Human ; Infant, Newborn ; Mass Screening ; Neonatal Screening ; Censuses

Infant, Newborn ; Mass Screening ; Neonatal Screening

Objective:To determine the effectiveness of a one-stage hearing screening protocol in detecting hearing loss in high risk newborns at the Neonatal Intensive Care Unit of the Jose R. Reyes Memorial Medical Center.

Methods:
Design:Cross-Sectional Study
Setting:Tertiary Government Training Hospital
Population:High-risk newborns admitted at the Neonatal Intensive Care Unit of the Jose R. Reyes Memorial Medical Center from March to December 2023 underwent a one stage universal newborn hearing screening protocol. Excluded from the study were patients who were admitted for less than 48 hours, without consent from their parents or guardians and babies who were not cleared medically to undergo testing, and those who presented with aural atresia and/or any physical anomaly of the head and the external ear.

Results:A total of 169 babies were initially seen with 16 babies lost to follow up resulting in a final total of 153 babies (or 306 ears) tested. The refer and false positive rates were 9.8% and 8.92%, respectively, on average comparable to or even better than the two-step protocol in most studies. Sensitivity was determined to be 100% while specificity was 91.08%. The incidence of hearing loss in the study population was 19.8/1000, consistent with various study outcomes for high risk newborns. There was no reported incidence of auditory neuropathy in this study. The primary risk factors that were present in babies with hearing loss were: low birth weight, prematurity, neonatal intensive care unit admission of more than 5 days and exposure to ototoxic medications.

Conclusion:The one-staged Automated Auditory Brainstem Response (AABR) is an effective and efficient newborn hearing screening protocol for high-risk newborns in the Neonatal Intensive Care Unit (NICU) setting and eventually, may be considered as an alternative hearing screening technique whenever available in this cohort. More studies about improving newborn hearing screening, cost-analysis, diagnostics and interventions of hearing loss should be pursued in implementation of the Universal Hearing Screening Law in the Philippines.

OBJECTIVES: To evaluate the clinical value of next-generation sequencing (NGS) in neonatal disease screening, particularly its advantages when combined with tandem mass spectrometry (MS/MS). METHODS: A prospective study was conducted involving blood samples from 1 999 neonates born at the Shenzhen Guangming District People's Hospital, between May and August 2021. All samples were initially screened using MS/MS and fluorescence immunoassay, followed by NGS to detect high-frequency variation sites in 135 related pathogenic genes. Suspected positive variants were validated using Sanger sequencing or multiplex ligation-dependent probe amplification in family studies. RESULTS: No confirmed positive cases were found in the MS/MS analysis of the 1 999 neonates. Genetic screening identified 58 positive cases (2.90%), 732 carriers of pathogenic genes (36.62%), and 1 209 negative cases (60.48%). One case of neonatal intrahepatic cholestasis was diagnosed (0.05%, 1/1 999). Fluorescence immunoassay identified 39 cases of glucose-6-phosphate dehydrogenase (G6PD) deficiency (1.95%, 39/1 999), while genetic screening identified 43 cases of G6PD deficiency (2.15%, 43/1 999). The fluorescence immunoassay also detected 6 cases of hyperthyrotropinemia (0.30%, 6/1 999), all of whom carried DUOX2 gene variants. The top ten pathogenic gene carrier rates were G6PD (12.8%), DUOX2 (8.7%), HBB (8.2%), ATP7B (6.6%), GJB2 (5.7%), SLC26A4 (5.6%), PAH (5.6%), ACADSB (4.6%), SLC25A13 (4.2%), and SLC22A5 (4.1%). CONCLUSIONS NGS can serve as an effective complement to MS/MS, significantly improving the detection rate of inherited metabolic disorders in neonates. When combined with family validation, it enables precise diagnosis, particularly demonstrating complementary advantages in screening for monogenic diseases such as G6PD deficiency.
Humans ; Infant, Newborn ; High-Throughput Nucleotide Sequencing/methods* ; Neonatal Screening/methods* ; Tandem Mass Spectrometry ; Prospective Studies ; Female ; Male ; Infant, Newborn, Diseases/diagnosis* ; Genetic Testing

OBJECTIVES: To evaluate the application value of genetic newborn screening (gNBS) in the Yunnan region. METHODS: A prospective study was conducted with a random selection of 3 001 newborns born in the Yunnan region from February to December 2021. Traditional newborn screening (tNBS) was used to test biochemical indicators, and targeted next-generation sequencing was employed to screen 159 genes related to 156 diseases. Positive-screened newborns underwent validation and confirmation tests, and confirmed cases received standardized treatment and long-term follow-up. RESULTS: Among the 3 001 newborns, 166 (5.53%) were initially positive for genetic screening, and 1 435 (47.82%) were genetic carriers. The top ten genes with the highest variation frequency were GJB2 (21.29%), DUOX2 (7.27%), HBA (6.14%), GALC (3.63%), SLC12A3 (3.33%), HBB (3.03%), G6PD (2.94%), SLC25A13 (2.90%), PAH (2.73%), and UNC13D (2.68%). Among the initially positive newborns from tNBS and gNBS, 33 (1.10%) and 47 (1.57%) cases were confirmed, respectively. A total of 48 (1.60%) cases were confirmed using gNBS+tNBS. The receiver operating characteristic curve analysis demonstrated that the areas under the curve for tNBS, gNBS, and gNBS+tNBS in diagnosing diseases were 0.866, 0.982, and 0.968, respectively (P<0.05). DeLong's test showed that the area under the curve for gNBS and gNBS+tNBS was higher than that for tNBS (P<0.05). CONCLUSIONS gNBS can expand the range of disease detection, and its combined use with tNBS can significantly shorten diagnosis time, enabling early intervention and treatment.
Humans ; Infant, Newborn ; Neonatal Screening ; Genetic Testing ; Female ; Male ; Follow-Up Studies ; Prospective Studies ; China

OBJECTIVES: To develop a quality control indicator system for neonatal screening of inherited metabolic diseases in obstetric settings, so as to provide a standardized tool for quality control in clinical neonatal screening of inherited metabolic diseases. METHODS: From March to May 2024, a literature review combined with expert clinical experience was conducted to develop a preliminary questionnaire on quality control indicators for neonatal screening of inherited metabolic diseases. The final indicator system was established after two rounds of the Delphi method, and the Analytic Hierarchy Process was used to determine indicator weights. RESULTS: Sixteen questionnaires were distributed in each of the two consultation rounds, with a valid response rate of 100% for both. The expert authority coefficients were 0.863 and 0.876, respectively. Kendall's coefficient of concordance for the importance and feasibility of the indicators ranged from 0.091 to 0.125. The final indicator system comprised 3 primary indicators, 8 secondary indicators, and 28 tertiary indicators for neonatal screening of inherited metabolic diseases in obstetric settings. CONCLUSIONS The quality control indicator system developed using the Delphi method demonstrates a strong systematic structure, high clinical adaptability, and strong operability, and can be effectively applied to quality control in neonatal screening of inherited metabolic diseases in obstetric settings.
Humans ; Infant, Newborn ; Neonatal Screening/standards* ; Quality Control ; Metabolism, Inborn Errors/diagnosis* ; Metabolic Diseases/diagnosis* ; Delphi Technique ; Female ; Quality Indicators, Health Care ; Pregnancy

OBJECTIVES: To evaluate the clinical utility and translational potential of a remote jaundice monitoring system for home-based screening of neonatal hyperbilirubinemia. METHODS: A prospective self-controlled study was conducted, enrolling 538 newborns with gestational age ≥35 weeks, birth weight ≥2 000 g, and postnatal age ≤14 days at the Women's Hospital of Nanjing Medical University from March to October 2023. Four screening protocols with different predictive indicators were developed based on the Chinese Neonatal Transcutaneous Hourly Bilirubin Nomogram. The effectiveness of the system was evaluated, and the feasibility of using the remote jaundice monitoring system in actual home settings was analyzed. RESULTS: A total of 538 paired transcutaneous bilirubin (TcB) and total serum bilirubin (TSB) measurements showed a strong correlation (r=0.85, P<0.001), with 95.0% (511/538) of samples within the 95% limits of agreement. Using TcB ≥ the 95th percentile as the predictive indicator, the system achieved 100% sensitivity, 46.2% specificity, and an area under the receiver operating characteristic curve of 0.731 (95%CI: 0.682-0.780). This approach could reduce unnecessary hospital visits by 41.4% (221/538). CONCLUSIONS The system integrates the QBH-801 transcutaneous bilirubinometer, intelligent early warning, and remote guidance services, establishing a closed-loop "hospital-to-home" management model. It demonstrates high safety and feasibility, with significant clinical translational value.
Humans ; Infant, Newborn ; Female ; Male ; Bilirubin/blood* ; Feasibility Studies ; Prospective Studies ; Hyperbilirubinemia, Neonatal/diagnosis* ; Neonatal Screening/methods* ; Jaundice, Neonatal/diagnosis*

Objective:To analyze the hearing phenotypes of p. V37I homozygote and compound heterozygote mutation in GJB2 gene, and to provide basis for genetic counseling. Methods:Fifty-three subjects with p. V37I homozygote and compound heterozygote mutation were recruited at Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital from January 2023 to March 2024. All subjects received universal newborn hearing screening（UNHS）, 23-site chip neonatal deafness genetic screening and audiological tests, including ABR, acoustic immittance, DPOAE, ASSR. The results of newborn hearing screening and hearing diagnosis were compared between homozygous mutation group of 30 cases and compound heterozygous mutation group of 23 cases. Results:In 53 cases, the overall refer rate of UNHS was 64.15%（34/53）, the refer rate of homozygous mutation group was 80.00%（24/30）, which was higher than that of compound heterozygous mutation group（43.48%, 10/23）, the difference between the two groups was statistically significant（P<0.05）. Three subjects with p. V37I compound heterozygous mutation had passed UNHS and diagnosed with unilateral mild hearing loss. The average age of diagnosis of 53 cases was （3.77±1.40） months, 25 cases with hearing loss accounted for 47.17%, including 13 cases with unilateral, 12 cases with bilateral, 28 cases with normal hearing accounted for 52.83%. There was no significant difference between homozygous mutation group（56.67%, 17/30） and compound heterozygous mutation group（34.78%, 8/23） in the proportion of confirmed hearing loss（P>0.05）. Among 37 ears of 25 patients with hearing loss, the proportion of mild, moderate and profound hearing loss were 70.27%（26/37）, 27.03%（10/37） and 2.70%（1/37）, respectively. The hearing loss degree of the homozygous mutation group and the compound heterozygous mutation group were mainly mild, accounting for 70.37%（19/27） and 70.00%（7/10） respectively. There was no significant difference between the two groups in the distribution of hearing loss degree（P>0.05）. Conclusion:The probability of hearing loss was 47.17% in infants of GJB2 gene p. V37I homozygote and compound heterozygote mutation, mainly mild hearing loss. There was no difference in the probability of hearing loss and the distribution of hearing loss degree between the two groups. Patients with p. V37I homozygous and compound heterozygous mutation currently diagnosed as normal hearing need continuous clinical follow-up.
Humans ; Connexin 26 ; Heterozygote ; Homozygote ; Female ; Phenotype ; Male ; Mutation ; Connexins/genetics* ; Infant ; Infant, Newborn ; Hearing Tests ; Neonatal Screening ; Deafness/genetics* ; Genetic Testing

OBJECTIVE: To assess the value of genetic screening by high-throughput sequencing (HTS) for the early diagnosis of neonatal diseases. METHODS: A total of 2 060 neonates born at Ningbo Women and Children's Hospital from March to September 2021 were selected as the study subjects. All neonates had undergone conventional tandem mass spectrometry metabolite analysis and fluorescent immunoassay analysis. HTS was carried out to detect the definite pathogenic variant sites with high-frequency of 135 disease-related genes. Candidate variants were verified by Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA). RESULTS: Among the 2 060 newborns, 31 were diagnosed with genetic diseases, 557 were found to be carriers, and 1 472 were negative. Among the 31 neonates, 5 had G6PD, 19 had hereditary non-syndromic deafness due to variants of GJB2, GJB3 and MT-RNR1 genes, 2 had PAH gene variants, 1 had GAA gene variants, 1 had SMN1 gene variants, 2 had MTTL1 gene variants, and 1 had GH1 gene variants. Clinically, 1 child had Spinal muscular atrophy (SMA), 1 had Glycogen storage disease II, 2 had congenital deafness, and 5 had G6PD deficiency. One mother was diagnosed with SMA. No patient was detected by conventional tandem mass spectrometry. Conventional fluorescence immunoassay had revealed 5 cases of G6PD deficiency (all positive by genetic screening) and 2 cases of hypothyroidism (identified as carriers). The most common variants identified in this region have involved DUOX2 (3.93%), ATP7B (2.48%), SLC26A4 (2.38%), GJB2 (2.33%), PAH (2.09%) and SLC22A5 genes (2.09%). CONCLUSION Neonatal genetic screening has a wide range of detection and high detection rate, which can significantly improve the efficacy of newborn screening when combined with conventional screening and facilitate secondary prevention for the affected children, diagnosis of family members and genetic counseling for the carriers.
Child ; Infant, Newborn ; Humans ; Female ; Prospective Studies ; Connexins/genetics* ; Connexin 26/genetics* ; Glucosephosphate Dehydrogenase Deficiency ; Mutation ; Sulfate Transporters/genetics* ; DNA Mutational Analysis ; Genetic Testing/methods* ; Deafness/genetics* ; Neonatal Screening/methods* ; Hearing Loss, Sensorineural/genetics* ; High-Throughput Nucleotide Sequencing ; Solute Carrier Family 22 Member 5/genetics*

OBJECTIVE: To analyze the clinical significance of combined newborn hearing and deafness gene screening in Yuncheng area of Shanxi Province. METHODS: Results of audiological examinations, including transient evoked otoacoustic emission and automatic discriminative auditory brainstem evoked potentials, for 6 723 newborns born in Yuncheng area from January 1, 2021 to December 31, 2021, were retrospectively analyzed. Those who failed one of the tests were considered to have failed the examination. A deafness-related gene testing kit was used to detect 15 hot spot variants of common deafness-associated genes in China including GJB2, SLC26A4, GJB3, and mtDNA12S rRNA. Neonates who had passed the audiological examinations and those who had not were compared using a chi-square test. RESULTS: Among the 6 723 neonates, 363 (5.40%) were found to carry variants. These have included 166 cases (2.47%) with GJB2 gene variants, 136 cases (2.03%) with SLC26A4 gene variants, 26 cases (0.39%) with mitochondrial 12S rRNA gene variants, and 33 cases (0.49%) with GJB3 gene variants. Among the 6 723 neonates, 267 had failed initial hearing screening, among which 244 had accepted a re-examination, for which 14 cases (5.73%) had failed again. This has yielded an approximate prevalence of hearing disorder of 0.21% (14/6 723). Among 230 newborns who had passed the re-examination, 10 (4.34%) were found to have carried a variant. By contrast, 4 out of the 14 neonates (28.57%) who had failed the re-examination had carried a variant, and there was a significant difference between the two groups (P < 0.05). CONCLUSION Genetic screening can provide an effective supplement to newborn hearing screening, and the combined screening can provide a best model for the prevention of hearing loss, which can enable early detection of deafness risks, targeted prevention measures, and genetic counseling to provide accurate prognosis for the newborns.
Infant, Newborn ; Humans ; Connexins/genetics* ; Retrospective Studies ; Deafness/genetics* ; Connexin 26/genetics* ; Neonatal Screening/methods* ; Mutation ; Genetic Testing/methods* ; China/epidemiology* ; Hearing ; DNA Mutational Analysis