Dose–response relationship between gestational blood glucose levels and risk of pre-eclampsia in singleton pregnancies: A retrospective multicenter study

BACKGROUND: Pre-eclampsia remains a leading cause of maternal and perinatal mortality and morbidity. Whether risks of pre-eclampsia are associated with severity of blood glucose concentrations or glycemic control is still unknown. This study aimed to analyze the association of blood glucose concentrations during pregnancy and the risk of pre-eclampsia. METHODS: A retrospective cohort study was conducted using data of 53,054 singleton pregnant women aged 18-49 years from 121 maternity hospitals in China between 2015 and 2018. Logistic regression models with restricted cubic splines were performed to reveal a non-linear association of blood glucose concentrations in the first trimester and the gestational change with pre-eclampsia. The association of the categories of blood glucose concentrations with pre-eclampsia was further examined by performing robust Poisson regression. RESULTS: A total of 1356 (2.55%, 1356/53,054) participants were diagnosed with pre-eclampsia. Higher risk was observed in those with higher blood glucose in the first trimester and those with greater increase in blood glucose during gestation, with the incidence of pre-eclampsia ranging from 1.27% (24/1883) to 6.03% (29/481). Compared with women with blood glucose (BG) concentrations of <4.4 mmol/L in the first trimester, the risk of pre-eclampsia was significantly increased in women with 4.4 ≤BG <5.1 mmol/L (adjusted relative risk [aRR] = 1.347, 95% confidence interval [CI]: 1.185-1.531), 5.1 ≤BG <5.6 mmol/L (aRR = 1.750, 95% CI: 1.441-2.124), and BG ≥5.6 mmol/L (aRR = 2.431, 95% CI: 1.958-3.019), respectively, after adjusting for basic characteristics of women, including region, age, education, ethnicity, residential status, assisted reproductive technology, primigravida, pre-pregnancy body mass index and categories of gestational change of blood glucose concentrations. The association of gestational change of blood glucose concentrations during gestation with pre-eclampsia was presented as a U-shaped curve after controlling the blood glucose concentrations in the first trimester. CONCLUSIONS: The findings highlight that higher blood glucose concentration in the first trimester and greater gestational variations of blood glucose contribute to higher risks of pre-eclampsia. Therefore, maintaining optimal blood glucose in early pregnancy and minimizing gestational glucose fluctuations is recommended to reduce the risk of pre-eclampsia.