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Neurological consequences of systemic inflammation in the premature neonate

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Neural Regeneration Research 2017年第6期12卷 890-896页

作者： Aparna Patra Hong Huang John A.Bauer Peter J.Giannone OMNI Academic Service Line and Division of neonatology Department of Pediatrics Kentucky Children's Hospital College of MedicineUniversity of Kentucky

Despite substantial progress in neonatal care over the past two decades leading to improved survival of extremely premature infants, extreme prematurity continues to be associated with long term neurodevelopmental impairments. Cerebral white matter injury is the predominant form of insult in preterm brain leading to adverse neurological consequences. Such brain injury pattern and unfavorable neurologic sequelae is commonly encountered in premature infants exposed to systemic inflammatory states such as clinical or culture proven sepsis with or without evidence of meningitis, prolonged mechanical ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis and chorioamnionitis. Underlying mechanisms may include cytokine mediated processes without direct entry of pathogens into the brain, developmental differences in immune response and complex neurovascular barrier system that play a critical role in regulating the cerebral response to various systemic inflammatory insults in premature infants. Understanding of these pathologic mechanisms and clinical correlates of such injury based on serum biomarkers or brain imaging findings on magnetic resonance imaging will pave way for future research and translational therapeutic opportunities for the developing brain.

关键词： premature consequences inflammation prematurity extremely translational dysplasia sepsis necrotizing neurological

Recombinant human erythropoietin for repair of white matter damage

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Neural Regeneration Research 2011年第8期6卷 635-640页

作者： Wei Zhou Xiao Rong Li Tao Weineng Lu Guangzhou Women and Children Medical Center Department of Neonatology Guangzhou Children's Hospital Guangzhou 510120Guangdong Province China

Erythropoietin has been shown to exhibit neuroprotective effects in animal models. A neonatal rat model of hypoxic-ischemic white matter damage was established via bilateral carotid artery ligation in 4-day-old Sprague-Dawley rats. The rats were subsequently treated with recombinant human erythropoietin to observe pathological changes in the brain and long-term neurobehavioral functions before and after intervention. Results showed that the number of myelin basic protein-positive cells, which reflected myelin/oligodendrocyte damage, significantly increased, although the number of amyloid precursor protein-positive cells, which reflected axonaf injury, significantly decreased in periventricular white matter at 72 hours and 7 days following erythropoietin intervention. The number of glial fibrillary acidic protein-positive cells, indicating astrocytic damage, significantly decreased in periventricular white matter of erythropoietin-treated rats at 48 hours, 72 hours, 7 days and 26 days. Following erythropoietin intervention in the 30-day-old rats, head-turning time in the slope test was shortened and open-field test scores increased. These results suggested that erythropoietJn promoted repair of white matter damage, as well as improved neurobehavioral functions in a rat model of hypoxic-ischemic injury.

关键词： white matter injury erythropoietin neonatal rats neural behavior neuroprotection

Artificial womb:a paradigm shift for saving extremely premature infants

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Chinese Medical Journal 2023年第14期136卷 1759-1761页

作者： Zhelan Huang Tiantian Xiao Wenhao Zhou department of neonatology Children’s HospitalFudan UniversityShanghai 201102China department of neonatology Chengdu Women’s and Children’s Central HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan 610000China

To the Editor:Approximately 15 million preterm babies,i.e.,those delivered at<37 weeks of gestational age(GA),are born globally every year,and of them,0.4%are extremely premature infants(EPIs),i.e.,those delivered at<28 weeks of GA.^([1])Iterations of neonatal care have significantly extended the viability of preterm ***,improved viability is accompanied by an increased risk of unreversed injuries,such as bronchopulmonary dysplasia and intraventricular ***,a more physiological simulating in utero status is needed to protect EPIs’immature organs during the transitional period and ensure that they develop in the same manner that they would have in the womb.

关键词： injuries organs reversed

The Alexandria retinopathy of prematurity model(Alex-ROP): postnatal weight gain screening algorithm application in a developing country

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International Journal of Ophthalmology(English edition) 2019年第2期12卷 296-301页

作者： Islam SH Ahmed Adham AO Badeeb department of Ophthalmology Faculty of MedicineAlexandria Main University Hospital department of Pediatrics and neonatology Faculty of Medicine Alexandria University maternity Hospital

AIM: To suggest a novel retinopathy of prematurity(ROP) screening model in developing countries incorporating postnatal weight gain ratios(PWGR) to traditional parameters to maintain sensitivity and improve specificity in detecting ROP. METHODS: Analysis of weekly PWGR of infants from one tertiary referral center during six months to determine the age at which the PWGR with the highest predictability for ROP development which was referred to as the postnatal net weight gain ratio(NWGR). NWGR was added to conventional criteria to describe a new model(The Alex-ROP model). RESULTS: Of 560 infants were included. NWGR 28 d after birth was the most predictive factor for the development of ROP. A new model Alex-ROP recommending screening infants with gestational age(GA) ≤33 wk or birth weight ≤1500 g and NWGR at 28 d after birth <0.3 was suggested. A second screening model referred to as High-grade AlexROP(Hg Alex-ROP) model to detect worse grade ROP(Both type 1 and type 2) recommending a cutoff point of NWGR <0.15 between birth and 28^(th) day. CONCLUSION: Both Alex-ROP and Hg Alex-ROP models are easy to apply to improve the specificity of ROP screening in developing countries while maintaining high sensitivity.

关键词： screening retinopathy of prematurity postnatal weight gain

Decreased connexin 43 in astrocytes inhibits the neuroinflammatory reaction in an acute mouse model of neonatal sepsis

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Neuroscience Bulletin 2015年第6期31卷 763-768页

作者： Jing-Jing Zhou Cheng Cheng Zilong Qiu Wen-Hao Zhou Guo-Qiang Cheng department of neonatology Children's Hospital of Fudan University Institute of Neuroscience Shanghai Institutes for Biological SciencesChinese Academy of Sciences

Neonatal sepsis is common in neonatal intensive care units, often complicated by injury to the immature brain. Previous studies have shown that the expression of the gap junction protein connexin 43 （Cx43） in the brain decreases when stimulated by neuro-inflammatory drugs such as lipopolysaccharide （LPS）. Here we showed that partial deletion of Cx43 in astrocytes resulted in weakened inflammatory responses. The up-regulation of pro-inflammatory cytokines was significantly reduced in mice with partial deletion of Cx43 in astrocytes compared with wild-type littermates after systemic LPS injection. Moreover, microglial activation was inhibited in mice with partial deletion of Cx43. These results showed that Cx43 in astrocytes plays a critical role in neuro-inflammatory responses. This work provides a potential therapeutic target for inhibiting neuro- inflammatory responses in neonatal sepsis.

关键词： astrocyte gap junction Cx43 neonatalsepsis

Differential impact of flow and mouth leak on oropharyngeal humidification during high-flow nasal cannula: a neonatal bench study

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World Journal of Pediatrics 2018年第3期14卷 305-309页

作者： Tim Leon Ullrich Christoph Czernik Christoph Bührer Gerd Schmalisch Hendrik Stefan Fischer department of neonatology CharitéUniversity Medical CenterCharitéplatz 110117 BerlinGermany

Background Heated humidification is paramount during neonatal high-flow nasal cannula (HFNC) therapy. However, there is little knowledge about the influence of flow rate and mouth leak on oropharyngeal humidification and temperature. Methods The effect of the Optiflow HFNC on oropharyngeal gas conditioning was investigated at flow rates of 4, 6 and 8 L min-1 with and without mouth leak in a bench model simulating physiological oropharyngeal air conditions during spontaneous breathing. Temperature and absolute humidity (AH) were measured using a digital thermo-hygrosensor. Results Without mouth leak, oropharyngeal temperature and AH increased significantly with increasing flow (P < 0.001). Mouth leak did not affect this increase up to 6 L min-1, but at 8 L min-1, temperature and AH plateaued, and the eff ect of mouth leak became statistically significant (P < 0.001). Conclusions Mouth leak during HFNC had a negative impact on oropharyngeal gas conditioning when high flows were applied. However, temperature and AH always remained clinically acceptable.

关键词： Humidity Infant Non-invasive ventilation Temperature

Clinical characteristics, diagnosis and management of respiratory distress syndrome in full-term neonates

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Chinese Medical Journal 2010年第19期123卷 2640-2644页

作者： LIU Jing SHI Yun DONG Jian-ying ZHENG Tian LI Jing-ya LU Li-li LIU Jing-jing LIANG Jing ZHANG Hao FENG Zhi-chun department of neonatology & NICU Bayi Children's Hospital Affiliated to General Hospital of Beijing Military Command Beijing 100700 China

Background Respiratory distress syndrome （RDS） is one of the most common causes of neonatal respiratory failure and neonatal death, however, its clinical characteristics are very different from premature RDS, and these characteristics have not been well documented as yet. This study was to investigate the pathogenesis, clinical characteristics and management strategies of RDS in full-term neonates, with the aim of developing a working protocol for improving the outcome in full-term neonates with RDS. Methods A total of 125 full-term infants with RDS were enrolled in this study. Their clinical and laboratory data were collected for analyzing the characteristics of full-term neonatal RDS. Results （1） The 125 cases included 94 male and 31 female infants, vaginal delivery occurred in 80 cases and cesarean section in 45 cases. （2） The onset time of RDS was （3.11±3.59） hours after birth. （3）The possible reasons included severe perinatal infections in 63 patients, elective cesarean section in 34 cases, severe birth asphyxia in 12 patients, meconium aspiration syndrome in 9 patients, pulmonary hemorrhage in 4 patients and maternal diabetes in 3 patients. （4） Complications included multiple organ system failure （MOSF） in 49 patients, persistent pulmonary hypertension of newborn （PPHN） in 25 patients, acute renal failure in 18 patients, severe hyperkalemia in 25 patients, severe metabolic acidosis in 6 cases, severe myocardial injury in 9 cases, pulmonary hemorrhage in 3 cases, disseminated intravascular coagulation in 14 patients and shock in 12 patients.（5） Four patients died, the mortality was therefore 3.2% with the main cause of septicemia complicating of MOSF, but their prognosis was improved while comprehensive treatment measures including early mechanical ventilation and broad spectrum antibiotics were taken into account. Conclusions RDS is not an uncommon disease in full-term infants and is associated with a higher mortality, its clinical characteristics are very dif

关键词： respiratory distress syndrome clinical characteristics diagnostic criteria management strategies newborn full-term

Short-term developmental outcomes in neonates born to mothers with COVID-19 from Wuhan, China

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World Journal of Pediatrics 2021年第3期17卷 253-262页

作者： Ling-Kong Zeng Hua-Ping Zhu Tian-Tian Xiao Si-Cong Peng Wen-Hao Yuan Jian-Bo Shao Lai-Shuan Wang Fei-Fan Xiao Shi-Wen Xia Shoo K.Lee Kai Yan Wen-Hao Zhou department of neonatology Wuhan Children's Hospital(Wuhan Maternal and Child Healthcare Hospital)Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina department of neonatology Maternal and Child Health Hospital of Hubei ProvinceWuhanChina National Children’s Medical Center Children’s Hospital of Fudan UniversityShanghaiChina department of neonatology Chengdu Women's and Children's Central HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduChina department of neonatology Children's Hospital of Fudan UniversityNational Children's Medical CenterShanghaiChina Maternal-Infant Care Research Center(MiCARE)and department of Pediatrics Mount Sinai HospitalTorontoONCanada department of Pediatrics Department of Obstetrics and Gynecology and Dal la Lana School of Public HealthUniversity of TorontoTorontoONCanada

Background Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is an emerging *** consequences of SARS-CoV-2 exposure in infants remain ***,this study aims to investigate whether neonates born to mothers with COVID-19 have adverse brain *** This multicenter observational study was conducted at two designated maternal and children's hospitals in Hubei Province,China's Mainland from February 1,2020 to May 15,*** born to mothers with COVID-19 were *** magnetic resonance imaging(MRI)findings,and volumes of grey and white matters,and physical growth parameters were observed at 44 weeks corrected gestational *** Of 72 neonates born to mothers with COVID-19,8(11%)were diagnosed with COVID-19,8(11%)were critically ill,and no deaths were *** the eight neonates that underwent brain MRI at corrected gestational age of 44 weeks,five neonates were diagnosed with *** these five neonates,three presented abnormal MRI findings including abnormal signal in white matter and delayed myelination in newborn 2,delayed myelination and brain dysplasia in newborn 3,and abnormal signal in the bilateral periventricular in newborn *** other three neonates without COVID-19 presented no significantly changes of brain MRI findings and the volumes of grey matter and white matter compared to those of healthy newborns at the equivalent age(P>0.05).Physical growth parameters for weight,length,and head circumference at gestational age of 44 weeks were all above the 3rd percentile for all *** Some of the neonates born to mothers with COVID-19 had abnormal brain MRI findings but these neonates did not appear to have poor physical *** findings may provide the information on the follow-up schedule on the neonates exposed to SARS-CoV-2,but further study is required to evaluate the association between the abnormal MRI findings and the exposure

关键词： Coronavirus disease 2019 Follow-up Neonate Severe acute respiratory syndrome coronavirus 2

Treatment of retinopathy of prematurity: a review of conventional and promising new therapeutic options

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International Journal of Ophthalmology(English edition) 2013年第2期6卷 228-236页

作者： Fatih Mehmet Mutlu Umit Serdar Sarici department of Ophthalmology Gülhane Military Medical Academy and Medical School department of Pediatrics Division of Neonatology Gülhane Military Medical Academy and Medical School

Retinopathy of prematurity (ROP), a retinal vascular disease of premature infants, continues to be a major cause of preventable childhood blindness all over the world. The incidence of ROP varies among countries, being influenced by the quality of the level of neonatal intensive care. Here, we discuss the potential treatments that are now available or will soon or probably be available for ROP. Although ablation of the avascular retina with laser photocoagulation remains the current gold standard and well established therapy for ROP, some new therapeutic options including angiostatic therapies are being explored based on our knowledge of the pathophysiology of the ROP and complications and efficacy of laser treatment. However, prevention of the development of severe ROP and screening for ROP seem to be the best strategy in avoiding visual impairment caused by ROP in premature infants. New therapeutic interventions including vascular endothelial growth factor antibody administration, gene therapy and supplemental therapies should be supported with evidence-based data for the treatment of ROP.

关键词： retinopathy of prematurity laser retina vascular endothelial growth factor propranolol