Objective:China was the first country suffering from the SARS-CoV-2 pandemic and one of the countries with stringent mother-neonate isolation measure implemented.Now increasing evidence suggests that coronavirus disea...Objective:China was the first country suffering from the SARS-CoV-2 pandemic and one of the countries with stringent mother-neonate isolation measure implemented.Now increasing evidence suggests that coronavirus disease 2019(COVID-19)should not be taken as an indication for formula feeding or isolation of the infant from the mother.Methods:We conducted a retrospective cohort study in 44 hospitals from 14 provinces in China to investigate the management of neonates whose mothers have confirmed or suspected COVID-19.In addition,65 members of Chinese Neonatologist Association(CNA)were invited to give their comments and suggestions on the clinical management guidelines for high-risk neonates.Results:There were 121 neonates born to 118 mothers suspected with COVID-19 including 42 mothers with SARS-CoV-2 positive results and 76 mothers with SARS-CoV-2 negative results.All neonates were born by caesarean section,isolated from their mothers immediately after birth and were formula-fed.Five neonates were positive for SARSCoV-2 at initial testing between 36 and 46 h after birth.Regarding the confusion on the clinical management guidelines,58.78%of the newborns were put into isolation,32.22%were subject to PCR tests,and 5.16%and 2.75%received breastfeeding and vaccination,respectively.Conclusion:The clinical symptoms of neonates born to mothers with confirmed SARS-CoV-2 were mild,though five neonates might have been infected in utero or during delivery.Given the favorable outcomes of neonates born to COVID-confirmed mothers,full isolation may not be warranted.Rather,separation of the mother and her newborn should be assessed on a case-by-case basis,considering local facilities and risk factors for adverse outcomes,such as prematurity and fetal distress.展开更多
Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury respons...Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury response,including inflammation and repair.Although colony-stimulating factor 1 receptor inhibitors such as PLX5622 enable the selective depletion of microglia,their therapeutic potential in neonatal germinal matrix hemorrhage remains underexplored.Here,we used a collagenase-induced germinal matrix hemorrhage model in postnatal day 5 mice,and intraperitoneally administered PLX562272 hours post-germinal matrix hemorrhage to achieve targeted,temporary microglial depletion during the peak injury response.We then assessed the effects of this delayed intervention on oligodendrocyte lineage cell maturation,white matter integrity,and neurobehavioral outcomes.Additionally,RNA sequencing data from a germinal matrix hemorrhage rat model were analyzed using weighted gene co-expression network analysis to identify the critical phases for interventions.RNA sequencing data revealed a critical period in which key synaptic functions declined while immune responses intensified post-germinal matrix hemorrhage,thus pinpointing the critical response phases for potential interventions.Delayed PLX5622 treatment effectively depleted activated microglia,protecting against white matter injury and enhancing oligodendrocyte lineage cell maturation and myelination in subcortical white matter regions.Moreover,magnetic resonance imaging analysis revealed reduced brain lesion volumes in treated mice.Behaviorally,PLX5622-treated mice exhibited significant improvements in motor coordination and reduced hyperactivity compared with vehicle-treated germinal matrix hemorrhage model mice.These findings suggest that,when timed to avoid interference with initial oligodendrocyte lineage cell proliferation,targeted microglial depletion with PLX5622 significantly mitigates white matter damage and improves neurobehavioral outcomes in neonatal germinal matrix hemorrhage.The present study highlights the therapeutic potential of selectively modulating microglial reactivity to support neurodevelopment in preterm infants with brain injury.展开更多
基金Funding from the Department of Maternal and Child Health,National Health Commission of the People's Republic of China:Construction and Evaluation of Neonatal Intensive Care System in China(201906063).
文摘Objective:China was the first country suffering from the SARS-CoV-2 pandemic and one of the countries with stringent mother-neonate isolation measure implemented.Now increasing evidence suggests that coronavirus disease 2019(COVID-19)should not be taken as an indication for formula feeding or isolation of the infant from the mother.Methods:We conducted a retrospective cohort study in 44 hospitals from 14 provinces in China to investigate the management of neonates whose mothers have confirmed or suspected COVID-19.In addition,65 members of Chinese Neonatologist Association(CNA)were invited to give their comments and suggestions on the clinical management guidelines for high-risk neonates.Results:There were 121 neonates born to 118 mothers suspected with COVID-19 including 42 mothers with SARS-CoV-2 positive results and 76 mothers with SARS-CoV-2 negative results.All neonates were born by caesarean section,isolated from their mothers immediately after birth and were formula-fed.Five neonates were positive for SARSCoV-2 at initial testing between 36 and 46 h after birth.Regarding the confusion on the clinical management guidelines,58.78%of the newborns were put into isolation,32.22%were subject to PCR tests,and 5.16%and 2.75%received breastfeeding and vaccination,respectively.Conclusion:The clinical symptoms of neonates born to mothers with confirmed SARS-CoV-2 were mild,though five neonates might have been infected in utero or during delivery.Given the favorable outcomes of neonates born to COVID-confirmed mothers,full isolation may not be warranted.Rather,separation of the mother and her newborn should be assessed on a case-by-case basis,considering local facilities and risk factors for adverse outcomes,such as prematurity and fetal distress.
基金supported by the National Key Research and Development Program of China,No.2022YFC2704801(to CZhu)the National Natural Science Foundation of China,Nos.U21A20347(to CZhu),82203969(to YX),82371472(to XZ)+3 种基金Health Commission of Henan Province,Nos.SBGJ202303039(to XZ),SBGJ202301009(to CZhu),YQRC2024018(to XZ),YQRC2024019(to YX)Henan Science and Technology Department,Nos.242102311054(to XZ),241111521300(to CZhu),GZS2023003(to XW)Swedish Research Council,Nos.2022-01019(to CZhu),2021-01950(to XW)Swedish Governmental Grants to Scientists Working in Healthcare,Nos.ALFGBG-1005209(to CZhu),ALFBG-1005257(to XW),ALFGBG-965197(to CZhu).
文摘Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury response,including inflammation and repair.Although colony-stimulating factor 1 receptor inhibitors such as PLX5622 enable the selective depletion of microglia,their therapeutic potential in neonatal germinal matrix hemorrhage remains underexplored.Here,we used a collagenase-induced germinal matrix hemorrhage model in postnatal day 5 mice,and intraperitoneally administered PLX562272 hours post-germinal matrix hemorrhage to achieve targeted,temporary microglial depletion during the peak injury response.We then assessed the effects of this delayed intervention on oligodendrocyte lineage cell maturation,white matter integrity,and neurobehavioral outcomes.Additionally,RNA sequencing data from a germinal matrix hemorrhage rat model were analyzed using weighted gene co-expression network analysis to identify the critical phases for interventions.RNA sequencing data revealed a critical period in which key synaptic functions declined while immune responses intensified post-germinal matrix hemorrhage,thus pinpointing the critical response phases for potential interventions.Delayed PLX5622 treatment effectively depleted activated microglia,protecting against white matter injury and enhancing oligodendrocyte lineage cell maturation and myelination in subcortical white matter regions.Moreover,magnetic resonance imaging analysis revealed reduced brain lesion volumes in treated mice.Behaviorally,PLX5622-treated mice exhibited significant improvements in motor coordination and reduced hyperactivity compared with vehicle-treated germinal matrix hemorrhage model mice.These findings suggest that,when timed to avoid interference with initial oligodendrocyte lineage cell proliferation,targeted microglial depletion with PLX5622 significantly mitigates white matter damage and improves neurobehavioral outcomes in neonatal germinal matrix hemorrhage.The present study highlights the therapeutic potential of selectively modulating microglial reactivity to support neurodevelopment in preterm infants with brain injury.
