Pitfalls of prenatal diagnosis associated with mosaicism

M R C O G PA R T 2 · S O S P O C K E T C A R D · K N O W L E D G E A R E A 5 – A N T E N ATA L C A R E

Pitfalls of Prenatal Diagnosis Associated with Mosaicism Reilly K, Doyle S, Hamilton SJ. Pitfalls of prenatal diagnosis associated with mosaicism. TOG 2023;25:28–37. doi:10.1111/tog.12850

2–3% 59% 1–2% PREGNANCIES WITH FETAL PLACENTAL CPM RISK IN CVS AFTER HIGH-RISK NIPT FOR CVS SAMPLES SHOWING MOSAICISM MOSAICISM 45,X

DO N' T-M IS S FA C TS

  1. Commonest cause of a retrospectively false positive NIPT result = confined placental mosaicism (CPM)

  2. CVS mosaicism risk after high-risk NIPT: 2% T21, 4% T18, 22% T13, 59% 45,X

  3. In CPM the fetus is normal; in TFM the fetus is abnormal – key to interpreting CVS discordance

  4. Beyond 15 weeks gestation, amniocentesis (not CVS) is the recommended invasive test given rising CPM incidence

  5. QF-PCR 1:1:1 triallelic pattern = diagnostic (meiotic-origin trisomy); biallelic pattern raises CPM suspicion → await full culture

  6. Monosomy X: false positive NIPT rate up to 91% – do not offer NIPT for sex chromosome aneuploidy

  7. CPM alone ↑risk of FGR and fetal loss – needs regular growth surveillance even if fetal karyotype normal

  8. NIPT for social fetal sexing is unethical and unreliable for sex aneuploidy – not recommended

CPM TYPES AT A GLANCE

CPM 1/2/3: fetus normal TFM 4/5/6: fetus abnormal

ABBREVIATION KEY

NIPT — non-invasive prenatal testing FGR — fetal growth restriction

cffDNA — cell-free fetal DNA FSA — fetal structural anomaly

CPM — confined placental mosaicism FASP — Fetal Anomaly Screening Programme

TFM — true fetal mosaicism PPV/NPV — positive/negative predictive value

CVS — chorionic villus sampling SCA — sex chromosome aneuploidy

QF-PCR — quantitative fluorescence polymerase chain reaction TOP — termination of pregnancy

STC/LTC — short-term culture / long-term culture RCOG — Royal College of Obstetricians and Gynaecologists

NDJ — non-disjunction NICE — National Institute for Health and Care Excellence

UPD — uniparental disomy ACGS — Association for Clinical Genomic Science

Source: The Obstetrician & Gynaecologist (TOG), RCOG journal — doi:10.1111/tog.12850

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