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.

Can maternal inflammatory and nutritional status, evaluated by the hemoglobin, albumin, lymphocyte, and platelet (HALP) score and the prognostic nutritional index (PNI) in the first trimester, predict late-onset fetal growth restriction?

OBJECTIVE: The aim of this study was to evaluate the potential of immunonutritional markers, specifically the hemoglobin, albumin, lymphocyte, and platelet (HALP) score and the prognostic nutritional index (PNI), in predicting late-onset fetal growth restriction (LO-FGR) during the first trimester. MATERIALS AND METHODS: This retrospective study was conducted at a tertiary care center between October 2022 and August 2023. The study included a total of 213 singleton pregnancies, with 99 women in the LO-FGR group and 114 in the healthy control group, matched by maternal age and gestational age at delivery. All blood samples were collected between 11 and 14 weeks of gestation (during the first-trimester screening test). We analyzed first-trimester laboratory parameters, specifically focusing on hemoglobin levels, white blood cells (WBCs), lymphocytes, platelets, and albumin levels. Afterwards, we calculated the HALP score and PNI, and then compared the values of both groups. RESULTS: Both HALP score (3.58 ± 1.31 vs. 4.19 ± 1.8, p = 0.012) and PNI (36.75 ± 2.9 vs. 39.37 ± 3.96, p < 0.001) were significantly lower in the FGR group than in the control group. The HALP score cut-off value of < 3.43 in predicting FGR had a sensitivity of 62.3% and specificity of 54.5% (AUC = 0.600, 95% CI: 0.528-0.672, p = 0.012). The PNI cut-off value of < 37.9 in predicting FGR had a sensitivity of 65.8% and specificity of 62.9% (AUC = 0.707, 95% CI: 0.632-0.778, p < 0.001). While the HALP score was not a significant predictor of composite adverse neonatal outcomes in the FGR group, PNI showed a cut-off value of < 37.7 with a sensitivity of 60.9% and specificity of 59.7% (AUC = 0.657, 95% CI: 0.581-0.733, p < 0.001). CONCLUSION: The HALP score and PNI are valuable prognostic tools for predicting the risk of FGR in the first trimester. Low PNI values are also associated with composite adverse neonatal outcomes in pregnancies complicated by FGR.

Arterial and Venous Doppler in Evaluation of the "At-risk" Fetus.

Our practice utilizes Doppler ultrasound as one of the most objective and effective methods to assess at-risk pregnancies. This review will discuss the application of arterial and venous Doppler techniques in assessing and managing various diseases and conditions for high-risk fetuses.

Liver damage parameters and peripheral blood parameters for prediction and diagnosis of intrahepatic cholestasis in pregnancy.

OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) manifests in late pregnancy. Elevated serum bile acid is a diagnostic criterion: however, its measurement is troublesome. Prediction of ICP by blood markers is not established. Serum bile acid level is associated with liver damage and inflammation. We hypothesized that the following markers could predict the occurrence of ICP and have diagnostic value for it: Liver damage-indicating scores (albumin-bilirubin [ALBI], Model for End-Stage Liver Disease [MELD], aspartate aminotransferase-to-platelet ratio [APRI]) and inflammatory markers (platelet-to-lymphocyte ratio [PLR] and neutrophil-to-lymphocyte ratio [NLR]). METHODS: Eighty ICP patients and 200 controls were studied. The values of MELD, APRI, ALBI, PLR, and NLR were measured in the 1st trimester and at the time of diagnosis. RESULTS: Patients with ICP had significantly higher ALBI, MELD, and APRI scores both in the first trimester and at diagnosis. Multivariate logistic regression (MLR) showed that age, ALBI, MELD, and APRI scores were statistically significant (p < 0.05). By receiver operating characteristic (ROC) analysis, the sensitivity of MELD, ALBI, APRI, and NLR in the first trimester was 62%, 73%, 58%, and 29%, respectively, and MELD, ALBI, APRI, and PLR at diagnosis was 28%, 38%, 57%, and 8%, respectively, with a fixed false-positive rate of 10%. CONCLUSION: This study has demonstrated the usability of the MELD, ALBI, and APRI scores in predicting and diagnosing ICP. They are easy to obtain and might be used in routine practice.

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.

Evaluation of Anterior and Middle Brain Structures With Cerebrovascular Flow in Fetuses With Fetal Growth Restriction: A Prospective Study.

OBJECTIVE: To investigate the adaptation of the anterior cerebral artery (ACA) in fetuses with fetal growth restriction (FGR) and assess if forebrain and midbrain structures are affected by vascular adaptations. METHODS: A prospective case-control study involving normally developed fetuses and those with late-onset FGR (estimated fetal weight < 3rd percentile and/or abdominal circumference < 3rd percentile). Doppler indices of the middle cerebral artery (MCA), ACA and umbilical artery (UA) were determined between 32 + 0 and 37 + 0 weeks. Neurosonography assessed the depth of the insula, the sylvian fissure, and the antero-posterior diameter of the frontal lobes (FAPD). RESULTS: The cerebral-placental ratio (CPR) and cerebro-placental-uterine ratio (CPUR) were lower in FGR cases. ACA PI percentile values were significantly lower in the FGR group (p = 0.020). Sylvian fissure depth was significantly lower in FGR fetuses. CONCLUSION: The ACA may be the first cranial vascular structure affected in fetuses with FGR. This may be related to the impact on postnatal cognitive functions in FGR patients. TRIAL REGISTRATION: NCT06215690.

A New Antioxidant Marker in Cord Blood of Fetuses with Late Fetal Growth Restriction: Humanin.

Purpose: This study investigated the Humanin levels in the umbilical cord blood of fetuses with late fetal growth restriction (FGR) and -evaluated their association with perinatal outcomes. Materials and Methods: A total of 95 single pregnancies between 32-41 wk (45 with late FGR and 50 controls) were included. Doppler parameters, birth weight and the need for neonatal intensive care unit admission (NICU) were assessed. Correlations between Humanin levels and these parameters were analyzed. Results: Higher Humanin levels were found in fetuses with late FGR compared to the control group (p < 0.05). No significant correlation was observed between Humanin levels and Doppler parameters. Elevated Humanin levels were associated with an increased need for NICU (p < 0.05). Conclusions: The statistically higher levels of Humanin in fetuses with late FGR may suggest the potential of Humanin as an indicator of late FGR. Further research is needed to explore the clinical utility of Humanin.

The association between gestational diabetes mellitus and DNA damage in umbilical cord leukocytes and placental samples.

Objective(s): To evaluate the relation between gestational diabetes mellitus (GDM) and maternal and/or fetal DNA integrity. Method: 59 pregnant women were classified into two groups on the basis of 75 g oral glucose tolerance test (OGTT) and glycemic profile (GP): Control group (OGTT and GP normal, n = 29) and GDM group (abnormal 75 g OGTT, n = 30). The umbilical cord blood and placental samples obtained from the maternal side were collected at the time of delivery. Alkaline comet assay was performed for the determination of DNA damage. The trial was approved with the protocol number 72867572.050.01.04-299082. Result(s): Body mass index (BMI), weight gain during pregnancy, glycemic means and fetal weight were increased in GDM group compared control group (p = .01, .0001, .04, and .01, respectively). In the GDM group, the number of large-for-gestational-age (LGA) infants was significantly higher compared to the nondiabetic group (p = .04). Tail DNA percentages in placental samples were higher in the GDM group compared to controls (p = .01); however, DNA integrity in umbilical cord leukocytes was similar between the groups (p = 0.1). In contrast to umbilical cord DNA damage, placental DNA damage showed positive correlation with maternal glycemia in the whole group and within each group. The positive association of placental DNA damage and GDM remained after adjusting for age, BMI, smoking, glycemia, gestational age at delivery, fetal weight at delivery, and delivery type (p = .01). Conclusion(s): Placental DNA damage is associated with GDM and placental cells seem to be more vulnerable to DNA damage compared to fetal blood cells.

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.

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.

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.

Factors Affecting Obstetric Outcomes in Patients Who Underwent Cold-Knife and Loop Electrosurgical Excision Procedure Conization Due to CIN 2 or CIN 3.

Objective: To determine factors affecting obstetric outcomes in pregnancies after conization by loop electrosurgical excision procedure (LEEP) or cold-knife conization (CKC) due to cervical intraepithelial neoplasia (CIN). Material and Methods: The maternal and clinical characteristics and obstetric outcomes of CKC, LEEP and control groups were evaluated and compared. Risk factors for adverse pregnancy outcomes were evaluated using multiple logistic regression analyses. Results: The incidence of preterm delivery, PPROM, low APGAR scores, fetal mortality, and late-period spontaneous abortus was highest in patients who underwent CKC (p<0.05). Cone depth of CKC was longer than LEEP (p=0.025). Cervical length (CL) at pregnancy was CKC