Gestational diabetes mellitus (GDM) occurs in approximately 9–25% of pregnancies and, if left undiagnosed or inadequately controlled, can lead to adverse outcomes for both the mother and the fetus, short and long term. GDM is characterized by glucose intolerance with onset or first recognition during pregnancy and is a multifactorial condition with a pathophysiology that remains incompletely understood. It is strongly associated with a chronic low-grade inflammatory state that contributes to insulin resistance, a hallmark of GDM pathogenesis. Among the fundamental pro-inflammatory cytokines implicated in this process, TNF-α and IL-6 play central roles. TNF-α is a cytokine primarily secreted by activated macrophages, as well as by adipocytes in the context of obesity. Many studies have shown that its levels are elevated in pregnant women with GDM compared to normoglycemic pregnant individuals. IL-6 is another pro-inflammatory cytokine secreted by immune cells, adipose tissue, and the placenta. It is found in higher concentrations in the maternal circulation during pregnancies complicated by GDM. Both TNF-α and IL-6 act synergistically to perpetuate a pro-inflammatory intrauterine environment. Their combined effects exacerbate insulin resistance and may impair pancreatic β-cell compensation during pregnancy, facilitating the onset of GDM in genetically or metabolically susceptible individuals. Recent research has identified various maternal serum biomarkers, such as TNF-α and IL-6, that may hold promise for the early detection of GDM. The aim of our study is to evaluate whether TNF-α and IL-6 can be used as diagnostic tools for the early diagnosis of GDM, allowing for timely intervention and reducing the risk of associated maternal and fetal complications.

Preeclampsia (PE) occurs in approximately 2–8% of all pregnancies worldwide and represents one of the primary causes of maternal and fetal morbidity and mortality. Angiogenic growth factors such as placental growth factor (PlGF) and vascular endothelial growth factor (VEGF), along with their tyrosine kinase receptor (Flt-1), play a central role in placental and fetal development. Impaired placentation results in the excessive release of the antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) which is pivotal in the pathogenesis of PE. By binding to and neutralizing angiogenic factors, sFlt-1 disrupts normal angiogenic signaling, creating an imbalance that is often detectable before clinical symptoms of PE appear. Recent studies have highlighted the prognostic potential of the sFlt-1/PlGf ratio as an early indicator of PE risk, since this ratio has demonstrated value in both confirming and excluding PE in the high-risk population. Its incorporation into routine medical care has the potential to reduce unnecessary hospital admissions, intensive management, and premature deliveries, ultimately lowering healthcare costs. The objective of this review is to highlight the clinical utility of the sFlt-1/PlGf ratio in the prediction, diagnosis, and management of preeclampsia and to emphasize the cost-effectiveness of implementing sFlt-1/PlGF ratio measurement in the care of women at risk of developing PE.

Fetal surgery has emerged as a viable option for the management of selected congenital anomalies that result in severe or lethal outcomes if left untreated until birth. Conditions such as spina bifida, urinary tract obstruction, congenital cystic adenomatoid malformation, diaphragmatic hernia, sacrococcygeal teratoma, and twin–twin transfusion syndrome have shown improved prognosis after in utero intervention, open, or fetoscopically. Despite significant advances in surgical methods and anesthesia, preterm labor remains a primary concern. Stem cell transplantation and in utero gene therapy are developing, and they have the potential to expand the treatment window, as they minimize maternal complications. Hematopoietic stem cell transplantation, which is based on the immaturity of the fetal immune system, is a promising treatment for inherited disorders. Although many procedures of fetal interventions are now established, their safety and efficacy must be ensured and this requires optimal patient selection and choice of appropriate timing for intervention, adherence to ethical principles, and continuous research. Therefore, a multidisciplinary team, including specialists in maternal–fetal medicine, pediatric surgery, anesthesiology, neonatology, psychosocial support, and bioethics, is essential to guide comprehensive, patient-centered care. Fetal surgery is an evolving field that offers hope for conditions previously considered untreatable before birth.

Background/Objectives: This study evaluates the diagnostic performance of DNA methylation testing, alone and in combination with cervical cytology, for high-grade squamous intraepithelial lesion (HSIL) detection. Methods: A prospective study was conducted on 170 high-risk HPV (hr-HPV)-positive women. DNA methylation (QIAsure^®) and cervical cytology were performed prior to cervical large loop excision of the transformation zone (LLETZ). Sensitivity, specificity, and area under the curve (AUC) metrics were calculated, including stratified analyses for HPV16/18 and other hr-HPV genotypes. Results: DNA methylation alone achieved a sensitivity of 69.7%, specificity of 79%, and an AUC of 0.796 for HSIL detection. The combination of cervical cytology and DNA methylation improved sensitivity to 94.7%, specificity to 76.3%, and AUC to 0.860. Stratification by HPV genotype revealed that in HPV16/18-positive cases, DNA methylation alone reached an AUC of 0.790, while the combination with cytology significantly enhanced performance to 0.917. DNA methylation alone demonstrated an AUC of 0.744 for other hr-HPV types, and the combined approach achieved an AUC of 0.849. Specificity for the combined approach was notably higher in HPV16/18-positive women (88.9%) than in other hr-HPV cases (72.4%), whereas the sensitivity of the combined approach was significantly higher in both groups (94.5% vs. 95%, respectively). Conclusions: The integration of DNA methylation with cervical cytology significantly enhances diagnostic accuracy for CIN2+ lesions, especially in HPV16/18-positive cases. However, the comparatively lower AUC and specificity observed in other hrHPV types suggest the need for further optimization to enhance accuracy in non-16/18 infections. These findings support the integration of methylation-based testing with cytology as a valuable triage strategy for improving cervical cancer screening and patient management.

Background/Objectives: Obstetric ultrasound is one of the most commonly used imaging modalities during pregnancy to detect any fetal abnormalities. The aim of this systematic review was to appraise all available scientific literature and summarize current evidence regarding the safety of fetal ultrasound by using the thermal index (TI) and mechanical index (MI). Methods: We applied the PRISMA guidelines in order to prepare the review, and a 2-step process was performed in order to evaluate the available literature and decide which studies to be included. A thorough search of the Medline, Scopus, and Google Scholar databases was performed. Randomized and non-randomized studies were considered for review. The MI and TI were available in ultrasound machines after 1993; thus, studies before that year would not provide data on these two indexes. Results: A total of 21 studies were included in this review, including prospective, retrospective, cross-sectional, and survey-type studies. A common theme of the majority of the studies is the increased acoustic output available to the machines with time and the limited awareness of where the MI/TI indexes are from the operators. Conclusions: This review indicates that, while obstetric ultrasound is predominantly safe, there is a need for operators to consistently observe MI/TI indexes and adhere to the ALARA principle to minimize potential risks.

Background: It is well established in the literature that pregnancy-associated plasma protein-A (PAPP-A) is linked to several adverse pregnancy outcomes, including pre-eclampsia (PE), fetal growth restriction (FGR), and preterm birth (PTB) in singleton pregnancies. However, data regarding such an association in twin pregnancies are lacking. The primary goal of this systematic review and meta-analysis was to assess the potential value of low PAPP-A levels in the prediction of the subsequent development of hypertensive disorders of pregnancy (HDPs), PTB, and small for gestational age (SGA)/FGR fetuses in twin pregnancies and investigate its association with the development of gestational diabetes, intrauterine death (IUD) of at least one twin, and birth weight discordance (BWD) among the fetuses. Methods: Medline, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception until 31 July 2024. All observational studies reporting low PAPP-A levels after the performance of the first-trimester combined test as part of the screening for chromosomal abnormalities with reported adverse pregnancy outcomes were included. Results: The current systematic review encompassed a total of 11 studies (among which 6 were included in the current meta-analysis) that enrolled a total of 3741 patients. Low PAPP-A levels were not associated with HDPs (OR 1.25, 95% CI 0.78, 2.02, I-square test: 13%). Low PAPP-A levels were positively associated with both the development of preterm birth prior to 32 (OR 2.85, 95% CI 1.70, 4.77, I-square test: 0%) and 34 weeks of gestational age (OR 2.09, 95% CI 1.34, 3.28, I-square test: 0%). Furthermore, low PAPP-A levels were positively associated with SGA/FGR (OR 1.58, 95% CI 1.04, 2.41, I-square test: 0%). Prediction intervals indicated that the sample size that was used did not suffice to support these findings in future studies. Conclusions: Our study indicated that low PAPP-A levels are correlated with an increased incidence of adverse perinatal outcomes in twin pregnancies. Identifying women at elevated risk for such adversities in twin pregnancies may facilitate appropriate management and potential interventions, but additional studies are required to identify the underlying mechanism linking PAPP-A with those obstetrical complications.