Antecedents of Bronchopulmonary Dysplasia

BACKGROUND:

The Phenobarbital Prophylaxis for Neonatal Intracranial Hemorrhage Study was a clinical trial supported by the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS), and enrolled 280 infants at three Harvard Neonatal Intensive Care Units between June 1981 and April 1984. Babies were recruited for the study if their birth weights were 1,750 grams or less, they had no demonstrable intraventricular hemorrhage by cranial ultrasound and they required intubation within the first twelve hours of life. Data collected included maternal history, infant health status, and events of hospitalization.

The Antenatal Risk Factors for Intraventricular Hemorrhage Study, also funded by NINCDS, was composed of 520 infants, at or less than 1,500 grams birth weight who were born at two Harvard teaching hospitals between July 1984 and September 1986. Babies were enrolled if they were alive when their mothers were interviewed, usually 24-48 hours after delivery. Procedures in the delivery room and findings on early examinations were recorded. Information about the first five days of life was collected daily.

Bronchopulmonary dysplasia/chronic pulmonary disease of prematurity is a substantial long-term problem in survivors of neonatal intensive care. This disorder is seen in 15 to 35 percent of surviving infants whose birth weight was less than 1,500 grams. It is estimated that 5 percent of all neonatal intensive care unit admissions develop the affliction. Affected infants require prolonged neonatal intensive care unit (NICU) hospitalizations.

When the study was begun in 1988, infants with BPD who survived to NICU discharge required home oxygen therapy for months to years. In addition, they had a 50-69 percent chance of re-hospitalization and an 11-36 percent probability of death in the first year of life. Although improvement with age was often seen, pulmonary function abnormalities persisted into late childhood or beyond in at least 75 percent. Among other associated morbid sequelae were myocardial and pulmonary vascular dysfunction, cor pulmonale, systemic hypertension, growth failure, and neurodevelopmental abnormalities. Pathologic studies showed structural pulmonary and myocardial abnormalities in the most severely affected infants.