| OBJECTIVE In 2004-2007, two multicenter epidemiologic surveys (Pediatrics 2008, Neonatology 2010) from the Collaborative Study Group of Neonatal Respiratory Diseases showed that the incidence and mortality of neonatal respiratory failure (NRF) were 13.2-16.9% and 32%, respectively, in the provincial and sub-provincial NICUs, at costs equivalent to total annual income of an urban family. A trend of increasing capacity, use of continuous positive airway pressure (CPAP) and surfactant therapy was noted. With recently nationwide progression of NICU at sub-provincial tertiary centers, we questioned whether there would be a steady progression towards increased incidence and reduced mortality of NRF, and whether there were alterations in the impact of perinatal-neonatal risk factors, primary diseases pattern, clinical management, and disease burden, in these NICUs. We also assessed the outcomes of NRF in very immature infants and analyzed the clinical management of NRF in NICUs of different sizes and areas.METHODS Information on admissions with NRF was retrospectively collected from 55 NICUs in 12 consecutive months in 2008. NRF was defined as respiratory disorder requiring respiratory support with either mechanical ventilation (MV) or nCPAP(?)24 hours. Outcomes impacted by perinatal-neonatal risk factors, primary diseases, efficiency in clinical management, and burden of care were also assessed.RESULTS1. General analysis of NRFThere were 6,864 NRF (19.7% of total admissions), with 62.8%(n=4,315) as preterm and 2.3%(n=159) as extremely preterm with gestational age (GA)<28 weeks, 16.4%(n=1,127) as birth weight (BW)<1,500 g. Major underlying diseases of NRF were respiratory distress syndrome (RDS,43.9%), pneumonia/sepsis (21.7%), aspiration of amniotic fluid(14.7%), transient tachypnea (8.1%), and meconium aspiration syndrome (MAS,7.0%). In those with birth weight (BW)<1,500 g,5.6% had peri- and intraventricuar hemorrhage,6.3% bronchopulmonary dysplasia,3.3% necrotizing enterocolitis,4.7% retinopathy of prematurity and 1.7% periventricular leukomalasia. Surfactant was given to 26.8% of NRF. Mean (SD) first dose of surfactant administration was 109±40 mg/kg (Curosurf(?)). Respiratory support was given to 94.4% of NRF in the first 3 days of life,42.1% were treated by nCPAP only, 30.8% by MV, and 27.1% by both. High frequency oscillation (HFOV) was applied in 5.1% of NRF. Of NRF infants treated by MV initially, synchronized intermittent mandatory ventilation (SIMV,53.5%) and assist/control ventilation (A/C,26.2%) were the most common modes. The median (interquartile range) ventilation time in the survivors was 72 hours (48-116) and their length and costs of hospital stay were 16 days (11-24) and 11,792 Yuan (6,584-19,661), respectively. The overall mortality of NRF was 24.7%, which consisted of hospital death (8.6%) and withdrawal from the treatment (16.1%), nearly half (46.2%) infants of those giving up treatments were due to the parents'limited affordability for the high medical cost. Death rate of MAS and pneumonia/sepsis was 29.7% and 28.6%, respectively. The death rate was 41.9% in BW<1,500 g, whereas in GA at 25,26,27 and 28 weeks, it was 94.1% 70.2%,50% and 48%, respectively. Logistic regressions showed that vaginal delivery, presence of a major anomaly, delivery room resuscitation, VLBW, higher SNAPPE?score, MV, no surfactant thearpy, pneumonia/sepsis, air leak and pulmonary hemorrhage were associated with an increased risk for death.2. Characteristics and outcomes of RDSMajor underlying disease of NRF was RDS (43.9%). The mean (SD) BW was 1,915±672 g, with a GA of 32.8±3.3 weeks. Surfactant was used in 54.8% of RDS, and 64.2% in those with BW<1,500 g. The proportion of prophylactic and early rescue surfactant (<6 hours after birth) in RDS with BW<1,500g was 44.7% (365/816). The median (QR) age of RDS infants on receiving the first dose of surfactant was 5.0 hours (2.1-12) and mean (SD) dose of surfactant administration was 110+40 mg/kg (Curosurf(?)).72.4% of RDS infants were treated by nCPAP, but only 40.6% were applied to nCPAP only. The mortality of surfactant-treated RDS was 20.1% compared to 28.2% in non-surfactant-treated (p<0.001,23.8% as combined), and 40.2% compared to 47.8% in those with BW<1,500 g (p=0.035).3. Clinical management of NRF in NICUs of different regions and sizesResults from the well developed and underdeveloped regions, or provincial and sub-provincial, or types of hospitals (children's, maternity and general) indicate that, socio-economic status and the volume of NICUs had an impact on the outcomes of NRF. There were more infants withdrawal from treatment in underdeveloped regions than well developed ones, while the survival rate of NRF infants was higher in well developed regions than underdeveloped ones, but there were differences in GA, BW, adimission age, ventilation time, surfactant and nCPAP use between the two regions. At the sametime, we found the lower the NRF numbers of NICUs, the lower the incidence and the higher the mortality of NRF infants. However, the admission characteristics and SNAPPE-?of NRF infants can't explain this difference.4. Differences between the three surveysThe results revealed a new trend in the incidence, mortality and costs of NRF, representative of current status of respiratory support of NRF in the provincial and sub-provincial NICUs in 2008. Compared with the previous two surveys, this study had 731 cases of severe illness per NICU (31% increment from 2004-2005 survey), and 125 NRF/NICU (67% increment). RDS remained as the major underlying disease, but constituted 43.9% of NRF (from previous 35%). There appears improved use of CPAP (64.1% increment) and surfactant (23.2% increment) in NRF, which continuously showed efficacy in increasing the survival rate (by 8% net increment), however, on one hand, relatively low survival rate, especially in extremely premature infants, and in those of MAS and pneumonia/sepsis, remains a challenge; on the other hand, the relatively lower first dose and higher costs in surfactant-treated NRF require further effort to approach more relevant strategy as a part of standard of care with respiratory support.CONCLUSIONS1. Fifty-five NICUs from 24 provinces, autonomous regions and municipalities were enrolled in this survey, which covered 3/4 of provinces of China, and almost half were NICUs from sub-provincial tertiary centers, along with four times of NRF as targeted subjects compared with the previous nation-wide survey. Therefore, the current results provided a more objective profile of the clinical incidence, management and outcome of NRF as well as for assessment of efficiency of respiratory support in sub-provincial NICUs.2. The incidence of NRF in NICUs increased and the mortality of NRF decreased from 32% to 24.7%(a net of 7% reduction), however, relatively low survival rate, especially in extremely premature infants, and in those of MAS and pneumonia/sepsis, remains a challenge.3. There was 50%, or even lower, survival rate in the extremely immature infants whose GA were below 28 weeks and/or BW below 1,000 g, despite they were treated with increasing nCPAP and surfactant over time, which is still significantly lower than the developed countries in later 80's and early 90's.4. Results from the well developed and underdeveloped regions, or provincial and sub-provincial, or types of hospitals (children's, maternity and general) indicate that, socio-economic status and the volume of NICUs had an impact on the outcomes of NRF. |
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