Detection of trisomy 21 in the first trimester of pregnancy combined assessment of PAPP-A, free β-hCG and nuchal translucency

Abstract

Background: Prenatal diagnosis of Down syndrome (DS) is based on non-invasive and invasive methods. Non-invasive, genetic testing of fetal DNA is expensive, while biochemical methods remain valuable. Amniocentesis is the most commonly used invasive diagnostic method, with a diagnostic accuracy of 99.8% and a miscarriage risk of less than 1%1. Trisomy 21 (T21), also known as Down syndrome, is the most common chromosomal disorder worldwide, occurring in 1 in 319-1000 live births2. Duplication of chromosome 21 is the most frequently diagnosed result of abnormal chromosome segregation, occurring in 95%3. Aim: The aim of the study was to investigate the relationship between of the fetal nuchal translucency values and multiples of the normal median of PAPP-A, free β-hCG levels in antenatal detection of trisomy 21 in the first trimester of pregnancy. Materials and Methods: The study was conducted between 2020 and 2022 among 236 pregnant women who underwent examination for as high-risk of trisomy 21 (<1:250) at 11+0-13+6 weeks of pregnancy, and whose fetal karyotype was analyzed by amniocentesis in the genetic laboratory of the National Health Center. In the combined screeing method, biochemical markers such as pregnancy-associated serum protein A (PAPP-A) and free chorionic gonadotropin (β-hCG) and NT values were analyzed for the predefined ranges. Results: 60.86% of trisomy 21 had PAPP-A MoM below 0.5 and 39.12% had elevated free β-hCG MoM>1.5. The β-hCG MoM (> 1.5) and PAPP-A MoM (< 0.5) selected ranges (typical form) of trisomy21 showed that NT levels were not increased in all fetuses with trisomy 21 whereasTrisomy 21 was present in only 14.28% of cases. In 69.56% of cases, there was an atypical form. Conclusion: Free β-hCG MoM, PAPP-A and ultrasound-based nuchal translucency values were independent markers for the diagnosis of trisomy 21. Combined biochemical and ultrasound evaluation is essential for the detection of trisomy 21 in the first trimester of pregnancy. ​​