Abstract Objective This study aimed to research risk factors of hearing loss among neonates in the neonatal intensive care unit. Method Hearing screening tests were performed on 572 neonates in the neonatal intensive care unit. Those who failed screening tests were referred for diagnostic tests. Results The pass rates for automated auditory brainstem response, distortion product otoacoustic emission and acoustic impedance tests at first hearing screening were 69.93 per cent, 70.02 per cent and 92.92 per cent for 1144 ears. Failure in the first screening correlated with preterm birth, very low birth weight, revised advanced maternal age, neonatal hyperbilirubinaemia and Activity, Pulse, Grimace, Appearance, Respiration score less than 8. Thirty cases failed in diagnostic hearing tests for brainstem auditory evoked potentials, 28 failed in otoacoustic emissions and 33 failed in acoustic impedance, which correlated with preterm birth, very low birth weight, twins, advanced maternal age and revised advanced maternal age. Conclusion Abnormalities in the hearing levels of most neonates who needed hearing retests were completely or partially reversible. Preterm birth, very low birth weight, twins and advanced maternal age are potential risk factors for hearing impairment.

Variations in the POU Class 3 Homeobox 4 ( POU3F4 ) gene are associated with X-linked mixed deafness. Here, the identification of a novel variant of POU3F4 in a male paediatric patient (the proband) with incomplete partition type III (IP-III) hearing impairment, is described. Clinical data were collected from the proband and his biological parents. Whole exome sequencing of the proband revealed a novel frameshift insertion mutation in POU3F4 (c.717_718ins GTGCCTTGCAG : p.Leu240Valfs*5) in a hemizygous state. This variant likely truncates the protein within the POU-specific domain, and the proband’s biological mother was found to be a carrier of this variant. After excluding all contraindications, the proband underwent cochlear implantation in the right ear in June 2020. Cerebrospinal fluid (CSF) gushing was observed during surgery, but there were no postoperative complications, such as CSF leak, meningitis, or facial nerve stimulation. A novel pathogenic frameshift variant of POU3F4 was identified, enriching the known mutation spectrum of POU3F4 . Effective perioperative prevention and response measures should be taken to reduce the incidence of CSF gushing and meningitis in patients receiving IP-III cochlear implantation. Keywords Incomplete partition type III , POU3F4 , Novel variant , Cochlear implantation , X-linked deafness , Frameshift

目的 探讨新生儿动脉血血气分析指标与听力筛查结果的关系.方法 回顾性分析医学中心新生儿科496例患儿听力筛查结果和入院时动脉血血气分析指标.结果 自动听觉脑干反应(AABR)、畸变产物耳声发射(DPOAE)和声导抗和总听力筛查通过率分别为61.9％ (307/496)、61.3％ (304/496)、90.1％(447/496)和56.7％ (281/496).三种听力筛查方法通过率差异有统计学意义(x2=131.00,P＜0.001).AABR与DPOAE测试结果一致性极强(Kappa=0.817,P＜0.001),两者与声导抗测试一致性较弱(Kappa值分别为0.262、0.256,P均＜0.001).单因素Logisitic分析显示乳酸升高(OR=0.544,P=0.001)、二氧化碳分压升高(OR=1.917,P=0.009)、pH降低(OR=1.692,P=0.021)与听力筛查不通过显著相关.多因素Logisitic分析显示,乳酸(OR=0.627,P=0.018)、氧分压(OR=1.493,P=0.047)与听力筛查结果不通过显著相关.二氧化碳分压、pH和血氧饱和度和听力筛查结果无明显相关性(P＞0.05).结论 新生儿缺氧及其伴随的血气变化可能会影响听力筛查结果.

Variations in the POU Class 3 Homeobox 4 (POU3F4) gene are associated with X-linked mixed deafness. Here, the identification of a novel variant of POU3F4 in a male paediatric patient (the proband) with incomplete partition type III (IP-III) hearing impairment, is described. Clinical data were collected from the proband and his biological parents. Whole exome sequencing of the proband revealed a novel frameshift insertion mutation in POU3F4 (c.717_718ins GTGCCTTGCAG: p.Leu240Valfs*5) in a hemizygous state. This variant likely truncates the protein within the POU-specific domain, and the proband's biological mother was found to be a carrier of this variant. After excluding all contraindications, the proband underwent cochlear implantation in the right ear in June 2020. Cerebrospinal fluid (CSF) gushing was observed during surgery, but there were no postoperative complications, such as CSF leak, meningitis, or facial nerve stimulation. A novel pathogenic frameshift variant of POU3F4 was identified, enriching the known mutation spectrum of POU3F4. Effective perioperative prevention and response measures should be taken to reduce the incidence of CSF gushing and meningitis in patients receiving IP-III cochlear implantation.

Objective:To investigate the failure in the hearing screening test among twin neonates in neonatal intensive care unit （NICU） and to further clarify the etiology of neonatal hearing impairment, thus to provide insights into prevention and early intervention. Methods:Automated auditory brainstem response（AABR）, distortion product otoacoustic emission（DPOAE） and acoustic immittance were performed on 1452 neonates（including 130 twins） admitted in NICU from January 2015 to June 2018 and the risk factors including premature birth, hyperbilirubinemia, neonatal respiratory distress syndrome, etc. were analyzed retrospectively by univariate chi-square test and multivariate logistic regression analysis. Results:The incidence of C-section, premature birth, hyperbilirubinemia, low birth weight, very low birth weight, in-vitro fertilization, pregnancy-induced hypertension syndrome and formula or mixed feeding among twin neonates were significantly higher than those of singleton neonates （P<0.05）. The pass rates of the first-time AABR, DPOAE and acoustic immittance were significantly lower than singleton neonates. The proportion of twin neonates who failed the initial screening but recovered in the following test was as high as 72.86%. AABR pass rate was correlated with congenital heart disease, neonatal respiratory distress syndrome, C-section and （very） low birth weight. The pass rate of DPOAE was correlated with low birth weight and C-section. The pass rate of acoustic immittance was correlated with preterm birth, C-section, low birth weight, gestational diabetes and gestational hypertension. The pass rate of diagnostic ABR was associated with gestational diabetes. And the pass rate of diagnostic DPOAE was associated with maternal age ≥40 years old. Conclusion:The first-time hearing screening pass rate of twin neonates in NICU is lower than that of neonatal singleton. Most twin neonates who fail in the first screening test will recover. Preterm birth, neonatal respiratory distress syndrome, （very） low birth weight, congenital heart disease, gestational diabetes, pregnancy-induced hypertension syndrome, maternal age ≥ 40 years old and C-section are associated with the first-time failure in hearing screening tests among twin neonates, thus entailing close follow-up.

Objective: The aim of the study was to investigate into the risk factors for failure in the first-time screening test among high-risk neonates in neonatal intensive care unit (NICU) in order to further clarify the etiology of neonatal hearing impairment, thus providing insights into early prevention and intervention. Methods: We performed automated auditory brainstem response (AABR), distortion product otoacoustic emission (DPOAE), and acoustic immittance (AI) on 2,194 high-risk neonates admitted into the NICU of Shanghai Children’s Medical Center from January 2015 to December 2019, and the risk factors, including premature birth, hyperbilirubinemia, and infant respiratory distress syndrome, were analyzed retrospectively by the univariate χ2 test and multivariate stepwise logistic regression analysis. Results: The pass rates of AABR, DPOAE, and AI were 70.21, 78.44, and 93.12%, respectively, in 2,194 cases of high-risk neonates screened, which are significantly lower than those of healthy controls. The most common diagnoses included artificial feeding, preterm birth, C-section, low birth weight (LBW), neonatal hyperbilirubinemia (NHB), neonatal respiratory distress syndrome (NRDS), congenital heart disease (CHD), gestational diabetes mellitus, pregnancy-induced hypertension syndrome, advanced maternal age (AMA), twins, and in vitro fertilization. Stepwise logistic regression analysis indicated that the AABR pass rate was negatively correlated with LBW (p = 0.002), NHB (p < 0.001), NRDS (p = 0.007), artificial or mixed feeding (p = 0.018), and CHD (p = 0.005). The pass rate of DPOAE was negatively correlated with artificial or mixed feeding (p = 0.041), NHB (p < 0.001), LBW (p = 0.007), very LBW (VLBW) (p = 0.008), and C-section (p < 0.001). The pass rate of AI was negatively correlated with revised AMA (≥40 year) (p < 0.001), NHB (p = 0.043), C-section (p = 0.005), and artificial/mixed feeding (p = 0.036). Conclusion: The hearing screening pass rates of high-risk neonates in the NICU were lower than those of normal neonates, among which the rate of AABR was significantly lower than that of DPOAE. NRDS, NHB, LBW, revised AMA, CHD, C-section, and artificial feeding are potential risk factors of hearing impairment. The combination of different hearing screening tests is necessary for accurate diagnosis of congenital hearing disorders.

Noonan syndrome is a multisystem disease with widespread heterogeneity regarding the genetic and clinical characteristics, which can be accompanied by distinctive facial dysmorphism, congenital heart defects, short stature, cryptorchidism, lymphatic malformations, bleeding disorders and skeletal malformations. Some patients have hearing impairment. Noonan syndrome is a rare cause of sensorineural hearing loss. The study describes a Noonan syndrome patient with profound bilateral hearing loss. He received a cochlear implantation successfully. The patient had clinical characteristics of Noonan syndrome, and the diagnosis was confirmed by the detection of pathogenic variants in PTPN11 by whole exome sequencing. According to the authors' knowledge, this is the first report regarding cochlear implantation in a Noonan syndrome patient in China.

耳聋可由遗传因素或环境因素导致,至少一半的耳聋可归因于遗传因素,其中同时具备其他特殊临床特征的称为综合征性耳聋(syndromic hearing loss, SHL),不具备其他临床特征的称为非综合征性耳聋(nonsyndromic hearing loss, NSHL)[1, 2].前庭水管扩大(enlarged vestibular aqueduct, EVA)是导致NSHL的常见内耳畸形,典型特征为进展性感音神经性听力下降[3],诊断主要依靠颞骨CT及MRI影像学检查[4].

Objective · To investigate the risk factors of hearing damage in child patients with severe neonatal hyperbilirubinemia (NHB) and follow up their prognosis. Methods · Clinical data of 106 newborns with severe NHB in neonatal ward of Shanghai Children's Medical Center from June 2015 to June 2016 were retrospectively analyzed. According to total serum bilirubin (TSB) level, they were divided into three groups, severe NHB group (342.0 μmol/L<TSB peak <427.5 μmol/L), very severe NHB group (TSB peak range 427.5-513.0 μmol/L), and fatal NHB group (TSB peak >513.0 μmol/L). Automatic auditory brainstem response (AABR) was used to evaluate the hearing ability of children in hospital, while those who got abnormal results would undergo diagnostic test of auditory brainstem response (ABR) when 3 months old. Auditory behavioral response of all 106 child patients at 3 and 6 months old were followed up. Results · There were totally 106 cases in three groups, among which 33 cases (33/106, 31.13%) got abnormal results at hearing screening in hospital, 22 cases (22/86, 25.58%) in severe NHB group, 9 cases (9/16, 56.25%) in very severe NHB group, and 2 cases (2/4, 50.00%) in fatal NHB group. The difference between groups was statistically significant (all P<0.05). All 33 patients not passing AABR in hospital came to undergo diagnostic test of ABR through regular education by a specially assigned person when 3 months old. Two children were diagnosed mild hearing damage. One of them was considered being caused by tympanitis. All children had good situation of auditory behavioral response at 3 and 6 months old in follow-up. Conclusion · Severe NHB is one of the high risk factors of hearing damage in neonates. The morbidity of hearing damage was higher with the increase of TSB level. The hearing damage caused by severe NHB might be reversible. It also suggested that the follow-up plan should be improved. The hearing damage caused by severe NHB might have no obvious effect on children in daily life, but long term follow-up of these children is still needed.

Background: Diffuse pulmonary lymphangiomatosis (DPL) mainly affects the lung and pleura. There are very few pathological reports of lung damage accompanied by diffuse involvement of the extrapulmonary lymph nodes and surrounding soft tissue. The clinicopathological significance of coexistence of pulmonary and extrapulmonary lesions is unknown. Methods: Here, we report a 16-year-old male patient. The pathological specimens of the supraclavicular lymph node and soft tissue together with the lung biopsy were analyzed by pathological observation and immunohistochemical staining. Literatures were reviewed and clinical and imaging findings were discussed. Results: The patient presented with coughing and expectoration for 1 year and intermittent hemoptysis for 4 months. Ultrasound revealed swollen lymph nodes in bilateral neck, left armpit, and pubic symphysis. Chest CT scan showed diffuse grid and linear shadows, bilateral pleural thickening, and nodule formation. Multiple enlarged lymph nodes were mainly investigated in bilateral hilar, mediastinal, para-aortic, lesser curvature, and retroperitoneal. Supraclavicular lymph node biopsy confirmed the lymphatic hyperplasia and expansion in the capsule and surrounding soft tissue. The thoracoscopic examination found bloody chylothorax on the left chest. And lung biopsy showed the lymphatic vessel hyperplasia and expansion on the pleura and adjacent lung tissue. Immunohistochemical stains showed that the lymphatic endothelial cells were positive for D2-40 and CD31. Lymphangiomatosis involving the pulmonary and extrapulmonary lymph nodes and surrounding soft tissue was diagnosed based on the aforementioned histological findings. Conclusion: Lymphangiomatosis of superficial lymph node mainly involves the capsule of lymph nodes and its surrounding soft tissue. The information obtained from the lymph node biopsy can prompt and assist the diagnosis of DPL.

Objective To explore and analyze the relationship of transtympanic administration effect with inner ear MRI visualization in patients with Meniere′s disease and idiopathic sudden hearing loss.Methods 17 cases(13 cases of idiopathic sudden hearing loss and 4 cases of Meniere′s disease)were enrolled in the study.Gadolium,dexamethason or gentimycin were trans-tympanically injected,and all patients were scanned with MRI 1 h,1 d,and 6 d after operation.The relationship of the effect with MRI visualization was observed and analyzed.Results 9 cases(5 cases of idiopathic sudden hearing loss and 4 cases of Meniere′s disease) of the 17 had inner ear high signal 1h to 6d after gadolium was injected.The other 8 cases had neither signal in the inner ear nor improved hearing.Conclusion If transtympanically injected gadolium can permeate into the inner ear,dexamethoson and gentimycin would also permeate into it,and the therapy would have a good effect.