Best Sample for Chromosomal Analysis in Stillbirth
Amniotic fluid is the best sample for chromosomal analysis in stillbirth cases, as it provides the highest success rate for cell culture and karyotyping with established protocols that maximize diagnostic yield. 1
Primary Recommendation
The American College of Medical Genetics recommends amniotic fluid as the preferred specimen for chromosomal analysis in stillbirth, as it contains fetal cells shed from multiple sources (fetal skin, bladder, gastrointestinal tract, and amnion) and allows for successful culture and karyotyping. 1
Why Amniotic Fluid is Superior
- Amniotic fluid has well-established protocols for specimen handling and processing that maximize diagnostic success in stillbirth cases 1
- The cells obtained from amniotic fluid are truly representative of the fetus, unlike placental tissue which may show confined placental mosaicism 1
- Amniotic fluid can be collected at the time of delivery in stillbirth cases and provides reliable chromosomal analysis 2
Why Other Options Are Less Optimal
Placental Tissue (Option D) - Major Limitations
- Fresh placental tissue has significantly lower success rates for chromosomal analysis, particularly when formalin-fixed paraffin-embedded tissue is used, which many laboratories do not accept 1
- Confined placental mosaicism is a major limitation - the placenta may show chromosomal abnormalities not present in the fetus, or vice versa 2, 1
- Extensive testing of placental tissue is not recommended as it may not be representative of the actual fetal chromosomes 2
Fetal Cord Blood (Option C) - Postnatal Context
- Fetal cord blood is the standard specimen for postnatal chromosomal analysis when the infant has been delivered alive and requires karyotyping 3
- In stillbirth cases, cord blood may be difficult to obtain or may be of poor quality due to autolysis 4
- This option is more relevant for live births rather than stillbirth scenarios 3
Umbilical Cord Sampling (Option A) - Not Standard
- Umbilical cord tissue itself is not the standard specimen for chromosomal analysis in stillbirth 1
- While cord blood can be used, the tissue of the umbilical cord is not the preferred source 3
Modern Considerations: Chromosomal Microarray Analysis
While the question asks about traditional chromosomal analysis, it's important to note:
- Chromosomal microarray analysis (CMA) has a significantly higher success rate than conventional karyotyping in stillbirth cases (100% vs. 80%) 5
- CMA provides a relative increase in diagnosis of genetic abnormalities of 41.9% in all stillbirths compared to karyotype analysis 4
- CMA is especially valuable because it does not require live cells, making it superior for nonviable tissue 4, 6
- The incremental yield of CMA over conventional karyotyping is 4% for pathogenic copy-number variants, and 6% in structurally abnormal fetuses 6
Critical Pitfalls to Avoid
- Never rely solely on placental tissue due to confined placental mosaicism - this can lead to false positive or false negative results 1
- Avoid specimens like hair, vitreous fluid, synovial fluid, and urine as they yield low amounts of DNA and have high contamination risk 1
- Specimens should be collected as soon as possible after diagnosis of fetal demise, with documentation of time of collection and proper storage conditions 1
- If using skin fibroblasts as an alternative, clean skin with alcohol only, never iodine-containing compounds, as iodine inhibits cell culture growth 1
Answer to the Question
Among the options provided, amniotic fluid (Option B) is the best choice for chromosomal analysis in stillbirth cases due to its superior success rate, established protocols, and true representation of fetal chromosomes without the confounding factor of placental mosaicism. 1