Volume 54, Issue 3

Introduction Pregnancy poses an immunological paradox: the maternal immune system must tolerate a semi-allogeneic fetus while maintaining defense against infections. Rather than being an immunosuppressed state, gestation is now recognized as a dynamic, highly regulated immune condition. Content This review applies the cancer-derived immunoediting framework – elimination, equilibrium, and escape – to maternal–fetal immune tolerance. We examine how immune checkpoints, regulatory T cells, non-classical MHC molecules, and placental exosomes coordinate to create a localized tolerant environment. Integrating knowledge from oncology and reproductive immunology, this perspective provides a unifying concept for pregnancy immune regulation. Summary The immunoediting framework reinterprets obstetric disorders such as preeclampsia, recurrent pregnancy loss, and preterm birth as failures of distinct immune phases rather than isolated pathologies. This conceptual shift allows for a broader understanding of how immune balance influences implantation, placental development, and fetal growth. Outlook Adopting an immunoediting perspective highlights potential clinical advances, including immune checkpoint modulation, regulatory T-cell therapies, and exosome-based biomarkers, paving the way for innovative diagnostic and therapeutic strategies in pregnancy care.

Introduction Effective prenatal counseling relies on clear communication of fetal development and potential complications. Conventional 2D and 3D ultrasound images often fail to intuitively convey complex anatomy to expectant parents, limiting engagement and informed decision-making. Content Virtual fetal holography combines advanced image processing and 3D/4D ultrasound data to generate interactive, life-like fetal models. This review synthesizes current literature on its technological basis, clinical applications, and patient-centered outcomes. Evidence from cardiology, surgical planning, and anatomy education demonstrates how holography improves spatial understanding, supports multidisciplinary counseling, and enhances patient experience compared to standard imaging. Applications in anomaly counseling, maternal–fetal bonding, and clinical training are highlighted, alongside workflow models integrating mixed reality headsets and AI algorithms. Summary Virtual fetal holography shows potential for improving prenatal education and emotional engagement. Current evidence is largely descriptive and feasibility-based, with limited empirical validation of its impact on clinical decision-making or patient outcomes. Outlook Future research should address cost, technical complexity, ethical considerations, and standardized clinical protocols. Large-scale trials and cost-effectiveness analyses are needed to define its role in routine prenatal care.

Objectives The purpose of the study is to explore the potential of novel genetic markers in predicting and diagnosing hypertensive conditions during pregnancy, focusing on their role in key pathological processes. The relevance of this study is determined by the necessity to improve methods for the early detection and effective management of pregnancy complications, particularly those associated with elevated blood pressure, which pose a threat to the health of both mother and foetus. Methods The research methodology involves a systematic analysis of scientific literature from the past five years, specifically from 2019 to 2024, emphasising the integration of data from various populations and research approaches within the field of molecular medicine. Results The main findings demonstrate that certain molecular markers reflecting gene activity exhibit high accuracy in predicting the risks of complications associated with hypertension of pregnancy. It is established that these markers can detect disturbances in the regulation of vascular tone, angiogenesis processes, and inflammatory responses long before the onset of clinical symptoms. This opens up opportunities for timely medical intervention and a personalised approach to pregnancy management. Conclusions The results of the study confirm the potential of utilising genetic markers in clinical practice to improve pregnancy outcomes and reduce risks for both mother and child. The practical value lies in the possibility of developing new screening programmes and therapeutic strategies based on the individual characteristics of patients, contributing to more effective management of hypertensive disorders during pregnancy.

Objectives The rate of cesarean delivery (CD) in Qatar is rising at an alarming rate. Vaginal birth after cesarean section (VBAC) is associated with lower maternal morbidity and is an important option for younger mothers. This study compared the pregnancy outcomes of second pregnancies in women with prior CD, according to their age groups, with the aim of individualising VBAC counselling. Methods This retrospective study divided women in their second pregnancies based on age: young group (YG<25 years), control group (CG, 25–35 years), and advanced age group (AG>35 years). The primary outcome was the mode of delivery. Results Out of 2,729 women, 18.2 % had a VBAC (27.4 % in YG vs. 9.5 % in AG). Nearly 48 % agreed to a TOLAC (57.9 % in YG and 41.8 % in AG), 38 % of whom had a successful VBAC. Among those who opted for TOLAC, 47.3 % in YG had a successful VBAC, compared to only 22.8 % in AG (p<0.001). While hypertension, diabetes, macrosomia and preterm birth reduced VBAC, postdated and uncomplicated pregnancies increased the rates. Compared to CG, YG had 35 % lower odds of repeat CD (aOR=0.64, CI=0.49–0.85, p=0.002), while AG had nearly two times higher odds (CI=1.26–2.95, p=0.003), after adjusting for confounders. Conclusions Maternal age emerged as an important predictor of repeat cesarean, with younger mothers having a much higher chance of successful VBAC. More than half with uncomplicated pregnancies opted for an elective CD, highlighting the requirement for improving counselling services that motivate women to take up VBAC and improve their confidence in the healthcare system.

Objectives To explore serum vascular endothelial growth factor (VEGF), β-subunit human chorionic gonadotropin (β-hCG), and soluble Fms-like tyrosine kinasereceptor 1 (sFlt-1) levels in pregnant women with placenta accreta spectrum (PAS) and their prognostic implications. Methods Serum levels were measured in PAS patients and non-PAS controls. Depending on the depth of placental penetration into the uterine wall, PAS patients were further classified into placenta accreta, placenta increta and placenta percreta subgroups. Diagnostic efficacy of individual biomarkers and combined indices was evaluated using receiver operating characteristic curves. Correlations between biomarker levels, disease severity, and prognosis were analyzed. Results Serum levels of VEGF and β-hCG showed significant positive correlations with the extent of PAS invasion, whereas sFlt-1 levels were inversely associated with disease progression. Combined pregnancy complications, elevated serum VEGF levels and decreased serum sFlt-1 levels were risk factors for poor prognosis in patients with PAS. The AUC values of the indicators combined to predict the diagnosis and prognosis of patients with PAS were greater than serum VEGF, hCG, and sFlt-1 levels alone. Conclusions Serum levels of VEGF, β-hCG, and sFlt-1 demonstrate the potential to differentiate between women with and without PAS, and further exhibit a correlation with the depth of myometrial invasion in PAS cases. The combined use of these serum markers enhances both the sensitivity and specificity of prenatal diagnosis and prognostic assessment for PAS compared to individual markers, thereby offering valuable guidance for clinical diagnosis and management of PAS.

Objectives To assess the predictive value of the neutrophil-to-lymphocyte ratio (NLR) for clinical chorioamnionitis in term pregnancies complicated by meconium-stained amniotic fluid (MSAF). Methods This retrospective case-control study included women with singleton pregnancies at ≥37 weeks with documented MSAF during labor. The NLR was calculated from maternal blood samples collected at admission. Clinical and hematological parameters were compared between women with and without clinical chorioamnionitis. A multivariable logistic regression model was constructed to identify independent predictors, and a predictive risk score was developed. Results Among 2,014 women with MSAF, 106 (5.3 %) developed clinical chorioamnionitis. Among those with compared to without clinical chorioamnionitis, the mean NLR was higher (5.0 ± 3.8 vs. 4.3 ± 2.3, p = 0.008) and an NLR >3 was more common (85.8 % vs. 76.9 %, p = 0.042). C-reactive protein and white blood cell levels were comparable between the groups. In multivariable analysis, nulliparity (adjusted odds ratio (aOR) 3.087, 95 % confidence interval (CI):1.808–5.273), longer rupture of membranes (aOR 1.092, 95 % CI:1.092–1.189), and NLR (aOR 1.095, 95 % CI:1.025–1.171) were independently associated with clinical chorioamnionitis. A predictive model incorporating nulliparity, rupture of membranes >10 h, and NLR >3 demonstrated an area under the curve of 0.742 (95 % CI: 0.693–0.791, p < 0.001) for predicting clinical chorioamnionitis. Conclusions NLR at admission was independently associated with clinical chorioamnionitis in term pregnancies complicated by MSAF. Incorporating NLR into a predictive model enhanced risk stratification, suggesting that NLR could be a practical biomarker for early identification of increased risk of infection among women with MSAF.

Objectives To determine the genetic causes of miscarriage by analyzing products of conception (POC). Methods Chromosomal microarray (CMA) using the Affymetrix Cytoscan HD array was performed in 172 POC specimens from women experiencing spontaneous miscarriage before 20 weeks of gestation to detect aneuploidies, copy number variants (CNVs), and loss of heterozygosity (LOH). Whole exome sequencing (WES) with Roche KAPA HyperExome V2 probes was used for cases where CMA results were normal. Results Common clinical indications included recurrent pregnancy loss, first-time miscarriage, absence of cardiac activity, intrauterine death, and fetal growth restriction (FGR), making up 72.55 % of cases. CMA identified chromosomal abnormalities in 38.37 % of samples, with numerical anomalies in 16.86 % and structural anomalies in 21.51 %. Turner syndrome (5.8 %) and various trisomies (5.8 %) were frequent numerical anomalies. Mosaicism and LOH were observed in 11.04 and 2.91 % of cases. WES detected pathogenic or likely pathogenic mutations in 21 genes (e.g., KCNQ1, KCNE1, COL1A2, ROBO1) in 18 cases, adding a 10.46 % diagnostic yield. K-means clustering grouped 17 of these genes into three pathways: chondrocyte differentiation, fibrin clot formation, and Ehlers-Danlos syndrome. Conclusions Combining CMA and WES provides a diagnostic yield of 48.83 %, offering a powerful approach to uncover genetic causes of pregnancy loss and guide clinical care.

Objectives We aim to clarify the association and strength of association between antiphospholipid syndrome (APS) and adverse pregnancy outcomes. Methods Our study included an analysis of 191 hospitalized singleton pregnant women with APS and 984 healthy singleton pregnant women at Obstetrics and Gynecology Hospital Affiliated to Fudan University from July 2017 to September 2023. The exposure factor was diagnosed as antiphospholipid syndrome, and the main outcomes were adverse pregnancy outcomes, including miscarriage, preterm birth, low birth weight, gestational hypertension, and eclampsia. Results Our analysis indicated that the odds ratio (OR) for miscarriage in APS patients was 2.50 (95 % CI, 1.025 ± 15.794; p=0.046), for preterm birth was 2.8 (95 % CI, 1.025 ± 15.794; p=0.046), for low birth weight was 2.28 (95 % CI, 1.025 ± 15.794; p=0.046), and for fetal growth restriction was OR=2.48 (1.45, 4.23) p<0.05. The OR for preeclampsia was 1.00, and for gestational hypertension was 0.96, p>0.05. After adjustment for confounders of age and BMI confounders, the odds ratio (OR) for miscarriage was 2.50 (95 % CI: 1.52–4.11) p<0.05. Preterm birth was 2.89 (95 % CI: 1.79–4.65) p<0.05, low birth weight was 2.28 (95 % CI: 1.52–3.55) p<0.05, intrauterine growth restriction was 2.48 (95 % CI: 1.45–4.23) p<0.05. The OR of preeclampsia was 1.00 (95 % CI: 0.59–1.71) p>0.05, and that of pregnancy-induced hypertension was 0.96 (95 % CI: 0.53–1.75) p>0.05. After adjustment for confounders of age, BMI, eclampsia and diabetes, the OR for preterm infants were 3.06 (95 % CI: 1.87–5.00) p<0.05, and those of low birth weight infants were 2.55 (95 % CI: 1.49–4.37) p<0.05. After adjustment for confounders of age, BMI, diabetes, eclampsia, and gestational week, the OR for low birth weight infants was 2.02 (95 % CI: 1.26–3.26) p<0.05. Conclusions Antiphospholipid syndrome was significantly associated with the risk of miscarriage, preterm birth, low birth weight, and intrauterine growth restriction as adverse pregnancy outcomes.

Objectives The use of technological methods in childbirth is becoming increasingly common. This study aimed to evaluate the effects of virtual reality (VR) glasses on fear of childbirth, duration of labor, and fetal well-being in women undergoing term vaginal delivery. Methods This single-blind randomized controlled trial included 144 pregnant women, equally divided into VR and control groups, stratified by parity. The intervention group watched nature videos via VR glasses in two sessions during the active phase of labor. Data were collected using clinical record forms, a nonstress test (NST) monitoring form, and the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ-A/B). Results The use of VR significantly reduced fear of childbirth and shortened the active phase of labor among both primiparous and multiparous women (p<0.05). No significant differences were found in the total duration of labor or other phases. While significant differences were observed in fetal movements and accelerations between groups, no clinically adverse effects on fetal well-being were reported. No side effects or complications related to the VR intervention were observed. Conclusions VR appears to be a safe and effective non-pharmacological method to reduce childbirth fear and shorten the active phase of labor. Further studies are recommended to confirm its effects on labor physiology and neonatal outcomes.

Objectives The sFlt-1/PlGF ratio is a predictive biomarker for preeclampsia (PE)–related outcomes. In women with signs of PE at ≤34 weeks, it may guide the timing of antenatal corticosteroid (ACS) administration. Methods We retrospectively analyzed 702 women presenting with signs of PE and/or fetal growth restriction (FGR) between 22+0- and 33+6-weeks. High risk was defined as an sFlt-1/PlGF ratio ≥85. The predictive accuracy of the ratio for PE-related preterm birth at ≤34+0 weeks was assessed using receiver operating characteristic (ROC) analysis. Differences in remaining pregnancy duration and gestational age at delivery between risk groups were analyzed using the log-rank test (p<0.05). Results Among 702 patients, 165 (23.5 %) had a PE-related delivery ≤34+0 weeks. A high sFlt-1/PlGF ratio (≥85) was observed in 128 (18.2 %) women who received ACS and in 44 (6.3 %) who didn’t. The sFlt-1/PlGF ratio predicted PE-related delivery at ≤34+0 weeks – and thus the need for ACS with an AUC of 0.95 (95 % CI 0.93–0.97), yielding an optimal cut-off of 52.5 with sensitivity 87.9 % (95 % CI 82.0–92.0) and specificity 87.9 % (95 % CI 84.9–90.4). The median remaining pregnancy duration was 7.0 days (IQR 3.0–17.8), with delivery at 29+5 weeks (IQR 26+6–32+0) in women with ACS and a ratio ≥85, vs. 60.0 days (IQR 42.0–80.0) and delivery at 38+1 weeks (IQR 37+0–39+3) in women with a ratio <85 and no ACS. Conclusions In women with signs of PE and FGR <34 weeks of gestation, the sFlt-1/PlGF ratio is a strong predictor of PE-related preterm delivery and may support clinical decision-making regarding timely ACS administration.

Objectives This study reviews early unfavorable outcomes following selective in-utero cord occlusion in monochorionic twin pregnancies at risk of hemodynamic accidents by a single operator. Methods The study analyzed laser ablation (LA), laser transection (LT), radiofrequency ablation (RFA), and bipolar diathermy (BD) procedures performed between 14 and 22 weeks of gestation from 2006 to 2022. Outcomes included: (1) technical failure (abandonment before cessation of Doppler flow), (2) intraoperative events (hemodynamic instability in the woman or co-twin), and (3) complications (e.g., fluid leakage, infection, abruption, co-twin demise, or miscarriage) within 1 week post-procedure. Results Ten LAs were performed at 14–15 weeks for discordant anomalies, all without complications. Two LTs were conducted at 20 weeks for umbilical cord knotting; with one procedure experienced technical failure. All twin reversed arterial perfusion sequence (TRAPS) (n=55) received RFA, with one procedure experienced technical failure. All twin-to-twin transfusion syndrome (TTTS) (n=25) received BD, with one procedure experienced technical failure. Selective intrauterine growth restriction (sIUGR) (n=30) received RFA (n=5) and BD (n=25), with 1 RFA (25 %) and 1 BD (4 %) experienced technical failure. (p<0.01) All four technical failure cases had extensive anterior placenta. There were no intraoperative events. McDonald cervical cerclage was performed in 8/25 TTTS cases with pre-operative cervical length of ≤25 mm and/or funneling of the internal cervical os. Early procedure-related complications were experienced in two sIUGR cases receiving BD, both of which had extensive anterior placenta. Conclusions Early unfavorable outcomes were associated with sIUGR as an indication.

Objectives Fetal death is a major pregnancy complication, with rates of 5.5 per 1,000 births in the United States and substantially higher in India (24.7/1,000) and Pakistan (44.5/1,000). Maternal vascular malperfusion (MVM) is the most frequent placental lesion associated with fetal death, occurring in 58 % of fetal deaths and 31 % of preterm neonatal deaths in South Asia. Angiogenic imbalance, characterized by a low placental growth factor (PlGF) to soluble fms-like tyrosine kinase-1 (sFlt-1) ratio, has been associated with MVM and fetal death in high-income countries. We examined whether maternal serum concentrations of PlGF, sFlt-1, and their ratio differ between mothers with and without MVM among stillbirths and preterm neonatal deaths in India and Pakistan. Methods This retrospective cohort analysis used data from the PURPOSe study (Project to Understand and Research Preterm Pregnancy Outcomes and Stillbirths in South Asia). Maternal blood was collected at delivery, and placental histopathology was classified according to the Amsterdam criteria. Serum PlGF and sFlt-1 were measured using Elecsys ® immunoassays, with analyses stratified by gestational age. Results Placental MVM was present in 44–57 % of stillbirths and 31–38 % of preterm neonatal deaths. Between 28 and 36 weeks, women with MVM had significantly lower PlGF and higher sFlt-1 and sFlt-1/PlGF ratios (p<0.001). A tenfold decrease in PlGF or increase in the ratio was associated with MVM (OR 0.5 and 1.7, respectively). Conclusions The maternal sFlt-1/PlGF ratio identifies pregnancies with fetal or neonatal death associated with placental MVM, particularly between 28 and 36 weeks’ gestation.

Objectives Historically, baseline fetal heart rate variability (FHRV) with an amplitude of greater than 25 beats per minute, and lasting for more than 30 min, was defined as the saltatory pattern. Several experimental animal models have reported an association between saltatory pattern and poor perinatal outcomes. However, recent studies have suggested that the classically defined saltatory pattern is very uncommon during labor, and a new CTG pattern, called the “ZigZag” pattern (ZZP), has been reported. ZZP has been defined as a rapid, erratic repetitive oscillations in the FHR with an amplitude of >25 bpm and has been claimed as a potential marker to identify fetuses at risk of intra-partum and perinatal compromise during labour. A recent international expert consensus has recommended that ZZP persisting for >1 min requires an urgent intervention to avoid poor perinatal outcomes. The aim of the present systematic review was to determine the intra-partum and perinatal outcomes of fetuses with the ZZP compared to the control group not showing the ZZP during labor. Methods Medline, Embase and Cochrane databases were searched. Inclusion criteria were studies reporting the intra-partum and perinatal outcome of fetuses showing compared to those not showing ZZP during labour. The outcomes observed were operative vaginal delivery, caesarean section, umbilical artery pH<7.1, base excess <−11, mean pH and base excess, admission to neonatal intensive care unit (NICU), abnormal post-natal brain imaging and occurrence of late decelerations later on the CTG trace. Random-effect meta-analyses were used to combine data and results reported as pooled odd ratios (OR) for categorical and pooled mean differences (MD) for continuous variables with their 95 % confidence intervals (CI). Results Six studies (18,136 fetuses) were included. Fetuses showing ZZP on CTG trace during labor had a higher risk of operative vaginal delivery (OR: 2.22, 95 % CI 1.69–2.91; p<0.001), cesarean delivery (OR: 1.71, 95 % CI 1.37–2.15; p<0.001), umbilical artery pH<7.1 (OR: 2.48, 95 % CI 1.56–3.94; p<0.001), Apgar score <7 at 5 min (OR: 2.13, 955 CI 1.05–4.31; p=0.004) and the occurrence of late decelerations later on during labor (OR: 9.51, 95 % CI 7.80–11.61; p<0.001) compared to those not showing this pattern, while there was no difference in the risk of NICU admission (p=0.209) and respiratory support after birth (p=0.755). Likewise, umbilical artery pH was significantly lower in fetuses showing compared to those not showing ZZP during labour (pooled MD: −0.10, 95 % CI −0.11 to −0.09; p<0.001), while there was no difference in the value of mean base excess between the two groups (p=0.156). Conclusions Fetuses showing the ZZP on CTG trace during labour are at higher risk of operative vaginal delivery, caesarean section and adverse intrapartum and perinatal outcomes.

Objectives This study aims to investigate the role of fetal thymus and adrenal medulla dimensions in the pathogenesis of preterm prelabor rupture of membranes (PPROM). Methods A prospective, case-control study was conducted involving 45 pregnant women with PPROM between 28 and 37 weeks of gestation and 45 matched healthy controls. Ultrasonographic measurements of fetal thymus (width, length, thymothoracic ratio (TTR)) and adrenal glands (length, width, depth, volume), including the adrenal medulla, were performed. Biochemical markers (WBC, CRP) and neonatal outcomes were recorded. Statistical analyses included comparisons between groups, correlation assessments, and ROC curve analysis to evaluate predictive parameters. Results The fetal thymus dimensions and TTR ratio were significantly smaller in the PPROM group. The adrenal medulla volume, length, and depth were notably reduced, while total adrenal gland size showed no significant difference. Moderate negative correlations were observed between inflammatory markers and TTR. ROC analysis indicated that TTR and adrenal medulla volume could predict NICU admission with moderate sensitivity and specificity. Conclusions The findings suggest that alterations in fetal thymus and adrenal medulla sizes are associated with PPROM and may serve as potential biomarkers for its diagnosis and prognosis. Further large-scale studies are warranted to validate these parameters and explore their clinical applications.

Objectives To evaluate fetal brain midline structures, cortical structures, and brain volume using sonography in cases of fetal growth restriction (FGR) and to compare these findings with those of fetuses demonstrating normal growth. Methods This prospective case-control study included 80 FGR cases and 80 fetuses with normal growth curves between 24 and 37 weeks of gestation. Multiplanar neurosonography was performed in all cases according to the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) guidelines. The corpus callosum (CC; length, thickness, and fastigium distance), cavum septi pellucidi (CSP), sylvian fissure (SF), parieto-occipital fissure (POF), calcarine fissure (CF), insula, olfactory sulcus (OS), and brain volume were evaluated. Measurements were made using the ultrasound device’s electronic calipers, and brain volume was calculated using the Virtual Organ Computer-aided Analysis (VOCAL) application. Results In the FGR group, CSP width, CC length, and thickness were significantly increased, while CCFL and POF depths were decreased (p < 0.05, for all). Mean brain volumes were similar in the FGR and control groups (349.30 ± 61.77 vs. 368.42 ± 68.51, p = 0.066). In FGR group, middle cerebral artery peak systolic velocity (MCA PSV) was positively correlated with most brain structures but negatively correlated with CC thickness. There was no relationship between cerebroplacental ratio (CPR) and brain volume or fetal brain structures. Conclusions Our findings showed that FGR affects the fetal brain through neuroanatomical structures such as the CC, CSP, CCFL, and POF during the prenatal period. In our cohort, fetal brain volume did not differ significantly in FGR. Furthermore, there was no association between CPR and fetal brain structures.

Objectives Post-mortem magnetic resonance imaging (pmMRI) has emerged as a promising, non-invasive alternative to conventional autopsy for detecting cardiac anomalies in fetal and perinatal deaths and we aimed to systematically evaluate the diagnostic accuracy of pmMRI in detecting cardiac anomalies in fetal and perinatal deaths. Methods A systematic search of electronic databases and grey literature was conducted following PRISMA 2020 guidelines to analyse studies comparing pmMRI findings to conventional autopsy. Data extraction and quality assessment were independently performed by two reviewers using the QUADAS-2 tool. Meta-analysis was conducted using a bivariate random-effects model to calculate pooled sensitivity, specificity, and diagnostic odds ratios (DOR). Results Sixteen studies were included in the systematic review, and 12 studies (n=1810 fetuses) were meta-analyzed. The pooled sensitivity and specificity of pmMRI for detecting cardiac anomalies were 76 % (95 % CI: 71–80 %) and 96 % (95 % CI: 95–97 %), respectively. The diagnostic odds ratio was 55.35 (95 % CI: 22.73–134.79), with an area under the SROC curve of 0.89, indicating excellent diagnostic performance. Subgroup analyses showed comparable sensitivity between 1.5 and 3 T scanners, though specificity was slightly higher for 1.5 T. Diagnostic accuracy was generally better in larger fetuses and when higher field strength MRI (9.4 T) was used. Conclusions pmMRI demonstrates high specificity and moderate sensitivity for detecting cardiac anomalies in fetal and perinatal deaths and may serve as a valuable non-invasive adjunct to conventional autopsy. Standardization of imaging protocols and further research into high-field pmMRI integration are recommended to optimize diagnostic reliability.

Objectives To investigate the impact of intrauterine pathologies, including twin-to-twin transfusion syndrome (TTTS) and selective intrauterine growth restriction (sIUGR), on the development of retinopathy of prematurity (ROP) in monochorionic diamniotic (MCDA) twins and to establish risk prediction models. Methods A retrospective case-control study was conducted including 466 MCDA preterm twins born before 37 weeks. Participants were categorized into three groups (TTTS, sIUGR, and uncomplicated). Clinical and laboratory data were analyzed. Significant predictors were identified via random forest algorithm and multivariate logistic regression. ROC and DCA analyses were used to evaluate predictive models. Results ROP incidence was significantly higher in the TTTS group (37.8 %) compared with sIUGR (8.2 %) and uncomplicated twins (10.7 %) (p<0.0125). TTTS was confirmed as an independent risk factor (OR=2.846, p<0.05). Gestational age was the strongest predictor. Four risk models showed AUCs of 0.796–0.919. The risk of ROP onset increases significantly in MCDA twin preterm infants from a birth gestational age of 30 weeks (TTTS group), 31.3 weeks (sIUGR group), and 32 weeks (uncomplicated group); infants with these birth gestational ages are a high-risk population for ROP. Conclusions TTTS significantly elevates ROP risk in MCDA twins. Personalized screening protocols based on intrauterine pathology may improve ROP detection and outcomes.

Objectives This study aimed to evaluate the predictive value of inflammatory biomarkers fibrinogen/albumin ratio (FAR), platelet/albumin ratio (PAR), and AST/platelet ratio (APRI) in identifying poor neonatal outcomes among pregnancies complicated by IHCP. Methods This retrospective comparative study included 165 pregnant women diagnosed with IHCP and 155 healthy pregnant women matched for age and gestational age, who delivered at a tertiary care hospital between January 2023 and January 2025. Demographic, clinical, laboratory, and perinatal characteristics were reviewed. FAR, PAR, and APRI were calculated from standard laboratory data. A composite poor neonatal outcome was defined as the presence of at least one of the following: Apgar score <7 at 5 min, respiratory distress syndrome (RDS), meconium aspiration, neonatal sepsis, or admission to the neonatal intensive care unit (NICU). Diagnostic performance was assessed using receiver operating characteristic (ROC) curves and multivariate logistic regression. Results FAR and APRI values were significantly higher in the IHCP group compared to controls (p<0.05). Among neonates with adverse outcomes, only FAR levels were significantly elevated (p = 0.015). However, its discriminative ability was limited (AUC = 0.607; sensitivity: 58 %, specificity: 63 %) and it was not an independent predictor in multivariate analysis. Conclusions FAR and APRI levels are elevated in pregnancies with IHCP, yet FAR alone demonstrates limited predictive value for adverse neonatal outcomes. It may serve as a supportive, rather than standalone, marker. Further large-scale prospective studies are warranted.

Objectives To examine the incidence of hypervitaminosis D in very low birth weight (VLBW) infants and any associated maternal or neonatal factors. Methods In this single center retrospective study, we studied serum vitamin D (25[OH]D) levels, maternal and neonatal demographic and clinical factors. We included VLBW infants (≤32 weeks gestational age (GA) and ≤1,500 g birthweight, n = 130) born between 2021 and 2023. VLBWs receive 400 IU/day cholecalciferol once TPN is discontinued. Hypervitaminosis D was defined as 25[OH]D levels >60 ng/mL. We considered 11 variables with plausibility to influence this outcome. Variables with p < 0.20 in univariate logistic regression were entered into a multivariable logistic model to assess associations with the primary outcome. A linear mixed model assessed the association between calcium and 25[OH]D levels, with time as a fixed effect and subject as a random effect. Results 63 VLBWs (48 %) developed hypervitaminosis D. Maternal age > 35 years (OR = 2.2, 95 % CI 0.96–5.06) associated with excess 25[OH]D approached statistical significance (p = 0.06). Our findings indicate that in GA ≥ 28 weeks (OR = 0.77, 95 % CI 0.64–0.92) and maternal hypertension (OR = 0.32, 95 % CI 0.14–0.73) were associated with reduced likelihood of hypervitaminosis D. Conclusions 25[OH]D supplementation of 400 IU/day in VLBWs is associated with a high incidence of hypervitaminosis D. The above findings reveal a significant effect of maternal demographic and clinical factors on newborn metabolic health. Further work is needed to identify causes of hypervitaminosis D. Long term prospective studies are needed to understand the impact of hypervitaminosis D in VLBWs.

Objectives To evaluate diagnostic accuracy of urinary immune biomarkers (IBM) for late-onset sepsis (LOS) in very preterm infants. Methods This multicenter, prospective diagnostic accuracy study, included preterm infants <32 weeks of gestation and birth weight <1,500 g, needing evaluation for suspected LOS. Urine samples obtained concurrent to blood culture and sepsis screen were evaluated for interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) levels using enzyme immunoassay. Positive blood and/or CSF culture served as reference standards. Receiver operating characteristic curves were used to evaluate performance of urinary IBM for detection of LOS. Results During September 2021–September 2023, we evaluated 136 preterm, very low birth weight infants (mean gestational age: 28.2 weeks, mean birth weight: 933 g) for sepsis after 72 h of postnatal age and prior to 37 weeks postmenstrual age. Twenty four infants had culture-positive sepsis. Median IL-8 and MCP-1 levels in neonates with LOS were 86.5 pg/mL and 230.2 pg/mL and those in non-infected neonates were 66.5 pg/mL and 212.1 pg/mL. Urinary IL-8 had sensitivity and specificity of 42 and 51 % [AUC: 0.46 (0.35–0.57)] and urinary MCP-1 had sensitivity and specificity of 46 and 53 % [AUC: 0.49 (0.38–0.60)] for detection of LOS. Conclusions Urinary IL-8 and MCP-1 had low sensitivity and specificity for diagnosis of LOS in very preterm infants. These findings underscore the need to establish reference ranges for urinary IBM in preterm neonates.