Results of complex prenatal examinations in cases of chromosome 21 imbalance in the fetus

Abstract

Purpose - to characterize the cases of chromosome 21 imbalance in fetuses of high-risk pregnant women, to describe prenatal cytogenetic diagnosis and associated ultrasound findings - structural anomalies and soft markers. Materials and methods. The results of complex prenatal examination of high-risk pregnant women in the Department of Fetal Medicine of the SI “Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine” during 5 years period were analyzed: results of ultrasound and cytogenetic exams of 200 cases of chromosome 21 imbalance in the fetus. Results. Among 4,748 prenatal cytogenetic testing of fetuses of high-risk women abnormal karyotypes with an imbalance of chromosome 21 were found in 200 (4.21%) cases. In the majority of cases Down's syndrome (DS) was diagnosed (n=199; 99.5%), in 1 (0.2%) case - deletion of chromosome 21. In DS, regular trisomy of chromosome 21 was found in 191 (95.97%) cases, translocant forms - in 5 (2.51%) cases, in 1 (0.5%) case there was there was an additional sex chromosome, and in 1 (0.5%) - a variant with two cell lines. In 1 (0.5%) case limited placental mosaicism was present, with a false negative result that required verification by the analysis of fetal lymphocytes obtained during cordocentesis. Advanced maternal age (≥35 years) was registered in less than half of fetal DS cases (n=92/199, 46.2%). The main indications for invasive procedures and their types are described. It was demonstrated that ultrasound findings (structural anomalies and/or “soft” markers for chromosomal pathology) were present in 78% of fetal chromosome 21 imbalance; nevertheless in 22% ultrasound findings were absent, and the indication for invasive procedures were advanced maternal age or isolated changes of biochemical markers. Conclusions. Chromosome 21 imbalance in fetuses is mainly represented by trisomy, cases of chromosome 21 deletion are extremely rare. Targeted ultrasound examination is important for screening and diagnosis of fetal chromosomal abnormalities. High-risk pregnant women shouldn’t be reassured in case of “normal” ultrasound exam results. Under certain conditions, it is advisable to perform placental biopsy in the II trimester of pregnancy, but only in specialized tertiary centers or departments. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.