Risk Factors in Bronchopulmonary Dysplasia (Newborn Lung Project)

BACKGROUND:

Despite many improvements in neonatal intensive care during the decade from 1977 to 1987, infant respiratory distress syndrome remained a major public health problem. Increasing survival among premature infants led to the emergence of BPD as the major chronic respiratory disorder of infancy. The vast majority of BPD occurs in very low birth weight infants weighing less than 1,500 grams.

Although the incidence of low birth weight births declined from 1977 to 1987, the rate of very low birth weight births remained unchanged. These infants had a relative risk of neonatal death almost 200 times greater than full-term infants. Among survivors, eight percent had evidence of chronic pulmonary disease at forty weeks of age. The Institute of Medicine reported that very low birth weight infants who survived to one year of age were hospitalized for an average of 57 days after birth versus 3.5 days for full-term infants. Up to forty percent of these infants would be re-hospitalized almost two times for an average of 16 days versus 8.7 percent of normal birth weight infants for an average of 8 days.

DESIGN NARRATIVE:

The study had a nested case-control design. In the first year of the project, the diagnosis of BPD was standardized and a scoring system developed for grading the severity of the disease. Baseline data were collected on very low birth weight neonates admitted to seven participating neonatal intensive care units. Maternal interviews were conducted for neonates surviving seven days. The purpose of the interview was to collect information which m;ight be related to a predisposition to BPD, respiratory distress syndrome, or prematurity. Specific areas addressed included familial diseases in general and respiratory diseases in particular, familial patterns of prematurity, pregnancy and birth history, circumstances surrounding delivery, environmental exposures, health habits such as smoking, and socioeconomic variables. Severity scoring and diagnosis of the infants were based on the hospital log and routine x-rays. Final analysis compared infants with BPD to those without BPD, controlling for confounders and placing special emphasis on interaction effects. Full-term neonates served as controls.

The study was renewed in 1994 in order to re-contact at age 4-5, an existing cohort of 634 children with birth weight below 1501 grams. This cohort was unique in being representative of all very low birth weight survivors in a geographic area, and in being born during a time period of rapid advances in neonatal care (Aug 1, 1988-June 30, 1991). These children were enrolled at admission to any of 6 neonatal intensive care units (NlCUs) in Wisconsin and Iowa, and had extensive data already collected. The re-contact consisted of a telephone interview with parents, including standardized functional assessment. Information on health care and major diagnoses was also collected and verified by medical record abstracting. Information on socioeconomic and insurance status was obtained. The study responded to a need for global assessment of very low birth weight survivors, since most previous studies in the United States focused on specific morbidity outcomes. Special features of already existing data included scoring of respiratory distress syndrome and bronchopulmonary dysplasia severity with new validated severity indices, baseline family health history information and perinatal data. The cohort also spanned the time period from before general availability of exogenous surfactant to its availability as an investigational new drug (8/1/89) and availability for marketing (8/1/90). The study therefore provided an opportunity to investigate the long term effectiveness of this new therapy in an unselected NlCU population. The data were analyzed to describe the overall status of the cohort, to examine trends in outcomes across the time period, to find predictors of outcome among the neonatal and socioeconomic indicators and to investigate whether there was variability between centers.

The study was renewed in 1998 to continue follow-up of the cohort of 403 very low birth weight neonatal care survivors, born during August 1988-June1991. The time period of birth includes the approval dates for surfactant therapy. Hence, the first children to be treated with surfactant in general neonatal intensive care units (NICU) are now entering school age, providing an opportunity to evaluate school performance and to assess true chronicity of respiratory limitations. A large NICU and follow-up data base on the cohort contains extensive baseline assessment of respiratory disease, neonatal treatments and diagnoses, as well as functional assessment, health status and health care utilization at ages 4-6. The addition of data up to age 10 will confirm or dispute findings that functional outcome may be lower among children born after surfactant was released for marketing, and that the prevalence of long-term respiratory problems has remained the same. The new outcome data to be collected include school performance from school records and parent and teacher questionnaires, respiratory function by peak flow meters and respiratory symptoms and medications by parent interviews and questionnaires.

The study was renewed in 2002 to continue research in the evolving risk factors and outcomes of bronchopulmonary dysplasia (BPD) and other neonatal conditions of very low birth weight (VLBW, < 1500g) infants and children. The renewal will comprehensively document the neonatal and early childhood course and outcomes of all VLBW births in Wisconsin occurring during the calendar years 2003 and 2004 (800-850 per year), using established methodology with added risk factor information to examine currently proposed inflammatory hypotheses of BPD etiology. The study will also implement and validate new diagnostic criteria for the severity of BPD developed by a recent NIH workshop.