At midpregnancy, sonographic markers can effectively differentiate normal pregnancies from those with fetal hemoglobin Bart disease. Among couples at risk with no sonographic markers, the risk of having an affected child is nearly eliminated. The most sensitive marker was the cardiothoracic ratio, followed by placental thickness.

Prenatal diagnosis of severe thalassaemia is conventionally diagnosed by fetal DNA analysis but it can not be widely used due to its drawbacks of high cost and technical effort. This prospective study describes a new prenatal strategy in preventing severe thalassaemia by a more simple and inexpensive way. The strategy included: (1) genetic counselling; (2) identification of pregnancies at risk by retrospective screening (history of known risk) and prospective screening for asymptomatic women; (3) cordocentesis at 16-22 weeks' gestation; (4) fetal blood analysis with high performance liquid chromatography (HPLC); (5) termination of affected pregnancy. The prospective screening consisted of 2 min osmotic fragility (OF) and HbE screening test in women with no risk, and testing the husbands of the women with a positive result. If both of the couple had a positive result, the diagnostic test (HbA(2) level and PCR alpha-thal 1) for the carrier was needed. A pregnancy in which both of the couple were carriers was considered at risk. This strategy identified 181 and 108 couples at risk by prospective (from 7954 pregnancies) and retrospective screening, respectively. Two hundred and forty-two underwent cordocentesis, 108 from retrospective screening and 134 from prospective screening, and 62 were proven to have severe thalassaemia (29 and 33 in retrospective and prospective screening, respectively). The strategy identified nearly all, if not all, fetuses with severe thalassaemia without false positives among the screened couples. In conclusion, the strategy proves to be highly effective in the control of severe thalassaemia.

The objective of this study is to evaluate the efficacy of sonographic cardiothoracic ratio at midpregnancy in predicting fetal hemoglobin Bart disease. Among 17,254 pregnant women screened for severe thalassemia between June 1994 and November 1998, 345 pregnant women at risk for having a fetus with hemoglobin Bart disease underwent ultrasonographic examination and cordocentesis at 18 to 21 weeks' gestation. Before cordocentesis, the cardiothoracic ratio was determined and recorded. The definite fetal diagnosis was based on fetal blood analysis with high performance liquid chromatography. Among 345 pregnancies in which sonographic examination and cordocentesis were performed, 70 fetuses were affected by hemoglobin Bart disease. The mean cardiothoracic ratio was significantly higher than that of unaffected fetuses (0.55 versus 0.45, Student's t-test, P<0.001). The sensitivity and specificity of the cardiothoracic ratio in prediction were calculated for various cutoff values. On the basis of the receiver operating characteristic curve, the best cutoff value was 0.50 (greater than 0.50 considered abnormal), giving the sensitivity of 98.6% and a specificity of 98.9%. In conclusion, the cardiothoracic ratio has very high accuracy in predicting hemoglobin Bart disease in pregnancies at risk. This finding suggests that invasive diagnostic method should be reserved for only the fetuses who have a cardiothoracic ratio of 0.5 or more; however, further studies are needed to confirm this observation.

At 11 to 14 weeks of gestation, sonographic markers can effectively differentiate affected from unaffected pregnancies. The most sensitive marker was CT ratio plus MCA-PSV. Of couples at risk with no any sonographic markers, the risk of having an affected fetus is nearly eliminated.

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