China has a large population of about 1.4 billion people in 2015, accounting for around a fifth of the world population (1). According to the governmental 2010 population census, there were about 15.9 million live births in China, with a crude birth rate of 11.9 births per 1,000 population (2). With the rapid economic growth and development of China, the incidence of premature birth has shown an increasing trend, and the number of preterm infants cared for in Chinese neonatal intensive care units (NICUs) has increased (3). More NICUs are being established across the country (4). The advancement of perinatal-neonatal medicine has resulted in an increasing survival rate of preterm infants in China. However, the development of neonatology as a subspecialty is uneven among different districts and there is high variability in under-5 mortality rates, with more than 10-fold difference in infant mortality rates between under-developed areas in west China and the relatively more developed areas in east China (5,6).
In the last two decades several reports have suggested that there has been little or only marginal further improvement in preterm outcomes (7,8). This issue may stem from problems with the quality of neonatal care provided, including practice variations (9). As such, as in North America, there has been a significant focus on using quality improvement (QI) methods to improve neonatal care.
The Evidence-based Practice for Improving Quality (EPIQ) method of QI was developed in Canada by Dr. Shoo Lee, and has been implemented in NICUs across Canada. EPIQ combines the use of evidence from the published literature and outcomes data from participating hospitals with consideration of site-specific contextual factors affecting QI implementation to facilitate change (10). The method uses a network approach where sites share information and support each other through collaborative learning. In this manner, knowledge is effectively disseminated across a large number of sites, sites remain motivated, and a culture for change is created. A cluster randomized controlled trial of the EPIQ method targeting hospital acquired infection (HAI) and bronchopulmonary dysplasia (BPD) in Canadian NICUs resulted in a 32% decrease in HAI and 15% decrease in BPD among the participating sites (10). In a subsequent study targeting mortality and all five major neonatal morbidities [BPD, severe intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP), HAI, and necrotising enterocolitis (NEC)], EPIQ resulted in a 25% decrease in HAI, a 24% decrease in ROP, a 20% decreased in NEC, and a 7% increase in neonatal survival without major morbidity (11). Thus, the EPIQ method offers a comprehensive and effective approach to improving neonatal outcomes with the flexibility to be adapted to different NICU environments.
Preterm birth is the leading cause of childhood mortality in China (12,13). The mortality in very low birth weight (VLBW, birth weight <1,500 g) infants with infection is threefold higher when compared with VLBW infants without infection (14). In addition to the worsening of short-term outcomes, HAIs are associated with long-term neurodevelopmental problems that develop after discharge as a result of neurological changes caused by the infection (15).
While the immature immunity of preterm infants put them at high risk to develop infection after birth, patients admitted to a NICU with a high rate of HAI because of sub-optimal practices are at a significant disadvantage to those who have access to a NICU that implements best practices. HAIs can be reduced by seemingly simple practices changes, such as increased hand hygiene compliance, removal of ventilation devices as soon as appropriate, use of practice guidelines for the insertion and maintenance of CLs, removing vascular access when infants reach a total fluid intake of 120 mL/kg/day via nasogastric or oral feeds, and promoting breast milk feeding (16). However, the effective implementation of even simple practice changes can be difficult to achieve without a rigorous QI method. In China, very few studies have been conducted to reduce HAI in the NICU through QI methods.
The International Training Program in Neonatal-Perinatal Medicine was established in April 2004 in Shanghai. It is a joint venture of the Canadian Neonatal NetworkTM and the Children’s Hospital of Fudan University (FUCH) in Shanghai and endorsed by the Canadian Pediatric Society. This program upgraded standards of care and training at the FUCH in Shanghai, and also created unprecedented new opportunities for collaboration between Canadian and Chinese doctors and hospitals on a wide range of issues, including research (17).
With the objective of improving neonatal outcomes, we have adopted the EPIQ method and started systemic practice changes in a single center in China since 2008. Following this, we collaborated with 24 NICUs across China to reduce HAI through evidence-based practice improvement from 2015 to 2018.
Examples of QI in a single NICU
The pilot QI project was conducted in the NICU of FUCH, which is a 693-bed academic tertiary care center affiliated with Fudan University, Shanghai, China. The NICU had 30 beds, which was increased to 50 beds after moving to its new location in June 2008. All the staff neonatologists in the NICU have had 1 or 2 years of clinical training in Canadian Neonatal Network Hospitals and received standardized training about the EPIQ program before our NICU QI program started.
Ventilator associated pneumonia (VAP)
As increasing numbers of very premature babies are surviving, many of them require mechanical ventilation (MV), and VAP has become a major challenge in China. As reported previously, VAP was the most frequent nosocomial infection (NI) in our NICU, accounting for 41.3% of NI cases (18). In June 2008, relocation of our hospital to a new site prompted the implementation of a comprehensive infection control program to reduce VAP in the NICU.
A bundle of comprehensive preventive measures against VAP was gradually implemented over a 1-year period from August 1, 2008, to July 31, 2009 in our NICU following relocation to a new facility. Several measures were implemented including reinforcement of hand hygiene practices, rational waste disposal, enhancement of patient isolation and ventilator disinfection, periodic educational activities on VAP prevention, shortened duration of MV, enhanced respiratory management of patients, and rational use of antibiotics.
Of 491 patients receiving MV during the study period, 92 (18.7%) developed VAP corresponding to 27.33 per 1,000 ventilator-days in total. The VAP rate decreased from 48.84 per 1,000 ventilator-days in pre-intervention phase to 18.50 per 1,000 ventilator-days in the post-intervention phase (P<0.001). Overall mortality rate of admitted neonates significantly decreased from 14.0% to 2.7% (P<0.001).
The study (19) demonstrates that a bundle of infection control practices can effectively reduce the occurrence of VAP among neonatal patients in China.
CLABSI has been emerged as the dominant nosocomial infection among premature infants during the last decade as CLs have become routine practice in Chinese NICUs. Hence, we conducted a 3-year study to characterize CLABSIs among neonates in the NICU of FUCH and to evaluate the impact of a multifaceted evidence-based practice for improving quality program to decrease CLABSI.
The intervention measures were developed in accordance with the EPIQ method, which including enhanced hand hygiene practices, dedicated PICC teams and monitor groups, use of an all-inclusive CL cart and prepackaged kits, evaluating CLs daily and removal of non-essential CLs, and providing education and simulation training.
A total of 171 patients with CLs were observed; 29 of them developed CLABSI corresponding to 7.35 per 1,000 catheter days, with a CL utilization ratio of 37.9%. Overall CLABSI rate decreased gradually from 16.7 per 1,000 CL days in pre-intervention phase to 5.2 per 1,000 CL days in post-intervention phase (P<0.01) although the CL utilization rate increased.
This study (20) showed that a bundle of preventive measures can have a significant positive impact on CLABSI rates in Chinese NICUs. These simple, inexpensive measures can potentially be generalized to other NICUS in developing countries.
Mother’s own milk feeding (not published data)
The nutritional benefits of human milk are well-established, especially for infants born preterm. Previous research from developed countries has shown that mother’s milk feeding rates can be significantly improved by implementing structured evidence-based practices to promote mother’s milk use in the NICU (21). However, there has been a lack of QI initiatives to improve mother’s milk feeding in NICUs in China. We carried out a multi-disciplinary QI initiative aimed at increasing the prevalence of mother’s own milk feeding in infants born at <1,500 grams, and evaluated the impact of our mother’s milk promotion program by comparing the mother’s milk consumption rates and neonatal outcomes of infants before and during the initiative.
Preliminary results were positive and resulted in the establishment of a hospital-based human milk bank in the NICU at FUCH.
Implement EPIQ in Chinese NICUs through collaborative study
Based on the success of the study at a single site in FUCH, we proceeded to broaden the scope and apply the EPIQ methodology to improve outcomes in other centers across China, incorporating the lessons learned from our previous study.
Population-based data on the incidence of HAIs in Chinese NICUs are not available and the reported incidence of HAI varies greatly between different units and regions. Reported rates of HAI in the general NICU patient population (all admissions) range from 3.1% (22) to 17.2% (18,22-25). In preterm or VLBW infants the incidence of HAI is higher than in the general NICU population with reported rates ranging from 16.7% to 61.2% (24-26).
By building on our work in the FUCH NICU and the existing collaborations between the CNN and FUCH (International Training Program in Neonatal-Perinatal Medicine based in FUCH since 2004), a cluster randomized controlled trial (clinical trials ID: NCT0260015) was conducted targeting all types of HAI in 24 NICUs across China (Reduction of infection in neonatal intensive care units using the Evidence-based Practice for Improving Quality, REIN-EPIQ) with collaboration between FUCH and CNN and Maternal-Infant Care (MICare). The overall goal of the project was to evaluate the impact of the EPIQ method on HAI in Chinese NICUs using a cluster randomized controlled trial.
The baseline data from REIN-EPIQ in 2015–2016 showed that mortality and morbidity (including BPD, HAIs, IVH/PVL) of preterm infants remain high in China with significant variations among NICUs (27). The incidence of VAP in Chinese NICUs is similar to that in developed countries. However, there is substantial variability in different NICUs (28).
We anticipate that a direct result of this project will be the reduction of HAI in participating NICUs, which has the potential to have an impact on the long-term outcomes of enrolled infants including improved neurodevelopmental outcomes. A reduction in HAI will also decrease resource utilization associated with neonatal care.
Established Chinese Neonatal Network (CHNN) for national collaboration
CHNN was launched in 2018, which includes 53 NICUs in China. CHNN is a group of multi-disciplinary researchers who collaborate on research issues related to neonatal care. The Network established and maintains a high quality neonatal-perinatal database with sustainable infrastructure necessary to facilitate collaborative research.
As described above, the outcomes of patients in NICUs varied significantly. Wide variations in mortality and serious morbidities of preterm infants between NICUs exist even though the participating NICUs were all tertiary units in metropolitan cities. In China there is a great need to bring NICUs together to share knowledge and establish a formal QI process to improve neonatal outcomes and quality of care. The EPIQ method has already been tested in a single center and offers a comprehensive solution to the problem of implementing collaborative coordinated QI in China. By building on a foundation of collaborative learning and targeted practice change, implementing EPIQ in China will improve the quality of care, identify novel approaches to neonatal care and knowledge translation, and reduce the inequity that exists due to differing standards of care. The results from REIN-EPIQ showed that the incidences of severe IVH among VLBWI and ELBWI was still significantly higher than those of developed countries. The incidences of severe IVH in ELBWI and in preterm infants with gestational age ≤28 weeks were 13.5% (160/1,185) and 13.1% (368/2,800), respectively (29). Currently collaborative QI initiatives have been initiated to reduce infections in Chinese NICUs. Further QI initiatives are needed to ensure infants receive appropriate care and reduce adverse neonatal outcomes in China. Knowledge gained from this initiative will be valuable in the future for targeting other neonatal morbidities, such as NEC, BPD, ROP and IVH.
The authors acknowledge the invaluable assistance of Dr. Shoo Lee for implement EPIQ to China.
Funding: This study was funded by the China Medical Board (Grant Number: 14-194), and the Canadian Institutes of Health Research (Grant Number: CTP 87518).
Conflicts of Interest: The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
- Nations U. World population prospects: The 2015 revision, key findings and advance tables. Rep No. ESA/P/WP 241, 2015. Available online: https://population.un.org/wpp/Publications/Files/Key_Findings_WPP_2015.pdf
- National Bureau of Statistics of China. China 2010 population census data. Beijing: National Bureau of Statistics of the People’s Republic of China. Inc., 2012.
- Sun B, Shao X, Cao Y, et al. Neonatal-perinatal medicine in a transitional period in China. Arch Dis Child Fetal Neonatal Ed 2013;98:F440-4. [Crossref] [PubMed]
- Wei KL, Yang YJ, Yao YJ, et al. Epidemiologic survey on hospitalized neonates in China. Transl Pediatr 2012;1:15-22. [PubMed]
- Coordination Group for Present Situation of Neonatal Subspecialty in the Mainland of China. Present situation of neonatal subspecialty in the mainland of China: a survey based on 109 hospitals. Zhonghua Er Ke Za Zhi 2012;50:326-30. [PubMed]
- Wang Y, Li X, Zhou M, et al. Under-5 mortality in 2851 Chinese counties, 1996-2012: a subnational assessment of achieving MDG 4 goals in China. Lancet 2016;387:273-83. [Crossref] [PubMed]
- Fanaroff AA, Stoll BJ, Wright LL, et al. Trends in neonatal morbidity and mortality for very low birthweight infants. Am J Obstet Gynecol 2007;196:147.e1-8. [Crossref] [PubMed]
- Horbar JD, Carpenter JH, Badger GJ, et al. Mortality and neonatal morbidity among infants 501 to 1500 grams from 2000 to 2009. Pediatrics 2012;129:1019-26. [Crossref] [PubMed]
- Agency for Healthcare Research and Quality. Improving Health Care Quality. Rockville, MD: Agency for Healthcare Research and Quality, 2002. Report No. 02-P032.
- Lee SK, Aziz K, Singhal N, et al. Improving the quality of care for infants: a cluster randomized controlled trial. CMAJ 2009;181:469-76. [Crossref] [PubMed]
- Lee SK, Shah PS, Singhal N, et al. Improvement in neonatal outcomes of preterm <29 weeks GA: Results from a national prospective quality improvement cohort study (EPIQ2) [Abstract]. Vancouver: Annual Meeting of the Pediatric Academic Societies, 201.
- Lu R, Li X, Guo S, et al. Neonatal mortality in the urban and rural China between 1996 and 2013: a retrospective study. Pediatr Res 2016;79:689-96. [Crossref] [PubMed]
- He C, Liu L, Chu Y, et al. National and subnational all-cause and cause-specific child mortality in China, 1996-2015: a systematic analysis with implications for the Sustainable Development Goals. Lancet Glob Health 2017;5:e186-97. [Crossref] [PubMed]
- Kaufman D, Fairchild KD. Clinical microbiology of bacterial and fungal sepsis in very-low-birth-weight infants. Clin Microbiol Rev 2004;17:638-80. [Crossref] [PubMed]
- Chau V, Brant R, Poskitt KJ, et al. Postnatal infection is associated with widespread abnormalities of brain development in premature newborns. Pediatr Res 2012;71:274-9. [Crossref] [PubMed]
- Polin RA, Denson S, Brady MT, et al. Strategies for prevention of health care-associated infections in the NICU. Pediatrics 2012;129:e1085-93. [Crossref] [PubMed]
- REIN-EPIQ Study Group. Reduction of Infection in Neonatal Intensive Care Units using the Evidence-based Practice for Improving Quality (REIN-EPIQ): a Study Protocol. Chin J Evid Based Pediatr 2018;13:452-7.
- Cai XD, Cao Y, Chen C, et al. Investigation of nosocomial infection in the neonatal intensive care unit. Zhongguo Dang Dai Er Ke Za Zhi 2010;12:81-4. [PubMed]
- Zhou Q, Lee SK, Jiang SY, et al. Efficacy of an infection control program in reducing ventilator-associated pneumonia in a Chinese neonatal intensive care unit. Am J Infect Control 2013;41:1059-64. [Crossref] [PubMed]
- Zhou Q, Lee SK, Hu XJ, et al. Successful reduction in central line-associated bloodstream infections in a Chinese neonatal intensive care unit. Am J Infect Control 2015;43:275-9. [Crossref] [PubMed]
- Lee HC, Kurtin PS, Wight NE, et al. A quality improvement project to increase breast milk use in very low birth weight infants. Pediatrics 2012;130:e1679-87. [Crossref] [PubMed]
- Wu J, Wu BQ, Huang JJ, et al. Risk factors and pathogen distribution in premature infants with nosocomial sepsis. Zhongguo Dang Dai Er Ke Za Zhi 2012;14:93-6. [PubMed]
- Lam BC, Lee J, Lau YL. Hand hygiene practices in a neonatal intensive care unit: a multimodal intervention and impact on nosocomial infection. Pediatrics 2004;114:e565-71. [Crossref] [PubMed]
- Mai JY, Dong L, Lin ZL, et al. Investigation and analysis of nosocomial infection in neonates. Zhonghua Er Ke Za Zhi 2011;49:915-20. [PubMed]
- Xu XF, Ma XL, Chen Z, et al. Clinical characteristics of nosocomial infections in neonatal intensive care unit in eastern China. J Perinat Med 2010;38:431-7. [Crossref] [PubMed]
- Xing Y, Cui Y, Han T, et al. Analysis of very low birth weight infants with nosocomial infection within eleven years. Chin J Perinat Med 2011;14:39-44.
- REIN-EPIQ Study Group. Outcomes of very low birth weight infants at discharge: a multicentered cross-sectional study of 25 tertiary neonatal intensive care units in China. Chin J Perinat Med 2018;21:394-400.
- Li SJ, Yan SY, Zhou Y, et al. Ventilator-associated pneumonia among premature infants <34 weeks’ gestational age in neonatal intensive care unit in China: a multicenter study. Zhonghua Er Ke Za Zhi 2017;55:182-7. [PubMed]
- REIN-EPIQ Study Group. Severe intraventricular hemorrhage and its risk factors of very low and extremely low birth weight infants: a multi-center study. Zhonghua Er Ke Za Zhi 2019;57:258-64. [PubMed]