Abstract
The purpose of this study was to explore the copy number variations (CNVs) associated with miscarriage during early and middle pregnancy and provide useful genetic guidance for pregnancy and prenatal diagnosis. A total of 505 fetal specimens were collected and CNV sequencing (CNV-seq) analysis was performed to determine the types and clinical significance of CNVs, and relevant medical records were collected. The chromosomal abnormality rate was 54.3% (274/505), among which the numerical chromosomal abnormality rate was 40.0% (202/505) and structural chromosomal abnormality rate was 14.3% (72/505). Chromosomal monosomy mainly occurred on sex chromosomes, and chromosomal trisomy mainly occurred on chromosomes 16, 22, 21, 15, 13, and 9. The incidence of numerical chromosomal abnormalities in ≥35 year-old age pregnant women was significantly higher than <35 year-old age group. The highest incidence of pathogenic CNV (pCNV) was found in fetuses at ≤6 weeks of pregnancy (5.26%), and the incidence of variants of unknown significance (VOUS) CNVs decreased gradually with the increase of gestational age. The rate of chromosomal abnormalities of fetuses in early pregnancy (59.5%) was higher than that of fetuses in middle pregnancy (27.2%) (p < 0.001). There were 168 genes in VOUS + pCNV regions. 41 functions and 12 pathways (p < 0.05) were enriched of these genes by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Some meaningful genetic etiology information such as genes and pathways has been obtained, it may provide useful genetic guidance for pregnancy and prenatal diagnosis.
Highlights
Miscarriage is a clinical event that termination of pregnancy at less than 28 weeks, and the fetal weight is less than 1000 g, occurs in before 12 gestational weeks is called miscarriage during early pregnancy, occurs in 13–27 gestational weeks is called miscarriage during middle pregnancy (Muttukrishna et al, 2002)
There were 261 (51.7%) pregnant women under the age of 30 years, 142 (28.1%) pregnant women between 30 and 34 years of age, 78 (15.4%) pregnant women between 35 and 39 years of age, and 24 (4.8%) pregnant women over 40 years of age. Among these fetuses with miscarriage, there were 410 (81.2%) fetuses aborted in the early pregnancy (≤12 weeks) and 95 (18.8%) fetuses in the middle pregnancy (13–27 weeks)
There was no fetal pathogenic CNV (pCNV) was detected in other age groups
Summary
Miscarriage is a clinical event that termination of pregnancy at less than 28 weeks, and the fetal weight is less than 1000 g, occurs in before 12 gestational weeks is called miscarriage during early pregnancy, occurs in 13–27 gestational weeks is called miscarriage during middle pregnancy (Muttukrishna et al, 2002). The etiology of miscarriage is closely related to environmental factors (Zhou et al, 2017), genetic factors(Pereza et al, 2017), body immune state (Wang et al, 2021). Studies have shown that genetic factors play an important role in early miscarriage, with about 50% of the cases caused by chromosomal abnormalities (van den Berg et al, 2012; Ozawa et al, 2019), while the risk factors of late miscarriage (≥28 gestational weeks) are mainly immune and environmental factors (Meng et al, 2020). A study has shown that copy number variations (CNVs) (known as microdeletion/microduplication) accounts for about 2.7% miscarriages, second only to aneuploidy and polyploidy (Wang Y. et al, 2020). Regardless of the cause, the etiological analysis of miscarriage is of great significance to the aborted fetuses and the pregnancy of women with childbearing age
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