Genomic Sequencing and Personalized Treatment for Birth Defects in Neonatal Intensive Care Units

NCT02551081 | Recruiting DMC

• 1 other identifier: CHFudanU_NNICU2
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of study is to evaluate the benefits of using the Next Generation Sequencing Technology to diagnose birth defects and genetic diseases. The results from genomic sequencing can also significantly shorten the time of examination, improve the diagnosis rate, guide the clinical treatments. So the ultimate goal is individualized or personalized therapy and promote prognosis.

Conditions

Genetic Disease; Multiple Malformation; Congenital Malformation

Outcome Measures

Primary Outcomes (3)

• Mortality

  The relative frequency of deaths in each group.

  At corrected age of 18 months

• Disability Rate

  Disability, defined as a physical or mental handicap, especially one that prevents a person from living a full, normal life or from holding a gainful job.

  At corrected age of 18 months

• Gene Mutation

  To detect the mutation and characterize the genetic architecture and risk variants of neonatal malformation using different genomic methods.

  In 30 days after receipt of the sample

Secondary Outcomes (3)

• Neurodevelopment(Bayley Scores)

  At corrected age of 18 months

• Respiratory Support

  In 14 days after results disclosure

• Care Level

  In 14 days after results disclosure

Other Outcomes (4)

• The total cost for hospitalization

  At corrected age of 18 months

• Average days of hospitalization

  At corrected age of 18 months

• Parents' understanding of study results

  At corrected age of 3 months

Study Arms (1)

Birth Defects

Neonates were diagnosed as birth defects who were recieving genomic sequencing and personalized treatment in NICU.

Eligibility Criteria

• Age: Up to 28 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

The study population will be recruited from Hospital inpatient population, primarily the neonatal intensive care unit who has some anomaly or abnormal laboratory testing suggestive of a genetic disease.

You may qualify if:

• One of the following criteria required.
• Neonates admitted to the Neonatal Intensive Care Units in one of the study hospitals
• Clinical genetic testing or a genetic consult is ordered
• Subject has one major structural anomaly or three or more minor anomalies
• Abnormal laboratory testing suggestive of a genetic disease
• Abnormal response to standard therapy for a major underlying condition

You may not qualify if:

• Previously performed exome/genome sequencing on patient
• Any infant in which clinical considerations preclude drawing 1.0 ml of blood
• Has features pathognomonic for a large chromosomal aberration (Trisomy 13, 18, 21 or other)
• Parents are unwilling to have genomic reports placed in the medical record or sent to their primary care pediatrician
• Parents refuse consent

Sponsors & Collaborators

• Children's Hospital of Fudan University: lead
• Xiamen Children's Hospital, Fujian of China: collaborator
• Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region: collaborator
• Guangzhou Women and Children's Medical Center: collaborator
• Second Affiliated Hospital of Wenzhou Medical University: collaborator
• Maternal and Child Health Hospital of Hubei Province: collaborator
• The Maternal & Children Health Hospital of Dehong, Yunnan of China: collaborator

Study Sites (1)

Children Hospital of Fudan University

Shanghai, Shanghai Municipality, China

RECRUITING

Related Publications (10)

• Viggiano E, Marabotti A, Burlina AP, Cazzorla C, D'Apice MR, Giordano L, Fasan I, Novelli G, Facchiano A, Burlina AB. Clinical and molecular spectra in galactosemic patients from neonatal screening in northeastern Italy: structural and functional characterization of new variations in the galactose-1-phosphate uridyltransferase (GALT) gene. Gene. 2015 Apr 1;559(2):112-8. doi: 10.1016/j.gene.2015.01.013. Epub 2015 Jan 13.

  PMID: 25592817 BACKGROUND

• Yang D, Sun YY, Bhaumik SK, Li Y, Baumann JM, Lin X, Zhang Y, Lin SH, Dunn RS, Liu CY, Shie FS, Lee YH, Wills-Karp M, Chougnet CA, Kallapur SG, Lewkowich IP, Lindquist DM, Murali-Krishna K, Kuan CY. Blocking lymphocyte trafficking with FTY720 prevents inflammation-sensitized hypoxic-ischemic brain injury in newborns. J Neurosci. 2014 Dec 3;34(49):16467-81. doi: 10.1523/JNEUROSCI.2582-14.2014.

  PMID: 25471584 BACKGROUND

• Scully MA, Farrell PM, Ciafaloni E, Griggs RC, Kwon JM. Cystic fibrosis newborn screening: a model for neuromuscular disease screening? Ann Neurol. 2015 Feb;77(2):189-97. doi: 10.1002/ana.24316. Epub 2014 Dec 13.

  PMID: 25425541 BACKGROUND

• Hamilton ST, van Zuylen W, Shand A, Scott GM, Naing Z, Hall B, Craig ME, Rawlinson WD. Prevention of congenital cytomegalovirus complications by maternal and neonatal treatments: a systematic review. Rev Med Virol. 2014 Nov;24(6):420-33. doi: 10.1002/rmv.1814. Epub 2014 Oct 14.

  PMID: 25316174 BACKGROUND

• Matic M, Simons SH, van Lingen RA, van Rosmalen J, Elens L, de Wildt SN, Tibboel D, van Schaik RH. Rescue morphine in mechanically ventilated newborns associated with combined OPRM1 and COMT genotype. Pharmacogenomics. 2014 Jul;15(10):1287-95. doi: 10.2217/pgs.14.100.

  PMID: 25155931 BACKGROUND

• Kwan A, Abraham RS, Currier R, Brower A, Andruszewski K, Abbott JK, Baker M, Ballow M, Bartoshesky LE, Bonilla FA, Brokopp C, Brooks E, Caggana M, Celestin J, Church JA, Comeau AM, Connelly JA, Cowan MJ, Cunningham-Rundles C, Dasu T, Dave N, De La Morena MT, Duffner U, Fong CT, Forbes L, Freedenberg D, Gelfand EW, Hale JE, Hanson IC, Hay BN, Hu D, Infante A, Johnson D, Kapoor N, Kay DM, Kohn DB, Lee R, Lehman H, Lin Z, Lorey F, Abdel-Mageed A, Manning A, McGhee S, Moore TB, Naides SJ, Notarangelo LD, Orange JS, Pai SY, Porteus M, Rodriguez R, Romberg N, Routes J, Ruehle M, Rubenstein A, Saavedra-Matiz CA, Scott G, Scott PM, Secord E, Seroogy C, Shearer WT, Siegel S, Silvers SK, Stiehm ER, Sugerman RW, Sullivan JL, Tanksley S, Tierce ML 4th, Verbsky J, Vogel B, Walker R, Walkovich K, Walter JE, Wasserman RL, Watson MS, Weinberg GA, Weiner LB, Wood H, Yates AB, Puck JM, Bonagura VR. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA. 2014 Aug 20;312(7):729-38. doi: 10.1001/jama.2014.9132.

  PMID: 25138334 BACKGROUND

• Morrone A, Caciotti A, Atwood R, Davidson K, Du C, Francis-Lyon P, Harmatz P, Mealiffe M, Mooney S, Oron TR, Ryles A, Zawadzki KA, Miller N. Morquio A syndrome-associated mutations: a review of alterations in the GALNS gene and a new locus-specific database. Hum Mutat. 2014 Nov;35(11):1271-9. doi: 10.1002/humu.22635. Epub 2014 Sep 17.

  PMID: 25137622 BACKGROUND

• Mercimek-Mahmutoglu S, Cordeiro D, Cruz V, Hyland K, Struys EA, Kyriakopoulou L, Mamak E. Novel therapy for pyridoxine dependent epilepsy due to ALDH7A1 genetic defect: L-arginine supplementation alternative to lysine-restricted diet. Eur J Paediatr Neurol. 2014 Nov;18(6):741-6. doi: 10.1016/j.ejpn.2014.07.001. Epub 2014 Jul 27.

  PMID: 25127453 BACKGROUND

• Eldar-Geva T, Srebnik N, Altarescu G, Varshaver I, Brooks B, Levy-Lahad E, Bromiker R, Schimmel MS. Neonatal outcome after preimplantation genetic diagnosis. Fertil Steril. 2014 Oct;102(4):1016-21. doi: 10.1016/j.fertnstert.2014.06.023. Epub 2014 Jul 23.

  PMID: 25064409 BACKGROUND

• Chen X, Yan K, Gao Y, Wang H, Chen G, Wu B, Qin Q, Yang L, Zhou W. Feeding difficulty is the dominant feature in 12 Chinese newborns with CHD7 pathogenic variants. BMC Med Genet. 2019 May 30;20(1):93. doi: 10.1186/s12881-019-0813-z.

  PMID: 31146700 DERIVED

Related Links

• Surveying Parents About Genome Screening of Newborns
• Gene Therapy for Netherton Syndrome
• Genes Associated With Bronchopulmonary Dysplasia and Retinopathy of Prematurity
• Clinical Characteristics and Genetic Profiles of Severe Combined Immunodeficiency in China
• Gene Transfer for X-Linked Severe Combined Immunodeficiency in Newly Diagnosed Infants

MeSH Terms

Conditions

Genetic Diseases, Inborn; Congenital Abnormalities

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Wenhao Zhou, Doctor

  Children's Hospital of Fudan University

  STUDY CHAIR

Central Study Contacts

Wenhao Zhou, Doctor

CONTACT

zwhchfu@126.com

Guoqiang Cheng, Doctor

CONTACT

gqchengcm@163.com

Study Design

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

Study Record Dates

• First Submitted: September 4, 2015
• First Posted: September 16, 2015
• Study Start: October 1, 2015
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: September 5, 2025

Record last verified: 2025-09

Locations

CN (1)