An overview of current prenatal genetic screening and diagnosis guidelines.

The landscape of prenatal genetics continues to evolve rapidly, with improvements in processing speed and technology. Clinicians are tasked with staying current with the latest recommendations for prenatal genetic screening and diagnosis in order to provide patient-centered and evidence-based care. We present a review of 15 societal guidelines that have been published or reaffirmed between 2016 and 2023 from the American College of Obstetricians and Gynecologists (ACOG), Society for Maternal Fetal Medicine (SMFM), American College of Medical Genetics and Genomics (ACMG), and International Society for Prenatal Diagnosis (ISPD). We provide a summary of the current guidance for carrier screening, cell-free DNA (cfDNA) screening, and prenatal diagnostic testing, and also discuss key genetic principles. In brief, there are several approaches to prenatal carrier screening that range from a few select conditions (hemoglobinopathies, spinal muscular atrophy, cystic fibrosis) to several hundreds through expanded carrier screening panels. Both ACOG and ACMG support prenatal (ideally preconception) carrier screening, although have differing guidance about the optimal approach and number of conditions to screen. With regards to cfDNA screening, ACOG, SMFM, ACMG, and ISPD recommend offering all patients the option to screen for common aneuploidies, with consideration of sex chromosome aneuploidies after counseling. While ACOG, SMFM, and ISPD do not endorse microdeletion screening with cfDNA, ACMG supports cfDNA screening for 22q11.2 deletion syndrome. The societies are unanimous in recommending against cfDNA evaluation of rare autosomal trisomies. Finally, in terms of diagnostic testing, ACOG, SMFM, ACMG, and ISPD recommend offering chromosomal microarray for evaluation of fetal structural anomalies, stillbirth, and confirmation of screening results. Next-generation sequencing with fetal exome or genome sequencing is recommended by ACMG, ISPD, and SMFM for evaluation of fetal anomalies following normal karyotype and/or microarray. ACOG, on the other hand, does not currently endorse fetal exome or genome sequencing outside of a research setting. Clinicians must have robust genetic literacy in order to understand current guidance and testing methodologies, discuss the benefits and limitations of genetic screening and diagnostic testing options, and engage in equitable and evidence-based clinical practice.