Severe fetal growth restriction remains a critical concern for obstetricians and neonatologists worldwide. This condition often results from placental insufficiency, yet genetic factors play a vital role. A recent study by Mossayebi MH et al. evaluated the diagnostic yield of genetic testing in singleton pregnancies. Specifically, the researchers focused on isolated cases diagnosed before 32 weeks of gestation. By analyzing antenatal and postnatal results, the team provided clear insights into the clinical utility of modern genomic tools.

Diagnostic Yield of Severe Fetal Growth Restriction Testing

The research compared various modalities including karyotype (KT) and chromosomal microarray (CMA). Furthermore, exome and genome sequencing (ES/GS) data were analyzed in a specific subset of the population. Consequently, the study found that advanced sequencing significantly increases the detection of underlying monogenic disorders. For instance, while CMA effectively identifies copy number variants, ES/GS uncovers subtle genetic changes that standard tests often miss. This incremental yield is especially pronounced in early-onset cases where fetal growth is profoundly affected.

Additionally, the investigators noted that cases diagnosed before 32 weeks carry a higher risk of a specific genetic etiology. Therefore, providing these patients with comprehensive genetic counseling is essential for informed decision-making. In conclusion, clinicians should consider exome sequencing when standard genetic results are negative in severe cases. This approach ensures more accurate prognosis and optimized management strategies for the newborn. Similarly, it aids in assessing recurrence risks for future pregnancies.

Frequently Asked Questions

What is the diagnostic yield of CMA in isolated FGR?

Chromosomal microarray generally identifies pathogenic variants in approximately 6% to 10% of isolated FGR cases. However, this diagnostic yield tends to be higher in early-onset or severe presentations compared to late-onset growth restriction.

When should exome sequencing be considered for FGR?

Clinicians should prioritize exome sequencing for severe early-onset FGR when initial karyotype and CMA results are normal. This modality provides a significant incremental yield by identifying monogenic causes that explain the growth phenotype.

Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice or a professional relationship. Always seek the advice of a qualified healthcare provider regarding any medical condition. Refer to the latest local and national guidelines for clinical practice.

References

Mossayebi MH et al. Severe Early-Onset Fetal Growth Restriction: The Yield of Antenatal and Postnatal Genetic Testing. Prenat Diagn. 2026 May 19. doi: 10.1002/pd.70182. PMID: 42153347.

Langeois M et al. Moderate Diagnostic Yield of Exome Sequencing in Fetal Growth Restriction: Retrospective Insights. Prenat Diagn. 2026 Jan 11. doi: 10.1002/pd.70064.

Pauta M et al. Diagnostic yield of exome sequencing in isolated fetal growth restriction: Systematic review and meta‐analysis. Prenat Diagn. 2023; 43(7): 901-912.