Is confined placental mosaicism (CPM) or fetal mosaicism more common?

Confined Placental Mosaicism is Significantly More Common Than Fetal Mosaicism

Confined placental mosaicism (CPM) occurs in 1-2% of pregnancies, while true fetal mosaicism is much rarer, confirmed in only about 2.5% of cases where placental mosaicism is detected. 1

Understanding Mosaicism in Pregnancy

Mosaicism refers to the presence of two or more genetically different cell lines within a tissue. In the context of pregnancy, this can occur in:

1. Confined Placental Mosaicism (CPM):

   • Chromosomal abnormalities present only in placental tissue
   • Occurs in approximately 1-2% of viable pregnancies 1
   • Detected in chorionic villus sampling (CVS) at 9-11 weeks 2
   • The fetus typically has a normal karyotype

2. True Fetal Mosaicism (TFM):

   • Chromosomal abnormalities present in both the fetus and placenta
   • Much rarer than CPM
   • When mosaicism is detected in CVS, follow-up amniocentesis confirms true fetal mosaicism in only a small percentage of cases

Epidemiological Evidence

The 2023 ACMG guideline provides clear statistics on the relative frequency:

• Mosaicism identified at CVS occurs in 1-2% of pregnancies 1
• Of these, "the large majority represent confined placental mosaicism" 1
• In a large series of 52,673 CVS cases, only 8 of 316 (2.53%) mosaic rare autosomal trisomies identified at CVS were confirmed through amniocentesis 1

This demonstrates that CPM is approximately 40 times more common than true fetal mosaicism when mosaicism is detected in placental tissue.

Clinical Implications

Diagnostic Testing Considerations

When mosaicism is detected through CVS or non-invasive prenatal testing (NIPT):

• Follow-up amniocentesis is recommended to distinguish between CPM and TFM 1
• A mosaic result on CVS cannot be considered confirmatory of an affected fetus 1
• Certain aneuploidies, including trisomy 13 and monosomy X, are more likely to be found in mosaic form on CVS 1

Pregnancy Outcomes

CPM is not benign and has been associated with:

• Increased risk of intrauterine growth restriction (IUGR) 3, 4
• Studies show CPM occurs in 15.7-25% of IUGR cases compared to only 1.4-8.3% in normal growth controls 3, 4
• Recent evidence (2024) indicates 42.6% of CPM cases show adverse perinatal outcomes 5
• Higher mosaic ratios correlate with worse pregnancy outcomes, though clear thresholds are difficult to establish 5

Technical Considerations

When interpreting mosaicism:

• Microarray analysis provides a relative level of copy number across cells but cannot determine cell-by-cell copy number variations 1
• Different cell layers in chorionic villi (syncytiotrophoblast, cytotrophoblast, mesenchymal core) may have different genetic compositions 1
• Mosaicism in prenatal samples may represent culture artifact (pseudomosaicism), true fetal mosaicism, or CPM 1

Clinical Management Algorithm

1. When mosaicism is detected on CVS or NIPT:

   • Always proceed with follow-up amniocentesis to distinguish CPM from TFM
   • Do not rely on CVS results alone for definitive diagnosis

2. If CPM is confirmed (normal amniocentesis):

   • Implement increased fetal surveillance for growth restriction
   • Monitor for other pregnancy complications (preterm birth, hypertensive disorders)
   • Consider the specific chromosome involved (e.g., trisomy 16 has higher risk)

3. If TFM is confirmed (abnormal amniocentesis):

   • Provide genetic counseling regarding the specific chromosomal abnormality
   • Management depends on the specific chromosomal abnormality and level of mosaicism

Common Pitfalls to Avoid

• Do not assume that mosaicism detected on CVS represents the fetal karyotype
• Do not consider a normal pregnancy outcome guaranteed with CPM, as it increases risk for complications
• Do not rely solely on NIPT for diagnosis of mosaicism, as it cannot distinguish between maternal, placental, and fetal contributions to cell-free DNA
• Do not forget that CVS and NIPT both analyze placental DNA, so they may detect the same placental mosaicism rather than confirming each other