Study on the correlation between the concentration of maternal serum biomarkers and the risk of fetal presenting with copy number variation
10.19405/j.cnki.issn1000-1492.2026.08.017
- VernacularTitle:孕中期母体血清学生物标志物浓度与胎儿携带拷贝数变异风险的相关性研究
- Author:
Mengting ZHANG
1
;
Dandan LI
2
;
Yue GAO
1
;
Dong WU
1
;
Hai XIAO
1
;
Liangjie GUO
1
;
Hongdan WANG
1
Author Information
1. Institute of Medical Genetics，
2. NHC Key Laboratory of Birth Defects Prevention， Henan Academy of Innovations in Medical Science， Zhengzhou 451163
- Publication Type:Journal Article
- Keywords:
free beta-human chorionic gonadotropin;
alpha fetoprotein;
unconjugated estriol;
inhibin A;
karyotype analysis;
copy number variation
- From:
Acta Universitatis Medicinalis Anhui
2026;61(8):1458-1463
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the association between the concentration of maternal serum biomarkers， including free beta-human chorionic gonadotropin （fβ-hCG）， alpha fetoprotein （AFP）， unconjugated estriol （uE3）， and inhibin A （INH A） during the second trimester pregnancy and the risk of fetal presenting with copy number variation （CNV）. MethodsA retrospective analysis was conducted on the diagnostic results of pregnant women who were identified as high risk in the second trimester quadruple serological screening. These pregnant women underwent the interventional prenatal diagnosis and performed amniotic fluid karyotype analysis and comparative genomic hybridization array （aCGH） or CNV sequencing （CNV-seq） simultaneously.The detection rates of different diagnostic methods were calculated. The concentration of serum biomarkers， fβ-hCG， AFP， uE3， and INH A were divided into three levels： abnormally low， normal， and abnormally high. The prevalence of these serum biomarkers concentration in pregnant women with aberrant aCGH/CNV-seq results compared to normal controls was statistically calculated. ResultsAmong the 1 516 cases with high-risk quadruple serological screening in the second trimester， 59 chromosomal abnormalities were revealed by karyotype analysis， while 87 abnormalities were detected by aCGH/CNV-seq， indicating a significant statistical difference in detection rate. In comparison to the result of karyotype analysis， aCGH/CNV-seq identified an additional 46 cases of fetal CNV abnormalities， whereas it failed to detect 18 cases of chromosomal structural abnormalities. Among the 1 457 cases with normal karyotype results， the most frequent abnormality was observed in the concentration of fβ-hCG， followed by abnormalities in INH A and uE3 concentrations， yet the least common abnormality was noted in AFP concentration. When the maternal serum uE3 concentration was less than 0.5 multiples of median （MoM）， there was a significant difference in the risk of fetal CNV compared to the CNV results corresponding to normal concentration of uE3. No significant differences were found in the levels of fβ-hCG， AFP， and INH A between the two groups. ConclusionLow serum uE3 concentration （<0.5 MoM） is associated with an increased risk of fetal presenting with aberrant CNV.
