Brain development in newborns and infants after ECMO.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) not only significantly improves survival rates in severely ill neonates but also is associated with long-term neurodevelopmental issues. To systematically review the available literature on the neurodevelopmental outcomes of neonates and infants who have undergone ECMO treatment, with a focus on motor deficits, cognitive impairments, sensory impairments, and developmental delays. This review aims to understand the incidence, prevalence, and risk factors for these problems and to explore current nursing care and management strategies. DATA SOURCES: A comprehensive literature search was performed across PubMed, EMBASE, and Web of Science using a wide array of keywords and phrases pertaining to ECMO, neonates, infants, and various facets of neurodevelopment. The initial screening involved reviewing titles and abstracts to exclude irrelevant articles, followed by a full-text assessment of potentially relevant literature. The quality of each study was evaluated based on its research methodology and statistical analysis. Moreover, citation searches were conducted to identify potentially overlooked studies. Although the focus was primarily on neonatal ECMO, studies involving children and adults were also included due to the limited availability of neonate-specific literature. RESULTS: About 50% of neonates post-ECMO treatment exhibit varying degrees of brain injury, particularly in the frontal and temporoparietal white matter regions, often accompanied by neurological complications. Seizures occur in 18%-23% of neonates within the first 24 hours, and bleeding events occur in 27%-60% of ECMO procedures, with up to 33% potentially experiencing ischemic strokes. Although some studies suggest that ECMO may negatively impact hearing and visual development, other studies have found no significant differences; hence, the influence of ECMO remains unclear. In terms of cognitive, language, and intellectual development, ECMO treatment may be associated with potential developmental delays, including lower composite scores in cognitive and motor functions, as well as potential language and learning difficulties. These studies emphasize the importance of early detection and intervention of potential developmental issues in ECMO survivors, possibly necessitating the implementation of a multidisciplinary follow-up plan that includes regular neuromotor and psychological evaluations. Overall, further multicenter, large-sample, long-term follow-up studies are needed to determine the impact of ECMO on these developmental aspects. CONCLUSIONS: The impact of ECMO on an infant's nervous system still requires further investigation with larger sample sizes for validation. Fine-tuned management, comprehensive nursing care, appropriate patient selection, proactive monitoring, nutritional support, and early rehabilitation may potentially contribute to improving the long-term outcomes for these infants.

Risk stratification of hemodynamically significant patent ductus arteriosus by clinical and genetic factors.

BACKGROUND: Hemodynamically significant patent ductus arteriosus (hsPDA) is associated with increased comorbidities in neonates. Early evaluation of hsPDA risk is critical to implement individualized intervention. The aim of the study was to provide a powerful reference for the early identification of high-risk hsPDA population and early treatment decisions. METHODS: We enrolled infants who were diagnosed with PDA and performed exome sequencing. The collapsing analyses were used to find the risk gene set (RGS) of hsPDA for model construction. The credibility of RGS was proven by RNA sequencing. Multivariate logistic regression was performed to establish models combining clinical and genetic features. The models were evaluated by area under the receiver operating curve (AUC) and decision curve analysis (DCA). RESULTS: In this retrospective cohort study of 2199 PDA patients, 549 (25.0%) infants were diagnosed with hsPDA. The model [all clinical characteristics selected by least absolute shrinkage and selection operator regression (all CCs)] based on six clinical variables was acquired within three days of life, including gestational age (GA), respiratory distress syndrome (RDS), the lowest platelet count, invasive mechanical ventilation, and positive inotropic and vasoactive drugs. It has an AUC of 0.790 [95% confidence interval (CI) = 0.749-0.832], while the simplified model (basic clinical characteristic model) including GA and RDS has an AUC of 0.753 (95% CI = 0.706-0.799). There was a certain consistency between RGS and differentially expressed genes of the ductus arteriosus in mice. The AUC of the models was improved by RGS, and the improvement was significant (all CCs vs. all CCs + RGS: 0.790 vs. 0.817, P < 0.001). DCA demonstrated that all models were clinically useful. CONCLUSIONS: Models based on clinical factors were developed to accurately stratify the risk of hsPDA in the first three days of life. Genetic features might further improve the model performance. Video Abstract (MP4 86834 kb).

[Clinical practice of whole-genome sequencing in the rapid diagnosis of critically ill neonates]. / é‡‡ç”¨å ¨åŸºå› ç»„æµ‹åºæŠ€æœ¯å¿«é€Ÿè¯Šæ–­å±é‡ç—‡æ–°ç”Ÿå„¿çš„ä¸´åºŠå®žè·µ.

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.

Monkeypox and the perinatal period: what does maternal-fetal medicine need to know?

BACKGROUND: After the global elimination of smallpox, monkeypox has become the most threatening orthopoxvirus to human health. Very few studies have been reported on pregnant women and newborns. In the case of monkeypox infection, the virus can cause serious adverse pregnancy events in women, which can lead to fetal or neonatal death. DATA SOURCES: We made a comprehensive review after an extensive literature search in the PubMed/Medline database and websites concerning smallpox and monkeypox. RESULTS: Two case reports reported a total of nine pregnant women, six of whom had fetal deaths. In the autopsy of a stillbirth, researchers found that the placenta was infected with monkeypox virus, but the mechanism of infection remains unclear. Smallpox vaccine should be administered to acutely exposed pregnant women and newborns. Several novel recombinant vaccinia immunogloblin (rVIG) and human-specific monoclonal antibodies are being developed for the prevention and treatment of monkeypox virus infection. After the fetus was delivered, the newborn should take a bath as soon as possible to remove the amniotic fluid and dirt from the body. The appropriate isolation protocol for the newborn should be selected according to the infection status of the mother. It is not known whether monkeypox virus is present in breast milk, and pasteurized breast milk can be given to newborns when breastfeeding is considered. CONCLUSION: This review presents an overview of monkeypox in the perinatal period and guides the future research direction.

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

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease. The consequences of SARS-CoV-2 exposure in infants remain unknown. Therefore, this study aims to investigate whether neonates born to mothers with COVID-19 have adverse brain development. METHODS: This multicenter observational study was conducted at two designated maternal and children's hospitals in Hubei Province, mainland China from February 1, 2020 to May 15, 2020. Neonates born to mothers with COVID-19 were enrolled. Brain magnetic resonance imaging (MRI) findings, and volumes of grey and white matters, and physical growth parameters were observed at 44 weeks corrected gestational age. RESULTS: 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 reported. Among the eight neonates that underwent brain MRI at corrected gestational age of 44 weeks, five neonates were diagnosed with COVID-19. Among 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 5. The 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 neonates. CONCLUSIONS: 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 growth. These 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 to SARS-CoV-2.

Effects of SARS-CoV-2 infection on neuroimaging and neurobehavior in neonates.

BACKGROUND: We collected neonatal neurological, clinical, and imaging data to study the neurological manifestations and imaging characteristics of neonates with coronavirus disease 2019 (COVID-19). METHODS: This case-control study included newborns diagnosed with COVID-19 in Wuhan, China from January 2020 to July 2020. All included newborns had complete neurological evaluations and head magnetic resonance imaging. We normalized the extracted T2-weighted imaging data to a standard neonate template space, and segmented them into gray matter, white matter, and cerebrospinal fluid. The comparison of gray matter volume was conducted between the two groups. RESULTS: A total of five neonates with COVID-19 were included in this study. The median reflex scores were 2 points lower in the infected group than in the control group (P = 0.0094), and the median orientation and behavior scores were 2.5 points lower in the infected group than in the control group (P = 0.0008). There were also significant differences between the two groups in the total scale score (P = 0.0426). The caudate nucleus, parahippocampal gyrus, and thalamus had the strongest correlations with the Hammersmith neonatal neurologic examination (HNNE) score, and the absolute correlation coefficients between the gray matter volumes and each part of the HNNE score were all almost greater than 0.5. CONCLUSIONS: We first compared the neurological performance of neonates with and without COVID-19 by quantitative neuroimaging and neurological examination methods. Considering the limited numbers of patients, more studies focusing on the structural or functional aspects of the virus in the central nervous system in different age groups will be carried out in the future.

[Clinical features and SLC6A8 gene mutations of cerebral creatine deficiency syndrome I: an analysis of two families].

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.

Analysis on Mechanisms of Modified Guipitang in Treatment of Yin-Fire Insomnia with Anxiety Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To explore the mechanism of modified Guipitang in the treatment of Yin-Fire insomnia with anxiety with the help of network pharmacological analysis technology. Method:Traditional Chinese Medicine Systems Pharmacology (TCMSP) was used to screen the main components and target genes of modified Guipitang. GeneCards and Online Mendelian Inheritance in Man (OMIM) were used to establish the target gene sets of insomnia and anxiety. STRING 11.0 software was used to analyze the interaction between the overlapping genes, and Cytoscape_3.6.1 software analysis and Matthews correlation coefficient (MCC) algorithm were used to screen the core genes. Based on the results of network analysis, 48 SD female rats were randomly divided into blank control group, model group, eszopiclone tablets group (0.2 mg·kg-1·d-1), modified Guipitang low，medium，and high-dose groups (0.31，1.25，5 g·kg-1·d-1). The model of insomnia with anxiety was established by intraperitoneal injection of Para-chlorophenylalanine (PCPA) and these rats were treated with corresponding drugs for 7 days. Then the frequency, time and distance of the activities were observed in the experiment of autonomic activity. Real-time quantitative polymerase chain reaction (PCR) was used to detect the mRNA expressions of proactivated protein kinase 8 (MAPK8), RAC-alpha serine/threonine protein kinase (Akt1), mitogen-activated protein kinase 3 (MAPK3) and interleukin-6 (IL-6) in rat hippocampus. Result:A total of 228 active compounds were screened from TCMSP database and 181 intersecting genes of diseases and drugs were obtained by comparing with GeneCards and OMIM comprehensive database. 9 core genes, including MAPK3, MAPK8, Akt1 and IL-6 were identified by STRING software and MCC algorithm. Animal experiments showed that the number of activity times, time and distance of modified Guipitang in high and medium dose groups were significantly lower than those in the model group. The high and middle dose groups of modified Guipitang could significantly inhibit the mRNA expression of MAPK3, MAPK8, Akt1 and IL-6 in hippocampus（P<0.01）, while the low dose group had no significant effect. Conclusion:The mechanism of modified Guipitang in treating Yin-fire insomnia with anxiety may be related to the regulation of MAPK3, MAPK8, Akt1 and IL-6 genes.

Analysis of anti-fatigue mechanism and potential targets of ginseng / 中国中药杂志

Ginseng has effects in reinforcing vital energy,invigorating health effectively and relieving fatigue symptoms,and ginsenoside( GS) is the main component of its anti-fatigue effect. Totally 17 active components and 92 drug targets of ginseng compounds were screened from Traditional Chinese Medicine Systems Pharmacology; and 78 intersecting genes of diseases and drug targets were obtained based on R Language Technology. The protein-protein interaction( PPI) network was constructed by STRING 11. 0 software,and Matthews Correlation Coefficient( MCC) algorithm was used to screen core target genes. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to analyze the major genes and their roles in regulatory networks. The results indicated that ginseng could regulate the core target genes,including AKT serine/threonine kinase( AKT1),interleukin-1β,Toll-like receptor binding molecule 1( ICAM1),mitogen-activated protein kinase 8( MAPK8),AP-1 transcription factor subunit( JUN),transducer and activator of transcription 1( STAT1) and prostaglandin peroxidase synthase 2( PTGS2). It could participate in the functions of cytokine receptor binding,cell adhesion molecule binding and tumor necrosis factor receptor superfamily binding,and also regulate the signal pathways of tumor necrosis factor,interleukin 17 and c-type lectin receptor,so as to exert an anti-fatigue effect. Based on the results of network analysis,32 four-week-old male SPFACR mice were randomly divided into control group,low-dose ginsenoside group,middle-dose ginsenoside group and high-dose ginsenoside group. The corresponding drugs were administrated for 3 weeks. The results showed that GS could significantly up-regulate the expressions of STAT1 and AKT1( P<0. 01,P<0. 05),and downregulate the expressions of PTGS2 and JUN( P<0. 01). However,there was no significant effect on MAPK8,IL-1β and ICAM1. Ginseng's anti-fatigue regulation network was constructed through network pharmacology,and the results were verified by experiments,in order to reveal the anti-fatigue mechanism of ginseng and provide scientific basis for its clinical application.