The application of late amniocentesis: a retrospective study in a tertiary fetal medicine center in China

Abstract

Background To assess the indications and complications of late amniocentesis and the advanced genetic test results in a tertiary university fetal medical medicine unit. Methods In this retrospective study, women that underwent amniocentesis at 24+ 0 to 39+ 4 weeks, between January 2014 and December 2019, were recruited. Indications, complications, genetic test results, and pregnancy outcomes were reported for each pregnancy and compared with those who underwent the traditional amniocentesis at 16+ 0 to 23+ 6 weeks (control group). Information was retrieved from patient medical records, checked by research staff, and analyzed. Results Of the 1287 women (1321 fetuses) included in the late amniocentesis group, late detected sonographic abnormalities (85.5%) were the most common indication. The overall incidence of preterm birth and intrauterine demise after amniocentesis were 2.5 and 1.3%, respectively. Sixty-nine fetuses with aneuploidy (5.3%) and seventy-two fetuses with pathogenic copy number variations (5.5%) were identified by chromosomal microarray analysis. The maximal diagnostic yield (70%) was in the subgroup of fetuses with the abnormal diagnostic test results, followed by abnormal NIPT results (35.7%) and multiple abnormalities (23.8%). And 35.4% of the pregnancies were finally terminated. Conclusions Due to the high detection rates of advanced genetic technologies and the safety of the invasive procedure (3.9% vs 4.0%), it is reasonable to recommend late amniocentesis as an effective and reliable method to detect late-onset fetal abnormalities. However, chromosomal microarray and whole-exome sequencing may result in uncertain results like variants of uncertain significance. Comprehensive genetic counseling is necessary.

Perinatal outcomes and genomic characteristics of fetal copy number variants: An individual record linkage study of 713 pregnancies

“…Our cohort of 483 fetal VUS is the second largest reported to date. Our live birth rate for fetuses with a VUS (64%) was higher than for those with a pCNV (20%) and was within the range reported in other fetal VUS cohorts (35%–90%) 10–13,15,16,19 . Similarly to Chen et al., who followed up 721 fetal VUS, we found that an inherited VUS was more likely to result in a live birth than a non‐inherited VUS 17 .…”

“…The prevalence of pCNVs in our cohort was 3.3%, which was similar to that reported in a published review of 23,865 pCNVs 29 . Our study of 230 pCNVs is the largest to include birth outcomes, with previous publications containing smaller cohorts (range 5–93) and/or only reporting perinatal outcomes for a small subset 10–14,18 . Our summary statistics on preterm birth and low birth weight provide general prognostic information that can be used for counseling couples about obstetric outcomes for pCNVs, particularly for rare pCNVs where data on obstetric outcomes are lacking and planning ongoing management in a high risk model of prenatal care.…”

“…Our VUS prevalence of 7.0% was higher than some studies, 1,3,10–16,19,33,34 but comparable to 7.2% recorded in the Belgium national prenatal cohort 33 . The most common VUS in our study was the 15q11.2 deletion, which has a highly variable phenotype including neurodevelopmental delay, autism spectrum disorders, and obsessive‐compulsive disorders 35 .…”

“…Had CMA only been performed in pregnancies with an ultrasound abnormality, 27.9% (90/322, Table 3) of pCNVs in our cohort would have gone undetected before birth. 3 Our VUS prevalence of 7.0% was higher than some studies, 1,3,[10][11][12][13][14][15][16]19,33,34 but comparable to 7.2% recorded in the Belgium national prenatal cohort. 33 The most common VUS in our study was the 15q11.2 deletion, which has a highly variable phenotype including neurodevelopmental delay, autism spectrum disorders, and obsessive-compulsive disorders.…”

“…There is a dearth of current literature on perinatal outcomes of fetal pCNVs and VUS, in terms of the number of live births and perinatal deaths. Published studies are limited by small sample sizes, selection bias due to limited indications for prenatal diagnosis, and incomplete reporting of perinatal outcomes 10–19 . Perinatal outcomes are likely influenced by indication for prenatal diagnosis, such as an ultrasound abnormality, as well as genomic location and CNV size.…”