Development of neonatal respiratory and intensive care: Chinese perspectives.

Recent economic improvements in China have allowed the development of perinatal-neonatal care in sub-provincial regions. However, variations in neonatal respiratory and intensive care exist, especially in regions with limited resources. We conducted a series of collaborative clinical investigations into neonatal hypoxemic respiratory failure (NRF). In the study period from 2004 to 2005, this nationwide study found an incidence of NRF of 13.4% of total admissions to neonatal intensive care units (NICUs), with a mortality of 32%. Fewer than 30% of infants with respiratory distress syndrome (RDS) received surfactant treatment. Most cases of NRF had birth weights (BWs) of 1,000-1,500 g. Approximately 60% of deaths were due to withdrawal of respiratory support because of economic restraints despite initial response to therapy. Extremely low BW or gestational age accounted for less than 2% of all NRF cases, and their survival rate was less than 50%. A prospective clinical epidemiologic study of NRF in 14 NICUs, mainly sub-provincial centers, in Hebei province was undertaken in the study period from 2007 to 2008. NRF made up 16.9% of total NICU admissions, with increased use of surfactant (>50%) and continuous positive airway pressure (>80%) in this study. However, mortality due to RDS, meconium aspiration syndrome and pulmonary infection/sepsis remained higher than 30%, in part affected by socioeconomic factors. With measures to assist hospitalized neonates from low income families in urban areas, as well as the 'new rural cooperative health care program' to subsidize families from rural areas, the quality and affordability of NICU services may be improved in the forthcoming years.

Effects of inhaled nitric oxide in neonatal hypoxemic respiratory failure from a multicenter controlled trial.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Current status of neonatal acute respiratory disorders: a one-year prospective survey from a Chinese neonatal network.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Effects of androgen on the expression of brain aromatase cytopigment and nerve growth factor in neonatal rats with hypoxic-ischemic brain damage.

OBJECTIVE: To study the effects of androgen on the expression of aromatase cytopigment P450 (AROM) and nerve growth factor (NGF) in the brain and brain ultrastructure in neonatal rats with hypoxic-ischemic brain damage (HIBD) in order to investigate the mechanism underlying the protective effect of androgen against HIBD. METHODS: Ninety-six seven-day-old Sprague-Dawley rats were randomly divided into three groups: sham-operation, HIBD and androgen treatment (n=32 each). HIBD was induced by the ligation of left common carotid artery and hypoxia exposure. The rats in the androgen treatment and the HIBD groups were injected intraperitoneally with testosterone propionate (25 mg/kg) and arachis oil respectively immediately after hypoxia-ischemia (HI). After 24 and 72 hrs and 7 and 10 days of HI, AROM and NGF expression in the cortex and the hippocampus was detected with the immunohistochemical method. The ultrastructural changes of neurons in the cortex and the hippocampus were observed under a transmission electron microscope. RESULTS: Nerve cells of the HIBD group showed obvious injuries including cell organ decreasing, cellularoedema, nuclear swelling, chromatic agglutination, mitochondria decreasing and swelling, as well as an increase in apoptotic cells. Compared with the HIBD group, the nerve cells in the androgen treatment group had integrated nuclear membrane, well-distributed chromatin and abundant cell organs, and less cell apoptosis and increased axon regeneration. There was a positive expression of NGF and AROM in the brain cortex and the hippocampus in the HIBD group 24 hrs after HI. The expression of NGF and AROM increased significantly 72 hrs after HI, peaked 7 days after HI and then began to decrease but remained at a higher level than that in the sham-operation group 10 days after HI. The NGF and AROM expression in the cortex and the hippocampus in the androgen treatment group was significantly higher than that in the sham-operation and the HIBD groups 72 hrs, and 7 and 10 days after HI. CONCLUSIONS: Androgen treatment can promote axon regeneration and morphous recovery of neurons and decrease neural apoptosis in neonatal rats with HIBD. The neuroprotection of androgen is produced possibly through an increase in the expression of NGF and AROM in the brain.

[Effects of androgen on phosphacan and NG2 proteoglycan expression and neurite regeneration in neonatal rats with hypoxic-ischemic brain damage].

OBJECTIVE: To study the effects of androgen on the expression of phosphacan and NG2 proteoglycan (NG2) and neurite regeneration in neonatal rats with hypoxic-ischemic brain damage (HIBD) and the potential mechanism underlying the protective effect of androgen against HIBD. METHODS: One hundred and twenty neonatal Sprague-Dawley rats were randomly divided into three groups: sham-operated, HIBD and androgen treatment. HIBD was induced by the ligation of left common carotid artery and hypoxia exposure. The androgen treatment group rats were injected with testosterone propionate (25 mg/kg) immediately after HIBD. Phosphacan and NG2 expression in the cortex and the hippocampus was detected with the immunohistochemical method 24 and 72 hrs and 7 and 10 days after hypoxia-ischemia (HI). The ultrastructure and neurite regeneration of neurons in the cortex and the hippocampus were observed under a transmission electron microscope. RESULTS: The neurite regeneration was obvious in the sham-operated group, but seldom in the HIBD group. The androgen treatment group showed increased neurite regeneration compared with the HIBD group. There were fewer phosphacan and NG2 positive cells in the cortex and the hippocampus in the sham-operated group. Phosphacan and NG2 expression in the cortex and the hippocampus was observed at 24 hrs, increased at 72 hrs, and peaked at 7 days after HI in the HIBD group and remained at a higher expression 10 days after HI than in the sham-operated group. The levels of phosphacan and NG2 expression in the cortex and the hippocampus in the androgen treatment group were significantly reduced compared with those in the HIBD group 24 and 72 hrs and 7 and 10 days after HI (P<0.01). CONCLUSIONS: Phosphacan and NG2 may be important inhibitory factors for neurite regeneration following HIBD in neonatal rats. The neuroprotection of androgen against neonatal HIBD is produced possibly through an inhibition of phosphacan and NG2 expression.

Neonatal respiratory failure: a 12-month clinical epidemiologic study from 2004 to 2005 in China.

OBJECTIVES: In the past decade, neonatal special care services in China have been established, during which time various therapies for neonatal respiratory failure have been introduced. The objective of this study was to investigate the incidence, management, outcome, and cost of neonatal respiratory failure treated by mechanical ventilation in 23 tertiary NICUs of major hospitals in southeastern and midwestern China. METHODS: Data were collected over 12 consecutive months from 2004 to 2005 for neonates with neonatal respiratory failure. Eligible infants were those who required endotracheal intubation and mechanical ventilation and/or nasal continuous positive airway pressure for at least 24 hours and infants who died within 24 hours of ventilation during their first 7 days of life. Data characterized demographics, antenatal and perinatal history, illness severity score, primary disease, respiratory care, complications, survival, and clinical burden. RESULTS: From a total of 13,070 NICU admissions, there were 1722 (13.2%) cases of neonatal respiratory failure with respiratory distress syndrome, pneumonia/sepsis, and meconium aspiration syndrome as major causes. For infants who survived until discharge, the median length of ventilation was 70 hours. Overall, in-hospital mortality for neonatal respiratory failure was 32.1%. Logistic regressions showed that lower gestational age, vaginal delivery, fetal distress before delivery, presence of a major anomaly, and high severity score in preterm infants were associated with an increased risk for death. In term and postterm infants, only the presence of a major anomaly and a high severity score were significant risk factors for death. Mean length and cost of stay in hospital were 19.2 +/- 14.6 days and 14,966 +/- 13,465 Yuan in the survivors. CONCLUSIONS: Neonatal respiratory failure in the NICU of the provincial cities of China has high mortality and cost that are linked to geographic variability, a male predominance, and low proportion of very preterm infants, characteristic of sociocultural confounding background.

Carboxylated, heteroaryl-substituted chalcones as inhibitors of vascular cell adhesion molecule-1 expression for use in chronic inflammatory diseases.

Starting from a simple chalcone template, structure-activity relationship (SAR) studies led to a series of carboxylated, heteroaryl-substituted chalcone derivatives as novel, potent inhibitors of vascular cell adhesion molecule-1 (VCAM-1) expression. Correlations between lipophilicity determined by calculated logP values and inhibitory efficacy were observed among structurally similar compounds of the series. Various substituents were found to be tolerated at several positions of the chalcone backbone as long as the compounds fell into the right range of lipophilicity. The chalcone alpha,beta-unsaturated ketone moiety seemed to be the pharmacophore required for inhibition of VCAM-1 expression. Compound 19 showed significant antiinflammatory effects in a mouse model of allergic inflammation, indicating that this series of compounds might have therapeutic value for human asthma and other inflammatory disorders.

Discovery of novel heteroaryl-substituted chalcones as inhibitors of TNF-alpha-induced VCAM-1 expression.

Novel chalcone derivatives have been discovered as potent inhibitors of TNF-alpha-induced VCAM-1 expression. Thienyl or benzothienyl substitution at the meta-position of ring B helps boost potency while large substitution at the para-position on ring B is detrimental. Various substitutions are tolerated on ring A. A lipophilicity-potency relationship has been observed in several sub-series of compounds.

Lead discovery of alpha,beta-unsaturated sulfones from a combinatorial library as inhibitors of inducible VCAM-1 expression.

alpha,beta-Unsaturated sulfones have been discovered from a combinatorial library as leads for a new series of inhibitors of inducible VCAM-1 expression. Although not essential, further conjugation of the sulfonyl group to another vinyl group or a phenyl group increases the potency dramatically.