# Routine antenatal molecular testing for α-thalassemia at a tertiary referral hospital in China: ten years of experience

## TL;DR

This study shows that routine α-thalassemia gene testing during pregnancy in China over ten years helped prevent severe cases and reduced costs.

## Contribution

The study proposes new cutoff points for α-thalassemia screening that could reduce costs while maintaining diagnostic accuracy.

## Key findings

- α-thalassemia mutations were found in 41.78% of 91,852 patients tested over ten years.
- New cutoff points for screening could save approximately 10 million yuan by reducing missed diagnoses.
- Prenatal diagnosis identified four cases of fetal anemia and two of severe fetal edema.

## Abstract

This study aimed to evaluate the efficacy of α-thalassemia gene testing as a part of an antenatal intervention program over a 10-year period.

All patients underwent α-thalassemia gene testing, which included the analysis of three types of deletions and mutations. Rare α-thalassemia gene testing was performed using Sanger sequencing, multiplex ligation-dependent probe amplification, and sequencing techniques. Prenatal diagnosis was performed in high-risk couples using chorionic villus sampling or amniocentesis.

From 2010 to 2019, among the 91,852 patients examined, α-thalassemia mutations were identified in 41.78% of patients. The most frequent α0 gene mutation was--SEA, followed by--THAI. Two rare α0-thalassemia gene mutations at --32.8 and --230, were also observed. A total of 2,235 high-risk couples were identified, of which 562 were affected, including three with the--SEA/--THAI genotype and one with the--SEA/--230 genotype. Additionally, prenatal diagnosis revealed four cases of fetal anemia and/or mild edema, along with two cases of severe fetal edema. Chromosome and gene chip results were normal. Thalassemia gene testing showed an αCSα/αCSα genotype in four patients with anemia and/or mild edema, while two patients with severe fetal edema had one--SEA/αCSα genotype and one--SEA/--GX genotype. Using the cut-off points of 74.6 fL and 24.4 pg as criteria for identifying α0-thalassemia carriers and HbH disease, the detection rate of missed diagnoses in high-risk couples is consistent with national guidelines for standards, potentially saving 10,217,700 ¥.

Routine molecular testing for α-thalassemia in high-risk prenatal populations effectively prevented severe α-thalassemia births. Despite the high cost, the cutoff points proposed by this study suggest that implementing screening using a new parameter has the potential to reduce current expenses.