{"title":"母体血清胆红素水平与散发性和复发性流产的关系：双向双样本孟德尔随机研究。","authors":"Sai Kong, Yiwen Wang, Mingyu Yu, Zhigang Zhang, Yanping Qian, Yong Wu, Manyin Zhai, Lijuan Jiang","doi":"10.1080/15513815.2025.2495683","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background:</b> The association between maternal serum bilirubin levels and miscarriage risk remains unclear. This study investigates the causal link between maternal bilirubin levels and both sporadic and recurrent miscarriage using Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC). <b>Methods:</b> A bidirectional two-sample MR analysis examined genetic associations between maternal serum bilirubin (direct and total) and miscarriage. Genetic instruments were derived from genome-wide association studies (GWAS). LDSC was used to assess shared genetic architecture. Odds ratios (OR) and <i>p</i> values were employed to determine statistical significance. <b>Results:</b> Elevated maternal direct bilirubin levels were significantly associated with sporadic miscarriage (OR = 1.028, <i>p</i> = 0.019) and recurrent miscarriage (OR = 1.016, <i>p</i> = 0.005). Similarly, maternal total bilirubin was linked to sporadic miscarriage (OR = 1.022, <i>p</i> = 0.030) and recurrent miscarriage (OR = 1.013, <i>p</i> = 0.007). In contrast, reverse MR showed no significant association between maternal bilirubin level and miscarriage. Furthermore, LDSC confirmed no shared genetic architecture. <b>Conclusion:</b> Elevated maternal serum bilirubin may increase miscarriage risk, warranting further investigation.</p>","PeriodicalId":50452,"journal":{"name":"Fetal and Pediatric Pathology","volume":" ","pages":"1-13"},"PeriodicalIF":0.7000,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Relationship Between Maternal Serum Level of Bilirubin with Sporadic and Recurrent Miscarriage: A Bidirectional 2-Sample Mendelian Randomization Study.\",\"authors\":\"Sai Kong, Yiwen Wang, Mingyu Yu, Zhigang Zhang, Yanping Qian, Yong Wu, Manyin Zhai, Lijuan Jiang\",\"doi\":\"10.1080/15513815.2025.2495683\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Background:</b> The association between maternal serum bilirubin levels and miscarriage risk remains unclear. This study investigates the causal link between maternal bilirubin levels and both sporadic and recurrent miscarriage using Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC). <b>Methods:</b> A bidirectional two-sample MR analysis examined genetic associations between maternal serum bilirubin (direct and total) and miscarriage. Genetic instruments were derived from genome-wide association studies (GWAS). LDSC was used to assess shared genetic architecture. Odds ratios (OR) and <i>p</i> values were employed to determine statistical significance. <b>Results:</b> Elevated maternal direct bilirubin levels were significantly associated with sporadic miscarriage (OR = 1.028, <i>p</i> = 0.019) and recurrent miscarriage (OR = 1.016, <i>p</i> = 0.005). Similarly, maternal total bilirubin was linked to sporadic miscarriage (OR = 1.022, <i>p</i> = 0.030) and recurrent miscarriage (OR = 1.013, <i>p</i> = 0.007). In contrast, reverse MR showed no significant association between maternal bilirubin level and miscarriage. Furthermore, LDSC confirmed no shared genetic architecture. <b>Conclusion:</b> Elevated maternal serum bilirubin may increase miscarriage risk, warranting further investigation.</p>\",\"PeriodicalId\":50452,\"journal\":{\"name\":\"Fetal and Pediatric Pathology\",\"volume\":\" \",\"pages\":\"1-13\"},\"PeriodicalIF\":0.7000,\"publicationDate\":\"2025-05-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Fetal and Pediatric Pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/15513815.2025.2495683\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Fetal and Pediatric Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/15513815.2025.2495683","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：母体血清胆红素水平与流产风险之间的关系尚不清楚。本研究使用孟德尔随机化（MR）和连锁不平衡评分回归（LDSC）研究母体胆红素水平与偶发性和复发性流产之间的因果关系。方法：双向双样本MR分析检测了母体血清胆红素（直接和总）与流产之间的遗传关联。遗传仪器来源于全基因组关联研究（GWAS）。LDSC用于评估共享遗传结构。比值比（OR）和p值确定统计学显著性。结果：母体直接胆红素水平升高与散发性流产（OR = 1.028, p = 0.019）和复发性流产（OR = 1.016, p = 0.005）显著相关。同样，母体总胆红素与散发性流产（OR = 1.022, p = 0.030）和复发性流产（OR = 1.013, p = 0.007）有关。相反，反向磁共振显示产妇胆红素水平与流产之间无显著关联。此外，LDSC证实没有共享的遗传结构。结论：母体血清胆红素升高可能增加流产风险，值得进一步研究。
Relationship Between Maternal Serum Level of Bilirubin with Sporadic and Recurrent Miscarriage: A Bidirectional 2-Sample Mendelian Randomization Study.
Background: The association between maternal serum bilirubin levels and miscarriage risk remains unclear. This study investigates the causal link between maternal bilirubin levels and both sporadic and recurrent miscarriage using Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC). Methods: A bidirectional two-sample MR analysis examined genetic associations between maternal serum bilirubin (direct and total) and miscarriage. Genetic instruments were derived from genome-wide association studies (GWAS). LDSC was used to assess shared genetic architecture. Odds ratios (OR) and p values were employed to determine statistical significance. Results: Elevated maternal direct bilirubin levels were significantly associated with sporadic miscarriage (OR = 1.028, p = 0.019) and recurrent miscarriage (OR = 1.016, p = 0.005). Similarly, maternal total bilirubin was linked to sporadic miscarriage (OR = 1.022, p = 0.030) and recurrent miscarriage (OR = 1.013, p = 0.007). In contrast, reverse MR showed no significant association between maternal bilirubin level and miscarriage. Furthermore, LDSC confirmed no shared genetic architecture. Conclusion: Elevated maternal serum bilirubin may increase miscarriage risk, warranting further investigation.
期刊介绍：
Fetal and Pediatric Pathology is an established bimonthly international journal that publishes data on diseases of the developing embryo, newborns, children, and adolescents. The journal publishes original and review articles and reportable case reports.
The expanded scope of the journal encompasses molecular basis of genetic disorders; molecular basis of diseases that lead to implantation failures; molecular basis of abnormal placentation; placentology and molecular basis of habitual abortion; intrauterine development and molecular basis of embryonic death; pathogenisis and etiologic factors involved in sudden infant death syndrome; the underlying molecular basis, and pathogenesis of diseases that lead to morbidity and mortality in newborns; prenatal, perinatal, and pediatric diseases and molecular basis of diseases of childhood including solid tumors and tumors of the hematopoietic system; and experimental and molecular pathology.
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