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

NCT ID: NCT02551081

Last Updated: 2025-09-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

2000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-10-01

Study Completion Date

2025-12-30

Brief Summary

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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.

Detailed Description

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Neonatal congenital malformation is one of the most frequent cause of infant death in the western world and major cities of China. There are many different types of congenital malformations, and some of these can be caused by changes in gene mutation. Next generation sequencing (NGS) is a high-throughput parallel sequencing that can provide genetic information with high accuracy. It is a faster and cost-effective method to detect gene mutations compared to Sanger sequencing. We hope to couple genomic techniques with more traditional methods involved in genetic discovery in order to investigate a broad range of conditions for which there is strong evidence that genetic factors are involved. So In this study, we evaluated the clinical role of NGS testing for neonatal genetic disease in newborns compared to Sanger sequencing to observe whether this new technology can significantly shorten the time of examination, improve the diagnosis rate, guide the intervention treatments and promote prognosis.

These neonates who have an undiagnosed illness, and partial families, will be eligible to participate in the study. The study population will be recruited from Children's Hospital of Fudan University inpatient population, primarily the neonatal intensive care unit (NICU), with a subpopulation presenting to other hospitals in China. All affected study participants will receive a genetic screening according to their clinical symptom. All subjects will have blood drawn for DNA isolation and genomic sequencing at the time of enrollment in the study. All blood sample volumes will adhere to the Fudan procedure on maximum blood in pediatric patients. In addition, cerebrospinal fluid and tissue samples may be collected and stored in the bank of biosamples. DNA will be isolated and prepared for NGS or Sanger with Fudan protocols at the Translational Medicine Center of Children's Hospital of Fudan University. Partial familial samples will also be obtained, and nucleic acids will also be sequenced, as indicated, to assist in diagnosis of the genetic disease in the newborn. All sequencing data will be stored in the Genome Center Biorepository. In the case of positive study findings that may be diagnostic, our investigator will perform confirmatory clinical diagnostic testing and, if confirmed, a standard clinical diagnostic report will be placed in the patient's medical record. Follow up with the patient's family will be guided by the clinical care team. Both molecular diagnoses results and duration to diagnosis will be recorded as primary outcomes.

In addition, this information will help alleviate anxiety on the part of the family, and also provides a mechanism for patient crossover into the rapid NGS arm if the patient is clinically deteriorating, and at the clinical care team's request. Each time a study participant is enrolled, the clinician and parents will be asked to fill out a survey prior to NGS testing and after return of results. We will also review the patient's medical record and collect clinical variables including laboratory testing, radiology results, medications and other treatments received to further analyze the effect NGS has on clinical care. So the ultimate goal is individualized or personalized therapy. We plan to follow up with families annually up to 18 months post enrollment and record clinical outcomes related to this study.

Conditions

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Genetic Disease Multiple Malformation Congenital Malformation

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Birth Defects

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

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

One of the following criteria required.

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

Exclusion Criteria

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

28 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Xiamen Children's Hospital, Fujian of China

OTHER

Sponsor Role collaborator

Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region

OTHER

Sponsor Role collaborator

Guangzhou Women and Children's Medical Center

OTHER

Sponsor Role collaborator

Second Affiliated Hospital of Wenzhou Medical University

OTHER

Sponsor Role collaborator

Maternal and Child Health Hospital of Hubei Province

OTHER

Sponsor Role collaborator

The Maternal & Children Health Hospital of Dehong, Yunnan of China

OTHER

Sponsor Role collaborator

Children's Hospital of Fudan University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Wenhao Zhou, Doctor

Role: STUDY_CHAIR

Children's Hospital of Fudan University

Locations

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Children Hospital of Fudan University

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Wenhao Zhou, Doctor

Role: CONTACT

Guoqiang Cheng, Doctor

Role: CONTACT

Facility Contacts

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Wenhao Zhou, Doctor

Role: primary

(+86)021-64931003

References

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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Reference Type BACKGROUND
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Reference Type BACKGROUND
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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.

Reference Type DERIVED
PMID: 31146700 (View on PubMed)

Related Links

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http://ClinicalTrials.gov/show/NCT01736501

Surveying Parents About Genome Screening of Newborns

http://ClinicalTrials.gov/show/NCT01545323

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http://ClinicalTrials.gov/show/NCT01780155

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http://ClinicalTrials.gov/show/NCT02231983

Clinical Characteristics and Genetic Profiles of Severe Combined Immunodeficiency in China

http://ClinicalTrials.gov/show/NCT01512888

Gene Transfer for X-Linked Severe Combined Immunodeficiency in Newly Diagnosed Infants

Other Identifiers

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CHFudanU_NNICU2

Identifier Type: -

Identifier Source: org_study_id

NCT02607189

Identifier Type: -

Identifier Source: nct_alias

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