Early Pregnancy Thyroid and Liver Abnormalities Linked to Heightened Complication Risks

A large-scale retrospective cohort study investigating 91,941 pregnant women in Shanghai has identified significant associations between first-trimester thyroid function, liver enzyme abnormalities, and the subsequent development of serious pregnancy complications. Published in the European Journal of Medical Research, the study examined clinical records spanning from 2014 to 2020 to clarify the poorly understood relationships within the maternal thyroid–hepatic axis during early gestation.

Researchers observed that early pregnancy liver biochemical abnormalities are known to be connected to adverse outcomes, yet the potential role and determinants involving thyroid function have remained incompletely understood. To address this question, the investigative team tracked maternal free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations alongside liver function test results during the first trimester to determine how individual and co-occurring abnormalities correlated with subsequent pregnancy-related hepatic disorders.

The methodological framework relied on multivariable logistic regression and restricted cubic spline models to characterize these relationships. The statistical models revealed significant U-shaped, nonlinear associations between first-trimester concentrations of both FT4 and TSH and the presence of liver enzyme abnormalities, with the test for nonlinearity reaching a high degree of significance (P-nonlinearity < 0.001).

When compared directly against the reference category, pregnant women exhibiting FT4 levels above the 97.5th percentile demonstrated significantly higher odds of liver enzyme abnormalities, yielding an adjusted odds ratio (aOR) of 1.89 with a 95% confidence interval (CI) of 1.59 to 2.24. Similarly, women presenting with suppressed first-trimester TSH concentrations below the 2.5th percentile experienced elevated odds of liver enzyme abnormalities, registering an aOR of 2.47 (95% CI, 2.13–2.87).

Subgroup analyses stratified by clinical characteristics indicated that these associations varied substantially across maternal baseline conditions, particularly prepregnancy body mass index (BMI) and hepatitis virus status. High maternal FT4 levels showed a stronger association with liver enzyme abnormalities among women categorized as underweight prior to pregnancy, generating an aOR of 2.86 (95% CI, 1.90–4.28). Women with confirmed hepatitis virus positivity who exhibited high FT4 also faced elevated odds of liver enzyme abnormalities, with an aOR of 2.27 (95% CI, 1.02–5.07).

The study also evaluated the clinical consequences of simultaneous biochemical disruptions. The researchers found that the co-occurrence of elevated TSH and alanine aminotransferase (ALT) levels exceeding twice the upper limit of normal (>2×ULN) was associated with the highest observed risks for subsequent gestational conditions. Specifically, this combined profile was linked to higher risk for hypertensive disorders of pregnancy, yielding an aOR of 4.54 (95% CI, 1.77–11.63), as well as intrahepatic cholestasis of pregnancy, with an aOR of 6.09 (95% CI, 1.44–25.87).

In their conclusions, the authors noted that early gestational thyroid function displays pronounced nonlinear associations with liver enzyme abnormalities, while subgroup variations highlight the importance of factoring in prepregnancy BMI and hepatitis virus status. Given the heightened odds of subsequent hypertensive disorders of pregnancy and intrahepatic cholestasis when thyroid and liver abnormalities co-occur, the researchers noted that integrated biochemical assessment in early pregnancy may help clinicians identify patients who warrant closer evaluation.

Subject of Research: Associations between early pregnancy thyroid dysfunction, liver biochemical abnormalities, and subsequent pregnancy complications

Article Title: 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

Article References: Cao, Y., Wang, Z., Zhang, S., Zhou, Y., Li, L., Song, F., & Wu, W. (2026). 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. European Journal of Medical Research. https://doi.org/10.1186/s40001-026-05345-1

Image Credits: AI Generated

DOI: 10.1186/s40001-026-05345-1

Keywords: thyroid dysfunction, liver biochemistry, first trimester, pregnancy complications, hypertensive disorders of pregnancy, intrahepatic cholestasis of pregnancy, free thyroxine, thyroid-stimulating hormone, alanine aminotransferase, retrospective cohort study, body mass index, hepatitis virus infection, maternal health, restricted cubic splines, liver enzyme abnormalities, Shanghai cohort