背景:妊娠期母体血清总胆汁酸(sTBA)水平升高与不良胎儿结局相关。sTBA升高的女性可能会并发肝功能障碍或血管疾病(妊娠期高血压疾病,HDP),这加剧了不良的胎儿结局。然而,sTBA级别之间的关系,肝功能障碍,HDP和不良胎儿结局仍然是虚幻的。
目的:我们旨在探讨肝功能障碍或血管疾病(HDP)是否介导sTBA水平升高与不良胎儿结局之间的关联。
方法:在2014年1月至2022年12月期间,对117,789名单胎分娩的中国孕妇进行了一项大型回顾性队列研究。因果介导分析用于评估肝功能障碍(丙氨酸转氨酶>40U/L)或HDP在解释高母体sTBA水平(≥10μmol/L)与不良胎儿结局之间的关系中的中介作用。包括低出生体重(LBW),小于胎龄(SGA),早产(PTB)。
结果:sTBA水平与LBW呈正相关(调整比值比(aOR)=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]),分别。对于LBW,HDP介导的总关联的估计比例为47%[95%CI:31%-63%],SGA的24%[95%CI:13%-35%],PTB的34%[95%CI:19%-49%],除了高sTBA水平的直接影响。肝功能障碍作为介质的贡献在高sTBA水平对胎儿结局之间的关联上较弱,由于介导的比例和95%CI为16%[4%-29%],4%[-6%-14%],32%[15%-50%]的LBW,SGA,还有PTB,分别。此外,在敏感性分析中排除HDP病例后,肝功能异常的中介效应几乎消除.
结论:通过HDP的实质性中介效应强调了其在与sTBA水平升高相关的不良胎儿结局中的重要作用。这些发现还激发了新的见解,以了解与sTBA水平升高相关的不良胎儿结局的机制和开发临床管理策略(即血管保护)。
BACKGROUND: 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.
OBJECTIVE: We aimed to explore whether hepatic dysfunction or vascular disorders (HDP) mediated the associations between elevated sTBA level and adverse fetal outcomes.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.