Table of Content

15 October 2023 Volume 41 Issue 10

  

Commentary

Clinical application of non-invasive high-frequency oscillatory ventilation in premature infants

ZHU Xingwang, SHI Yuan

Journal of Clinical Pediatrics. 2023, 41(10):  641-645.  doi:10.12372/jcp.2023.23e0789

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Noninvasive high-frequency oscillatory ventilation(NHFOV) is based on the application of a continuous flow, generating a constant distending positive pressure with superimposed oscillations, delivered all over the spontaneous breathing cycle. NHFOV matches together the advantages of high-frequency ventilation (no need for synchronisation, high efficacy in removing CO₂) and nasal continuous positive airway pressure (NCPAP, non-invasive interface, increase in functional residual capacity allowing oxygenation to improve). As it represents another “brick in the wall” of the non-invasive respiratory support, it has been increasing applied in neonatal intensive care unit (NICU). At present, there is no consensus guidelines on the application of NHFOV, the application of NHFOV is largely based on the local practices and comfort. This article summarizes the physiology of NHFOV, indications, ventilator device, interfaces, parameter settings, and clinical evidence based on a PubMed literature search.

Expert Review

Progress and challenges in clinical research of umbilical cord blood transplantation for the treatment of premature infant diseases

LI Fang, WANG Li

Journal of Clinical Pediatrics. 2023, 41(10):  646-653.  doi:10.12372/jcp.2023.23e0634

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Despite great progress in the treatment of neonatal diseases, complications of preterm infants such as bronchopulmonary dysplasia, perinatal brain injury and necrotizing enterocolitis are still leading causes of neonatal mortality and long term morbidity. Exploring more effective therapies for the prevention or treatment for the complications of preterm infants are the concerns in neonatology. Stem cell therapy especially umbilical cord blood transplantation, have been explored as a new therapeutic option in premature infant diseases, with very promising preclinical and clinical results over the past 20 years. This article outlined the clinical progress, prospects and challenges of stem cells derived from umbilical cord blood in preterm diseases.

Etiologies of death and preventive strategies in extremely preterm infants

ZHOU Jianguo

Journal of Clinical Pediatrics. 2023, 41(10):  654-657.  doi:10.12372/jcp.2023.23e0715

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With the development of perinatal and neonatal medicine in China, as well as the improvement of the overall willingness to treat extremely preterm infants (gestational age <28 weeks, EPI), the number of them has increased. As a result, EPI has become the leading cause of neonatal death in neonatal intensive care units (NICUs). According to the experience of foreign developed countries, with the improvement of China's social and economic development level, the proportion of EPI in NICU deaths will be further increased. Therefore, the EPI care is and will remain an important and challenging issue in the future. Reducing the mortality risk of EPI depends on the establishment and improvement of perinatal medical centers, neonatal medical centers and professional neonatal transport systems, the implementation of comprehensive management programs for preterm infants, the integration of prenatal, intrapartum and postnatal factors, and comprehensive obstetric and neonatal cooperation.

Neonatal Disease

Related factors analysis of clinical outcome after pulmonary hemorrhage in very low birth weight infants

ZHU Wen, ZOU Yunsu, WU Yue, LU Keyu, CHENG Rui, TONG Meiling, YANG Yang

Journal of Clinical Pediatrics. 2023, 41(10):  658-664.  doi:10.12372/jcp.2023.22e0562

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Objective To explore the important prognostic factors of pulmonary hemorrhage in very low birth weight (VLBW) infants. Methods The clinical data of VLBW infants diagnosed with pulmonary hemorrhage admitted to NICU from January 1, 2018 to December 31, 2021 were retrospectively analyzed. Results A total of 64 VLBW neonates were included, 39 in the death group and 25 in the survival group. In the death group, there were 21 neonates with gestational age <28 weeks, 17 with gestational age of 28-31⁺⁶ weeks, and 1 with gestational age of 32-33⁺⁶ weeks. There were 17 neonates with birth weight <1000 g, 13 with 1000-1250 g, and 9 with 1250-1500 g. Compared with the survival group, the death group had lower birth weight and gestational age, lower age of pulmonary hemorrhage occurrence, higher rates of gestational age <28 weeks and resuscitation by tracheal intubation, and higher rates of Ⅲ-Ⅳ respiratory distress syndrome, symptomatic ductus arteriosus and early-onset sepsis, with statistical significance (P<0.05). Compared with the survival group, the death group had higher peak inspiratory pressure within 24h after birth, higher fraction of inspired oxygen before pulmonary hemorrhage, and higher fraction of inspired oxygen and peak inspiratory pressure after pulmonary hemorrhage; In the death group, the proportion of arterial blood BE<-5mmol/L after birth was higher, and the proportion of arterial blood pH<7.1, BE<-5 mmol/L, PaCO₂>50 mmHg was higher when pulmonary hemorrhage occurred; Prothrombin time (PT) and thrombin time were prolonged during pulmonary hemorrhage in the death group. The differences were statistically significant (P<0.05). Binary logistic regression analysis showed that resuscitation by tracheal intubation and PT≥30 s during pulmonary hemorrhage were independent risk factors for death in children with pulmonary hemorrhage (P<0.05). Log-rank test showed that the median survival time in the resuscitation group was shorter than that in the non-resuscitation group, and the median survival time in the PT≥30 s group was shorter than that in the PT<30 s group, the difference was statistically significant (P<0.001). Conclusions In clinical work, attention should be paid to the intrauterine hypoxia of VLBW infants, the reasonable application of tracheal intubation resuscitation after birth, and the active correction of coagulation dysfunction after bleeding, so as to reduce the mortality of pulmonary hemorrhage.

Analysis of clinical features and risk factors of death in extremely preterm infants

ZHANG Ye, QI Min, SHI Chunyan, YANG Shibing, JIANG Zhou

Journal of Clinical Pediatrics. 2023, 41(10):  665-669.  doi:10.12372/jcp.2023.22e1118

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Objective To investigate the risk factors of death in extremely preterm infants (EPI). Methods The clinical data of EPI hospitalized in the neonatology department from January 1, 2018 to December 31, 2021 were retrospectively analyzed. According to the clinical outcome at the time of discharge, the patients were divided into the survival group and the death group, and the clinical characteristics between the two groups were compared to analyze the risk factors of EPI death. Results A total of 114 EPI patients (58 boys and 56 girls) were included. The median gestational age was 27.0 (26.0-27.6) weeks, the mean birth weight was (921±179) g, and 24 (21.1%) died. There were no significant differences in the proportions of advanced maternal age, cervical insufficiency, gestational diabetes mellitus, premature rupture of membranes, prenatal use of glucocorticoids and antibiotics between the two groups (P>0.05). Multivariate logistic regression analysis showed that birth weight ≤750g, severe neonatal respiratory distress syndrome, pulmonary hemorrhage within 1 week after birth, insulin use within 1 week after birth, and septic shock were independent risk factors for EPI death (P<0.05). Conclusions Body weight ≤750g, severe neonatal respiratory distress syndrome, septic shock, and pulmonary hemorrhage within 1 week after birth, or insulin use within 1 week after birth have a higher death risk in EPI.

Predictive value of neonatal sequential organ failure assessment score for mortality risk of late-onset sepsis in very/extremely low birth weight infants

HAO Qingfei, CHEN Jing, LIU Lijun, LI Gaopan, CHEN Haoming, ZHANG Jing, GUO Hongxiang, CHENG Xiuyong

Journal of Clinical Pediatrics. 2023, 41(10):  670-674.  doi:10.12372/jcp.2023.22e1395

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Objective To explore the predictive value of neonatal sequential organ failure assessment (nSOFA) score for the death risk of late-onset sepsis in very/extremely low birth weight infants. Methods The clinical data of very/extremely low birth weight infants diagnosed with late-onset sepsis admitted from January 2017 to December 2021 were retrospectively analyzed. The nSOFA score was calculated at 5 time points (T-24, T-12, T0, T12, T24) before and after the diagnosis of sepsis. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of nSOFA score for mortality risk of children. Results A total of 135 children (66 boys and 69 girls) were included, and the age at diagnosis of sepsis was 21.0 (13.5-25.0) days. One hundred and thirteen children survived and 22 died (case fatality rate 16.3%). There were statistically significant differences in nSOFA scores between survival group and death group at T-12, T0, T12 and T24 time points (P<0.05). ROC curve analysis showed that the sensitivity of nSOFA score at T-12, T0, T12 and T24 to predict the death risk of late-onset sepsis in very/extremely low birth weight infants was 59.1%, 81.8%, 93.2% and 98.3%, and the specificity was 63.6%, 71.7%, 73.7% and 89.9%, respectively. The areas under the curve were 0.64, 0.79, 0.89 and 0.95, respectively. The sensitivity, specificity and area under the curve of nSOFA score were the largest at T24. Conclusions The nSOFA score has a predictive value for the risk of death from late-onset sepsis in very/extremely low birth weight infants. The higher the nSOFA score, the greater the risk of death from sepsis.

Related factors affecting delayed thyroid stimulating hormone elevation in preterm infants with gestational age <34 weeks

LU Xiaoyan, CHEN Shaohong, CHEN Yingying, ZHOU Wenjun, ZHOU Chan, SONG Yan, LI Luquan, TANG Wenyan

Journal of Clinical Pediatrics. 2023, 41(10):  675-679.  doi:10.12372/jcp.2023.22e1648

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Objective To evaluate the related factors of delayed thyroid stimulating hormone elevation (dTSH) in premature infants with gestational age <34 weeks. Methods The clinical data, preliminary screening and venous blood thyroid stimulating hormone (TSH) results at 15-28d after birth of preterm infants with gestational age <34 weeks born in Jiangxi Maternal and Child Health Hospital and admitted to intensive care unit from March 2020 to September 2021 were retrospectively analyzed. Results A total of 441 preterm infants (253 boys and 188 girls) with gestational age <34 weeks were included, with an average gestational age of (30.0±2.0) weeks. There were 17 cases of dTSH (3.9%), including 7 cases of transient hyperthyrotropinemia and 10 cases of congenital hypothyroidism (CH). The TSH level in dTSH group was higher than that in normal group at first screening and 15 to 28 days after birth, and the difference was statistically significant (P<0.05). Multivariate logistic regression analysis showed that dopamine use, low birth weight and 5-minute Apgar score <7 were independent risk factors for dTSH development (P<0.05). Conclusions Preterm infants with gestational age <34 weeks may present with dTSH. Low birth weight, 5-minute low Apgar score, and use of dopamine are more likely to present dTSH. Attention should be paid to dynamic monitoring of thyroid function in preterm infants.

Neonatal screening and gene variation analysis of primary carnitine deficiency in Hefei City

HU Haili, LI Weidong, WANG Yan, SONG Wangsheng, MA Qingqing

Journal of Clinical Pediatrics. 2023, 41(10):  680-684.  doi:10.12372/jcp.2023.22e1344

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Objective To analyze the screening status and genetic variation characteristics of primary carnitine deficiency (PCD) in neonates in Hefei. Methods A total of 631839 newborn screening samples screened by Hefei Neonatal Disease Screening Center from January 2016 to December 2021 were detected by tandem mass spectrometry. Newborns and their mothers with positive initial screening were recalled for re-screening. If the re-screening results were still lower than the critical reference value, high-throughput second-generation gene sequencing was performed. Results A total of 32 neonates were diagnosed with PCD (overall incidence: 1/19745). Among 32 neonates, 31 underwent high-throughput sequencing combined with Sanger validation, 1 had no genetic variation and 30 had genetic variation (18 boys and 12 girls). There were 25 cases of complex heterozygous variation and 5 cases of homozygous variation, and the gene diagnosis rate was 96.8%. Among the 60 variants of SLC22A5 gene in 30 positive children, c.1400C>G had the highest variation ratio, accounting for 48.3% (29/60), followed by c.51C>G, accounting for 15.0% (9/60). Conclusions The overall incidence of neonatal PCD in Hefei was not significantly different from that in other areas of China. c.1400C>G and c.51C>G were the common sites of PCD gene variation in newborns in Hefei City.

General Report

Phase Ⅲ clinical trial of recombinant human growth hormone for injection in treatment of idiopathic short stature

LIANG Huan, SHENG Hai, WEI Haiyan, YANG Yu, DU Hongwei, LIU Fang, YANG Li, WANG Meina, WANG Li, MA Qin, ZHANG Huiwen, GU Xuefan

Journal of Clinical Pediatrics. 2023, 41(10):  685-691.  doi:10.12372/jcp.2023.22e1018

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Objective To evaluate the efficacy and safety of recombinant human growth hormone (rhGH) for injection in the treatment of prepubertal children with idiopathic short stature (ISS) in China. Methods This study was a randomized, open-label, controlled, multicenter, phase Ⅲ clinical trial of prepubertal ISS from December 27, 2016 to July 30, 2020. Participants were randomly assigned to the high-dose group, low-dose group and control group in a ratio of 3:3:1, and the administration cycle of rhGH was 52 weeks. Changes in height standard deviation scores (ΔHT-SDS) of actual age before and after treatment, annual height velocity (HV) and bone maturity at the end of treatment were observed. At the same time, the rhGH safety during treatment was investigated. Results A total of 150 participants completed the trial. At baseline, there were no significant differences in age, bone age, sex, height, weight, body mass index, HT-SDS, annual HV and insulin-like growth factor 1 levels among all groups (P>0.05). Both full analysis set (FAS) and per protocol set (PPS) analysis found statistically significant differences in ΔHT SDS among the high-dose, low-dose and control groups at week 26, 39 and 52 (P<0.001). Pairwise comparison showed that ΔHT SDS in the high-dose and low-dose groups were higher than those in the control group, and the differences were statistically significant (P<0.05). FAS analysis showed statistically significant differences in HV among the high-dose, low-dose and control groups at week 13, 26, 39, and 52 (P<0.001). Pairwise comparison showed that HV in the high-dose and low-dose groups was higher than that in the control group, and the differences were statistically significant (P<0.05). At week 52, there was no significant difference in bone maturity among all groups (P>0.05). During the study, no serious adverse reaction occurred in each group. Conclusions The rhGH injection is effective in treating ISS, and there is a significant growth in stature after 52 weeks of treatment, but more observation and evaluation of the effect and safety of lifetime height are needed.

Metabolic and genetic analysis of abnormal 3-hydroxyisovalerylcarnitine in children from northern China

ZHANG Wanqiao, YAN Lei, ZHU Lina, MA Xiuwei

Journal of Clinical Pediatrics. 2023, 41(10):  692-696.  doi:10.12372/jcp.2023.22e0556

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Objective To investigate the significance of elevated blood 3-hydroxyisovalerylcarnitine (C5OH) in the diagnosis of inherited metabolic diseases (IMD) and to explore the disease spectrum and genetic characteristics of children with abnormal C5OH in the population of northern China. Methods The data of IMD screening and diagnosis in hospitalized children from November 2012 to October 2021 were retrospectively analyzed, including tandem mass spectrometry (MS/MS) screening of blood metabolites, gas chromatography-mass spectrometry (GC-MS) analysis of urine metabolites and high-throughput sequencing analysis of gene variations. The blood and urine metabolic spectrum and gene variation spectrum of children with abnormal C5OH were analyzed. Results Among 53119 hospitalized children aged 0 to 7 years who underwent MS/MS screening for IMD, 48 (0.090%) children with increased C5OH were detected. Combined with urine GC-MS analysis, 9 (0.017%) children obtained biochemical diagnosis of IMD which verified by gene analysis. Of the 4 children with multiple carboxylase deficiency (MCD), 2 had HLCS gene variation and were confirmed as holocarboxylase synthetase deficiency, while the other 2 had BTD gene variation and were confirmed as biotinidase deficiency. ACAT1 variation was detected in 2 children with β-ketothiolase deficiency, and HMGCL variation was detected in 1 child with 3-hydroxy-3-methyl-glutaricacidemia. In 2 children with suspected MCD or 3-methylcrotonyl coenzyme A carboxylase deficiency that were not classified by biochemical diagnosis, HLCS variation was detected in 1 child, and BTD variation was detected in the other child, and MCD was finally diagnosed. The false positive rate of C5OH detection was 0.073% and the positive predictive value was 18.75%. The false positive rate of C5OH combined with other indicators (C4OH, C3 and C5:1) was 0.009%, and the positive predictive value was 58.33%. There was no false positive in the analysis of C5OH combined with urinary GC-MS, and the positive predictive value was 100%. Conclusions MCD is the main disease type in children with increased C5OH. For C5OH-related IMD, MS/MS combined with GC-MS metabolic analysis has high diagnostic efficiency and clinical value of guiding intervention in advance.

Clinical features of severe Pneumocystis pneumonia in non-HIV-infected children

GONG Qinqiang, HUANG Yuping, LI Xueping, WU Cairong, XIAO Qin, WANG Qiongqiong, CHEN Dongyan, HONG Jie, TAO Jianping, LIANG Yufeng

Journal of Clinical Pediatrics. 2023, 41(10):  697-702.  doi:10.12372/jcp.2023.22e0566

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Objective To investigate the clinical characteristics of severe Pneumocystis pneumonia (PCP) in non-HIV-infected children, and to improve the understanding of such disease among pediatricians. Methods The clinical data of non-HIV-infected children with severe pneumonia hospitalized from March 2018 to March 2021 were retrospectively analyzed. The patients diagnosed with PCP by metagenomic next-generation sequencing (mNGS) were classified into the case group and the patients with severe pneumonia infected by other respiratory pathogens were included in the control group. The clinical characteristics, prognosis and complications were compared between the two groups. Results A total of 60 patients (38 boys and 22 girls) were enrolled in the study, and the median age was 1.6 (0.7-4.3) years. There were 20 patients in the case group and 40 in the control group. Compared with the control group, the proportions of primary immunodeficiency, renal connective tissue disease, use of immunosuppressive agents, and glucocorticoids use ≥1 month in the case group were higher, and the differences were statistically significant (P<0.05). Compared with the control group, the proportion of lung rales, the arterial oxygen pressure/ inhaled oxygen concentration value within 24 hours, CD4⁺ T cell count and CD4⁺ /CD8⁺ in the case group were lower, the oxygenation index within 24 hours was higher, and the proportion of cytomegalovirus (CMV), Epstein-Barr virus (EBV) and other fungal infections were higher in the case group, and the differences were statistically significant (P<0.05). The proportion of ground glass shadow, strip shadow, incidence of air leakage and mortality in the case group were higher than those in the control group, the proportion of patchy consolidation and pleural effusion were lower than those in the control group, and the invasive ventilation time was longer than that in the control group, and the differences were statistically significant (P<0.05). Conclusions Most non-HIV infected children with severe PCP had a history of glucocorticoid and immunosuppressant use or primary immunodeficiency before the onset of the disease. The hypoxemia was severe and long lasting, and the fatality rate was high. The main manifestations of chest CT were diffuse ground glass shadow and strip shadow. Laboratory tests suggested a low cellular immune function.

Rare Disease & the Difficult and Complicated Disease

Myelin oligodendrocyte glycoprotein antibody-associated disease in children with prominent manifestation of optic neuritis caused by Mycoplasma pneumoniae infection: a case report

GUO Fang, KANG Lei, DU Feifan, JIA Yanhong, XU Meixian

Journal of Clinical Pediatrics. 2023, 41(10):  703-707.  doi:10.12372/jcp.2023.22e0638

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Objective To investigate the clinical manifestations, treatment and prognosis of pediatric Mycoplasma pneumoniae (MP)-associated optic neuritis (ON). Methods The clinical data of 1 child with MP-ON were retrospectively analyzed, and the cases of MP-ON in domestic and foreign databases were retrieved and analyzed. Results The patient was a 10-year-old prepubertal girl, and her onset symptoms were fever and headache. Her serum MP antibody titer was >1:1280. After intravenous infusion of azithromycin, the child's fever and headache were quickly relieved. On day 23 of the disease course, the patient developed acute vision loss with pain of eye rotation, visual field defects, papilledema, and abnormal visual evoked potentials. There were no other manifestations of nervous system involvement and no manifestations of encephalopathy. Laboratory test found positive serum myelin oligodendrocyte glycoprotein-antibody (MOG-Ab). Cerebrospinal fluid and MRI results were abnormal. After intravenous infusion of high dose methylprednisolone combined with human immunoglobulin, the vision of the child returned to the pre-onset level, and no recurrence was observed 3 months later. Conclusions MP infection can be complicated by ON, which is related to demyelinating changes caused by autoimmunity or immune complex. Intractable headache has suggestive significance. Serum antibodies detection of central nervous system demyelinating disease is beneficial to clinical classification and guidance of treatment.

Literature Review

Research progress on characterization and therapeutics for recurrent medulloblastoma in children

ZHANG Zaiyu, WU Yuxin, LIANG Ping

Journal of Clinical Pediatrics. 2023, 41(10):  708-714.  doi:10.12372/jcp.2023.22e1112

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Medulloblastoma (MB) is a common intracranial malignancy in children with a high recurrence rate despite standardized multimodal initial treatment. The prognosis of recurrent children is very poor even after intensive treatment. In recent years, the in-depth understanding of the clinical and biological characteristics of MB recurrence can guide the clinical design of relevant treatment strategies and implement of clinical trials. This paper reviews the research progress of the above contents, hoping to promote the speed of its clinical transformation and application, and finally benefit the clinical practice.

Continuing Medical Education

Influencing factors of respiratory tract microecology and its significance in bronchopulmonary dysplasia

REN Shuying, ZHANG Qin

Journal of Clinical Pediatrics. 2023, 41(10):  715-720.  doi:10.12372/jcp.2023.22e1186

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Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants with gestational age ≤32 weeks, which has long-term adverse effects on respiratory and nervous system development of newborns. BPD is caused by the combined action of many factors and its etiology is complex. The diversity of respiratory tract microecology and its abnormal evolution mode will increase the risk of BPD. The microecology of the respiratory tract is affected by many factors, and its imbalance can increase the risk of developing various systemic diseases later in life. This paper reviews the influencing factors of respiratory tract microecology and their significance and research progress in BPD, aiming to strengthen the understanding of their relationship and provide a new entry point for the prevention and treatment of BPD.