Key points
- Patent ductus arteriosus (PDA) is a common congenital heart defect in which a normal fetal structure (the ductus arteriosus) connecting the pulmonary artery and descending aorta persists beyond the first 10 days of life
- PDA is present from birth, but patients can develop symptoms at any age. Clinical presentation depends on the size of the PDA: Infants with a small PDA are often asymptomatic; those with a larger PDA may have growth retardation, heart failure, and a predisposition to lower respiratory tract infections
- Closure of the defect can be attempted medically in premature infants using indomethacin or ibuprofen lysine
- Nonpharmacologic treatment include various percutaneous techniques in the catheterization lab. Surgery is reserved for patients who did not respond to initial treatment or those in whom other treatments are contraindicated
- Morbidity and mortality are related to the volume of blood flowing through the PDA
- Neonates with a large PDA may require supplemental oxygen and assisted mechanical ventilation to correct hypoxemia. These infants usually require transfer to a neonatal intensive care unit
Background
Description
- PDA is a common congenital heart defect in which the ductus arteriosus connecting the pulmonary artery and descending aorta persists beyond the first 10 days of life
- Depending on the size of the PDA, there is variable left-to-right shunt of blood from the aorta to the pulmonary artery. Morbidity and mortality are related to volume of blood flow
- Clinical presentation depends on the size of the PDA; infants with a small PDA are often asymptomatic; those with a larger PDA may have symptoms of heart failure, growth retardation, and may be prone to lower respiratory tract infections. Although present from birth patients may become symptomatic at any age
- A PDA may not become symptomatic until adulthood with the development of endocarditis, pulmonary hypertension, or heart failure secondary to left ventricular overload
- The cause is unknown, but PDA is associated with prematurity, persistent high levels of prostaglandins, and neonatal hypoxia. There is also a strong association between maternal rubella infection in early pregnancy and PDA in the infant
- PDA can be associated with other congenital heart disease and can be an important source of systemic blood flow in infants with specific cardiac abnormalities such as aortic coarctation
- Term infants with a small PDA are asymptomatic, although a heart murmur may be detected on physical examination. In these patients a continuous 'machinery' murmur usually heard most clearly at the left-upper sternal border is characteristic of PDA. Term infants with a large PDA may present after 4 to 6 weeks with feeding difficulties, failure to thrive, and tachypnea; there may be signs of congestive heart failure including pulmonary congestion and jugular venous distention
- Unlike in full-term infants, a PDA in a premature infant often closes spontaneously: 60% within 3 days and 75% within 3 months. Premature infants on the other hand may present with a rough systolic murmur or with no murmur at all
- Premature infants with coexisting respiratory distress syndrome often improve in the days after birth, but then cannot be weaned off the ventilator due to unexpected increased ventilator or oxygen requirements. Episodes of apnea or bradycardia may be noted in infants not on ventilators
- Infants and children with a hemodynamically significant PDA may have bounding peripheral pulses and a widened pulse pressure greater than 60 mm Hg. On cardiac auscultation a diastolic rumble may be heard
- Common complications of PDA are congestive heart failure and failure to thrive. Endocarditis is a rare complication. In patients with a large, untreated PDA the increasing high pressure and blood flow to the pulmonary vascular bed results in irreversible pulmonary vascular occlusive disease and pulmonary hypertension. Shunt reversal can occur in severe cases of pulmonary hypertension
- Patients with a small untreated PDA are at low risk for developing pulmonary hypertension or heart failure, but they are at an increased risk for endocarditis
Epidemiology
Incidence and prevalence:
- Incidence is inversely correlated with gestational age; PDA is the most common congenital heart defect in preterm infants
- Approximately 80 cases per 10,000 live births for PDA diagnosed by echocardiography. Incidence may be as low as 6 cases per 10,000 live births for clinically significant PDA
- Up to 60% of infants born at less than 28-weeks' gestation have PDA
- PDA represents 5% to 10% of all congenital heart defects
Demographics:
- Inversely correlated with gestational age. A patent ductus is common in premature infants and much less so among fullterm neonates
- Is three times more common in female than male neonates
- PDA has no racial predilection
- No single genetic cause has been identified, but PDA can be seen in association with genetic disorders such as Char syndrome, trisomy 21 and 18, CHARGE syndrome, cri du chat syndrome, Noonan syndrome, and Holt-Oram syndrome. There is a 2% to 4% increased incidence of PDA in siblings of affected patients
- PDA is more common in infants born at high altitude, reflecting hypoxia as a cause of PDA
- An increased incidence of PDA has been reported in patients of low socioeconomic status, although this most likely reflects a higher incidence of premature birth
Causes and risk factors
Causes:
- The cause(s) of PDA are unknown, but there are several associated factors that may contribute to the etiology including the following:
- Persistently elevated levels of prostaglandins help maintain an open ductus arteriosus. Premature infants have higher levels of circulating prostaglandins, since prostaglandins are metabolized by mature lungs characteristic of infants born at or near term
- Maternal rubella infection in early pregnancy is associated with PDA in up to 85% of infants
- Relative hypoxia as may occur in infants born with immature lungs, at high altitudes, and/or with coexisting congenital cardiac defects. Normally, the sudden increase in oxygen tension at birth causes a decrease in pulmonary vascular resistance and contraction of smooth muscle in the ductus arteriosus resulting in closure
- Maternal rubella infection in early pregnancy is a serious cause
- PDA is associated with serious genetic disorders such as Char syndrome, trisomy 21 and 18, CHARGE syndrome, cri-du-chat syndrome, Noonan syndrome, and Holt-Oram syndrome. These disorder are associated with noncardiac abnormalities as well
Risk factors:
- Prematurity, particularly infants born below 28-weeks' gestation, due to high levels of circulating prostaglandins and underdeveloped lungs
- Maternal rubella infection in early pregnancy
- Delivery at high altitudes due to relative hypoxia
Associated disorders
- Commonly associated with other congenital cardiac disorders
- Also associated with Char syndrome, trisomy 21 and 18, CHARGE syndrome, cri du chat syndrome, Noonan syndrome, and Holt-Oram syndrome
Screening
Not applicable.
Primary prevention
Summary approach
- Prevention of rubella infection in pregnant women, through the routine assessment of rubella titers and the immunization or re-immunization of susceptible individuals, will decrease the incidence of the disorder
- Minimizing the time that pregnant women spend at high altitudes may also reduce the prevalence of PDA in their offspring
Population at risk
Premature infants.
Preventive measures
Chemoprophylaxis:
- Indomethacin can be administered prophylactically within 6 hours of birth to preterm infants weighing less than 1,000 g
- Prophylactic indomethacin lowers the incidence of symptomatic PDA, the need for PDA surgical ligation, and severe intraventricular hemorrhage. Meta-analyses found no evidence of increased mortality or of severe neurologic developmental disability at age 18 months or at age 36 months. Although one large, randomized, controlled trial (RCT) found a decreased incidence of mental retardation at age 4 years, subsequent long-term neurodevelopmental follow-up showed no difference at age 12 years. There is no evidence that chemoprophylaxis decreases other PDA-associated morbidities
- Prophylactic ibuprofen lysine is equally efficacious in PDA closure. It significantly decreases the incidence of PDA, decreases the need for rescue treatment with cyclooxygenase inhibitors, and decreases the need for surgical ligation. However, treatment with ibuprofen lysine is associated with an increased incidence of sepsis and does not have the same effects as indomethacin in decreasing intraventricular hemorrhage. Additionally, experts have reservations about its use in this context as it displaces protein-bound bilirubin in neonatal plasma to levels that are consistent with kernicterus. Therefore, ibuprofen lysine is not recommended for use in PDA prophylaxis
- There is no consensus among specialists on whether to provide prophylaxis for PDA. Some experts recommend prophylaxis for any preterm infant weighing less than 1,000 g, although other experts feel that prophylaxis results in unnecessary medication in up to 64% of treated infants
- There has been one unblinded, single-center, randomized trial of prophylactic surgical ligation of PDA within the first 24 hours of life in premature infants less than or equal to 1,000 g. This study was performed prior to the routine use of antenatal corticosteroids or exogenous surfactant. This study showed a decrease in severe necrotizing enterocolitis. The study was underpowered for other secondary outcomes, but did not demonstrate any difference in mortality or other PDA-associated morbidities. Subsequent reanalysis of this study using modern definitions of bronchopulmonary dysplasia revealed that prophylactic surgical ligation increased the risk of bronchopulmonary dysplasia
Evidence
There is some evidence for the use of prophylactic indomethacin for the prevention of PDA in preterm infants.
- A systematic review of 19 RCTs included 2,872 infants, mostly of very low to extremely low birth weight. Infants treated with prophylactic indomethacin had a significantly decreased incidence of both symptomatic PDA (RR .44; 95% CI = .38-.50) and PDA surgical ligation (estimated RR .51; 95% CI = .37-.71) as compared with untreated infants. There was no significant difference between treated and untreated infants in mortality (estimated RR .96; 95% CI = .81-1.12) or severe neurodevelopmental disability for up to 3 years.[1]Level of evidence: 1
There is some evidence that prophylactic ibuprofen lysine should not be used in place of indomethacin in the prevention of PDA in preterm infants.
- A systematic review identified 4 RCTs that compared prophylactic ibuprofen versus placebo or no medication in the prevention of PDA in 672 preterm and/or low birthweight infants. Prophylactic ibuprofen significantly decreased the incidence of PDA (typical RR .37; 95% CI = .29-.49), decreased the need for rescue treatment with cyclooxygenase inhibitors (typical RR .17; 95% CI = .11-.27), and decreased the need for surgical ligation (typical RR .34, 95% CI = .14-.81) by day 3. However, the authors noted that in control infants 60% of PDA closed spontaneously by day 3 as well. Treatment with ibuprofen was associated with an increased rate of short-term renal dysfunction. The authors noted the lack of long-term follow-up studies on infants treated with ibuprofen.[2]Level of evidence: 1
