The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai 200030, China.
Global Center for Asian Women's Health, Yong Loo Lin School of Medicine, National University of Singapore, 117549, Singapore; Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, 117549, Singapore.
Clin Chim Acta. 2024 Aug 15;562:119896. doi: 10.1016/j.cca.2024.119896. Epub 2024 Aug 3.
Elevated maternal serum total bile acids (sTBA) level during pregnancy was associated with adverse fetal outcomes. Women with elevated sTBA could complicate with hepatic dysfunction or vascular disorders (hypertensive disorders of pregnancy, HDP), which aggravated adverse fetal outcomes. However, the relationships among sTBA level, hepatic dysfunction, HDP and adverse fetal outcomes were still illusive.
We aimed to explore whether hepatic dysfunction or vascular disorders (HDP) mediated the associations between elevated sTBA level and adverse fetal outcomes.
A large retrospective cohort study encompassing 117,789 Chinese pregnant women with singleton delivery between Jan 2014 and Dec 2022 was conducted. Causal mediation analysis was applied to assess the mediating role of hepatic dysfunction (alanine transaminase > 40 U/L) or HDP in explaining the relationship between high maternal sTBA level (≥10 μmol/L) and adverse fetal outcomes, including low birth weight (LBW), small for gestational age (SGA), and preterm birth (PTB).
sTBA level were positively associated with LBW (adjusted odds ratio (aOR) = 1.40; [95 % confidence interval (CI): 1.24-1.59]), SGA (aOR=1.31; [95 % CI: 1.18-1.46]), and PTB (aOR=1.27; [95 % CI: 1.15-1.41]), respectively. The estimated proportions of the total associations mediated by HDP were 47 % [95 % CI: 31 %-63 %] for LBW, 24 % [95 % CI: 13 %-35 %] for SGA, and 34 % [95 % CI: 19 %-49 %] for PTB, excepting the direct effects of high sTBA level. The contribution of hepatic dysfunction as a mediator was weaker on the association between high sTBA level on fetal outcomes, as the proportions mediated and 95 % CI were 16 % [4 %-29 %], 4 % [-6%-14 %], 32 % [15 %-50 %] for LBW, SGA, and PTB, respectively. Moreover, the mediating effect of hepatic dysfunction was nearly eliminated after excluding cases of HDP in the sensitivity analysis.
The substantial mediating effects through HDP highlighted its significant role in adverse fetal outcomes associated with elevated sTBA level. The findings also provoked new insights into understanding the mechanism and developing clinical management strategies (i.e. vascular protection) for adverse fetal outcomes associated with elevated sTBA level.
孕期母体血清总胆汁酸（sTBA）水平升高与不良胎儿结局相关。sTBA 升高的女性可能并发肝功能障碍或血管疾病（妊娠高血压疾病，HDP），从而加重不良胎儿结局。然而，sTBA 水平、肝功能障碍、HDP 与不良胎儿结局之间的关系仍不清楚。
本研究旨在探讨肝功能障碍或血管疾病（HDP）是否介导了 sTBA 水平升高与不良胎儿结局之间的关联。
对 2014 年 1 月至 2022 年 12 月期间进行单胎分娩的 117789 例中国孕妇进行了一项大型回顾性队列研究。采用因果中介分析评估了肝功能障碍（丙氨酸氨基转移酶>40 U/L）或 HDP 在解释高母体 sTBA 水平（≥10μmol/L）与不良胎儿结局（包括低出生体重[LBW]、小于胎龄儿[SGA]和早产[PTB]）之间的关系中的中介作用。
sTBA 水平与 LBW（调整后的优势比[aOR]为 1.40；[95%置信区间[CI]：1.24-1.59]）、SGA（aOR=1.31；[95%CI：1.18-1.46]）和 PTB（aOR=1.27；[95%CI：1.15-1.41]）呈正相关。HDP 介导的总关联的估计比例分别为 LBW 占 47%[95%CI：31%-63%]、SGA 占 24%[95%CI：13%-35%]和 PTB 占 34%[95%CI：19%-49%]，但排除了 sTBA 水平升高对不良结局的直接影响。肝功能障碍作为中介的贡献较弱，与 sTBA 水平与胎儿结局之间的关联，介导的比例和 95%CI 分别为 16%[4%-29%]、4%[-6%-14%]和 32%[15%-50%]，用于 LBW、SGA 和 PTB。此外，在敏感性分析中排除 HDP 病例后，肝功能障碍的中介作用几乎消除。
通过 HDP 产生的显著中介效应突出了其在与 sTBA 水平升高相关的不良胎儿结局中的重要作用。这些发现还为理解与 sTBA 水平升高相关的不良胎儿结局的机制和制定血管保护等临床管理策略提供了新的见解。
