This study revealed that the inflammatory markers CRP and procalcitonin may have predictive value in the prediction of some obstetric and neonatal complications. C-reactive protein is an acute–phase reactant synthesized by the liver in response to proinflammatory cytokines and is a sensitive index of systemic inflammation [2]. Previous studies have not consistently monitored CRP and procalcitonin levels across all three trimesters or examined the obstetric and neonatal outcomes associated with unexplained elevations of these markers. The strength of this study is its prospective design, which allowed for the systematic investigation of the relationships between CRP and procalcitonin levels and between CRP and neonatal outcomes. Additionally, we examined whether unexplained elevations in these inflammatory markers contribute to adverse pregnancy or neonatal complications, providing a comprehensive evaluation of both maternal and neonatal health.
Notably, the mean levels of CRP in healthy pregnant women appear to be higher than the standardized levels in people who are not pregnant. A study of CRP levels in healthy pregnant women without antepartum complications revealed that CRP levels measured serially from 22 weeks gestation until delivery ranged from 0.7 to 0.9 mg/dL, depending on gestational age, in women who did not give birth [19]. In our study, 6.72 mg/L was found to be the cutoff value for CRP for the incidence of obstetric and neonatal complications.
In a previous study, a procalcitonin threshold of 1.9 ng/mL was used, and the sensitivity and specificity of maternal serum procalcitonin levels for the early diagnosis of neonatal infection and histologic chorioamnionitis were reported to range from 53 to 75% and 45–45%, respectively [9]. In our study, we found that the predictive value of PCT levels during pregnancy for predicting obstetric complications was 0.0385 ng/mL, with a sensitivity of 60% and specificity of 61%.
C-reactive protein (CRP) has been investigated as a potential early biomarker for chorioamnionitis in women with premature rupture of membranes, as well as a predictor of outcomes in preterm labor. Spontaneous preterm labor is associated with a range of causal and contributing factors [20, 21]. In a study conducted by Lee et al., maternal serum CRP levels below 8 mg/dL demonstrated a high negative predictive value for early-onset neonatal sepsis and funisitis. Similarly, other studies have reported that low maternal CRP levels strongly indicate the absence of chorioamnionitis or neonatal infection [22, 23]. In the present study, no cases of chorioamnionitis were recorded, and no significant associations were found between CRP levels and preterm labor or PPROM. This lack of association may be attributed to the nonspecific nature of CRP and the multifactorial etiology of preterm labor.
Preeclampsia is a common complication of pregnancy, with clinical manifestations including hypertension, proteinuria, and end-organ damage due to endothelial dysfunction thought to be the result of a maternal inflammatory response [24,25,26]. Although systemic inflammation has been implicated in the pathogenesis of preeclampsia, it is not known whether elevated levels of C-reactive protein measured early in pregnancy are associated with the subsequent development of preeclampsia. In a recent study by Gencheva et al., 36 patients with gestational hypertension, 37 patients with preeclampsia and 50 patients were used as controls, and high-sensitivity CRP levels were compared between the 20th and 34th weeks of pregnancy. High-sensitivity CRP levels were significantly higher in the gestational hypertension group than in the control group, similar to the findings of our study. Although higher sensitivity CRP levels were observed in the preeclampsia group than in the control group [27]. In a recent study by Wolf et al. consisting of 40 preeclampsia and 80 control groups, CRP levels were found to be higher in the preeclampsia group (4.6 mg/L compared with 2.3 mg/L), similar to our study [6]. A systematic review concluded that high first-trimester CRP levels may increase the risk of preeclampsia, and measures such as aspirin initiation should be taken above 15 mg/L [28]. The mean CRP level was 16 mg/L in patients with obstetric complications in our study. In the studies by Cao et al. and Barden et al. investigating susceptibility to preeclampsia in women with GDM, CRP levels were found to be higher in the group that developed preeclampsia, suggesting that elevated CRP levels may be useful biomarkers for predicting the development of preeclampsia [29, 30]. In other studies, CRP levels were found to be significantly higher in patients with preeclampsia than in those with normal pregnancies [31,32,33]. In the present study, both preeclampsia and gestational hypertension were significantly more prevalent among patients with elevated levels of CRP and PCT, supporting the hypothesis that systemic inflammation may play a role in the pathophysiology of hypertensive disorders during pregnancy. The significant increase in CRP and PCT levels in these groups suggests that these biomarkers could serve not only as reflections of an ongoing inflammatory response, but also as potential predictive indicators for the development of hypertensive complications. This finding aligns with previous studies that have identified inflammatory markers as contributors to endothelial dysfunction and vascular pathology in pregnancy-related hypertension. We recommend screening for CRP and procalcitonin, to help predict preeclampsia. However, further prospective studies are warranted to clarify the causal relationships and to evaluate their clinical utility in risk stratification and early intervention.
A study involving 450 women revealed that high-sensitivity CRP values in the first trimester are associated with the development of gestational diabetes mellitus later in pregnancy [34]. In a prospective study by Westergaard et al. including 1049 patients, there was no association between GDM and CRP levels [35]. In a study in which the cutoff value for CRP was set at 3 mg/dL, a significant increase in CRP was found in the group of patients with GDM compared with the control group [36]. In a Chinese study involving 36 GDM patients and 36 control groups, when fasting and 1 st hour CRP levels were measured during the OGTT, the levels were significantly greater in the GDM group than in the control group, suggesting that this difference was related to oxidative stress [37]. In our study, GDM was observed in a greater number of patients with elevated CRP in all trimesters, but this difference did not reach statistical significance. This may have been due to the small number of patients with GDM among the participants due to other risk factors.
In studies that have investigated the role of CRP in pregnancy loss, no association between high levels of CRP and pregnancy loss has been reported, similar to our study [38, 39]. Consequently, it is suggested that pregnancy loss is not associated with increased maternal systemic inflammation. In contrast, another study revealed that patients who experienced pregnancy loss had significantly higher CRP levels than patients with ongoing pregnancy and the control group did [40]. In our study, pregnancy loss was more common in patients with elevated CRP and procalcitonin levels, but no significant associations were found. Therefore, for the prediction of pregnancy loss, CRP and procalcitonin screening is not recommended.
Early detection of sepsis is critical to reduce morbidity and mortality and improve outcomes in infants with sepsis. Therefore, the availability of predictive tests for neonatal sepsis may be effective in clinical management. In a study of 25 patients with neonatal sepsis and 62 patients without sepsis, the mean maternal CRP protein levels of mothers with neonatal sepsis were significantly greater than those of control mothers [41]. In our study, there was no significant relationship between CRP or PCT and neonatal sepsis because of the small number of neonatal sepsis patients.
The incidence of composite neonatal complications and the need for neonatal intensive care increased significantly with elevated CRP and procalcitonin levels. According to our data, the highest need for intensive care is due to RDS. While procalcitonin elevation significantly increased RDS, no significant relationship was found between CRP elevation and RDS.
The limitation of this study is that, due to the prospective design, the number of patients with obstetric complications and neonatal complications in each group was inadequate for statistical significance. The CRP and PCT cut-off values derived from ROC curve analyses demonstrated relatively low sensitivity and specificity, which may limit their predictive utility.The number of patients whose CRP and PCT levels were analyzed in each trimester was low because of problems with patient follow-up.
