Abnormal liver function biomarkers in early pregnancy and risk of preterm birth: a retrospective cohort study

The importance of liver health in pregnant women is widely acknowledged; The aim of this study was to examine the relationships between abnormal liver function tests (LFTs) in early pregnancy and PTB. This retrospective cohort study included all singleton pregnant women who underwent LFTs at their first antenatal visit from 6 to 19 + 6 weeks of gestation(inclusive) and delivered in a tertiary care hospital in Shanghai, China. Among 57,386 initially screened singleton pregnancies, 48,032 women were included in the final analysis. Binary logistic regression was used to estimate the odds of total PTB (any PTB vs. term birth), and multinomial logistic regression (term birth as the reference category) was used jointly for spontaneous and iatrogenic PTB, across different liver function biomarker levels (ALT, AST, GGT, TBiL and DBiL), controlling for key covariates. Four-level stratified categorical variables for ALT–GGT and AST–GGT combinations were constructed to explore separate and joint associations with different PTB subtypes. Elevated ALT and AST (> 80U/L) were associated with higher odds of iatrogenic PTB, whereas no significant associations were found for spontaneous PTB. Compared with the reference ALT 0–40 U/L group, ALT of 81–200 U/L was associated with 42.3% higher adjusted odds of iatrogenic PTB (aOR = 1.423, 95% CI 1.021–1.983). ALT > 200 U/L was associated with elevated odds of total PTB (aOR = 1.287, 95% CI 1.008–1.645), and conferred 3.28-fold greater adjusted odds of iatrogenic PTB (aOR = 3.282, 95% CI 1.315–8.194).Moderately elevated AST (81–200 U/L) corresponded to 2.00-fold higher adjusted odds of iatrogenic PTB (aOR = 1.998, 95% CI 1.088–3.671) For GGT, all subgroups above the 0–12 U/L reference exhibited significantly elevated odds for both PTB phenotypes, with association magnitudes gradually rising alongside increasing GGT concentrations. No statistically significant multiplicative interaction was detected for ALT/AST elevation × GGT elevation for any subtype of PTB. Stratified results for ALT & GGT showed isolated GGT elevation and concurrent ALT & GGT elevation were significantly associated with elevated risk of iatrogenic PTB, whereas isolated ALT elevation showed no significant association. Stratified results for AST & GGT showed isolated GGT elevation and concurrent AST & GGT elevation predicted higher odds of iatrogenic PTB. Isolated AST elevation was not significantly related to any preterm subtype. Elevated early-pregnancy liver biomarkers, particularly GGT, were associated with subsequent PTB risk. Further prospective studies are needed to determine whether these biomarkers improve risk stratification.