Abstract：
OBJECTIVE: To explore the association between the concentration of maternal serum biomarkers and the risk of fetal carrying chromosome copy number variants (CNVs).
METHODS: Pregnant women identified as high risk in the second-trimester serological triple screening and underwent traditional amniotic fluid karyotype analysis, along with comparative genomic hybridization array (aCGH)/copy number variation sequencing (CNV-seq), were included in the study. We divided the concentration of serum biomarkers, free beta-human chorionic gonadotropin (fβ-hCG), alpha fetoprotein (AFP) and unconjugated estriol (uE3), into three levels: abnormally low, normal and abnormally high. The prevalence of abnormally low, normal and abnormally high serum fβ-hCG, AFP and uE3 levels in pregnant women with aberrant aCGH/CNV-seq results and normal controls was calculated.
RESULTS: Among the 2877 cases with high risk in the second-trimester serological triple screening, there were 98 chromosome abnormalities revealed by karyotype analysis, while 209 abnormalities were detected by aCGH/CNVseq (P＜0.001) . The carrying rate of aberrant CNVs increased significantly when the maternal serum uE3 level was less than 0.4 multiple of median (MoM) of corresponding gestational weeks compared to normal controls, while the carrying rate of aberrant CNVs decreased significantly when the maternal serum fβ-hCG level was greater than 2.5 MoM compared to normal controls. No significant difference was found in the AFP group.
CONCLUSIONS: Low serum uE3 level (<0.4 MoM) was associated with an increased risk of aberrant CNVs.
METHODS: Pregnant women identified as high risk in the second-trimester serological triple screening and underwent traditional amniotic fluid karyotype analysis, along with comparative genomic hybridization array (aCGH)/copy number variation sequencing (CNV-seq), were included in the study. We divided the concentration of serum biomarkers, free beta-human chorionic gonadotropin (fβ-hCG), alpha fetoprotein (AFP) and unconjugated estriol (uE3), into three levels: abnormally low, normal and abnormally high. The prevalence of abnormally low, normal and abnormally high serum fβ-hCG, AFP and uE3 levels in pregnant women with aberrant aCGH/CNV-seq results and normal controls was calculated.
RESULTS: Among the 2877 cases with high risk in the second-trimester serological triple screening, there were 98 chromosome abnormalities revealed by karyotype analysis, while 209 abnormalities were detected by aCGH/CNVseq (P＜0.001) . The carrying rate of aberrant CNVs increased significantly when the maternal serum uE3 level was less than 0.4 multiple of median (MoM) of corresponding gestational weeks compared to normal controls, while the carrying rate of aberrant CNVs decreased significantly when the maternal serum fβ-hCG level was greater than 2.5 MoM compared to normal controls. No significant difference was found in the AFP group.
CONCLUSIONS: Low serum uE3 level (<0.4 MoM) was associated with an increased risk of aberrant CNVs.
摘要：
目的：探讨母体血清生物标志物浓度与胎儿携带染色体拷贝数变异（CNVs）风险之间的关系。
方法：在妊娠中期血清学三联筛查中确定为高危孕妇，并进行传统羊水核型分析，随着比较基因组杂交阵列（aCGH）/拷贝数变异测序（CNV-seq），包括在研究中。我们划分了血清生物标志物的浓度，游离β-人绒毛膜促性腺激素（fβ-hCG），甲胎蛋白（AFP）和非结合雌三醇（uE3），分为三个级别:异常低，正常和异常高。患病率异常低，正常和异常高的血清fβ-hCG，计算aCGH/CNV-seq结果异常的孕妇和正常对照组的AFP和uE3水平。
结果：在妊娠中期血清学三联筛查的2877例高风险患者中，通过核型分析发现了98个染色体异常，aCGH/CNVseq共检出209例异常(P＜0.001)。与正常对照组相比，当母体血清uE3水平低于相应孕周的中位数（MoM）的0.4倍时，异常CNV的携带率显着增加，与正常对照组相比，当母体血清fβ-hCG水平大于2.5MoM时，异常CNV的携带率显着降低。AFP组无显著差异。
结论：低血清uE3水平(<0.4MoM)与异常CNVs的风险增加相关。
方法：在妊娠中期血清学三联筛查中确定为高危孕妇，并进行传统羊水核型分析，随着比较基因组杂交阵列（aCGH）/拷贝数变异测序（CNV-seq），包括在研究中。我们划分了血清生物标志物的浓度，游离β-人绒毛膜促性腺激素（fβ-hCG），甲胎蛋白（AFP）和非结合雌三醇（uE3），分为三个级别:异常低，正常和异常高。患病率异常低，正常和异常高的血清fβ-hCG，计算aCGH/CNV-seq结果异常的孕妇和正常对照组的AFP和uE3水平。
结果：在妊娠中期血清学三联筛查的2877例高风险患者中，通过核型分析发现了98个染色体异常，aCGH/CNVseq共检出209例异常(P＜0.001)。与正常对照组相比，当母体血清uE3水平低于相应孕周的中位数（MoM）的0.4倍时，异常CNV的携带率显着增加，与正常对照组相比，当母体血清fβ-hCG水平大于2.5MoM时，异常CNV的携带率显着降低。AFP组无显著差异。
结论：低血清uE3水平(<0.4MoM)与异常CNVs的风险增加相关。
