Objective: The aim of the study was to compare the performances of cardiothoracic diameter ratio (CTR) and middle cerebral artery peak systolic velocity (MCA-PSV) in predicting fetal hemoglobin (Hb) Bart’s disease and identify the best CTR cut-off for each gestational period. Methods: Pregnancies at risk of fetal Hb Bart’s disease (gestational ages of 12–36 weeks) were prospectively recruited to undergo ultrasound examination. The measurements of CTR and MCA-PSV were performed and recorded before invasive diagnosis. Results: During the study period (2005–2019), a total of 1,717 pregnancies at risk of fetal Hb Bart’s disease met the inclusion criteria and were available for analysis, including 329 (19.2%) fetuses with Hb Bart’s disease. The mean gestational age at the time of diagnosis was 19.30 ± 5.6 weeks, ranging from 12 to 36 weeks. The overall performance of CTR Z-scores is superior to that of MCA-PSV multiple of median (MoM) values; area under curve of 0.866 versus 0.711, p value <0.001. The diagnostic indices of CTR and MCA-PSV are increased with gestational age. Based on receiver operating characteristic curves of CTR Z-scores, the best cut-off points of CTR at 12–14, 15–17, 18–20, 21–23, and ≥24 weeks are 0.48, 0.49, 0.50, 0.51, and 0.54, respectively. The best cut-off of MCA-PSV is 1.3 MoM, giving the best performance at 21–23 weeks with a sensitivity of 91.8% and specificity of 85.5%. Conclusion: The performance of CTR is much better than MCA-PSV in predicting fetal anemia caused by Hb Bart’s disease. Nevertheless, whether this can be reproduced in anemia due to other causes, like isoimmunization, is yet to be explored.

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