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

Abstract Background 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 foetal development. As a common but easily to be neglected metabolic disorder, little is known about whether and how maternal abnormal liver function in early pregnancy contribute to the incidence of SPL. Methods This is retrospective cohort study included 10175 pregnant womenwho were leveraged from the Maternal Health Care Information System (MHCIS) in Shanghai City from Jan 2017 to Dec 2021. Maternal 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 with binomial family and log link function were used to estimate crude and adjusted risk ratios (aRRs) and 95% confidence intervals (CIs). Results Among 10175 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; 1.13, 1.07–1.20, respectively). These observed positive associations remained significant even after adjustment for multiple corrections. Similar magnitudes of associations between liver dysfunction and SPL were observed in the subgroups of normal weight and overweight pregnant women. Conclusions We provide new evidence that maternal abnormal liver function in early pregnancy, as well as GGT and APL, predisposes to an increased risk of SPL. Primary healthcare providers may need to offer appropriate preconception counseling on the management of this modifiable risk factor in women of reproductive age.