Maternal Abnormal Liver Function in Early Pregnancy and Spontaneous Pregnancy Loss: A Retrospective Cohort Study

Spontaneous pregnancy loss (SPL) precedes an increased risk of reduced fertility, while its etiology mechanism remains largely unknown. Liver dysfunction presenting in early pregnancy may represent a pre-existing undiagnosed liver condition affecting fetal development. Here, we investigated whether maternal abnormal liver function in early pregnancy contributed to the incidence of SPL.

Data on pregnant women were leveraged from the Maternal Health Care Information System in Shanghai City from 2017 to 2021. Liver dysfunction status was defined as having any elevated liver function biomarker levels (LFBs) at the first antenatal visit. SPL cases were defined as fetal death occurring before 28 weeks gestation. Generalized linear models were used to estimate crude and adjusted risk ratios (RRs and aRRs, respectively) and 95% confidence intervals (CIs).

Among 10,175 leveraged pregnant women, 918 (9.0%) SPL cases were recorded. Maternal liver dysfunction in early pregnancy was associated with a 49% increased risk of SPL (RR 1.49; 95% CI, 1.22-1.84). This positive association persisted after adjustment for covariates (aRR 1.55; 95% CI, 1.26-1.92). Higher γ-glutamyl transferase (GGT) and alkaline phosphatase (ALP) levels were also linked with increased risk of SPL in a linear fashion (aRRs per 1 standard deviation increase: 1.13; 95% CI, 1.08-1.17 and 1.13; 95% CI, 1.07-1.20, respectively). Similar magnitudes of associations were observed between normal weight and overweight pregnant women in subgroup analysis.

We provide new evidence that maternal abnormal liver function in early pregnancy, as well as GGT and ALP, predisposes to an increased risk of SPL.