Status of fungal sepsis among preterm infants in 25 neonatal intensive care units of tertiary hospitals in China / 中华儿科杂志

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.

Risk factors for neonatal asphyxia and establishment of a nomogram model for predicting neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture: a multicenter study / 中国当代儿科杂志

OBJECTIVES@#To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia.@*METHODS@#A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively.@*RESULTS@#Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia.@*CONCLUSIONS@#The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.

Research research on the use of melatonin in combination with therapeutic hypothermia for the treatment of neonatal hypoxic-ischemic encephalopathy / 中国当代儿科杂志

Neonatal hypoxic-ischemic encephalopathy (HIE) remains one of the leading causes of death and long-term neurodevelopmental disorders in full-term neonates, and there is currently no curative treatment. Therapeutic hypothermia is now a standard therapy for HIE in the neonatal intensive care unit, but its safety and efficacy in remote areas remains unclear. Melatonin is an indole endocrine hormone mainly produced by the pineal gland and it has the ability to easily penetrate the blood-brain barrier. Through receptor and non-receptor mechanisms, melatonin exerts anti-oxidative and anti-inflammatory effects and participates in the regulation of organelle function and the inhibition of cell death. Melatonin is considered one of the most promising drugs for the treatment of HIE based on its reliable safety profile and clinical/preclinical results. This article reviews the recent research on the use of melatonin in combination with therapeutic hypothermia for the treatment of neonatal HIE.

Clinical significance of amplitude-integrated electroencephalography in preterm infants with bronchopulmonary dysplasia / 中国当代儿科杂志

OBJECTIVE@#To study the changes and clinical significance of amplitude-integrated electroencephalography (aEEG) in preterm infants with bronchopulmonary dysplasia (BPD).@*METHODS@#A total of 156 preterm infants with a gestational age of ≤ 32@*RESULTS@#Compared with the non-BPD group, the BPD group had a significantly lower total aEEG score at the corrected gestational age of 33-34@*CONCLUSIONS@#Preterm infants with BPD (especially moderate to severe BPD) have a lower aEEG score than those without BPD, suggesting that their nervous system development may lag behind that of non-BPD preterm infants with the same gestational age. Therefore, early nervous system evaluation and intervention are necessary for preterm infants with BPD.

Effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia: a multicenter study in Hubei Province, China / 中国当代儿科杂志

OBJECTIVES@#To study the effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia.@*METHODS@#A retrospective analysis was performed on the medical data of the neonates with asphyxia who were admitted to 52 hospitals in Hubei Province of China from January to December, 2018 and had blood glucose data within 12 hours after birth. Their blood glucose data at 1, 2, 6, and 12 hours after birth (with an allowable time error of 0.5 hour) were recorded. According to the presence or absence of brain injury and/or death during hospitalization, the neonates were divided into a poor prognosis group with 693 neonates and a good prognosis group with 779 neonates. The two groups were compared in the incidence of glucose metabolism disorders within 12 hours after birth and short-term prognosis.@*RESULTS@#Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of neonates from secondary hospitals (48.5% vs 42.6%, @*CONCLUSIONS@#Recurrent hyperglycemia in neonates with asphyxia may suggest poor short-term prognosis, and it is necessary to strengthen the early monitoring and management of the nervous system in such neonates.

Incidence of neonatal asphyxia and contributing factors for the develpment of severe asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture: a multicenter study / 中国当代儿科杂志

OBJECTIVE@#To investigate the incidence of neonatal asphyxia and possible contributing factors for the development of severe asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture, China.@*METHODS@#A total of 16 hospitals in Hubei Enshi Tujia and Miao Autonomous Prefecture were selected as research centers. A retrospective analysis was performed for the clinical data of 22 294 live births in these 16 hospitals from January to December, 2016 to investigate the incidence rate of neonatal asphyxia and possible contributing factors for the development of severe asphyxia.@*RESULTS@#Of the 22 294 neonates born alive, 733 (3.29%) were diagnosed with neonatal asphyxia, among whom 627 had mild asphyxia and 106 had severe asphyxia. The neonates with low maternal education level, maternal anemia during pregnancy, chorioamnionitis, abnormal amniotic fluid, abnormal umbilical cord, placenta previa, placental abruption, Tujia Minority, preterm birth, and low birth weight had a higher incidence of severe asphyxia (P<0.05).@*CONCLUSIONS@#The incidence rate of neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture is higher. Low maternal education level, maternal anemia during pregnancy, chorioamnionitis, abnormal amniotic fluid, abnormal umbilical cord, placenta previa, placental abruption, Tujia Minority, preterm birth, and low birth weight may be related to the development of severe neonatal asphyxia.

Analysis of In-hospital Neonatal Death in the Tertiary Neonatal Intensive Care Unit in China: A Multicenter Retrospective Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Globally, the proportion of child deaths that occur in the neonatal period remains a high level of 37-41%. Differences of cause in neonate death exist in different regions as well as in different economic development countries. The specific aim of this study was to investigate the causes, characteristics, and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit (NICU) of China.</p><p><b>METHODS</b>All the dead neonates admitted to 26 NICUs were included between January l, 2011, and December 31, 2011. All the data were collected retrospectively from clinical records by a designed questionnaire. Data collected from each NICU were delivered to the leading institution where the results were analyzed.</p><p><b>RESULTS</b>A total of 744 newborns died during the 1-year survey, accounting for 1.2% of all the neonates admitted to 26 NICUs and 37.6% of all the deaths in children under 5 years of age in these hospitals. Preterm neonate death accounted for 59.3% of all the death. The leading causes of death in preterm and term infants were pulmonary disease and infection, respectively. In early neonate period, pulmonary diseases (56.5%) occupied the largest proportion of preterm deaths while infection (27%) and neurologic diseases (22%) were the two main causes of term deaths. In late neonate period, infection was the leading cause of both preterm and term neonate deaths. About two-thirds of neonate death occurred after medical care withdrawal. Of the cases who might survive if receiving continuing treatment, parents' concern about the long-term outcomes was the main reason of medical care withdrawal.</p><p><b>CONCLUSIONS</b>Neonate death still accounts for a high proportion of all the deaths in children under 5 years of age. Our study showed the majority of neonate death occurred in preterm infants. Cause of death varied with the age of death and gestational age. Accurate and prompt evaluation of the long-term outcomes should be carried out to guide the critical decision.</p>

Mortality and Morbidity of Extremely Low Birth Weight Infants in the Mainland of China: A Multi-center Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>With the progress of perinatal medicine and neonatal technology, more and more extremely low birth weight (ELBW) survived all over the world. This study was designed to investigate the short-term outcomes of ELBW infants during their Neonatal Intensive Care Unit (NICU) stay in the mainland of China.</p><p><b>METHODS</b>All infants admitted to 26 NICUs with a birth weight (BW) < l000 g were included between January l, 2011 and December 31, 2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors.</p><p><b>RESULTS</b>A total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age (GA) was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants (23.3%) died and another 69 infants (26.7%) died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas (53.6% vs. 35.3%, P = 0.019). BW < 750 g and GA < 28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization.</p><p><b>CONCLUSIONS</b>Our study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.</p>

Clinical application of nasal intermittent positive pressure ventilation in initial treatment of neonatal respiratory distress syndrome / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the clinical effectiveness and safety of nasal intermittent positive pressure ventilation (NIPPV) in the initial treatment of neonatal respiratory distress syndrome (NRDS) and the initial setting of NIPPV parameters.</p><p><b>METHODS</b>One hundred neonates with NRDS were divided into NIPPV group (n=50) and nasal continuous positive airway pressure (NCPAP) group (n=50). A randomized controlled study was conducted to compare the effectiveness of NIPPV versus NCPAP in the initial treatment of NRDS from the following aspects: reducing CO2 retention, improving oxygenation, reducing second endotracheal intubation and second use of pulmonary surfactant (PS), reducing the duration of invasive respiratory support, reducing the duration of oxygen use, and reducing the incidence of air leak, abdominal distension and ventilator-associated pneumonia.</p><p><b>RESULTS</b>After 1 and 6 hours of noninvasive respiratory support, the NIPPV group was superior to the NCPAP group with respect to the reduction in CO2 retention and improvement in oxygenation (P<0.05); in addition, compared with the NCPAP group, the NIPPV group had significantly lower rates of second endotracheal intubation and second PS use, significantly shorter duration of invasive respiratory support and time of FiO2 >0.21, and significantly lower incidence of apnea and ventilator-associated pneumonia (P<0.05); there were no significant differences in the incidence of air leak and abdominal distention between the two groups.</p><p><b>CONCLUSIONS</b>NIPPV is effective and safe in the initial treatment of NRDS and holds promise for clinical application.</p>

Effects of inhaled nitric oxide in neonatal hypoxemic respiratory failure from a multicenter controlled trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hypoxemic respiratory failure (HRF) is one of the most common causes for neonatal infants requiring aggressive respiratory support. Inhaled nitric oxide (iNO) has been established routinely as an adjunct to conventional respiratory support in developed countries. The aim of this study was to investigate effects of iNO in neonates with HRF in resource limited condition with no or limited use of surfactant, high frequency oscillatory ventilation (HFOV) and extracorporeal membrane oxygenation.</p><p><b>METHODS</b>A non-randomized, open, controlled study of efficacy of iNO was conducted over 18 months. Eligible term and near-term neonates from 28 hospitals with HRF (oxygenation index > 15) were enrolled prospectively into two groups as either iNO or control. Oxygenation improvement and mortality as primary endpoint were determined in relation with dosing and timing of iNO, severity of underlying diseases, complications and burden. Intention-to-treat principle was adopted for outcome assessment. Response to iNO at 10 or 20 parts per million (ppm) was determined by oxygenation in reference to the control (between-group) and the baseline (within-group).</p><p><b>RESULTS</b>Compared to 93 controls, initial dose of iNO at 10 ppm in 107 treated infants significantly improved oxygenation from first hour (P = 0.046), with more partial- and non-responders improved oxygenation with subsequent 20 ppm NO (P = 0.018). This effect persisted on days 1 and 3, and resulted in relatively lower mortalities (11.2% vs. 15%) whereas fewer were treated with surfactant (10% vs. 27%), HFOV (< 5%) or postnatal corticosteroids (< 10%) in both groups. The overall outcomes at 28 days of postnatal life in the iNO-treated was not related to perinatal asphyxia, underlying diseases, severity of hypoxemia, or complications, but to the early use of iNO. The cost of hospital stay was not significantly different in both groups.</p><p><b>CONCLUSIONS</b>With relatively limited use of surfactant and/or HFOV in neonatal HRF, significantly more responders were found in the iNO-treated patients as reflected by improved oxygenation in the first three days over the baseline level. It warrants a randomized, controlled trial for assessment of appropriate timing and long-term outcome of iNO.</p>

Current status of neonatal acute respiratory disorders: a one-year prospective survey from a Chinese neonatal network / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>We conducted a prospective, multicenter investigation of incidence, management and outcome of neonatal acute respiratory disorders (NARD), and evaluated related perinatal risk factors and efficacy of respiratory therapies in neonatal intensive care units (NICUs) in a Chinese neonatal network.</p><p><b>METHODS</b>Data were prospectively collected in 2004 - 2005 from infants with NARD defined as presence of respiratory distress and oxygen requirement during the first 3 days of life.</p><p><b>RESULTS</b>A total of 2677 NARD was classified (20.5% of NICU admissions). There were 711 (5.44%) with respiratory distress syndrome (RDS), 589 (4.51%) pulmonary infection, 409 (3.13%) meconium aspiration syndrome, 658 (5.03%) aspiration of amniotic fluid and 239 (1.83%) transient tachypnoea. Meconium aspiration syndrome had the highest rate with fetal distress, transient tachypnoea from cesarean section, and RDS with maternal disorders. Assisted mechanical ventilation was applied in 53.4% of NARD, and in above five disorders with 84.7%, 52.3%, 39.8%, 24.5%, and 53.6%, respectively. Corresponding mortality in these disorders was 31.4%, 13.6%, 17.8%, 4.1% and 5.0%, respectively. Surfactant was provided to 33.9% of RDS. In all RDS infants, the survival rate was 78.8% if receiving surfactant, and 63.4% if not (P < 0.001).</p><p><b>CONCLUSIONS</b>This study provided NICU admission-based incidence and mortality of NARD, reflecting efficiency of advanced respiratory therapies, which should be a reference for current development of respiratory support in NICU at provincial and sub-provincial levels, justifying efforts in upgrading standard of care in emerging regions through a collaborative manner.</p>

Risk factors and pathogens of nosocomial infection in preterm infants / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the risk factors and the pathogens of nosocomial infection in preterm infants.</p><p><b>METHODS</b>The medical data of 197 preterm infants with nosocomial infection were retrospectively studied.</p><p><b>RESULTS</b>The incidence of nosocomial infection was 22.2% (197/887). Small gestational age (OR=4.125, p<0.05), low birth weight (OR=5.450, p<0.05), mechanical ventilation therapy (OR=4.435, p<0.05) and delayed enteral feedings (OR=3.765, p<0.05) were found to be important risk factors for nosocomial infection. Klebsiella was the main pathogen (22.3%), followed by Staphylococcus (18.4%).</p><p><b>CONCLUSIONS</b>Hygienic handwashing, decreasing invassive procedures and an early start of enteral feeding are crucial for preventing nosocomal infection in preterm infants. Klebsiella is the main pathogen of nosocomal infections.</p>

The preparation and application of cross-linked urease aggregates / 生物工程学报

Urease was immobilized in a simple and effective way by physical aggregation using a precipitant-ammonium sulfate, followed by chemical cross-linking using a bifunctional reagent-glutaraldehyde to form insoluble Cross-linked urease aggregates (CLUAs). The optimum pH, optimum temperature and Km of CLUAs were 8.0, 70 degrees C and 0.021 mol/L respectively. Compared with that of free urease, the thermal stability, storage stability and resistance of cross-linked urease aggregates to the exogenous proteolysis were enhanced. The efficacy of CLUAs for the treatment of rats with chronic renal failure was also studies. The rats with chronic renal failure caused by adenine were divided into 3 groups randomly:the control group (fed with 10 mL water /kg per day), Coated Aldehyde Oxystarch (CAO) group (fed with 20 g CAO /kg and 10 mL water /kg per day) and CLUAs + CAO group (fed with 20 g CAO /kg and 10 mL CLUAs /kg per day) in which CAO was used to absorb the ammonia produced from urea. The contents of BUN and Scr in serum before and after 2 weeks treatment were determined. In three groups, the level of Scr decreased slightly (P = 0.922, 0.972 and 0.225 > 0.05 respectively) after treatment. The level of BUN was not changed (P = 0.211 > 0.05) in the control group, but decreased greatly BUN in both CAO group and CLUAs + CAO group (P = 0.004 < 0.05 and P < 0.001 respectively). Furthermore, the decrease of the BUN level after treatment in the CLUAs + CAO group was more remarkable than that in the CAO group (P = 0.016 < 0.05), which showed that the CLUAs + CAD system was more efficient than the CAO system for the removal of urea in serum.