Multicenter Prospective Clinical Epidemiologic Study On Neonatal Acute Respiratory Disorders

During the last two decades, a series of randomized clinical trials (RCTs) aimed to improve the outcomes of high-risk neonates had been carried out. These studies consistently bring new evidence into neonatal clinical practice, support the continuous and sustained development of neonatology. However, there is few RCT study in clinical neonatology conducted in China. In 2001-2003, the clinical trial on neonatal respiratory failure based on RCT conception was carried out for the first time. During the implementation process, the researchers can strongly feel the poor compliance of the participating centers in accordance with the pre-designed research protocol. The condition seems not ripe for initiating interventional clinical trial at that time in China. Besides that, the researchers recognized that the descriptive survey should be the first step towards the multicenter clinical trial. From then on, they switched their research direction to descriptive studies. Therefore, the first part of this dissertation is a clinical epidemiology survey of neonatal respiratory failure (NRF) in Hebei Province. The second part is an area-based study of live births in Julu County in Hebei. We hope, by this way, we can rich the perinatal epidemiology data, explore an effective way to improve the perinatal care level in this area, and develop the base of neonatal clinical epidemiology in China.Part I Neonatal respiratory failure in 14 NICUs in Hebei:a multicenter clinical epidemiologic studyBackground NRF is the most common reason for neonates requiring intensive care. To some extent, the outcomes of NRF neonates can reflect the quality of intensive care. Incidence and mortality of NRF in neonatal intensive care units (NICUs) at national and provincial level are 13.2%and 32.1%, respectively. Mean length and cost of stay in hospital were 19±15 days and 14,966±13,465 Yuan in the survivors. [Qian LL et al. Pediatrics.2008; 121 (5); e1115-e1124]. However, it remains unclear what these NRF figures are at sub-provincial tertiary centers for neonatal special care in the economically underdeveloped region in mid China.Objective To provide a profile of the incidence, mortality, risk factors, primary diseases, disease burden of NRF in regional neonatal centers representative of average levels in Hebei Province of China. To explore potential ways of improving the efficiency and efficacy of NICU care in this area.Methods Information on admissions with NRF (within 7 days of postnatal age) to 14 tertiary level III NICUs in sub-provincial city hospitals was prospectively collected from July 1,2007 to June 30,2008. NRF was defined as requiring tracheal mechanical ventilation (MV) or nasal continuous positive airway pressure (nCPAP). Children's Hospital of Fudan University designed and initiated this study. Coordination center for this study was based at Hebei Provincial Children's Hospital. Center staffs were in charge of the data check, establishment of the thorough database using Microsoft Excel. Data analysis was conducted using software SPSS version 16.0.Results Over the 12-month study period, a total of 1875 infants were enrolled in the 14 participating hospitals. The incidence of NRF in these NICUs was 16.9%. There were 92 infants met the inclusion criteria but mechanical ventilation was not established because of parental decision. Mean (SD) gestational age (GA) of the study population was 35.0±4.0 weeks,62.5%were preterm (GA<37 weeks) and only 1.6% were extremely preterm (GA<28 w). Mean birth weight (BW) was 2267±804 g and 64.3%of them had BW<2500 g. Of the studied population,22.2%were small for gestational age newborns (SGA),92.8%were admitted within the first 2 days of life. Male/female ratio of NRF infants was 2.6:1.0. Primary diseases requiring assisted ventilation were respiratory distress syndrome (RDS,44.2%), aspiration of amniotic fluid (AAF,24.1%), meconium aspiration syndrome (MAS,7.7%), pulmonary infection (PI,8.4%), transient tachypnea of neonates (TTN,5.0%) and apnea of prematurity (2.9%). Persistent pulmonary hypertension of neonate (PPHN) was diagnosed in 118 infants (6.3%). Of all infants with NRF,538 (28.7%) received surfactant. The percentage of surfactant use in RDS was 55.6%. CPAP was used in 73.3%, only CPAP in 51.0%, conventional mechanical ventilation (CMV) in 47.5% and high frequency oscillatory ventilation (HFOV) in 1.6%of the studied infants. Pressure-control ventilation (PCV) was the most commonly used modality. For infants who survived before discharge, the ventilation time was 96±61 hours, mean length of stay in hospital and costs were 16±10 days and 12,390±8,905 Chinese Yuan (CNY), respectively. The lower BW, the higher cost needed. The mortality of NRF was 31.4% including hospital death (8.1%) and withdrawal from the treatment (23.3%). Univariate logistic regression revealed the following statistically significant risk factors for death:low GA, SGA, later admission,5 min Apgar≤7, lack of prenatal care, presence of a major anomaly, low revenue income, low NICU volume, high SNAPPE-II. Among infants with BW>2000 g, a significant reduction in mortality for the inborn compared with the outborn. Wide variation in NICU volume, clinical practice and outcomes of NRF were observed among centers.Conclusions Our findings serve as useful reminder that, although rescue surfactant and CPAP as adjunctive therapies to conventional mechanical ventilation has been widely used for NRF infants in Hebei, the mortality among full-term and moderate-sized low-birth-weight neonates remains very high. Large quality improvement aimed to decrease the mortality of NRF under resource limited condition is therefore urgently required.Part II A 12-month prospective survey of the perinatal characteristics of live births in Julu County, HebeiBackground Knowledge of real epidemiological data allows people to assess possible changes in the occurrence of pathology, to evaluate the effectiveness of new strategies for its prevention and treatment, and to plan the distribution of economic resources. Despite the sample survey and retrospective study, there is a paucity of area-based prospective study on the perinatal data of live births in China. We therefore conducted an epidemiology survey to explore the perinatal characteristics, incidence of neonatal acute respiratory disorders (ARD) and the short-term outcomes of live births based on the population of Julu County in Hebei Province.Objective To provide a profile of the demographic characteristic of live births and the pattern of perinatal care in Julu County in China, where levels of economy and perinatal care were both underdeveloped. Methods As almost all deliveries were in three local county hospitals (serving for about 366619 residents of the county), the survey was carried out in these hospitals. We prospectively collected the records of all live births delivered in September 1, 2007 to August 30,2008. We then excluded babies whose usual home address was not in this county. The prenatal and demographic data of each newborn were collected in a standardized form (Form 1), while a second form (Form 2) about the postnatal care was completed for newborns who admitted to the neonatology ward. Coordination center for this study was based at Hebei Provincial Children's Hospital. Data analysis was conducted using software SPSS version 16.0.Results There were 5822 live births in these hospitals during this period. Mean (SD) gestational age (GA) of the studied population was 39.7±1.6 w, the prematurity rate was 4.5%. Mean (SD) BW was 3348±503 g, LBW (BW<2500 g) accounted for 3.8% of the total births. Male-to-female ratio was 1.16:1.00. LGA, SGA and multibirths represented 22.8%,6.5%and 2.8%of the studied population, respectively. The overall cesarean section rate was 30.2%, of which 68.6%was elective c-section. There were 8.4%of infants had antenatal fetal distress,13.4%were born through meconium stained amniotic fluid, the 1-minute Apgar score was found to be lower than 7 in 5.9%. Over fifty percent (53.7%) of infants born at≤34 weeks received antenatal steroids. Mean age of mothers was 27.0±4.0 years. About 11.0%deliveries had significant prenatal risk factors such as gestational hypertension (4.6%), history of spontaneous abortion or stillbirth (2.2%) and premature rupture of membrane (2.1%).A total number of 745 infants (12.8%of live births) were admitted to local neonatal wards within 7 days of postnatal life, of which 24.2%was prematurity. Postnatal asphyxia was the major reason for admission to a neonatal ward (48.3%),19.3%were because of the disorders related to preterm. Acute respiratory disorder was developed in 6.3%(364/5822) of the infants. The incidence of AAF, MAS, TTN and RDS was 3.4%,1.5%,0.6%and 0.5%, respectively. The main method of oxygen administration to infants was through nasal cannulae or incubator; only 30 were treated with nCPAP. No surfactant treatment or conventional mechanical ventilation was available. The mean length of hospital stay and cost were 7±6 days and 1558±1723 CNY, respectively. Sixteen infants died in the delivery room, while 28 died before discharge from the hospital. Only 9 infants were transported to other medical centers for level III intensive care. Thus the neonatal mortality rate in this county was about 7.6/1000 (44/5822). Compared with the infants delivered by vaginal method, there were more infants delivered by c-section required postnatal care. No significant difference was found in the occurance of oxygen supplementation and mortality between the two groups (P>0.05).Conclusion This study provided the area-based perinatal data of live births and neonatal mortality in condition of lacking advanced prenatal care and special neonatal care for the first time. Neonatal respiratory disorders related to perinatal asphyxia are still serious clinical problems in this county. Upgrading perinatal and neonatal intensive care service should be considered to provide higher level of prevention and rescue for those fetuses and newborns at high risk of death.