母体血清胆汁酸水平升高、妊娠高血压疾病与胎儿不良结局：一项针对 117 789 名中国孕妇的队列研究。

IF 3.2 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta Pub Date : 2024-08-03 DOI:10.1016/j.cca.2024.119896

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引用次数: 0

摘要

背景：孕期母体血清总胆汁酸（sTBA）水平升高与胎儿不良结局有关。sTBA 升高的妇女可能并发肝功能异常或血管疾病（妊娠高血压疾病，HDP），从而加重对胎儿的不良影响。然而，sTBA 水平、肝功能异常、HDP 和胎儿不良结局之间的关系仍不明确：我们旨在探讨肝功能异常或血管紊乱（HDP）是否介导了 sTBA 水平升高与胎儿不良结局之间的关系：方法：我们对2014年1月至2022年12月期间117789名单胎分娩的中国孕妇进行了一项大型回顾性队列研究。应用因果中介分析评估肝功能异常（丙氨酸转氨酶>40 U/L）或HDP在解释高母体sTBA水平（≥10 μmol/L）与低出生体重（LBW）、小于胎龄（SGA）和早产（PTB）等不良胎儿结局之间的中介作用。结果：sTBA 水平分别与低出生体重（调整后比值比 (aOR) = 1.40；[95 % 置信区间 (CI)：1.24-1.59]）、SGA（aOR=1.31；[95 % CI：1.18-1.46]）和早产（aOR=1.27；[95 % CI：1.15-1.41]）呈正相关。除高 sTBA 水平的直接影响外，估计 HDP 介导的总关联比例为：LBW：47% [95 % CI：31%-63%]；SGA：24% [95 % CI：13%-35%]；PTB：34% [95 % CI：19%-49%]。肝功能异常作为介导因素对高 sTBA 水平与胎儿结局相关性的贡献较弱，其介导比例和 95 % CI 分别为：LBW 16 % [4 %-29 %]、SGA 4 % [-6 %-14 %]、PTB 32 % [15 %-50 %]。此外，在敏感性分析中排除肝功能异常病例后，肝功能异常的中介效应几乎被消除：结论：通过 HDP 产生的巨大中介效应凸显了其在与 sTBA 水平升高相关的不良胎儿结局中的重要作用。结论：HDP的巨大中介效应凸显了其在TBA水平升高相关的不良胎儿结局中的重要作用，这些发现也为了解sTBA水平升高相关的不良胎儿结局的机制和制定临床管理策略（即血管保护）提供了新的视角。

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Elevated maternal serum bile acids level, hypertensive disorders of pregnancy and adverse fetal outcomes: a cohort study of 117,789 pregnant women in China

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.

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来源期刊

Clinica Chimica Acta 医学-医学实验技术

CiteScore

10.10

自引率

2.00%

发文量

1268

审稿时长

23 days

期刊介绍： The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.