To evaluate the values of ultrasound testing markers for prediction of fetal severe α-thalassemia in the first trimester pregnancy(11^{+ 0}-13^{+ 6} weeks of gestational age).

From January 3, 2015 to December 30, 2016, a total of 282 cases of fetuses with singleton pregnancy whose parents both were mild α-thalassemia gene carriers and received regular prenatal examinations at the Guangzhou Women and Children′s Medical Center were selected as research subjects. All the fetuses received ultrasound screening in the first trimester pregnancy. And ultrasound testing markers including fetal cardiothoracic ratio (CTR), peak systolic velocity of middle cerebral artery (MCA-PSV), and placental thickness (PT) were prospectively assessed and recorded. For those with positive results of the above-mentioned ultrasound testing markers, chorionic puncture or amniocentesis was used to detect α-thalassemia gene and diagnose fetal severe α-thalassemia; for those with negative results, they were followed up until birth, and the umbilical cord blood hemoglobin (Hb) electrophoretic analysis was performed routinely after birth to diagnose whether the fetus was severe α-thalassemia. According to the α-thalassemia gene detection results or Hb electrophoretic analysis results, all fetuses were divided into severe group (homozygous α-thalassemia-1 fetus) and control group (mild α-thalassemia fetus and healthy fetus). The values of fetal CTR, MCA-PSV and PT in the first trimester pregnancy of severe group and control group were compared by independent-samples t test. The receiver operator characteristic (ROC) curves of fetal CTR, MCA-PSV and PT of ultrasound testing in the first trimester pregnancy for prediction of fetal severe α-thalassemia were drawn, and the area under ROC curve (ROC-AUC) were calculated. The optimal critical values of fetal CTR, MCA-PSV and PT in the first trimester pregnancy for prediction of fetal severe α-thalassemia were obtained when the Youden index reaching the maximum value. And their sensitivities, specificities and likelihood ratios were calculated. The procedures followed in this study were in accordance with the ethical standards established by the Human Subjects Trial Committee of Guangzhou Women and Children′s Medical Center, and this study was approved by this committee (Approval No. 2014120106).

①According to the follow-up results of 282 fetuses, 61 cases (21.6%) were diagnosed as severe α-thalassemia fetus and included in severe group (n=61), and 221 cases as mild α-thalassemia or healthy fetus were included in control group (n=221). There was no significant difference between the two groups in general clinical data such as the ratio of different gestational age (P>0.05). ②The CTR, MCA-PSV and PT values in the first trimester pregnancy of fetuses in severe group were (0.52±0.04), (1.61±0.58) cm/s, (1.30±0.20) mm respectively, which were significantly higher than those of control group (0.44±0.03), (1.20±0.30) cm/s, (1.00±0.30) mm, and there were significant differences between two groups (t=19.470, 9.320, 6.700; all P<0.001). ③ROC curve analysis showed that the ROC-AUC of fetal CTR, MCA-PSV and PT values in the first trimester pregnancy for prediction of fetal severe α-thalassemia were 0.949 (95%CI: 0.909-0.990, P<0.001), 0.811 (95%CI: 0.741-0.811, P<0.001), 0.778 (95%CI: 0.720-0.856, P<0.001) respectively. According to the maximum principle of Yoden index, the optimal cut-off values of CTR, MCA-PSV and PT in the first trimester pregnancy for prediction of fetal severe α-thalassemia were 0.48, 1.50 MoM and 1.50 MoM (multiples of the median), and the sensitivities for prediction of fetal severe α-thalassemia were 92.7%, 48.2% and 24.6% respectively, and the specificities were 95.5%, 90.8% and 94.1% respectively, and the likelihood ratios were 20.6, 5.2 and 5.0 respectively.

The ultrasound testing markers in the first trimester pregnancy can effectively predict fetal severe and non-severe α-thalassemia, and the most sensitive marker was fetal CTR. For fetuses with high-risk of severe α-thalassemia, if all the ultrasound testing markers are normal in the first trimester pregnancy, the probability of severe α-thalassemia is low.