Objectives: To develop a machine learning (ML)-based framework using red blood cell (RBC) parameters for the prediction of the α⁺-thalassemia trait (α⁺-thal trait) and to compare the diagnostic performance with a conventional method using a single RBC parameter or a combination of RBC parameters. Methods: A retrospective study was conducted on possible couples at risk for fetus with hemoglobin H (Hb H disease). Subjects with molecularly confirmed normal status (not thalassemia), α⁺-thal trait, and two-allele α-thalassemia mutation were included. Clinical parameters (age and gender) and RBC parameters (Hb, Hct, MCV, MCH, MCHC, RDW, and RBC count) obtained from their antenatal thalassemia screen were retrieved and analyzed using a machine learning (ML)-based framework and a conventional method. The performance of α⁺-thal trait prediction was evaluated. Results: In total, 594 cases (female/male: 330/264, mean age: 29.7 ± 6.6 years) were included in the analysis. There were 229 normal controls, 160 cases with the α⁺-thalassemia trait, and 205 cases in the two-allele α-thalassemia mutation category, respectively. The ML-derived model improved the diagnostic performance, giving a sensitivity of 80% and specificity of 81%. The experimental results indicated that DeepThal achieved a better performance compared with other ML-based methods in terms of the independent test dataset, with an accuracy of 80.77%, sensitivity of 70.59%, and the Matthews correlation coefficient (MCC) of 0.608. Of all the red blood cell parameters, MCH < 28.95 pg as a single parameter had the highest performance in predicting the α⁺-thal trait with the AUC of 0.857 and 95% CI of 0.816–0.899. The combination model derived from the binary logistic regression analysis exhibited improved performance with the AUC of 0.868 and 95% CI of 0.830–0.906, giving a sensitivity of 80.1% and specificity of 75.1%. Conclusions: The performance of DeepThal in terms of the independent test dataset is sufficient to demonstrate that DeepThal is capable of accurately predicting the α⁺-thal trait. It is anticipated that DeepThal will be a useful tool for the scientific community in the large-scale prediction of the α⁺-thal trait.

A total of 30 hydropic fetuses, including 25 cases from published reports and 5 from our own series, were reviewed, validated, and analyzed. This review yielded the following key findings: (1) Unlike most cases of nonimmune hydrops fetalis (NIHF), hydrops caused by syphilis is not only preventable but also treatable, with complete resolution possible when appropriately managed. (2) Syphilis-associated hydrops carries a poor prognosis if timely and appropriate treatment is not administered. (3) Based on limited data, intravenous penicillin G is probably more effective than intramuscular benzathine penicillin in treating hydropic fetuses. (4) Middle cerebral artery peak systolic velocity (MCA-PSV) measurements are increasingly used as a reliable and noninvasive tool for assessing fetal anemia, determining the need for intrauterine transfusion (IUT), and monitoring treatment response. (5) A significant number of cases did not receive prenatal treatment due to false-negative serologic results caused by the prozone effect, as well as the omission of syphilis from the differential diagnosis of NIHF, leading to missed prenatal diagnoses. (6) IUT may help mitigate cellular damage in developing vital organs caused by anemic hypoxia, particularly while awaiting the effects of medical treatment. In conclusion, the modern approach to managing this ancient disease includes: (1) prioritizing intensive intravenous penicillin G therapy over conventional intramuscular benzathine penicillin G; (2) utilizing MCA-PSV in conjunction with other indicators of anemia to monitor its severity; and (3) implementing IUT to prevent anemic hypoxic injury in cases where the hematocrit falls below 30%.

Ring chromosome 15, a rare genetic disease, is very rarely prenatally diagnosed. We present a unique case of fetal ring chromosome 15 with ultrasound findings at 32 weeks of gestation including congenital diaphragmatic hernia, hypoplasia of the aorta with persistent left SVC, growth restriction, clubfeet and scoliosis. We also performed an analytical literature review of prenatal sonographic findings of the disease. This review suggests that ring chromosome 15 has a relatively specific sonographic pattern that could facilitate early detection. The specific sonographic features of ring chromosome 15 include fetal growth restriction, congenital diaphragmatic hernia, abnormal limb postures, cardiac defects, low-set ears and other less frequent, non-specific anomalies that can be identified in more than 50% of cases.