Patent Ductus Arteriosus: Looking for the Right Approach of Management

editorial

Indian Pediatr 2012;49: 611-612

Patent Ductus Arteriosus: Looking for the Right Approach of Management

Deepak Chawla

Department of Pediatrics, Government Medical College and Hospital, Sector 32,　Chandigarh, India.

In majority of healthy preterm neonates, ductus arteriosus closes spontaneously by 3-7 days after birth [1]. However, three-fourth of very preterm neonates with respiratory distress may continue to have a patent ductus arteriosus (PDA) at end of first week of life. Persistent patency of ductus arteriosus increases blood flow through pulmonary vascular bed and decreases blood flow through cerebral, mesenteric and renal vascular beds. PDA has been associated with decreased survival and increased incidence of pulmonary hemorrhage and bronchopulmonary dysplasia. Ever since initial reports of effect of indomethacin in inducing ductal closure were published in 1970s, impact of prophylactic and therapeutic administration of prostaglandin inhibitors on short- or long-term outcomes of preterm neonates has been an active research issue [2]. During the last decade, acquisition of basic echocardiographic skills by neonatologists has led to earlier recognition and treatment of PDA before the associated clinical features make their appearance. However, questions on selecting appropriate biomarker of hemodynamic significance, optimal timing (prophylactic, pre-symptomatic or symptomatic) of administration of prostaglandin inhibitors, and even necessity of inducing PDA closure remain largely unanswered.

In this issue of Indian Pediatrics, Popat, et al. [3] present their data on closure rate of PDA with indomethacin. PDA was treated on appearance of clinical symptoms and up to three course of indomethacin were administered. Two-thirds of neonates born at less than 29 weeks gestation had significant PDA. Although, 90% responded to multiple courses of indomethacin, treatment of PDA was not associated with improved neonatal morbidities. Neonates who did not respond to multiple courses of indomethacin were more likely to be females, born at earlier gestation, and tended to have higher sickness severity scores and culture-proven sepsis.

Indomethacin is the drug of choice for inducing PDA closure in preterm neonates. However, non-response or reopening of PDA after single course of indomethacin administration is not uncommon. Lack of exposure to antenatal steroids, small-for-gestation status, significant respiratory distress, lower gestation age, liberal fluid intake and a shorter duration of indomethacin treatment are associated with a decreased probability of treatment response [4]. Once indomethacin treatment fails to induce ductal closure, options include ductal ligation, repeated courses of indomethacin or conservative management waiting for spontaneous closure. Surgical ligation of PDA has its own set of associated morbidities (vocal cord paralysis, pneumothorax, chylothorax, scoliosis and infection) and may lead to impaired lung growth and increased incidence of BPD [4]. Indomethacin administration has not only been unsuccessful in improving survival or decreasing incidence of BPD and pulmonary hemorrhage, its infusion induces vasoconstriction in different vascular beds leading to decreased end-organ perfusion. Repeated courses may have cumulative detrimental effect. As a result, advocacy for investigating the third option of conservative watch of PDA is now gaining more voice [5].

Prophylactic administration of indomethacin within 24 h of birth has been associated with decreased incidence of intraventricular or pulmonary hemorrhage and risk of developing symptomatic PDA [6]. Although no improvement in survival without disability was reported at 18 months, gender-specific effect on neurological outcome has been proposed [1]. The need and length of subsequent courses of therapeutic indomethacin may also influence the neurological outcome.

Preterm neonates constitute a heterogenous group in which PDA may close spontaneously, respond to prostaglandin inhibitors or remain open despite multiple attempts of medical closure. Search continues for a select subgroup of neonates, who, identified through a suitable biomarker, will benefit from prophylactic, early therapeutic or repeated administrations of prostaglandin inhibitors.

Funding: Nil; Competing interests: None stated.

References

1. Hamrick SE, Hansmann G. Patent ductus arteriosus of the preterm infant. Pediatrics. 2010;125:1020-30.

2. Heymann MA, Rudolph AM, Silverman NH. Closure of the ductus arteriosus in premature infants by inhibition of prostaglandin synthesis. N Engl J Med. 1976;295:530-3.

3. Popat H, Kapoor V, Travadi J. Patent ductus arteriosus in infants <29 weeks gestation outcomes and factors Affecting closure. Indian Pediatr. 2012;49:615-20.

4. Clyman RI, Couto J, Murphy GM. Patent ductus arteriosus: are current neonatal treatment options better or worse than no treatment at all? Semin Perinatol. 2012;36:123-9.

5. Benitz WE. Patent ductus arteriosus: to treat or not to treat? Arch Dis Child Fetal Neonatal Ed. 2012;97:F80-2.

6. Fowlie PW, Davis PG, McGuire W. Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. Cochrane Database Syst Rev. 2010:CD000174.