Available online 1 March 2023, 151718

Author links open overlay panel, Abstract

A persistent left-to-right shunt through a patent ductus arteriosus (PDA) increases the rate of pulmonary hydrostatic fluid filtration, impairs pulmonary mechanics, and prolongs the need for respiratory support. Infants with a moderate/large PDA shunt that persists for more than 7-14 days are at increased risk for developing bronchopulmonary dysplasia (BPD) if they also require invasive ventilation for more than 10 days. In contrast, infants who require invasive ventilation for less than 10 days have similar rates of BPD no matter how long they are exposed to a moderate/large PDA shunt. Although pharmacologic PDA closure decreases the risk of abnormal early alveolar development in preterm baboons that are ventilated for 2 weeks, the findings from recent randomized controlled trials, as well as a quality improvement project, suggest that routine early targeted pharmacologic treatments, as currently employed, do not appear to alter the incidence of BPD in human infants.

Section snippetsAcute pulmonary alterations due to a patent ductus arteriosus

In preterm infants the effects of a patent ductus arteriosus (PDA) on the immature lung depends on the magnitude of the left-to-right shunt through the PDA and on the cardiac and pulmonary responses to the shunt. Diastolic dysfunction is often observed in extremely preterm infants. The immature neonatal myocardium is less distensible than at term and has impaired contractility due to a decreased proportion of contractile elements, altered calcium release, and decreased sympathetic innervation

PDA induced pulmonary alterations in preterm baboons

Preterm newborn baboons, delivered at 67% term gestation and mechanically ventilated for 2 weeks, have been used as a preclinical model to examine the effects of a PDA on pulmonary mechanics and BPD13. Baboons were either treated with a cyclooxygenase inhibitor to close the ductus on the day of birth or allowed to have a moderate size PDA left-to-right shunt persist for 2 weeks. Early closure of the PDA resulted in improved pulmonary mechanics during the study period. Exposure to a persistent

PDA and BPD in preterm infants: interpreting the results of clinical trials

In human infants, early pharmacologic PDA treatment is effective in closing the PDA and decreasing the incidence of several short-term morbidities (early hemorrhagic pulmonary edema20, 21, 22, hypotension, and the amount of early inotropic and ventilator support26,27). Whether the PDA plays a causal role in the development of BPD in human infants is still a matter of debate. This is due primarily to the discordant findings between the preclinical studies performed in baboons and the clinical

Conclusions1

Infants with a moderate/large PDA shunt are at increased risk for BPD. However, this only occurs when the shunt persists for longer than 7-14 days.

2

The relationship between PDA exposure and BPD also depends on the infant's need for respiratory support. Prolonged PDA exposure is unlikely to alter BPD rates in infants who require <10 days of intubation.

3

In risk adjusted models, targeted prophylactic indomethacin treatment did not decrease the incidence of BPD. Nor did it alter the rates of sIVH,

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