Clinical trial NCT04905537: Study on Early Genetic Screening and Precise Strategy of Neonatal Critical Illness
Official title: Study on Early Genetic Screening and Precise Strategy of Neonatal Critical Illness
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Genetic Screening
Hereditary Disease
Newborn
Stillbirth
Lead sponsor: Children's Hospital of Fudan University
Sponsor class: OTHER
Collaborators: name: International Peace Maternity and Child Health Hospital
name: Obstetrics & Gynecology Hospital of Fudan University
name: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: Shanghai Children's Medical Center
name: Shanghai Children's Hospital
First posted: 2021-05-27
Enrollment: 4000
Sex: ALL
Maximum age (years): 100
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The subjects were all from all the member organizations participating in this research. They were hospitalized in the neonatal department or stillbirth in obstetrics department of each member hospital.

Brief summary: The researchers hope to establish an overall program of early genetic screening for neonatal critical illness in China, and to develop precise intervention strategies to assist clinical diagnosis and treatment of hereditary critical illness.

Detailed description: Reducing the rate of neonatal death and disability is an important part of health education in China, and genetic diseases are an important cause of neonatal death. At present, with the development of life support platform technology, the treatment level of critically ill newborns has been rapidly improved. How to quickly diagnose and early precise intervention is the key to further break through the diagnosis and treatment of genetic diseases. Based on the "neonatal genome project" carried out in the early stage, the research group based on the genetic diagnosis results of over 10000 cases of neonatal critical illness cohort, studied the genetic disease spectrum of neonatal critical illness in line with the actual situation in China. In terms of detection technology, based on the second-generation sequencing technology, we established a critical illness screening gene sequencing combination including 300 genes; In the aspect of data analysis, an intelligent analysis process integrating clinical phenotype and gene sequencing data was established; In terms of clinical diagnosis and treatment, we cooperated with 5 maternity and children's hospitals in Shanghai to carry out multi center clinical verification, and formed the implementation plan of early universal genetic screening for neonatal critical illness. Through this project, we will carry out genetic disease screening research on neonatal critical diseases, focus on typical clinical manifestations such as encephalopathy, immunodeficiency, metabolic diseases, and carry out molecular autopsy on neonatal death cases to identify potential genetic causes, so as to provide basis for the research of corresponding early precise intervention strategies, and achieve the purpose of reducing neonatal death and disability rate.

Eligibility criteria: Inclusion Criteria:

* Postnatal age less than 100 days;
* Perinatal death after 20 weeks of gestation (more than 500 g)
* Can be retained biological samples for genetic screening;
* Biological parent or guardian's informed consent.

Exclusion Criteria:

* Reluctance of parents to use genetic sequencing data for subsequent research;
* Parents under 18 years of age or incapacitated for decision-making;
* subjects older than 100 days;
* Perinatal death less than 20 weeks of gestation or weight less than 500 g;
* Inherited metabolic diseases with chromosomal abnormalities;
* Multiple pregnancies;
* Lack of access to biological samples from which DNA can be extracted;
* Failure to sign informed consent.

Primary outcomes:
measure: Gene Mutation
timeFrame: In 3 months after receipt of the samples
Secondary outcomes:
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
state: Shanghai
Study officials:
affiliation: Children's Hospital of Fudan University
name: Wenhao Zhou
role: STUDY_CHAIR
References:
citation: Yang L, Liu X, Li Z, Zhang P, Wu B, Wang H, Hu L, Cheng G, Wang L, Zhou W. Genetic aetiology of early infant deaths in a neonatal intensive care unit. J Med Genet. 2020 Mar;57(3):169-177. doi: 10.1136/jmedgenet-2019-106221. Epub 2019 Sep 9.
citation: Stevenson DA, Carey JC. Contribution of malformations and genetic disorders to mortality in a children's hospital. Am J Med Genet A. 2004 May 1;126A(4):393-7. doi: 10.1002/ajmg.a.20409.
citation: Willig LK, Petrikin JE, Smith LD, Saunders CJ, Thiffault I, Miller NA, Soden SE, Cakici JA, Herd SM, Twist G, Noll A, Creed M, Alba PM, Carpenter SL, Clements MA, Fischer RT, Hays JA, Kilbride H, McDonough RJ, Rosterman JL, Tsai SL, Zellmer L, Farrow EG, Kingsmore SF. Whole-genome sequencing for identification of Mendelian disorders in critically ill infants: a retrospective analysis of diagnostic and clinical findings. Lancet Respir Med. 2015 May;3(5):377-87. doi: 10.1016/S2213-2600(15)00139-3. Epub 2015 Apr 27.
citation: Daoud H, Luco SM, Li R, Bareke E, Beaulieu C, Jarinova O, Carson N, Nikkel SM, Graham GE, Richer J, Armour C, Bulman DE, Chakraborty P, Geraghty M, Lines MA, Lacaze-Masmonteil T, Majewski J, Boycott KM, Dyment DA. Next-generation sequencing for diagnosis of rare diseases in the neonatal intensive care unit. CMAJ. 2016 Aug 9;188(11):E254-E260. doi: 10.1503/cmaj.150823. Epub 2016 May 30.
citation: Amberger JS, Hamosh A. Searching Online Mendelian Inheritance in Man (OMIM): A Knowledgebase of Human Genes and Genetic Phenotypes. Curr Protoc Bioinformatics. 2017 Jun 27;58:1.2.1-1.2.12. doi: 10.1002/cpbi.27.
citation: Ceyhan-Birsoy O, Murry JB, Machini K, Lebo MS, Yu TW, Fayer S, Genetti CA, Schwartz TS, Agrawal PB, Parad RB, Holm IA, McGuire AL, Green RC, Rehm HL, Beggs AH; BabySeq Project Team. Interpretation of Genomic Sequencing Results in Healthy and Ill Newborns: Results from the BabySeq Project. Am J Hum Genet. 2019 Jan 3;104(1):76-93. doi: 10.1016/j.ajhg.2018.11.016.
citation: Berg JS, Agrawal PB, Bailey DB Jr, Beggs AH, Brenner SE, Brower AM, Cakici JA, Ceyhan-Birsoy O, Chan K, Chen F, Currier RJ, Dukhovny D, Green RC, Harris-Wai J, Holm IA, Iglesias B, Joseph G, Kingsmore SF, Koenig BA, Kwok PY, Lantos J, Leeder SJ, Lewis MA, McGuire AL, Milko LV, Mooney SD, Parad RB, Pereira S, Petrikin J, Powell BC, Powell CM, Puck JM, Rehm HL, Risch N, Roche M, Shieh JT, Veeraraghavan N, Watson MS, Willig L, Yu TW, Urv T, Wise AL. Newborn Sequencing in Genomic Medicine and Public Health. Pediatrics. 2017 Feb;139(2):e20162252. doi: 10.1542/peds.2016-2252. Epub 2017 Jan 17.
citation: Sanford EF, Clark MM, Farnaes L, Williams MR, Perry JC, Ingulli EG, Sweeney NM, Doshi A, Gold JJ, Briggs B, Bainbridge MN, Feddock M, Watkins K, Chowdhury S, Nahas SA, Dimmock DP, Kingsmore SF, Coufal NG; RCIGM Investigators. Rapid Whole Genome Sequencing Has Clinical Utility in Children in the PICU. Pediatr Crit Care Med. 2019 Nov;20(11):1007-1020. doi: 10.1097/PCC.0000000000002056.