Pathophysiology
Clinical meaning
Advanced prenatal assessment integrates maternal-fetal physiology, genetic screening science, and fetal surveillance techniques to identify and manage high-risk conditions before they become emergencies. The physiological basis of prenatal screening relies on detecting biomarkers that reflect fetoplacental function. Cell-free fetal DNA (cfDNA) in maternal blood originates from placental trophoblast apoptosis: as syncytiotrophoblast cells are shed into maternal circulation, they release DNA fragments that are fetal in origin (actually placental, which is why confined placental mosaicism can cause false-positive results). By 10 weeks gestation, fetal cfDNA constitutes 10-20% of total cell-free DNA in maternal plasma, enabling detection of fetal aneuploidy through shotgun sequencing or targeted analysis โ overrepresentation of chromosome 21 sequences indicates trisomy 21 with >99% sensitivity. First-trimester nuchal translucency (NT) screening measures fluid accumulation behind the fetal neck at 11-14 weeks: increased NT (>3.0 mm) occurs because lymphatic drainage is developmentally delayed in aneuploid fetuses and because cardiac defects cause jugular venous congestion โ elevated NT is associated with trisomies 21, 18, 13, Turner syndrome, and congenital heart defects. Fetal surveillance in the third trimester assesses placental function and fetal...