Shi Yanan, Zhang Naiyao, Du Na, Zheng Tongxi, Yu Ying, Li Youjin
Shanghai Jiao Tong University, School of Medicine, Hainan Branch of Shanghai Children's Medical Center, Department of Otorhinolaryngology, Sanya, China.
Shanghai Jiao Tong University, School of Medicine, Hainan Branch of Shanghai Children's Medical Center, Department of Neonatology, Sanya, China.
Braz J Otorhinolaryngol. 2025 Mar-Apr;91(2):101541. doi: 10.1016/j.bjorl.2024.101541. Epub 2025 Jan 3.
We aimed to investigate the correlation between prevalent risk factors for high-risk neonates in neonatal intensive care unit and their hearing loss, and to examine the audiological features and genetic profiles associated with different deafness mutations in our tertiary referral center. This research seeks to deepen our understanding of the etiology behind congenital hearing loss.
We conducted initial hearing screenings, including automated auditory brainstem response, distortion product otoacoustic emission, and acoustic immittance on 443 high-risk neonates within 7 days after birth and 42 days (if necessary) after birth. Neonates who failed initial screenings underwent further diagnostic tests at 3 months. The risk factors were analyzed retrospectively by Chi-Square test and stepwise logistic regression. Genetic analysis involved a deafness sequencing panel targeting 19 pathogenic variants across four genes (GJB2, GJB3, SLC26A4, and MT-RNR), applied to both the study cohort and a larger hearing screening cohort of 14863 neonates from our center and different medical centers in the same region.
Out of the 443 high-risk neonates, 222 failed their diagnostic hearing tests. Logistic regression identified preterm birth, neonatal hyperbilirubinemia and advanced maternal age (≧35 yr) as significant risk factors for hearing loss. Genetic screening of 33 neonates who failed the diagnostic tests revealed that 7 (21.21%) carried at least one pathogenic variant, with identified 1 homozygotes and 3 heterozygotes in the GJB2, 1 homozygotes and 1 heterozygotes in the SLC26A4 gene, and 1 homoplasmic variant in the MT-RNR (12SrRNA). In the larger hearing screening cohort, 497 (3.34%) were genetically positive for deafness mutations, among whom 29 had the diagnostic hearing tests and 7 eventually diagnosed with hearing loss. Of the rest 468 neonates who didn't have the diagnostic tests, 445 (95.09%) passed the hearing screening tests.
Preterm birth, neonatal hyperbilirubinemia and advanced maternal age are critical risk factors for hearing impairment in high-risk neonates. Mutations such as c.235delC in GJB2 and c.919-2A>G in SLC26A4 are the most common. Long-term follow-up of neonates carrying heterozygous variants, particularly in genes like GJB3, is necessary to understand their progression and hearing outcomes. This study highlights the importance of deafness gene screening in neonates to ensure accurate diagnosis and effective intervention.
Level 3.
我们旨在研究新生儿重症监护病房高危新生儿的常见风险因素与其听力损失之间的相关性，并在我们的三级转诊中心检查与不同耳聋突变相关的听力学特征和基因谱。本研究旨在加深我们对先天性听力损失病因的理解。
我们在出生后7天内以及出生后42天（如有必要）对443例高危新生儿进行了初步听力筛查，包括自动听性脑干反应、畸变产物耳声发射和声导抗测试。初次筛查未通过的新生儿在3个月时接受进一步的诊断测试。通过卡方检验和逐步逻辑回归对风险因素进行回顾性分析。基因分析涉及一个针对四个基因（GJB2、GJB3、SLC26A4和MT-RNR）中19个致病变异的耳聋测序panel，应用于研究队列以及来自我们中心和同一地区不同医疗中心的14863例新生儿的更大听力筛查队列。
在443例高危新生儿中，222例诊断性听力测试未通过。逻辑回归确定早产、新生儿高胆红素血症和高龄产妇（≧35岁）是听力损失的重要风险因素。对33例诊断性测试未通过的新生儿进行基因筛查发现，7例（21.21%）携带至少一种致病变异，其中在GJB2基因中鉴定出1例纯合子和3例杂合子，在SLC26A4基因中鉴定出1例纯合子和1例杂合子，在MT-RNR（12SrRNA）中鉴定出1例同质变体。在更大的听力筛查队列中，497例（3.34%）基因检测为耳聋突变阳性，其中29例进行了诊断性听力测试，7例最终被诊断为听力损失。其余468例未进行诊断性测试的新生儿中，445例（95.09%）通过了听力筛查测试。
早产、新生儿高胆红素血症和高龄产妇是高危新生儿听力损害的关键风险因素。GJB2基因中的c.235delC和SLC26A4基因中的c.919-2A>G等突变最为常见。对携带杂合变体的新生儿进行长期随访，尤其是在GJB3等基因中，对于了解其进展和听力结果是必要的。本研究强调了新生儿耳聋基因筛查对于确保准确诊断和有效干预的重要性。
3级。
