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Incidence, Distribution, Disease Spectrum, and Genetic Deficits of Congenital Heart Defects in China: Implementation of Prenatal Ultrasound Screening Identified 18,171 Affected Fetuses From 2,452,249 Pregnancies

Background: Congenital heart defects (CHDs) are the most common cause of birth defects. Assessment of the incidence, distribution, disease spectrum, and genetic deficits of fetal CHDs in China is urgently needed. 
 
Methods: A national echocardiography screening program for fetal CHDs was implemented in 92 prenatal screening–diagnostic centers in China. 
 
Findings: A total of 18,171 fetal CHD cases were identified from 2,452,249 pregnancies, resulting in 7·4/1,000 as the national incidence rate of fetal CHD. The incidences of fetal CHD in the six geographical regions, the southern, central, eastern, southwestern, northern, and northwestern, were 8·174 (CI: 7·802–8·554), 7·839 (CI: 7·680–8·000), 7·647 (CI: 7·383–7·915), 7·562 (CI: 7·225–7·907), 5·618 (CI: 5·337–5·906), and 4·716 (CI: 4·341–5·108), respectively, per 1,000 pregnancies. A total of 76·24% cases of fetal CHD were found to be an isolated intracardiac single defect. Among all extracardiac malformations, the CNS was the most common tissue with extracardiac anomalies associated with CHD, accounting for 22·89% of fetal CHD cases. Chromosomal karyotyping identified trisomy 18 as the most common chromosomal abnormality in fetal CHD. Molecular genetic study of copy number variations characterized microdeletion and/or microrepetition/duplication and uniparental disomy. CHD-associated syndromes could be identified with a comprehensive approach integrating prenatal ultrasound, MRI, pathological autopsy, and cytogenetics and molecular genetics. 
 
Interpretation: Implementation of prenatal echocardiography is a practically feasible platform to screen fetal CHD, which may reduce the financial and emotional burden of CHD. 
 
Funding: This study was supported in part by the Key Project of Science and Technology Planning Project of Hubei Province (2010CDA038), the Hubei Province Natural Science Foundation (2012FFB01203), the Key Project of Hubei Province Natural Science Foundation (2011CDA012 and 2014CFA062), and the New York State Research Foundation for Mental Hygiene (914-3280, 914-3257). 
 
Declaration of Interest: All authors have declared that there are no financial conflicts or conflicts of interest with other individuals or organizations. 
 
Ethical Approval: The procedures and protocols implemented were reviewed and approved by the Ethics Committees of Maternal and Child Health Hospital of Hubei Province.