Fetal copy number variation (CNV) refers to increase or decrease in copy number of DNA fragments with more than 1 kb in length, and it also includes the deletion and duplication of chromosome fragments at submicroscopic level. Diseases caused by fetal CNV are collectively referred as microdeletion and microduplication syndromes (MMS). Through technologies such as chromosome microarray analysis (CMA) and CNV sequencing, CNV and numerical chromosome abnormalities can be detected accurately and quickly, as well as chimera and mosaic individuals with mosaic ratio ≥30%. CMA or/and CNV sequencing can increase the detection rate of MMS by 1.0%-1.7% compared with karyotype analysis. Since there are no obvious and characteristic imaging abnormalities in most diseases during fetal period, judgment of fetal pathogenicity CNV (pCNV) and genetic counseling have become main challenges in current prenatal diagnosis service. Therefore, relevant principles for pCNV sequencing are as follows. ①Judgement of pCNV fragment is not only based on its fragment size, but also needs to be evaluated based on fragment′s location, the number of gene mutations, and whether gene has a dose effect. It is often necessary to further test parental chromosome karyotype, parental CNV and combined with clinical phenotype of parents, thus conducting a comprehensive evaluation of pCNV. ②A fetal CNV with fragment <1 Mb in length and inherited from one parental generation has limited pathogenicity, while a CNV with fragment ≥ 1 Mb length and being a new mutation means that it bears higher pathogenic risk. ③When CNV of the same size are compared with each other, clinical impact of chromosome deletion is greater than that of duplicates. CNV scoring system on the ClinGen website can be used to quickly determine fetal pCNV: CNV with a score ≥0.99 are judged as pCNV, those with a score between 0.9 to 0.98 are likely pCNV (LpCNV), CNV scored between -0.89 to 0.89 are regarded as variants of uncertain significance (VUS) CNV, and those with a score between -0.98 to -0.9 are determined as likely benign (LB) CNV, and the rest with a score ≤ -0.99 are benign CNV. Benign CNV is widespread in normal population. Clinical manifestations of some pCNV may not be serious. Only when it is confirmed that fetal pCNV can cause death or serious birth defects, clinicians should advice pregnant women terminate pregnancy in time to prevent major birth defects.