Early screening for neonatal jaundice has always been essential to neonatal health care. In recent years, there have been advancements and updates in the methods and equipment employed for early screening of neonatal jaundice, including visual assessment, icterometer, point-of-care testing of serum bilirubin, jaundice screening utilizing smartphone applications, and end-tidal carbon monoxide detection. This article reviews the relevant research and progress associated with the methods above, aiming to offer a reference and guidance for scientific research and clinical practices.

Objective:To study the distribution and antibiotics resistance of the main pathogens of neonatal purulent meningitis in different regions of China.Methods:A retrospective descriptive clinical epidemiological study was conducted in children with neonatal purulent meningitis which admitted to 18 tertiary hospitals in different regions of China between January 2015 to December 2019. The test results of blood and cerebrospinal fluid, and drug sensitivity test results of the main pathogens were collected. The distributions of pathogenic bacteria in children with neonatal purulent meningitis in preterm and term infants, early and late onset infants, in Zhejiang Province and other regions outside Zhejiang Province, and in Wenzhou region and other regions of Zhejiang Province were analyzed. The chi-square test was used for statistical analysis.Results:A total of 210 neonatal purulent meningitis cases were collected. The common pathogens were Escherichia coli ( E. coli)(41.4%(87/210)) and Streptococcus agalactiae ( S. agalactiae)(27.1%(57/210)). The proportion of Gram-negative bacteria in preterm infants (77.6%(45/58)) with neonatal purulent meningitis was higher than that in term infants (47.4%(72/152)), and the difference was statistically significant ( χ2=15.54, P=0.001). There were no significant differences in the constituent ratios of E. coli (36.5%(31/85) vs 44.8%(56/125)) and S. agalactiae (24.7%(21/85) vs 28.8%(36/125)) between early onset and late onset cases (both P>0.05). The most common pathogen was E. coli in different regions, with 46.7%(64/137) in Zhejiang Province and 31.5%(23/73) in other regions outside Zhejiang Province. In Zhejiang Province, S. agalactiae was detected in 49 out of 137 cases (35.8%), which was significantly higher than other regions outside Zhejiang Province (11.0%(8/73)). The proportions of Klebsiella pneumoniae, and coagulase-negative Staphylococcus in other regions outside Zhejiang Province (17.8%(13/73) and 16.4%(12/73)) were both higher than those in Zhejiang Province (2.9%(4/137) and 5.1%(7/137)). The differences were all statistically significant ( χ2=14.82, 12.26 and 7.43, respectively, all P<0.05). The proportion of Gram-positive bacteria in Wenzhou City (60.8%(31/51)) was higher than that in other regions in Zhejiang Province (38.4%(33/86)), and the difference was statistically significant ( χ2=6.46, P=0.011). E. coli was sensitive to meropenem (0/45), and 74.4%(32/43) of them were resistant to ampicillin. E. coli had different degrees of resistance to other common cephalosporins, among which, cefotaxime had the highest resistance rate of 41.8%(23/55), followed by ceftriaxone (32.4%(23/71)). S. agalactiae was sensitive to penicillin, vancomycin and linezolid. Conclusions:The composition ratios of pathogenic bacteria of neonatal purulent meningitis are different in different regions of China. The most common pathogen is E. coli, which is sensitive to meropenem, while it has different degrees of resistance to other common cephalosporins, especially to cefotaxime.

Animal models play a critical role in the research on the pathogenesis and treatment of white matter injury in premature infants. Rodent modeling is often used to mimic the pathological manifestations of white matter injury in premature human infants. Currently, the most used models include the common carotid artery occlusion combined with the hypoxia model, prenatal/postpartum infection model, chronic hypoxia model, hyperoxia exposure model, neuronal excitotoxicity model, transgenic model, etc. This article reviews the modeling methods, advantages, and disadvantages of the above models.

Objective:To summarize the clinical characteristics, diagnosis, treatment, and prognosis of neonatal meningitis caused by Mycoplasma hominis. Methods:We present the clinical data, diagnosis and treatment of a premature infant with Mycoplasma hominis meningitis who was admitted to the Department of Neonatology, the Second Affiliated Hospital of Wenzhou Medical University in June 2020. Relevant literature up to May 2021 was retrieved with the strategy of "( Mycoplasma hominis) AND (meningitis OR central nervous system OR cerebrospinal fluid) AND (newborn)" from CNKI, Wanfang, and PubMed database. The clinical manifestations, examinations, diagnosis, treatments and prognosis of cases with complete clinical data were summarized using two-sample rank sum test. Results:A premature female infant at gestational age of 27 +4 weeks presented with repeated low-grade fever and apnea since the 7 days of life. Cerebrospinal fluid testing in a local hospital showed neutrophil-based leukocytosis, which indicated purulent meningitis. However, empiric antibiotic treatment did not improve the infant's condition. The patient was transferred to our hospital due to dyspnea for 32 days and repeated fever for 25 days. Mycoplasma hominis was detected from the cerebrospinal fluid samples using metagenomic next generation sequencing (NGS). Treatment with erythromycin was ineffective, but the patient improved and discharged after changing to chloramphenicol for 18 d without any side effects. A total of 21 English articles were retrieved, and no Chinese literature was retrieved, involving 22 infants. Of the 23 cases including the present case, 14 were preterm, eight were term and one with no available data; 19 were born by vaginal delivery; the median age of onset was 11.0 d ( P25- P75: 7.0-18.0 d). The initial symptoms included fever, convulsions, irritability, and apnea. Blood routine examination showed elevated white blood cell count in ten cases and elevated C-reactive protein in seven cases. In the cerebrospinal fluid testing, white blood cell count increased in 19 cases, protein increased in 20 cases, and glucose decreased in 13 cases. Eight cases were confirmed by 16S RNA polymerase chain reaction amplification technology, seven by serum antibodies test, two cases by culture and microscopic findings, two cases by culture alone, one case by Mycoplasma kit, and one by NGS. The main treatment was the administration of tetracyclines, quinolones, chloramphenicol, lincosamides, etc. (alone or in combination). Two cases improved without using special anti- Mycoplasma drugs. Of the 23 patients, 15 had hydrocephalus, eight had intracranial hemorrhage, four had cerebral ischemic infarction, and two had cerebral abscess. Four cases had good prognosis,16 cases had adverse prognosis, and other three without available data. The median time to start sensitive antibiotic therapy in children with good prognosis was 4.5 d(3.6-5.0 d) after diagnosis, which was earlier than that in children with adverse prognosis [16.8 d (7.0-25.0 d)]( Z=－2.27, P=0.023). Conclusions:Mycoplasma hominis infection has non-specific clinical manifestations and should be considered for infants with intracranial infection that is not responding to empirical antibiotic treatment. NGS is helpful in detecting Mycoplasma hominis and chloramphenicol can be an option for the treatment.

Objective:To study the changes and influencing factors of splanchnic regional saturation before and after feeding in preterm infants with feeding intolerance (FI).Methods:From December 2018 to August 2019, preterm infants with FI admitted to the neonatal intensive care unit of our hospital within 24 hours after birth were prospectively enrolled in this same-patient before-after study. Splanchnic regional saturation (rSsO 2) and cerebral regional oxygenation (rSc0 2) 5 minutes before feeding and 1 hour after feeding were monitored using near-infrared spectroscopy (NIRS). The average values of rScO 2, rSsO 2 and splanchnic-cerebral oxygenation ratio (SCOR) before and after feeding were calculated. The clinical data including postnatal age, corrected gestational age and feeding methods (breastfeeding or formula feeding) were collected. Single-factor correlation analysis and multiple linear regression were used to analyze the influencing factors of rSsO 2 before and after feeding. Results:A total of 41 preterm infants were included. No significant differences existed in rSsO 2, rScO 2 and SCOR before and after feeding ( P>0.05). The feeding methods showed relative prominent influences on the changes of rSsO 2 and SCOR before and after feeding. The breastfeeding infants had smaller changes of rSsO 2 and SCOR before and after feeding compared with formula feeding infants, the regression equations were Y=5.538-4.065X (model complex correlation coefficient was 0.414 determination coefficient R2=0.171, F=8.050, P<0.01) and Y=0.109-0.075X (model complex correlation coefficient was 0.405 determination coefficient R=0.1642, F=7.655, P<0.01). Conclusions:Proper feeding will not increase rSsO 2 in preterm infants with FI. Comparing with formula feeding infants, breastfeeding infants has more stable post-feeding rSsO 2.Breastfeeding should be the first choice for preterm infants with FI.

Objective:To study the correlation between transcutaneous bilirubin (TcB) level measured from shielded skin and total serum bilirubin (TSB) level after phototherapy in premature infants.Methods:From July 2019 to July 2021,preterm infants with jaundice admitted to the Department of Neonatology of our hospital and received phototherapy were prospectively enrolled in the study. The infants were assigned into 26~31w group, 32~34w group and 35~36w group according to their gestational ages. During phototherapy, the forehead, the chest and the perineum were shielded. TcBs were measured at the above mentioned areas three times each before and after phototherapy and TSB was measured from venous blood samples.Results:A total of 306 premature infants were included, with 51 cases in 26~31w group, 126 cases in 32~34w group and 129 cases in 35~36w group. Before phototherapy, TcBs of the forehead, the chest and the perineum of all infants were correlated with TSB ( r=0.699, 0.913, 0.734, P<0.001) with TcB of the chest showed the best correlation. A linear regression equation was established using the TSB before phototherapy and the TcB of the chest: TSB=0.634+0.912TcB. After phototherapy, TcBs of the forehead, the chest and the perineum of all infants were also correlated with TSB ( r=0.586, 0.879, 0.690, P<0.001) with TcB of the chest showed the best correlation and the linear regression equation was TSB=1.910+0.736TcB. Conclusions:For preterm infants with gestational age of 26~36w, TcB of the shielded chest skin after phototherapy is correlated with TSB and a linear regression model can be established.

Objective:To study the clinical characteristics of purulent meningitis complicated with hydrocephalus in neonates, and to analyze the risk factors of the disease.Methods:Neonates diagnosed with purulent meningitis complicated with hydrocephalus who hospitalized in the department of neonatology of the Second Affiliated Hospital of Wenzhou Medical University from January 2002 to August 2021 were selected as the case group. Neonates with positive pathogen cultures but no hydrocephalus during the same period were assigned by random number table method as the control group. The ratio of the control group and the case group was 2 ∶1. The clinical data such as bacteria distribution, cranial imaging, therapy and prognosis were compared between the two groups. The risk factors for hydrocephalus were predicted. Statistical analysis was conducted using chi-square test and multiple logistic regression analysis.Results:There were 33 cases in the case group and 66 cases in the control group. A total of 27 cases had confirmed pathogen results, of which 20 cases (74.1%) were Gram-negative bacteria and seven cases (25.9%) were Gram-positive bacteria. The time of diagnosis for hydrocephalus were 13.0(5.5, 28.5) days after the onset. Twenty-six cases received non-surgical treatment, while seven cases received surgery. The cure rate of case group was 42.4%(14/33), which was lower than that of control group (72.7%, 48/66), and the difference was statistically significant ( χ2=8.63, P=0.003). Univariate analysis showed that the incidences of protein>3 g/L in cerebrospinal fluid, glucose<2 mmol/L in cerebrospinal fluid, convulsions, central respiratory failure, intracranial hemorrhage and encephalomalacia in the case group were all higher than those in the control group, with statistical significance ( χ2=19.72, 12.04, 19.04, 5.73, 11.85 and 17.48, respectively, all P<0.050). Multivariate logistic regression analysis showed that convulsions (odds ratio ( OR)=4.476, 95% confidence interval ( CI) 1.091 to 18.363, P=0.037), intracranial hemorrhage ( OR=8.031, 95% CI 1.894 to 34.059, P=0.005) and encephalomalacia ( OR=35.189, 95% CI 2.954 to 419.150, P=0.005) were risk factors for neonatal purulent meningitis complicated with hydrocephalus. Conclusions:Gram-negative bacteria are common pathogen of neonatal purulent meningitis complicated with hydrocephalus. Convulsions, intracranial hemorrhage and encephalomalacia are important predictors for neonatal purulent meningitis complicated with hydrocephalus.

Objective:To explore the relationship between endotracheal tube-bacterial biofilm (ETT-BF) in mechanically ventilated neonates and ventilator-associated pneumonia (VAP).Methods:A total of 30 mechanically ventilated neonates whose mechanical ventilation time were ≥48 h in the Department of Neonatology in The Second Affiliated Hospital of Wenzhou Medical University from January 2019 to January 2020 were included.According to the indwelling time of endotracheal tube, all cases were divided into three groups including group A(two to six days), group B(seven to 14 days) and group C (over 14 days). The morphological results of ETT-BF were scanned by scanning electron microscope (SEM). The incidence of VAP, the positive rates of strains isolated from endotracheal tube surface and lower respiratory tract secretion, the detection of strains and drug resistance were analyzed. Chi-squared test were used for statistical analysis.Results:The results of SEM showed that sheet matrix could be observed on the surface of the inner cavity of endotracheal tube in three days of tracheal catheter retention, and cocci adhered to it in four days. With prolonged indwelling time of endotracheal tube, the structure of bacterial biofilm (BF) had improved.The positive rate of strains isolated from the secretion of lower respiratory tract in 30 neonates was 23.3%(7/30) and all of them were Gram-negative bacteria. There was no patient developed VAP in group A, while there were two patients with VAP in group B, and five patients with VAP in group C. The incidences of VAP in the three groups were statistically significant ( χ2=10.82, P=0.004). There was no significant difference in the positive rate of strains isolated from the surface of endotracheal tube under different indwelling time in 30 cases ( χ2=1.03, P=0.598). Among of 13 neonates in group A, there were seven strains isolated from ETT-BF, mainly Gram-positive bacteria which turned out to be mainly Gram-negative bacteria with the prolongation of endotracheal tube indwelling time. Of the seven VAP cases, strains isolated from the lower respiratory tract secretion were consistent with the strains isolated from the surface of the corresponding endotracheal tube in five cases, which were Serratia liquefaciens, Klebsiella acidogenes, Serratia marcescens, Flavobacterium meningosepticum and Stenotrophomonas maltophilia, and the drug resistance was consistent. Conclusions:The colonization bacteria of early ETT-BF may come from the upper respiratory tract, with less migration which rarely causes VAP. With the prolongation of endotracheal tube indwelling time, the incidence of VAP in neonates increases. The same pathogen can be found in the ETT-BF and lower respiratory tract secretion. The source of pathogen needs further study.

Inflammation plays an important part in neonatal hypoxic-ischemic brain damage (HIBD). High mobility group box-1 protein (HMGB1), a neuroinflammatory trigger, has a dual effect on HIBD: in the acute stage, it amplifies the ischemic tissue injury; in the later stage, it is involved in the neurovascular repair and reconstruction. The significance of HMGB1 in the pathogenesis of HIBD is still not fully understood. This review summarizes the role of HMGB1 in HIBD, including its effects on neurons, glial cells and blood-brain barrier, and the underlying mechanisms as well as the progress in research on HMGB1 in immature brain, hoping to provide new ideas for neuroprotection in HIBD.

Iron overload, as a pathological feature of many nervous system diseases, can cause oxidative stress and lead to abnormal iron metabolism and injury of nerve cells. Hypoxia inducible factor (HIF) can participate in brain iron metabolism by regulating brain iron uptake, storage, excretion and intracellular regulation. So, HIF is expected to become a therapeutic target to inhibit brain iron overload in nervous system diseases. This paper reviews the physiological/pathological mechanism of HIF in regulating brain iron metabolism, in order to provide new treatment ideas and methods for nervous system diseases characterized by brain iron overload.