Patent Ductus Arteriosus of the Preterm Infant

Abstract

Postnatal ductal closure is stimulated by rising oxygen tension and withdrawal of vasodilatory mediators (prostaglandins, nitric oxide, adenosine) and by vasoconstrictors (endothelin-1, catecholamines, contractile prostanoids), ion channels, calcium flux, platelets, morphologic maturity, and a favorable genetic predisposition. A persistently patent ductus arteriosus (PDA) in preterm infants can have clinical consequences. Decreasing pulmonary vascular resistance, especially in extremely low gestational age newborns, increases left-to-right shunting through the ductus and increases pulmonary blood flow further, leading to interstitial pulmonary edema and volume load to the left heart. Potential consequences of left-to-right shunting via a hemodynamically significant patent ductus arteriosus (hsPDA) include increased risk for prolonged ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis or focal intestinal perforation, intraventricular hemorrhage, and death. In the last decade, there has been a trend toward less aggressive treatment of PDA in preterm infants. However, there is a subgroup of infants who will likely benefit from intervention, be it pharmacologic, interventional, or surgical: (1) prophylactic intravenous indomethacin in highly selected extremely low gestational age newborns with PDA (<26 + 0/7 weeks' gestation, <750 g birth weight), (2) early targeted therapy of PDA in selected preterm infants at particular high risk for PDA-associated complications, and (3) PDA ligation, catheter intervention, or oral paracetamol may be considered as rescue options for hsPDA closure. The impact of catheter-based closure of hsPDA on clinical outcomes should be determined in future prospective studies. Finally, we provide a novel treatment algorithm for PDA in preterm infants that integrates the several treatment modalities in a staged approach.

Conflict of interest statement

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Copyright © 2020 by the American Academy of Pediatrics.

Figures

FIGURE 1

Factors affecting postnatal DA closure and preterm PDA. A and B, Postnatal DA closure (A) and preterm DA patency (B) are regulated by a combination of molecular, physiologic, and structural factors. Of note, several studies have identified distinct variants in CYP2C9*2 that are associated with failure of PDA closure in response to indomethacin., cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; O2, oxygen.

FIGURE 2

Determinants of risk for preterm infants with an hsPDA. AAO, ascending aorta; ACA, anterior cerebral artery; CPAP, continuous positive airway pressure; CW, continuous wave; DAO, descending aorta; Fio2, fraction of inspired oxygen; HFNC, high-flow nasal cannula; ID, inner diameter; LA/Ao, left atrium to aortic root diameter ratio; LPA, left pulmonary artery; LVEF, left ventricular ejection fraction; MPA, mean pulmonary artery; MV, mechanical ventilation; NIRS, near-infrared spectroscopy; NIV, noninvasive ventilation; PEEP, positive end-expiratory pressure; PIP, positive inspiratory pressure; PLAX, parasternal short axis; PSAX, parasternal short axis; RI, resistance index; Spo2, pulse oxygen saturation; Vmax, maximum velocity.

FIGURE 3

Treatment algorithm of PDA in the preterm infant. The proposed treatment algorithm incorporates the following 4 main treatment categories into a stepwise approach: (1) early targeted prophylaxis, (2) targeted therapy of asymptomatic infants (a Some units attempt for early catheter intervention (eg, after the first failed pharmacologic treatment cycle. ELBW, extremely low birth weight (<1000 g); FiO2, fraction of inspired oxygen; GA, gestational age.