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 metabolic bone disease of prematurity in very/extremely low birth weight infants: a multicenter investigation in China / 中国当代儿科杂志

OBJECTIVE@#To investigate the incidence rate and risk factors for metabolic bone disease of prematurity (MBDP) in very low birth weight/extremely low birth weight (VLBW/ELBW) infants.@*METHODS@#The medical data of 61 786 neonates from multiple centers of China between September 1, 2013 and August 31, 2016 were retrospectively investigated, including 504 VLBW/ELBW preterm infants who met the inclusion criteria. Among the 504 infants, 108 infants diagnosed with MBDP were enrolled as the MBDP group and the remaining 396 infants were enrolled as the non-MBDP group. The two groups were compared in terms of general information of mothers and preterm infants, major diseases during hospitalization, nutritional support strategies, and other treatment conditions. The multivariate logistic regression analysis was used to investigate the risk factors for MBDP.@*RESULTS@#The incidence rate of MBDP was 19.4% (88/452) in VLBW preterm infants and 38.5% (20/52) in ELBW preterm infants. The incidence rate of MBDP was 21.7% in preterm infants with a gestational age of < 32 weeks and 45.5% in those with a gestational age of < 28 weeks. The univariate analysis showed that compared with the non-MBDP group, the MBDP group had significantly lower gestational age and birth weight, a significantly longer length of hospital stay, and a significantly higher incidence rate of extrauterine growth retardation (@*CONCLUSIONS@#A lower gestational age, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis may be associated an increased risk of MBDP in VLBW/ELBW preterm infants. It is necessary to strengthen perinatal healthcare, avoid premature delivery, improve the awareness of the prevention and treatment of MBDP among neonatal pediatricians, and adopt positive and reasonable nutrition strategies and comprehensive management measures for preterm infants.

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>

Epidemiology of neonatal purulent meningitis in Hebei Province, China: a multicenter study / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics, diagnosis and main pathogenic bacteria, and outcomes of neonatal purulent meningitis.</p><p><b>METHODS</b>A prospective epidemiological study was conducted in neonates with purulent meningitis admitted to 23 cooperating hospitals between 2013 and 2014. Clinical data were collected and clinical characteristics and outcomes were analyzed.</p><p><b>RESULTS</b>A total of 301 neonates with purulent meningitis from the 23 cooperating hospitals were included. Neonatal pneumonia was the most common primary disease (167 cases, 55.5%). Fever was the most common manifestation (214 cases, 71.1%). Blood culture findings were positive in 72 patients (23.9%), with Escherichia coli, Klebsiella pneumoniae and Staphylococcus epidermidis as the most common bacteria. Positive cerebrospinal fluid (CSF) culture was found in 36 patients (36/264, 13.6%) , with Escherichia coli and Staphylococcus epidermidis as the most common bacteria. The median of CSF WBC counts was 80/mm(3) (range: 0-9 2500/mm(3)), and 11 cases (3.7%) had CSF WBC counts of <20/mm(3) and 154 cases (51.2%) had CSF WBC counts of >100/mm(3). There were 258 patients (85.7%) who were cured or improved at discharge and 15 deaths (15/298, 5.0%).</p><p><b>CONCLUSIONS</b>The most common primary disease of neonatal purulent meningitis is neonatal pneumonia in this area. The patients with neonatal purulent meningitis most often present with fever. Escherichia coli is the leading pathogenic bacteria causing neonatal purulent meningitis. A normal CSF WBC count can barely be used to exclude the possibility of this diosorder.</p>

Investigation of risk factors for hearing impairment in premature infants / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the risk factors for hearing impairment in premature infants.</p><p><b>METHODS</b>A total of 895 premature infants who were admitted to the neonatal intensive care unit from January to December 2010 were evaluated using distortion product otoacoustic emission to detect hearing impairment. The failure rates in initial screening and secondary screening were recorded. The risk factors for failure to pass hearing screenings were elucidate using multivariate logistic regression analysis.</p><p><b>RESULTS</b>The failure rate in initial screening was 38.4%, and the failure rate in secondary screening was 18.3%. In the auditory brainstem response test conducted at three months after birth, the failure rate was 22.2%. In premature infants with a gestational age of 28-29(+6) weeks, 60.5% did not pass the initial screening; 48.1% of the premature infants with a birth weight of 1 001-1 499  g failed the initial screening; 70.0% of the premature infants with a birth weight of ≤1 000  g failed the initial screening; 53.8% of the premature infants who had severe asphyxia failed the initial screening; 45.0% of the premature infants who used invasive ventilation failed the initial screening; 47.9% of the premature infants with a total bilirubin of ≥340 µmol/L failed the initial screening; 54.6% of the premature infants with septicemia failed the initial screenings. The multivariate logistic regression analysis revealed the following independent risk factors for failing the initial and secondary hearing screenings: gestational age, birth weight, hyperbilirubinemia and septicemia.</p><p><b>CONCLUSIONS</b>Premature infants are susceptible to hearing impairment because they have immature organs and tissues and incomplete blood-brain barrier function and are sensitive to such factors as hyperbilirubinemia and infection. Early hearing screening and follow-up are necessary for premature infants to ensure timely interventions.</p>

Prospective study on in-hospital mortality and its risk factors in very low birth weight infants requring mechanical ventilation / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To describe the clinical features, treatments and prognosis of very low birth weight infants (VLBWIs) requring mechanical ventilation, to assess the risk factors associated with the mortality of VLBWIs, and to evaluate the significance of the scoring system based on clinical risk index for babies (CRIB) and the score for neonatal acute physiology-perinatal extension II (SNAPPE-II) for predicting mortality risk for premature infants in China.</p><p><b>METHODS</b>Perinatal data were collected from 127 VLBWIs requring mechanical ventilation who were admitted to the neonatal intensive care unit (NICU) from January 2010 to October 2011.</p><p><b>RESULTS</b>The enrolled infants had a mean gestational age of 31±2 weeks, a mean birth weight of 1290±170 g, a male/female ratio of 1.23∶1, and extremely low birth weight infant accounting for 6.3%. Of the 127 cases, 48.0% were administered with pulmonary surfactant (PS), and 49.6% received endotracheal intubation ventilation. The overall in-hospital mortality was 41.7%. Multivariate logistic regression revealed the following independent risk factors for mortality: low birth weight, multiple birth, cesarean section, and low PaO2/FiO2 ratio (OR = 1.611, 7.572, 4.062, and 0.133 respectively; P<0.05). SNAPPE-II and CRIB showed good performance in predicting prognosis, with areas under the ROC curve of 0.806 and 0.777 respectively.</p><p><b>CONCLUSIONS</b>The overall mortality rate of VLBWIs is still relatively high. The high-risk factors for VLBWI mortality include low birth weight, multiple birth, cesarean section, and low PaO2/FiO2 ratio. The neonatal illness severity scoring system (using SNAPPE-II and CRIB) can be used to quantify illness severity in premature infants.</p>

Effect of pulmonary surfactant on Th1/Th2 balance in neonates with respiratory distress syndrome / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of pulmonary surfactant (PS) on the Th1/Th2 balance and serum levels of interleukin-4 (IL-4), interferon-γ (IFN-γ) and IgE in neonates with respiratory distress syndrome (RDS).</p><p><b>METHODS</b>A total of 58 neonates with RDS were divided into control (n=20) and PS treatment groups (n=38). The control group underwent mechanical ventilation and other conventional treatment, while the PS treatment group received with bovine PS treatment within 1 hour of being admitted to the hospital together with mechanical ventilation and other conventional treatment. Enzyme-linked immunosorbent assay was used to measure serum levels of IL-4, IFN-γ and IgE before treatment and 24, 48 and 72 hours after treatment. Simultaneously, arterial blood gas, respiratory system compliance, and other ventilator parameters were recorded.</p><p><b>RESULTS</b>Compared with the control group, the PS treatment group showed significantly shorter duration of mechanical ventilation and oxygen exposure time (P<0.05), significantly better respiratory system compliance and significantly lower oxygenation index 24, 48 and 72 hours after treatment (P<0.05). At 48 and 72 hours after treatment, serum levels of IFN-γ were significantly lower in the PS treatment group than in the control group (120±46 ng/L vs 229±59 ng/L, P<0.05; 141±40 ng/L vs 282±44 ng/L, P<0.05), and serum levels of IL-4 were significantly higher in the PS treatment group than in the control group (263±48 pg/mL vs 152±45 pg/mL, P<0.05; 417±49 pg/mL vs 201±46 pg/mL, P<0.05). At 72 hours after treatment, serum level of IgE was significantly lower in the PS treatment group than in the control group (115±44 pg/mL vs 199±43 ng/mL; P<0.05).</p><p><b>CONCLUSIONS</b>PS treatment can shorten the duration of mechanical ventilation and oxygen exposure time, regulate serum levels of IFN-γ, IL-4 and IgE, and influence Th1/Th2 balance in neonates with RDS, thus inhibiting lung inflammatory response and reducing lung injury.</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>

Treatment of newborns with severe injured brain with transplantation of human neural precursor cells / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the therapeutic effect of human neural precursor cells transplantation in treatment of neonates with severe brain injury.</p><p><b>METHOD</b>The transplantation was performed on 6 newborns, one of them was diagnosed as extremely severe carbon monoxide poisoning at 5(th) day after birth; one of them was diagnosed as severe hypoglycemia; the others had asphyxia at birth with Apgar scores from 1 to 3 and were diagnosed as severe neonatal asphyxia, severe hypoxic ischemic encephalopathy according to images, electroencephalogram, biochemical examination and clinical manifestation. With the approval of hospital ethics committee and informed consent of the family members, the newborns received human neural precursor cells transplantation at the 4(th) to 20(th) day after birth. With the agreement of a pregnant woman, forebrain cells were obtained from the forebrain of her 12-week old fetus after spontaneous abortion. The cells from the fetal brain were amplified into human neural precursor cells in vitro and were injected into the cerebral ventricle of the patients.</p><p><b>RESULT</b>On the 2(nd) day after transplantation, sucking and swallowing reflexes gradually appeared in all the patients, muscular tension was also improved, and convulsion stopped. NBNA scoring in 3 of the patients reached normal level on the 28(th) day after birth. The 6 patients were followed up for 12 months. Four patients were normal in psychomotor development and scores of each scale reached normal level. Two patients have cerebral palsy.</p><p><b>CONCLUSION</b>hNPCs transplantation is safe and effective in treatment of severe neonatal brain injury. More clinical trials and further observation are needed.</p>

Randomized controlled study of targeted tidal volume ventilation for treatment of severe neonatal respiratory distress syndrome / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of targeted tidal volume ventilation in the treatment of severe neonatal respiratory distress syndrome (RDS).</p><p><b>METHODS</b>Eighty-four neonates with severe RDS between June 2008 and January 2010 were randomly assigned to 3 groups according to the ventilation mode: synchronized intermittent positive pressure ventilation plus volume guarantee (SIPPV+VG; n=31), high frequency oscillation ventilation (HFOV; n=23) and intermittent mandatory ventilation (IMV; n=30). The oxygenation status, the durations of oxygen exposure and ventilation and the incidence of complications were observed.</p><p><b>RESULTS</b>The oxygenation status (P/F and a/APO2) in the SIPPV+VG and the HFOV groups was improved significantly 12 hrs after ventilation (P<0.05). While in the IMV group, the oxygenation status was not improved until 24 hrs after ventilation. The durations of oxygen exposure and ventilation in the SIPPV+VG and the HFOV groups were shorter than in the IMV group (P<0.05). The incidences of air leak syndrome and ventilation-associated pneumonia (VAP) were lower in the SIPPV+VG and the HFOV groups than in the IMV group (P<0.05). The incidence of severe intracranial hemorrhage in the HFOV group was higher than in the other two groups (P<0.05).</p><p><b>CONCLUSIONS</b>Compared with IMV, SIPPV+VG and HFOV can improve the oxygenation status more quickly, shorten the ventilation duration and decrease the incidences of air leak syndrome and VAP in neonates with severe RDS.</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>

A 12-month prospective survey of perinatal outcome of liveborn neonates in Julu County, China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Population based epidemiologic study on the main diseases and birth status of liveborn neonates remains scarce in China, especially in rural areas where a large number of neonates are born. The aim of this study was to establish an epidemiological basis of live births in Julu County, a representative of the northern and mid-western parts of China in terms of demography, disease pattern and women and children's health care infrastructure.</p><p><b>METHODS</b>The perinatal data of all live births were prospectively collected in three participating county-level hospitals from September 1, 2007 to August 30, 2008.</p><p><b>RESULTS</b>There were 5822 live births in these hospitals. Among all live births, 53.7% were male and 4.5% were born prematurely. Mean (SD) birth weight (BW) was (3348 ± 503) g. The low (< 2500 g) and very low BW (< 1500 g) infants accounted for 3.8% and 0.5% of the total births, with 6.5% as small for gestational age and 2.8% as multi-births. Cesarean section rate was 30.2%, of which 68.6% were elective. There were 745 infants (12.8% of the live births) admitted to local neonatal wards within 7 days of postnatal life, in which 48.3% and 19.3% were due to perinatal asphyxia and prematurity, respectively. The incidences of perinatal aspiration syndrome, transient tachypnea and respiratory distress syndrome were 4.9%, 0.6% and 0.5%, respectively. Neonatal mortality was 7.6‰ (44/5822), with 16 in delivery room and 28 in neonatal ward before discharge.</p><p><b>CONCLUSIONS</b>This study provided a population-based perinatal data of live births and neonatal mortality in a northern China county with limited resources. Neonatal disorders related to perinatal asphyxia remain a serious clinical problem, which calls for sustained education of advanced neonatal resuscitation and improvement in the quality of perinatal-neonatal care.</p>

Effects of selective head cooling with mild hypothermia on serum levels of caspase-3 and IL-18 in neonates with hypoxic-ischemic encephalopathy / 中国当代儿科杂志

<p><b>OBJECTIVE</b>The study examined the changes of serum caspase-3 and IL-8 levels following selective head cooling with mild hypothermia (SHC) treatment in neonates with hypoxic-ischemic encephalopathy (HIE) in order to explore the mechanism of neuroprotection of SHC against HIE.</p><p><b>METHODS</b>Thirty-three neonates with moderate or severe HIE were randomly assigned to two groups: SHC treatment (n=16) and conventional treatment (n=17). Serum levels of caspase-3 and IL-18 were measured using ELISA before treatment and 24 hrs, 48 hrs, 72 hrs and 5 days after treatment.</p><p><b>RESULTS</b>Serum caspase-3 levels in the SHC group decreased 24 and 48 hrs after treatment (3.8±1.9 and 2.6±1.2 ng/mL, respectively) compared with 6.1±2.3 ng/mL at 24 hrs and 7.2±3.1 ng/mL at 48 hrs in the conventional treatment group (P<0.05). Serum IL-18 levels in the SHC group decreased 24 hrs, 48 hrs and 72 hrs after treatment (119±30, 76±33 and 71±40 ng/mL, respectively) compared with those in the conventional treatment group (138±28 ng/mL at 24 hrs, 156±60 ng/mL at 48 hrs and 182±54 ng/mL at 72 hrs; P<0.01).</p><p><b>CONCLUSIONS</b>SHC treatment can inhibit the release of caspase-3 and the expression of IL-18 in neonates with moderate or severe HIE. This may contribute to the neuroprotection of SHC against HIE.</p>

Interleukin-4 and interleukin-13 concentrations in bronchoalveolar lavage fluid in neonates with respiratory distress syndrome and concurrent ventilator-associated pneumonia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the concentrations of IL-4 and IL-13 in bronchoalveolar lavage fluid (BALF) in neonates with respiratory distress syndrome (RDS) and concurrent ventilator-associated pneumonia (VAP).</p><p><b>METHODS</b>Sixty-eight neonates with RDS undergoing mechanical ventilation for over 48 hrs were enrolled. IL-4 and IL-13 levels in BALF were measured using ELISA 1, 72 and 96 hrs after mechanical ventilation. The results were compared between the neonates with concurrent VAP (n=37) and without (n=31).</p><p><b>RESULTS</b>The levels of BALF IL-4 96 hrs after ventilation in the VAP group (35.34+/-1.78 ng/mL) were significantly higher than those in the non-VAP group (13.69+/-2.47 ng/mL, P<0.05). The levels of BALF IL-13 96 hrs after ventilation in the VAP group (33.74+/-2.74 ng/mL) also increased significantly compared with those in the non-VAP group (13.50+/-3.81 ng/mL) (P<0.05). There were significant differences in BALF IL-4 and IL-13 levels between 1 hr and 96 hrs in the VAP group (P<0.05).</p><p><b>CONCLUSIONS</b>BALF IL-4 and IL-13 levels increase in neonates with RDS and concurrent VAP. IL-4 and IL-13 may involve in the regulation of the inflammatory immune response.</p>

A randomized controlled study on the efficacy of inhaled nitric oxide in treatment of neonates with meconium aspiration syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>Meconium aspiration syndrome (MAS) is a disease of the term and near-term infant that is associated with considerable respiratory morbidity. The purpose of this study was to investigate effects of inhaled nitric oxide (iNO) in oxygenation and outcome of newborns with MAS.</p><p><b>METHODS</b>Eligible patients diagnosed as severe MAS admitted consecutively to the neonatal intensive care unit (NICU) of Hebei Children's Hospital from January 2004 to June 2006 were included in the study. The patients with an oxygenation index (OI) > or = 15 were randomized in a nonblinded manner to receive either iNO (NO group, n = 21) or no NO (control group, n = 25). Patients with an OI > or = 15 after enrollment were treated with iNO at 15 ppm initially. The response to iNO was assessed according to the increase in arterial PaO(2) and oxygen saturation (SpO(2)) after exposure to the starting concentration for 60 minutes. A response of 10 mm Hg (1 mm Hg = 0.133 kPa) increase in PaO(2) and a 10% increase in SpO(2) was assessed responsive to iNO. All patients were treated in the same neonatal unit and received the same standard therapy throughout the study period. Arterial blood gas tensions, pulmonary arterial pressure and systemic arterial blood pressures were recorded at baseline, 1 hour, and 24 hours in all patients. Methemoglobin levels were obtained at 12 - 24 hours after inhaled NO treatment. Parameters of fraction of inspired oxygen (FiO(2)), OI, mortality, ventilation time, and incidence of intraventricular hemorrhage (IVH, grade III-IV) were recorded. Informed consent was obtained from parents before enrollment. The protocol and the informed consent forms were approved by the ethic committee of the hospital before patient enrollment.</p><p><b>RESULTS</b>There was no significant difference in gestational age, birth weight, gender ratio, age at admission in hours, c-section delivery between the two groups, and no significant difference was found in respiratory mechanics parameters between the two groups at baseline. The duration of iNO was 34.90 +/- 16.41 hours. At the beginning of the treatment, no significant differences were detected in the OI and PAP between the two groups. One hour later, OI and PAP of NO group decreased significantly (OI, F = 35.27, P < 0.01, PAP, F = 24.30, P < 0.01), while in control group the difference was not found until 24 hours (OI, F = 20.16, P < 0.01, PAP, F = 101.22, P < 0.01). There were significant differences in PAP at 1, 24 hours between the two groups (1 h, t = 2.41, P < 0.05; 24 h, t = 3.11, P < 0.01). The methemoglobin levels were normal. Compared to the controls, hospital stay (t = 2.86, P < 0.05), duration of the need for oxygen supplement (t = 2.53, P < 0.05) and ventilation time were shorter (t = 2.41, P < 0.05), whereas mortality (chi(2) = 0.21, P > 0.05) and incidence of IVH (chi(2) = 0.00, P > 0.05) were not significantly different between the groups.</p><p><b>CONCLUSIONS</b>iNO could effectively improve the oxygenation and shorten the ventilation time and hospital stay without augmentation of risk of IVH and pneumothorax in these neonatal patients.</p>

Prospective clinical survey of respiratory failure in neonates from the Children's Hospital of Hebei Province / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Neonatal respiratory failure (RF) is a serious clinical problem associated with high mortality. This study aimed to investigate the incidence and outcome of neonatal RF in the Children's Hospital of Hebei Province.</p><p><b>METHODS</b>The medical data of 304 RF infants who were admitted to the neonatal intensive care unit (NICU) of the Children's Hospital of Hebei Province between March 2004 and February 2005 were prospectively studied.</p><p><b>RESULTS</b>The incidence of RF was 35.7% in the NICU during the 12-month period. Respiratory distress syndrome (28.4%), amniotic fluid aspiration syndrome (22.9%), and pneumonia (14.7%) were leading diseases resulting in RF. Of the 304 patients, 17 (5.6%) died of RF, 96 (31.6%) discontinued therapy on account of various causes and 191 (62.8%) recovered or improved. The mean length of hospital stay was 14.9+/-7.1 days and the mean medical cost was 7977+/-3 426 CNY for the 191 survivors.</p><p><b>CONCLUSIONS</b>The morbidity, mortality and medical costs of neonatal RF are high in Hebei Province. It is essential to improve the quality in respiratory therapy and perinatal care in order to reduce the morbidity and mortality related to high-risk pregnancies.</p>

Expression of nuclear factor-kappaB and its inhibitor in alveolar macrophages of patients with neonatal hyaline membrane disease / 中华儿科杂志

<p><b>OBJECTIVE</b>Inflammatory reaction and injury in immature lungs are associated with activation of nuclear factor-kappa B (NF-kappaB) to trigger proinflammatory cytokine release, but the mechanism thereof is not fully understood. The present study was conducted to understand possible relationship between expression of NF-kappaB and its inhibitor and severity and outcome of neonates with hyaline membrane disease (HMD).</p><p><b>METHODS</b>Serial samples of bronchoalveolar lavage fluid (BALF) were obtained during mechanical ventilation from 31 preterm infants with HMD. These infants were divided into two groups: survivors group [n = 22, birth weight (1500 +/- 320) g and gestational age (31.2 +/- 1.8) weeks] and nonsurvivors group [birth weight (1340 +/- 280) g, gestational age (30.8 +/- 2.1) weeks]. Nineteen preterm infants [birth weight (1470 +/- 280) g, gestational age (30.6 +/- 1.9) weeks] without respiratory disorders were enrolled as control subjects. Alveolar macrophages (AM) were isolated by differential adherence. AM was cultured and treated with lipopolysaccharide (LPS) for 1 hr. Then, nuclear extracts of AM were analyzed by electrophoretic mobility shift assay (EMSA) for NF-kappaB expression. NF-kappaB inhibitor (IkappaB-alpha protein) in cytoplasmic extracts was detected by using Western blotting and IL-1beta and IL-8 in BALF by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>NF-kappaB complexes were observed by EMSA, they were characterized by competition with cold oligonucleotide and p65-specific antibodies. The addition of an excess of cold oligonucleotide, corresponding to the NF-kappaB binding site, turned off the signal of the band, showing that the band was specific. An excess of an irrelevant oligonucleotide (corresponding to the SP-1) did not show any effect. The addition of an anti-p65 antibody caused the supershift of the two upper bands. After EMSA, the NF-kappaB complexes were quantified by using a ImageQuant software. NF-kappaB expression in AM at 24 hrs was higher in all the patients with HMD as compared with control subjects (survives/control, 34.1 vs 11.4 RDU, P < 0.01; nonsurvivors/control, 55.2 vs 11.4 RDU, P < 0.01). The NF-kappaB expression in AM at 72 hrs was higher than that in control subjects but not for nonsurvivors (survivors/control, 47.8 vs 25.6 RDU, P < 0.01; nonsurvivors/control, 21.8 vs 25.6, P > 0.05). The NF-kappaB expression in AM from nonsurvivors was depressed at 72 hrs as compared to 24 hrs (21.8 vs 55.2, P < 0.01), whereas the NF-kappaB expression in AM from survivors was still higher at 72 hrs than that at 24 hrs (47.8 vs 34.1, t = 4.43, P < 0.01).</p><p><b>CONCLUSION</b>Altered NF-kappaB activation in AM of BALF of neonates with HMD was observed, and it may be mediated by decreased IkappaB synthesis, increased IkappaB degradation, or both. In HMD nonsurvivors NF-kappaB translocation was hampered upon LPS activation.</p>

Changes of Serum Platelet Activating Factor,Thrombomodulin in Neonates with Meconium Aspiration Syndrome / 实用儿科临床杂志

Objective To detect levels of serum platelet activating factor(PAF),thrombomodulin(TM) and white blood cell(WBC),platelet count(PLT) in neonates with meconium aspiration syndrome(MAS),and observe changes of mediators of inflammation and function of endotheliocute.Methods All cases were taken vein blood in 24 h and 72-96 h after birth.Surm PAF and TM were detected by EILSA technique,at the same time,blood cell counts were determined.Results PAF and WBC in neonates with MAS increased,which were relevant to the patients′ condition.TM of neonates with MAS increased significantly,especially in 72-96 h after birth and(aggrava)-ted with the patients′ condition.Conclusion Neonates with MAS have inflammatory reaction and injured endotheliocyte,which are(inte)-raction.

Significance of soluble intercellular adhesion molecule-1 and procalcitonin in diagnosis of neonatal septicemia / 中华儿科杂志

<p><b>OBJECTIVE</b>Neonatal septicemia is a critical disease in neonatal period. Its incidence among live births is between 1 per thousand and 8 per thousand. Mortality of neonatal septicemia may be as high as 50% for infants who are not treated. The early signs of septicemia in the newborn are generally nonspecific. Blood culture and the other clinical diagnostic measures are not sufficiently sensitive. The present study aimed at evaluating potential use of soluble intercellular adhesion molecule-1 (sICAM-1), procalcitonin (PCT) and C-reactive protein (CRP) in diagnosis of septicemia.</p><p><b>METHODS</b>The experimental group consisted of 50 newborns with septicemia who were treated in Hebei Provincial Children's Hospital from April 1, 2002 to December 30, 2002. Thirty of the 50 cases had positive blood culture. The control group included 35 healthy newborns. Fasting blood samples were taken for bacterial cultures and sICAM-1, CRP, PCT determination. PCT and CRP contents were determined immediately after the specimens were collected. Analyses of sICAM-1 were done after inclusion of the last patient. Serum was separated from each specimen and stored at -20 degrees C within 2 hours. The analyses of sICAM-1 were performed by ELISA technique. CRP was analyzed by immunoturbidimetry assay (ITA). Immunochromatographic test was performed for detection of PCT from 200 ul serum. SPSS 10.0 was used to process the data. P values < 0.05 was considered to be statistically significant. One way analysis of variance (ANOVA), multiple comparison, chi-square test, paired-samples T test, linear correlation, Spearman correlation analysis, ROC curve were used for statistical analysis. The sensitivity, specificity, positive and negative predictive values, accuracy, Youden's index for sICAM-1, PCT, CRP and WBC count were calculated. These values were compared with each other.</p><p><b>RESULTS</b>(1) The content of sICAM-1 in control group varied widely from 79 to 1252 ng/ml. Comparison of the data indicated that there was significant difference among the three groups in the content of sICAM-1, CRP and PCT (P < 0.05), but not in WBC count. These markers are considered positive if sICAM-1 >or= 300 ng/ml, CRP >or= 8 mg/l, PCT >or= 2 ng/ml. Their sensitivity was higher than WBC (P < 0.05). Among these indices, PCT has the highest specificity (94.3%), positive predictive (95.6%), negative predictive (82.5%), accuracy (89.4%), and Youden's index (80.3%). (2) No significant difference was found in sICAM-1 between pre- and post-treatment (P > 0.05); however, there was significant difference in CRP and PCT. (3) sICAM-1 was in direct proportion to CRP (r = 0.339,P < 0.01). PCT is correlated with sICAM-1, CRP (the spearman correlation coefficient 0.569, 0.482, P < 0.01).</p><p><b>CONCLUSION</b>Different individual is in different immune status; The level of sICAM-1 is related with neonatal septicemia. sICAM-1 concentration may be used as a diagnostic tool with high sensitivity (85%) and moderate specificity (54.3%) in neonates suspected of infection. The sensitivity and specificity of CRP (>or= 8 mg/l) were accordingly 87.5% and 54.3%. WBC count had low sensitivity for diagnosis (30.0%); Among these indices, PCT had the highest specificity (94.3%), positive predictive (95.6%), negative predictive (82.5%) Values, accuracy (89.4%), Youden's index (80.3%); No correlation was found between sICAM-1 concentration and their ages in day accordingly. CRP, PCT may be used to estimate the effect of therapy. The correlation of the infectious indices indicates that the body may mobilize many organs at the same time to resist the invasion of organism.</p>