Background Congenital heart defects (CHDs) are the most common type of birth defects. The genetic aetiology of CHD is complex and incompletely understood. The overall distribution of genetic causes in patients with CHD from neonatal intensive care units (NICUs) needs to be studied.
Methods CHD cases were extracted from the China Neonatal Genomes Project (2016–2021). Next-generation sequencing results and medical records were retrospectively evaluated to note the frequency of genetic diagnosis and the respective patient outcomes.
Results In total, 1795 patients were included. The human phenotype ontology term of atrial septal defect, patent ductus arteriosus and ventricular septal defect account for a large portion of the CHD subtype. Co-occurring extracardiac anomalies were observed in 35.1% of patients. 269 of the cases received genetic diagnoses that could explain the phenotype of CHDs, including 172 copy number variations and 97 pathogenic variants. The detection rate of trio-whole-exome sequencing was higher than clinical exome sequencing (21.8% vs 14.5%, p<0.05). Further follow-up analysis showed the genetic diagnostic rate was higher in the deceased group than in the surviving group (29.0% vs 11.9%, p<0.05).
Conclusion This is the largest cohort study to explore the genetic spectrum of patients with CHD in the NICU in China. Our findings may benefit future work on improving genetic screening and counselling for NICU patients with CHD.
Data availability statement
Data are available upon reasonable request. WZ, Children’s Hospital of Fudan University, Shanghai, China, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
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HW and FX are joint first authors.
Contributors HW and FX collected the data and wrote the manuscript. YQ, BW, XD, YL, LY, QN, RL, GL, PZ, XL, XP, YW and HC interpreted medical exome results and conducted analysis on the aggregated large cohort data. GC, LW, KY, LC, WK, LL, XP, QW, DZ, DC, ZY, LY, FL, XM and YC collected, supervised and reviewed the clinical data. WZ and GH supervised the study, critically examined and revised the manuscript. WZ is responsible for the overall content as guarantor
Funding This study was supported by National Key Research and Development Program (2021YFC2701000, Professor Huang), Chinese Academy of Medical Sciences Research Unit (2018RU002, Professor Huang), Shen Kang Hospital Development Centre Clinical Science and Technology innovation project of Shanghai (SHDC2020CR6028-002, Professor Zhou), Shanghai Sailing Programme (18YF1402600, Dr Qian), Shanghai Municipal Science and Technology Major Project (Grant No. 20Z11900600, Professor Zhou), the project of Shanghai Key Laboratory of Birth Defects (13DZ2260600) and Shanghai Municipal Science and Technology Major Project (Grant No. 2017SHZDZX01, Professor Zhou).
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Competing interests None declared.
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