From Isolated to Complex: Diagnostic Yield of Chromosomal Microarray and Exome Sequencing in Fetal Growth Restriction.

This retrospective cohort covers 320 consecutive pregnancies with fetal growth restriction (FGR) presenting at 20 weeks or later to a tertiary fetal medicine unit (2020-2025), all assessed by a dedicated anatomical survey including neurosonography. FGR was isolated in 62.2% of cases, early-onset (before 32 weeks) in 68.1% and associated with abnormal Doppler in 30%. Chromosomal microarray (CMA), performed in 237 cases, detected an abnormality in 5.5%, but only 2.1% (5/237) were considered causative of FGR. Exome sequencing, performed in 149 cases, had an FGR-causative yield of 10.7% (16/149), higher in non-isolated than isolated FGR (18.5% vs 4.8%; p = 0.014), and abnormal Doppler did not preclude a monogenic diagnosis (5 of 16 causative cases).

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

Two practical messages: exome sequencing adds clearly more than CMA in FGR, including isolated FGR (4.8%), and an abnormal Doppler suggesting a placental cause should not deter genetic investigation. Exome was performed in fewer than half of the pregnancies, so the yields are likely subject to selection bias. These data support offering exome in a phenotype-graded way rather than as a last resort.

Analysis by Dr Thibaut Benquey