Incidence of Confined Placental Mosaicism for Trisomy 21
The incidence of confined placental mosaicism (CPM) for trisomy 21 is approximately 46% of cases where trisomy 21 mosaicism is detected in chorionic villus sampling (CVS). 1
Understanding Confined Placental Mosaicism
Confined placental mosaicism is characterized by the presence of chromosomally distinct cell lines that are limited to the placenta and not present in the fetus. This phenomenon occurs in approximately 2% of viable pregnancies studied by chorionic villus sampling at 9-11 weeks of gestation 2.
Key characteristics of CPM:
- Represents tissue-specific chromosomal mosaicism affecting only the placenta
- Diagnosed when chromosomal mosaicism is detected in CVS but subsequent amniocentesis shows a normal karyotype
- Can involve various chromosomes with significantly different outcomes depending on which chromosome is affected
Trisomy 21 CPM: Incidence and Significance
According to the most recent comprehensive data from a Danish study examining 528 cases of autosomal trisomy mosaicism detected in CVS:
- Among 41 cases of trisomy 21 mosaicism detected in CVS, 46% (19/41) showed fetal involvement 1
- This means that 54% of trisomy 21 mosaicism cases detected in CVS represent confined placental mosaicism
- This is significantly higher than many other chromosomes (e.g., trisomy 7 has 0% fetal involvement) 1
Clinical Implications and Risk Factors
The level of mosaicism in CVS samples appears to be clinically significant:
- Higher levels of mosaicism suggest increased likelihood of fetal involvement
- Mean mosaic level was 55% in true fetal mosaics vs. 28% in cases confined to the placenta 1
In cases of CPM (regardless of chromosome involved):
- 14% risk of delivering small-for-gestational-age neonates
- 15% risk of preterm birth (before 37 weeks)
- 22% collective risk of adverse pregnancy outcomes 1
Detection and Monitoring
Modern screening methods have improved detection of CPM:
- Introduction of combined first-trimester screening increased detection of placental mosaicism with fetal involvement
- The risk of detecting fetal involvement increased from 9% before 2004 to 15% after 2004 1
- Multiple-of-the-median (MoM) values of pregnancy-associated plasma protein A can be predictive of adverse outcomes 1
Mosaic Ratio and Pregnancy Outcomes
Recent research indicates:
- A significantly higher mosaic ratio is found in cases with adverse pregnancy outcomes compared to those with normal outcomes
- However, no clear threshold value can be established to predict outcomes, except potentially for trisomy 16 3
Clinical Considerations
When trisomy 21 mosaicism is detected in CVS:
- Follow-up amniocentesis is essential to differentiate between generalized mosaicism and CPM
- Fluorescent in situ hybridization (FISH) on uncultured amniotic fluid cells can help make this distinction 4
- Detailed ultrasound monitoring is warranted even in confirmed CPM cases due to increased risk of adverse pregnancy outcomes
Unlike some other trisomies (such as trisomy 7), trisomy 21 CPM appears to have a higher rate of fetal involvement, making careful follow-up particularly important in these cases 5.