Safety, efficacy, and outcomes of invasive prenatal diagnosis for hemoglobinopathies in rural and semiurban India

Hemoglobinopathies, such as thalassemia and sickle cell disease, are prevalent genetic disorders in India that disproportionately affect rural and underserved populations. Although prenatal diagnostics have advanced in metropolitan areas, access remains limited in rural regions. This study evaluates the implementation and outcomes of an invasive prenatal diagnosis (IPND) program for the prevention of hemoglobinopathies by Sankalp India Foundation across 5 states in India. From June 2023 to September 2024, pregnant women at ≤20 weeks of gestational age were screened across 82 districts using a targeted 3-step model: high-performance liquid chromatography testing, molecular confirmation of hemoglobinopathy in both partners, and IPND for at-risk couples, supported by comprehensive counseling at each stage. Fetal samples were collected at local centers and analyzed at centralized laboratories for causative mutations. Pregnant individuals carrying a fetus diagnosed with severe hemoglobinopathy received counseling and were able to make informed decisions regarding medical termination of pregnancy (MTP) in accordance with the country’s legal and ethical guidelines. A total of 81 139 women were screened, identifying 802 high-risk couples. Of these, 531 couples registered for IPND, and 495 successfully underwent IPND. In addition, the approach also identified 0.2% of the couples who did not require an IPND; 137 fetuses (27.3%) were diagnosed with severe hemoglobinopathy, and 64.2% of the couples opted for MTP. The program exhibited high safety, with a 0.6% complication rate and 0.2% failure rate; 8 couples (1.6%) returned in their subsequent pregnancies, reflecting community trust and awareness. This initiative shows that IPND can be safely delivered in low-resource settings, offering a scalable approach to reducing hemoglobinopathies in India.