Association of intrahepatic cholestasis of pregnancy with preterm birth and low birth weight in offspring: A prospective cohort and Mendelian randomization study

Background

Intrahepatic cholestasis of pregnancy (ICP) is a common complication of pregnancy, which may lead to an increased risk of adverse pregnancy outcomes. This study aimed to use two different methods to explore the association of ICP with preterm birth (PTB) and low birth weight (LBW) in offspring.

Methods

First, a large early pregnancy cohort with a sample size of 34 104 was used to explore the association of ICP with PTB and LBW by using logistic regression analysis. Second, using a two-sample Mendelian randomization, we further assessed the effect of ICP on PTB and birth weight based on 15 single nucleotide polymorphisms from a genome-wide association study of ICP (n = 210 870).

Results

The results of the cohort study show that maternal ICP was associated with an increased risk of both PTB (aOR = 1.760, 95% CI: 1.443, 2.146, p < 0.001) and LBW (aOR = 2.220, 95% CI: 1.797, 2.741, p < 0.001) after adjusting for potential confounders. Mendelian randomization analyses suggested a potential causal effect of ICP on the risk of PTB (OR = 1.037, 95% CI: 1.011, 1.063, p = 0.005) and that ICP significantly reduced birth weight (beta = −0.010, 95% CI: −0.016, −0.004, p = 0.002).

Conclusions

Our findings suggest that ICP increases the risk of PTB and LBW, providing further evidence of these associations and highlighting the need for increased clinical monitoring of pregnant women with ICP.