Introduction: Persistent ductus arteriosus (PDA) is found with increased incidence in preterm infants, significantly affecting neonatal morbidity and mortality rates.
Aim: To evaluate the association between the presence of PDA and the severity of clinical condition at birth in critically ill preterm infants, with gestational ages (GA) ≤ 32 weeks and severe respiratory distress.
Methods: All preterm infants with GA ≤ 32 weeks admitted to the neonatal intensive care unit (NICU) of the Clinical County Emergency Hospital, Sibiu between 1 January 2010 and 31 December 2015 were included in the study. These were categorized as Group 1 [Preterm infants with PDA; n=154] and Group 2 [Preterm infants without PDA; n=186]. Epidemiological and clinical data were collected in the National Registry for Respiratory Distress Syndrome for all children, and data related to prenatal period, clinical characteristics at birth i.e GA, weight, gender, Apgar scores, and clinical features such as resuscitation at birth, surfactant administration, need and duration of respiratory support, neonatal sepsis, complications associated with prematurity, and death, were analyzed.
Results: Group 1 infants had significantly lower GA and birth weights, were more often out born (p=0.049, HR 1.69), and had significantly lower Apgar scores at 1 and 10 minutes (p=0.022, p=0.000). They presented a significantly higher need for surfactant administration (42.9% vs 24.7%, p<0.0001) and respiratory support (96.8% vs 90.3%, HR 3.19, p=0.019 for need of CPAP and 22.1% vs 10.8%, HR 2.35, p=0.004 for mechanical ventilation). Duration of respiratory support was also significantly higher in the Group 1 (7.6%±7.5 vs. 5.1±3.8 days, p<0.0001 for CPAP and 20.1±22.5 vs. 12.0±15.7 days, p<0.0001 for mechanical ventilation).
Conclusion: In very preterm infants, PDA may be associated with a critical clinical condition leading to serious complications. The presence of PDA after the seventh day of life was associated with an increased need for respiratory support, both CPAP and mechanical ventilation, increased severity of the respiratory distress syndrome, requiring a longer duration of respiratory support, and increased the hospitalization length. In very preterm infants, PDA presence was also associated with a higher rate of severe complications and death, indicating the need for a careful and proper management of these critical cases in neonatal intensive care units.
8. Hermes-DeSantis ER, Clyman RI. Patent ductus arteriosus: pathophysiology and management. J Perinatol. 2006;26:S14-8. DOI: 10.1038/sj.jp.7211465
9. Clyman RI. Ibuprofen and patent ductus arteriosus. N Engl J Med. 2000;343:728-39. DOI: 10.1056/NEJM200009073431009
10. Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002;39:1890-900.
11. Fortescue EB, Lock JE, Galvin T, McElhinney DB. To Close or Not to Close: The Very Small Patent Ductus Arteriosus. Congenit Heart Dis. 2010;5:354-65. doi: 10.1111/j.1747-0803.2010.00435.x.
12. Toganel R. Critical Congenital Heart Diseases as Lifethreatening Conditions in the Emergency Room. Journal of Cardiovascular Emergencies. 2016;2:7-10. DOI: 10.1515/jce-2016-0002.
13. Feng YS, Yu V. Management of Patent Ductus Arteriosus in Very Preterm Infants in the Post-surfactant Era. HK J Paediatr (new series). 2003;8:93-100.
14. Hammoud MS, Elsori HA, Hanafi E-AM, Shalabi AA, Fouda IA, Devarajan LV. Incidence and risk factors associated with the patency of ductus arteriosus inpreterm infants with respiratory distress syndrome in Kuwait. Saudi Med J. 2003;24:982-5.
15. Lee JA, Kim M-J, Oh S, Choi BM. Current Status of Therapeutic Strategies for Patent Ductus Arteriosus in Very-Low-Birth-Weight Infants in Korea. J Korean Med Sci. 2015;30:S59-66. doi: 10.3346/jkms.2015.30.S1.S59.
17. Evans N. Preterm patent ductus arteriosus: should we treat it? J Paediatr and Child Health. 2012;48:753-8. doi: 10.1111/j.1440-1754.2012.02542.x.
18. Meyer S. PDA in neonates—please doctor act individually! Acta Paediatr. 2012;101:e145-6. DOI: 10.1111/j.1651-2227.2012.02617.x.
19. Koch J, Hensley G, Roy L, Brown S, Ramaciotti C, 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. DOI: 10.1542/peds.2005-1528.
20. Hamrick SE, Hansmann G. Patent ductus arteriosus of the preterm infant. Pediatrics. 2010;125:1020-30. doi: 10.1542/peds.2009-3506.
21. Chen H-L, Yang R-C, Lee W-T, et al. Lung function in very preterm infants with patent ductus arteriosus under conservative management: an observational study. BMC Pediatrics. 2015;15:167. DOI: 10.1186/s12887-015-0480-y.
22. Du J-F, Liu T-T, Wu H. Risk factors for patent ductus arteriosus in early preterm infants: a case-control study. Zhongguo Dang Dai Er Ke Za Zhi. 2016;18:15-9.
23. Garcıa-Munoz RF, Galan HG, Figueras AJ, Garcıa-Alix PA. Outcomes of very-low-birth-weight infants exposed to maternal clinical chorioamnionitis: a multicentre study. Neonatology 2014;106:229-34. doi: 10.1159/000363127.
24. Park HW, Choi Y-S, Kim KS, Kim S-N. Chorioamnionitis and Patent Ductus Arteriosus: A Systematic Review and Meta-Analysis. PLoS ONE. 2015;10:e0138114. doi: 10.1371/journal.pone.0138114.
25. Gonzalez A, Sosenko IR, Chandar J, et al. Influence of infection on patent ductus arteriosus and chronic lung disease in premature infants weighing 1000 grams or less. J Pediatr. 1996;128:470-8.
26. Seppanen MP, Ojanpera OS, Kaapa PO, Kero PO. Delayed postnatal adaptation of pulmonary hemodynamics in infants of diabetic mothers. J Pediatr. 1997;131:545-8.
27. Rakza T, Magnenant E, Klosowski S, Tourneux P, Bachiri A, Storme L. Early hemodynamic consequences of patent ductus arteriosus in preterm infants with intrauterine growth restriction. J Pediatr. 2007;151:624-8. DOI: 10.1016/j.jpeds.2007.04.058.
28. Agarwal R, Deorari AA, Paul VK. Patent Ductus Arteriosus in Preterm Neonates. Indian J Pediatr. 2008;75:277. doi: 10.1007/s12098-008-0059-9.
29. Saeidi R, Mahmoodi E, Eslami M, Gholami M. Evaluation of Risk Factors Related with Neonatal Patent Ductus Arteriosus in Hospitalized Neonates of Neonatal Intensive Care Unit. Zahedan J Res Med Sci (ZJRMS). 2012;14:33-5.
30. Bell EF, Acarregui MJ. Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants. Cochrane Database Syst Rev. 2008;(1):CD000503. doi: 10.1002/14651858.CD000503.pub2.
31. Green TP, Thompson TR, Johnson DE, Lock JE. Furosemide promotes patent ductus arteriosus in premature infants with the respiratory distress syndrome. N Engl J Med. 1983;308:743-8.
32. Simon SR, van Zogchel L, Bas-Suárez MP, Cavallaro G, Clyman RI, Villamor E. Platelet Counts and Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-Analysis. Neonatology. 2015;108:143-51. doi: 10.1159/000431281.
33. Shimada S, Kasai T, Hoshi A, Murata A, Chida S. Cardiocirculatory effects of patent ductus arteriosus in extremely low-birth-weight infants with respiratory distress syndrome. Pediatr Int. 2003;45:255-62.
34. Noori S, Patel D, Friedlich P, Siassi B, Seri I, Ramanathan R. Effects of low oxygen saturation limits on the ductus arteriosus in extremely low birth weight infants. J Perinatol. 2009;29:553-7. doi: 10.1038/jp.2009.60.
35. Kaapa P, Seppanen M, Kero P, Saraste M. Pulmonary hemodynamics after synthetic surfactant replacement in neonatal respiratory distress syndrome. J Pediatr. 1993;123:115-9.
36. Soll R, Özek E. Prophylactic protein free synthetic surfactant for preventing morbidity and mortality in preterm infants. Cochrane Database Syst Rev. 2010;(1):CD001079. doi: 10.1002/14651858.CD001079.pub2.
37. Rosenfeld W, Sadhev S, Brunot V, Jhaveri R, Zabaleta I, Evans HE. Phototherapy effect on the incidence of patent ductus arteriosus in premature infants: prevention with chest shielding. Pediatrics. 1986;78:10-4.
38. Sadecka LSR, Leoneb CR, Procianoyc RS, et al. Effects of therapeutic approach on the neonatal evolution of very low birth weight infants with patent ductus arteriosus. J Pediatr (Rio J). 2014;90:616-23. doi: 10.1016/j.jped.2014.04.010.
39. Hajjar ME, Vaksmann G, Rakza T, Kongolo G, Storme L. Severity of the ductal shunt: a comparison of different markers. Arch Dis Child Fetal Neonatal Ed. 2005;90:F419-22. DOI: 10.1136/adc.2003.027698.
40. Kluckow M, Evans N. Ductal shunting, high pulmonary blood flow, and pulmonary hemorrhage. J Pediatr. 2000;137:68-72.
41. Mosalli R, Alfaleh K. Prophylactic surgical ligation of patent ductus arteriosus for prevention of mortality and morbidity in extremely low birth weight infants. Cochrane Database Syst Rev. 2008;(1):CD006181. doi: 10.1002/14651858.CD006181.pub2.
42. Noori S. Patent ductus arteriosus in the preterm infant: to treat or not to treat? J Perinatol. 2010;30 Suppl:S31-7. doi: 10.1038/jp.2010.97.
43. 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;40:184-8.
44. McPherson C, Gal P, Smith M, et al. Necrotizing Entrocolitis and Intestinal Perforation in Preterm Infants with Patent Ductus Arteriosus: Does indomethacin increase the risk? Journal of Neonatal-Perinatal Medicine. 2008;1:209-16.
45. Sellmer A, Bjerre JV, Schmidt MR, et al. Morbidity and mortality in preterm neonates with patent ductus arteriosus on day 3. Arch Dis Child Fetal Neonatal Ed. 2013;98:F505-10. doi: 10.1136/archdischild-2013-303816.
46. Evans N, Kluckow M. Early ductal shunting and intraventricular haemorrhage in ventilated preterm infants. Arch Dis Child Fetal Neonatal Ed. 1996;75:F183-6.
47. Noori S, McCoy M, Friedlich P, et al. Failure of ductus arteriosus closure is associated with increased mortality in preterm infants. Pediatrics. 2009;123:e138-44. doi: 10.1542/peds.2008-2418.
48. Benitz WE. Treatment of persistent patent ductus arteriosus in preterm infants: time to accept the null hypothesis? J Perinatol. 2010;30:241-52. doi: 10.1038/jp.2010.3.
49. 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. doi: 10.1053/j.semperi.2011.09.022.
50. Ivey KN, Srivastava D. The paradoxical patent ductus arteriosus. J Clin Invest. 2006;116:2863-5. Doi: 10.1172/JCI30349.
51. Vermont-Oxford trials network database project. Manual of Operations, Release 2.0. Neonatal Research and Technology Assessment, Inc. Burlington, 1993.
52. Nemerofsky SL, Parravicini E, Bateman D, Kleinman C, Polin RA, Lorenz JM. The ductus arteriosus rarely requires treatment in infants > 1000 grams. Am J Perinatol. 2008;25:661-6. doi: 10.1055/s-0028-1090594.
53. Fanaroff AA, Hack M, Walsh MC. The NICHD Neonatal Research Network: changes in practice and outcomes during the first 15 years. Semin Perinatol. 2003;27:281-7.
54. 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.
55. Eronen M, Kari A, Pesonen E, Hallman M. The effect of antenatal dexamethazone administration on the fetal and neonatal ductus arteriosus. A randomized double-blind study. Am J Dis Child. 1993;147:187-92.
56. Halliday HL, Ehrenkranz RA, Doyle LW. Early (< 8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2009;(1):CD001146. doi: 10.1002/14651858.CD001146.pub2.
57. Kim ES, Kim EK, Choi CW, et al. Intrauterine inflammation as a risk factor for persistent ductus arteriosus patency after cyclooxygenase inhibition in extremely low birth weight infants. J Pediatr. 2010;157:745-50.e1. doi: 10.1016/j.jpeds.2010.05.020.
58. Shah DM, Shenai JP, Vaughn WK. Neonatal outcome of premature infants of mothers with preeclampsia. J Perinatol. 1995;15:264-7.
59. Tsai M-L, Lien R, Chiang M-C, et al. Prevalence and Morbidity of Late Preterm Infants: Current Status in a Medical Center of Northern Taiwan. Pediatr Neonatol. 2012;53:171-7. doi: 10.1016/j.pedneo.2012.04.003.
60. Ognean ML, Stoicescu SM, Boanta O, Nastase L, Gliga C, Cucerea M. Intubation-Surfactant: Extubation on Continuous Positive Pressure Ventilation. Who are the best candidates? J Crit Care Med. 2016;2:73-9. DOI: 10.1515/jccm-2016-0010.
61. Pegoli W. Pericardium and great vessels. In: Oldham KT, Colombiani PM, et al. (eds). Principles and Practice of Pediatric Surgery. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins 2005; 1019.
62. Smith GC. The pharmacology of the ductus arteriosus. Pharmacol Rev. 1998;50:35-58.
63. Sweet Dg, Carnielli V, Greisen G, et al. European consensus guidelines on the management of neonatal respiratory distress syndrome in preterm infants--2013 update. Neonatology. 2013;103:353-68. doi: 10.1159/000349928.
64. Tauzin L, Joubert C, Noel A-C, Bouissou A, Moulies M-E. Effect of persistent patent ductus arteriosus on mortality and morbidity in very low-birthweight infants. Acta Paediatr. 2012;101:419-23. doi: 10.1111/j.1651-2227.2011.02550.x.
65. Ferreira CH, Carmona F, Martinez FE. Prevalence, risk factors and outcomes associated with pulmonary hemorrhage in newborns. J Pediatr (Rio J). 2014;90:316-22. doi: 10.1016/j.jped.2013.12.008.
67. Stucin Gantar I, Babnik J, Kornhauser Cerar L, Sinkovec J, Wraber B. Prenatal and postnatal risk factors for developing bronchopulmonary dysplasia. Signa Vitae. 2011;6:46-51.
68. Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev. 2013;(4):CD003481. doi: 10.1002/14651858.CD003481.pub5.
69. Benitz WE. Patent ductus arteriosus: to treat or not to treat? Arch Dis Child Fetal Neonatal Ed. 2012;97:F80-2. doi: 10.1136/archdischild-2011-300381.
70. Marshall DD, Kotelchuck M, Young TE, Bose CL, Kruyer L, O’Shea TM. Risk factors for chronic lung disease in the surfactant era: a North Carolina population-based study of very low birth weight infants. North Carolina Neonatologists Association. Pediatrics. 1999;104:1345-50.
71. Noerr B. Current controversies in the understanding of necrotizing enterocolitis Part 1. Adv Neonatal Care. 2003;3:107-20.
72. Shortland DB, Gibson NA, Levene MI, Archer LNJ, Evans DH, Shaw DE. Patent ductus arteriosus and cerebral circulation in preterm infants. Dev Med Child Neurol. 1990;32:386-93.
73. Ibrahim TK, Haium AAA, Chandran S, Rajadurai VS. Current Controversies in the Management of Patent Ductus Arteriosus in Preterm Infants. Indian Pediatr. 2014;51:289-94.