Associations of CRP and PCT levels with obstetric and neonatal outcomes: a prospective study

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The aim of this study was to determine the cutoff values for CRP and PCT levels during pregnancy and to evaluate the associations of any elevation with obstetric and neonatal outcomes. Methods: This prospective study was conducted from June 2023 to December 2024. The study included 411 singleton pregnant women aged 18–44 years with no apparent clinical infection. Venous blood samples were collected during the visit for routine antenatal care during all three trimesters. Categorical variables were compared between groups via the chi-square test, and Student's t-test was used to compare normally distributed continuous variables. The area under the ROC curve was used to detect sensitivity and specificity and to set a cutoff. Regression analysis was performed to evaluate the effects of age and BMI on obstetric complications. P values < 0.05 were considered statistically significant. Results: The mean CRP and PCT levels in the study group were 10.9 ±16.7 and 0.17 ±1.8, respectively. ROC curves were used to analyze the ability of CRP and PCT values during pregnancy to predict obstetric complications. A cutoff value of 6.72 mg/L (sensitivity: 67%; specificity: 60%) and 0.0385 (sensitivity: 60%; specificity: 61%) was revealed. The incidence of composite obstetric complications was significantly greater in patients with elevated CRP levels (32.4% vs. 67.6%) (p 6,72. The incidence of composite obstetric complications was significantly greater in patients with elevated PCT levels (59% vs. 41%) (p<0.001). Patients with elevated PCT levels had a greater frequency of preterm labor or PPROM, neonatal complications, need for intensive care, and RDS. Conclusions: Elevated CRP and PCT are associated with increased rates of obstetric and neonatal complications. CRP and PCT, which are inexpensive and available, may be used for screening to predict obstetric and neonatal complications during patient follow-up. Trial registration This study was approved by the institutional ethical committee of the Gazi University Faculty of Medicine (Approval No:05.06.2023/479). C-reactive protein Procalcitonin Obstetric complications Neonatal outcomes Pregnancy Figures Figure 1 Background Prenatal care and continuous monitoring during pregnancy are essential for mitigating obstetric and neonatal complications, which are directly associated with maternal and neonatal morbidity and mortality. These complications include preterm birth, stillbirth, intrauterine growth restriction (IUGR), preeclampsia, gestational diabetes mellitus (GDM), and chorioamnionitis [1]. The primary objective of prenatal follow-up is to evaluate the health status of both the pregnant individual and the fetus while systematically monitoring the pregnancy to identify and manage potential risks. Prenatal care is a critical component of ensuring maternal and fetal well-being throughout pregnancy. The initial visit during the first trimester typically includes a comprehensive array of assessments aimed at identifying potential risks and establishing baseline health data. These follow-up visits play a vital role in detecting potential obstetric complications and ensuring early intervention when necessary. Therefore, the identification and monitoring of specific biomarkers that can guide the prenatal follow-up process is of paramount importance. C-reactive protein (CRP) is an acute-phase reactant synthesized by the liver in response to inflammation, and it is commonly used as a biomarker in various clinical contexts [2]. Although CRP is not specific to infectious processes, it has been widely utilized in the diagnostic workup of conditions such as chorioamnionitis during pregnancy [3]. CRP levels are generally elevated in normal pregnant individuals compared with nonpregnant individuals. The utility of CRP has been investigated in several obstetric scenarios, including its role in diagnosing subclinical infections in cases of premature rupture of membranes (PROM) [4], assessing the risk of preterm birth[5], and evaluating its association with the development of preeclampsia[6, 7]. Procalcitonin (PCT), a 116-amino acid precursor to the hormone calcitonin, has emerged as another important acute-phase biomarker, particularly in the context of bacterial infections[8]. PCT levels rise rapidly within 3 to 6 hours following bacterial infection, making PCT a sensitive marker for distinguishing bacterial from nonbacterial infections. Owing to its rapid response, PCT has gained clinical acceptance in obstetrics, particularly in the diagnosis and management of bacterial infections during pregnancy[3]. In a recent study conducted by Torbé et al., maternal serum procalcitonin levels were evaluated as a potential biomarker for the early diagnosis of neonatal infection and histologic chorioamnionitis. The study revealed that with a threshold of 1.9 ng/mL, the sensitivity of maternal procalcitonin levels for diagnosing neonatal infection and histologic chorioamnionitis was 53% and 75%, respectively, whereas the specificity was reported to be 45% for both conditions[9]. The associations of procalcitonin levels with other pregnancy complications, to our knowledge, have not been previously investigated. The present study investigated the relationships of CRP and procalcitonin levels across trimesters with obstetric and neonatal outcomes. Specifically, this study aimed to assess whether elevated levels of CRP and procalcitonin are predictive of potential obstetric or neonatal complications and whether these biomarkers could be utilized as effective screening tools in prenatal care. Methods Study population and design This prospective study was conducted at the Gazi University Faculty of Medicine Department of Obstetrics and Gynecology (Ankara, Turkey) between June 2023 and December 2024. This study was approved by the institutional ethical committee of the Gazi University Faculty of Medicine (Approval No: 05.06.2023/479). The study included 411 singleton pregnant women aged 18–44 years with no apparent clinical infection. The exclusion criteria were (1) multiple pregnancies; (2) maternal diseases (rheumatological, endocrinological, nephrological, neurological, hematological, oncological, etc.); and (3) clinical maternal infection during blood sample collection (chorioamnionitis, upper respiratory tract infection, urinary tract infection, gastroenteritis, etc.). All patients who participated in the study were informed of the study, and informed consent was obtained from all participants. The patient's last menstrual period and first trimester ultrasound scans were used to determine gestational age. Preterm labor, PPROM, IUGR, preeclampsia, gestational hypertension (GHT), gestational diabetes mellitus, pregnancy loss, hypothyroidism and cholestasis were included in the composite obstetric complications. Respiratory distress syndrome (RDS), neonatal sepsis, necrotizing enterocolitis (NEC) and intraventricular hemorrhage were included in the composite neonatal complications. Pregnancy loss is defined as the termination of pregnancy before 20 weeks of gestation [10]. Preterm labor is characterized by the delivery of a fetus between 20 weeks and 0 days and between 36 weeks and 6 days of gestation [11]. Preterm premature rupture of membranes (PPROM) refers to the rupture of fetal membranes prior to 37 weeks of gestation [12]. Preeclampsia was defined as a blood pressure increase of more than 140/90 mmHg after 20 weeks of gestation combined with proteinuria, either more than 300 mg per 24 hours or 2 + or more by dipstick[13]. In the absence of proteinuria, preeclampsia is diagnosed as hypertension associated with thrombocytopenia (platelet count less than 100,000/microliter), impaired liver function (elevated blood levels of liver transaminases to twice the normal concentration), new-onset renal insufficiency (elevated serum creatinine greater than 1.1 mg/dL or a doubling of serum creatinine), the development of cerebral or visual disturbances, or pulmonary edema[13]. Gestational hypertension is an increase in blood pressure after 20 weeks of gestation in the absence of proteinuria or any systemic findings [13]. GDM was diagnosed between the 24th and 32nd weeks of gestation, according to the criteria of the International Association of Diabetes and Pregnancy Study Group [14]. Neonatal sepsis is a pathological process that occurs in infants within the first four weeks of life and is characterized by hemodynamic and respiratory alterations resulting from a systemic inflammatory response to an infectious process[15]. Neonatal respiratory distress syndrome is a pulmonary condition that leads to respiratory difficulties in newborns shortly after birth [16]. CRP and Procalcitonin Measurement Venous blood samples were collected during the antenatal visit for routine antenatal care during all three trimesters. CRP and procalcitonin measurements were carried out on the same day that blood was taken. The serum CRP levels were evaluated via nephelometric methods on a Siemens brand BN 2 (Siemens Healthineers Corp. Erlangen, Germany) autoanalyzer, and the serum procalcitonin levels were evaluated via electrochemiluminescence methods on a Roche brand Cobas e 601 (Roche Diagnostics GmbH, Hoffmann-La Roche Ltd, Mannheim, Germany) hormone autoanalyzer. Statistical analysis SPSS 25.0 statistical software (IBM SPSS Inc., Chicago, IL) was used for data analysis. Categorical variables were compared between groups via the chi-square test. Student's t test was used to compare normally distributed continuous variables. The area under the receiver operating characteristic (ROC) curve was used to detect sensitivity, specificity, and cutoff. Regression analysis was performed to evaluate the effects of age and body mass index (BMI) on obstetric complications. P values < 0.05 were considered statistically significant. Results This study included a total of 411 patients. CRP analysis was conducted in 232 patients during the first trimester, 131 during the second trimester, and 131 during the third trimester. Procalcitonin analysis was performed in 228 patients during the first trimester, 117 during the second trimester, and 122 during the third trimester. Pregnancy loss occurred before 20 weeks of gestation in 14 patients. The mean age of the patients in our study was 29.8 years. The mean gravida was 2, and the mean parity was 0.7. The mean BMI, number of gestational weeks at the time of delivery and mean birth weight were 25.2, 38, 2 days, and 3131 g, respectively. The incidence of composite obstetric complications was 27%, whereas composite neonatal complications occurred in 10.6% of cases. Gestational cholestasis was observed in five patients, and hypothyroidism was observed in eight patients. The incidence rates of specific complications among the study population were as follows: preterm labor (13.4%), PPROM (7.8%), IUGR (1.5%), preeclampsia (3.3%), gestational hypertension (2.7%), gestational diabetes mellitus (5.4%), gestational cholestasis (1.2%), hypothyroidism (1.9%), and pregnancy loss (3.4%). The incidence rates of neonatal complications were as follows: respiratory distress syndrome (RDS) 1.9%, neonatal sepsis 1.2%, necrotizing enterocolitis (NEC) 0.2%, and intraventricular hemorrhage (IVH) 0.5%. The need for intensive care was observed in 10.5% of the patients. The mean CRP level for all patients included in the study was 10.9 ± 16.7. The mean CRP levels in patients with and without obstetric complications were 16 ± 23.9 and 9 ± 12.7, respectively, indicating a statistically significant difference (p = 0.004). The mean procalcitonin level for all patients included in the study was 0.17 ± 1.8. The mean procalcitonin levels in patients with and without obstetric complications were 0.55 ± 3.52 and 0.04 ± 0.05, respectively, with no statistically significant difference (p = 0.14). The ROC curve was used to analyze the value of CRP values during pregnancy regardless of trimester to predict the presence of composite obstetric complications and revealed a cutoff value of 6.72 mg/L, with a sensitivity of 67% and specificity of 60% (Fig. 1 - A). Similarly, the ROC curve was used to analyze the predictive value of PCT values during pregnancy for predicting obstetric complications and revealed a cutoff value of 0.0385 for a sensitivity of 60% and a specificity of 61%. This value was determined as the cutoff value for PCT to predict obstetric complications (Fig. 1 -B). The comparisons of demographic and obstetric data between those below and above the threshold values of CRP and PCT are shown in Table 1 . The mean age and BMI of patients in the present study were significantly greater in those with CRP levels above the cutoff than in those with low CRP levels (p = 0,003 and p = 0,003, respectively). However, there was no statistically significant difference in birth weight between the two groups (Table 1 ). The mean age, BMI, and birth weight did not differ significantly between groups stratified by PCT levels above or below the cutoff (Table 1 ). In contrast, the mean gestational age at delivery was significantly greater in patients with low CRP and low PCT levels than in those with elevated CRP and PCT levels (Table 1 ). Table 1 Clinical characteristics of patients with and without elevated CRP and PCT levels CRP ≤ 6,72 CRP > 6,72 p Value PCT ≤ 0,0385 PCT > 0,085 p Value Age (years) 29,1 ± 4,9 30,7 ± 5,4 0,003 29,5 ± 5,1 29,8 ± 5,3 0,58 BMI(kg/m 2 ) 24,4 ± 3,7 26,0 ± 4,4 0,001 24,9 ± 4,1 25,4 ± 4,1 0,272 Birth Weight (g) 3169,4 ± 421,7 3089,4 ± 604,0 0,132 3175,6 ± 432,0 3073,9 ± 596,4 0,064 Gestational age at the time of delivery (weeks) 38,4 ± 1,5 38 ± 2,4 0,049 38,5 ± 1,7 37,9 ± 2,3 0,004 A comparison of patients with and without elevated CRP levels in any trimester revealed a significantly greater frequency of composite obstetric complications in the elevated CRP group (32.4% − 67.6%) (p 6,72 (Table 2 ). In addition, the prevalence of preeclampsia and the incidence of GHT were significantly greater in patients with elevated first trimester CRP levels (p < 0.003). No statistically significant differences were observed in the frequency of preterm labor, PPROM, IUGR, GDM or pregnancy loss in patients with elevated CRP above the cutoff (Table 2 ). The regression analysis indicated that only CRP elevation was a significant factor, while both age and BMI were not significant predictors of obstetric complications. The incidence of composite obstetric complications was significantly greater in patients with elevated PCT (59% vs. 41%) (p < 0.001) (Table 2 ). No statistically significant difference was observed in the frequency of preeclampsia, gestational hypertension, IUGR, GDM, or pregnancy loss in patients with elevated PCT. However, patients with elevated PCT levels had a greater frequency of preterm labor or PPROM (18.6%), neonatal complications (14.8%), need for intensive care (15.5%), and RDS (3.6%) (Table 2 ). Table 2 Comparison of obstetric and neonatal outcomes in patients with and without elevated CRP and PCT CRP ≤ 6,72 n (%) CRP > 6,72 n (%) P Value PCT ≤ 0,0385 n (%) PCT > 0,085 n (%) P Value Composite Obstetric Complications 36 (16,7%) 75 (38,3%) 0,001 43 (19,6%) 62 (34,8%) 0,001 Preeclampsia 2 (0,9%) 11 (5,9%) 0,006 4 (1,9%) 7 (4,1%) 0,225 GHT 0 11 (5,9%) 0,001 3 (1,4%) 6(3,6%) 0,191 GDM 9 (4,3%) 13 (7%) 0,237 11 (5,1%) 9 (5,3%) 0,936 IUGR 1 (0,5%) 5 (2,7%) 0,103 2 (0,9%) 3 (1,8%) 0,658 PPROM/Preterm labor 24 (11,2%) 30 (15,3%) 0,278 19(8,7%) 33 (18,6%) 0,003 1st trimester pregnancy loss 4 (1,9%) 10 (5,1%) 0,07 5(2,3%) 9(5,1%) 0,136 Composite Neonatal Complications 15 (7,1%) 28 (14,5%) 0,017 15 (7%) 25(14,8%) 0,013 RDS 3(1,4%) 5 (2,7%) 0,481 1 (0,5%) 6 (3,6%) 0,047 Neonatal Sepsis 2(1%) 3(1,6%) 0,668 2(0,9%) 3(1,8%) 0,658 NEC 1(0,5%) 0 1 1(0,5%) 0 1 The need for intensive care 15(7,1%) 28(15,1%) 0,010 15(7%) 26(15,5%) 0,008 Discussion 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 0.7–0.9 mg/dL, depending on gestational age, in women who did not give birth [17]. 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 53–75% 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 [18]. 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 [19, 20]. In the present study, no cases of chorioamnionitis were recorded, and no significant associations were found between CRP or procalcitonin 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[21, 22]. 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 [23]. 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 [24]. 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 [25, 26]. In other studies, CRP levels were found to be significantly higher in patients with preeclampsia than in those with normal pregnancies [27–29]. In the present study, the levels of CRP and PCT were significantly greater in the preeclampsia and gestational hypertension groups. The associations between CRP and PCT levels and preeclampsia support the hypothesis that systemic inflammation plays a role in the pathogenesis of preeclampsia. We recommend screening for CRP and procalcitonin, especially CRP in the first trimester, to help predict preeclampsia. 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 [30]. In a prospective study by Westergaard et al. including 1049 patients, there was no association between GDM and CRP levels [31]. 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 [32]. In a Chinese study involving 36 GDM patients and 36 control groups, when fasting and 1st 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[33]. 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 [34, 35]. 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 [36]. 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 [37]. 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, owing to the prospective design, the number of patients with obstetric complications and neonatal complications in each group was inadequate for statistical significance. The number of patients whose CRP and PCT levels were analyzed in each trimester was low because of problems with patient follow-up. Conclusions In conclusion, this is the first prospective study in which pregnant women were screened for CRP and PCT in different trimesters, and obstetric and neonatal outcomes were analyzed. Elevated CRP and PCT are associated with increased obstetric and neonatal complications. CRP and PCT, which are inexpensive and available, may be used for screening to predict obstetric and neonatal complications during patient follow-up. We recommend that the study be repeated with a larger number of patients for routine clinical use. Abbreviations BMI Body mass index CRP C-reactive protein IUGR Intrauterine Growth Restriction IVH Intraventricular hemorrhage GDM Gestational diabetes mellitus GHT Gestational hypertension NEC Necrotizing enterocolitis PCT Procalcitonin PROM Premature Membrane Rupture PPROM Preterm premature rupture of membranes ROC Receiver operating characteristic Declarations Ethics approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki and approved by the institutional ethical committee of the Gazi University Faculty of Medicine (Approval No:479). All patients who participated in the study were informed of the study, and informed consent was obtained from all participants. Consent for publication Not applicable Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Competing interests The authors declare that they have no competing interests. Funding None Authors' contributions ME, PC and MA designed the study. MA, AGA, CY, and IMH collected the data. ME, PC and MA analyzed the data. MA drafted the work; PC, AE, and ME revised it substantially. All the authors read and approved the final manuscript. Acknowledgments Not applicable Authors' information (optional) Not applicable References Liston, R., D. Sawchuck, and D. Young, Fetal health surveillance: antepartum and intrapartum consensus guideline. J Obstet Gynaecol Can, 2007. 29 (9 Suppl 4): p. S3-56. Yudkin, J.S., et al., C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol, 1999. 19 (4): p. 972-8. 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Cite Share Download PDF Status: Published Journal Publication published 21 Aug, 2025 Read the published version in BMC Pregnancy and Childbirth → Version 1 posted Editorial decision: Revision requested 03 Jun, 2025 Reviews received at journal 30 May, 2025 Reviewers agreed at journal 27 May, 2025 Reviewers agreed at journal 22 May, 2025 Reviews received at journal 21 May, 2025 Reviews received at journal 11 May, 2025 Reviewers agreed at journal 11 May, 2025 Reviewers agreed at journal 10 May, 2025 Reviewers invited by journal 07 May, 2025 Editor invited by journal 28 Apr, 2025 Editor assigned by journal 25 Apr, 2025 Submission checks completed at journal 25 Apr, 2025 First submitted to journal 23 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6515536","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":454878395,"identity":"72b350a5-0f58-4449-a4f7-4e0884bf8149","order_by":0,"name":"Merve Ates","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIiWNgGAWjYPCCBBDB+ABI8PCRooXZAKSFjRQtbBJgkpBa3fbeZxIfGNISt0sfflb5NcdOho2B+eGjG3i0mJ05biY5gyEncWdfmtlt2W3JQIexGRvn4NNyI43ZmIehInHDGR6225LbmIFaeNik8Wq5/4zZ+A9US7HktnoitNxgY3zMAHQYSAvjx22HidByJo3xYY9BmvGGM2zG0ozbjvOwMRPyy/FjDAd+VCTLbjjD/PDjz23V9vzszQ8f49MCAQYMjg1AipkHxGEmqBwC7EEE4w8iVY+CUTAKRsHIAgC9pEMSpSdGQQAAAABJRU5ErkJggg==","orcid":"","institution":"Gazi University","correspondingAuthor":true,"prefix":"","firstName":"Merve","middleName":"","lastName":"Ates","suffix":""},{"id":454878396,"identity":"78ef250d-deef-4f46-a79a-8b4d98a77e9f","order_by":1,"name":"Pinar Tokdemir Calis","email":"","orcid":"","institution":"Gazi University","correspondingAuthor":false,"prefix":"","firstName":"Pinar","middleName":"Tokdemir","lastName":"Calis","suffix":""},{"id":454878397,"identity":"e83b73c8-fced-4e3c-bada-25c719f5813b","order_by":2,"name":"Ayse Gokcen Artıktay","email":"","orcid":"","institution":"Gazi University","correspondingAuthor":false,"prefix":"","firstName":"Ayse","middleName":"Gokcen","lastName":"Artıktay","suffix":""},{"id":454878398,"identity":"6222754f-6241-4c77-b48f-a3da217d3ecd","order_by":3,"name":"Canan Yilmaz","email":"","orcid":"","institution":"Gazi University","correspondingAuthor":false,"prefix":"","firstName":"Canan","middleName":"","lastName":"Yilmaz","suffix":""},{"id":454878399,"identity":"84d4cf35-cebc-440d-a08f-0b0b61ea91ee","order_by":4,"name":"Ibrahim Murat Hirfanoglu","email":"","orcid":"","institution":"Gazi University","correspondingAuthor":false,"prefix":"","firstName":"Ibrahim","middleName":"Murat","lastName":"Hirfanoglu","suffix":""},{"id":454878400,"identity":"9c2dc269-387c-4ffe-a3b1-754275d5a7ce","order_by":5,"name":"Ahmet Erdem","email":"","orcid":"","institution":"Gazi University","correspondingAuthor":false,"prefix":"","firstName":"Ahmet","middleName":"","lastName":"Erdem","suffix":""},{"id":454878401,"identity":"357a8e39-d84f-4678-8591-8f16eab0cd71","order_by":6,"name":"Mehmet Erdem","email":"","orcid":"","institution":"Gazi University","correspondingAuthor":false,"prefix":"","firstName":"Mehmet","middleName":"","lastName":"Erdem","suffix":""}],"badges":[],"createdAt":"2025-04-23 21:23:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6515536/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6515536/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12884-025-07970-w","type":"published","date":"2025-08-21T16:29:30+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82620834,"identity":"9e2b8869-10f2-4fc9-982e-b64d812ad17a","added_by":"auto","created_at":"2025-05-13 12:17:17","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":76268,"visible":true,"origin":"","legend":"\u003cp\u003eA: ROC curve for CRP levels\u003c/p\u003e\n\u003cp\u003eB: ROC curve for PCT levels\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6515536/v1/683e1806b8fd4165da44afa3.png"},{"id":89847318,"identity":"58c44dd3-5224-4e10-b8da-e8066f095af8","added_by":"auto","created_at":"2025-08-25 16:43:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":935137,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6515536/v1/84718bfb-d140-41e0-8e07-413ac00d6e1c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Associations of CRP and PCT levels with obstetric and neonatal outcomes: a prospective study","fulltext":[{"header":"Background","content":"\u003cp\u003ePrenatal care and continuous monitoring during pregnancy are essential for mitigating obstetric and neonatal complications, which are directly associated with maternal and neonatal morbidity and mortality. These complications include preterm birth, stillbirth, intrauterine growth restriction (IUGR), preeclampsia, gestational diabetes mellitus (GDM), and chorioamnionitis [1]. The primary objective of prenatal follow-up is to evaluate the health status of both the pregnant individual and the fetus while systematically monitoring the pregnancy to identify and manage potential risks.\u003c/p\u003e \u003cp\u003ePrenatal care is a critical component of ensuring maternal and fetal well-being throughout pregnancy. The initial visit during the first trimester typically includes a comprehensive array of assessments aimed at identifying potential risks and establishing baseline health data. These follow-up visits play a vital role in detecting potential obstetric complications and ensuring early intervention when necessary. Therefore, the identification and monitoring of specific biomarkers that can guide the prenatal follow-up process is of paramount importance.\u003c/p\u003e \u003cp\u003eC-reactive protein (CRP) is an acute-phase reactant synthesized by the liver in response to inflammation, and it is commonly used as a biomarker in various clinical contexts [2]. Although CRP is not specific to infectious processes, it has been widely utilized in the diagnostic workup of conditions such as chorioamnionitis during pregnancy [3]. CRP levels are generally elevated in normal pregnant individuals compared with nonpregnant individuals. The utility of CRP has been investigated in several obstetric scenarios, including its role in diagnosing subclinical infections in cases of premature rupture of membranes (PROM) [4], assessing the risk of preterm birth[5], and evaluating its association with the development of preeclampsia[6, 7].\u003c/p\u003e \u003cp\u003eProcalcitonin (PCT), a 116-amino acid precursor to the hormone calcitonin, has emerged as another important acute-phase biomarker, particularly in the context of bacterial infections[8]. PCT levels rise rapidly within 3 to 6 hours following bacterial infection, making PCT a sensitive marker for distinguishing bacterial from nonbacterial infections. Owing to its rapid response, PCT has gained clinical acceptance in obstetrics, particularly in the diagnosis and management of bacterial infections during pregnancy[3]. In a recent study conducted by Torb\u0026eacute; et al., maternal serum procalcitonin levels were evaluated as a potential biomarker for the early diagnosis of neonatal infection and histologic chorioamnionitis. The study revealed that with a threshold of 1.9 ng/mL, the sensitivity of maternal procalcitonin levels for diagnosing neonatal infection and histologic chorioamnionitis was 53% and 75%, respectively, whereas the specificity was reported to be 45% for both conditions[9]. The associations of procalcitonin levels with other pregnancy complications, to our knowledge, have not been previously investigated.\u003c/p\u003e \u003cp\u003eThe present study investigated the relationships of CRP and procalcitonin levels across trimesters with obstetric and neonatal outcomes. Specifically, this study aimed to assess whether elevated levels of CRP and procalcitonin are predictive of potential obstetric or neonatal complications and whether these biomarkers could be utilized as effective screening tools in prenatal care.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population and design\u003c/h2\u003e \u003cp\u003eThis prospective study was conducted at the Gazi University Faculty of Medicine Department of Obstetrics and Gynecology (Ankara, Turkey) between June 2023 and December 2024. This study was approved by the institutional ethical committee of the Gazi University Faculty of Medicine (Approval No: 05.06.2023/479).\u003c/p\u003e \u003cp\u003eThe study included 411 singleton pregnant women aged 18\u0026ndash;44 years with no apparent clinical infection.\u003c/p\u003e \u003cp\u003eThe exclusion criteria were (1) multiple pregnancies; (2) maternal diseases (rheumatological, endocrinological, nephrological, neurological, hematological, oncological, etc.); and (3) clinical maternal infection during blood sample collection (chorioamnionitis, upper respiratory tract infection, urinary tract infection, gastroenteritis, etc.). All patients who participated in the study were informed of the study, and informed consent was obtained from all participants.\u003c/p\u003e \u003cp\u003eThe patient's last menstrual period and first trimester ultrasound scans were used to determine gestational age. Preterm labor, PPROM, IUGR, preeclampsia, gestational hypertension (GHT), gestational diabetes mellitus, pregnancy loss, hypothyroidism and cholestasis were included in the composite obstetric complications. Respiratory distress syndrome (RDS), neonatal sepsis, necrotizing enterocolitis (NEC) and intraventricular hemorrhage were included in the composite neonatal complications.\u003c/p\u003e \u003cp\u003ePregnancy loss is defined as the termination of pregnancy before 20 weeks of gestation [10]. Preterm labor is characterized by the delivery of a fetus between 20 weeks and 0 days and between 36 weeks and 6 days of gestation [11]. Preterm premature rupture of membranes (PPROM) refers to the rupture of fetal membranes prior to 37 weeks of gestation [12].\u003c/p\u003e \u003cp\u003ePreeclampsia was defined as a blood pressure increase of more than 140/90 mmHg after 20 weeks of gestation combined with proteinuria, either more than 300 mg per 24 hours or 2\u0026thinsp;+\u0026thinsp;or more by dipstick[13]. In the absence of proteinuria, preeclampsia is diagnosed as hypertension associated with thrombocytopenia (platelet count less than 100,000/microliter), impaired liver function (elevated blood levels of liver transaminases to twice the normal concentration), new-onset renal insufficiency (elevated serum creatinine greater than 1.1 mg/dL or a doubling of serum creatinine), the development of cerebral or visual disturbances, or pulmonary edema[13]. Gestational hypertension is an increase in blood pressure after 20 weeks of gestation in the absence of proteinuria or any systemic findings [13]. GDM was diagnosed between the 24th and 32nd weeks of gestation, according to the criteria of the International Association of Diabetes and Pregnancy Study Group [14].\u003c/p\u003e \u003cp\u003eNeonatal sepsis is a pathological process that occurs in infants within the first four weeks of life and is characterized by hemodynamic and respiratory alterations resulting from a systemic inflammatory response to an infectious process[15]. Neonatal respiratory distress syndrome is a pulmonary condition that leads to respiratory difficulties in newborns shortly after birth [16].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCRP and Procalcitonin Measurement\u003c/h3\u003e\n\u003cp\u003eVenous blood samples were collected during the antenatal visit for routine antenatal care during all three trimesters. CRP and procalcitonin measurements were carried out on the same day that blood was taken. The serum CRP levels were evaluated via nephelometric methods on a Siemens brand BN 2 (Siemens Healthineers Corp. Erlangen, Germany) autoanalyzer, and the serum procalcitonin levels were evaluated via electrochemiluminescence methods on a Roche brand Cobas e 601 (Roche Diagnostics GmbH, Hoffmann-La Roche Ltd, Mannheim, Germany) hormone autoanalyzer.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eSPSS 25.0 statistical software (IBM SPSS Inc., Chicago, IL) was used for data analysis. Categorical variables were compared between groups via the chi-square test. Student's t test was used to compare normally distributed continuous variables. The area under the receiver operating characteristic (ROC) curve was used to detect sensitivity, specificity, and cutoff. Regression analysis was performed to evaluate the effects of age and body mass index (BMI) on obstetric complications. \u003cem\u003eP\u003c/em\u003e values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThis study included a total of 411 patients. CRP analysis was conducted in 232 patients during the first trimester, 131 during the second trimester, and 131 during the third trimester. Procalcitonin analysis was performed in 228 patients during the first trimester, 117 during the second trimester, and 122 during the third trimester. Pregnancy loss occurred before 20 weeks of gestation in 14 patients. The mean age of the patients in our study was 29.8 years. The mean gravida was 2, and the mean parity was 0.7. The mean BMI, number of gestational weeks at the time of delivery and mean birth weight were 25.2, 38, 2 days, and 3131 g, respectively.\u003c/p\u003e \u003cp\u003eThe incidence of composite obstetric complications was 27%, whereas composite neonatal complications occurred in 10.6% of cases. Gestational cholestasis was observed in five patients, and hypothyroidism was observed in eight patients. The incidence rates of specific complications among the study population were as follows: preterm labor (13.4%), PPROM (7.8%), IUGR (1.5%), preeclampsia (3.3%), gestational hypertension (2.7%), gestational diabetes mellitus (5.4%), gestational cholestasis (1.2%), hypothyroidism (1.9%), and pregnancy loss (3.4%).\u003c/p\u003e \u003cp\u003eThe incidence rates of neonatal complications were as follows: respiratory distress syndrome (RDS) 1.9%, neonatal sepsis 1.2%, necrotizing enterocolitis (NEC) 0.2%, and intraventricular hemorrhage (IVH) 0.5%. The need for intensive care was observed in 10.5% of the patients.\u003c/p\u003e \u003cp\u003eThe mean CRP level for all patients included in the study was 10.9\u0026thinsp;\u0026plusmn;\u0026thinsp;16.7. The mean CRP levels in patients with and without obstetric complications were 16\u0026thinsp;\u0026plusmn;\u0026thinsp;23.9 and 9\u0026thinsp;\u0026plusmn;\u0026thinsp;12.7, respectively, indicating a statistically significant difference (p\u0026thinsp;=\u0026thinsp;0.004). The mean procalcitonin level for all patients included in the study was 0.17\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8. The mean procalcitonin levels in patients with and without obstetric complications were 0.55\u0026thinsp;\u0026plusmn;\u0026thinsp;3.52 and 0.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05, respectively, with no statistically significant difference (p\u0026thinsp;=\u0026thinsp;0.14).\u003c/p\u003e \u003cp\u003eThe ROC curve was used to analyze the value of CRP values during pregnancy regardless of trimester to predict the presence of composite obstetric complications and revealed a cutoff value of 6.72 mg/L, with a sensitivity of 67% and specificity of 60% (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e- A). Similarly, the ROC curve was used to analyze the predictive value of PCT values during pregnancy for predicting obstetric complications and revealed a cutoff value of 0.0385 for a sensitivity of 60% and a specificity of 61%. This value was determined as the cutoff value for PCT to predict obstetric complications (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e-B).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe comparisons of demographic and obstetric data between those below and above the threshold values of CRP and PCT are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean age and BMI of patients in the present study were significantly greater in those with CRP levels above the cutoff than in those with low CRP levels (p\u0026thinsp;=\u0026thinsp;0,003 and p\u0026thinsp;=\u0026thinsp;0,003, respectively). However, there was no statistically significant difference in birth weight between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The mean age, BMI, and birth weight did not differ significantly between groups stratified by PCT levels above or below the cutoff (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In contrast, the mean gestational age at delivery was significantly greater in patients with low CRP and low PCT levels than in those with elevated CRP and PCT levels (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of patients with and without elevated CRP and PCT levels\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCRP \u0026le; 6,72\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCRP\u0026thinsp;\u0026gt;\u0026thinsp;6,72\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e Value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePCT \u0026le; 0,0385\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePCT\u0026thinsp;\u0026gt;\u0026thinsp;0,085\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e29,1 \u0026plusmn; 4,9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e30,7 \u0026plusmn; 5,4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0,003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e29,5 \u0026plusmn; 5,1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e29,8 \u0026plusmn; 5,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0,58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI(kg/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e24,4 \u0026plusmn; 3,7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e26,0 \u0026plusmn; 4,4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0,001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e24,9 \u0026plusmn; 4,1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e25,4 \u0026plusmn; 4,1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0,272\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBirth Weight (g)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3169,4 \u0026plusmn; 421,7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3089,4 \u0026plusmn; 604,0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e3175,6 \u0026plusmn; 432,0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e3073,9 \u0026plusmn; 596,4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0,064\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGestational age at the time of delivery (weeks)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e38,4 \u0026plusmn; 1,5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e38 \u0026plusmn; 2,4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0,049\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e38,5 \u0026plusmn; 1,7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e37,9 \u0026plusmn; 2,3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0,004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eA comparison of patients with and without elevated CRP levels in any trimester revealed a significantly greater frequency of composite obstetric complications in the elevated CRP group (32.4% \u0026minus;\u0026thinsp;67.6%) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The frequencies of preeclampsia, gestational hypertension, neonatal complications and the need for intensive care were significantly greater in patients with CRP levels\u0026thinsp;\u0026gt;\u0026thinsp;6,72 (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In addition, the prevalence of preeclampsia and the incidence of GHT were significantly greater in patients with elevated first trimester CRP levels (p\u0026thinsp;\u0026lt;\u0026thinsp;0.003). No statistically significant differences were observed in the frequency of preterm labor, PPROM, IUGR, GDM or pregnancy loss in patients with elevated CRP above the cutoff (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The regression analysis indicated that only CRP elevation was a significant factor, while both age and BMI were not significant predictors of obstetric complications.\u003c/p\u003e \u003cp\u003eThe incidence of composite obstetric complications was significantly greater in patients with elevated PCT (59% vs. 41%) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). No statistically significant difference was observed in the frequency of preeclampsia, gestational hypertension, IUGR, GDM, or pregnancy loss in patients with elevated PCT. However, patients with elevated PCT levels had a greater frequency of preterm labor or PPROM (18.6%), neonatal complications (14.8%), need for intensive care (15.5%), and RDS (3.6%) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of obstetric and neonatal outcomes in patients with and without elevated CRP and PCT\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCRP \u0026le; 6,72\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCRP\u0026thinsp;\u0026gt;\u0026thinsp;6,72\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePCT \u0026le; 0,0385\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePCT\u0026thinsp;\u0026gt;\u0026thinsp;0,085\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComposite Obstetric Complications\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (16,7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75 (38,3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0,001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e43 (19,6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e62 (34,8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0,001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003ePreeclampsia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0,9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (5,9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0,006\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (1,9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7 (4,1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,225\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eGHT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (5,9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0,001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 (1,4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6(3,6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,191\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eGDM\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (4,3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,237\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11 (5,1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9 (5,3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,936\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eIUGR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0,5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (2,7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (0,9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3 (1,8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,658\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003ePPROM/Preterm labor\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (11,2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (15,3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,278\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19(8,7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e33 (18,6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0,003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e1st trimester pregnancy loss\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (1,9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (5,1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5(2,3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9(5,1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,136\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComposite Neonatal Complications\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (7,1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (14,5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0,017\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15 (7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e25(14,8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0,013\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eRDS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(1,4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (2,7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,481\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (0,5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6 (3,6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0,047\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNeonatal Sepsis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(1,6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,668\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2(0,9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3(1,8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0,658\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNEC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(0,5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1(0,5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eThe need for intensive care\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(7,1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28(15,1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0,010\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15(7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e26(15,5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0,008\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis 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\u003cb\u003e-\u003c/b\u003ephase 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.\u003c/p\u003e \u003cp\u003eNotably, 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\u0026ndash;0.9 mg/dL, depending on gestational age, in women who did not give birth [17]. In our study, 6.72 mg/L was found to be the cutoff value for CRP for the incidence of obstetric and neonatal complications.\u003c/p\u003e \u003cp\u003eIn 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\u0026ndash;75% and 45\u0026ndash;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%.\u003c/p\u003e \u003cp\u003eC-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 [18]. 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 [19, 20]. In the present study, no cases of chorioamnionitis were recorded, and no significant associations were found between CRP or procalcitonin 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.\u003c/p\u003e \u003cp\u003ePreeclampsia 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[21, 22]. 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 [23]. 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 [24]. 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 [25, 26]. In other studies, CRP levels were found to be significantly higher in patients with preeclampsia than in those with normal pregnancies [27\u0026ndash;29]. In the present study, the levels of CRP and PCT were significantly greater in the preeclampsia and gestational hypertension groups. The associations between CRP and PCT levels and preeclampsia support the hypothesis that systemic inflammation plays a role in the pathogenesis of preeclampsia. We recommend screening for CRP and procalcitonin, especially CRP in the first trimester, to help predict preeclampsia.\u003c/p\u003e \u003cp\u003eA 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 [30]. In a prospective study by Westergaard et al. including 1049 patients, there was no association between GDM and CRP levels [31]. 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 [32]. In a Chinese study involving 36 GDM patients and 36 control groups, when fasting and 1st 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[33]. 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.\u003c/p\u003e \u003cp\u003eIn 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 [34, 35]. 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 [36]. 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.\u003c/p\u003e \u003cp\u003eEarly 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 [37]. In our study, there was no significant relationship between CRP or PCT and neonatal sepsis because of the small number of neonatal sepsis patients.\u003c/p\u003e \u003cp\u003eThe 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.\u003c/p\u003e \u003cp\u003eThe limitation of this study is that, owing to the prospective design, the number of patients with obstetric complications and neonatal complications in each group was inadequate for statistical significance. The number of patients whose CRP and PCT levels were analyzed in each trimester was low because of problems with patient follow-up.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, this is the first prospective study in which pregnant women were screened for CRP and PCT in different trimesters, and obstetric and neonatal outcomes were analyzed. Elevated CRP and PCT are associated with increased obstetric and neonatal complications. CRP and PCT, which are inexpensive and available, may be used for screening to predict obstetric and neonatal complications during patient follow-up.\u003c/p\u003e \u003cp\u003eWe recommend that the study be repeated with a larger number of patients for routine clinical use.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eBMI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBody mass index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eCRP\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eC-reactive protein\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eIUGR\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntrauterine Growth Restriction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eIVH\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntraventricular hemorrhage\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eGDM\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGestational diabetes mellitus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eGHT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGestational hypertension\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNEC\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNecrotizing enterocolitis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ePCT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProcalcitonin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ePROM\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePremature Membrane Rupture\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ePPROM\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePreterm premature rupture of membranes\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eROC\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eReceiver operating characteristic\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki and\u0026nbsp;approved by the institutional ethical committee of the Gazi University Faculty of Medicine (Approval No:479). All patients who participated in the study were informed of the study, and informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eME, PC and MA designed the study. MA, AGA, CY, and IMH collected the data. ME, PC and MA analyzed the data. MA drafted the work; PC, AE, and ME revised it substantially. All the authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' information (optional)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eListon, R., D. Sawchuck, and D. Young, \u003cem\u003eFetal health surveillance: antepartum and intrapartum consensus guideline.\u003c/em\u003e J Obstet Gynaecol Can, 2007. \u003cstrong\u003e29\u003c/strong\u003e(9 Suppl 4): p. S3-56.\u003c/li\u003e\n \u003cli\u003eYudkin, J.S., et al., \u003cem\u003eC-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue?\u003c/em\u003e Arterioscler Thromb Vasc Biol, 1999. \u003cstrong\u003e19\u003c/strong\u003e(4): p. 972-8.\u003c/li\u003e\n \u003cli\u003eBakar, R.Z., et al., \u003cem\u003eMaternal serum procalcitonin levels in prediction of chorioamnionitis in women with preterm premature rupture of membranes.\u003c/em\u003e Arch Med Sci, 2021. \u003cstrong\u003e17\u003c/strong\u003e(3): p. 694-699.\u003c/li\u003e\n \u003cli\u003eLoukovaara, M.J., et al., \u003cem\u003eSerum highly sensitive C-reactive protein in preterm premature rupture of membranes.\u003c/em\u003e Eur J Obstet Gynecol Reprod Biol, 2003. \u003cstrong\u003e110\u003c/strong\u003e(1): p. 26-8.\u003c/li\u003e\n \u003cli\u003eHvilsom, G.B., et al., \u003cem\u003eC-reactive protein: a serological marker for preterm delivery?\u003c/em\u003e Acta Obstet Gynecol Scand, 2002. \u003cstrong\u003e81\u003c/strong\u003e(5): p. 424-9.\u003c/li\u003e\n \u003cli\u003eWolf, M., et al., \u003cem\u003eObesity and preeclampsia: the potential role of inflammation.\u003c/em\u003e Obstet Gynecol, 2001. \u003cstrong\u003e98\u003c/strong\u003e(5 Pt 1): p. 757-62.\u003c/li\u003e\n \u003cli\u003eDjurovic, S., et al., \u003cem\u003eAbsence of enhanced systemic inflammatory response at 18 weeks of gestation in women with subsequent preeclampsia.\u003c/em\u003e Bjog, 2002. \u003cstrong\u003e109\u003c/strong\u003e(7): p. 759-64.\u003c/li\u003e\n \u003cli\u003ePerrakis, A., et al., \u003cem\u003ePrognostic and diagnostic value of procalcitonin in the posttransplant setting after liver transplantation.\u003c/em\u003e Arch Med Sci, 2016. \u003cstrong\u003e12\u003c/strong\u003e(2): p. 372-9.\u003c/li\u003e\n \u003cli\u003eTorb\u0026eacute;, A. and R. 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Dey, and S.J. Fisher, \u003cem\u003ePreterm labor: one syndrome, many causes.\u003c/em\u003e Science, 2014. \u003cstrong\u003e345\u003c/strong\u003e(6198): p. 760-5.\u003c/li\u003e\n \u003cli\u003eErnest, J.M., et al., \u003cem\u003eC-reactive protein: a limited test for managing patients with preterm labor or preterm rupture of membranes?\u003c/em\u003e Am J Obstet Gynecol, 1987. \u003cstrong\u003e156\u003c/strong\u003e(2): p. 449-54.\u003c/li\u003e\n \u003cli\u003eKurki, T., et al., \u003cem\u003eC-reactive protein in preterm premature rupture of the membranes.\u003c/em\u003e Arch Gynecol Obstet, 1990. \u003cstrong\u003e247\u003c/strong\u003e(1): p. 31-7.\u003c/li\u003e\n \u003cli\u003eRedman, C.W., G.P. Sacks, and I.L. Sargent, \u003cem\u003ePreeclampsia: an excessive maternal inflammatory response to pregnancy.\u003c/em\u003e Am J Obstet Gynecol, 1999. \u003cstrong\u003e180\u003c/strong\u003e(2 Pt 1): p. 499-506.\u003c/li\u003e\n \u003cli\u003eRoberts, J.M., \u003cem\u003eEndothelial dysfunction in preeclampsia.\u003c/em\u003e Semin Reprod Endocrinol, 1998. \u003cstrong\u003e16\u003c/strong\u003e(1): p. 5-15.\u003c/li\u003e\n \u003cli\u003eGencheva, D.G., et al., \u003cem\u003eHigh-sensitivity CRP levels in women with gestational hypertension, preeclampsia and in normotensive pregnant women and its correlations.\u003c/em\u003e Folia Med (Plovdiv), 2021. \u003cstrong\u003e63\u003c/strong\u003e(4): p. 511-518.\u003c/li\u003e\n \u003cli\u003eHamadeh, R., et al., \u003cem\u003eC-Reactive Protein for Prediction or Early Detection of Pre-Eclampsia: A Systematic Review.\u003c/em\u003e Gynecologic and Obstetric Investigation, 2021. \u003cstrong\u003e86\u003c/strong\u003e(1-2): p. 13-26.\u003c/li\u003e\n \u003cli\u003eCao, W., et al., \u003cem\u003eMaternal lipids, BMI and IL-17/IL-35 imbalance in concurrent gestational diabetes mellitus and preeclampsia.\u003c/em\u003e Exp Ther Med, 2018. \u003cstrong\u003e16\u003c/strong\u003e(1): p. 427-435.\u003c/li\u003e\n \u003cli\u003eBarden, A., et al., \u003cem\u003eFactors predisposing to preeclampsia in women with gestational diabetes.\u003c/em\u003e J Hypertens, 2004. \u003cstrong\u003e22\u003c/strong\u003e(12): p. 2371-8.\u003c/li\u003e\n \u003cli\u003eKashanian, M., F. Aghbali, and N. Mahali, \u003cem\u003eEvaluation of the diagnostic value of the first-trimester maternal serum high-sensitivity C-reactive protein level for prediction of preeclampsia.\u003c/em\u003e Journal of Obstetrics and Gynecology Research, 2013. \u003cstrong\u003e39\u003c/strong\u003e(12): p. 1549-1554.\u003c/li\u003e\n \u003cli\u003eKUPFERMINC, M.J., et al., \u003cem\u003eSoluble Tumor Necrosis Factor Receptors and Interleukin-6 Levels in Patients With Severe Preeclampsia.\u003c/em\u003e Obstetrics \u0026amp; Gynecology, 1996. \u003cstrong\u003e88\u003c/strong\u003e(3): p. 420-427.\u003c/li\u003e\n \u003cli\u003eHwang, H.S., et al., \u003cem\u003eMaternal serum highly sensitive C-reactive protein in normal pregnancy and preeclampsia.\u003c/em\u003e International Journal of Gynecology \u0026amp; Obstetrics, 2007. \u003cstrong\u003e98\u003c/strong\u003e(2): p. 105-109.\u003c/li\u003e\n \u003cli\u003eOzgu-Erdinc, A.S., et al., \u003cem\u003ePrediction of gestational diabetes mellitus in the first trimester: comparison of C-reactive protein, fasting plasma glucose, insulin and insulin sensitivity indices.\u003c/em\u003e J Matern Fetal Neonatal Med, 2015. \u003cstrong\u003e28\u003c/strong\u003e(16): p. 1957-62.\u003c/li\u003e\n \u003cli\u003eWestergaard, D., et al., \u003cem\u003eImmune changes in pregnancy: associations with preexisting conditions and obstetrical complications at the 20th gestational week-a prospective cohort study.\u003c/em\u003e BMC Med, 2024. \u003cstrong\u003e22\u003c/strong\u003e(1): p. 583.\u003c/li\u003e\n \u003cli\u003eKumari, R. and H. Singh, \u003cem\u003eThe prevalence of elevated high-sensitivity C-reactive protein in normal pregnancy and gestational diabetes mellitus.\u003c/em\u003e J Family Med Prim Care, 2017. \u003cstrong\u003e6\u003c/strong\u003e(2): p. 259-264.\u003c/li\u003e\n \u003cli\u003eZhu, C., et al., \u003cem\u003eAssociation of oxidative stress biomarkers with gestational diabetes mellitus in pregnant women: a case‒control study.\u003c/em\u003e PLoS One, 2015. \u003cstrong\u003e10\u003c/strong\u003e(4): p. e0126490.\u003c/li\u003e\n \u003cli\u003eJauniaux, E., et al., \u003cem\u003eEvaluation of the role of maternal serum high-sensitivity C-reactive protein in predicting early pregnancy failure.\u003c/em\u003e Reproductive BioMedicine Online, 2015. \u003cstrong\u003e30\u003c/strong\u003e(3): p. 268-274.\u003c/li\u003e\n \u003cli\u003eBoggess, K.A., et al., \u003cem\u003eMaternal serum C-reactive protein concentration early in pregnancy and subsequent pregnancy loss.\u003c/em\u003e Am J Perinatol, 2005. \u003cstrong\u003e22\u003c/strong\u003e(6): p. 299-304.\u003c/li\u003e\n \u003cli\u003eLotfy, A.M., W.S. Taha, and M.A. Abdelmoaty, \u003cem\u003eEvaluation of serum level of C-reactive protein (CRP) and its correlation with fetal ultrasound parameters in the prediction of threatened miscarriage in the first trimester.\u003c/em\u003e Qatar Med J, 2024. \u003cstrong\u003e2024\u003c/strong\u003e(1): p. 9.\u003c/li\u003e\n \u003cli\u003eManandhar, J., et al., \u003cem\u003e***ECD*** maternal C-reactive protein as a predictor of neonatal sepsis.\u003c/em\u003e Psychology, Health \u0026amp; Medicine, 2024. \u003cstrong\u003e29\u003c/strong\u003e(6): p. 1134-1141.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"C-reactive protein, Procalcitonin, Obstetric complications, Neonatal outcomes, Pregnancy","lastPublishedDoi":"10.21203/rs.3.rs-6515536/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6515536/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eC-reactive protein (CRP) and procalcitonin (PCT) levels may be elevated under inflammatory conditions. The aim of this study was to determine the cutoff values for CRP and PCT levels during pregnancy and to evaluate the associations of any elevation with obstetric and neonatal outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThis prospective study was conducted from June 2023 to December 2024. The study included 411 singleton pregnant women aged 18–44 years with no apparent clinical infection. Venous blood samples were collected during the visit for routine antenatal care during all three trimesters. Categorical variables were compared between groups via the chi-square test, and Student's t-test was used to compare normally distributed continuous variables. The area under the ROC curve was used to detect sensitivity and specificity and to set a cutoff. Regression analysis was performed to evaluate the effects of age and BMI on obstetric complications.\u003cem\u003e \u003c/em\u003eP values \u0026lt; 0.05 were considered statistically significant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe mean CRP and PCT levels in the study group were 10.9 ±16.7 and 0.17 ±1.8, respectively. ROC curves were used to analyze the ability of CRP and PCT values during pregnancy to predict obstetric complications. A cutoff value of 6.72 mg/L (sensitivity: 67%; specificity: 60%) and 0.0385 (sensitivity: 60%; specificity: 61%) was revealed. The incidence of composite obstetric complications was significantly greater in patients with elevated CRP levels (32.4% vs. 67.6%) (p\u0026lt;0.001). The incidence of preeclampsia, GHT, neonatal complications and the need for intensive care were significantly greater in patients with CRP levels \u0026gt; 6,72. The incidence of composite obstetric complications was significantly greater in patients with elevated PCT levels (59% vs. 41%) (p\u0026lt;0.001). Patients with elevated PCT levels had a greater frequency of preterm labor or PPROM, neonatal complications, need for intensive care, and RDS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eElevated CRP and PCT are associated with increased rates of obstetric and neonatal complications. CRP and PCT, which are inexpensive and available, may be used for screening to predict obstetric and neonatal complications during patient follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the institutional ethical committee of the Gazi University Faculty of Medicine (Approval No:05.06.2023/479).\u003c/p\u003e","manuscriptTitle":"Associations of CRP and PCT levels with obstetric and neonatal outcomes: a prospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-13 12:17:12","doi":"10.21203/rs.3.rs-6515536/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-03T07:58:11+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-30T16:28:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"331744425976559761371530773808538933270","date":"2025-05-27T16:19:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"3401709951952064282003004026980066991","date":"2025-05-22T05:52:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-21T15:46:37+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-11T12:09:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"276603464489091851596662297235738077178","date":"2025-05-11T11:29:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"275479301841699178540188033541898155264","date":"2025-05-10T13:25:40+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-07T17:55:45+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-04-28T10:10:26+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-26T00:55:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-26T00:53:45+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2025-04-23T21:15:15+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"860fa71f-fba1-425b-8e65-08ce73ec401c","owner":[],"postedDate":"May 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-25T16:35:58+00:00","versionOfRecord":{"articleIdentity":"rs-6515536","link":"https://doi.org/10.1186/s12884-025-07970-w","journal":{"identity":"bmc-pregnancy-and-childbirth","isVorOnly":false,"title":"BMC Pregnancy and Childbirth"},"publishedOn":"2025-08-21 16:29:30","publishedOnDateReadable":"August 21st, 2025"},"versionCreatedAt":"2025-05-13 12:17:12","video":"","vorDoi":"10.1186/s12884-025-07970-w","vorDoiUrl":"https://doi.org/10.1186/s12884-025-07970-w","workflowStages":[]},"version":"v1","identity":"rs-6515536","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6515536","identity":"rs-6515536","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}