PERINATOLOGY • Vol 24 • No. 1 • May–Aug 2023 • 31 Discussion Thalassemias are responsible for significant morbidity and mortality worldwide, more so in low- and middleincome countries.18,19 In India, approximately 12,000 children are born with β-thalassemia major annually; hence, prevention of these births is imperative.4 Cost– benefit analysis in Israel showed that the ratio of the cost of treatment to prevention was 4:1. In Iran, the ratio was 16:1.6.20-22 The ideal method of prevention is premarital screening of the population and antenatal diagnosis, as shown by many thalassemia prevention programs worldwide.23-25 However, there are several hinderances to the implementation of such programs in India because of the lack of awareness about thalassemia, a predominant rural population, and religious and social taboos. In such a scenario, antenatal counseling and screening of pregnant women and their husbands to identify at-risk couples are considered acceptable.6 Indeed, couples are most receptive to medical advice during the antenatal period, especially because it involves the safety and well-being of the fetus. In our study, 84.6% of the women agreed for the screening, which is comparable to that reported in previous studies,26,27 and 15.4% of the women refused to undergo screening tests, with the most common concern being the cost of testing. This emphasizes the need for government funding for antenatal diagnosis and prevention of hemoglobinopathies.6,26,27 There are a limited number of studies about the prevalence of BTT and feasibility of antenatal screening and diagnosis done in South India, which was the main reason for us to conduct this study. We found 3.2% and 1.6% prevalence of BTT and other hemoglobinopathy traits, respectively; this is comparable to studies done in Maharashtra, an Indian state that is geographically closer to the study center.28 The overall rate of consanguinity was high (22.9%) in our study cohort, and it was significantly high (45%) in the BTT group, which probably explains the high prevalence (38.89%) of BTT in the husbands of the women with BTT. Estimation of the HbA2 level using HPLC is the gold standard for the diagnosis of BTT; however, it is not widely available, especially in remote areas, and it is not economical. Hence, the naked eye single tube red cell osmotic fragility test and RBC indices (MCV < 80 fL, MCH < 27 pg, RBC count > 5 million/mm3) are sometimes employed as the screening methods. As in other studies, we too found a high specificity and NPV of the RBC indices in our study cohort.29,30 However, the RBC indices lack sensitivity. This is probably because of the high prevalence of iron deficiency in India, which gives rise to high false positive rates and makes HPLC testing for BTT imperative.30 An added advantage of HPLC is its ability to identify other clinically significant hemoglobin variants such as HbS, HbD, and HbE. With HPLC testing, we were able to identify 10 other hemoglobinopathy traits, in addition to BTT in 20 women in the cohort. Despite adequate counseling, only 25 of the 30 husbands agreed for hemoglobinopathy carrier screening. Husbands of 7 women with a hemoglobinopathy trait other than BTT had a normal pattern on HPLC testing, while 7 of the 18 (38.89%) husbands of women with BTT also turned out to have BTT, thus indicating a high risk of this genetic disease in their progenies. The higher rate of BTT in the husbands was probably because the couples belonged to the same community and the high rate of consanguinity. Colah et al6 also found 3 times higher prevalence of BTT in husbands of women with BTT. Of the 7 at-risk couples in our study, 6 women underwent antenatal diagnosis after genetic counseling, and the fetuses of 4 of these women were found to be homozygous for β-thalassemia; all 4 couples opted for pregnancy termination. Further, we found that all these fetuses carried the same mutation namely IVS-I-5(G>C) with genotype β+/β+ in the homozygous state, which is the most common mutation found in the Indian population.31,32 Thus, we could prevent the birth of 4 fetuses with homozygous β-thalassemia among 615 pregnancies. In our study, the approximate cost of prevention of one β-thalassemia birth was INR 1,11,750 (USD 1354). A recent study done in India reported the approximate cost of treatment of thalassemia per year to be in the range of INR 41,514 to 1,51,800 (USD 503 to 1839).33 This clearly indicates that universal screening Original Article Sampagar A, et al. Feasibility and Cost Analysis of Antenatal Screening and Diagnosis of Hemoglobinopathies
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