Chromosomal Analysis in Fetal Stillbirth at 28 Weeks
For chromosomal analysis in a fetal stillbirth at 28 weeks gestation, amniotic fluid sampling (amniocentesis) is the most indicated diagnostic method, as it provides reliable fetal cells for karyotyping and can be performed immediately after diagnosis of demise. 1
Rationale for Amniotic Fluid Sampling
Amniotic fluid contains fetal cells shed from the fetal skin, bladder, gastrointestinal tract, and amnion, making it an excellent source for chromosomal analysis. 2 These cells can be successfully cultured and karyotyped to detect chromosomal abnormalities that may have contributed to the stillbirth. 3, 4
Key Advantages of Amniocentesis in This Clinical Scenario:
Amniocentesis can reliably detect all types of chromosomal abnormalities including aneuploidies (trisomy 21,18,13), sex chromosome abnormalities, structural rearrangements, and mosaicism. 5, 4
The procedure can be performed immediately after diagnosis of fetal demise at 28 weeks, with specimens successfully cultured in over 97% of cases. 3
Amniotic fluid AFP results can be reliably interpreted between 13 to 25 weeks of gestation, providing additional diagnostic information if needed. 2
Why Other Options Are Less Optimal:
Placental Tissue (Option D):
While placental tissue can be used for chromosomal analysis, fresh placental tissue must be collected immediately after delivery and transported appropriately, avoiding prolonged formalin fixation, as formalin-fixed paraffin-embedded tissue has low success rates. 1 The risk of confined placental mosaicism makes placental tissue less reliable than amniotic fluid for determining true fetal karyotype. 6
Umbilical Cord/Fetal Cord Sampling (Options A & C):
Umbilical cord blood sampling would require cordocentesis, which is technically more challenging in a stillbirth scenario and carries higher procedural risks. 5 After fetal demise, obtaining viable cells from cord blood becomes increasingly difficult with time elapsed since death.
Fetal Skin Fibroblasts:
Although skin fibroblasts are particularly valuable for detecting mosaicism according to the American College of Medical Genetics 1, this requires delivery and tissue collection, which may not be immediately available at the time of stillbirth diagnosis.
Critical Technical Considerations:
Specimens should be collected as soon as possible after diagnosis of demise, with documentation of time of collection after death and storage conditions for laboratory acceptance. 1
Amniotic fluid cells can be successfully cultured using conventional G-banded methods with analysis by experienced cytogeneticists. 4
For rapid diagnosis if needed, fluorescence in situ hybridization (FISH) can be performed on uncultured amniotic fluid cells to detect common aneuploidies (chromosomes 13,18,21, X, Y) within 24 hours. 5, 4
Expected Diagnostic Yield:
Among pregnancies undergoing amniocentesis for various indications, the overall chromosomal abnormality detection rate is approximately 2.8%, with aneuploidy being the most common pattern (59.8% of abnormalities), followed by autosomal structural abnormalities (24.7%) and mosaicism (12.4%). 4 In stillbirth cases specifically, the yield of chromosomal abnormalities is expected to be significantly higher.
The most common abnormality detected is trisomy 21 (35.6% of all abnormalities), followed by autosomal balanced structural rearrangements (20.6%), mosaicism (12.4%), and trisomy 18 (11.3%). 4