NIPT of Maternal Plasma-Originated cfDNA: Applications and Guide for the Implementation.

Abstract

The implementation of non-invasive prenatal testing (NIPT) in maternal plasma, based on cell-free DNA (cfDNA) analysis, has progressed over the last two decades and is now integrated into the Spanish National Health System. However, there remains significant heterogeneity in its indications, technical methodologies, and reporting standards, reflecting international variability. This guide, developed by experts from the Spanish Association of Prenatal Diagnosis (AEDP) and the Spanish Association of Human Genetics (AEGH), provides recommendations to standardize NIPT application. It addresses key aspects such as technical and analytical requirements, integration with invasive diagnostic methods, pre- and post-test genetic counseling, and legal considerations. Additionally, the guide discusses the detection of common aneuploidies, the limitations in identifying structural chromosomal abnormalities and rare variants, and the impact of biological and clinical factors on test performance. By establishing a minimum framework based on scientific evidence, this document aims to optimize NIPT implementation in a cost-effective manner, ensuring clinical validity and informed decision-making for both healthcare professionals and pregnant women.