Postnatal Chromosomal Analysis: Fetal (Umbilical) Cord Blood is the Preferred Sample

For chromosomal analysis after delivery, collect blood from the fetal (umbilical) cord, not the maternal cord or amniotic fluid. 1

Sample Collection Algorithm

Peripheral blood from the umbilical cord (fetal side) is the standard specimen for postnatal chromosomal analysis when the infant has been delivered and requires karyotyping. 1
Blood chromosome analysis should be performed even when prenatal testing (amniocentesis or CVS) was normal, as mosaicism may have been undetected or banding resolution may be higher in postnatal preparations. 1
For newborns with dysmorphic features or suspected chromosomal abnormalities, blood karyotype with minimum 550-band resolution is indicated. 1

Maternal cord blood reflects maternal chromosomes, not fetal chromosomes, making it useless for fetal genetic diagnosis. 1
Amniotic fluid is a prenatal specimen collected before delivery via amniocentesis; after delivery, it is no longer accessible or relevant for postnatal testing. 1
The umbilical cord connects the fetus to the placenta, and blood within it is fetal blood, making it the appropriate source for fetal chromosomal analysis. 1

If peripheral blood analysis is normal but clinical suspicion remains high for chromosomal abnormality, skin fibroblast culture can detect mosaicism that may not be present in circulating T-lymphocytes. 1
Certain chromosomal abnormalities (mosaic tetrasomy 12p/Pallister-Killian syndrome, mosaic trisomy 17) are not compatible with T-cell survival and will only be detected in fibroblasts. 1
Clean skin with alcohol only—never use iodine-containing compounds, as iodine inhibits cell culture growth. 1, 2

Fresh placental tissue can be used for chromosomal microarray analysis (CMA) when collected immediately after delivery, avoiding prolonged formalin fixation. 2
However, extensive placental tissue testing is not recommended for routine clinical care of the infant, as it may not reflect the true fetal karyotype due to confined placental mosaicism. 1

Abnormal physical examination consistent with suspected aneuploidy (trisomy 13,18,21, or sex chromosome abnormalities). 1
Positive noninvasive prenatal screening (NIPS) where parents declined prenatal diagnostic testing. 1
Discordance between prenatal ultrasound findings and normal prenatal karyotype. 1

If initial blood karyotype is normal but phenotype suggests mosaicism, extended chromosome analysis with additional cell counts or interphase FISH may be warranted. 1
For suspected microdeletion/microduplication syndromes or when smaller copy-number changes were detected prenatally, CMA on blood is recommended. 1

Do not rely on placental tissue alone, as confined placental mosaicism occurs in a significant proportion of cases and may not represent the true fetal genotype. 1, 3, 4
Do not assume normal prenatal testing excludes postnatal chromosomal abnormalities—tissue-limited mosaicism or low-level mosaicism may have been missed. 1, 3
Do not test maternal blood when fetal chromosomal analysis is needed; maternal screening for mosaic sex chromosome abnormalities is typically not relevant for infant care. 1