Identifying physiological factors that could reduce pregnant women's risk for developing gestational diabetes mellitus (GDM) is crucial for early prevention and intervention. We aimed to examine whether higher serum levels of total bilirubin (TBIL) were associated with a decreased risk of GDM.

We conducted a retrospective cohort study in a tertiary care hospital in Shanghai, China. A total of 92,885 pregnant women were included. Serum TBIL levels were determined during the first antenatal visit before 24 weeks of gestation and GDM was diagnosed with a 75-g oral glucose tolerance test (OGTT) at 24–28 weeks of gestation.

A total of 13,037 GDM cases were identified, a prevalence of 14.0 % (13,037/92,885). These women had a higher median TBIL concentration 7.9 versus 7.6 mmol/l (P < 0.001). For the 91,051 women with TBIL within the physiologically normal range (≤ 17.1 μmol/l), a one interquartile range increase in TBIL (3.4 μmol/l) was associated with a decreased risk of GDM: adjusted odds ratio (OR)=0.89 [95 % CI 0.87;0.92]. For these women, the adjusted ORs for GDM across TBIL quartiles were: 0.92 [0.88;0.97] for the second, 0.85 [0.81;0.90] for the third, and 0.78 [0.74;0.83] for the fourth quartile in comparison with the first quartile.

Our study demonstrated that elevated serum TBIL levels were associated with decreased risk of GDM and supported its potential role in the prevention and early intervention of GDM.