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Oligohydramnios or polyhydramnios, is associated with chromosomal aberrations, particularly aneuploidy. However, its correlation with copy number variation (CNV) remains unclear.We retrospectively analyzed 428 cases with an abnormal level of amniotic fluid, comprising of 139 cases of single ultrasound findings (SU group) and 289 cases of multiple ultrasound findings (MU group), by CNV sequencing (CNV-Seq) and followed their pregnancy outcomes.The overall detection rate of clinically significant findings was 8%, with 5% in the SU group and 11% in MU group. Besides, 18 microdeletion/microduplication syndromes were detected, with the highest rate of renal cysts and diabetes syndrome (22%, 4/18). Also, the rate of termination of pregnancy in MU group was much higher than that in the SU group (29% vs. 10%, ***p 0.001), and in the MU-oligohydramnios subgroup, it was the highest (34%), regardless of cases with chromosomal anomaly and lost to follow-up.Our results showed that the abnormal level of amniotic fluid, especially combined with other ultrasound abnormalities, is closely related to chromosomal abnormalities and genetic CNVs. CNV-Seq may be useful in investigating pregnancies with an abnormal amniotic fluid level.

Objectives To evaluate the clinical potential of a higher resolution noninvasive prenatal screening (NIPS-Plus) test for detection of microdeletion/microduplication syndromes (MMS) in addition to common aneuploidies. Methods In a multicenter prospective study, 37,002 pregnant women with unremarkable first-trimester ultrasound scans had a NIPS-Plus test. Ultrasound screen positive women were not included in this study. Results Of 36,970 ultrasound negative women there were 291 NIPS-Plus screen positive results indicating 237 aneuploidies and 54 MMS. Following amniocentesis, 171 (72%) were confirmed as genuine, comprising 3 T13s, 10 T18s, 61 T21s, 70 SCAs and 27 MMS. The PPV for MMS with unremarkable ultrasound findings was 50%. Routine clinical examination of children born from NIPS-Plus negative pregnancies revealed no obvious signs of chromosome disease syndromes at one year of age. Conclusions NIPS-Plus has the potential for clinical utility not only for routine aneuploid screening but also for MMS that do not show overt signs during early pregnancy ultrasound screening. We suggest that ultrasound with NIPS-Plus in combination with appropriate counselling could be considered as a comprehensive first-tier prenatal screening approach for all pregnant women.

Aim Families with an adverse history of monogenic disease focus on single‐gene diagnosis instead of low‐depth whole‐genome sequence, during subsequent pregnancies. The aim of this study was to assess the potential usefulness of low‐depth whole‐genome sequencing (copy number variant sequencing [CNV‐seq]) detection following monogenic disease exclusion in prenatal diagnosis. Methods A total of 285 families with a history of monogenic disease (of 41 different types; eliminated during the current pregnancy) were recruited and retrospectively analyzed. Low‐depth whole‐genome sequencing (CNV‐Seq, Next‐Seq CN500 platform) was performed for all fetuses. Results The CNV detection results of the 285 samples were as follows: one case of 18‐trisomy chimera (0.35%), one case of pathogenic 3q29 microdeletion syndrome CNV (0.35%), four cases of variant of uncertain significance (VUS) CNVs (1.40%), and four cases of Duchenne muscular dystrophy (DMD) carriers (1.40%); and the remaining samples were normal (96.15%). Of note, 2/285 (0.70%) samples still exhibited pathogenic abnormalities. All positive samples were followed up where the two cases of pathogenic abnormalities elected the pregnancy termination, while the four VUS cases and four DMD‐carrier cases were born healthy. Conclusion In cases where prenatal fetal monogenic disease has been ruled out, CNV detection is still beneficial and should be performed to prevent missed pathogenic CNVs. However, the costs need to be balanced against benefits, and the research will need to assess other types of testing.