The impact of hypothyroidism on the risk of intrahepatic cholestasis of pregnancy: a large-scale study based on pregnant women with hypothyroidism in Shanghai, China

Background: The relationships among clinical hypothyroidism (CH), subclinical hypothyroidism (SCH), and intrahepatic cholestasis in pregnancy (ICP) remain unclear. We aimed to determine the relationship between hypothyroidism and the risk for ICP. Methods: We conducted this retrospective cohort study at a tertiary care hospital. We used logistic regression analysis to study the risk of ICP, and restricted cubic splines to clarify the quantitative relationship between thyrotropin (TSH) or free thyroxine (FT4) and ICP. We used the Kaplan-Meier method and Cox regression to evaluate the relationship between hypothyroidism and the onset of ICP. Lastly, we checked the Cox proportional hazards assumption using the Schoenfeld residual test. Results: We included 42 615 pregnant women in the final study. The risk of ICP was higher in the CH group (adjusted odds ratio (aOR) = 3.03; 95% confidence interval (CI) = 2.00-4.58, P < 0.001) than in the euthyroidism group. Thyroid peroxidase antibody (TPOAb)(+) CH was also significantly associated with the risk of ICP (aOR = 3.30; 95% CI = 1.92-5.68, P < 0.001). However, SCH was not significantly associated with the risk of ICP. Consistent results were observed in the subgroup analysis of ICP based on onset time and severity. Furthermore, reduced FT4 and elevated TSH levels had a dose-response relationship with ICP. Additionally, ICP occurred earlier in the TPOAb(+) CH subgroup than in other groups (log-rank P < 0.001; hazard ratio = 3.50; 95% CI = 2.05-5.98, P < 0.001). Conclusions: We found that CH was significantly associated with a greater risk of ICP. CH, especially TPOAb(+) CH, is associated with a greater risk of both early and severe ICP. Furthermore, the prevalence of ICP increases with increasing TSH and decreasing FT4.