Pre-Eclampsia-Induced Maternal Liver Dysfunction: Systematic Review, Meta-Analysis and Meta-Regression of Observation Studies

TL;DR

This study finds that pre-eclampsia significantly affects liver function in pregnant women, as shown by elevated liver enzymes.

Contribution

The study provides a comprehensive meta-analysis and meta-regression of observational data to quantify liver dysfunction in pre-eclampsia.

Findings

Pre-eclampsia is significantly associated with elevated AST, ALT, ALP, and total serum bilirubin levels.

Older maternal age and study quality moderate the effect sizes of ALP and total serum bilirubin.

Higher BMI is linked to reduced ALT effect size in pre-eclampsia.

Abstract

Introduction: Pre-eclampsia (PE) is a pregnancy-related hypertensive condition defined by the onset of hypertension after 20 weeks of gestation that is associated with proteinuria and maternal organ damage or uteroplacental dysfunction. It continues to be a leading cause of maternal and perinatal morbidity and mortality globally. PE is linked to systemic inflammation, endothelial dysfunction, and oxidative stress, which may compromise hepatic function. Aim: This meta-analysis assesses the impact of PE on maternal liver function by evaluating hepatic biomarkers, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total serum bilirubin. Methods: This meta-analysis of observational studies in Epidemiology (MOOSE) involved a search of PubMed and Scopus and manual screening of studies published between 2000 and 2025. Eligible studies included cross-sectional, case–control, and cohort designs. The quality of the studies was evaluated using the Newcastle–Ottawa Scale. Statistical analysis was conducted using the online meta-analysis, Jamovi version 2.6.44, and IBM SPSS Statistics version 30, and effect estimates were reported as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: Forty-five studies, comprising 257,929 women 9420 with PE; 248,509 normotensive, were included. Women with PE had elevated AST, MD = 1.81 (95% CI: 1.51 to 2.10; p < 0.0001) and ALT, SMD = 1.73 (95% CI: 1.38 to 2.07; p < 0.0001); ALP, SMD = 1.43 (95% CI: 0.97 to 1.88; p < 0.0001); and total serum bilirubin (TSB), SMD = 0.62 (95% CI: 0.36 to 0.88; p < 0.0001) in comparison to normotensive controls. In the meta-regression, maternal age and quality were significant moderators, with older age and high-quality studies associated with smaller and larger effect sizes, respectively, for ALP (β = −0.720 and β = 1.444) and TSB (β = −0.304 and β = 0.761). For every 1-unit increase in body mass index, there was a significant 0.406-unit decrease in ALT effect size. Conclusions: PE is significantly associated with elevated maternal hepatic enzyme levels, indicating hepatocellular damage and impaired liver function. These findings emphasise the necessity for routine liver function monitoring in pregnant women with hypertensive disorders.

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