Whole Genome Sequencing in Prenatal Diagnostics: The Danish Approach to Guideline Formation and Implementation Within Public Healthcare

Objective

To describe the implementation of whole genome sequencing (WGS) in prenatal diagnostics and outline the national guideline system facilitating this.

Methods

Clinical guidelines for WGS in prenatal diagnostics were developed and implemented by the Danish Fetal Medicine Society.

Results

Guidelines were developed by expert consensus following a review of 75 studies. Diagnostic yield served as a key factor in prioritizing WGS for various phenotypes, improving diagnostic accuracy and informing clinical decisions. Phenotypes for WGS include nuchal translucency = 6.0 mm, multiple anomalies, skeletal dysplasia, neuromuscular diseases, non-immune hydrops fetalis, central nervous system malformations, congenital diaphragmatic hernia and severe fetal growth restriction (< 3 SDs not explained by placental insufficiency). Small regional variations exist in indications, bioinformatics, and funding, but WGS is now routinely used nationwide for these indications.

Conclusion

The Danish Fetal Medicine Society's guideline development, emphasizing diagnostic yield and gradual implementation, has supported the relatively uniform integration of WGS into prenatal diagnostics.