%0 Journal Article
%T Non-invasive cell-free DNA-based approach for the diagnosis of clinical miscarriage: A retrospective study.
%A Balaguer N
%A Rodrigo L
%A Mateu-Brull E
%A Campos-Galindo I
%A Castellón JA
%A Al-Asmar N
%A Rubio C
%A Milán M
%J BJOG
%V 131
%N 2
%D 2024 Jan 2
%M 37533357
%F 7.331
%R 10.1111/1471-0528.17629
%X OBJECTIVE: To evaluate cell-free DNA (cfDNA) testing as a non-invasive approach to detecting aneuploidies in clinical miscarriages.
METHODS: A retrospective cohort study of women with pregnancy loss.
METHODS: Hospitals and genetic analysis laboratories.
METHODS: Pregnancy losses in the period 2021-2022.
METHODS: Results derived from non-invasive cfDNA testing (Veriseq NIPT Solution V2) of maternal blood and invasive analysis of products of conception (POC) (Ion ReproSeq) compared in 120 women who suffered a miscarriage.
METHODS: Concordance rate results, cfDNA testing performance, non-informative rate (NIR) and fetal fraction (FF).
RESULTS: We found no significant differences in the NIR between invasive (iPOC) and non-invasive (niPOC) analysis of POC (10.0% [12/120] versus 16.7% [20/120]). Of 120 samples, 90 provided an informative result in iPOC and niPOC groups (75%). cfDNA analysis correctly identified 74/87 (85.1%) samples (excluding triploidies). Sensitivity and specificity were 79.4% and 100%, respectively; all discordant cases were female. A binomial logistic model suggested fetal sex as the only variable influencing the concordance rate (P = 0.035). A Y-chromosome-based FF estimate allowed the optimal reclassification of cfDNA of non-informative male fetuses and a more accurate evaluation of cfDNA testing performance. The difference between the two FF estimates (native algorithm and Y-chromosome-based) suggests that female non-concordant cases may represent non-informative cases.
CONCLUSIONS: Cell-free DNA-based testing provides a non-invasive approach to determining the genetic cause of clinical miscarriage.