Trisomy 16 is one of the most frequently encountered rare autosome abnormalities in first-trimester abortion. Full of trisomy 16 is not compatible with life, almost cases of trisomy 16 is mosaicism. Trisomy 16 mosaicism is viable and reported extensively in prenatal diagnosis, it is considered to be associated with adverse pregnancy outcome [4, 7]. And it is important for clinical counseling to exactly detected trisomy 16 mosaicism.
In the last few decades, cytogenetic technology is the main technique of prenatal diagnosis area. First trimester cytogenetic prenatal diagnosis on chorionic villi (CV) can be complicated by the detection of mosaicism, and chorionic villus sampling (CVS) is routinely used between 10–14 weeks of gestation. Trisomy 16 mosaicism is more often detected by CV analysis comparing amniocentesis. However, the result of chorionic villi analyze is not completely represented for fetus karyotype . Presently, amniocentesis is the most widely used invasive prenatal diagnosis, and it is applicable at 16–18 weeks of pregnancy. Invasive prenatal diagnosis, including CVS and amniocentesis, exists risk of miscarriage (amniocentesis is 1.7% , CVS is about ~ 0.5-2% ). Amniocentesis may bring high anxiety during the period of waiting for results. Thus, a fast and non-invasive method will be very popular for patients. NIPT basing on cell-free DNA is a new sequencing technique. It is available for gestational week greater than 12, earlier than amniocentesis. In the present study, the earliest gestational of NIPT predicted high risk of T16 was 13 weeks, which meant NIPT could serve as a fast and early prenatal screening to provide guidance for pregnancy, and termination of pregnancy is medically safer when it is performed in the earlier pregnancy.
Previously study reported that the mosaic trisomy 16 pregnancies birth weights for the live births were below the gestational age corrected mean birth weights in the general population [4, 11]. In our study, a true mosaic trisomy 16 pregnancy was continued, and the baby was born with the weight of 1.9kg which was a low weight infant. Of the 9 false positive cases, all the pregnancies were continued and all infants was born with low birth weight except case 7. This indicates that some level of below average growth is a nearly universal phenomenon in trisomy 16 mosaicism, and supports the hypothesis of undetected trisomy mosaicism as an aetiological factor in both severe and mild idiopathic intrauterine growth restriction. In addition, there were 2 premature babies in this study, which suggests that trisomy 16 pregnancies may be at higher risk for preterm delivery. Further research is needed to determine whether there is truly a higher risk of preterm delivery in an unbiased population.
As we all know, cell-free DNA comes from the apoptosis cells of cytotrophoblast, so the NIPT result shows a high risk of trisomy 16 representing there was a certain extent trisomic cells in the placenta. It is recognized that the main source of false positive results is confined placental mosaicism (CPM). CPM is a type of chromosomal mosaicism in which the chromosome abnormality is present in chorionic villi/placenta, but not in the fetus itself. In our study, 9 cases were false positive. We highly suspected that it was caused by the CPM. But, this study was a retrospective study and all the pregnancies were finished, we couldn’t obtain placenta samples to verify this point, which was a limitation of our study. Although the fetus whether it is involved or not can’t be investigated accurately by NIPT, it is considered as a useful and valuable tool for predicting placental mosaicism . In the Diane Van O with his colleagues’ research, they found that cases with abnormal NIPT T16 results most likely caused by placental aberration mostly manifests IUGR or SGA . Another research of Yi H et al showed IUGR could found in the 20% of CPM cases for T16 detected by NIPT with the evidence of placenta . And in recently study, T16 was considered as the only individual RAT worth looking for and reporting through cfDNA screening, which associated with poor outcomes . In our series of cases, all the false positive cases were low birth weight babies except case 7. We speculated low birth weight also related to CPM. But, it need more samples to verification, which will also be one of our near future research directions.
had two LOH in 16p13.3-p12.3 and 16q23.3-q24.3. The deletion sizes of fragments were 20.4 Mb and 6.1 Mb. There is no evidence that the two LOH in this area is pathogenic, but if there is a recessive genetic disease carrying genes in this section, it will increase the risk of recessive genetic disease.
In conclusion, trisomy 16 mosaicism is complex,however, it could serve as a fast and early prenatal screening to provide guidance for pregnancy and termination of pregnancy is medically safer when it is performed in the earlier pregnancy. combination cytogenetic techniques and molecular methods can accurately detect trisomy 16 mosaicism. The pregnant outcome is diverse and hard to prediction, genetic counseling should be cautious.