The ductus arteriosus is, in developmental terms, a remnant of the sixth aortic arch and connects the pulmonary artery to the proximal descending aorta just after the left subclavian artery origin. It is a normal structure in fetal life.

In utero the lungs are not expanded. Gas exchange occurs at the placenta and only about 10% of the circulation passes through the lungs. The ductus arteriosus connects the pulmonary artery to the aorta to shunt most of the blood away from the lungs. After delivery it closes and the blood passes through the opened lungs. Failure of the ductus to close can lead to overloading of the lungs. The shunt is left to right unless pulmonary hypertension occurs and pulmonary pressure exceeds systemic pressure. Only then will there be cyanosis.

In utero the ductus is kept patent by the production of prostaglandin E2 (PGE2). Functional closure of the ductus occurs within 15 hours of birth in a normal full term infant but true closure with the inability to re-open takes about 3 weeks. The initial closure is by abrupt contraction of the muscular wall of the ductus with an infant's first breath. True persistence of a patent ductus arteriosus (PDA) is often taken as one persisting after 3 months of age. It seems that the pO₂ rises as the first breath is taken and this is an important trigger.¹

Epidemiology²

• It is said to be one of the commonest forms of congenital heart disease in children but really it is an abnormality of the circulation, not the heart.
• The incidence can only be approximate as closure can be incomplete and thus presents late (even in adolescence).
• In full term infants the incidence is probably between 6 and 20 per 100,000 births.
• It affects girls twice as often as boys but in congenital rubella syndrome the sex incidence is equal.

Risk factors

• It is commoner in premature infants.³ Perinatal asphyxia usually delays rather than prevents closure.
• Children born at high altitudes where the ambient pO₂ is low are also at risk. They also appear to be at risk of atrial septal defects.⁴
• It is commoner with congenital rubella syndrome, fetal alcohol syndrome and maternal use of phenytoin and amfetamines.
• Most children who are found to have the condition have no risk factors.

Presentation⁵

History

• Often there are no problems to suggest the diagnosis and the typical child with a PDA is asymptomatic.
• There may be prematurity or respiratory distress syndrome.
• There may, particularly with large PDAs, be feeding difficulties and poor growth during infancy, with failure to thrive.⁶ Gross congestive heart failure is rare.

Examination

• About a third of children with PDA are small for age.
• If the pulmonary circulation is markedly overloaded there will be tachycardia, tachypnoea and a wide pulse pressure.
• The apex is displaced laterally and there may be a thrill in the suprasternal notch or in the left infraclavicular region.
• The first heart sound is normal but the second is often obscured by the murmur.
• The murmur:
  • As with other murmurs, is caused by turbulent flow. Blood flow is usually laminar and so silent. The more gross the turbulence the louder will be the murmur. A widely patent ductus may produce less turbulence than one that is nearly closed and so the loudness of a murmur gives no indication of the severity of a lesion.
  • The classical description is of a continuous machinery murmur but it may be accentuated in systole.
  • The murmur is best heard in the left upper chest. If the left to right blood flow ratio exceeds 2:1 there may be a mitral rumble from the high flow rate across the mitral valve. There is often an aortic ejection murmur too.
  • These last features will be absent with a narrow PDA but inspiration may accentuate the murmur as resistance in the pulmonary circulation falls.
• Peripheral pulses are bounding as the run off into the pulmonary circulation drops the diastolic pressure and causes a wide pulse pressure.
• In the premature infant of low birthweight, the classical signs are usually absent. The continuous murmur is rarely heard. There may be a rough systolic murmur along the left sternal border but a small baby with a large PDA and significant pulmonary over-circulation may have no murmur. Precordial activity is increased and peripheral pulses are bounding. The increased precordial activity is caused by the large left ventricular stroke volume.

Click here to hear an example of the murmur

Differential diagnosis⁵

• Coronary artery fistula
• Fallot's tetralogy (with absent pulmonary valve)
• Aneurysm of the sinus of Valsalva
• Aortopulmonary septal defect
• Venous hum
• Atrioventricular malformation

Investigations

• If the shunt is significant, chest X-ray will show enlargement of the pulmonary arteries, veins, left atrium and left ventricle. Such features usually require a ratio of pulmonary flow to systemic flow of at least 2:1. In older people a patent ductus arteriosus (PDA) may be calcified and visible on a plain film.
• The diagnosis is confirmed by 2-dimensional echocardiography. Typically the PDA connects the junction of the main pulmonary artery and the left pulmonary artery with the aorta just below and opposite the left subclavian artery. There is continuous flow from the aorta to the main pulmonary artery although the rate of flow is variable. This is shown by Doppler echocardiography. In diastole there may even be reversal of flow from the aorta back into the PDA.
• ECG is often normal but with marked extra flow there may be signs of left ventricular hypertrophy with a tall R in V6. In a premature baby with a large shunt there may even be T wave inversion and ST depression suggesting ischaemia from the high workload.

Management⁵

• A premature baby is usually treated initially with intravenous indometacin. Most non-steroidal anti-inflammatory drugs (NSAIDs) are prostaglandin synthetase inhibitors but indometacin also has direct anti-prostaglandin action. Indometacin is effective at closing the ductus but the result may be temporary and surgery is still required.⁷ Ibuprofen may possibly be a safer alternative that is less likely to cause oliguria.^8,9 However a Cochrane review concludes that indometacin should remain the drug of choice for treatment of a PDA.⁹ The risks of surgery are high with prematurity.
• B-type natriuretic peptide (BNP) levels can be used to guide treatment and one study found that babies monitored by this means needed to have fewer doses of intravenous indometacin.
• Diuretics and restriction of fluid used to be recommended whilst awaiting spontaneous closure. However, the evidence base is poor and a systematic review of furosemide in preterm neonates with respiratory distress symptoms showed no long-term benefits and increased the risk of symptomatic PDA.
• It is by no means certain that indometacin or ibuprofen are superior to surgical ligation of the ductus. Experienced paediatric cardiovascular surgeons get very good results.
• If the child is over 1 year old the most commonly used technique is occlusion at cardiac catheterisation. Various techniques have been developed but the best is probably the Gianturco spring occluding coil. Usually the technique completely closes the ductus but sometimes, with large defects, it is incomplete but thrombus completes the occlusion over the next few days. National Institute for Health and Clinical Excellence (NICE) guidance has been produced and considers that current evidence on the safety and efficacy of endovascular patent ductus arteriosus (PDA) appears to support the use of this procedure.⁶ The procedure should be performed in units where there are arrangements for cardiac surgical support in the event of complications.
• The Amplatzer® patent ductus arteriosus device is more reliable and easier to implant than occluding coils.
• Patients who have cardiac catheter closure of a PDA are usually sent home that same day but, if thoracotomy is required, another 2 or 3 days in hospital are required. A longer stay is necessary if there are still complications after closure.
• Children who have had a PDA closed need no further restrictions on their lives.
• Whilst the ductus arteriosus is patent, then the risk of endocarditis should be considered (there is no increased risk of endocarditis once repair complete). During invasive procedures (e.g. urinary or gastrointestinal procedures) involving areas of sepsis, suitable antibiotics should be given promptly (to cover all the likely organisms, including any known to cause endocarditis).¹⁰

Complications

Possible complications include endocarditis, cardiac failure, obstruction of the pulmonary vessels and rupture of the aorta. Patent ductus arteriosus (PDA) is also an independent risk factor for the development of necrotising enterocolitis.¹¹ Premature infants with a PDA are at greater risk of bronchopulmonary dysplasia.

Prognosis

In premature babies with significant patent ductus arteriosus (PDA) there is risk of bronchopulmonary dysplasia. If a child with respiratory distress syndrome (RDS) is found to have PDA too this is an adverse prognostic sign.¹² If a premature infant does not have RDS or it is uncomplicated, the timing of spontaneous closure of the ductus is normal.¹³ In most patients who have had successful closure of a PDA there are no further complications.

Prevention

In infants weighing less than 1000 g, prophylactic NSAID may aid closure and reduce the risk of subsequent morbidity.^14,15 However there is no evidence of long-term benefit.^15,16

Document references

1. Heymann MA, Rudolph AM; Control of the ductus arteriosus. Physiol Rev. 1975 Jan;55(1):62-78. [abstract]
2. Schneider DJ, Moore JW; Patent ductus arteriosus. Circulation. 2006 Oct 24;114(17):1873-82.
3. Quinn D, Cooper B, Clyman RI; Factors associated with permanent closure of the ductus arteriosus: a role for prolonged indomethacin therapy. Pediatrics. 2002 Jul;110(1 Pt 1):e10. [abstract]
4. Miao CY, Zuberbuhler JS, Zuberbuhler JR; Prevalence of congenital cardiac anomalies at high altitude. J Am Coll Cardiol. 1988 Jul;12(1):224-8. [abstract]
5. Neish SR; Patent Ductus Arteriosus, eMedicine, Jul 2009.
6. Endovascular closure of patent ductus arteriosus, NICE (2004)
7. Ramsay JM, Murphy DJ Jr, Vick GW 3rd, et al; Response of the patent ductus arteriosus to indomethacin treatment. Am J Dis Child. 1987 Mar;141(3):294-7. [abstract]
8. Van Overmeire B, Smets K, Lecoutere D, et al; A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N Engl J Med. 2000 Sep 7;343(10):674-81. [abstract]
9. Ohlsson A, Walia R, Shah S; Ibuprofen for the treatment of a patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev. 2003;(2):CD003481. [abstract]
10. Antimicrobial prophylaxis against infective endocarditis, NICE Clinical Guideline (March 2008)
11. Dollberg S, Lusky A, Reichman B; Patent ductus arteriosus, indomethacin and necrotizing enterocolitis in very low birth weight infants: a population-based study. J Pediatr Gastroenterol Nutr. 2005 Feb;40(2):184-8. [abstract]
12. Dudell GG, Gersony WM; Patent ductus arteriosus in neonates with severe respiratory disease. J Pediatr. 1984 Jun;104(6):915-20. [abstract]
13. Reller MD, Colasurdo MA, Rice MJ, et al; The timing of spontaneous closure of the ductus arteriosus in infants with respiratory distress syndrome. Am J Cardiol. 1990 Jul 1;66(1):75-8. [abstract]
14. Mahony L, Carnero V, Brett C, et al; Prophylactic indomethacin therapy for patent ductus arteriosus in very-low-birth-weight infants. N Engl J Med. 1982 Mar 4;306(9):506-10. [abstract]
15. Fowlie PW, Davis PG; Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. Cochrane Database Syst Rev. 2002;(3):CD000174. [abstract]
16. Fowlie PW, Davis PG; Prophylactic indomethacin for preterm infants: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2003 Nov;88(6):F464-6. [abstract]

Internet and further reading

• British Heart Foundation

Acknowledgements