Ultrasound features in early pregnancy for predicting abnormal karyotype in first-trimester miscarriage

To investigate whether combining abnormal morphological features observed on ultrasound in live pregnancies that ended in a first-trimester miscarriage can predict an abnormal karyotype.

This retrospective observational cohort study was conducted at the early-pregnancy assessment unit at University College London Hospital, London, UK, between January 2017 and February 2024. Cytogenetic testing was offered routinely to patients experiencing recurrent miscarriage (at least two miscarriages) or was made available through self-funding. Eligible participants had a singleton, normally sited pregnancy with evidence of cardiac activity on at least one ultrasound scan, and were subsequently diagnosed with a first-trimester miscarriage, with successful cytogenetic testing of pregnancy tissue. Crude ultrasound measurements of gestational sac mean diameter (GSMD), yolk sac mean diameter (YSMD), crown-rump length (CRL) and embryonic heart rate from the last live ultrasound scan were converted to centiles according to established biometric reference data. Univariable and multivariable logistic regression analysis was used to assess associations between sonographic features and karyotype result.

Among 158 cases included in the final analysis, 46 (29.1%) had a normal karyotype and 112 (70.9%) had an abnormal karyotype. Those with an abnormal karyotype had a significantly higher median maternal age at conception (38 (interquartile range (IQR), 34-41) years vs 35 (IQR, 33-38) years; P = 0.0005). Median GSMD centile (P = 0.005) and median CRL centile (P = 0.003) were lower in pregnancies with an abnormal karyotype, while bradycardia (heart rate < 5^th centile) (P = 0.04) and enlarged YSMD (≥ 95^th centile) (P = 0.03) were more common in this group. A combination of four abnormal morphological features (GSMD < 5^th centile + YSMD ≥ 95^th centile + CRL < 5^th centile + bradycardia), termed the 'tetrad of aneuploidy', predicted an abnormal karyotype (odds ratio, 7.51 (95% CI, 2.41-140.22); P < 0.001), with a specificity of 100% (95% CI, 92.29-100%), for cases last examined sonographically ≤ 10 weeks' gestation.

The presence of a specific combination of abnormal early-pregnancy ultrasound markers, termed the tetrad of aneuploidy, is a strong predictor of chromosomal abnormality in pregnancies presenting initially with a live embryo. Recognition of this pattern could improve patient counseling and inform clinical decision-making in early pregnancy. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.