[Karyotype analysis of amniotic fluid cells and comparison of chromosomal abnormality rate during second trimester]

To investigate the karyotypes of amniotic fluid cells and compare the incidence of chromosomal abnormality as well as to evaluate the clinical significance of abnormal karyotypes.

A total of 13 648 pregnant women came to Shanghai Jiai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University to do amniocentesis from September 1998 to November 2010, and 13 795 amniotic fluid specimens were successfully extracted and cultured, thus 13 795 fetuses received karyotype diagnosis. These fetuses were grouped according to different indications. If maternal age was ≥ 35, the fetuses were grouped into the advanced maternal age group (4065); and if maternal serum screening test revealed high-risk of trisomy 18 or trisomy 21, the fetuses were grouped into the high-risk serum screening group (6462); and those with abnormal signs of ultrasound screening were grouped into the abnormal ultrasound signs group (1539); and if either of the parents was with chromosome abnormalities, the fetus was grouped into the paternal/maternal abnormality group (108); whereas the remainder were grouped in other factors group (1621). The amniotic fluid cells were in-situ cultured on coverslips, harvested by conventional G-banded methods, and then analyzed by two doctors. In order to get rapid diagnosis, some pregnant women whose gestational age ≥ 26 weeks accepted fluorescense in situ hybridization (FISH). FISH was done on 78 uncultured amniotic fluid specimens using probes located at chromosome 13, 18, 21, X, Y. Some parents were required to analyze lymphocyte karyotype to help judging the origin of abnormal karyotype.

(1) Classification and composition of abnormal karyotypes in each group: a total of 388 abnormal karyotypes were found among 13 795 fetuses, and the abnormal rate was 2.813% (388/13 795). Of the 388 fetuses, aneuploidy was the most common pattern which was up to 59.8% (232/388); autosomal structural abnormality rate was 24.7% (96/388); mosaicism was 12.4% (48/388). Other uncommon abnormal karyotypes included marker chromosome (5/388, 1.3%), sex chromosomal structural abnormality (4/388, 1.0%) and triploid (3/388, 0.8%). Aneuploidy was the most common in most groups except the paternal/maternal abnormality group. There were four cases of rare aneuploid in the advanced maternal age group, the high-risk serum screening group and the abnormal ultrasound signs group respectively. Every type of abnormality could be found in the abnormal ultrasound signs group, and autosomal structural abnormalities were concentrated in paternal/maternal abnormality group. Mosaicism mainly distributed in the high-risk serum screening group, accounting for 20.0% (29/145) of abnormalities in this group. (2) Abnormal types and the incidence: the most common type was trisomy 21 (138/388, 35.6%), followed by autosomal balanced structural rearrangements (80/388, 20.6%), mosaicism (48/388, 12.4%) and trisomy 18 (44/388, 11.3%). Others included non-balanced autosomal structural rearrangements (16/388, 4.1%), 45, X0 (16/388, 4.1%) and 47, XXY (15/388, 3.9%). (3) Lymphocyte karyotype analysis of the couples: parents of 153 fetuses were analyzed to determine the origin of abnormal karyotype. Fifty-eight familial and 95 de novo abnormalities were found. FISH results were the same with G-banding karyotype, and two of these were trisomy 21.

Abnormal karyotype composition is different according to different maternal amniocentisis indications. There is a variety of abnormal karyotypes in the second trimester pregnancy, and the risk of fetal malformation is related with the kind of abnormal karyotype.