patent ductus arteriosus

Last edited 12/2022 and last reviewed 02/2023

The ductus arteriosus is a normal vascular channel during intrauterine life. It is a large vessel with a muscular wall which courses between the pulmonary artery and the aorta.

The ductus arteriosus normally closes within the first 48 hours of life. If it remains patent longer than this it is unlikely to close spontaneously. The exception is in premature babies where closure should occur within 3 months.

A persistently patent ductus is a common congenital heart lesion, occurring either singly or in combination with other defects.

It is more common in:

• girls than in boys
• congenital rubella syndrome
• premature babies

For a hemodynamically significant PDA that does not spontaneously close, a medical or surgical intervention may be chosen to achieve ductal closure.

• procedural interventions include surgical ligation and transcatheter occlusion
• pharmacological agents include cyclooxygenase inhibitors, such as ibuprofen or indomethacin, and acetaminophen (paracetamol), which is a derivative of acetanilide with weak anti-inflammatory properties
  • a review states that there was no significant difference between paracetamol and ibuprofen or indomethacin in the PDA closure rates. However, paracetamol caused less adverse effects (6)
  • a Cochrane review however had different conclusions and states (7):
    • prophylactic indomethacin probably results in a small reduction in severe intraventricular haemorrhage (IVH) and moderate reduction in mortality and surgical PDAclosure (moderate-certainty), may result in a small increase in chronic lung disease (CLD) (low-certainty) and results in trivial differences in necrotizing enterocolitis (NEC) (high-certainty),gastrointestinal perforation (moderate-certainty) and cerebral palsy (low-certainty)
    • prophylactic ibuprofen probably results in a smallreduction in severe IVH and moderate reduction in surgical PDA closure (moderate-certainty), may result in a moderate reduction inmortality (low-certainty) and trivial differences in CLD (low-certainty) and NEC (high-certainty)
    • the evidence is very uncertain about theeffect of acetaminophen on any of the clinically-relevant outcomes

Notes:

• fetal circulation relies on the placenta, as well as on a patent ductus arteriosus (PDA)
• ductus arteriosus connects the main pulmonary artery to the proximal descending aorta, allowing the vast majority of right ventricular output to
  bypass the pulmonary circulation
• shortly after birth, with initiation of breathing and separation of the low resistance placenta, functional closure of the ductus arteriosus commences
• physiological mechanisms for closure include:
  • increased oxygen tension and decreased circulating prostaglandin (PGEQ) and prostacyclin (PGIQ)
  • generally occurs within 24 to 72 hours of birth in the term infant (3)
  • note that the ductus arteriosus frequently fails to close in the preterm infant, with an inverse relationship between gestational age and ductal patency (3)
    • failure of the ductus arteriosus to close in preterm infants is partially related to altered physiological mechanisms, including increased ductal sensitivity to the vasodilatory effects of prostaglandins and nitric oxide
    • 70% of infants born before 28 weeks' gestational age have historically received medical or surgical closure of the PDA (3)
    • infants with respiratory distress syndrome (RDS), as well as those with perinatal asphyxia, are more likely to have a significant PDA present, as are infants who receive large volumes of fluid early in their life (4)
    • likelihood of spontaneous closure of a PDA in infants less than or equal to 1500 grams remains high, reaching 85% in one cohort before discharge (5)
• expectant management in extremely premature infants was noninferior to early ibuprofen treatment with respect to necrotizing enterocolitis, bronchopulmonary dysplasia, or death at 36 weeks' postmenstrual age (8)

Reference:

• D. Hull & D.I. Johnston in Essential Paediatrics, 3rd edition, Churchill Livingstone, Edinburgh, p.138-9
• R.S. Cotran, V. Kumar and S.L. Robbins in Robbins Pathologic Basis of Disease, 4th edition, W.B. Saunders Co., Philadelphia, p.623-4
• Clyman RI. Ibuprofen and patent ductus arteriosus. New England Journal of Medicine 2000;343(10):728-30.
• Bell EF et al. Effect of fluid administration on the development of symptomatic patent ductus arteriosus and congestive heart failure in premature infants. New England Journal of Medicine 1980;302(11):598-604
• Semberoval J et al. Spontaneous closure of patent ductus arteriosus in infants </=1500 g. Pediatrics 2017;140(2):e20164258
• Katsaras, DN, Katsaras, GN, Chatziravdeli, VI, et al. Comparative safety and efficacy of paracetamol versus non-steroidal anti-inflammatory agents in neonates with patent ductus arteriosus: a systematic review and meta-analysis of randomized controlled trials. Br J Clin Pharmacol. 2022
• Mitra S, Gardner CE, MacLellan A, Disher T, Styranko DM, Campbell-Yeo M, Kuhle S, Johnston BC, Dorling J. Prophylactic cyclo-oxygenase inhibitor drugs for the prevention of morbidity and mortality in preterm infants: a network meta-analysis. Cochrane Database of Systematic Reviews 2022, Issue 4. Art. No.: CD013846. DOI: 10.1002/14651858.CD013846.pub2
• Hundscheid T et al. Expectant Management or Early Ibuprofen for Patent Ductus Arteriosus. NEJM December 6, 2022