Gestational hypertension during pregnancy is defined as high blood pressure that develops after 20 weeks of gestation, and without the presence of urinary protein. It is observed in approximately 5% of all pregnancies. Gestational hypertension is a primary factor leading to maternal and fetal mortality. Risks associated with gestational hypertension include stroke, multiorgan dysfunction syndrome, and disseminated intravascular coagulation. Additionally, the fetus is at risk of developmental delays (in 25% of preeclampsia cases), premature birth (in 27% of preeclampsia cases) and intrauterine fetal demise (in 4% of preeclampsia cases) [1]. According to an analysis by the World Health Organization (WHO), the maternal mortality rate in developed countries is 16.1%, whereas in Asian countries, it is 9.1% [2]. Annually, preeclampsia is identified as the cause of 42% of global maternal deaths, and it is also responsible for 15% of premature births [3, 4].

The utilization of markers, particularly those already established, is considered a prognostic measure for various conditions such as coronary artery disease and heart failure [5, 6]. As a result, monitoring biomarkers such as creatinine, uric acid (UA), and cystatin C is crucial in predicting and managing preeclampsia. UA concentration, in particular, is used to monitor renal function and correlate with the severity of preeclampsia, serving as both a prognostic marker and a factor in its pathophysiology [7, 8]. Despite its utility, there remains uncertainty in the accuracy of UA in predicting hypertensive disorders of pregnancy [3].

Previous studies have shown that individual biomarkers like UA, creatinine, and cystatin C can predict the risk and outcomes of preeclampsia [9, 10]. However, these studies focused on the prognostic value of single markers Our study addresses this gap in current research by evaluating multiple biomarkers simultaneously, providing a more comprehensive approach to predicting preeclampsia and severe preeclampsia in patients with gestational hypertension. By integrating several biomarkers, we aim to enhance prognostic accuracy and improve the identification of high-risk pregnancies. This novel method holds the potential to inform more effective diagnostic and management strategies, ultimately reducing complications for both mothers and infants.

The rate of preeclampsia/severe preeclampsia was found to be 20.6%, particularly within the age group of 20–40 years. In the preeclampsia/severe preeclampsia group, SBP, DBP, white blood cell count, red blood cell count, urea levels, microalbuminuria, urine albumin/creatinine ratio, urinary creatinine, cystatin C, and UA levels were all significantly elevated compared to the non-preeclampsia group, with differences reaching statistical significance (p 0.05). Conversely, the platelet count was markedly lower in the preeclampsia/severe preeclampsia group compared to the non-preeclampsia group, and this difference was also statistically significant (p 0.05). The Z-scores for SBP, DBP, red blood cell count, urea, uric acid, cystatin C, microalbumin, albumin-to-creatinine ratio, and urinary creatinine indicate highly significant differences (Table 1, Fig. 2).

Fig. 2.

Age and blood pressure distribution.

In the logistic regression analysis employing the backward: Wald method, SBP, creatinine, serum uric acid (SUA), and microalbuminuria emerged as independent predictors of preeclampsia/severe preeclampsia in patients with gestational hypertension (p 0.05) (Table 2).

Microalbuminuria, with a cut-off point of 126.25 mg/L, showed a sensitivity of 96.2%, specificity of 96%, and an area under the curve of 0.981. Regarding SBP, the cut-off threshold, sensitivity, and specificity were 155 mmHg, 65.4%, and 91%, respectively. SUA, with a cut-off threshold of 352.7, demonstrated a sensitivity of 92.3%, and specificity of 67%, and proved to be a significant predictive value for preeclampsia/severe preeclampsia in gestational hypertensive patients (p 0.001). Meanwhile, serum creatinine showed a sensitivity and specificity of 50% and 78%, respectively, in predicting preeclampsia/severe preeclampsia with p $>$ 0.05. Combining all four factors (SBP, SUA, serum creatinine, microalbumin) shows an AUC of 0.994 with a sensitivity of 96% and a specificity of 97% (Table 3, Fig. 3).

Fig. 3.

ROC curves of microalbuminuria, serum uric acid, systolic blood pressure, serum creatinine in predicting preeclampsia/severe preeclampsia. ROC, receiver operating characteristic; BP, blood pressure.

Our study indicates a preeclampsia/severe preeclampsia rate of 20.6%. Within this, the age group ranges between 20–40 years, and SBP, creatinine, SUA, and microalbuminuria are identified as independent risk factors predicting preeclampsia/severe preeclampsia in pregnant women with gestational hypertension. Notably, elevated serum UA levels, with an odds ratio (OR) of 1.019, serve as an important early marker of renal failure and predict adverse fetal outcomes, particularly in cases of severe gestational hypertension. A study by Bellos et al. (2020) [16] also demonstrated that serum uric acid levels are elevated in preeclampsia and can be used to predict disease severity and pregnancy complications. Another study also recommended the use of serum UA as a reliable marker of preeclampsia severity [17]. In our study, the UA concentration in the preeclampsia/severe preeclampsia group was 443.95 $\pm$ 112.3 µmol/L aligns with previous research. Le et al.’s (2019) research [9] has found UA levels of 328.99 µmol/L in preeclampsia and 427.60 µmol/L in severe preeclampsia groups, supporting the reliability of uric acid as a marker for preeclampsia. Additionally, in Y Padma et al.’s (2013) study [10], using an SUA cut-off of 6 mg/dL, the differences between pregnant women with gestational hypertension and those without were minimal. The preeclampsia group had slightly elevated levels compared to the normal threshold, averaging 6.13 mg/dL, distinguishing it from the other groups [10]. Bar et al. [15] studied 276 participants, with 142 in the study group and 134 in the control group. Their logistic and linear regression analyses found that early third-trimester microalbuminuria significantly increased the risk of hypertensive complications and was a strong predictor of birth weight. However, its reliability in predicting intrauterine growth retardation and neonatal outcomes was lower [15]. Baseline serum creatinine levels may help predict persistent hypertension and identify women at risk for chronic hypertension. Despite some debate on the predictive value of uric acid, which is linked to shorter gestational periods, lower birth weights, increased preeclampsia risk, and small-for-gestational-age infants, it remains a significant prognostic marker comparable to proteinuria for assessing risk in gestational hypertension [18].

Microalbuminuria at a threshold of 126.25 mg/L showed high sensitivity and specificity, with an area under the curve of 0.981, indicating its strong predictive value for preeclampsia. SUA at a threshold of 352.7 mg/L demonstrated significant predictive capability with a sensitivity of 92.3% and a specificity of 67%. In contrast, serum creatinine had lower predictive performance, with sensitivity at 50% and specificity at 78%. Several studies on the cut-off thresholds, sensitivity, and specificity of various markers in predicting preeclampsia and severe preeclampsia have been conducted [9, 15, 19]. However, the values vary depending on the demographic characteristics of each study. Notably, emerging biomarkers such as serum endostatin and serum cystatin C showed promising results, with serum endostatin achieving a sensitivity of 86.36% and specificity of 91.18% at initial sampling and serum cystatin C achieving an AUC of 0.934 in the second sampling. These new markers offer the potential for improving the early identification of preeclampsia [20]. ROC plots showed that serum creatinine had greater diagnostic accuracy than SUA, and SUA was more accurate than serum cystatin C [10].

Our study has several limitations that should be considered. Firstly, the single-center design may limit the generalizability of our findings and introduce potential selection bias, as the study sample may not fully represent the broader population. Additionally, there is a possibility of measurement bias due to the reliance on specific diagnostic criteria and assessment methods used at our center. Furthermore, the relatively short follow-up period might not capture long-term outcomes or the full impact of the interventions. Despite these limitations, the favorable outcomes observed in our study suggest that future research could benefit from exploring the use of simple, readily available markers to enhance both treatment and prevention strategies.

Starting from the 20th week of gestation onwards, pregnant women who develop hypertension should be tested for creatinine, serum uric acid, and microalbuminuria, as these factors independently predict the risk of preeclampsia/severe preeclampsia. Microalbuminuria, with its remarkable predictive value and diagnostic accuracy, stands out as one of the most valuable predictive markers for preeclampsia/severe preeclampsia. To effectively apply these findings in clinical practice, it is crucial to integrate these biomarkers into routine prenatal care protocols, with a focus on early detection and intervention. This could involve regular screening and a tiered management approach based on the severity of the test results, while also considering resource availability and the risk of over-treatment.

The data are available from the corresponding author on reasonable request.

Conceptualization: HHN, LTN, THN, AVT; methodology: HHN, THN; software: THN, KTN; formal analysis: PHT, THN, CMT; data curation: PHT, SKT, THN; writing original draft preparation: AVT, THN, HHN, KTN, CMT; writing – review & editing: HHN, THN, CMT. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

This study was conducted by the principles outlined in the Helsinki Declaration. All patients gave informed consent and were aware of the study’s purpose and methods. They could withdraw at any time without affecting their treatment. The study was approved by the Ethics Committee in Biomedical Research at Can Tho University of Medicine and Pharmacy (No.105 Date:10/5/2022).

This research received no external funding.

The authors declare no conflict of interest.