Enhancing Diagnostic Precision in Non-Immune Hydrops Fetalis: The Incremental Value of Whole Exome Sequencing-A Prospective Cohort Study.

Heterogeneous aetiologies combining aneuploidies and monogenic disorders, the latter revealed by exome sequencing and more frequent in consanguineous families.

This prospective cohort from Western Rajasthan, India, enrolled 80 consecutive fetuses with non-immune hydrops fetalis between January 2020 and March 2026, after excluding immune hydrops and twin-to-twin transfusion syndrome. All underwent detailed fetal ultrasonography and echocardiography, targeted infectious screening and conventional genetic evaluation with karyotyping with or without chromosomal microarray, with exome sequencing reserved for unresolved cases. A diagnosis was reached in 40 of 80 cases (50.0%), genetic in 27 of 40 (67.5%), comprising 12 aneuploidies (15.0% of the cohort) and 15 monogenic disorders (18.8%); non-genetic causes included structural anomalies, parvovirus B19 infection and lower urinary tract obstruction. WES, performed in 41 fetuses, identified pathogenic or likely pathogenic variants in 15 cases, a diagnostic yield of 36.6%, and variants of uncertain significance in 6 cases (14.6%), giving an overall incremental yield of 18.8% (15/80). Consanguinity was associated with a markedly higher WES yield (69.2% vs 21.4%; odds ratio 8.25; p = 0.005).

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The 18.8% incremental yield is in line with other series and supports exome sequencing in the workup of unexplained non-immune hydrops once karyotype and microarray are negative. The consanguinity effect, however, rests on small subgroups with no confidence interval reported, and a single-centre Rajasthan cohort does not transfer directly to a non-consanguineous population. In practice the question is no longer whether to sequence but how fast: the value for obstetric decision-making depends on turnaround within the pregnancy, which this study does not document.

Analysis by Dr Thibaut Benquey