The efficacy and ocular safety following aflibercept, conbercept, ranibizumab, bevacizumab, and laser for retinopathy of prematurity: a systematic review and meta-analysis.

BACKGROUND: Retinopathy of prematurity (ROP) is typically treated with laser photocoagulation and/or intravitreal anti-vascular endothelial growth factor (anti-VEGF). To the best of our knowledge, most systematic reviews have focused on comparing anti-VEGF against laser treatment while comparisons between different anti-VEGF agents are lacking. Thus, we conducted this meta-analysis to compare the efficacy and safety of different anti-VEGF agents or laser after primary ROP therapy. METHODS: We conducted a comprehensive search across multiple databases up to November 2022. We included studies that used anti-VEGF or laser for ROP with comparable cohorts. RESULTS: Overall, 44 studies were included in this meta-analysis. When comparing anti-VGEF with laser, we found that the anti-VEGF group had a significantly higher retreatment rate (RR = 1.56, 95%CI = [1.06, 2.31], p = 0.03), a longer time from treatment to retreatment (WMD = 5.99 weeks, 95%CI = [4.03, 7.95], p < 0.001), a lower retinal detachment rate (RR = 0.55, 95%CI = [0.30, 0.91], p = 0.02), higher spherical equivalent (WMD = 1.69D, 95%CI = [0.61, 2.77], p = 0.002), lower myopia rate (RR = 0.69, 95%CI = [0.50, 0.97], p = 0.03) and lower anisometropia rate (RR = 0.44, 95%CI = [0.29, 0.67], p = 0.0001). In comparisons between ranibizumab and bevacizumab, the intravitreal ranibizumab (IVR) group was associated with higher recurrence rate (RR = 2.02, 95%CI = [1.49, 2.73], p < 0.0001), higher retreatment rate (RR = 1.70, 95%CI = [1.17, 2.47], p = 0.0006), and lower high myopia rate (RR = 0.31, 95%CI = [0.12, 0.77], p = 0.01). Similarly, when compared to aflibercept and conbercept, the IVR cohort also demonstrated higher recurrence and retreatment rates. While no significant differences were observed in any of the variables included in the statistical analysis in the comparison between bevacizumab and aflibercept. CONCLUSIONS: Anti-VEGF was associated with higher retreatment and lesser incidence of myopia as compared to laser. Laser therapy was linked to more complications like retinal detachment and myopia. Ranibizumab exhibited higher recurrence and retreatment rates compared to bevacizumab, aflibercept, and conbercept.

[Establishment of a nomogram model for predicting the risk of early-onset sepsis in very preterm infants]. / 预测极早产儿早发型败血症发生风险的列线图模型的构建.

OBJECTIVES: To identify risk factors associated with early-onset sepsis (EOS) in very preterm infants and develop a nomogram model for predicting the risk of EOS. METHODS: A retrospective analysis was conducted on 344 very preterm infants delivered at the First Affiliated Hospital of Zhengzhou University and admitted to the Department of Neonatology between January 2020 and December 2022. These infants were randomly divided into a training set (241 infants) and a validating set (103 infants) in a 7:3 ratio. The training set was further divided into two groups based on the presence or absence of EOS: EOS (n=64) and non-EOS (n=177). Multivariate logistic regression analysis was performed to identify risk factors for EOS in the very preterm infants. The nomogram model was developed using R language and validated using the validating set. The discriminative ability, calibration, and clinical utility of the model were assessed using receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis, respectively. RESULTS: The multivariate logistic regression analysis revealed that gestational age, need for tracheal intubation in the delivery room, meconium-stained amniotic fluid, serum albumin level on the first day of life, and chorioamnionitis were risk factors for EOS in very preterm infants (P<0.05). The area under the ROC curve for the training set was 0.925 (95%CI: 0.888-0.963), and that for the validating set was 0.796 (95%CI: 0.694-0.898), confirming the model's good discrimination. The Hosmer-Lemeshow goodness-of-fit test suggested that the model was well-fitting (P=0.621). The calibration curve analysis and decision curve analysis demonstrated that the model had high predictive efficacy and clinical applicability. CONCLUSIONS: Gestational age, need for tracheal intubation in the delivery room, meconium-stained amniotic fluid, serum albumin level on the first day of life, and chorioamnionitis are significantly associated with the development of EOS in very preterm infants.The nomogram model for predicting the risk of EOS in very preterm infants, constructed based on these factors, has high predictive efficacy and clinical applicability.

The effect of time interval between antenatal corticosteroid administration and delivery on outcomes in late preterm neonates born to mothers with diabetes: a retrospective cohort study.

Objectives: The study aims to investigate whether the time interval between administering antenatal corticosteroids (ACS) and delivery influences the neonatal outcomes in late preterm (LPT) neonates (34 + 0 to 36 + 6 weeks) born to mothers with diabetes. Study design: This retrospective cohort study included women with any type of diabetes who gave birth between 34 + 0 weeks and 36 + 6 weeks of gestation. Based on the time interval between the first dose of corticosteroid and delivery, the cases were stratified into the following groups: <2, 2-7, and >7 days. Women unexposed to ACS served as the control group. The primary outcomes included the incidence of neonatal hypoglycemia and respiratory distress syndrome/transient tachypnea of the newborn. Multivariate logistic regression was used to assess the relationship between the time interval and neonatal outcomes and adjust for potential confounders. Results: The study enrolled a total of 636 parturients. Among them, 247 (38.8%) delivered within 2 days after ACS administration, 169 (26.6%) within 2-7 days, and 126 (19.8%) at >7 days. Baseline characteristics such as type of diabetes, methods of glycemic control, preterm premature rupture of membrane, placenta previa, cesarean delivery, indication for delivery, percentage of large for gestational age, birth weight, and HbA1c in the second or third trimester were significantly different among the four groups. The multivariate analysis showed no statistically significant difference in the incidence of primary or secondary neonatal outcomes between the case and control groups. Conclusions: ACS treatment was not associated with neonatal hypoglycemia and respiratory outcomes in LPT neonates born to diabetic mothers, regardless of the time interval to delivery.

Global, regional, and national burden of neonatal sepsis and other neonatal infections, 1990-2019: findings from the Global Burden of Disease Study 2019.

To provide an overview of the global, regional, and national incidence and mortality of neonatal sepsis and other neonatal infections (NS) and their change trends from 1990 to 2019, based on the data from the 2019 Global Burden of Disease study. This was a retrospective demographic analysis based on aggregated data. Annual incident cases, deaths, age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR) and their percentage changes of NS during 1990-2019 were collected from the 2019 Global Burden of Disease study. Globally, the incident cases of NS increased by 12.79% (from 5.59 million in 1990 to 6.31 million in 2019), and the deaths decreased by 12.93% (from 0.26 million in 1990 to 0.23 million in 2019). In the globe, the ASIR of NS per 100,000 population increased by 14.35% (from 85.21 in 1990 to 97.43 in 2019), and the ASMR decreased by 11.91% (from 3.97 in 1990 to 3.5 in 2019). CONCLUSION: Increasing trends in incidence and decreasing trends in mortality of NS were observed worldwide from 1990 to 2019. More robust epidemiological research and effective health strategies are urgently needed to reduce the disease burden of neonatal sepsis worldwide. WHAT IS KNOWN: • Neonatal sepsis has significant impacts on neonatal health, but estimates on the global burden and trends of neonatal sepsis are scarce and existing findings vary considerably. WHAT IS NEW: • Globally, there were 6.31 million incident cases of neonatal sepsis and 0.23 million deaths due to neonatal sepsis. • Increasing trends in incidence and decreasing trends in mortality of neonatal sepsis were observed worldwide from 1990 to 2019, with the highest absolute burden in sub-Saharan Africa and Asia.

[Risk factors for recurrence after intravitreal anti-vascular endothelial growth factor injection for retinopathy of prematurity]. / çŽ»ç’ƒä½“è ”å† æ³¨å°„æŠ—è¡€ç®¡å† çš®ç”Ÿé•¿å› å­æ²»ç–—æ—©äº§å„¿è§†ç½‘è†œç— å¤å‘çš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To investigate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection in the treatment of retinopathy of prematurity (ROP) and the risk factors for recurrence. METHODS: A retrospective analysis was performed on the medical data of 159 infants with ROP who were born in the First Affiliated Hospital of Zhengzhou University and underwent anti-VEGF treatment from January 2016 to December 2021. According to the presence or absence of recurrence within the follow-up period after initial anti-VEGF treatment, they were divided into a recurrence group with 24 infants and a non-recurrence group with 135 infants. The medical data were compared between the two groups, and a multivariate logistic regression analysis was used to investigate the risk factors for the recurrence of ROP after anti-VEGF treatment. RESULTS: After one-time anti-VEGF treatment, all 159 infants showed regression of plus disease. Recurrence was observed in 24 infants (15.1%) after anti-VEGF treatment, with a mean interval of (8.4±2.6) weeks from treatment to recurrence. The multivariate logistic regression analysis showed that preoperative fundus hemorrhage and prolonged total oxygen supply time were risk factors for the recurrence of ROP (P<0.05), while gestational hypertension was a protective factor (P<0.05). CONCLUSIONS: Intravitreal anti-VEGF injection is effective for ROP. Preoperative fundus hemorrhage and long duration of oxygen therapy may increase the risk of ROP recurrence, and further studies are needed to investigate the influence of gestational hypertension on the recurrence of ROP.

Walking alone milestone combined reading-frame rule improves early prediction of Duchenne muscular dystrophy.

Objective: To explore the potential of walking alone milestone combined reading-frame rule to improve the early diagnosis of Duchenne muscular dystrophy (DMD). Method: To retrospectively describe the genotype and phenotype of Duchenne and Becker muscular dystrophies (BMD) patients with deletions and duplicates in the dystrophin gene. The sensitivity and specificity of the reading frame rule were calculated and compared to that of the combined reading frame rule and walking alone milestone. The diagnostic coincidence rate of two different methods was analyzed. Result: One hundred sixty-nine male DMD/BMD patients were enrolled, including 17 cases of BMD and 152 cases of DMD. The diagnostic coincidence rate, diagnostic sensitivity, and specificity of the reading-frame rule for DMD/BMD were 85.2, 86.8, and 70.59%, respectively. The sensitivity and specificity of the reading frame principle combined with the walking alone milestone for DMD/BMD were 96.05 and 70.59%, respectively. The diagnostic coincidence rate increased to 93.49%, significantly different from that predicted by reading- frame rule (P < 0.05). Conclusion: The reading-frame rule combined with the walking alone milestone significantly improved the early diagnosis rate of DMD.

The Impact of Time Interval Between First Extubation and Reintubation on Bronchopulmonary Dysplasia or Death in Very Low Birth Weight Infants.

Objective: To explore the association between time from first extubation to reintubation and moderate-to-severe bronchopulmonary dysplasia (BPD) or death in very low birth weight infants. Study Design: Infants weighing <1,500 g at birth, requiring mechanical ventilation, and undergoing their initial extubation were retrospectively included from January 2014 to December 2021. They were divided into the moderate-to-severe BPD/death group and the comparison group according to the incidence of moderate-to-severe BPD or death. We defined time to reintubation as the time interval between first extubation and reintubation. In a stepwise multivariate logistic regression analysis, we examined the association between time to reintubation and moderate-to-severe BPD/death using different observation windows after initial extubation (24-h intervals). Results: A total of 244 infants were recruited, including 57 cases in the moderate-severe BPD/death group and 187 cases in the comparison group, and 93 (38.1%) cases were reintubated at least one time after their first extubation. Univariate analysis showed that reintubation rates within different observation windows in the moderate-to-severe BPD/death group were statistically significantly (p < 0.05) higher than those in the comparison group. Multivariate regression analysis showed that reintubation within observation windows 48 h or 72 h post-extubation was an independent risk factor in moderate-to-severe BPD/death and death, but not moderate-to-severe BPD. When the time window was 48 h, the probability of moderate-to-severe BPD/death [odds ratio (OR): 3.778, 95% confidence interval (CI): 1.293-11.039] or death (OR: 4.734, 95% CI: 1.158-19.354) was highest. While after extending the observation window to include reintubations after 72 h from initial extubation, reintubation was not associated with increased risk of moderate-to-severe BPD and/or death. Conclusions: Not all reintubations conferred increased risks of BPD/death. Only reintubation within 72 h from initial extubation was independently associated with increased likelihood of moderate-to-severe BPD/death and death in very low birth weight infants, and reintubation within the first 48 h post-extubation posed the greatest risk.

The risk factors of preterm birth: A multicentre case-control survey in China in 2018.

OBJECTIVES: To investigate the risk profile of preterm birth (PTB) in 2018 in China. METHOD: A prospective multicentre case-control study was conducted in 15 hospitals located in seven provinces throughout three geographical areas (the Eastern, South-Central and North-Western regions) in China. A total of 3147 preterm (<37+0 weeks) and 3147 term (37+0 to 41+6 weeks) live-birth mothers were included. Designed questionnaires were used to investigate maternal and fetal information. We calculated multivariable logistic regression and population attributable risk (PAR). RESULTS: Iatrogenic PTB accounted for 48.1% of preterm mothers. Multivariable analysis showed PTB was significantly associated with six categories of maternal and fetal factors, adverse life-style and psychological conditions (adjusted odds ratio (aOR) 2.063, 95% confidence interval (CI) 1.601-2.657) had the highest PAR% (60.1%). High school and below education level (PAR% = 25.8%), living in town or village (PAR% = 24.4%), low pregnant weight gain (PAR% = 16.8%), hypertensive disorders in pregnancy (aOR: 5.010, 95% CI: 4.039-6.216, PAR% = 15.3%), placental abnormality (aOR: 4.242, 95% CI: 3.454-5.211, PAR% = 14.1%) and multiple pregnancy (aOR: 10.990, 95% CI: 7.743-15.599, PAR% = 11.8%) were significantly associated with PTB with high PAR% value. CONCLUSION: The main risk factors for PTB in China were placental abnormality, hypertensive disorders in pregnancy and multiple pregnancy. Adverse life-style and psychological conditions and socio-economic disadvantage had high public health significance.

Time Interval From Early-Term Antenatal Corticosteroids Administration to Delivery and the Impact on Neonatal Outcomes.

Objectives: To determine the association between the time interval from antenatal corticosteroids administration to delivery and neonatal complications in diabetic mothers undergoing early term (37+0 to 38+6 weeks) scheduled cesarean section (ETSCS). Study Design: A retrospective cohort study of women with any form of diabetes in pregnancy undergoing ETSCS was included. Cases were stratified into the following groups based on the time interval from the first dose of corticosteroids administration to delivery: <2, 2-7, and >7 days. Women undergoing ETSCS, who did not receive corticosteroids were included as controls. We assessed the association between the time interval and neonatal outcomes in a multivariate regression model that controlled for potential confounders. Primary outcomes were the incidence of respiratory distress syndrome (RDS)/transient tachypnea of the newborn (TTN) and neonatal hypoglycemia. Results: The study cohort comprised 1,165 neonates. Of those, 159 (13.6%) were delivered within 2 days of maternal corticosteroids administration, 131 (11.2%) were delivered within 2-7 days after maternal corticosteroids administration, and 137 (11.8%) delivered more than 7 days after maternal corticosteroids administration. The remaining 738 (63.3%) were not exposed to corticosteroids. Multivariate analysis demonstrated that delivery within any time of antenatal corticosteroids administration was not associated with decreased risks of RDS/TTN. The risk of neonatal hypoglycemia was highest in the delivery of <2 days group (adjusted odds ratio [aOR]: 2.684, 95% confidence interval [CI]: 1.647-4.374 for control group; aOR: 2.827, 95% CI: 1.250-6.392 for delivery 2-7 days group; aOR:2.975, 95% CI: 1.265-6.996 for delivery >7 days group). Conclusions: Corticosteroids treatment for diabetic mothers undergoing ETSCS was not associated with beneficial neonatal respiratory outcomes. In addition, delivery, <2 days after antenatal corticosteroids administration was associated with an increased risk of neonatal hypoglycemia.

Erythropoietin for preventing bronchopulmonary dysplasia in preterm infants: A systematic review and meta-analysis.

BACKGROUND: Recombinant erythropoietin (rEPO) has erythropoiesis and anti-inflammatory properties that might help reduce lung injury in preterm infants. OBJECTIVE: To conduct a systematic review and meta-analysis to evaluate the possible role of rEPO in altering the risk of bronchopulmonary dysplasia (BPD). METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library databases were searched to identify randomized controlled trials (RCTs) that evaluated the effects of rEPO for the prevention of BPD in preterm infants. RESULTS: Fourteen studies (3199 infants) were included. Our results could not demonstrate a significant effect of rEPO on the incidence of BPD36 (risk ratio [RR]: 0.97, 95% confidence interval [CI]: 0.87-1.09, p = 0.63, I2 = 0, 12 RCTs, high-quality evidence), BPD28 (RR: 1.28, 95% CI: 0.91-1.79, p = 0.15, I2 = 17%, three RCTs, low-quality evidence) and oxygen dependence days. The test for subgroup analysis by administration route of rEPO showed similar outcomes above. Some of the included trials reported a significant effect of intravenous rEPO on reduction of sepsis (RR: 0.82, 95% CI: 0.70-0.96, p = 0.01, I2 = 0, high-quality evidence) and any stage necrotizing enterocolitis (NEC) (RR: 0.75, 95% CI: 0.59-0.94, p = 0.01, I2 = 0, moderate-quality evidence). The incidence of mortality and stage II or higher NEC was comparable in rEPO and control infants. CONCLUSION: Our results suggest that rEPO does not affect the risk of developing BPD in preterm infants. Adequately powered RCTs are required to further confirm these findings.

Outcome Analysis of Severe Hyperbilirubinemia in Neonates Undergoing Exchange Transfusion.

OBJECTIVE: Severe neonatal hyperbilirubinemia can cause neurological disability or mortality if not effectively managed. Exchange transfusion (ET) is an efficient treatment to prevent bilirubin neurotoxicity. The purpose of this study was to evaluate outcomes in severe neonatal hyperbilirubinemia with ET and to identify the potential risk factors for poor outcomes. METHODS: Newborns of ≥28 weeks of gestational age with severe hyperbilirubinemia who underwent ET from January 2015 to August 2019 were included. Demographic data were recorded and analyzed according to follow-up outcomes at 12 months of corrected age. Poor outcomes were defined as death due to bilirubin encephalopathy or survival with at least one of the following complications: cerebral palsy, psychomotor retardation (psychomotor developmental index < 70), mental retardation (mental developmental index < 70), or hearing impairment. RESULTS: A total of 524 infants were eligible for recruitment to the study, and 62 infants were lost to follow-up. The outcome data from 462 infants were used for grouping analysis, of which 398 cases (86.1%) had normal outcomes and 64 cases (13.9%) suffered poor outcomes. Bivariate logistic regression analysis showed that peak total serum bilirubin (TSB) (odds ratio [OR] = 1.011, 95% confidence interval [CI] = 1.008-1.015, p = 0.000) and sepsis (OR = 4.352, 95% CI = 2.013-9.409, p < 0.001) were associated with poor outcomes of hyperbilirubinemia. Receiver operator characteristic curve analysis showed that peak TSB ≥452.9 µmol/L could predict poor outcomes of severe hyperbilirubinemia. CONCLUSION: Peak TSB and sepsis were associated with poor outcomes in infants with severe hyperbilirubinemia, and peak TSB ≥452.9 µmol/L could predict poor outcomes.

Short-term effects of intravitreal anti-vascular endothelial growth factor agents on body weight and multiple systems after treatment for retinopathy of prematurity.

Objectives: This study's goal was to assess the short-term effect on body weight and multiple systems following intravitreal injections of ranibizumab and aflibercept for retinopathy of prematurity (ROP). Methods: We retrospectively assessed infants with ROP who received intravitreal anti-vascular endothelial growth factor agents (VEGF) treatment at our hospital. They were classified into 2 groups based on the drugs administered: the intravitreal ranibizumab (IVR) group and the intravitreal aflibercept (IVA) group. The body weight (BW) gains for the pre-treatment week, the 1st week after treatment, and the 2nd week after treatment were compared for each group. Additionally, other parameters such as blood pressure, heart rate, oxygen concentration, volume of milk and output of urine at four time points were also measured. We used repeated measurement analysis of variance analyzed these data. Results: In total, 95 preterm infants were recruited, including 51 cases in the IVR group and 44 cases in the IVA group. The BW gain for the 1st week after treatment was significantly lower than the pre-treatment week in each group (P < 0.05), while there was no decrease in weekly BW gain in the 2nd week after treatment compared with that pre-treatment week. Based on the comparison between groups, the BW gain in the IVR group was significantly higher than in the IVA group in the second post-treatment week. Repeated measurement analysis of variance showed that there were no significant differences in blood pressure, heart rate, oxygen concentration, volume of milk and output of urine in both groups over time. Conclusions: IVR and IVA could have a short-term inhibitive effect on body weight gain in infants after treatment for ROP, whereas there is no significant impact on other systems.

A Cross-Sectional Nationwide Study on Accessibility and Availability of Neonatal care Resources in Hospitals of China: Current Situation, Mortality and Regional Differences: Neonatal Care Resources and Newborn Mortality in China.

BACKGROUND: To investigate the current situation of neonatal care resources (NCR), newborn mortality rates (NMR), regional differences and existing challenges in China. METHODS: By using a self-designed questionnaire form and the cross-sectional method, we conducted a survey of all hospitals equipped with neonatal facilities in China from March 2019 to March 2020 with respect to the level and nature of these hospitals, the number of newborn beds and NICU beds, the number of neonatal pediatricians, and the development of therapeutic techniques. The data about the newborn births and deaths were retrieved from the annual statistics of the health commissions of the related provinces, autonomous regions and municipalities. FINDING: Included in this nationwide survey were 3,020 hospitals from all 22 provinces, 5 autonomous regions and 4 municipalities directly under the Central Government of Mainland China, with a 100% response rate. They included 1,183 (39.2%) level-3 (L3) hospitals, 1629 (53.9%) L-2 hospitals and 208 (6.9%) L-1 hospitals. Geographically, 848 (31.4%) hospitals were distributed in Central China, 983 (32.5%) hospitals in East China, and 1,089 (36.1%) in West China. The 3,020 included hospitals were altogether equipped with 75,679 newborn beds, with a median of 20 (2-350) beds, of which 2,286 hospitals (75.7%) were equipped with neonatal intensive care units (NICU), totaling 28,076 NICU beds with a median of 5 (1-160) beds. There were altogether 27,698 neonatal pediatricians in these hospitals, with an overall doctor-bed ratio of 0.366. There were 48.18 newborn beds and 17.87 NICU beds per 10,000 new births in China. In East, Central and West China, the number of neonatal beds, NICU beds, neonatal pediatricians, and attending pediatricians or pediatricians with higher professional titles per 10,000 newborns was 42.57, 48.64 and 55.67; 17.07, 18.66 and 18.17; 16.26, 16.51 and 20.81; and 10.69, 10.81 and 11.29, respectively. However, when the population and area are taken into consideration and according to the health resources density index (HRDI), the number of newborn beds, NICU beds and neonatal pediatricians in West China was significantly lower than that in Central and East China. In addition, only 10.64% of the neonatal pediatricians in West China possessed the Master or higher degrees, vs. 31.7% in East China and 20.14% in Central China. On the contrary, the number of neonatal pediatricians with a lower than Bachelor degree in West China was significantly higher than that in Central and East China (13.28% vs. 7.36% and 4.28%). Technically, the application rate of continuous positive airway pressure (CPAP) and conventional mechanical ventilation (CMV) in L-1 hospitals of West China was lower than that in Central and East China. According to the statistics in 2018, the newborn mortality rate (NMR) in West China was significantly higher than that in Central and East China. INTERPRETATION: China has already possessed relatively good resources for neonatal care and treatment, which is the primary reason for the rapid decrease in the NMR in China. However, there are still substantial regional differences. The density of health resources, the level of technical development and educational background of neonatal pediatricians in West China still lag behind those in other regions of China and need to be further improved and upgraded. FUNDING: This research work was funded by National Natural Science Foundation of China (81671504) and United Nations International Children's Emergency Fund (CHINA-UNICEF501MCH).

miR-141-3p inhibits the activation of astrocytes and the release of inflammatory cytokines in bacterial meningitis through down-regulating HMGB1.

BACKGROUND: Bacterial meningitis (BM) is a serious infectious disease of the central nervous system that often occurs in children and adolescents. Many studies have suggested that microRNAs (miRNAs) are involved in BM. This study aimed to address the effects of miR-141-3p on astrocyte activation and inflammatory response in BM through HMGB1. METHODS: The 3-week-old rats were injected with Streptococcus pneumoniae (SP) into the lateral ventricle to establish a BM model. Loeffler scoring method was used to evaluate the recovery of neurological function. Brain pathological damage was observed by hematoxylin and eosin (H&E) staining. Primary astrocytes were isolated from brain tissues of BM or non-infected SD rats. The levels of TNF-α, IL-1ß, and IL-6 in brain tissues and astrocyte culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). The targeting relationship between miR-141-3p and HMGB1 was tested using dual-luciferase reporter assay. The expression of miR-141-3p, HMGB1, and the astrocytic marker glial fibrillary acidic protein (GFAP) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blotting. Methylation-specific PCR (MSP) analysis was performed to measure the methylation status of miR-141 promoter. RESULTS: The results showed that lower Loeffler scores were exhibited in rats with BM. The subarachnoid space of brain tissues of BM rats was widened, and obvious inflammatory cells were observed. miR-141-3p expression was reduced in BM rats and SP-treated astrocytes. Additionally, we found that overexpression of miR-141-3p led to the downregulation of HMGB1, GFAP, and inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in astrocytes. Furthermore, the results of dual-luciferase reporter assay confirmed that miR-141-3p directly targeted HMGB1. Overexpression of miR-141-3p inhibited the levels of GFAP, TNF-α, IL-1ß, and IL-6 in astrocytes, which was eliminated by the up-regulation of HMGB1. The results of MSP analysis indicated that miR-141 promoter was highly methylated in brain tissues and astrocytes. DNMT1 was involved in the methylation of miR-141 promoter in BM. CONCLUSION: The present study verified that miR-141-3p affected inflammatory response by suppressing HMGB1 in SP-induced astrocytes and BM rat model.

Neonatal hypoxic-ischemic encephalopathy diagnosis and treatment: a National Survey in China.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) affects as many as 100,000 infants each year in China. Therapeutic hypothermia reduces HIE related mortality and long-term neurodevelopmental disabilities. National guidelines for HIE management were published a decade ago. This study aimed to investigate the current status of HIE diagnosis and treatment in China. METHOD: This prospective cross-sectional national survey used a questionnaire evaluating practices related to HIE management. Descriptive statistics and Chi-square or Fisher's exact test were used, and a p-value of < 0.05 was considered significant. RESULTS: The 273 hospitals that completed the survey were located in 31 of the 34 provincial districts in China. Eighty-eight percent of the hospitals were Level III hospitals, and 74% treated 10 or more HIE cases annually. Awareness rates of the national guidelines for HIE diagnosis, HIE treatment, and therapeutic hypothermia protocol were 85, 63, and 78%, respectively. Neurological manifestations and blood gas were used as HIE diagnostic criteria by 96% (263/273) and 68% (186/273) of the hospitals, respectively. Therapeutic hypothermia was used in 54% (147/273) of hospitals. The percentage of general hospitals that implemented therapeutic hypothermia (43%, 71/165) was significantly lower than that in maternity and infant hospitals (67%, 49/73) (χ2 = 11.752, p = 0.001) and children's hospitals (77%, 27/35) (χ2 = 13.446, p < 0.001). Reasons for not providing therapeutic hypothermia included reduction of HIE cases in recent years (39%), high cost of cooling devices and treatment (31%), lack of training (26%), and safety concerns (4%). Among the hospitals that provided therapeutic hypothermia, 27% (39/147) were in full compliance with the recommended protocol. Eighty-one percent (222/273) of the hospitals treated HIE infants with putative neuroprotective agents alone or in combination with cooling. Ninety-one percent of the hospitals had long-term neurodevelopmental follow-up programs for infants with HIE. CONCLUSIONS: There is significant heterogeneity in HIE diagnosis and treatment in China. Therapeutic hypothermia has not become a standard of care for neonatal HIE nationwide. Unproven agents are widely used for HIE treatment. Nationwide standardization of HIE management and dissemination of therapeutic hypothermia represent the opportunities to reduce mortality and improve long-term neurodevelopmental outcomes of children affected by HIE.

Mortality and Morbidity of Infants Born Extremely Preterm at Tertiary Medical Centers in China From 2010 to 2019.

Importance: Extreme prematurity is associated with a substantial burden on health care systems worldwide. However, little is known about the prognosis of infants born extremely preterm in developing countries, such as China. Objective: To describe survival and major morbidity among infants born extremely preterm in China over the past decade. Design, Setting, and Participants: This retrospective cohort study was conducted from January 1, 2010, through December 31, 2019. Included individuals were infants with gestational age less than 28 weeks discharged from 1 of 68 neonatal intensive care units located in 31 provinces in China. Data were analyzed from August through October 2020. Exposure: Extremely preterm birth. Main Outcomes and Measures: Survival to discharge and major morbidity (ie, bronchopulmonary dysplasia, grades III-IV intraventricular hemorrhage, white matter injury, stage II-III necrotizing enterocolitis, sepsis, or severe retinopathy of prematurity) were measured. Results: Among 8514 eligible infants, 5295 (62.2%) were male and 116 infants (2.0%) were small for gestational age (SGA). Overall, 5302 infants (62.3%) survived to discharge. The survival rate was 1 of 21 infants (4.8%) at 22 weeks, 13 of 71 infants (18.3%) at 23 weeks, 144 of 408 infants (35.3%) at 24 weeks, 480 of 987 infants (48.6%) at 25 weeks, 1423 of 2331 infants (61.0%) at 26 weeks, and 3241 of 4692 infants (69.1%) at 27 weeks. Survival increased from 136 of 241 infants (56.4%; 95% CI, 50.1%-62.7%) in 2010 to 1110 of 1633 infants (68.0%; 95% CI, 65.7%-70.2%) in 2019 for infants born at 24 to 27 weeks (mean difference, 11.5%; 95% CI, 4.9%-18.2%; P < .001), without a significant change for infants born at less than 24 weeks. Major morbidity was found in 5999 of 8281 infants overall, for a rate of 72.4%, which increased from 116 of 223 infants (52.0%; 95% CI, 45.4%-58.6%) to 1363 of 1656 infants (82.3%; 95% CI, 80.5%-84.1%) from 2010 to 2019 (mean difference, 30.3%; 95% CI, 23.5%-37.1%, P < .001). Regional variations in survival were identified, with an almost 2-fold increase (1.94-fold; 95% CI, 1.66-2.27; P < .001) from 188 of 474 infants (39.7%) in northwest China to 887 of 1153 infants (76.9%) in north China. Gestational age (adjusted risk ratio [aRR], 1.084; 95% CI, 1.063-1.105; P < .001), birth weight (aRR, 1.028; 95% CI, 1.020-1.036; P < .001), premature rupture of membranes (aRR, 1.025; 95% CI, 1.002-1.048; P = .03), and antenatal steroids (aRR, 1.029; 95% CI, 1.004-1.055; P = .02) were associated with improved survival, while being born SGA (aRR, 0.801; 95% CI, 0.679-0.945; P = .01), being male (aRR, 0.975; 95% CI, 0.954-0.997; P = .02), multiple birth (aRR, 0.955; 95% CI, 0.929-0.982; P = .001), having a mother with gestational diabetes (aRR, 0.946; 95% CI, 0.913-0.981; P = .002), and low Apgar score (aRR, 0.951; 95% CI, 0.925-0.977; P < .001) were found to be risk factors associated with decreased chances of survival. Conclusions and Relevance: This study found that infants born extremely preterm were at increased risk of mortality and morbidity in China, with a survival rate that improved over time and a major morbidity rate that increased. These findings suggest that more active and effective treatment strategies are needed, especially for infants born at gestational age 25 to 27 weeks.

Electroencephalography monitoring in the neonatal intensive care unit: a Chinese perspective.

BACKGROUND: Electroencephalography (EEG) is an accessible technique for bedside monitoring of the cerebral function in the neonatal intensive care unit (NICU). The popularization of EEG in the field of newborns in China is relatively late compared with western countries. To learn more about current practices and improvement of EEG monitoring, we conducted a survey to describe current utilization of EEG in NICU in China. METHODS: A cross-sectional electronic survey with 21-items about EEG using in NICU was administered for pediatricians in China on the official website of "Questionnaire Star". RESULTS: A total of 251 participants were involved, in which 64% of them reported using EEG. EEG was employed in NICUs of Children's hospitals (97%), and grade III, class A hospitals (69%). Besides, neonatal encephalopathy and suspected seizures were the most common indications for use. In clinical practice, the vast majority of physicians managed their patients on the basis of EEG (93%). Pediatricians prefer to use conventional video-EEG (cEEG) to detect seizures and make the diagnosis of encephalopathy. Both amplitude integrated EEG (aEEG) (78%) and cEEG (56%) were mainly interpreted by neonatologists. However, only 56% of respondents had ever taken a formal EEG training course. Overall, 96% of the respondents reported that they would be interested in attending an education session on EEG in the NICU. aEEG interpretation was the most interesting part to learn (81%). For those who were not using EEG, cost (43%) and difficulty interpretation (30%) were reported as barriers to use. CONCLUSIONS: The utilization rate of EEG in NICU in China is significantly lower than the international level. There is an urgent need for standardized training and financial support for neonatologists in the use of EEG and interpretation of aEEG results.

[Gene variant analysis of a child presented with neonatal diabetes and multiple organ malformations].

OBJECTIVE: To explore the genetic basis for an infant with neonatal diabetes (NDM) and multiple malformations. METHODS: Genetic variants were detected by next generation sequencing (NGS). Suspected variant was verified by Sanger sequencing. RESULTS: A de novo heterozygous variant, c.1454_1455del(p.K485Rfs), was detected in exon 5 of the GATA6 gene. The variant was undetected in his parents and unreported previously. Bioinformatic analysis predicted the variant to be pathogenic. CONCLUSION: The heterozygous variant of c.1454_1455del(p.K485Rfs) of the GATA6 gene probably underlies the disease in this child. Genetic testing can facilitate diagnosis and genetic counseling for NDM.

Sirt1 Regulates Oxidative Stress in Oxygen-Glucose Deprived Hippocampal Neurons.

Oxidative stress is an important mechanism of neonatal hypoxic-ischemic brain damage. Sirtuin1 (Sirt1) is a deacetylase that depends on NAD+, which has an important role in antioxidant metabolism. Furthermore, peroxisome proliferator-activated receptor γ-co-activator 1α (PGC-1α) is a key regulator of mitochondrial oxidative stress, which is regulated by Sirt1. Here, we investigated the role of Sirt1 in the pathogenesis of brain injuries after modulating its activity in primary cultured hippocampal neurons. Our study shows that the expression of Sirt1 was downregulated after oxygen-glucose deprivation. Activation of Sirt1 with resveratrol improved cell's resistance to oxidative stress, whereas inhibition of Sirt1 with EX527 significantly reduced cell viability after cellular oxidative stress. Our study also shows that activation of Sirt1 with resveratrol exerts its antioxidant effect by regulating the expression of PGC-1α. In contrast, application of EX527 decreased the expression of PGC-1α. In summary, these results confirmed that Sirt1 is a potent protective factor for neurons subjected to oxidative stress, and the protective effect of Sirt1 is attributed to its regulation of PGC-1α.

Erythropoietin prevents necrotizing enterocolitis in very preterm infants: a randomized controlled trial.

BACKGROUND: Necrotizing enterocolitis (NEC) is one of the most severe complications in very preterm infants, but there are currently no accepted methods to prevent NEC. Studies have shown that erythropoietin (EPO) has the potential to prevent NEC or improve outcomes of preterm NEC. This study aimed to determine whether recombinant human EPO (rhEPO) could protect against NEC in very preterm infants. METHODS: The study was a prospective randomized clinical trial performed among four NICU centers. A total of 1327 preterm infants with gestational age ≤ 32 weeks were admitted to the centers, and 42 infants were excluded leaving 1285 eligible infants to be randomized to the rhEPO or control group. Infants in the rhEPO group were given 500 IU/kg rhEPO intravenously every other day for 2 weeks, while the control group was given the same volume of saline. The primary outcome was the incidence of NEC in very preterm infants at 36 weeks of corrected gestational age. RESULTS: A total of 1285 infants were analyzed at 36 weeks of corrected age for the incidence of NEC. rhEPO treatment significantly decreased the incidence of NEC (stage I, II and III) (12.0% vs. 17.1%, p = 0.010), especially confirmed NEC (stage II and III) (3.0% vs. 5.4%, p = 0.027). Meanwhile, rhEPO treatment significantly reduced the number of red blood cells transfusion in the confirmed NEC cases (1.2 ± 0.4 vs. 2.7 ± 1.0, p = 0.004). Subgroup analyses showed that rhEPO treatment significantly decreased the incidence of confirmed NEC at gestational age < 28 weeks (p = 0.019), and the incidence of all stages NEC in preterm infants with hemoglobin < 90 g/l (p = 0.000) and 5 min Apgar score > 5 (p = 0.028). CONCLUSION: Repeated low-dose rhEPO treatment is beneficial against NEC in very preterm infants. Trial registration The protocol was registered retrospectively at ClinicalTrials.gov (NCT03919500) on April 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03919500.