Cohort Of DEafness-gene Screening (CODES)

Cohort of Universal Newborn Deafness-gene Screening in Nantong City, China

This study was based on a concurrent newborn genetic and hearing screening program in Nantong city. From January 2016 to December 2020, newborn infants were recruited and received combined screening for free, funded in part by the municipal government and research project foundations. The population-based longitudinal databank for all children with hearing loss in Nantong city commenced in January 2016 and maintained indefinite recruitment and ongoing follow-up.

Study Overview

• Status: Active, not recruiting
• Conditions: Hearing Loss
• Intervention / Treatment: Genetic: Genetic screening test (Deafness gene variant detection array kit)

Detailed Description

The severity of hearing loss was graded as mild (26-40 dB), moderate (41-60 dB), severe (61-80 dB), and profound (≥81 dB).

Genomic DNA was extracted by a blood filter paper nucleic acid extraction kit (CapitalBio, Beijing, China) and tested using a deafness gene variant detection array kit (CapitalBio, Beijing, China) with LuxScan 10K-B Microarray Scanner (CapitalBio, Beijing, China). The genetic screening entailed genotyping 15 variants in 4 genes: c.35delG, c.176_191del16, c.235delC, c.299_300delAT (GJB2 gene); c.1174A>T, c.1226G>A, c.1229C>T, c.1975G>C, c.2027T>A, c.2168A>G, c.IVS7-2A>G, c.IVS15 + 5G>A (SLC26A4 gene); m.1494C>T, m.1555A>G (MT-RNR1 gene); c.538C>T (GJB3 gene). The results were categorized as (1) negative, (2) carrier (GJB2 or SLC26A4, heterozygous mutations; MT-RNR1 mutations; GJB3 mutations; or heterozygous mutations in multiple genes), and (3) refer (GJB2 or SLC26A4, homozygous or compound heterozygous mutations).

This study was approved by the ethics committees of Nantong municipal Health Commission and all hospitals involved. Written informed consent was obtained from the infant's parents.

This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies.

• Study Type: Observational
• Enrollment (Actual): 35920

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants were newborn infants born between January 2016 and December 2020 from the Han population in Nantong city, China.

Description

Inclusion Criteria:

1. The infants were born between January 2016 and December 2020;
2. The infants' health condition was good enough to tolerate the screening procedures;
3. The parents were urban residents of Nantong city;
4. The parents agreed to have their babies participating in the combined hearing and genetic screening program.

Exclusion Criteria:

1. The infants' blood samples were unqualified for the genetic tests according to criteria of the National Health Commission of China's technical specification for neonatal screening of congenital diseases;
2. The infants were lost to follow-up.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Combined screening; All newborns underwent combined hearing and genetic screening.

Genetic: Genetic screening test (Deafness gene variant detection array kit); Infant participants were screened for fifteen variants in four genes (i.e., GJB2, SLC26A4, MT-RNR1 and GJB3).; Other Names: Newborn hearing screening test (otoacoustic emission, OAE); Hearing re-screening test (OAE and automated auditory brainstem response [AABR]）; Hearing diagnostic test (auditory brainstem response [ABR] and auditory steady state response [ASSR])

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnosis of hearing loss at age of 3 months	Diagnosis of HL was confirmed by hearing diagnostic tests (ABR+ASSR) at age of 3 months. Auditory steady-state response (ASSR) were used as an alternative and adjunct to the auditory brainstem response (ABR) for threshold estimation.	From Jan 1, 2016 to Mar 31, 2021

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Language ability of HL children at ages of 5 years and 8 years	Mandarin sentence repetition task (MSRT) was used to reflect the children's language ability.	From Jan 1, 2021 to Dec 31, 2028
Receptive vocabulary of HL children at ages of 5 years and 8 years	The Chinese version of the Peabody Picture Vocabulary Test-Revised (C-PPVT-R, Lu & Liu, 1998) was used to evaluate children's expressive vocabulary ability. The possible score ranged from 0-125, and test-retest reliability was exceeded 0.9.	From Jan 1, 2021 to Dec 31, 2028
Non-verbal IQ of HL children at ages of 5 years and 8 years	The Chinese version of the Test of Nonverbal Intelligence, fourth edition (C-TONI-4, Lin et al., 2016) was used to evaluate children's nonverbal intelligence regarding problem solving and abstract reasoning. The possible score ranged from 0 to 48, and internal consistency reliability was 0.87.	From Jan 1, 2021 to Dec 31, 2028

Collaborators and Investigators

• Sponsor: Affiliated Hospital of Nantong University
• Collaborators: Nantong Maternal and Child Health Care Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): March 31, 2021
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: November 8, 2023
• First Submitted That Met QC Criteria: November 10, 2023
• First Posted (Estimated): November 16, 2023

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 10, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Cohort study; Newborn hearing screening; Genetic screening
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Hearing Loss; Deafness
• Other Study ID Numbers: BE2015655

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No