Objective To analyze the results of prenatal genetic diagnosis of thalassemia in fetuses in the early stage of pregnancy in Guangxi, providing genetic counseling for prenatal and postnatal care to prevent or reduce the birth of intermediate and major thalassemia fetuses. Methods Chorionic villi were extracted from 17 196 high⁃risk fetuses that might carry thelassemia gene. After extracting their DNA, Gap⁃PCR and PCR⁃reverse dot blot (RDB) were adopted to perform diagnosis of alpha thalassemia gene and beta thalassemia gene. For couples who had been detected to carry rare thalassemia genes or had given birth to children with rare types of thalassemia, further testing of their chorionic villi was conducted using gene chips, multiplex ligation⁃dependent probe amplification, Sanger sequencing, or specific primer Gap⁃PCR method to detect alpha thalassemia gene and beta thalassemia gene. Results (1) Among 17 196 chorionic villus samples from the early stage of pregnancy, 7012 samples underwent only α⁃thalassemia gene testing, of which 5444 tested positive for α⁃thalassemia gene (5444/7012, 77.64%); furthermore, 1919 samples underwent only β⁃thalassemia gene testing, of which 1392 tested positive for β⁃thalassemia gene (1392/1919, 72.54%); in addition, 8265 chorionic villus samples underwent both α⁃thalassemia and β⁃thalassemia gene testing, of which 1844 tested positive only for β⁃thalassemia gene (1844/8265, 22.31%), 3605 tested positive only for the α⁃thalassemia gene (3605/8265, 43.62%), and 1166 tested positive for both α⁃thalassemia and β⁃thalassemia genes (1166/8265, 14.11%). In total, 13 451 chorionic villus samples tested positive for thalassemia genes (13 451/17 196, 78.22%). (2) There was no statistically significant difference in the positive detection rate of fetal chorionic villus thalassemia genes across the years from 2018 to 2023 (P>0.05). (3) A total of 22 types of base deletions/mutations in α⁃thalassemia genes were detected, among which 16 were rare deletions/mutations. Additionally, 27 types of base deletions/mutations in β⁃thalassemia genes were identified, 8 of which were not included in the spectrum of 46 β⁃thalassemia gene point mutations previously documented in the Southern Chinese population. (4) The top five α⁃thalassemia genotypes by detection rate were ⁃⁃SEA/αα, ⁃⁃SEA/⁃⁃SEA, ⁃α3.7/αα, αCSα/αα, and ⁃⁃SEA/⁃α3.7. Among these, 1471 cases of hemoglobin H disease (Hb H disease) and 1682 cases of Hb Bart’s hydrops fetalis syndrome were detected. The top five β⁃thalassemia genotypes by detection rate were βCD41⁃42/βN, βCD17/βN, β⁃28/βN, βCD17/βCD41⁃42, and βCD41⁃42/βCD41⁃42. The top five genotypes with concurrent carriage of both α⁃thalassemia and β⁃thalassemia genes were as follows: ⁃⁃SEA/αα, βCD41⁃42/βN; ⁃⁃SEA/αα, βCD17/βN; ⁃α3.7/αα, βCD41⁃42/βN; ⁃α3.7/αα, βCD17/βN; and ⁃⁃SEA/⁃⁃SEA, βCD41⁃42/βN. (5) The testing identified 2103 cases of silent α⁃thalassemia, 4959 cases of minor α⁃thalassemia, 1471 cases of Hb H disease, 1682 cases of major α⁃thalassemia, and 3156 cases of minor β⁃thalassemia, 153 cases of intermediate β⁃thalassemia, 1093 cases of major β⁃thalassemia, therein 10 fetuses were diagnosed with co⁃inheritance of intermediate⁃major β⁃thalassemia and concomitant intermediate⁃major α⁃thalassemia. (6) Continuing the pregnancy was recommended for 12 495 fetuses, while for 1821 fetuses, the couples were advised to decide on medical intervention. Medical intervention was recommended for 2880 fetuses. Ultimately, pregnancy termination was performed in 3563 cases (3563/4701, 75.79%), with 4 cases where medical intervention was recommended but pregnancy termination was not carried out. Conclusion Prenatal diagnosis of chorionic villi in Guangxi detects a relatively high proportion of intermediate and major thalassemia. This indicates that prenatal diagnosis for high⁃risk couples can provide genetic counseling for prenatal and postnatal care, contribute to reducing the birth rate of fetuses with intermediate and major thalassemia, and has profound significance for improving the overall quality of the population in Guangxi.

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