Cytogenetic analysis of 3387 umbilical cord blood in pregnant women at high risk for chromosomal abnormalities

Abstract

Background: Cordocentesis in our practice is most commonly indicated for rapid karyotyping in the second or third trimester and is regarded as the gold standard for foetal chromosomal aberration diagnosis in pregnancies at high risk for chromosomal abnormalities. In this study, we investigated 3387 umbilical cord blood samples for karyotyping from pregnant women who underwent cordocentesis and explored the pregnancy outcomes of foetal sex chromosome mosaicism and chromosomal polymorphism. Results: Out of the 3387 samples, 182 abnormal karyotypes were detected. Ultrasound soft markers were the most common prenatal diagnostic indication, but the detection rate of abnormal karyotypes was 2.02%, while it was 46.97% in the genome-wide NIPT-positive group. The rate of aneuploidy was lower in the soft marker group than in the other groups. Out of 16 cases with sex chromosome mosaicism, three pregnant women with foetuses with a lower proportion of sex chromosome mosaicism delivered healthy foetuses; the foetus with karyotype 46,X,i(Y)(q10)[20]/45, X[6] showed unclear genitals. Three foetuses with chromosomal polymorphisms had postnatal disorders. Conclusions: NIPT should not be recommended as the first-tier screening for chromosomal aberration for pregnancies with ultrasound soft markers or pathological ultrasound findings, but NIPT can be considered an acceptable alternative for pregnancies with contraindications to cordocentesis or the fear of procedure-related foetal loss. Mosaicism found in amniotic fluid cell culture requires further cordocentesis for karyotype confirmation, and the continuation of pregnancy is safe when a normal karyotype is identified in foetal blood culture. Further genetic testing and parental karyotype analysis are needed for foetal chromosomal polymorphisms.

Retrospective cohort study of pregnancy terminations before the 24th week of pregnancy

“…The number of patients who received invasive karyotyping and were diagnosed with chromosomal anomalies of the fetus after positive prenatal screening tests is 146 (20.6%). This rate was similar with the other publications in the literature [14,15].…”

Chromosomal mosaicism detected by karyotyping and chromosomal microarray analysis in prenatal diagnosis

“…Others hold the opposite view that mosaicism in AF requires further cordocentesis for confirmation, and that the pregnancy is safe when a normal result is identified in CB. 29 There are a few drawbacks in our study. The first is our uncompleted long-term follow-up may lead to information loss for postnatal phenotypes.…”

“…Their results showed that CB and placentas were prone to a negative result when compared with AF, and array‐CGH on uncultured CB or FISH on cultured CB may be better to use for prenatal diagnosis. Others hold the opposite view that mosaicism in AF requires further cordocentesis for confirmation, and that the pregnancy is safe when a normal result is identified in CB 29 . These findings demonstrate that increased risk in genetic counselling is due to discordant CM from different specimens or testing methods.…”

Ultrasound markers of chromosome aberrations on routine second trimester screening

“…Although not pathological per se, the incidence of ultrasound soft markers is higher in fetuses with chromosomal aberrations. (SUN et al, 2020;ALI et al, 2012;PARK et al, 2015) Major abnormalities are observed in 25% of fetuses with chromosomal abnormalities, whereas one or more soft markers may be observed in at least 50% of affected fetuses (RANIGA et al, 2006). The finding of one major structural malformation or two or more soft markers increases the risk for chromosomal aberrations in fetuses, and in these cases there is a necessity for genetic informing of patients, and invasive prenatal testing (BENN et al, 2015).…”