Prenatal Screening for Aneuploidy
A 36-year-old G2P1 at 12 weeks gestation presents for prenatal care. She has a 3-year-old healthy child. She is anxious about the risk of Down syndrome and requests screening. She has no family history of genetic disorders. She is unsure about invasive testing. You discuss options: cell-free DNA (cfDNA), first-trimester combined screening, or diagnostic testing (CVS or amniocentesis).
1. What are the advantages and disadvantages of cfDNA screening compared to first-trimester combined screening?
Read the worked answer
cfDNA has higher sensitivity and specificity for trisomy 21, 18, and 13 (sensitivity >99% for T21) and can be done from 10 weeks. However, it is a screening test, not diagnostic, and false positives occur. It may be less accurate in obese women or those with vanishing twins. It does not screen for neural tube defects (though alpha-fetoprotein can be added). First-trimester combined screening (nuchal translucency, PAPP-A, hCG) has lower detection rates (about 85-90% for T21) but includes risk assessment for other conditions and can be done with ultrasound. It also screens for early preeclampsia. cfDNA is more expensive and may not be covered by insurance. Both are screening tests; diagnostic testing (CVS/amnio) is required for confirmation.
2. If she chooses cfDNA and it returns high risk for trisomy 21, what is the next step?
Read the worked answer
The next step is genetic counseling and diagnostic testing with chorionic villus sampling (CVS) or amniocentesis. cfDNA is a screening test, so a positive result requires confirmation. CVS can be done at 11-13 weeks, amniocentesis at 15 weeks or later. She should be counseled about the risks of invasive testing (miscarriage rate ~1/300-1/500 for amniocentesis, slightly higher for CVS). If she declines diagnostic testing, she can continue with serial ultrasounds for markers, but that is less reliable. She should also be offered a comprehensive ultrasound and possibly fetal echocardiogram if aneuploidy is confirmed.