ETS1 Ameliorates Hyperoxia-Induced Alveolar Epithelial Cell Injury by Regulating the TGM2-Mediated Wnt/ß-Catenin Pathway.

PURPOSE: Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects newborns who need oxygen therapy, and high-concentration oxygen therapy may cause neonatal morbidity and mortality in newborns. E26 oncogene homologue 1 (ETS1) and transglutaminase 2 (TGM2) have been reported to be associated with lung cell injury. However, the mechanism of ETS1 in regulating BPD is still unclear. METHODS: Hyperoxia-induced A549 cells to simulate hyperoxia-induced alveolar epithelial cell injury. MTT assays and colony formation assays were performed to investigate the proliferation of A549 cells. Flow cytometry was carried out to quantify the apoptosis of A549 cells. The expression levels of ETS1 and TGM2 were quantified by qRT-PCR. The protein expression levels of ETS1, TGM2, ß-catenin, c-Jun and MET were measured by western blot. Overexpression of ETS1, overexpression of TGM2, overexpression of ETS1 with downregulation of TGM2 and overexpression of TGM2 with inhibition of Wnt/ß-catenin pathway were performed to investigate the role of ETS1, TGM2 and Wnt/ß-catenin pathways in hyperoxia-induced alveolar epithelial cell injury. RESULTS: Hyperoxia decreased the proliferation and promoted the apoptosis of cells in a time-dependent manner. Moreover, overexpression of ETS1 rescued the effect of hyperoxia on proliferation and apoptosis. In addition, overexpression of TGM2 participated in the regulation of hyperoxia-induced proliferation and apoptosis. ETS1 regulated hyperoxia-induced alveolar epithelial cell injury through the Wnt/ß-catenin pathway via TGM2. CONCLUSION: ETS1 ameliorates hyperoxia-induced alveolar epithelial cell injury through the TGM2-mediated Wnt/ß-catenin pathway.

[A multicenter survey of antibiotic use in very and extremely low birth weight infants in Hunan Province].

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (rs=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (rs=0.196, P<0.01). CONCLUSIONS: Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.

[Clinical epidemiological characteristics of neonatal respiratory failure: an analysis of 1,108 neonates].

OBJECTIVE: To investigate the clinical epidemiological characteristics of neonatal respiratory failure in 1,108 neonates, and to provide a reference for improvement in clinical treatment and multicenter clinical studies. METHODS: The clinical data of 1,108 neonates with respiratory failure were collected with questionnaires, and statistical analysis was performed for the epidemiological indices including primary diseases, clinical therapeutic methods, treatment outcome, and fatality. RESULTS: In all the neonates with respiratory failure, the median gestational age was 37 weeks+1 day, the median birth weight was 2,600 g, the median age in days on admission to neonatal intensive care unit was 0.71 days (17 hours), and the boy/girl ratio was 3.1:1. The major primary diseases were respiratory distress syndrome (30.51%), pulmonary infection/sepsis (23.55%), and wet lung (13.18%). Of all the neonates, 48.64% received nasal continuous positive airway pressure (nCPAP), 12.81% received high-frequency oscillatory ventilation, 13.45% received pulmonary surfactant, and 8.66% received nitric oxide inhalation therapy. The fatality was 24.19%. CONCLUSIONS: The major primary disease for neonatal respiratory failure is respiratory distress syndrome. Pulmonary surfactant, nCPAP, high-frequency oscillatory ventilation, and nitric oxide inhalation therapy are major therapeutic methods for neonatal respiratory failure, but neonatal respiratory failure still has a high fatality.

[Neurodevelopmental outcomes of extremely low birth weight and very low birth weight infants and related influencing factors].

OBJECTIVE: To investigate the neurodevelopmental outcomes of extremely low birth weight (ELBW) and very low birth weight (VLBW) infants at a corrected age (CA) of 18 months and related factors influencing the outcomes. METHODS: The ELBW and VLBW infants who were admitted to the neonatal intensive care unit, survived, and discharged between January 2013 June 2014 were enrolled. These infants were followed up at CAs of 40 weeks and 1, 3, 6, 12, and 18 months to evaluate the neurodevelopmental outcomes. According to the neurodevelopmental status, the infants were divided into normal and abnormal neurodevelopment groups. The differences in clinical data were compared, and the risk factors for abnormal neurodevelopment in ELBW and VLBW infants were analyzed. RESULTS: A total of 338 ELBW and VLBW infants were enrolled, and 15 died during hospitalization. At the CA of 18 months, 145 infants (44.9%) survived and had complete follow-up data, 75 (23.2%) died, and 103 (31.9%) were lost to follow-up. Of the 145 infants who survived and had complete follow-up data, 71 (49.0%) had neurodevelopmental impairment (NDI), and 3 (2.1%) had cerebral palsy. No infants experienced visual damage with blindness in one or both eyes or hearing loss with a need for hearing aid. The logistic regression analysis showed that bronchopulmonary dysplasia (BDP) (OR=3.530, P<0.001) and sepsis (OR=2.528, P=0.035) were independent risk factors for NDI in ELBW and VLBW infants, and the incidence of NDI increased with the severity of BDP. CONCLUSIONS: Sepsis and BPD, especially severe BPD, are risk factors for NDI in ELBW and VLBW infants.

Validation of the Chinese Empowerment of Parents in the Intensive Care (EMPATHIC-30) Questionnaire Among Parents in Neonatal Intensive Care Units: A Prospective Cross-Sectional Study.

Background: There are no specific validated questionnaires assessing satisfaction of family-centered care experienced by parents of infants hospitalized in Chinese Neonatal Intensive Care Units (NICU). Aim: To adapt and test the reliability and validity of the Chinese version of the EMPATHIC-30 questionnaire in NICU settings. Methods: A prospective, cross-sectional design was adopted. The EMPATHIC-30 questionnaires were completed by parents of infants admitted to one of the four NICUs at Hunan Children's Hospital, China, between November 2018 and 2019. Inclusion criteria were parents whose infants were admitted to the NICU for at least 5 days. Exclusion criteria were parents whose children were discharged within 5 days after admission or whose infants died in the NICU. Reliability was tested with Cronbach's alpha. The congruent validity was tested using Spearman's Rank correlation analysis, and the non-differential validity was tested using Cohen's d. Results: Parents of 619 infants discharged from the NICUs completed and returned the questionnaire. Most infants were male (n = 337, 54.4%) and infants' length of stay was a median of 21 days (IQR = 14-37). Mostly, mothers completed the questionnaire (n = 523, 84.5%). The Cronbach's alpha values of the five individual domains were between 0.67 and 0.95, and the alpha of the total questionnaire was.90, providing an adequate internal consistency. Congruent validity was measured by correlating the five domains with four standard satisfaction scales, documenting a weak correlation (r s -0.025-0.327). Non-differential validity showed some significant effect size between four binary variables (mechanical ventilation, unplanned admission, admission after surgery, length of stay) four of the five domains. Conclusion: The Chinese version of EMPATHIC-30 questionnaire showed acceptable psychometric properties. This instrument might be considered a suitable instrument to measure parent satisfaction among Chinese parents whose infants are admitted to an NICU. Measuring parent satisfaction with this instrument might contribute to improving family-centered care initiatives in NICUs with Chinese parents.

Predicting the developmental outcomes of very premature infants via ultrasound classification: A CONSORT - clinical study.

OBJECTIVE: This study aimed to assess the accuracy of ultrasonic grading in determining brain injury in very premature infants and analyze the affecting factors of these neonatal morbidity and mortality, and to investigate the relationship between serial cranial ultrasound (cUS) classification and Mental Developmental Index (MDI)/Psychomotor Developmental Index (PDI) in premature infants. METHODS: A total of 129 very preterm infants (Gestational Age ≤ 28 weeks) were subjected to serial cUS until 6 months or older and classified into 3 degrees in accordance with classification standards. The MDI and PDI (Bayley test) of the infants were measured until the infants reached the age of 24 months or older. The consistency between Term Equivalent Age (TEA)-cUS and TEA- magnetic resonance imaging (MRI) was calculated. Ordinal regression was performed to analyze the relationship among severe disease, early cUS classifications, psychomotor and mental development, and death. Operating characteristic curve were used to analyze the relationship between serial cUS grades and MDI/PDI scores. RESULTS: The mortality and survival rates of 129 very preterm infants were 32.8% and 67.3%, respectively. Among the 86 surviving infants, 20.9% developed mild cerebral palsy (CP) and 5.8% to 6.9% developed severe CP. The consistency between TEA-cUS and TEA-MRI was 88%. Grades 2 and 3 at first ultrasound were associated with adverse mental (OR = 3.2, OR = 3.78) and motor (OR = 2.25, OR = 2.59) development. cUS classification demonstrated high sensitivity (79%-96%). Among all cUS classifications, the specificity of the first cUS was the lowest and that of TEA-cUS was the highest (57% for PDI and 48% for MDI). CONCLUSIONS: Moderate and severe brain injury at first ultrasound is the most important factor affecting the survival rate and brain development of very premature infants. The cUS classification had high sensitivity and high specificity for the prediction of CP, especially in TEA-cUS.

[Multicenter follow-up report of 147 premature infants with brain injuries from 6 hospitals in China].

OBJECTIVE: Sponsored by the Subspecialty Group of Neonatology of Pediatric Society, China Medical Association, more than 10 large-scale hospitals participated in the near two-year multicenter investigation for Brain Injuries in Premature Infants in China. The present study presents the follow-up results of 147 premature infants with brain injuries from 6 Third Class A Level hospitals. METHODS: All premature infants with intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL) diagnosed in the early neonatal period in the 6 hospitals were followed-up between January 2005 and August 2006. Based on the synthetic results of physical development, examination of nervous system, intelligence tests and cranial ultrasound, the premature infants with brain injuries were classified as normal development, marginal development and retarded development. RESULTS: One hundred and forty-seven premature infants with brain injuries from the 6 hospitals consisted of 141 cases of IVH and 36 cases of PVL (30 cases having IVH and PVL). Based on the synthetic follow-up results, 51.4% of premature infants with brain injuries were generally assessed as normal development, 38.4% as marginal development and 10.7% as retarded development. Among them, delayed growth in head circumference, height and weight was 13.4%; the occurrence frequency of cerebral paralysis (CP) was 7.1% in PVL grade I, 28.6% in PVL grade II and 100% in PVL grade III; 12.7% showed retarded development of intelligence; and 30% presented post-injurious changes on cranial sonography. CONCLUSIONS: The data of the multicenter follow-up can basically reflect the short-term prognosis of premature infants with brain injuries in major big cities of China. About 10% of them have retarded physical, motor-and mental developments. The long-term regular follow-up study is expected for more premature infants with brain injuries, and behavioral sequelae of brain injuries which may occur in peri-school age and adolescence should be paid particularly close attention.

Predictive Value of Cranial Ultrasound for Neurodevelopmental Outcomes of Very Preterm Infants with Brain Injury.

BACKGROUND: Compared with full-term infants, very preterm infants are more vulnerable to injury and long-term disability and are at high risk of death. The predictive value of ultrasound and imaging on the neurodevelopment is one of the hot topics. This study aimed to investigate the relationship between cranial ultrasound (cUS) variables and neurodevelopmental outcomes of very preterm infants. METHODS: Totally 129 very preterm infants (gestational age ≤28 weeks) in neonatal intensive care unit of Hunan Children's Hospital between January 2012 and November 2014 were included in this retrospective study. Serial cUS (weekly before discharge and monthly after discharge) was performed on the infants until 6 months or older. Magnetic resonance imaging (MRI) was performed on the infants at approximately the term-equivalent age. The mental developmental index (MDI) and psychomotor developmental index (PDI) were followed up until the infants were 24 months or older. The relationship between brain injury and MDI/PDI scores was analyzed. RESULTS: The consistency rate between cUS and MRI was 88%. At the first cUS, germinal matrix hemorrhage (GMH) Grades 3 and 4, hospitalization duration, and weight are significantly correlated with MDI/PDI and prognosis (MDI: odds ratio [OR] = 8.415, 0.982, and 0.042, P = 0.016, 0.000, and 0.004; PDI: OR = 7.149, 0.978, and 0.012, P = 0.025, 0.000, and 0.000, respectively). At the last cUS, gestational age, extensive cystic periventricular leukomalacia (c-PVL), and moderate and severe hydrocephaly are significantly correlated with MDI (OR = 0.292, 60.220, and 170.375, P = 0.004, 0.003, and 0.000, respectively). Extensive c-PVL and moderate and severe hydrocephaly are significantly correlated with PDI (OR = 76.861 and 116.746, P = 0.003 and 0.000, respectively). CONCLUSIONS: Very premature infants with GMH Grades 3 and 4, short hospitalization duration, and low weight have low survival rates and poorly developed brain nerves. Cerebral palsy can result from severe cerebral hemorrhage, moderate and severe hydrocephaly, and extensive c-PVL. The sustained, inhomogeneous echogenicity of white matter may suggest subtle brain injury.

Impact of family integrated care on infants' clinical outcomes in two children's hospitals in China: a pre-post intervention study.

BACKGROUND: Most Neonatal Intensive Care Units (NICUs) in China have restricted visiting policies for parents. This also implicates that parents are not involved in the care of their infant. Family Integrated Care (FIC), empowering parents in direct care delivery and decisions, is becoming the standard in NICUs in many countries and can improve quality-of-life and health outcomes of preterm infants. The aim of this study was to evaluate the impact of a FIC intervention on the clinical outcomes of preterm infants with Bronchopulmonary Dysplasia (BPD). METHODS: A pre-post intervention study was conducted at NICUs in two Chinese children's hospitals. Infants with BPD were included: pre-intervention group (n = 134) from December 2015 to September 2016, post-intervention (FIC) group (n = 115) and their parents from October 2016 to June 2017. NICU nurses were trained between July and September 2016 to deliver the FIC intervention, including parent education and support. Parents had to be present and care for their infant minimal three hours a day. The infants' outcome measures were length-of-stay, breastfeeding, weight gain, respiratory and oxygen support, and parent hospital expenses. RESULTS: Compared with control group (n = 134), the FIC group (n = 115) had significantly increased breastfeeding rates (83% versus 71%, p = 0.030), breastfeeding time (31 days versus 19 days, p < 0.001), enteral nutrition time (50 days versus 34 days, p < 0.001), weight gain (29 g/day versus 23 g/day, p = 0.002), and significantly lower respiratory support time (16 days versus 25 days, p < 0.001). Oxygen Exposure Time decreased but not significant (39 days versus 41 days p = 0.393). Parents hospital expenses in local Chinese RMB currency was not significant (84 K versus 88 K, p = 0.391). CONCLUSION: The results of our study suggests that FIC is feasible in two Chinese NICUs and might improve clinical outcomes of preterm infants with BPD. Further research is needed to include all infants admitted to NICUs and should include parent reported outcome measures. Our study may help other NICUs with limited parental access to implement FIC to enhance parental empowerment and involvement in the care of their infant.

Mortality and Morbidity of Extremely Low Birth Weight Infants in the Mainland of China: A Multi-center Study.

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

Incidence of brain injuries in premature infants with gestational age ≤ 34 weeks in ten urban hospitals in China.

BACKGROUND: There is a large number (1.5 million per year) of premature births in China. It is necessary to obtain the authentic incidences of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL), the common brain injuries, in Chinese premature infants. The present multicenter study aimed to investigate the incidence of brain injuries in premature infants in ten urban hospitals in China. METHODS: The research proposal was designed by the Subspecialty Group of Neonatology of Pediatric Society of the Chinese Medical Association. Ten large-scale urban hospitals voluntarily joined the multicenter investigation. All premature infants with a gestational age ≤ 34 weeks in the ten hospitals were subjected to routine cranial ultrasound within three days after birth, and then to repeated ultrasound every 3-7 days till their discharge from the hospital from January 2005 to August 2006. A uniform data collection sheet was designed to record cases of brain injuries. RESULTS: The incidences of overall IVH and severe IVH were 19.7% (305/1551) and 4.6% (72/1551), respectively with 18.4% (56/305) for grade 1, 58.0% (177/305) for grade 2, 17.7% (54/305) for grade 3 and 5.9% (18/305) for grade 4 in nine hospitals. The incidences of overall PVL and cystic PVL were 5.0% (89/1792) and 0.8% (14/1792) respectively, with 84.3% (75/89) for grade 1, 13.5% (12/89) for grade 2, and 2.2% (2/89) for grade 3 in the ten hospitals. The statistically significant risk factors that might aggravate the severity of IVH were vaginal delivery (OR=1.883, 95% CI: 1.099-3.228, P=0.020) and mechanical ventilation (OR=4.150, 95% CI: 2.384-7.223, P=0.000). The risk factors that might result in the development of cystic PVL was vaginal delivery (OR=21.094, 95% CI: 2.650-167.895, P=0.000). CONCLUSIONS: The investigative report can basically reflect the incidence of brain injuries in premature infants in major big cities of China. Since more than 60% of the Chinese population live in the rural areas of China, it is expected to undertake a further multicenter investigation covering the rural areas in the future.

Epidemiologic survey on hospitalized neonates in China.

OBJECTIVE: To carry out a nationwide epidemiologic survey on the neonates in urban hospitals with an attempt to understand the disease spectrum and treatment outcomes of hospitalized neonates in China. METHODS: The clinical data of 43,289 hospitalized neonates from 86 hospitals in 47 Chinese cities (22 provinces) between January 1, 2005 and December 31, 2005 were retrospectively analyzed. RESULTS: The male:female ratio was 1.73:1. Premature infants accounted for 26.2% of the hospitalized neonates, which was higher than that reported in 2002 (19.7%). The top three diseases during the neonatal period were jaundice, pneumonia, and hypoxic-ischemic encephalopathy. The incidences of pneumonia, meconium aspiration syndrome, and bilirubin encephalopathy in term infants were higher than those in premature infants, while the incidences of asphyxia, respiratory distress syndrome, and pulmonary hemorrhage in term infants were lower than those in premature infants. The incidences of asphyxia, small for gestational age infant, and wet lung were higher in neonates whose mother had pregnancy induced hypertension. The outcomes of these hospitalized neonates included: recovered, 63.9%; improved, 27.3%; discharged due to the family's own decisions, 7.6%, and died, 1.2%. Nearly half (46.4%) of the neonatal death occurred within 24 hrs after admission. CONCLUSION: The incidence of premature birth shows an increasing trend among hospitalized neonates. Since the neonatal deaths mainly occur within 24 hrs after admission, monitoring during this period should be enhanced.

Clinical and pathologic characteristics of pancreatic necrosis in critically ill children.

BACKGROUND: Pancreatic damage in critically ill patients is associated with the progressive failure of multiple organs, but little is known about its clinical characteristics. At present, no guidelines are available for the diagnosis and management of pancreatic damage. This study was undertaken to analyze the clinical and pathologic characteristics of pancreatic necrosis in critically ill children, and to find some biological markers of pancreatic damage or pancreatic necrosis. METHODS: We retrospectively reviewed the clinical data, laboratory results, and autopsy findings of 25 children, who were admitted to Hunan Children's Hospital, China from 2003 to 2009, and died of multiple organ failure. The autopsy revealed pancreatic necrosis in 5 children, in whom sectional or gross autopsy was performed. RESULTS: The 5 children had acute onset and a fever. Two children had abdominal pain and 2 had abdominal bulging, flatulence and gastrointestinal bleeding. Four children had abnormal liver function, characterized by decreased albumin and 3 children had elevated level of C-reactive protein (CRP). B-ultrasonography revealed abnormal acoustic image of the pancreas in all children, and autopsy confirmed pancreatic necrosis, which may be associated with the damage of the adrenal gland, liver, lung, heart, spleen, kidney, intestine, thymus, mediastinal and mesenteric lymph nodes and other organs. Children 1 and 2 died of acute hemorrhagic necrotizing pancreatitis (AHNP); children 3-5 died of multiple organ dysfunction syndrome (MODS) due to pancreatic necrosis. CONCLUSION: Pancreatic damage or pancreatic necrosis in critically ill children is characterized by acute onset, severity, short course, multiple organ damage or failure. It may be asymptomatic in early stage, and easy to be ignored.

Exhaled nitric oxide in neonates with or without hypoxemic respiratory failure.

BACKGROUND: Exhaled nitric oxide (eNO) is one of the airway condensate derived markers, reflecting mainly airway inflammation in asthma and other lung diseases. The changes of eNO levels as pathophysiology of neonatal hypoxemic respiratory failure (HRF) in early postnatal life have not been thoroughly studied. The present study was to establish a method for measuring eNO concentrations in neonates with or without HRF. METHODS: Twenty-two newborn infants with HRF and 26 non-NRF controls were included within the first 24 hours of postnatal life. Their eNO levels were detected with a rapid-response chemiluminescence analyzer daily during the first week of their postnatal life, and lung mechanics and gas exchange efficiency were monitored at the same time, such as pulse oxygen saturation (SpO2), inspired fraction of oxygen (FiO2) and other parameters. RESULTS: During the first two days of postnatal life, eNO values of HRF neonates were significantly higher than those of the control neonates (day 1, 7.9±3.2 vs. 5.8±1.8 parts per billion [ppb], P<0.05; day 2, 8.8±3.2 vs. 6.0±2.4 ppb, P<0.05), but there were no significant differences in the following days. With SpO2/FiO2 increasing, difference of eNO values between the HRF and non-HRF neonates became narrowed, but there was still a two-fold difference of eNO/[SpO2/(FiO2×100)] on days 5-7. CONCLUSION: We established a method for measuring eNO and found difference in neonates with or without HRF, which diminished with prolonged postnatal days, reflecting pathophysiological characteristics of HRF.

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.