Abstract
Human leukocyte antigen-G (HLA-G) has been widely acknowledged to play critical roles in fetal-maternal maintenance. However, the significance of using maternal serum sHLA-G to detect prenatal chromosomal abnormality has not been investigated. In China, prenatal screening using maternal α-fetoprotein (AFP), unconjugated estriol (uE3), and free β subunit human chorionic gonadotropin (β-hCG) in the second trimester has been widely applied. In this study, we evaluated the use of sHLA-G as a screening marker, compared with traditional second trimester prenatal screening. Serum samples from 1,019 singleton women in their second trimester were assessed. Among them, 139 infants were confirmed with trisomy 21 (T21) by karyotyping, 83 were confirmed with trisomy 18 (T18), and the remaining 797 infants had no abnormalities. The sHLA-G levels in maternal sera were significantly lower in pregnant women with T18 fetuses (median: 47.8 U/ml, range: 9.8–234.2 U/ml) and significantly higher in those with T21 fetuses (median: 125.7 U/ml, range: 28.7–831.7 U/ml), compared with the normal controls (median: 106.3 U/ml, range: 50.5–1136.4 U/ml) (p < 0.001). The risk values of the screening of T21 or T18 fetuses were assessed using mean and standard deviation log10 analyte multiples of median (MoM) which showed that the predictive values of sHLA-G were the same as free β-hCG, and superior to AFP and uE3 for T18 screening. Logistic regression analysis revealed that sHLA-G MoM was the highest risk factor associated with pregnant women carrying T18 fetuses [Exp(B): 171.26, 95% CI: 36.30–807.97, p < 0.001]. Receiver operating characteristic (ROC) analysis revealed that the area under ROC curve for sHLA-G MoM was 0.915 (95% CI, 0.871–0.959, p < 0.001), for AFP MoM was 0.796 (95% CI, 0.730–0.861, p < 0.001), for free β-hCG MoM was 0.881 (95% CI, 0.829–0.934, p < 0.001), and for uE3 MoM was 0.876 (95% CI, 0.828–0.923, p < 0.001) in the T18 group. sHLA-G MoM demonstrated the best sensitivity and negative predictive value. For the first time, our findings reveal that sHLA-G is a better second trimester screening marker for the detection of T18 fetuses and the combined application of sHLA-G with AFP, free β-hCG, and uE3 could improve clinical screening for T18 fetuses.
Highlights
China is a large country, with a population size of more than 1.3 billion people
Maternal sHLA-G levels in pregnant women carrying fetuses with normal chromosomes were at a median level of 106.3 U/ml, whereas women carrying trisomy 18 (T18) fetuses had a median level of 47.8 U/ml, and those with trisomy 21 (T21) fetuses had a median level of 125.7 U/ml
Statistical analyses showed that maternal sHLA-G levels in sHLA-G and Fetal Chromosomal Abnormality women carrying T21 fetuses were dramatically higher compared to women with normal fetuses (125.7 U/ml vs. 106.3 U/ml; p < 0.001), while maternal sHLA-G levels significantly decreased in pregnant women with T18 fetuses (47.8 U/ml vs. 106.3 U/ml; p < 0.001) compared to pregnant women with normal chromosome fetuses (Figure 2)
Summary
China is a large country, with a population size of more than 1.3 billion people. With an aging population in mind, the Chinese government canceled the birth control policy on October 29, 2015. Karyotype analysis was performed on the amniotic fluid from pregnant women in the amniocentesis group, which was further divided into two groups based on the reason for puncture: high risk of abnormality due to prenatal screening and other reasons. In the control group selected from the amniocentesis group, 297 pregnant women were at high risk of abnormality by prenatal screening, 115 pregnant women were diagnosed with abnormality by ultrasound (48 cases with polyhydramnios, 11 cases with oligohydramnios, 34 cases with bright light in the fetal ventricle, and 22 cases with single umbilical artery) and 49 women had normal pregnancies. This study was approved by the Ethics Committee of Taizhou Hospital of Zhejiang Province, and all patients provided informed consent after prenatal screening, in accordance with the Declaration of Helsinki Both karyotype analysis and physical examination were the screening gold standards in this study and were performed on all fetuses or babies. A p < 0.05 was considered to be statistically significant
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