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.

Evaluation of systemic immune-inflammation index for predicting late-onset fetal growth restriction.

INTRODUCTION: To determine a cut-off value for systemic immune-inflammation index (SII) (neutrophil × platelet/lymphocyte) in the prediction of fetal growth restriction (FGR). MATERIALS AND METHODS: This case-control study was conducted retrospectively at the Obstetrics-Gynecology and Perinatology Clinics of Etlik Zubeyde Hanim Women's Health Education and Training Hospital. Singleton pregnant women with late-onset FGR who were followed up in outpatient clinics or hospitalized and whose pregnancy resulted at our hospital were included in the study group (group I). Healthy early and full-term singleton pregnant women with spontaneous labor who were followed up in the same hospital and whose pregnancy resulted at the same hospital were included in the control group (group II). Receiver-operating characteristic curves were used to assess the performance of SII value in predicting FGR. RESULTS: We recruited 79 cases (pregnant with late-onset fetal growth restriction) and 79 controls (healthy pregnant), matched for age, body mass index, and parity. ΔSII was statistically significantly higher in the pregnant with late-onset FGR compared with healthy pregnant (123 vs - 65; p = 0.039). The values in ROC curves with the best balance of sensitivity/specificity were > 152 109/L (49% sensitivity, 70% specificity) and > 586 109/L (27% sensitivity, 90% specificity) for late-onset FGR. DISCUSSION: Higher ΔSII levels in maternal blood indicate an inflammatory process causing FGR. The cut-off value for ΔSII (> 586 109/L) at 90% specificity can be used as a screening test. In the presence of ΔSII levels > 586 109/L (27% sensitivity and 90% specificity), the physicians should be more cautious about risk for FGR. Therefore, pregnant women at risk for FGR should be checked more frequently and monitored closely. However, further studies are needed to confirm our findings.

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.

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.

The role of inflammation in cases with gestational diabetes mellitus: Systemic immune inflammatory index according to trimesters.

PROBLEM: This study aims to investigate the role of the systemic immune-inflammatory index (SII) in inflammation by analyzing SII values by trimester in gestational diabetes mellitus (GDM). METHOD OF STUDY: Between May 2019 and June 2020, we retrospectively enrolled 467 pregnant women who were followed from the first trimester to delivery in our hospital. We evaluated the sociodemographic characteristics, laboratory test results, SII values, Apgar scores, and newborn birth weights of pregnant women diagnosed with GDM. We also compared the SII values of GDM for the 1st, 2nd, and 3rd trimesters with the control group. RESULTS: When examining the SII values of the GDM group in these three trimesters, without including the control group, we found that the SII value of the GDM group in the 3rd trimester was significantly higher than in the 1st trimester, with a gradual increase with each trimester (p = .007). Additionally, the SII value was higher in the GDM group compared to the control group (p = .008). We conducted a Receiver Operating Characteristic (ROC) analysis of the SII value between the groups by trimester. The diagnostic significance of SII between the GDM and control groups was observed in the 3rd trimester, as the area under the curve (AUC) was close to 0.5 and not associated with a specific cutoff value. When examining the relationship between 3rd-trimester SII and study parameters, we found it had a positive and low correlation with the length of prepartum hospitalization, 50 g Oral Glucose Tolerance Test (OGTT), and maximal vertical pocket. CONCLUSION: SII levels were significantly higher in third-trimester GDM patients; however, despite elevated levels of inflammation, fetuses did not experience harm.

Can inflammatory biomarkers based on first trimester complete blood count parameters predict placental abruption ?: A case-control study.

OBJECTIVES: Placental abruption (PA) is associated with adverse maternal and neonatal outcomes and has an etiological mechanism that is not yet fully understood. The prediction of PA, which has been the subject of numerous studies, remains a challenge. In particular, there is evidence that PA can be considered a chronic process. So, this study aimed to show inflammatory biomarkers based on complete blood count parameters may be used to predict PA. STUDY DESIGN: A sample of 110 cases (pregnant women with PA) and 110 controls (healthy pregnant women with spontaneous labor) were required the study. The present case-control study included a total of 220 pregnant women. Inflammatory makers were used to evaluate the PA prediction RESULTS: Increases in body mass index, mean corpuscular volume and paletelet lymphocyte ratio are considered protective factors, while increases in neutrophil, the systemic inflammatory response index, neutrophil lymphocyte ratio and the pan-immune inflammation score are considered risk factors. Each 1 unit increase in neutrophil count increases the risk of a PA diagnosis by 1.81 times. CONCLUSION: Recent studies indicate a strong heterogeneity of clinical courses leading to PA in premature and term births. In the present study, our results showed that, inflammation is associated with PA.

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.

Evaluation of maternal serum sestrin-2 levels in intrauterine growth restriction.

BACKGROUND: Sestrin-2 (SESN2) is a antioxidant protein that can be activated by a number of conditions, including DNA damage and hypoxia. AIMS: Our objective was to evaluate maternal serum SESN2 levels in patients with intrauterine growth restriction (IUGR) and its association with adverse perinatal outcomes. METHODS: This prospective study included a total of 87 pregnant women admitted to our tertiary care center between 2018 August and 2019 July. The study group consisted of a total of 44 patients who had been diagnosed with IUGR. Forty-three low-risk and gestational age-matched pregnant women were taken as control group. Demographic data, maternal serum SESN2 levels, and maternal-neonatal outcomes were evaluated. SESN2 levels were analyzed by the enzyme-linked immunosorbent assay (ELISA) method and compared between groups. RESULTS: Maternal serum SESN2 levels were significantly higher in the IUGR group compared to control group (22.38 ng/ml vs. 13.0 ng/ml, p < 0.001). In correlation analysis, a negative significant correlation was found between SESN2 levels and gestational week at delivery (r = - 0.387, p < 0.001). The ideal cut-off value for detecting IUGR was 9.5 ng/ml, and the area under the curve was 0.719 (95%CI: 0.610-0.827). Birth interval, gestational week at birth, birth weight, and 1-5-min Apgar scores were lower in the IUGR group (p < 0.001). CONCLUSIONS: Maternal serum SESN2 levels are elevated in IUGR and are associated with adverse neonatal outcome. Considering that SESN2 is involved in pathogenesis, it can be used as a new marker for the evaluation of IUGR.