Cytogenetic Investigation in 136 Consecutive Stillbirths: Does the Tissue Type Affect the Success Rate of Chromosomal...

Chromosomal anomalies are a recognized cause of stillbirth, accounting for 6-17% of the cases. As a diagnostic laboratory method in this setting, conventional karyotyping has two main drawbacks: the need for viable fetal cells in a dead fetus and its limited resolution as compared to alternative techniques.

To assess the effectiveness of cytogenetic analysis in stillbirths between different testing methods and different sampled tissues.

From 2011 to 2017, 145 stillborn fetuses (defined as fetal losses after 22 weeks) were delivered in our center. The stillbirth protocol includes genetic testing by means of a karyotype, QF-PCR, or chromosomal microarray analysis (CMA), depending on the presence of fetal structural anomalies and the study time period. The success rates were compared between tests and between different sampled tissues.

Consent was granted for cytogenetic analysis in 136 stillbirths. Test success rate was 100% (38/38) for CMA independent of the sampled tissue, 99% (65/66) for QF-PCR, and 66% (65/98) for karyotyping. The success rate for karyotyping was 48% (69/145) of the total tissues samples, showing great variation according to the tissue sampled: 83% (40/48) in amniotic fluid, 78% (21/27) in the placenta, 13% (7/54) in fetal skin, and 6.3% (1/16) in fetal blood. Four full or partial aneuploidies (trisomy 9, trisomy 22, tetrasomy 18p, and monosomy X) and 2 microdeletions (del2p16.3 and del1q13.2q13.4) were found, resulting in a 3.9% (4/103) prevalence for full or partial aneuploidy and a 5.3% prevalence (2/38) for submicroscopic abnormalities.

Amniotic fluid should be the preferred tissue source in the cytogenetic analysis of stillbirth due to its high success rate. Between tests, CMA is a preferable method because of its higher test success rate, independent of the sampled tissue, and higher diagnostic yield including chromosomal and submicroscopic anomalies.