Genetic etiology and obstetric outcome analysis of fetal cystic hygroma in a single-center study

Abstract Cystic hygroma (CH) is a somewhat common observation in prenatal ultrasounds; however, there is no consensus regarding the clinical management of fetuses with CH. A retrospective analysis was performed on 40 pregnant patients whose fetuses had CH from November 2016 to June 2021. Villus, amniotic fluid, or umbilical cord blood samples were collected according to the corresponding gestational age for karyotype analysis and single-nucleotide polymorphism array (SNP-array). Among the 40 fetuses with CH, 16 (40.0%, 16/40) exhibited isolated CH and 24 (60.0%, 24/40) exhibited CH combined with other ultrasound abnormalities. The most common CH-comorbid ultrasound abnormalities in this study were congenital heart disease (25.0%, 6/24), followed by thickened nuchal translucency (20.8%, 5/24), and fetal edema (12.5%, 3/24). After karyotype and SNP-array analysis, an overall detection rate of 30.0% (12/40) was achieved. Using karyotype analysis, eight cases of pathogenic copy number variations (CNVs) were detected, among which 45, X was the most common. In addition to the above pathogenic CNV, four additional cases of pathogenic CNVs were detected by SNP-array. There was no significant difference in pathogenic CNVs of isolated CH and CH combined with other ultrasound (31.3% vs. 29.2%, P = 1). Karyotype analysis and SNP-array results influence whether fetal parents terminate pregnancy. When genetic abnormalities are detected in the fetus, the parents often choose to terminate the pregnancy. Genomic examination should be performed on fetuses with CH to confirm the etiology as soon as possible. During genetic counseling, all fetal characteristics should be carefully and comprehensively evaluated.