Tweetable abstract
Owing to considerable detection rates and safety, it is reasonable to serve late amniocentesis as an effective and safe method.

Introduction

Amniocentesis is a prenatal diagnostic procedure in which a small amount of amniotic fluid is withdrawn from the sac surrounding the fetus for testing. It has been a conventional method of obtaining fetal genetic information since the late 1960s1. It is traditionally performed between 16-24 gestational weeks in China, and it provides pregnant women and their families with an opportunity for early diagnosis of and appropriate intervention for the undesirable findings2. Nowadays, clinically available methods for analyzing fetal genetic information from amniotic fluid include traditional karyotyping, chromosomal microarray analysis (CMA), medical exome sequencing (MES), whole-genome sequencing (WGS) and whole-exome sequencing (WES). The detection ranges of them are different which result in different detection rates and costs. For example, compared with traditional karyotyping, CMA provides more genetic information of the fetus and has demonstrated to increase the diagnostic yield by 5-9% 3, 4. Consistently, 5.3% fetuses with late-appearing abnormal ultrasound findings and normal karyotype results showed pathogenic CMA results. Owing to its higher detection rate, shorter turnaround time, and affordable expense, CMA fleetly became the first-tier method in prenatal diagnosis associated with the occurrence of fetal structural anomalies and/or increased nuchal translucency (NT)1. Clinical implementation of next-generation sequencing (NGS) in field of prenatal diagnostics are widely available. Petrovski and co-workers noted that patients underwent WES by NGS had higher diagnostic yields (25–35%) among fetuses with genetic disorders, while negative findings were observed by either karyotyping or CMA techniques 5, 6. Although both WGS and WES can detect novel pathogenic genes, WGS analyzes the entire genome while WES and MES focus only on the exons7, 8. Since the exons generally have greater clinical relevance and applicability to human diseases, WES and MES were more frequently used in prenatal diagnosis. The chances of late-appearing abnormal ultrasound findings after a normal fetal-targeted organ scan before 24 gestational weeks are estimated at 5.5%-17% 9, 10. Late amniocentesis can be performed after 24 gestational weeks onwards which is considered to be safe and effective1. However, though it is associated with a higher risk of miscarriage than amniocentesis11, cordocentesis is still widely employed as the method of choice for prenatal diagnosis after 24 weeks in China. Clinical data remains lacking regarding the incidence, indications, complications, and outcomes associated with late amniocentesis. The aim of this retrospective study was to provide more detailed clinical data associated with late amniocentesis procedures in prenatal diagnosis.