What is the most indicative diagnostic test for chromosomal abnormality in a fetus sample from a 28-week pregnant G1P0 patient with fetal stillbirth and absent heartbeat?

Chromosomal Analysis in Fetal Stillbirth at 28 Weeks

For a fetal stillbirth at 28 weeks, amniotic fluid sampling (Option B) is the most indicated diagnostic test for chromosomal abnormality detection.

Rationale for Amniotic Fluid Sampling

Amniotic fluid is the optimal specimen because it contains fetal cells shed from multiple fetal tissues (skin, bladder, gastrointestinal tract, and amnion), providing reliable chromosomal analysis with established protocols for specimen handling and processing that maximize diagnostic success. 1

• Amniotic fluid can be collected at the time of delivery in stillbirth cases and allows for successful culture and karyotyping 1
• The specimen provides direct fetal genetic material rather than placental tissue, which may not accurately represent fetal chromosomes 1
• Standard cytogenetic protocols for amniotic fluid are well-established and reliable for detecting chromosomal abnormalities 2

Why Other Options Are Suboptimal

Placental Tissue (Option D) - Major Limitations

Placental tissue should be avoided as the primary diagnostic specimen due to confined placental mosaicism (CPM), which occurs in approximately 1-2% of cases and may show chromosomal abnormalities not present in the fetus, or vice versa. 1, 3, 4

• Fresh placental tissue has significantly lower success rates for chromosomal analysis, particularly when formalin-fixed paraffin-embedded tissue is used 1
• Extensive testing of placental tissue is not recommended as it may not be representative of actual fetal chromosomes 1
• CVS-derived results (which are placental in origin) cannot be considered confirmatory when mosaicism is present, requiring follow-up amniocentesis 2

Umbilical Cord Blood (Option A) and Fetal Cord Sampling (Option C)

While umbilical cord blood is the standard specimen for postnatal chromosomal analysis when an infant has been delivered alive 5, in a stillbirth scenario at 28 weeks, the practical considerations differ:

• Cord blood collection may be technically feasible but amniotic fluid remains the preferred specimen based on established stillbirth evaluation protocols 1
• The distinction between "umbilical cord sampling" and "fetal cord sampling" in the question options appears redundant, as both would refer to cord blood collection

Clinical Implementation

Collect amniotic fluid at the time of delivery or immediately after diagnosis of fetal demise, with proper documentation of time of collection and storage conditions for laboratory acceptance. 1

• Fresh tissue transport requires appropriate handling with ice or dry ice if previously frozen 1
• Specimens should be collected as soon as possible after diagnosis of demise to maximize cell viability for culture 1
• Chromosomal microarray analysis (CMA) can be performed on amniotic fluid as an alternative or adjunct to conventional karyotyping for detecting smaller copy-number changes 2

Common Pitfalls to Avoid

• Do not rely solely on placental tissue due to the significant risk of confined placental mosaicism leading to false-positive or false-negative results 1, 4
• Avoid specimens like hair, vitreous fluid, synovial fluid, and urine as they yield low amounts of DNA and have high contamination risk 1
• Never use iodine-containing compounds for skin cleaning if skin fibroblasts are collected as a secondary specimen, as iodine inhibits cell culture growth 1

Answer: B - Amniotic sampling