Prostaglandin E2 and patent ductus arteriosus in premature infants

Main Article Content

Mochammading Mochammading
Risma Kerina Kaban
Piprim Basarah Yanuarso
Mulyadi Djer


Background Patent ductus arteriosus (PDA) is a congenital heart disease most commonly occurring in premature infants. Spontaneous ductus arteriosus (DA) closure in premature infants has been suggested to be associated with duct lumen maturity and the DA sensitivity to prostaglandin E2 (PGE2).
Objective To assess for a possible correlation between serum PGE2 levels and PDA size in premature infants.
Methods This observational study using repeated measurements on premature infants with PDA detected at days 2-3 of life was undertaken in Cipto Mangunkusumo Hospital and Fatmawati Hospital, Jakarta, from April to May 2014. The PDA was diagnosed using 2-D echocardiography and PGE2 levels were measured by immunoassay. Pearson’s correlation test was used to evaluate a possible correlation between PGE2 level and DA diameter.
Results Thirty-three premature infants of median gestational age 31 (range 28-32) weeks and median birth weight 1,360 (range 1,000-1,500) grams were enrolled. Almost two-thirds of the subjects were male. Almost all (30/33) subjects had spontaneous DA closure before the age of 10 days. Subjects’ mean DA diameter was 2.9 (SD 0.5) mm with maximum flow velocity of 0.2 (SD 0.06) cm/sec, and left atrial-to-aortic root ratio (LA/Ao) of 1.5 (SD 0.2). Their mean PGE2 levels at the ages of 2-3, 5-7, and after 10 days were 5,238.6 (SD 1,225.2), 4,178.2 (SD 1,534.5), and 915.2 (SD 151.6) pg/mL, respectively. The PGE2 level at days 2-3 was significantly correlated with DA diameter (r = 0.667; P < 0.001), but not at days 5-7 (r = 0.292; P = 0.105) or at day 10 (r = 0.041; P = 0.941).
Conclusion There is a strong, positive correlation between the PGE2 level and DA diameter in preterm infants at 2-3 days of age. However, there is no significant correlation between PGE2 level and persistence of PDA.

Article Details

How to Cite
Mochammading M, Kaban R, Yanuarso P, Djer M. Prostaglandin E2 and patent ductus arteriosus in premature infants. PI [Internet]. 12May2016 [cited 13Aug.2020];56(1):8-4. Available from:
Pediatric Cardiology
Received 2016-03-30
Accepted 2016-03-30
Published 2016-05-12


1. Fyler DC. Patent ductus arteriosus. In: Fyler DC, editor. Nadas' Pediatric Cardiology. Boston: Hanley & Belfus, Inc; 1992. p. 598-608.
2. Hamrick SE, Hansmann G. Patent ductus arteriosus of the preterm infant. Pediatrics. 2010;125:1020-30.
3. Musewe NN, Olley PM. Patent ductus arteriosus. In: Freedom RM, Benson LN, Smallhorn JF, editors. Neonatal heart disease. London: Springer-Verlag; 1992. p. 593-609.
4. Sasi A, Deorari A. Patent ductus arteriosus in preterm infants. Indian Pediatr. 2011;48:301-8.
5. Coceani F, Baragatti B. Mechanisms for ductus arteriosus closure. Semin Perinatol. 2012;36:92-7.
6. Thebaud B, Lacaze-Mazmonteil T. Patent ductus artriosus in premature infants: a never-closing act. Paediatr Child Health. 2010;15:267-70.
7. Coceani F, Olley PM, Lock JE. Prostaglandins, ductus arteriosus, pulmonary circulation: current concepts and clinical potential. Eur J Clin Pharmacol. 1980;18:75-81.
8. Clyman RI, Mauray F, Roman C, Heymann MA, Payne B. Effect of gestational age on ductus arteriosus response to circulating prostaglandin E2. J Pediatr. 1983;102:907-11.
9. Hammerman C, Zaia W, Berger S, Strates E, Aldousany A. Prostaglandin levels: predictors of indomethacin responsiveness. Pediatr Cardiol. 1986;72:61-5.
10. Simmons DL, Botting RM. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev. 2004;56:387–437.
11. Kluckow M, Evans N. Early echocardiographic prediction of symptomatic patent ductus arteriosus in preterm infants undergoing mechanical ventilation. J Pediatr. 1995;127:774-9.
12. Cochrane Database of Systematic Reviews. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. [cited 2013 July 20]. Available from:
13. Nimeri N, Salama H. Short-term outcome of different treatment modalities of patent ductus arteriosus in preterm infants. Five years experiences in Qatar. Internet J Cardiovascular Res. 2010;7:15-20.
14. Mosalli R, Paes B. Patent ductus arteriosus: optimal fluid requirements in preterm infants. [cited 2012 October 8]. Available from:
15. Collins A, Joseph D, Bielaczyc K. Design Research: Theoretical and methodological issues. Journal Learning Sciences. 2004;13:15-42.
16. Sullivan LM. Repeated measures. Circulation. 2008;117:1238-43.
17. R&D Systems, Inc. 614 McKinley Place, Minneapolis, United States of America. The Parameter PGE2 Immunoassay 2010. [cited 2013 August 28]. Available from:
18. Evans N, Malcolm G. Diagnosis of patent ductusartreriosus in preterm infants. [cited 2012 October 8]. Available from:
19. Adriaan DWK, Lakkundi A, Kok J. Predicting ductal size. [cited 2012 October 8]. Available from:
20. Adriaan DWK. Central blood flow measurements in newborn infants. [cited 2012 October 8]. Available from:
21. Vanhaesebrouck S, Zonnenberg I, Vandervoort P, Bruneel E, Van Hoestenberghe MR, Theyskens C. Conservative treatment for patent ductus arteriosus in the preterm. Arch Dis Child Fetal Neonatal Ed. 2007;92:244-7.
22. Koch J, Hensley G, Roy L, Brown S, Ramaciotti C, MD, Rosenfeld CR. Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth weight of 1000 grams or less. Pediatrics. 2006;117:1113-21.
23. Obladen M. History of the ductus arteriosus: persisting patency in the preterm infant. Neonatology. 2011;99:163-9.
24. Obladen M. History of the ductus arteriosus: anatomy and spontaneous closure. Neonatology. 2011;99:83-9.
25. Stoller JZ, Demauro SB, Dagle JM, Reese J. Current perspectives on pathobiology of the ductus arteriosus. J Clin Exp Cardiolog. 2012;58:1-14.
26. Brunner B, Hoeck M, Schermer E, Streif W, Kiechl-Kohlendorfer U. Patent ductus arteriosus, low platelets, cyclooxygenase inhibitors, and intraventricular hemorrhage in very low birth weight preterm infants. J Pediatr. 2013;163:23-8.
27. Yokoyama U, Minamisawa S, Quan H, Akaike T, Suzuki S, Jin M, et al. Prostaglandin E2-activated Epac promotes neointimal formation of the rat ductus arteriosus by a process distinct from that of cAMP-dependent protein kinase A. J Biol Chem. 2008;283:28702–9.
28. Gruzdev A. Discerning the role of prostaglandins in ductus arteriosus remodeling. [cited 2013 August 20]. Available from:
29. Agren P, van der Sterren S, Cogolludo AL, Blanco CE, Villamor E. Developmental changes in the effects of prostaglandin E2 in the chicken ductus arteriosus. J Comp Physiol B. 2009;179:133-43.
30. Sehgal A, McNamara PJ. The ductus arteriosus: a refined approach!. Semin Perinatol. 2012;36:105-13.
31. Hermes-DeSantis ER, Clyman RI. Patent ductus arteriosus: pathophysiology and management. J Perinatol. 2006;26:S14-8