Each year, prematurity and low birth weight (LBW) impacts a small but significant proportion of all live births in the United States. In the United States and internationally, improving outcomes for these infants remains a high priority. Healthy people 2020 includes objectives to reduce LBW and premature births [1]. These objective include targets to reduce overall preterm births from 12.7 to 11.4% as well as specific objectives to reduce both very preterm and late preterm births by 10%, and to reduce the number of LBW (8.2–7.8%), and very LBW (VLBW) infants (1.5–1.4%) [1].
In the United States, overall infant mortality has declined from 100 per 1000 live births in 1900 to 6.05 per 1000 births in 2011 [2] while remaining one of the highest infant mortality rates among industrialized countries [3]. The development of medical and technological interventions has improved the survivability of premature and LBW infants. From 2000 to 2010 the infant mortality rate among preterm infants decreased from 37.88 deaths under age 1 per 1000 live births to 34.22 per 1000 live births, a decrease of almost 10 percent [4]. For infants born under 32 weeks, the mortality rate decreased almost 8% from 2000 to 2010, from 180.95 per 1000 live births to 165.57 per 1000 live births [4]. While overall infant mortality rates have decreased, they are still comparatively high and short- and long-term morbidities associated with prematurity and LBW have persisted [4, 5]. There are a number of potential morbidities that affect nearly every organ system and include conditions such as poor neurodevelopmental outcomes, retinopathy of prematurity, severe intraventricular hemorrhage, hearing loss, bronchopulmonary dysplasia, respiratory distress syndrome, patent ductus arteriosus, necrotizing enterocolitis, and sepsis are associated with LBW and prematurity, and may be complicated by interventions to improve mortality such as ventilation [5–13], transfusions and catheters. Common interventions provided during a typical neonatal intensive care unit (NICUs) hospitalization.
Monitoring both short- and long-term outcomes of infants affected by preterm birth, LBW and/VLBW is critical to advancing scientific and medical knowledge with respect to the development of more effective treatment guidelines, to improve quality of these treatments over time, and to minimize short- and long-term morbidities. Effective research can also inform integrated health care practices where surviving infants are treated through childhood and even into adulthood. However, studying infants affected by prematurity or LBW can be challenging due to small, single-center sample sizes, unknown quality of some administrative data, or limited availability of long-term follow-up data.
To address these challenges, a number of large-scale databases were developed to allow structured study of premature and LBW infants, including but not limited to those admitted to the NICU. In 1997, Wright and Papile [14] summarized existing neonatal databases and their uses. Their review provided detailed descriptions of four neonatal databases: the Kaiser Permanente Neonatal Minimum Data Set (KPNMDS), the Vermont Oxford Network (VON), the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN), and the National Perinatal Information Center (NPIC). Since 1997, there have been tremendous advances in neonatal care that have contributed to declines in infant mortality associated with prematurity or LBW, including the use of high-frequency ventilation and cooling caps. These clinical improvements are accompanied by an increasing number of studies aimed at evaluating neonatal intervention, understanding the progression of disease, and investigating outcomes of those infants affected by prematurity or LBW. The purpose of our current review is to provide an update on three of these databases, and to describe their use in epidemiologic studies, the study of specific clinical conditions associated with prematurity and LBW, and clinical outcomes for those infants.
Existing databases
Of the four originally described by White and Papile, we are reviewing research progress using three, KPNMDS, NICHD NRN, and VON [14]. The National Perinatal Information Center was not included in our review as their focus is on the perinatal period and not premature or LBW infants. The three databases have varying program goals, funding sources, strategies for data collection, and length of follow-up, but all focus on improving medical knowledge about and the quality of care provided to premature, LBW, and NICU admitted infants.
The Kaiser Permanente Neonatal Minimum Data Set (KPNMDS) originated in 1992 and is internally funded through the Kaiser Permanente (KP) system [15]. The KPNMDS was developed to obtain reliable data about the NICU admission, and to support research and quality improvement efforts. The database includes both inborn and outborn admissions to at least six KP NICUs in Northern California, although the total number of NICUs participating in KPNMDS has increased since Wright and Papile described the database in 1997. The KPNMDS includes data on the full NICU admission, and some prospective studies using KPNMDS data extend follow-up for months or years after discharge from the NICU. The primary criterion for inclusion in the database is NICU admission, not a specific birth weight or gestational age. KPNMDS supports both retrospective and prospective studies. Although KPNMDS focuses on NICU admissions, it is relevant to our study as many premature and LBW infants are treated in NICUs.
The Vermont Oxford Network (VON) originated in 1989 and seeks to “improve the quality and safety of medical care for newborn infants and their families through a coordinated program of research, education, and quality improvement projects” [16]. VON maintains two international databases, the very low birth weight database and the expanded database, with a total of over two million infant cases [16]. The very low birth weight database includes inborn and outborn (if admitted within 28 days of birth) infants with birth weights below 1500 g or gestational ages between 22 weeks 0 days and 29 weeks 6 days [17]. The Expanded Database includes all infants from the very low birth weight database as well as infants born at more than 1500 g and admitted to a NICU at a participating center, or “who die at any location in the center within 28 days of birth without first having gone home” [17]. In 2012, VON reported 369 centers reporting data on 153,093 infants into the expanded database, and 909 centers reporting data on 60,007 infants into the VLBW database [17]. VON members pay an annual membership fee and are eligible to use the data for studies, given strict adherence to data use guidelines set forth by VON leadership [18]. In general, VON includes infant data through discharge, death, or one year of age although some prospective studies using VON have longer follow-up periods. VON supports both retrospective and prospective studies. NICUs may apply to participate in VON using a membership application and must pay a membership fee.
The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN) began in 1986 and includes a registry to house data from multiple clinical trials funded through NICHD. NICHD supports the NRN financially. Originally, the NRN registry included data for inborn and outborn infants having a birth weight between 401 and 1500 g [14]. Since 2008, the database has included only inborn infants with a gestational age between 22 0/7 to 28 6/7 weeks and/or a birth weight between 401 and 1000 g [19]. It also includes follow-up data at 18–26 months, depending on the year of study and if the participating study site(s) assessed outcomes at such age as part of their research protocol [14, 19]. As of August 1, 2014, the NRN website listed 20 participating sites [20]. NICHD NRN supports both retrospective and prospective studies, specifically clinical intervention and epidemiologic studies funded through NICHD. Participation in the NICHD NRN requires funding through NICHD, which is typically provided through a competitive grant process.
All three databases use standardized forms and definitions for data submission by participating sites. In general, data use is open to participating sites contributing data to the database as long as database-specific requirements are met.
These databases have continued to expand and become more widely used since they were first reviewed in 1997. In the sections below we provide a summary of how the databases are being used to advance scientific and clinical knowledge about the epidemiology of prematurity and LBW and the clinical treatment of those infants. We focus specifically on database use in studies published in the peer-reviewed literature and provide aggregate information on study designs and areas of clinical focus. Our purpose is to offer clinical and health services researchers insight into how research on preterm and LBW infants has evolved, and to offer strengths and opportunities for continued research using these and other databases.
