Diagnostic Yield of Exome Sequencing for Pregnancies With and Without Fetal Anomalies and for Stillbirth

Authors

• Roni Zemet
• Christian M Parobek
• April D Adams
• Mohamad Ali Maktabi
• Lena Shay
• Linyan Meng
• Pengfei Liu
• Hongzheng Dai
• Fan Xia
• Christine Eng
• Ignatia B Van den Veyver
• Liesbeth Vossaert

Language

English

Publication Date

9-1-2025

Journal

Prenatal Diagnosis Journal

DOI

10.1002/pd.6817

PMID

40423626

PMCID

PMC13050391

PubMedCentral® Posted Date

9-1-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Objective: Exome sequencing (ES) benefits the genetic work-up for fetuses with structural anomalies, but data on its utility for fetuses without anomalies and stillbirths is more limited. We report our experience with prenatal ES for all three indications.

Method: We retrospectively reviewed results from 344 trio-ES performed for fetuses with structural anomalies (N = 262), stillbirths (N = 39), and fetuses without anomalies (N = 43), many of which had a relevant family history. We classified pathogenic variants (P), likely pathogenic variants (LP), or variants of uncertain significance (VUS) favoring pathogenicity in a gene consistent with the fetal phenotype as diagnostic results. We used Fisher's exact test for statistical analysis.

Results: Trio-ES provided a diagnosis for 93/262 (35.5%) fetuses with structural anomalies, with comparable yields for multiple and single anomalies (p = 0.81). A molecular diagnosis was made for 10/39 stillbirths (25.6%), of which all but one had structural anomalies, and 66.6% had multiple anomalies. In the absence of structural anomalies, one of 43 fetuses (2.3%) was found to have compound heterozygous pathogenic variants in ORC6 associated with Meier-Gorlin syndrome.

Conclusion: Prenatal trio-ES yields molecular diagnoses across a spectrum of indications. Larger studies are needed to further define the added benefits and challenges of diagnostic ES for fetuses without anomalies.

Keywords

Humans, Female, Pregnancy, Stillbirth, Exome Sequencing, Retrospective Studies, Congenital Abnormalities, Adult, Prenatal Diagnosis

Published Open-Access

yes

Recommended Citation

Zemet, Roni; Parobek, Christian M; Adams, April D; et al., "Diagnostic Yield of Exome Sequencing for Pregnancies With and Without Fetal Anomalies and for Stillbirth" (2025). Duncan NRI Faculty and Staff Publications. 219.
https://digitalcommons.library.tmc.edu/duncar_nri_pub/219