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Chinese Journal of Evidence -Based Pediatric ›› 2019, Vol. 14 ›› Issue (4): 247-253.DOI: 10.3969/j.issn.1673-5501.2019.04.002

• Original Papers • Previous Articles     Next Articles

Cross-sectional study on screening and diagnosis of neonatal birth defects in the Qinghai area by tandem mass spectrometry and high throughput sequencing

ZHAO De-xiong1,5, WU Meng-yuan 2,5, WU Bing-bing2, SUN Wei-hua2, PENG Xiao-min2, WU Hong-jiang2, WANG Sheng-lan1, HAI Yu-ting1, ZHOU Wen-hao2,3, WANG Hui-jun2, LU Wei4   

  1. 1 Obstetrics and Gynecology Department, Qinghai Red Cross Hospital,Qinghai 810000, China;
    2 Molecular Medical Center, Pediatric Research Institute, Children's Hospital of Fudan University, Shanghai 201102, China;
    3 Neonatal Department, Children's Hospital of Fudan University, Shanghai 201102, China;
    4 Department of Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai 201102, China;
    5 Co-first author
  • Received:2019-06-28 Revised:2019-08-20 Online:2019-08-25
  • Contact: LU Wei, E-mail:wei_lu77@163.com;WANG Hui-jun,E-mail: huijunwang@fudan.edu.cn

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Abstract: Objective To explore the value of tandem mass spectrometry (MS/MS) and targeted next-generation sequencing (NGS) for the prevention and intervention of neonatal birth defects, we examined the incidence and spectrum of genomic disorders in newborns in Qinghai using MS/MS and NGS.Methods Dried blood spots were collected to determine amino acids and acylcarnitines by MS/MS (including 20 kinds of amino acid metabolic diseases, 12 kinds of fatty acid metabolic diseases and 17 kinds of organic acid metabolic diseases) conducted in neonates from Qinghai, which were recruited between January 8 and October 12 in 2018. Among them neonates with abnormal tandem mass spectrometry screening results,special facial features and structural abnormalities, and their mothers with bad obstetric history were screened by high throughput sequencing (NGS, including 2,742 known pathogenic genes). The positive samples were verified by sanger sequencing.Results Four thousand and sixteen newborns in Qinghai were enrolled in this project, including 2,125 male cases (51.6%). The total group consisted of 58.1% Han people, 18.8% Tibetans and 16.4% Hui people, with 59 MS/MS screening positive (1.47%), including 5 cases indicating IMD and 54 of secondary changes. Three cases of IMD (0.074%) were further diagnosed by NGS analysis. The observed abnormalities comprised 2 of amino acid metabolic diseases (PKU 2 cases) and 1 fatty acid metabolism disease (PCD), with an overall IMD incidence of 1 in 1,339. Eight cases with genetic variation (including 3 cases of IMD) and 6 cases with copy number variation were identified by NGS. Additionally, differences were observed between Han, Tibetan and Hui populations on the concentration levels of amino acids and acylcarnitines.Conclusion The incidence of IMD in newborns in Qinghai is higher than that in other areas reported in China. Our results suggest that NGS can not only confirm the suspicious but uncertain results indicated by MS/MS, but also effectively detect risk and carrier status for a wide range of neonatal birth defects that are not detectable by MS/MS.

Key words: Birth defects, High altitude, Inherited metabolic disorders, Next-generation sequencing, Tandem mass spectrometry