Associations between thyroid dysfunction, liver biochemical abnormality in early pregnancy and subsequent risk of pregnancy complications: a retrospective cohort study of 91,941 pregnancies in China

Although abnormal liver biochemistry in early pregnancy is linked to adverse outcomes, the determinants and the potential role of the thyroid–hepatic axis remain incompletely understood. This study aims to investigate the associations between first-trimester thyroid and liver function test abnormalities and to evaluate how their co-occurrence relates to subsequent pregnancy-related hepatic complications. We conducted a large-scale retrospective cohort study involving 91,941 pregnant women in Shanghai from 2014 to 2020. Multivariable logistic regression and restricted cubic spline models were employed to evaluate the associations of first-trimester levels of free thyroxine (FT4), thyroid-stimulating hormone (TSH), and liver enzyme abnormalities with subsequent pregnancy-related hepatic disorders. Subgroup analyses were conducted by stratification according to prepregnancy body mass index (BMI) and hepatitis virus infection status. First-trimester FT4 and TSH exhibited significant U-shaped associations with liver enzyme abnormalities (P-nonlinearity < 0.001). Compared with the reference group, women with FT4 >97.5th percentile (aOR, 1.89; 95% CI, 1.59–2.24) or TSH <2.5th percentile (aOR, 2.47; 95% CI, 2.13–2.87) had higher odds of liver enzyme abnormalities. High FT4 was associated with higher odds of liver enzyme abnormalities among women with prepregnancy underweight (aOR, 2.86; 95% CI, 1.90–4.28) and those with hepatitis positivity (aOR, 2.27; 95% CI, 1.02–5.07). Notably, the co-occurrence of high TSH and alanine aminotransferase (ALT) >2×ULN was associated with the highest risk for hypertensive disorders of pregnancy (HDP; aOR, 4.54; 95% CI, 1.77–11.63) and intrahepatic cholestasis of pregnancy (ICP; aOR, 6.09; 95% CI, 1.44–25.87). In this observational cohort, first-trimester thyroid function was nonlinearly associated with liver enzyme abnormalities, with variation in the subgroup-specific estimates across prepregnancy BMI and hepatitis virus status categories. Co-occurring thyroid and liver biochemical abnormalities were associated with subsequent HDP and ICP. Integrated assessment in early pregnancy may help identify women who warrant closer clinical evaluation.