Background: Advances in genome-wide DNA-based technologies have fundamentally transformed prenatal genetic diagnostics, enabling detection of clinically significant submicroscopic chromosomal abnormalities that are not identifiable by conventional cytogenetic methods. These developments have important implications for the diagnosis and management of pregnancies complicated by fetal structural abnormalities, as they enable more accurate etiological diagnosis, improved prognostic assessment, and more informed clinical decision-making and reproductive counselling. Methods: This narrative review synthesizes contemporary international evidence on prenatal genetic diagnostic approaches, including conventional karyotyping, chromosomal microarray analysis (CMA), and genome-wide sequencing technologies. The review focuses on diagnostic performance, clinical utility, ethical considerations, and implementation within diverse healthcare systems. Results: Accumulating evidence demonstrates that genome-wide approaches—particularly CMA and sequencing-based methods—provide a higher diagnostic yield in fetuses with structural anomalies, with an incremental yield of approximately 3–5% over conventional karyotyping. This is mainly due to their ability to detect pathogenic copy number variants below the cytogenetic resolution of karyotyping. These technologies improve etiological insight, enhance genotype–phenotype correlation, and support more precise prognostication and reproductive counselling, especially in pregnancies with fetal structural anomalies. Emerging sequencing platforms further expand the diagnostic spectrum by integrating copy number and sequence-level variant detection. Conclusions: Genome-wide Copy Number Variation (CNV) analysis represents a critical component of contemporary prenatal diagnostics and should be integrated into invasive prenatal testing pathways in accordance with international recommendations. Genome-wide approaches need robust counselling frameworks and equitable health policy implementation to spread. The expense, lack of required experience, and variation in healthcare infrastructure across locations make widespread deployment difficult.

Pre-eclampsia and foetal growth restriction (FGR) are major pregnancy complications primarily driven by placental dysfunction, and remain leading causes of maternal and perinatal morbidity. Ultrasound imaging, Doppler studies, and angiogenic biomarkers like placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) constitute the main diagnostic modalities; however, these predominantly reflect established disease rather than early molecular disturbances underlying placentation. The identification of biomarkers directly associated with trophoblast signalling pathways has the potential to improve early risk stratification and enable mechanistic classifications. Kisspeptin signalling via its receptor (KISS1R) regulates trophoblast invasion, extracellular matrix remodelling, ERK1/2 activation, and angiogenic balance, thereby modulating spiral artery transformation. Kisspeptin-10 (KP-10), the minimal bioactive fragment of KISS1, is highly expressed in placental syncytiotrophoblasts and exerts its effects through the G-protein-coupled receptor KISS1R. Core features of early-onset FGR and pre-eclampsia (PE)—including defective placentation, maternal vascular malperfusion, and angiogenic imbalance—have been linked to dysregulation of this pathway. During normal gestation, maternal circulating kisspeptin concentrations rise exponentially. In contrast, pregnancies subsequently complicated by FGR or PE, particularly in the early gestation, are associated with reduced levels. However, the comparability of existing studies and their translational applicability are limited by a substantial methodological heterogeneity, including assay variability, gestational age dependence, and inadequate adjustment for maternal confounders. These limitations hinder robust conclusions regarding the role of kisspeptin in placental pathology. This review critically integrates molecular, pathophysiological, and clinical evidence relating to the role of KP-10 in placental dysfunction. The key question is whether KP-10 represents a mechanistic biomarker of trophoblast signalling dysfunction or merely a secondary marker of reduced placental mass; resolving this distinction is essential.

Objective : To summarize contemporary clinical algorithms for the management of high-risk pregnancy and to integrate international recommendations with regional clinical experience. Methods : Narrative review of international guidelines (ACOG, FIGO, NICE, WHO) and peer-reviewed literature, including data from Bulgarian obstetric practice. Results : Algorithm-based management improves early risk stratification, standardizes care, and supports individualized decision-making in hypertensive disorders, gestational diabetes, fetal growth abnormalities, and combined maternal–fetal risk. Conclusion : Clinical algorithms represent a cornerstone of modern high-risk pregnancy management. Integration of regional data enhances applicability without compromising international relevance.

Stickler syndrome is a monogenic connective tissue disorder primarily caused by pathogenic variants in collagen-related genes, most commonly COL2A1. Prenatal diagnosis remains challenging, particularly in healthcare systems with limited access to molecular genetic testing. We report a prenatal case of suspected craniofacial anomaly detected on second-trimester ultrasound. Fetal DNA obtained by amniocentesis underwent next-generation sequencing. Parental testing was performed to assess inheritance. It was confirmed that autosomal dominant Stickler syndrome type I (ORPHA:90653) was caused by a heterozygous pathogenic frameshift variant in COL2A1 (c.3137del) that was inherited from the mother and identified in the fetus. Micrognathia was identified during prenatal ultrasound, and postnatal evaluation revealed characteristics that were consistent with Pierre Robin sequence and connective tissue involvement. The molecular discoveries elucidated the observed phenotype and facilitated multidisciplinary perinatal management. This case underscores the indispensable function of molecular diagnostics in the prenatal identification of monogenic disorders, including Stickler syndrome, in cases where conventional karyotyping is inadequate. Targeted clinical surveillance and family counseling are facilitated by early genetic confirmation. The report also emphasizes the necessity of incorporating molecular diagnostics into routine prenatal care for rare genetic diseases and the systemic limitations in access to genomic testing. Although the identified variant has been previously reported, this case highlights the clinical and diagnostic value of prenatal molecular confirmation in a resource-limited healthcare setting.