Trisomy 21 (Down Syndrome) Risk Assessment and Management

The risk of having a child with Trisomy 21 increases significantly with advancing maternal age, with a baseline risk of approximately 1 in 356 at age 35, according to the American College of Obstetricians and Gynecologists 1, 2
Maternal age is the primary risk factor for Down syndrome, with risk increasing exponentially after age 35, as stated by the American College of Medical Genetics and Genomics 3, 4

Screening Options and Detection Rates

The Triple Screen (MSAFP, hCG, uE3) detects approximately 65% of Down syndrome cases, and the Quad Screen (MSAFP, hCG, uE3, INH-A) detects approximately 75% of cases in women under 35 and over 80% in women 35 and older, as reported by the National Society of Genetic Counselors 3, 5
Cell-free DNA (cfDNA) provides the highest detection rate for trisomy 21 and lowest residual risk, reducing risk by approximately 300-fold, according to the American College of Obstetricians and Gynecologists 1, 2

Alpha-fetoprotein (AFP) is typically lower than normal in Down syndrome cases, and human chorionic gonadotropin (hCG) is typically higher than normal, as stated by the National Society of Genetic Counselors 5
Unconjugated estriol (uE3) is typically lower than normal, and inhibin-A (INH-A) is typically higher than normal in Down syndrome cases, according to the American College of Medical Genetics and Genomics 5

The American College of Obstetricians and Gynecologists recommends assessing baseline risk based on maternal age and history of previous affected pregnancies, and offering appropriate screening based on gestational age 1, 3
For women with a negative cfDNA result, the residual risk is extremely low, and no further testing is needed, as stated by the American College of Obstetricians and Gynecologists 1, 2

The American College of Medical Genetics and Genomics emphasizes that screening vs. diagnostic testing is crucial, as only diagnostic testing (CVS or amniocentesis) provides definitive results 4, 7
Gestational age accuracy is important, and ultrasound dating improves screening accuracy, according to the National Society of Genetic Counselors 8
The American College of Obstetricians and Gynecologists recommends presenting risk as both ratios (e.g., 1 in 356) and percentages to improve patient understanding 4, 7