Historical Perspectives

Abstract

When pharmacologic closure of patent ductus arteriosus (PDA) in the preterm infant using indomethacin was introduced in 1976, there was a paucity of knowledge about the factors controlling the caliber of the ductus arteriosus both before and after birth. Additionally, mortality and morbidity of prematurity (associated with what was then usually referred to as hyaline membrane disease) was remarkably high in the early 1970s. As early as the 1950s, some neonatologists recognized PDA as a complication of what later became designated as “respiratory distress syndrome” (RDS), although it was not until the advent of intermittent mandatory ventilation (IMV) and continuous positive airway pressure (CPAP) that the concept gained prominence. Patency of the ductus appeared to be a major complication, especially in the smallest of preterm babies (at that time, < 1,350 g]) and usually carried a terminal prognosis. The advent of IMV and CPAP kept these small babies alive for a sufficient period of time for the patent ductus to become recognized progressively as a distinct clinical entity and an important early complication of preterm birth. Observant neonatologists noted that babies who had RDS often improved up to a point, beyond which they worsened. The usual story was that the baby experienced ventilatory failure, was treated with mechanical ventilation, and began to improve, with lower inspired oxygen requirements. After a few days, when discussions ensued about taking the baby off the ventilator, the infant’s improvement would cease. The radiographic picture changed from a clearing of the initial ground glass appearance coupled with a relatively small heart to an enlarging heart and the pulmonary edema of congestive heart failure due to a left-to-right shunt across the PDA. Beginning in the mid-1960s, aggressive surgeons advocated operative closure of the PDA in these small preterm infants, but multiple centers consistently reported unacceptably high …