Peripherally inserted central venous catheter-related thrombosis in a neonate / 中国当代儿科杂志

The female infant in this case study was admitted to the hospital 4 hours after birth due to preterm birth and respiratory distress. On the third day after birth, peripherally inserted central venous catheter (PICC) catheterization was performed. On day 42, thrombus was found at the entrance of the right atrium from the inferior vena cava during a cardiac ultrasound, and it was considered to be related to PICC placement. Low-molecular-weight heparin and urokinase were given. After two weeks of treatment, ultrasonic monitoring showed thrombus shrinkage. No bleeding or pulmonary embolism occurred during the treatment. The patient discharged after improvement. This article mainly introduces a multidisciplinary team approach to diagnosis and treatment of PICC-related thrombosis in neonates.

Neonate-onset ornithine transcarbamylase deficiency / 中国当代儿科杂志

The male neonate in this case study was admitted to the hospital at 15 hours of age due to respiratory distress for 15 hours and poor response for 3 hours after resuscitation from asphyxia. The neonate was highly unresponsive, with central respiratory failure and seizures. Serum ammonia was elevated (>1 000 μmol/L). Blood tandem mass spectrometry revealed a significant decrease in citrulline. Rapid familial whole genome sequencing revealed OTC gene mutations inherited from the mother. Continuous hemodialysis filtration and other treatments were given. Neurological assessment was performed by cranial magnetic resonance imaging and electroencephalogram. The neonate was diagnosed with ornithine transcarbamylase deficiency combined with brain injury. He died at 6 days of age after withdrawing care. This article focuses on the differential diagnosis of neonatal hyperammonemia and introduces the multidisciplinary management of inborn error of metabolism.

Clinical practice of whole-genome sequencing in the rapid diagnosis of critically ill neonates / 中国当代儿科杂志

OBJECTIVES@#To explore the application of whole-genome sequencing (WGS) in the rapid clinical diagnosis of critically ill neonates.@*METHODS@#The critically ill neonates who admitted to the neonatal intensive care unit of Children's Hospital of Fudan University and underwent WGS from August to September, 2019 were enrolled in this prospective study. The genetic testing results and clinical outcome were analyzed with reference to the sequencing data and clinical features of the neonates.@*RESULTS@#A total of 15 neonates were tested, among whom there were 9 boys and 6 girls. The main reason for hospitalization included abnormal breathing in 7 neonates, poor response in 2 neonates, feeding difficulty in 2 neonates, fever in 1 neonate, hypothermia in 1 neonate, preterm birth in 1 neonate, and convulsion in 1 neonate. The mean turn-around time was 4.5 days for WGS. Finally a genetic diagnosis was obtained for 3 neonates, with a positive diagnostic rate of 20% (3/15). Among the 3 neonates, 2 neonates were withdrawn from the treatment due to severe conditions and 1 neonate died on the day when the sample was sent for genetic testing, whose etiology could be explained by the results of genetic testing.@*CONCLUSIONS@#WGS technique can provide a timely and effective diagnosis for critically ill neonates suspected of genetic diseases and provide genetic evidence for clinical treatment of critically ill cases.

Evaluation of the clinical effect of an artificial intelligence-assisted diagnosis and treatment system for neonatal seizures in the real world: a multicenter clinical study protocol / 中国当代儿科杂志

Neonatal seizures are the most common clinical manifestations of critically ill neonates and often suggest serious diseases and complicated etiologies. The precise diagnosis of this disease can optimize the use of anti-seizure medication, reduce hospital costs, and improve the long-term neurodevelopmental outcomes. Currently, a few artificial intelligence-assisted diagnosis and treatment systems have been developed for neonatal seizures, but there is still a lack of high-level evidence for the diagnosis and treatment value in the real world. Based on an artificial intelligence-assisted diagnosis and treatment systems that has been developed for neonatal seizures, this study plans to recruit 370 neonates at a high risk of seizures from 6 neonatal intensive care units (NICUs) in China, in order to evaluate the effect of the system on the diagnosis, treatment, and prognosis of neonatal seizures in neonates with different gestational ages in the NICU. In this study, a diagnostic study protocol is used to evaluate the diagnostic value of the system, and a randomized parallel-controlled trial is designed to evaluate the effect of the system on the treatment and prognosis of neonates at a high risk of seizures. This multicenter prospective study will provide high-level evidence for the clinical application of artificial intelligence-assisted diagnosis and treatment systems for neonatal seizures in the real world.

Research advances in the clinical genetics of leukodystrophy in children / 中国当代儿科杂志

Leukodystrophy (LD) is a group of genetic heterogeneous diseases characterized by primary abnormalities in glial cells and myelin sheath, and it is a common nervous system disease in children and has significant genotype-phenotype correlation. In recent years, the improvement in high-throughput sequencing has changed the diagnostic and therapeutic mode of LD, and elaborative phenotype analysis, such as the collection of natural history and multimodal neuroimaging evaluation during development, also provides important information for subsequent genetic diagnosis. This article reviews LD from the perspective of clinical genetics, in order to improve the awareness of this disease among pediatricians in China.

Genetic characteristics of microtia-associated syndromes in neonates / 中国当代儿科杂志

Microtia is the second most common maxillofacial birth defect in neonates and has an prevalence rate of 3.06/10 000 in China, and 20%-60% of microtia cases is associated with a certain type of syndrome. This article elaborates on the clinical phenotypes and genetic characteristics of three microtia-associated syndromes (MASs) with high prevalence, high incidence rate of ear deformity, and definite genetic etiology, i.e., oculo-auriculo-vertebral spectrum, branchio-oto-renal spectrum disorder, and Treacher-Collins syndrome, and summarizes another three common MASs, so as to provide a reference for the genetic diagnosis of neonatal MAS.

Non-erythrocyte blood products transfusion in very preterm and extremely preterm infants in Chinese neonatal intensive care units / 中华儿科杂志

Objective: To describe the use of non-erythrocyte blood products transfusion in very preterm and extremely preterm infants in the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) in 2019, to explore the disparity between different centers, and to further investigate the rationality and standardability of non-erythrocyte blood products transfusion. Methods: This was a cross-sectional study based on the CHNN cohort of very preterm and extremely preterm infants. All 6 598 infants with gestational age (GA)<32 weeks and admitted to the 57 NICU of CHNN within 24 h of life in 2019 were enrolled. Non-erythrocyte blood products included platelet, plasma, albumin, immunoglobulin, cryoprecipitate and prothrombin complex. Infants who received at least one type of non-erythrocyte blood products were defined in transfusion group. The comparison between infants with and without transfusion was done by t-test, rank-sum test or χ2 test as appropriate. Linear regression model was used to generate adjusted transfusion rate of each center, and to investigate the correlation between adjusted rate and center-level characteristics. Results: A total of 6 598 infants were enrolled in the study, with gestational age of 30.0 (28.7, 31.0) weeks and birth weight of (1 353±312) g, and 43.6 % (2 877) of them were female. Among them, 42.7% (2 816) infants were enrolled in transfusion group, with the times of transfusion as 3 (1, 6) times. Compared to the infants without any transfusion of non-erythrocyte blood products, those infants received transfusion had lower gestational age (Z=17.62, P<0.01), lower birth weight (t=18.64, P<0.01), higher proportion of small-for-gestation age (χ2=31.06, P<0.01), multiple birth (χ²=12.82, P<0.01) and intensive resuscitation in delivery room (χ²=287.52, P<0.01), as well as lower proportion of females (χ²=10.68, P<0.01) and even lower proportion of infants born in this hospital (χ²=78.23, P<0.01). Among the entire study population, albumin (25.4%, 1 674 cases), immunoglobulin (21.5%, 1 417 cases) and plasma (18.9%, 1 245 cases) were the most commonly used non-erythrocyte blood products. Overall, 60.4% (544/901) infants with gestational age <28 weeks received transfusion 4 (2, 8) times. A total of 39.9% (2 272/5 697) infants between 28-31weeks received non-erythrocyte blood products 3 (1, 6) times. The non-erythrocyte blood products transfusion rates of critically-ill and non-critically-ill infants were 62.2% (1 693/2 723) and 29.0% (1 123/3 875) respectively, and the transfusion times were 4 (2,7) and 2 (1,4) times. The transfusion rates varied significantly among different NICU, and the disparities remained obvious after adjustment (adjusted χ²=153.48, P<0.01). Conclusion: Near half of very preterm and extremely preterm infants admitted to Chinese NICU in 2019 receive non-erythrocyte blood products during hospitalization with significant disparities among different hospitals.

Epigenetic clocks in the pediatric population: when and why they tick? / 中华医学杂志(英文版)

Recent research efforts have provided compelling evidence of genome-wide DNA methylation alterations in pediatrics. It is currently well established that epigenetic clocks, composed of DNA methylation sites, can estimate the gestational and chronological age of cells and tissues from different ages. Also, extensive research is aimed at their correlation with early life exposure and pediatric diseases. This review aimed to systematically summarize the epigenetic clocks in the pediatric population. Publications were collected from PubMed and Web of Science databases up to Apr 2021. Epigenetic clocks, DNA methylation clocks, epigenetic age acceleration or deceleration, pediatric and the pediatric population were used as search criteria. Here, we first review the currently applicative pediatric epigenetic clocks. We then highlight the interpretation for epigenetic age deviations in the pediatric population and their association with external factors, developmental trajectories, and pediatric diseases. Considering the remaining unknown of pediatric clocks, research strategies into them are also discussed. In all, pediatric epigenetic clocks may act as potent tools to understand development, growth and diseases in early life.

Influence of coronavirus disease 2019 on the nervous system of children / 中国当代儿科杂志

Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic and can occur at any age, including children. Children with COVID-19 can develop the clinical symptoms of multiple systems, among which symptoms of the nervous system have been reported increasingly, and thus it is particularly important to understand COVID-19-associated neurological damage in children. This article reviews the mechanisms and types of COVID-19-associated neurological damage in children.

A review on the genetic mechanism of chromatin remodeling in children with neurodevelopmental disorders / 中国当代儿科杂志

Neural development is regulated by both external environment and internal signals, and in addition to transcription factors, epigenetic modifications also play an important role. By focusing on the genetic mechanism of ATP-dependent chromatin remodeling in children with neurodevelopmental disorders, this article elaborates on the effect of four chromatin remodeling complexes on neurogenesis and the development and maturation of neurons and neuroglial cells and introduces the clinical research advances in neurodevelopmental disorders.

Clinical features and SLC6A8 gene mutations of cerebral creatine deficiency syndrome I: an analysis of two families / 中国当代儿科杂志

This article reports the clinical and genetic features of two cases of cerebral creatine deficiency syndrome I (CCDSI) caused by SLC6A8 gene mutations. Both children were boys. Boy 1 (aged 2 years and 10 months) and Boy 2 (aged 8 years and 11 months) had the clinical manifestations of delayed mental and motor development, and convulsion. Their older brothers had the same symptoms. The mother of the boy 1 had mild intellectual disability. The genetic analysis showed two novel homozygous mutations, c.200G>A(p.Gly67Asp) and c.626_627delCT(p.Pro209Argfs*87), in the SLC6A8 gene on the X chromosome, both of which came from their mothers. These two novel mutations were rated as possible pathogenic mutations and were not reported in the literature before. This study expands the mutation spectrum of the SLC6A8 gene and has great significance in the diagnosis of boys with delayed development, and epilepsy.

Application of simulation-based medicine education in pediatric resident training / 中国实用儿科杂志

Simulation-based medicine education(SBME)refers to the clinical teaching method of using medical simulation equipment or simulator design to simulate clinical scenes,replacing the actual content of real medical scenes in an interactive way and the actual patient. Simulation is particularly important in pediatric resident training,and a large amount of evidencebased evidence confirms that simulation training used in resident training ensures patients' safety and improves patients' outcomes. The paper mainly expounds the application principle,theoretical basis,main content and the method of establishing the simulation center in the training of pediatric resident in simulated medical education,intending to promote the further development of simulation training in the training of domestic pediatric resident.

Advanced molecular technologies for the diagnosis of congenital malformation in neonates / 中国当代儿科杂志

Congenital malformation is one of the most frequent causes of infant death in western countries and major cities in China. Though genetic screening of newborns remains a hot issue and concern, the mortality rate associated with birth defects has not been significantly reduced over the past 20 years. Many genetic diseases manifest symptoms during the first 28 days of life, but full clinical symptoms might not be evident in newborns. Moreover, genetic aberrations is highly heterogeneous. These complicated factors lead to the establishment of diagnosis based on nonspecific or obscure symptoms. Recently developed array comparative genomic hybridization (CGH) and next generation sequencing (NGS) techniques with efficient high-resolution allow to screening of the entire genome for DNA copy number variants and sequencing respectively. These new and powerful tools can shorten the differential diagnosis process and quicken to movement towards targeted treatment and genetic and prognostic counseling.

Application of tetrahydrobiopterin in treatment of phenylketonuria / 中华实用儿科临床杂志

Until recently,the common treatment for phenylketonuria (PKU) was a phenylalanine (Phe)-restricted diet.Increasing evidence of suboptimal outcomes was observed in diet-treated individuals.The observation of clinically significant reductions in blood Phe levels in a subset of patients with PKU following oral administration of tetrahydrobiopterin(BH4),a cofactor of phenylalanine hydroxylase.Clinical studies suggest that treatment with BH4 provides better Phe control and increases dietary Phe tolerance,allowing significant relaxation or even discontinuation of dietary Phe restriction.The current knowledge on this novel pharmacologic approach to the treatment of PKU will be discussed.

Changes in MLS-BAEP in newborn piglets with hypoxic-ischemic brain damage during selective moderate head cooling therapy / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effect of selective moderate head cooling therapy on maximum length sequences brainstem auditory evoked potential (MLS-BAEP) in newborn piglets with hypoxic-ischemic brain damage.</p><p><b>METHODS</b>Sixteen newborn piglets aged 5-7 day old were randomly divided into three groups: normothermic control (n=4), HI (n=6) and mild hypothermia-treated (n=6). HI was induced through temporary occlusion of both carotid arteries, followed by mechanical ventilation with low concentration of oxygen (FiO2=0.06) for 30 minutes. Mild hypothermia was induced by equipment via circulating water. MLS-BAER was recorded before HI and at 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, 4 days, 7 days, 10 days, 13 days and 15 days after HI.</p><p><b>RESULTS</b>Compared with the normothermic control group, all latencies and intervals tended to increase significantly at 72 hours in the HI group and reached peak values on day 7. From day 10, all latencies and intervals tended to decrease, but apart from wave I latency, still differed significantly from those of the normothermic control group. MLS-BAER variables did not reach normal values until day 15. Ⅲ latency, Ⅰ-Ⅲ interval and Ⅰ-Ⅴ interval were significantly reduced in the hypothermia-treated group between 60 and 7 days after HI compared with the HI group (P<0.05). V latency and Ⅲ-Ⅴ interval in the hypothermia-treated group were also reduced compared with the HI group between 72 hours and 7 days after HI (P<0.05).</p><p><b>CONCLUSIONS</b>Both peripheral and central auditory systems are disturbed by HI, which shows as a significant increase in MLS-BAER variables (all latencies and intervals) in newborn piglets. Involvement in central brainstem auditory system reaches a peak on day 7 after injury. MLS-BAER variables still cannot reach to normal values until day 15. Selective moderate head cooling therapy can significantly reduce brainstem damage induced by HI.</p>

Amplitude integrated electroencephalography characteristics of normal preterm newborns: a multicenter clinical study / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the characteristics of amplitude integrated electroencephalography (aEEG) in preterm infants and changes of maturation with gestational age.</p><p><b>METHODS</b>aEEG monitoring was done within 3 days of age with domestically produced digital aEEG set (CFM3000). Duration of each recording was at least 4 hours. The continuity, sleep-wake cycle, voltage and bandwidth of all aEEG tracing were analyzed.</p><p><b>RESULTS</b>The percent of continuity background increased from 30% of 28 weeks to 85.7% of 36 weeks (χ(2) = 28.2, P = 0.026); the percent of mature sleep-wake cycle increased from 10% of 28 weeks to 100% of 36 weeks (χ(2) = 192.4, P < 0.01). Low bound voltage increased with gestational age, from (6.8 ± 1.7) µV (28 w) to 9.7 - 10.1 µV (35 - 36 w) (F = 11.4, P < 0.01). Bandwidth of the narrow band decreases gradually with gestational age, from 1.45 cm (28 w) to (0.86 ± 0.24) cm (36 w) (F = 8.731, P < 0.01). The correlation coefficient for continuity, sleep-wake cycle, low bound voltage and bandwidth of narrow band, and total scores were 0.32, 0.81, 0.38, 0.55 and 0.78 respectively (P < 0.05).</p><p><b>CONCLUSION</b>The older the gestational age of infants at birth, the more mature the aEEG pattern, manifested as increased continuity and sleep-wake cycle, the higher low bound voltage and more narrowed bandwidth with increased gestational age.</p>

Neurogenesis in the subventricular zone of neonatal rats after ischemic brain injury / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the proliferation and differentiation of neural stem cells in the subventricular zone (SVZ) in neonatal rats after bilateral common arteries occlusion.</p><p><b>METHODS</b>Ninety-six 3-day-old Sparuge-Dawley rats were randomly divided into two groups: ischemia and control. Rats in the ischemia group were subjected to bilateral common arteries occlusion and the rats in the control group were sham-operated. All rats were administrated with 5-bromodeoxyuridine (BrdU) (50 mg/kg) via intraperitoneal injection. Rats were sacrificed and their brains were removed 1, 4, 7, 10, 14 and 35 days after ischemia. Using brain paraffin sections and immunofluorescence assays, the number of newborn cells in the SVZ was counted. Newborn neural stem cells and oligodendrocytes in the SVZ were observed, and then double marked with BrdU and nestin or osmium tetroxide (O4).</p><p><b>RESULTS</b>The number of BrdU+ cells (neural stem cells) in the SVZ in the ischemia group was greater than in the control group 4, 7, 10 and 14 days after ischemia, and reached a peak at 4 days after ischemia (253.1+/- 49.3 vs 133.5+/- 17.7; P< 0.01). By 35 days after ischemia, the number of BrdU+/O4+ cells (oligodendrocytes) in the corpus callosum (56.0+/- 7.2 vs 17.0+/- 6.4; P< 0.01), the septal nuclei (45.0+/- 11.9 vs 20.5+/- 5.0; P< 0.01), the striatum (34.5+/- 4.2 vs 14.5+/- 5.8; P< 0.01) and the olfactory bulb (46.5+/- 6.6 vs 23.5+/- 8.4; P< 0.01) in the ischemia group increased significantly as compared to the control group (P< 0.01).</p><p><b>CONCLUSIONS</b>Brain ischemia can activate the proliferation of neural stem cells in the SVZ and promote neural stem cells differentiation into oligodendrocytes. The immature brain may have the capacity for self-repair after ischemic brain injury.</p>

Effect of whole-body hypothermia on cardiac hemodynamics neonatal piglet after hypoxia-ischemia / 中华急诊医学杂志

Objective To determine the effect of mild hypothermia on neonatal piglet cardiac hemodynamic function after hypoxia-ischemia (HI).Method Twenty five 7-day-old piglets were used for hypoxic ischemic brain damage (HIBD) model by the method of temporary occlusion of the bilateral carotid arteries and followed by mechanical ventilation with low concentration of oxygen (FiO_2=6%) for 30 minutes.The piglets were randomly divided into three groups:group A (normothermia with body temperature to 39℃,n=9),group B (body temperature to 36℃for 72 hours,n=8),and group C (body temperature to 34℃for 72 hours,n=8).Mild hypothermia was initiated at 4 hours after HI,the systolic and diastole function were evaluated by Doppler echocardiography at pre-HI,post-Hi 4 hours and post-HI 72 hours.Results There were no significant differences in left ventrieular ejection time/left ventrieular ejection time (LPEP/LVEF),right ventricular ejection acceleration time/right ventricular ejection time (RACT/RVET) and CO at post-HI with hypothermia 72 hours in three groups,but the heart rate decreased in B and group C group.Compared with nonnothermia,mild hypothermia treatment showed no significant differences in MAP,LPEP/LVET,RACT/RVET,CO,SV at post-HI with hypothermia 72 hours.Conclusions Body temperature decreased by 3～5℃for 72 hours will not aggravate hemodynamic abnormity.

Effects of hypothermia on cardiac function in neonates with asphyxia / 中华儿科杂志

<p><b>OBJECTIVE</b>To study the effects of hypothermia on cardiac function in neonates after birth asphyxia.</p><p><b>METHODS</b>Fifty term newborns with Apgar score < 5 at 5 minutes were randomly divided into no cooling group (normothermia group, NG; rectal temperature = 36.5 degrees C +/- 0.5 degrees C, n = 27) and cooling group (hypothermia group, HG; rectal temperature = 34.5 degrees C +/- 0.3 degrees C, nasopharyngeal temperature = 34.0 degrees C +/- 0.5 degrees C, n = 23). The selective head cooling was applied to maintain nasopharyngeal temperature at 34 degrees C for 72 h in hypothermia group. Systolic and diastolic function was detected at the end of treatment by echocardiogram.</p><p><b>RESULTS</b>(1) The heart rate was obviously decreased during the hypothermia treatment, and there was a significant difference between HG and NG [(103 +/- 15) bpm vs. (126 +/- 14) bpm, P < 0.05]. No cardiac arrhythmia and hypotension were found in all neonates. (2) There were no significant differences on the ejection fraction, stroke volume and cardiac output of left ventricle between the two groups (P > 0.05). No significant difference was found in the numbers of left and right ventricular diastolic dysfunction, pulmonary hypertension between the two groups (P > 0.05). (3) The level of cardiac troponin T (cTnT) in plasma was (0.47 +/- 0.15) ng/ml in HG, and (0.35 +/- 0.21) ng/ml in NG, and there was no significant difference between the two groups (P > 0.05).</p><p><b>CONCLUSION</b>No significant cardiac dysfunction complication caused by the hypothermia treatment was found in term neonates after birth asphyxia.</p>