Prenatal Screening

Prenatal screening employs probabilistic methodology to identify pregnancies at increased risk for chromosomal aneuploidy, structural anomalies, and genetic conditions, enabling informed reproductive decision-making. The fundamental distinction between screening (risk stratification using non-invasive methods) and diagnostic testing (definitive diagnosis requiring invasive procedures with procedural risk) is critical for accurate patient counseling. Screening performance is characterized by sensitivity (detection rate), specificity, false-positive rate, and positive predictive value (PPV) — importantly, PPV is heavily influenced by disease prevalence (maternal age-related risk), so a positive cfDNA result in a 25-year-old has a lower PPV than the same result in a 40-year-old despite identical test sensitivity. Chromosomal aneuploidies arise from nondisjunction during meiotic cell division, where homologous chromosomes (meiosis I) or sister chromatids (meiosis II) fail to separate, producing gametes with extra or missing chromosomes. Maternal age is the strongest risk factor because oocytes remain arrested in meiosis I from fetal development until ovulation — decades of arrest allows degradation of cohesin proteins that hold chromosomes together, increasing nondisjunction risk (trisomy 21 risk: 1:1250 at age 25, 1:350 at age 35, 1:100 at age 40,...