What is the most indicated diagnostic method for chromosomal abnormality in a fetus sample after a stillbirth at 28 weeks?

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Amniotic Fluid Sampling for Chromosomal Analysis in Stillbirth at 28 Weeks

For chromosomal analysis after stillbirth at 28 weeks, amniotic fluid sampling (amniocentesis) is the most indicated diagnostic method, as it provides reliable fetal cells for successful culture and karyotyping with established protocols that maximize diagnostic success. 1

Rationale for Amniotic Fluid as the Preferred Specimen

  • Amniotic fluid contains fetal cells shed from the fetal skin, bladder, gastrointestinal tract, and amnion, making it an excellent source for chromosomal analysis that directly reflects the fetal karyotype 1

  • The American College of Medical Genetics specifically recommends using amniotic fluid for chromosomal analysis in stillbirth cases, as it allows for successful culture and karyotyping with established protocols for specimen handling and processing 1

  • Specimens should be collected as soon as possible after diagnosis of fetal demise, with documentation of time of collection after death and storage conditions for laboratory acceptance 1

Why Other Options Are Inferior

Placental Tissue (Option D) - Not Recommended

  • 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 of using placental tissue, which may show chromosomal abnormalities not present in the fetus, or vice versa 1, 2

  • Extensive testing of placental tissue is not recommended as it may not be representative of the actual fetal chromosomes 1

  • Among 21 gestations with confined placental abnormal karyotype, the chromosomal aberration was exclusively confined to the placenta and not reflective of fetal status 2

Umbilical Cord Blood Sampling (Options A & C) - Timing Issue

  • Fetal cord blood is the standard specimen for postnatal chromosomal analysis when the infant has been delivered, but this applies to live births requiring karyotyping 3

  • In the context of stillbirth at 28 weeks, cord blood may be compromised due to autolysis and time since fetal demise, making amniotic fluid more reliable 1

  • Maternal cord blood reflects maternal chromosomes, not fetal chromosomes, making it useless for fetal genetic diagnosis 3

Clinical Implementation

  • Collect amniotic fluid at the time of delivery or immediately upon diagnosis of stillbirth to maximize cell viability for culture 1

  • Transport fresh tissue appropriately with ice or dry ice if previously frozen; avoid prolonged formalin fixation 1

  • Consider chromosomal microarray analysis (CMA) in addition to conventional karyotyping, as CMA has higher success rates in stillbirth cases 1

Common Pitfalls to Avoid

  • Do not rely solely on placental tissue due to the high risk of confined placental mosaicism giving false results 1, 2

  • Avoid specimens like hair, vitreous fluid, synovial fluid, and urine as they yield low amounts of DNA and have high contamination risk 1

  • Do not delay specimen collection, as autolysis after fetal demise reduces diagnostic success rates 1

Answer: B - Amniotic sampling

References

Guideline

Chromosomal Analysis in Fetal Stillbirth

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Fetoplacental chromosomal discrepancy.

Prenatal diagnosis, 2000

Guideline

Postnatal Chromosomal Analysis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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