Serum biomarkers and their association with disease severity and perinatal outcomes in preeclampsia: a retrospective study

Abstract Background To investigate the associations of pre-delivery serum blood urea nitrogen (BUN), uric acid (UA), cystatin C (CysC), and serum calcium levels with the occurrence of preeclampsia (PE), disease severity, and birth weight, and to evaluate their discriminatory performance in distinguishing severe preeclampsia (sPE) from PE. Methods A total of 328 women with singleton pregnancies who delivered at our hospital between January 2020 and December 2022 and met the inclusion and exclusion criteria were retrospectively enrolled, including 113 women in the normal pregnancy group, 125 in the PE group, and 90 in the sPE group. Maternal demographic characteristics, gestational age at blood sampling, gestational age at delivery, birth weight and related perinatal outcomes, blood pressure measurements, and laboratory parameters were collected. Multivariable binary logistic regression analyses were performed to evaluate the associations between the major laboratory biomarkers and the occurrence of PE and sPE after adjustment for maternal age, body mass index (BMI), nulliparity, assisted reproductive technology (ART) conception, and gestational age at blood sampling. Spearman correlation analysis and multiple linear regression analysis were used to assess the associations between the major laboratory biomarkers and birth weight after further adjustment for gestational age at delivery. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the discriminatory performance of the major laboratory biomarkers and the combined model consisting of BUN, UA, and CysC in distinguishing sPE from PE. The calibration and clinical utility of the combined model were further evaluated using the Hosmer–Lemeshow goodness-of-fit test, calibration plots, and decision curve analysis (DCA). Results Significant differences in BUN, UA, CysC, and serum calcium levels were observed among the three groups. After adjustment for maternal age, BMI, nulliparity, ART conception, and gestational age at blood sampling, elevated BUN, UA, and CysC levels were independently associated with the occurrence of PE, with odds ratios (ORs) of 3.057, 4.432, and 6.738, respectively (all P < 0.001). Higher serum calcium levels were associated with a lower risk of PE (OR = 0.733, P = 0.019). Among women with PE, only UA remained significantly associated with sPE after adjustment for the above confounding factors (OR = 1.444, 95% confidence interval [CI]: 1.056–1.975, P = 0.021). Correlation analyses showed that BUN, UA, and CysC were negatively correlated with birth weight, whereas serum calcium was not significantly associated with birth weight. After further adjustment for gestational age at delivery, only BUN and UA remained significantly associated with reduced birth weight. ROC analysis showed that the area under the curve (AUC) values for BUN, UA, CysC, and serum calcium (evaluated in the lower-value direction) in distinguishing sPE from PE were 0.610, 0.626, 0.567, and 0.590, respectively. The combined model including BUN, UA, and CysC yielded an AUC of 0.627, with a sensitivity of 37.8%, specificity of 87.2%, positive predictive value of 68.0%, and negative predictive value of 66.1%. The Hosmer–Lemeshow goodness-of-fit test indicated no significant lack of model fit, and decision curve analysis demonstrated that the combined model provided greater net benefit than the treat-all and treat-none strategies across a threshold probability range of approximately 0.34–0.66. Conclusions Pre-delivery levels of BUN, UA, CysC, and serum calcium were associated with the occurrence of PE, with UA being independently associated with sPE. BUN and UA remained associated with reduced birth weight after adjustment for gestational age at delivery. However, the discriminatory performance of UA, the other individual biomarkers, and the combined model for distinguishing sPE from PE was limited, and they should not be used alone to determine disease severity. Markedly elevated UA levels may help identify women with PE who require closer clinical monitoring; however, disease severity should still be comprehensively assessed based on blood pressure, proteinuria, clinical symptoms, and evidence of organ dysfunction.