Protocols for High-Risk Pregnancy, 7th Edition Prenatal Screening for Chromosomal Abnormalities
Protocol 5 – In this protocol, Norton reviews the pathophysiology of fetal aneuploidy and the wide range of tests for it. Included are insights into cell-free DNA testing, combined first trimester screening, nuchal translucency (NT) ultrasound, and pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin (hCG ), as well as quadruple marker screening in the second trimester in appropriate cases, and combined first and second trimester screening.
Trisomies 21, 18 and 13 are the most common autosomal trisomies. Triploidy, deletions and duplications of portions of chromosomes also occur. With the advent of chromosomal microarray analysis, it is now possible to identify submicroscopic abnormalities associated with important genetic diseases.
- All pregnant women, regardless of age, should be offered prenatal screening and diagnostic tests for the detection of chromosomal abnormalities.
- Chorionic villus sampling is usually performed between 10 and 14 weeks of gestation, while genetic amniocentesis is performed between 15 and 20 weeks.
- cfDNA test, performed after
10 weeks gestation, is over 99% accurate for detecting fetal trisomy 21 and 98% for trisomy 18 with a combined false positive rate of 0.13% to 0.25%.
- Extended cfDNA panels, which are available from some laboratories, have not been clinically validated and are not recommended.
- About 85% of trisomy 21 cases can be detected between 10 and 14 weeks of gestation, based on a combination of maternal age, NT ultrasound, PAPP-A, and hCG. NT ultrasound should only be performed by accredited sonographers and physicians.
- Ultrasound markers of aneuploidy that may be seen during the first trimester include cystic hygroma, absence of nasal bone, abnormal Doppler blood flow in the ductus venous, and abnormal blood flow through the tricuspid valve with signs of tricuspid regurgitation. However, first-trimester assessment of these secondary markers is not recommended for general population screening.
- The optimal time for a genetic ultrasound is 18-22 weeks. Identification of a major structural malformation increases the risk of trisomy 21 from
20 to 30 times and should trigger
- Combined first and second trimester screening approaches include sequential screening and integrated screening. A serum-integrated screening approach has a relatively high detection rate but provides a