Chromosomal Analysis in Stillbirth: Specimen Selection
Amniotic fluid (Option B) is the best specimen for chromosomal analysis in a 38-week stillbirth with normal-appearing infant and placenta. 1, 2
Primary Recommendation
Amniotic fluid should be collected at the time of delivery for chromosomal analysis in stillbirth cases because it provides the highest success rate for conventional karyotyping (83%) and contains viable fetal cells that are essential for accurate genetic diagnosis. 2, 1
Why Amniotic Fluid is Superior
Success Rates by Tissue Type
- Amniotic fluid demonstrates an 83% success rate for karyotyping in stillbirth cases, significantly outperforming other tissue sources 2
- Fetal cord blood has only a 6.3% success rate for karyotyping in stillbirth, making it unreliable after fetal demise 2
- Placental tissue shows a 78% success rate but is limited by confined placental mosaicism, meaning chromosomal abnormalities in the placenta may not represent the actual fetal chromosomes 2, 1
- Fetal skin has only a 13% success rate for karyotyping 2
Technical Advantages
- Amniotic fluid contains fetal cells shed from fetal skin, bladder, gastrointestinal tract, and amnion, providing a representative sample of fetal genetic material 1
- The specimen can be collected at the time of delivery and allows for successful culture and karyotyping with established protocols 1
- Amniotic fluid is accessible even after fetal demise, unlike fetal cord blood which may be non-viable after a substantial interval has elapsed 1
Why Other Options Are Inferior
Umbilical Cord Sampling (Option A)
- While umbilical cord blood is the standard specimen for postnatal chromosomal analysis in live births, it has extremely poor viability in stillbirth cases 3, 2
- In stillbirth, fetal cord blood may be unavailable or non-viable for DNA extraction, with only a 6.3% success rate for karyotyping 1, 2
Fetal Cord Blood (Option C)
- This is essentially the same as umbilical cord sampling and suffers from the same limitations in stillbirth 2
- The 6.3% success rate makes this an unreliable choice 2
Placental Tissue (Option D)
- Confined placental mosaicism is a major limitation—the placenta may show chromosomal abnormalities not present in the fetus, or vice versa 1, 4
- Extensive testing of placental tissue is not recommended as it may not be representative of actual fetal chromosomes 1
- Fresh placental tissue has significantly lower success rates, and formalin-fixed paraffin-embedded tissue is not accepted by many laboratories 1
Modern Considerations
Chromosomal Microarray Analysis (CMA)
- If available, CMA should be performed in addition to or instead of conventional karyotyping, as it has a 100% success rate independent of tissue type and detects submicroscopic abnormalities 2, 5
- CMA provides a relative increase in diagnosis of genetic abnormalities of 41.9% in all stillbirths compared to karyotype analysis alone 6
- CMA is particularly valuable because it does not require viable cells, unlike conventional karyotyping 6
Diagnostic Yield
- Chromosomal abnormalities account for 6-17% of stillbirths, with full or partial aneuploidy prevalence of 3.9% and submicroscopic abnormalities prevalence of 5.3% 2, 7
- The most common aneuploidies in stillbirth include trisomy 16, monosomy X (45,X), trisomy 21,18, and 13 8, 7
Critical Pitfalls to Avoid
- Never rely solely on placental tissue due to confined placental mosaicism 1
- Avoid formalin-fixed tissue as it yields significantly lower success rates and is not accepted by many genetic testing laboratories 1
- Do not use fetal cord blood as first choice in stillbirth due to poor viability after fetal demise 2
- Collect specimens as soon as possible after diagnosis of demise, with documentation of time and storage conditions 1
- Clean skin with alcohol only, never iodine-containing compounds, as iodine inhibits cell culture growth if skin biopsy becomes necessary 9, 1