Genetic architecture in neonatal intensive care unit patients with congenital heart defects: a retrospective study from the China Neonatal Genomes Project.

BACKGROUND: Congenital heart defects (CHDs) are the most common type of birth defects. The genetic aetiology of CHD is complex and incompletely understood. The overall distribution of genetic causes in patients with CHD from neonatal intensive care units (NICUs) needs to be studied. METHODS: CHD cases were extracted from the China Neonatal Genomes Project (2016-2021). Next-generation sequencing results and medical records were retrospectively evaluated to note the frequency of genetic diagnosis and the respective patient outcomes. RESULTS: In total, 1795 patients were included. The human phenotype ontology term of atrial septal defect, patent ductus arteriosus and ventricular septal defect account for a large portion of the CHD subtype. Co-occurring extracardiac anomalies were observed in 35.1% of patients. 269 of the cases received genetic diagnoses that could explain the phenotype of CHDs, including 172 copy number variations and 97 pathogenic variants. The detection rate of trio-whole-exome sequencing was higher than clinical exome sequencing (21.8% vs 14.5%, p<0.05). Further follow-up analysis showed the genetic diagnostic rate was higher in the deceased group than in the surviving group (29.0% vs 11.9%, p<0.05). CONCLUSION: This is the largest cohort study to explore the genetic spectrum of patients with CHD in the NICU in China. Our findings may benefit future work on improving genetic screening and counselling for NICU patients with CHD.

Genetic spectrums and clinical profiles of critically ill neonates with congenital auricular deformity in the China Neonatal Genomes Project.

Congenital auricular deformity (CAD) is a complex phenotype that may occur as a single malformation or part of a congenital syndrome. The genetic architecture and utility of next-generation sequencing (NGS) in a sizable cross-sectional study of critically ill neonates with CAD have not yet been systematically investigated. This cross-sectional study investigated the genetic spectrum in critically ill neonates with CADs. Critically ill neonates with CADs (n = 251) were enrolled between August 8, 2016 and October 1, 2022. All neonates underwent NGS. The outcomes were molecular diagnostic yield, spectrum of genetic events, and clinical findings. Genetic findings were obtained in 107 neonates (42.6%), of which 67.3% (72/107) had pathogenic/likely pathogenic/variants of uncertain significance (P/LP/VUS) gene variations and 32.7% (35/107) had P/LP/VUS copy number variations (CNVs). The diagnostic rates of clinical exome sequencing were similar to those of exome sequencing. The logistic regression model revealed that CAD neonates with craniofacial abnormalities (OR = 4.15, 95% CI 2.29-7.53) or cardiovascular malformation (OR = 2.09, 95% CI 1.14-3.84) are more likely to be attributed to genetic causes. Follow-up analysis revealed that, compared to those in the undiagnosed group, the number of neonates whose care was withdrawn or who died was higher in the genetically diagnosed group (P < 0.05). This study identified a high incidence of genetic causes in critically ill neonates with CADs, with a combination of single-nucleotide variations and CNVs among the genetic causes of CAD. These findings highlight potential of NGS in the genetic testing of critically ill neonates with CADs.

Molecular characteristics of carbapenem-resistant gram-negative bacilli in pediatric patients in China.

BACKGROUND: Carbapenem-resistant gram-negative bacilli (CR-GNB) have been increasingly reported in China. However, dynamic monitoring data on molecular epidemiology of CR-GNB are limited in pediatric patients. RESULTS: 300 CR-GNB isolates (200 Carbapenem-resistant K. pneumoniae (CRKP), 50 carbapenem-resistant A.baumannii (CRAB) and 50 carbapenem-resistant P. aeruginosa (CRPA)) were investigated. The predominant carbapenemase gene was blaNDM-1 (73%) and blaKPC-2 (65%) in neonates and non-neonates. Meanwhile, the predominant STs were ST11 (54%) in neonates and ST17 (27.0%) and ST278 (20.0%) in non-neonates. Notably, a shift in the dominant sequence type of CRKP infections from ST17 /ST278-NDM-1 to ST11-KPC-2 was observed during the years 2017-2021 and KPC-KP showed relatively higher resistance to aminoglycosides and quinolones than NDM-KP.BlaOXA-23 was isolated from all the CRAB isolates while only one isolate expressing blaBIC and 2 isolates expressing blaVIM-2 were found in CRPA isolates. ST195 (22.0%) and ST244 (24.0%) were the most common in CRAB and CRPA isolates and all the STs of CRAB belonged to CC92 while CRPA presents ST types with diversity distribution. CONCLUSION: CRKP showed different molecular phenotypes in neonates and non-neonates and was changing dynamically and high-risk clone of ST11 KPC-KP should be paid more attention. Most CRKP and CRAB strains shared the same CCs, suggesting that intrahospital transmission may occur, and large-scale screening and more effective measures are urgently needed.

Shift in the dominant sequence type of carbapenem-resistant Klebsiella pneumonia infection from ST278-NDM-1 to ST11-KPC-2 in neonatal patients in a children's hospital in Shanghai, China, 2017-2021.

OBJECTIVES: To investigate the clinical characteristics and molecular epidemiology of CRKP infection in neonatal patients in a children's hospital in China from 2017 to 2021. METHODS: Species identification and antibiotic susceptibilities were tested with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and VITEK 2 systems. The clinical data were collected from medical records. Carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates were investigated by antimicrobial susceptibility testing, carbapenemase genes and multilocus sequence typing. RESULTS: Six kinds of resistant genes and 23 STs were detected. BlaNDM-1 (n=83, 55.3%) was the predominant carbapenemase gene, followed by blaKPC-2 (n=45, 30.0%), blaNDM-5 (n=7, 4.7%), blaIMP-38 (n=6, 4.0%). BlaNDM-1 was predominant in 2017 and 2018, whereas blaKPC-2 increased in 2019 and became the predominant gene from 2020 to 2021. ST11 accounted for most infections (n=35, 23.3%), followed by ST278 (n=23, 15.3%), ST17 (n=17, 11. 3%) and ST2735 (n=16, 10.7%). ST278 and ST17 were predominant in 2017 and 2018, whereas ST11 increased in 2019 and became the predominant sequence type from 2020 to 2021. Compared with blaNDM-1, the CRKP strains producing blaKPC-2 were characterized by high resistance to gentamicin, amikacin and levofloxacin and the change trend of drug resistance rate before and after COVID-19 was consistent with that of blaNDM-1 and blaKPC-2. CONCLUSIONS: The main sequence type of CRKP infection changed dynamically from ST278-NDM-1 to ST11-KPC-2 during the years 2017-2021 in the newborns. Antibiotic exposure and the prevalence of COVID-19 since 2020 may have led to changes in hospital population and lead to the changes.

Safety and efficacy of therapeutic hypothermia in neonates with mild hypoxic-ischemic encephalopathy.

BACKGROUND: Though there has been an increase in the number of neonates with hypoxic-ischemic encephalopathy (HIE) treated by therapeutic hypothermia (TH) in recent years, the effect of therapeutic hypothermia on mild HIE neonates is still uncertain. OBJECTIVES: This study aims to explore the safety and efficacy of therapeutic hypothermia in neonates with mild HIE. METHODS: Retrospectively collected between January 2010 to December 2022 at Children's Hospital of Fudan University, neonates with mild HIE were divided into TH and non-TH groups. Clinical data of the mild HIE neonates and their mothers' general information during pregnancy were collected. SPSS 23.0 was used to compare the general condition, the incidence of adverse events, and efficacy in the two groups. RESULTS: A total of 71 neonates with mild HIE were included, including 31 in the TH group and 40 in the non-TH group. Compared with the non-TH group, the TH group had significantly lower 5-minute Apgar scores [6 (5-7) points vs. 7 (5-8) points, p = 0.033 ], but a higher rate of tracheal intubation at birth (68%, 21/31 vs. 40%, 16/40, p = 0.02), a higher rate of chest compressions > 30 s (39%, 12/31 vs. 15%, 6/40, p = 0.023), the later initiation enteral feeding [4 (3-4) days vs. 1 (1-2) days, p < 0.001], a higher usage rate of analgesic and sedative drugs (45%, 14/31 vs. 18%, 7/40, p = 0.011) and the longer hospital stay [12.5 (11-14) days vs. 9 (7-13.9) days, p = 0.003]. There was no death in 71 mild HIE neonates. TH group had lower incidence of brain injury (16%, 5/31 vs. 43%, 17/40, p = 0.017) and encephalopathy progression (10%, 3/31 vs. 45%, 18/40, p = 0.001) than the non-TH group. There was no statistical significance in the incidence of adverse events between the two groups. CONCLUSION: Therapeutic hypothermia can reduce the incidence of brain injury in neonates with mild HIE.

[A case of interstitial lung and liver disease caused by MARS1 gene mutation]. / MARS1åŸºå› å˜å¼‚æ‰€è‡´é—´è´¨æ€§è‚ºç— åŠè‚ç— 1例.

The patient is a female infant, 4 months and 9 days old, who was admitted to the hospital due to recurrent fever, cough, and hepatomegaly for over a month. The patient was a healthy full-term infant with a normal birth history. At 2 months and 22 days after birth, she developed recurrent fever, cough, and respiratory distress. Chest imaging revealed diffuse bilateral lung lesions, and fiberoptic bronchoscopy showed interstitial changes in both lungs. These suggested the presence of interstitial lung disease. The patient also presented with hepatomegaly, anemia, hyperlipidemia, hypothyroidism, and malnutrition. Genetic testing indicated compound heterozygous variations in the MARS1 gene. This mutation can cause interstitial lung and liver disease, which is a severe rare disorder that typically manifests in infancy or early childhood. It is inherited in an autosomal recessive manner and characterized by early-onset respiratory insufficiency and liver disease in infants or young children. Since its first reported case in 2013, as of June 2023, only 38 related cases have been reported worldwide. This article reports the multidisciplinary diagnosis and treatment of interstitial lung and liver disease in an infant caused by MARS1 gene mutation.

[A rare case of neonatal-onset hepatic sinusoidal obstruction syndrome]. / æ–°ç”Ÿå„¿æœŸèµ·ç— çš„ç½•è§è‚çª¦é˜»å¡žç»¼åˆå¾1例.

A male infant, aged 1 month and 14 days, was admitted to the hospital due to abdominal distension lasting for 2 weeks and worsening for 3 days. The infant had a history of omphalitis. Physical examination revealed severe abdominal distension, prominent abdominal wall veins, hepatosplenomegaly, and massive ascites. There was a slight elevation in liver transaminase levels. Liver ultrasound and CT scans demonstrated the absence of visualization of the intrahepatic segment of the portal vein and the left, middle, and right veins of the liver, indicating occlusion of these vessels, along with surrounding fibrous hyperplasia. The clinical diagnosis was hepatic sinusoidal obstruction syndrome resulting from omphalitis. A large amount of bloody ascites developed after 12 days of hospitalization, resulting in hypovolemic shock and respiratory failure. The infant passed away following the family's decision to discontinue treatment. This article focuses on the diagnostic approach and multidisciplinary management of neonatal-onset hepatic sinusoidal obstruction syndrome, as well as provides insights into the differential diagnosis of hepatomegaly and ascites.

Clinical and Genetic Etiologies of Neonatal Unconjugated Hyperbilirubinemia in the China Neonatal Genomes Project.

OBJECTIVE: To investigate the clinical and genetic causes of neonatal unconjugated hyperbilirubinemia. STUDY DESIGN: We included 1412 neonates diagnosed with unconjugated hyperbilirubinemia (total serum bilirubin >95 percentile for age), from the China Neonatal Genomes Project between August 2016 and September 2019, in the current study. Clinical data and targeted panel sequencing data on 2742 genes including known unconjugated hyperbilirubinemia genes were analyzed. RESULTS: Among the 1412 neonates with unconjugated hyperbilirubinemia, 37% had severe unconjugated hyperbilirubinemia, with total serum bilirubin levels that met the recommendations for exchange transfusion. Known clinical causes were identified for 68% of patients. The most common clinical cause in the mild unconjugated hyperbilirubinemia group was infection (17%) and in the severe group was combined factors (21%, with infection combined with extravascular hemorrhage the most common). A genetic variant was observed in 55 participants (4%), including 45 patients with variants in genes associated with unconjugated hyperbilirubinemia and 10 patients with variants that were regarded as additional genetic findings. Among the 45 patients identified with unconjugated hyperbilirubinemia-related variants, the genes were mainly associated with enzyme deficiencies, metabolic/biochemical disorders, and red blood cell membrane defects. G6PD and UGT1A1 variants, were detected in 34 of the 45 patients (76%). CONCLUSIONS: Known clinical causes, which varied with bilirubin levels, were identified in approximately two-thirds of the patients. Genetic findings were identified in 4% of the patients, including in patients with an identified clinical cause, with G6PD and UGT1A1 being the most common genes in which variants were detected.

Use of medical exome sequencing for identification of underlying genetic defects in NICU: Experience in a cohort of 2303 neonates in China.

Emerging evidence demonstrates the clinical utility of genomic applications in newborn intensive care unit (NICU) patients with strong indications of Mendelian etiology. However, such applications' diagnostic yield and utility remain unclear for NICU cohorts with minimal phenotype selection. In this study, focused medical exome sequencing was used as a first-tier, singleton-focused diagnostic tool for 2303 unrelated sick neonates. Integrated analysis of single nucleotide variants (SNVs), small insertions and deletions (Indels), and large copy number variants (CNVs) was performed. The diagnostic rate in this NICU cohort is 12.3% (284/2303), with 190 probands with molecular diagnoses made from SNV/Indel analyses (66.9%), 93 patients with diagnostic aneuploidy/CNVs findings (32.8%), and 1 patient with both SNV and CNV (0.4%). In addition, 54 (2.3%) of patients had a reportable incidental finding. Multiple organ involvements, craniofacial abnormalities, and dermatologic abnormalities were the strongest positive predictors for a molecular diagnosis. Among the 190 cases with SNV/Indel defects, direct impacts on medical management were observed in 46.8% of patients after the results were reported. In this study, we demonstrate that focused medical exome sequencing is a powerful first-line diagnostic tool for NICU patients. Significant number of diagnosed NICU patients can benefit from more focused medical management and long-term care.

[Clinical features of children with coronavirus disease 2019 complicated by acute encephalitis and related research advances]. / æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žå„¿ç«¥åˆå¹¶æ€¥æ€§è„‘ç‚Žçš„ä¸´åºŠç‰¹ç‚¹åŠç ”ç©¶è¿›å±•.

Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic since the end of 2019. There is an increasing number of reports on nervous system symptoms, among which encephalitis is considered a serious neurological complication of COVID-19, but there are few reports of this complication in China. Acute encephalitis has severe symptoms. If it is not identified early and treated in time, the mortality is high and the prognosis is poor. During the current global epidemic, it is necessary to pay attention to the severe nervous system symptoms of COVID-19. Therefore, this article summarizes the clinical features of COVID-19 complicated by acute encephalitis through literature review and a detailed analysis of medical records, so as to provide a reference for clinicians to deal with the cases of COVID-19 complicated by acute encephalitis.

Diagnostic and clinical utility of next-generation sequencing in children born with multiple congenital anomalies in the China neonatal genomes project.

Multiple congenital anomalies (MCAs) at birth have emerged as an important cause of neonatal morbidity and mortality. This study aimed to investigate the genetic causes and characteristics of clinical outcomes in a large cohort of neonates with MCAs. Clinical exome sequencing/exome sequencing/genome sequencing were undertaken from December 1, 2016 to December 1, 2019 to detect single nucleotide variations (SNVs) and copy number variations (CNVs) simultaneously in individuals who met the inclusion criteria. A total of 588 neonates with MCAs were enrolled. One hundred sixty-one patients received diagnosis, with 71 CNVs and 90 SNVs detected, the overall diagnostic rate being 27.38%. Cardiovascular malformation was the most common anomaly (60%) and accounted for the top symptomatic proportion in both CNVs and SNVs. As the number of involved system increased from 2 to 3-4, and then to ≥5, the overall diagnostic rate increased gradually from 23.1% to 30.5%, and then to 52.2%, respectively. Patients who received genetic diagnoses were offered better clinical management or were referred to the specific disease clinic. In conclusion, this large cohort study demonstrates that both CNVs and SNVs contribute to the genetic causes of MCAs, and earlier genetic assertion may lead to better clinical management for patients.

Umbilical cord blood cells for the treatment of preterm white matter injury: Potential effects and treatment options.

Preterm birth is a global public health problem. A large number of preterm infants survive with preterm white matter injury (PWMI), which leads to neurological deficits, and has multifaceted etiology, clinical course, monitoring, and outcomes. The principal upstream insults leading to PWMI initiation are hypoxia-ischemia and infection and/or inflammation and the key target cells are late oligodendrocyte precursor cells. Current PWMI treatments are mainly supportive, and thus have little effect in terms of protecting the immature brain or repairing injury to improve long-term outcomes. Umbilical cord blood (UCB) cells comprise abundant immunomodulatory and stem cells, which have the potential to reduce brain injury, mainly due to anti-inflammatory and immunomodulatory mechanisms, and also through their release of neurotrophic or growth factors to promote endogenous neurogenesis. In this review, we briefly summarize PWMI pathogenesis and pathophysiology, and the specific properties of different cell types in UCB. We further explore the potential mechanism by which UCB can be used to treat PWMI, and discuss the advantages of and potential issues related to UCB cell therapy. Finally, we suggest potential future studies of UCB cell therapy in preterm infants.

Genetic aetiology of early infant deaths in a neonatal intensive care unit.

BACKGROUND: Congenital anomalies are the leading cause of early neonatal death in neonatal intensive care units (NICUs), but the genetic causes are unclear. This study aims to investigate the genetic causes of infant deaths in a NICU in China. METHODS: Newborns who died in the hospital or died within 1 week of discharge were enrolled from Children's Hospital of Fudan University between January 1, 2015 and December 31, 2017. Whole exome sequencing was performed in all patients after death. RESULTS: There were 223 deceased newborns with a median age at death of 13 days. In total, 44 (19.7%) infants were identified with a genetic finding, including 40 with single nucleotide variants (SNVs), two with CNVs and two with both SNVs and CNVs. Thirteen (31%, 13/42) patients with SNVs had medically actionable disorders based on genetic diagnosis, which included 10 genes. Multiple congenital malformation was identified as the leading genetic cause of death in NICUs with 13 newborns identified with variants in genes related to multiple congenital malformations. For newborns who died on the first day, the most common genetic cause of death was major heart defects, while metabolic disorders and respiratory failure were more common for newborns who died in the first 2 weeks. CONCLUSION: Our study shows genetic findings among early infant deaths in NICUs and provides critical genetic information for precise genetic counselling for the families. Effective therapies enable the improvement of more than a quarter of newborns with molecular diagnoses if diagnosed in time.

[An interpretation on perinatal and neonatal management plan for prevention and control of SARS-CoV-2 infection (2nd Edition)].

The epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues so far. The cases of SARS-CoV-2 infection have been reported in pregnant women and neonates as special groups. Perinatal and neonatal management plan for prevention and control of SARS-CoV-2 infection (2nd Edition) has been worked out by the Editorial Committee of Chinese Journal of Contemporary Pediatrics. This paper presents an interpretation on the 2nd Edition of the management plan, so as to facilitate readers to better understand it.

Implementation of the Smart Use of Antibiotics Program to Reduce Unnecessary Antibiotic Use in a Neonatal ICU: A Prospective Interrupted Time-Series Study in a Developing Country.

OBJECTIVES: We aimed to implement our Smart Use of Antibiotics Program to ensure the proper use of antimicrobials, improve patient care and outcomes, and reduce the risks of adverse effects and antimicrobial resistance. DESIGN: We compared the time periods before (baseline) and after (intervention) the implementation of an antibiotic protocol by performing surveillance and assessments of all antibiotic use during a 29-month interrupted period. SETTING: Level 3-4 neonatal ICU in one referral center. PATIENTS: All 13,540 infants who received antibiotics during their hospital stay from 2015 to 2017. INTERVENTIONS: Prospective audit of targeted antibiotic stewardship program. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the change in total antibiotic days of therapy per 1,000 patient-days between the baseline and intervention periods. The secondary outcomes included readmissions for infection, late-onset sepsis (length of stay), necrotizing enterocolitis, or death in infants at 32 weeks of gestation or younger and the prevalence of multidrug-resistant organism colonization. No differences in safety outcomes were observed between the intervention and baseline periods. Following the implementation of our Smart Use of Antibiotics Program, the total quantity of antibiotics in the intervention phase was significantly decreased from 543 days of therapy per 1,000 patient-days to 380 days of therapy/1,000 patient-days compared with that of baseline (p = 0.0001), which occurred in parallel with a reduction in length of stay from 11.4% during the baseline period to 6.5% during the intervention period (p = 0.01). A reduced multidrug-resistant organism rate was also observed following Smart Use of Antibiotics Program implementation (1.4% vs 1.0%; p = 0.02). The overall readmission rate did not differ between the two periods (1.2% vs 1.1%; p = 0.16). CONCLUSIONS: Smart Use of Antibiotics Program implementation was effective in reducing antibiotic exposure without affecting quality of care. Antibiotic stewardship programs are attainable through tailoring to special stewardship targets even in a developing country.

[Meta-analysis of prognostic tests in neonates over 35-week gestational age with hypoxic-ischemic encephalopathy].

OBJECTIVE: To explore the prognostic value of currently used clinical tests in neonatal patients over 35-week gestational age with perinatal asphyxia and hypoxic-ischemic encephalopathy (HIE). METHODS: "Neonate""hypoxic-ischemic encephalopathy " and "prognostic test" were used as key words. Searches were made on the databases of PubMed, EMBASE, CNKI and WanFang for studies published between January 1980 and December 2012. Studies were included if they (1) evaluated outcome in over 35-week gestational age neonates with perinatal asphyxia or HIE; (2) reported outcomes at minimal follow-up age of 18 months; (3) confirmed neurodevelopment with favorable or adverse outcomes. RevMan 5.2 software 1.4 was used for meta-analysis. And the evaluation criteria of each study were employed to assess and analyze the results comprehensively. RESULTS: Among 260 relevant studies, 20 were included. There are 7 tests contented our inclusion criteria: amplitude-integrated electroencephalography (aEEG), magnetic resonance imaging (MRI:T1/T2 weighted imaging, diffusion weighted imaging (DWI), apparent diffusion coefficient (ADC), magnetic resonance spectroscopy (MR S)), cerebral ultrasound (CUS) and HIE stage. The most promising tests were aEEG: sensitivity 0.936 (95%CI: 0.897-0.964) ; specificity 0.884 (95%CI: 0.836- 0.921). In imaging, T1/T2-weighted MRI sensitivity 0.913 (95%CI: 0.850-0.956), specificity 0.630 (95%CI: 0.544-0.711); diffusion weighted MRI sensitivity 0.933 (95%CI:0.817-0.956), specificity 0.694 (95%CI: 0.546-0.817); ADC sensitivity 0.778 (95%CI: 0.664-0.867) , specificity 0.971 (95%CI: 0.898-0.996); MRS sensitivity 0.918 (95%CI: 0.804-0.977), specificity 0.642 (95%CI: 0.515-0.755). CUS sensitivity 0.683 (95%CI: 0.519-0.819), specificity 0.459 (95%CI: 0.295-0.631). HIE stage sensitivity 0.967 (95%CI: 0.924-0.989) , specificity 0.314 (95%CI: 0.241-0.394). CONCLUSIONS: These evidence suggests an important role for aEEG, MRI (T1/T2-weight, DWI, ADC), CUS and HIE stage. The sensitivity and specificity of aEEG are both relatively high; HIE stage has good sensitivity; in imaging, T1/T2-weight,DWI and MRS yield better sensitivity while ADC has the best specificity. Mild hypothermia treatment reduces the predictive value of evaluation system.Each test has its advantages and disadvantages. Thus an integrated use of a variety of prognostic tests centering on clinical neurological assessment is optimal.

Development and validation of a nomogram prediction model for ADHD in children based on individual, family, and social factors.

OBJECTIVES: A reliable, user-friendly, and multidimensional prediction tool can help to identify children at high risk for ADHD and facilitate early recognition and family management of ADHD. We aimed to develop and validate a risk nomogram for ADHD in children aged 3-17 years in the United States based on clinical manifestations and complex environments. METHODS: A total of 141,356 cases were collected for the prediction model. Another 54,444 cases from a new data set were utilized for performing independent external validation. The LASSO regression was used to control possible variables. A final risk nomogram for ADHD was established based on logistic regression, and the discrimination and calibration of the established nomogram were evaluated by bootstrapping with 1000 resamples. RESULTS: A final risk nomogram for ADHD was established based on 13 independent predictors, including behavioral problems, learning disabilities, age, intellectual disabilities, anxiety symptoms, gender, premature birth, maternal age at childbirth, parent-child interaction patterns, etc. The C-index of this model was 0.887 in the training set, and 0.862 in the validation set. Internal and external validation proved that the model was reliable. CONCLUSIONS: A nomogram, a statistical prediction tool that assesses individualized ADHD risk for children is helpful for the early identification of children at high risk for ADHD and the construction of a conceptual model of society-family-school collaborative diagnosis, treatment, and management of ADHD.

Effect of Placental Transfusion on Long-Term Neurodevelopmental Outcomes in Premature Infants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The pathophysiology and the potential risks of placental transfusion (PT) differ substantially in preterm infants, necessitating specific studies in this population. This study aimed to evaluate the safety and efficacy of PT in preterm infants from the perspective of long-term neurodevelopmental outcomes. METHODS: We conducted a systematic literature search using placental transfusion, preterm infant, and its synonyms as search terms. Cochrane Central Register of Controlled Trials, Medline, and Embase were searched until March 07, 2023. Two reviewers independently identified, extracted relevant randomized controlled trials, and appraised the risk of bias. The extracted studies were included in the meta-analysis of long-term neurodevelopmental clinical outcomes using fixed-effects models. RESULTS: A total of 5612 articles were identified, and seven randomized controlled trials involving 2551 infants were included in our meta-analysis. Compared with immediate cord clamping (ICC), PT may not impact adverse neurodevelopment events. No clear evidence was found of a difference in the risk of neurodevelopmental impairment (risk ratio [RR]: 0.89, 95% confidence interval [CI]: 0.76 to 1.03, P = 0.13, I2 = 0). PT was not associated with the incidence of cerebral palsy (RR: 1.23, 95% CI: 0.59 to 2.57, P = 0.79, I2 = 0). Analyses showed no differences between the two interventions in cognitive, language, and motor domains of neurodevelopment. CONCLUSIONS: From the perspective of long-term neurodevelopment, PT at preterm birth may be as safe as ICC. Future studies should focus on standardized, high-quality clinical trials and individual participant data to optimize cord management strategies for preterm infants after birth.

A Sequential End-to-End Neonatal Sleep Staging Model with Squeeze and Excitation Blocks and Sequential Multi-Scale Convolution Neural Networks.

Automatic sleep staging offers a quick and objective assessment for quantitatively interpreting sleep stages in neonates. However, most of the existing studies either do not encompass any temporal information, or simply apply neural networks to exploit temporal information at the expense of high computational overhead and modeling ambiguity. This limits the application of these methods to multiple scenarios. In this paper, a sequential end-to-end sleep staging model, SeqEESleepNet, which is competent for parallelly processing sequential epochs and has a fast training rate to adapt to different scenarios, is proposed. SeqEESleepNet consists of a sequence epoch generation (SEG) module, a sequential multi-scale convolution neural network (SMSCNN) and squeeze and excitation (SE) blocks. The SEG module expands independent epochs into sequential signals, enabling the model to learn the temporal information between sleep stages. SMSCNN is a multi-scale convolution neural network that can extract both multi-scale features and temporal information from the signal. Subsequently, the followed SE block can reassign the weights of features through mapping and pooling. Experimental results exhibit that in a clinical dataset, the proposed method outperforms the state-of-the-art approaches, achieving an overall accuracy, F1-score, and Kappa coefficient of 71.8%, 71.8%, and 0.684 on a three-class classification task with a single channel EEG signal. Based on our overall results, we believe the proposed method could pave the way for convenient multi-scenario neonatal sleep staging methods.

Understanding endoscopic and clinicopathological features of patients with very early onset inflammatory bowel disease: Results from a decade of study.

BACKGROUND: Very early onset inflammatory bowel disease (VEOIBD) is associated with a unique disease course and distinct endoscopic features. AIMS: This study aims to provide a comprehensive description of the endoscopic and histologic features observed in a large cohort of patients with VEOIBD from a tertiary medical center. METHODS: A retrospective review of medical records from 2011 to 2021 was conducted to analyze clinical data, including disease phenotypes, endoscopic and histologic findings. Next generation sequencing was performed. RESULTS: A total of 225 VEOIBD subjects were included in this study. Monogenic defects were identified in 161 patients. Monogenic IBD patients more commonly had CD-like disease. Colonic involvement was more prevalent among those with monogenic IBD (P<0.001). Pseudo-polyps were significantly more common in the monogenic IBD group (P<0.001), while ileal edema and ulcers were significantly more prevalent in non-monogenic IBD cases. IL10RA deficiency were characterized by colonic ulcers and pseudo-polyps without upper gastrointestinal tract lesions, while patients with TNFAIP3 mutations demonstrated both upper and lower gastrointestinal tract involvement. The non-monogenic IBD patients showed a higher incidence of chronic architectural changes of crypt, increased apoptosis and eosinophils infiltration. CONCLUSIONS: Endoscopic and histologic analysis of children with VEOIBD plays a crucial role in facilitating accurate diagnosis. Various forms of monogenic IBD exhibit distinct endoscopic and pathologic changes.