脑积水风险降低及乳腺先天性畸形风险增加有关。早产与复杂心脏缺陷风险增加有关。胎位异常与唇裂风险降低相关。孕期泌尿生殖系统感染与心脏腔室及连接的先天性畸形风险增加有关。甘氨酸可能介导早产对复杂心脏缺陷风险影响的约1.1%。
采用MR阐明循环代谢物在这些不良事件对先天性畸形影响中的中介作用，为它们的因果关系提供了新见解。然而，潜在机制仍不清楚，需要进一步研究和临床试验来阐明这些关系。
