Failure of a repeat course of cyclooxygenase inhibitor to close a PDA is a risk factor for developing chronic lung disease in ELBW infants

Lynda Adrouche-Amrani, Robert S Green, Karen M Gluck, Jing Lin, Lynda Adrouche-Amrani, Robert S Green, Karen M Gluck, Jing Lin

Abstract

Background: The optimal treatment regimen or protocol for managing a persistent patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants has not been well established. This study was aimed at evaluating the failure rate of a cyclooxygenase (COX) inhibitor (COI) for PDA closure and to determine the incidence of a PDA requiring ligation in ELBW infants. We examined the clinical characteristics and risk factors that may predict the clinical consequences of failure of PDA closure by COI.

Methods: Medical information on 138 infants with birth weight (BW) < 1000 gm who survived for > 48 hours was retrieved. Clinical characteristics and outcomes of patients whose PDAs closed with COI were compared with those who did not close.

Results: Of the 138 patients, 112 survived to discharge. Eighty (71.4%) of those who survived received 1-3 courses of COI treatment for a symptomatic PDA. A total of 32 (40%) failed COI treatment and underwent PDA ligation. Multivariable logistic regression analysis suggests that the observed differences in the outcomes in infants with or without symptomatic PDA can be explained by the babies with symptomatic PDA being more immature and sicker. No significant difference was seen in the incidence of chronic lung disease (CLD) in infants whose PDA was treated medically versus those who failed medical treatment and then underwent ligation. However, after adjusting for disease severity and other known risk factors, the odds ratio of developing CLD for surviving babies with a persistent PDA compared to those whose PDA was successfully closed with 1-2 courses of COI is 3.24 (1.07-9.81; p = 0.038).

Conclusions: When successfully treated, PDA in ELBW infants did not contribute significantly to the adverse outcomes such as CLD, retinopathy of prematurity (ROP) and age at discharge. This suggests that it is beneficial for a hemodynamically significant PDA to be closed. The failure of a repeat course of COI to close a PDA is a major risk factor for developing CLD in ELBW infants.

References

    1. Duddell GG, Gersony M. Patent ductus arteriosus in neonates with severe respiratory disease. J Pediatr. 1984;104:915–20. doi: 10.1016/S0022-3476(84)80499-0.
    1. Hamrick SEG, Hansmann G. Patent ductus arteriosus of the preterm infant. Pediatr. 2010;125:1020–30. doi: 10.1542/peds.2009-3506.
    1. 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. Pediatr. 2006;117:1113–21. doi: 10.1542/peds.2005-1528.
    1. Brown ER. Increased risk of bronchopulmonary dysplasia in infants with patent ductus arteriosus. J Pediatr. 1979;95:865–6. doi: 10.1016/S0022-3476(79)80454-0.
    1. Weir FJ, Ohlosson A, Myhr TL, Fong K, Rayan ML. A patent ductus arteriosus is associated with reduced middle cerebral artery blood flow velocity. Euro J Pediatr. 1999;158:484–7. doi: 10.1007/s004310051125.
    1. Clyman RI, Chorne N. Patent ductus arteriosus: evidence for and against treatment. J Pediatr. 2007;150:216–9. doi: 10.1016/j.jpeds.2006.12.048.
    1. 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. doi: 10.1056/NEJM197609022951004.
    1. Friedman WF, Hirschklau MJ, Printz MP, Pitlick PT, Kirkpatrick SF. Pharmacologic closure of patent ductus arteriosus in the premature infant. N Engl J Med. 1976;295:526–9. doi: 10.1056/NEJM197609022951003.
    1. Van Overmeire B, Chemtob S. The pharmacological closure of the patent ductus arteriosus. Semin Fetal Neonatal Med. 2005;10:177–84. doi: 10.1016/j.siny.2004.10.003.
    1. Ivey HH, Kattwinkel J, Park TS, Krovetz LJ. Failure of indomethacin to close persistent patent ductus arteriosus in infants weighing under 1000 grams. Br Heart J. 1979;41:203–7.
    1. Richards J, Johnson A, Fox G, Campbell M. A second course of ibuprofen is effective in the closure of a clinically significant PDA in ELBW infants. Pediatr. 2009;124:e287–93. doi: 10.1542/peds.2008-2232.
    1. Kabra NS, Schmidt B, Roberts RS, Doyle LW, Papile L, Fanaroff A. the Trial of Indomethacin Prophylaxis in Preterms (TIPP) Investigators. Neurosensory impairment after surgical closure of patent ductus arteriosus in extremely low birth weight infants: results from the trial of indomethacin prophylaxis in preterms. J Pediatr. 2007;150:229–34. doi: 10.1016/j.jpeds.2006.11.039.
    1. Chorne N, Leonard C, Piecuch R, Clyman RI. Patent ductus arteriosus and its treatment as risk factors for neonatal and neurodevelopmental morbidity. Pediatr. 2007;119:1165–74. doi: 10.1542/peds.2006-3124.
    1. Subhedar NV, Tan AT, Sweeney EM, Shaw NJ. A comparison of indices of respiratory failure in ventilated preterm infants. Arch Dis Child Fetal Neonatal Ed. 2000;83:F97–100. doi: 10.1136/fn.83.2.F97.
    1. Parry G, Tucker J, Tarnow-Mordi W. for the UK neonatal staffing study collaborative group. CRIB II: an update of the clinical risk index for babies score. Lancet. 2003;361:1789–91. doi: 10.1016/S0140-6736(03)13397-1.
    1. Alexander F, Chiu L, Kroh M, Hammel J, More J. Analysis of outcome in 298 extremely low-birth-weight infants with patent ductus arteriosus. J Pediatr Surg. 2009;44:112–7. doi: 10.1016/j.jpedsurg.2008.10.019.
    1. Noori S, McCoy M, Friedlich P, Bright B, Gottipati V, Seri I, Sekar K. Failure of ductus arteriosus closure is associated with increased mortality in preterm infants. Pediatr. 2009;123:e138–44. doi: 10.1542/peds.2008-2418.
    1. 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. Pediatr. 1999;104:1345–50. doi: 10.1542/peds.104.6.1345.
    1. Noori S. Patent ductus arteriosus in the preterm infant: to treat or not to treat? J Perinatol. 2010;30:S31–7.
    1. Brooks JM, Travadi JN, Patole SK, Doherty DA, Simmer K. Is surgical ligation of patent ductus arteriosus necessary? The western Australian experience of conservative management. Arch Dis Child Fetal Neonatal Ed. 2005;90:F235–9. doi: 10.1136/adc.2004.057638.
    1. Gorden PV. Understanding intestinal vulnerability to perforation in the extremely low birth weight infant. Pediatr Res. 2009;65:138–44. doi: 10.1203/PDR.0b013e31818c7920.
    1. Attridge JT, Clark R, Walker MW, Gordon PV. New insights into spontaneous intestinal perforation using a national data set: (1) SIP is associated with early indomethacin exposure. J Perinatol. 2006;26:93–9. doi: 10.1038/sj.jp.7211429.
    1. Jhaveri N, Moon-Grady A, Clyman RI. Early surgical ligation versus a conservative approach for management of patent ductus arteriosus that fails to close after indomethacin treatment. J Pediatr. 2010;157:381–7. doi: 10.1016/j.jpeds.2010.02.062.
    1. Clyman R, Cassady G, Kirklin JK, Collins M, Philips JB. The role of patent ductus arteriosus ligation in bronchopulmonary dysplasia: reexamining a randomized controlled trial. J Pediatr. 2009;154:873–6. doi: 10.1016/j.jpeds.2009.01.005.
    1. Yang CZ, Lee J. Factors affecting successful closure of hemodynamically significant patent arteriosus with indomethacin in extremely low birth weight infants. World J Pediatr. 2008;4:91–6. doi: 10.1007/s12519-008-0017-7.
    1. Dani C, Bertini G, Corsini I, Elia S, Vangi V, Pratesi S. et al.The fate of ductus arteriosus in infants at 23-27 weeks of gestation: from spontaneous closure to ibuprofen resistance. Acta Paediatr. 2008;97:1176–80. doi: 10.1111/j.1651-2227.2008.00871.x.
    1. Carmo KB, Evans N, Paradisis M. Duration of indomethacin treatment of the preterm patent ductus arteriosus as directed by echocardiography. J Pediatr. 2009;155:819–22. doi: 10.1016/j.jpeds.2009.06.013.
    1. Hsu JH, Yang SN, Chen HL, Tseng HI, Dai ZK, Wu JR. B-type natriuretic peptide predicts responses to indomethacin in premature neonates with patent ductus arteriosus. J Pediatr. 2010;157:79–84. doi: 10.1016/j.jpeds.2009.12.045.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj