Chondroitin Sulfate Proteoglycan 4 (CSPG4) as a Potential Biomarker for Fetal Growth Restriction: Insights from an Umbilical Cord Blood Analysis.

BACKGROUND: This study aimed to evaluate the umbilical cord blood chondroitin sulfate proteoglycan 4 (CSPG4) concentrations in pregnancies complicated with fetal growth restriction (FGR) and aimed to investigate the rela-tionship between the CSPG4 levels in these pregnancies and adverse neonatal outcomes. METHODS: This prospective case-control study was conducted between August 2023 and January 2024. The study included 80 singleton pregnancies at 35 to 39 weeks of gestation. Among these, 40 were diagnosed with FGR and 40 served as the control group. After the delivery, samples of the cord blood were collected prior to the placental delivery. RESULTS: The CSPG4 levels were significantly higher in the study group (FGR), 1,153 (1,059 - 1,261) pg/mL, than in the control group, 1,107 (873 - 1,197) pg/mL (p = 0.024). When all patients were evaluated, the CSPG4 levels showed a positive correlation with the systolic/diastolic (S/D) ratio of the umbilical arteries (r = 0.276, p = 0.013). A statistically significant negative correlation was observed between the levels of CSPG4 in the umbilical cord blood and the Apgar scores at the 1st (r = -0.256, p = 0.022) and 5th (r = -0.250, p = 0.026) minutes. The discriminatory power of the umbilical cord CSPG4 level in the determination of composite adverse neonatal outcomes was evaluated by ROC analysis and a cutoff point of > 1,091.25 pg/mL, showing a sensitivity of 93.3%, a specificity of 46.2%, and an AUC of 0.661 (95% CI: 0.547 - 0.763, p = 0.019). CONCLUSIONS: Elevated levels of CSPG4 have been observed in the umbilical cord blood in pregnancies complicated by FGR; higher levels are associated with adverse neonatal outcomes.

Predictive value of inflammatory markers (NLR, PLR, MLR, SII, SIRI, PIV, IG, and MII) for latency period in Preterm premature rupture of membranes (PPROM) pregnancies.

BACKGROUND: Our study aimed to investigate the value of inflammatory indices in predicting the latency period until birth in patients with preterm premature rupture of membranes (PPROM). METHODS: This retrospective study was conducted on PPROM cases between 24 and 34 weeks of gestation at Ankara Etlik City Hospital Perinatology Department from October 2023 to April 2024. A total of 146 participants were divided into two groups: Group 1 included 73 patients who gave birth within 72 hours (h) of PPROM diagnosis, and Group 2 included 73 patients who gave birth after 72 h. RESULTS: This study evaluated the prognostic significance of various inflammatory markers neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), systemic immune inflammation index (SII), systemic inflammatory response index (SIRI), pan-immune inflammation value (PIV), immature granulocytes (IG), multi-inflammatory index (MII)-1, MII-2, and MII-3 in predicting the latency period in patients with PPROM. Only MII-1, MII-2, and MII-3 reliably predicted labor within 72 h. The cut-off value for MII-1 was > 48.3, with a sensitivity of 57.7% and specificity of 57.3% (AUC: 0.598, 95% CI: 0.503-0.692, p = 0.042). For MII-2, the cut-off was > 1037.6, with a sensitivity of 57.7% and specificity of 57.3% (AUC: 0.611, 95% CI: 0.516-0.705, p = 0.021). MII-3 had a cut-off of > 10919.9, with a sensitivity of 53.5% and specificity of 52% (AUC: 0.595, 95% CI: 0.501-0.690, p = 0.046). CONCLUSION: Our findings show that, among NLR, PLR, MLR, SII, SIRI, PIV, IG, MII-1, MII-2, and MII-3, only MII-1, MII-2, and MII-3 levels are statistically significant in predicting birth timing.

Delta neutrophil index (DNI) as a potential biomarker for fetal growth restriction: insights from maternal hematological changes and neonatal outcomes.

BACKGROUND: This study investigates the role of Delta Neutrophil Index (DNI), an inflammation marker, in late-onset fetal growth restriction (LO-FGR) and its prediction of composite adverse neonatal outcomes. METHODS: A retrospective study was conducted on 684 pregnant women (456 with normal fetal development and 228 with LO-FGR) who delivered at Health Sciences University Etlik Zubeyde Hanim Women's Health Training and Research Hospital between January 1, 2015, and June 30, 2018. Composite adverse neonatal outcomes were defined as at least one of the following: 5th minute APGAR score < 7, respiratory distress syndrome (RDS), or neonatal intensive care unit (NICU) admission. RESULTS: The FGR group had significantly higher levels of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), and DNI compared to controls (p < 0.05, for all). For FGR diagnosis, the DNI demonstrated the highest area under the curve (AUC = 0.677, 95% CI: 0.642-0.711) with a cut-off value of > -2.9, yielding a sensitivity of 78.41%, a specificity of 52.97%, a positive likelihood ratio (+ LR) of 1.68, and a negative likelihood ratio (-LR) of 0.37 (p < 0.001). For predicting composite adverse neonatal outcomes in the FGR group, DNI again demonstrated superior performance with an AUC of 0.635 (95% CI: 0.598-0.670), a cut-off value of > -2.2, a sensitivity of 69.90%, a specificity of 55.36%, a + LR of 1.56, and a -LR of 0.51 (p < 0.001). NLR, PLR, and MLR had AUCs below 0.55, indicating poor discriminative ability, with none reaching statistical significance. CONCLUSION: This study highlights the potential role of DNI as a promising biomarker for detecting inflammatory processes associated with LO-FGR and its complications.

Evaluation of controlling nutritional status (CONUT) score in the prognosis of hyperemesis gravidarum.

OBJECTIVE: To investigate the predictive value of the Controlling Nutritional Status (CONUT) score on hyperemesis gravidarum (HG) severity, hospitalization, and length of stay. MATERIALS AND METHODS: This retrospective cross-sectional study, conducted between December 2022 and June 2023, involved two groups. Group 1 comprised 52 pregnant women diagnosed with HG in the first trimester, receiving hospitalization and treatment. Group 2 included 105 pregnant women diagnosed with HG in the first trimester, managed and treated as outpatients. The CONUT score was calculated with the formula: Serum albumin score + total lymphocyte score + total cholesterol score. This score is calculated with a number of points between 0 and 12. The interpretation of the score involves four categories: normal (0-1), light (2-4), moderate (5-8), and severe (9-12). RESULTS: The CONUT score differed significantly between the hospitalized (4, IQR: 2.25-5) and outpatient groups (2, IQR: 2-3) (p < 0.001). A CONUT score >3 was associated with the need for hospitalization, demonstrating a sensitivity of 60%, a specificity of 84% (p < 0.001). The CONUT score was the parameter with the highest odds ratio (OR) value among the parameters related to the need for hospitalization, and each unit increase in the CONUT score increased the need for hospitalization by 1.683 times [OR = 1.683 (95% CI: 1.042-2.718), p = 0.033]. A positive correlation was found between the CONUT score and the duration of hospital stay (r = 0.316, p = 0.023). CONCLUSIONS: This study suggests CONUT score as a valuable tool for predicting HG severity, hospitalization need, and duration of hospital stay.

Amniotic-umbilical-to-cerebral ratio, a Doppler index for estimating adverse perinatal outcomes in fetal growth restriction.

OBJECTIVE: To evaluate amniotic fluid volume with Doppler parameters and its association with composite adverse perinatal outcomes (CAPOs) in fetal growth restriction (FGR). MATERIALS AND METHODS: This study was conducted prospectively in a tertiary referral center between 2023 and 2024 on pregnant women diagnosed with early- and late-onset FGR. Fetal ultrasonographic measurements, including deepest vertical pocket (DVP) for amniotic fluid, and Doppler parameters including uterine artery (UtA) systolic/diastolic (S/D) and pulsatility index (PI), middle cerebral artery (MCA) S/D and PI, and umbilical artery (UA) S/D and PI, were conducted following fetal biometry. The cerebroplacental ratio (CPR), cerebral ratio, cerebro-placental-uterine ratio (CPUR), and amniotic-umbilical-to-cerebral ratio (AUCR) were all calculated. Pregnant women diagnosed with FGR were planned to give birth after 37 weeks' gestation, unless a pregnancy complication requiring earlier delivery occurred. We assessed perinatal outcomes subsequent to delivery, with CAPOs defined as the presence of at least one adverse outcome: 5th minute APGAR score <7, respiratory distress syndrome (RDS), umbilical cord blood pH <7.2, and neonatal intensive care unit (NICU) admission. RESULTS: The study included 132 participants, divided into early- (n = 32) and late-onset FGR (n = 100) groups. AUCR was significantly lower in fetuses with late-onset FGR who experienced CAPOs. Multivariate analysis showed gestational age at birth and birth weight were significant predictors of CAPOs in early-onset FGR, while gestational age, birth weight, and AUCR were significant predictors in late-onset FGR. CPR, UCR, and CPUR did not show significance in predicting CAPOs in both early- and late-onset FGR on multivariate analysis. CONCLUSIONS: AUCR is a potential reliable marker for predicting adverse perinatal outcomes in late-onset FGR.

New Marker in the Umbilical Cord Blood of Fetuses with Fetal Growth Restriction: Serum Sortilin-1 Level.

Objective: To determine the role of sortilin in the pathogenesis of fetal growth restriction (FGR) by examining serum sortilin levels in fetal cord blood. Methods: This prospective case-control study was conducted at Ankara Etlik City Hospital between July 2023 and January 2024. Group 1 included 44 pregnant women with late FGR; Group 2 included 44 healthy pregnant women as controls. Results: Umbilical cord blood sortilin levels were significantly higher in the FGR group [2.96 (2.43-4.01)] compared to the control group [2.12 (1.74-3.18)] (p = 0.001). Sortilin levels negatively correlated with APGAR scores at 1 min (r=-0.281, p = 0.008) and 5 min (r=-0.292, p = 0.006). A sortilin threshold of 2.58 ng/ml predicted composite adverse neonatal outcomes with 66.7% sensitivity, 53.1% specificity, and an AUC of 0.652 (95% CI: 0.529-0.775, p = 0.031). Conclusion: This study showed that sortilin levels, which are indicators of oxidation, were higher in the cord blood of newborns with late FGR.

Effect of tumor type on response to adjuvant platinum-based chemotherapy and prognosis in patients with stage II-IV epithelial ovarian carcinoma.

OBJECTIVES: To evaluate the effect of histological subtype on oncological outcome and adjuvant platinum-based chemotherapy response in patients with epithelial ovarian cancer (EOC). MATERIAL AND METHODS: The study group was created with stage II-IV EOC patients. Progression-free survival (PFS) and disease-specific survival (DSS) estimates were determined by using the Kaplan-Meier method. The log-rank test and cox proportional hazards model were performed. RESULTS: A total 396 patients were included the study. Tumor type was serous in 332 (83.8%). Two hundred and thirty-one patients (58.3%) had maximal cytoreduction. Three hundred and twenty-seven (82.6%) patients received complete clinical response. Refractory disease was present in 69 (17.4%) patients. In patients with complete clinical response, 183 (56%) patients recurred. Five-year PFS was 32% in serous group and 31% in non-serous group (p = 0.755). Five-year DSS was 78% in serous group and 87% in non-serous group (p = 0.084). On multivariate analysis, recurrence rates 1.959 times (95% CI: 1.224-3.085; p = 0.004), death rates 2.624 times (95% CI: 1.328-5.185; p = 0.005) higher in patients with optimal cytoreduction than patients with maximal cytoreduction, respectively. CONCLUSIONS: Although the rate of maximal cytoreduction was higher in patients with non-serous tumor type, the rate of refractory disease was higher after adjuvant chemotherapy. However, the recurrence rate was higher in serous tumor type. Survival rates were similar in serous and non-serous tumor types. Maximal cytoreduction was an independent predictor factor for survival. Maximal cytoreduction should be the main target in EOC.

The Efficacy of C-Reactive Protein (CRP) to Albumin Ratio (CAR) and Fibrinogen to CRP Ratio (FCR) in Predicting the Latent Period of Preterm Labor.

OBJECTIVE: To investigate the role of inflammatory markers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR), c-reactive protein (CRP) to albumin ratio (CAR), fibrinogen to albumin ratio (FAR), and fibrinogen to CRP ratio (FCR) in predicting the latency period (≤72 vs. >72 hours) before preterm birth. MATERIALS AND METHODS: In a retrospective study, we assessed 135 patients meeting the specified criteria with signs of preterm labor (<34 weeks). The patients were categorized into two groups: 71 patients giving birth within 72 h (latency ≤ 72 h) and 64 patients giving birth after 72 h (latency > 72 h). We examined the demographic and medical characteristics and perinatal outcomes of all participants. Categorical variables between groups were compared using the Chi-square test. The Student's t-test was utilized for normally distributed continuous variables, and the Mann-Whitney U test was applied for non-normally distributed data. Receiver operating characteristic (ROC) curve analysis was conducted to identify the optimal cut-off levels for inflammatory markers in predicting the latency period before birth. RESULTS: Among the parameters examined, significant differences were observed between the groups only in terms of CAR and FCR. While CAR showed a significantly higher value in the group with latency period ≤72 h (0.537 ± 1.239 vs. 0.247 ± 0.325, p = 0.022), FCR showed a significantly lower value in the group with latency period ≤72 h (63.58 (2.99-1165) vs. 88.93 (9.35-1165), p = 0.013). The identified cut-off value for CAR was 0.190, providing a sensitivity of 57.7% and a specificity of 56.3% (p = 0.022). The cut-off value for FCR was 71.67, with a sensitivity of 42.3% and a specificity of 42.2% (p = 0.013). CONCLUSIONS: The CAR and the FCR, serving as predictive markers for preterm labor, may offer a simple, cost-effective, and easily accessible approach, particularly in resource-limited settings.

Evaluating the diagnostic potential of gelsolin in gestational diabetes mellitus: A case-control study.

OBJECTIVES: To investigate the association between gestational diabetes mellitus (GDM) and blood levels of gelsolin (an inflammation-related protein thought to be reduced in type 2 diabetes mellitus) and to determine its role in potential diagnosis and neonatal outcomes. METHODS: This prospective case-control study was conducted at Ankara Etlik City Hospital between November 2023 and February 2024 with 40 pregnant women with GDM and 40 normoglycemic women. Pregnant women aged 18-40 years who were in their 24th to 28th week of pregnancy and had no known chronic disease were included in the present study and it was investigated as to whether there was a significant difference between the two groups in terms of gelsolin levels and neonatal outcome. RESULTS: Gelsolin level was statistically significantly lower in the GDM group than in the control group (P = 0.004). In patients with fasting blood glucose <96 mg/dL, maternal serum gelsolin levels were associated with GDM, with a cut-off of 15.38 or less, showing a sensitivity of 73%, a specificity of 67%, and an area under the curve (AUC) of 0.703 (95% confidence interval [CI] 0.576-0.810, P = 0.002). There was no difference between groups in terms of adverse obstetric outcomes, but gelsolin levels were associated with composite neonatal adverse outcome (macrosomia, Apgar score at 5 min less than 7, preterm birth, need for neonatal intensive care), with a cut-off value of 16.66 or less showing a sensitivity of 84.6%, specificity of 40.7% and AUC of 0.644 (95% CI 0.529-0.748, P = 0.031). CONCLUSION: Gelsolin could potentially serve as a promising biomarker for the diagnosis of GDM.

Does Second Trimester Maternal Serum Zonulin Level Predict Gestational Diabetes Mellitus?

Zonulin, a protein that regulates intestinal permeability, has attracted attention as a potential biomarker for GDM. Therefore, this study aims to investigate whether there are differences in zonulin levels between the GDM group and control groups, especially between those receiving different treatments (diet and insulin). Based on this idea, we included 90 patients with a gestational age between 24 and 28 weeks in our study. While GDM was not detected in 33 of these patients, as a result of OGTT, 57 patients were diagnosed with GDM and these patients were followed throughout their pregnancy. Gestational diabetes was diagnosed by an OGTT performed between 24 and 28 weeks of gestation according to American Diabetes Association (ADA) standards. During follow-up, GDM patients were divided into two groups according to whether they required insulin treatment. Plasma zonulin levels were determined using enzyme-linked immunosorbent assay (ELISA) techniques. The GDM group had significantly higher plasma zonulin levels than the control group (p < 0.005). According to our research, zonulin may be a non-invasive biomarker involved in the etiology of GDM. Large-scale research on this topic is still needed.

Pregnancy outcomes and fertility after ligation of uterine artery only and hypogastric artery only in postpartum hemorrhage.

Objective: To determine and compare pregnancy outcomes after bilateral uterine artery ligation (BUAL) or bilateral hypogastric artery ligation (BHAL) for postpartum hemorrhage (PPH). Material and Methods: This retrospective cross-sectional study was conducted from January 2010 to June 2018 at a tertiary referral hospital. Patients who had undergone arterial ligation for PPH were included in the study. Patients who had undergone BUAL and BHAL were compared with a control group in terms of fertility and pregnancy outcomes. Results: A total of 156 patients were included, of whom 47 underwent BUAl, 59 underwent BHAL and 50 were in the control group. There was no significant difference between the groups in subsequent pregnancies in terms of the incidence of miscarriage, fetal growth restriction, preeclampsia, primary cesarean deliveries, and infertility (p>0.05). There was a significant difference between all groups in gestational age at birth and birthweight. Preterm birth was observed in 32.2% of patients in the BHAL group, and this rate was significantly higher than in the BUAL (12.8%) and control (6%) groups (p=0.001). Conclusion: PPH is a life-threatening obstetric problem. The effects of interventions performed to reduce pelvic blood flow in patients may lead to persistent problems, such as preterm birth and low birth weight in the next pregnancy. However, these interventions do not appear to affect the risk of miscarriage. In subsequent pregnancies of patients who received BHAL, special attention should be paid to preterm birth.

Evaluation of prognostic nutritional status and lipid profile in gestational diabetes.

OBJECTIVES: This study aimed to investigate the relationship between controlling nutritional status index (CONUT) and prognostic nutrition index (PNI) scores that are used to evaluate nutritional status and GDM. Also, lipid abnormalities and albumin levels in pregnant women with normal glucose tolerance and GDM were researched. MATERIAL AND METHODS: This study was conducted as a retrospective study at Ankara Etlik City Hospital, Turkey. The study included 67 pregnant women with singleton pregnancies (32 pregnant diagnosed with GDM and 35 pregnant known to be normoglycemic). RESULTS: There were no statistical differences between the groups in terms of maternal age, gravidity, parity, history of miscarriage and weight gain during pregnancy. Body mass index (BMI) was higher in the GDM group (p = 0.001). There was no difference in the CONUT score between the groups (p = 0.254). The PNI score was lower in the GDM group (p = 0.003). Of the laboratory data, only fasting blood glucose, triglycerides (TG) and total cholesterol (TC) were statistically significantly higher, and albumin was lower in the GDM group (p = 0.026, p = 0.007, p = 0.003 and p = 0.003, respectively). CONCLUSIONS: PNI has the potential to be a useful predictor of GDM, whereas CONUT does not. Low albumin levels and increased TG, and TC in the first trimester seem to be significant in the development of GDM.

The role of first trimester serum inflammatory indexes (NLR, PLR, MLR, SII, SIRI, and PIV) and the ß-hCG to PAPP-A ratio in predicting preeclampsia.

OBJECTIVE: The aim of this study was to investigate the predictive value of inflammation parameters and indices measured in the first trimester for the detection of preeclampsia. MATERIALS AND METHODS: In this retrospective analysis, we examined the medical records of 276 eligible pregnancies at a tertiary referral center from 2022 to 2023. The cases were categorized into the Control group (n = 171), the Mild Preeclampsia group (n = 63), and the Severe Preeclampsia group (n = 42). We examined the demographic characteristics and perinatal outcomes of all participants. Additionally, we analyzed laboratory parameters, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune inflammation index (SII) (neutrophil*platelet/lymphocyte), systemic inflammation response index (SIRI) (neutrophil*monocyte/lymphocyte), pan-immune inflammation value (PIV) (neutrophil*platelet*monocyte/lymphocyte), and the ß-hCG to PAPP-A ratio in the first trimester. Receiver operating characteristic curve (ROC) analysis was conducted to identify the optimal cut-off levels for inflammatory markers in predicting preeclampsia. RESULTS: SIRI and PIV exhibited statistical significance in differentiating between the preeclampsia and control groups for predicting preeclampsia. The determined cut-off value for SIRI was 1.5, providing a sensitivity of 56.2% and a specificity of 55.6% (p = 0.012). Likewise, the cut-off value for PIV was 394.4, with a sensitivity of 55.2% and a specificity of 55% (p = 0.013). NLR, PLR, MLR, SII, and ß-hCG to PAPP-A ratio could not predict preeclampsia. CONCLUSIONS: This study suggests that SIRI and PIV hold promise as potential tools for predicting the risk of preeclampsia during the first trimester.