Severity-dependent risk of chromosomal abnormalities in fetuses with short long bones: a 10-year cohort study

Short long bones (SLBs) detected prenatally are associated with chromosomal abnormalities; however, risk stratification according to phenotypic severity and associated anomalies remains incompletely defined.

In this 10-year retrospective cohort study (2015-2024), 790 fetuses with SLBs (≥ 2 SD below the gestational mean) underwent conventional karyotyping (CS) and/or chromosomal microarray analysis (CMA). SLBs were categorized by severity (mild, moderate, severe) and presentation (isolated vs. non-isolated). Detection rates were compared across subgroups.

Chromosomal abnormalities were identified in 38/790 fetuses (4.8%), including 2.2% numerical and 2.7% structural aberrations. The detection rate increased with limb shortening severity (3.1% in mild, 8.2% in moderate, and 8.8% in severe cases; P = 0.005). Non-isolated SLBs were associated with a significantly higher abnormality rate than isolated cases (7.7% vs. 2.2%, P < 0.001). CMA detected clinically relevant submicroscopic copy number variants missed by karyotyping, whereas karyotyping identified balanced rearrangements not detectable by CMA.

Chromosomal abnormalities represent a measurable but limited proportion of fetuses with SLBs, with risk significantly influenced by phenotypic severity and coexisting anomalies. These findings support a risk-stratified framework for prenatal genetic evaluation and may inform clinical counseling and management strategies.