Study on Early Genetic Screening and Precise Strategy of Neonatal Critical Illness

NCT04905537 | Recruiting

• 1 other identifier: CHFudanU_NNICU15
• Study Type: observational
• Target: 4,000
• Locations: 1 country
• Sites: 1

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.

Conditions

Genetic Screening; Hereditary Disease; Newborn; Stillbirth

Outcome Measures

Primary Outcomes (1)

• Gene Mutation

  To detect the mutation and characterize the genetic architecture and risk variants (911 variants of 146 genes, for example, AGT, AGTR1, CA12, CD2AP et al) of subjects using different genomic methods

  In 3 months after receipt of the samples

Study Arms (1)

Sick Neonates or Stillbirth

Infants and their parents enrolled through Neonatal Intensive Care Unit or stillbirths through Obstetrics Department of member hospitals who are un-randomized to receive genomic sequencing. Results disclosure sessions will include a discussion of: family history report, results from standard newborn screening, any potentially medically relevant findings from the baby's medical history/ physical exam, and the results of the genomic sequencing report.

Other: No intervention

Interventions

No intervention OTHER

It's only observational study. No interventions.

Sick Neonates or Stillbirth

Eligibility Criteria

• Age: Up to 100 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital of Fudan University: lead
• International Peace Maternity and Child Health Hospital: collaborator
• Obstetrics & Gynecology Hospital of Fudan University: collaborator
• Xinhua Hospital, Shanghai Jiao Tong University School of Medicine: collaborator
• Shanghai Children's Medical Center: collaborator
• Shanghai Children's Hospital: collaborator

Study Sites (1)

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, China

RECRUITING

Related Publications (8)

• 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.

  PMID: 31501239 BACKGROUND

• 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.

  PMID: 15098237 BACKGROUND

• 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.

  PMID: 25937001 BACKGROUND

• 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.

  PMID: 27241786 BACKGROUND

• 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.

  PMID: 28654725 BACKGROUND

• 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.

  PMID: 30609409 BACKGROUND

• 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.

  PMID: 28096516 BACKGROUND

• 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.

  PMID: 31246743 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

The researchers retained the neonates', infants' or stillbirths' 2ml peripheral blood, cord blood, amniotic fluid, muscle or saliva as a biological sample for gene screening.

MeSH Terms

Conditions

Genetic Diseases, Inborn; Stillbirth

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Fetal Death; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Wenhao Zhou

  Children's Hospital of Fudan University

  STUDY CHAIR

Central Study Contacts

Wenhao Zhou

CONTACT

+86-21-64931913; zhouwenhao@fudan.edu.cn

Lin Yang

CONTACT

yanglin_fudan@163.com

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2021
• First Posted: May 27, 2021
• Study Start: January 1, 2021
• Primary Completion: November 1, 2025
• Study Completion: December 1, 2025
• Last Updated: February 20, 2025

Record last verified: 2025-02

Locations

CN (1)