A Comparison of Early Ibuprofen and Indomethacin Administration to Prevent Intraventricular Hemorrhage Among Preterm Infants


Intraventricularhemorrhage (IVH) is one of thecommon morbidities among preterm neonates. In thepresentstudy, we set out to evaluate the efficacy of two prophylactic modalities (ibuprofen and indomethacin prophylaxis) for prevention of IVH in our local setting. A prospective study was carried out in Akbar-Abadi Hospital, Tehran-Iran (2013-2014). Ninety-six preterm neonates who cared in closed incubator entered the study. Neonates randomly assigned into 3 groups; control, oral indomethacin (0.2 mg/kg indomethacin daily for 3 days) and oral ibuprofen (10,5,5 mg/kg ibuprofen every 24 hours during 3) administration. For all subjects brain sonography examination was performed in 3rd day, first, 2nd week of life and when infants reached to 36 and 42 weeks of postmenstrual age. The IVH prevalence and the effectiveness of the drugs among groups were statistically assessed. Of all 93 subjects; 14 cases had IVH (15.1%). IVH was significantly more frequent in the controls than in other groups (P=0.049). Prophylactic treatment could significantly decrease the incidence of grade 3 or 4 IVH in experimental groups (P=0.008). There were no significant differences between the three experimental groups with respect to theincidence of GI bleeding, Oliguria, renal dysfunction or NEC (P>0.05). This study demonstrates that low-dose prophylactic indomethacin and ibuprofen are equally associated with a reduction of IVH without any significant side effects like renal dysfunction, GI bleeding or NEC.

Ryan JG, Dogbey E. Preterm Births: A Global Health Problem. MCN Am J Matern Child Nurs 2015;40(5):278-3.doi:10.1097/NMC.0000000000000174.

Basten M, Jaekel J, Johnson S, Gilmore C, Wolke D. Preterm Birth and Adult Wealth: Mathematics Skills Count. Psychol Sci 2015;26(10):1608-19. doi: 10.1177/0956797615596230. Epub 2015 Aug 31.

Iyer KK, Roberts JA, Hellström-Westas L, Wikström S, Hansen Pupp I, Ley D, Breakspear M, et al. Early Detection of Preterm Intraventricular Hemorrhage From Clinical Electroencephalography 2015;43(10):2219-27. doi: 10.1097/CCM.0000000000001190.

Mirza H, Oh W, Laptook A, Vohr B, Tucker R, Stonestreet BS. Indomethacin prophylaxis to prevent intraventricular hemorrhage: association between incidence and timing of drug administration. J Pediatr 2013 Sep;163(3):706-10.e1. doi: 10.1016/j.jpeds.2013.02.030. Epub 2013 Mar 22.

Fowlie PW: Prophylactic indomethacin; systematic review and meta-analysis. Arch Dis Child 1996; 74: F81-F87

Kumar Nair PA, Pai MG, Gazal HA, Da Costa DE, A Khusaiby SM. Indomethacin prophylaxis for intraventricular hemorrhage in very low birth weight babies. Indian Pediatr 2004;41(6):551-8.

Ment LR, Vohr BR, Makuch RW, Westerveld M, Katz KH, Schneider KC, Duncan CC, Ehrenkranz R, Oh W, Philip AG, Scott DT, Allan WC. Prevention of intraventricular hemorrhage by indomethacin in male preterm infants. J Pediatr 2004;145(6):832-4.

Aranda JV, Thomas R. Systematic review: intravenous Ibuprofen in preterm newborns. Semin Perinatol 2006;30:114.

McCrea HJ, Ment LR. The Diagnosis, Management and Postnatal Prevention of Intraventricular Hemorrhage in the Preterm Neonate. Clin Perinatol 2008; 35(4): 777–vii. doi:10.1016/j.clp.2008.07.014. McCrea, BS [MD/PhD student]a and Laura R. Ment, M.D

Dani C, Bertini G, Pezzati M, Poggi C, Guerrini P, Martano C, Rubaltelli FF. Prophylactic ibuprofen for the prevention of intraventricular hemorrhage among preterm infants: a multicenter, randomized study. Pediatrics 2005 Jun;115(6):1529-35.

NM Chan, CW Law, KF Kwan. Ibuprofen versus indomethacin treatment of patent ductus arteriosus: comparative effectiveness and complications Hong Kong Med J 2014;20:205-12

Shah R, Mullany LC, Darmstadt GL, Mannan I, Rahman SM, Talukder RR. Incidence and risk factors of preterm birth in a rural Bangladeshi cohort. BMC Pediatr 2014; 24(14)112. doi: 10.1186/1471-2431-14-112.

Khoshnood M, Karimi Z, Rezaienejad M, Basiri A, Torkestani F, Saleh Gargari S. Perinatal complications associated with preterm deliveries at 24 to 33 weeks and 6 days gestation (2011- 2012): A hospital-based retrospective study. Iran J Reprod Med 2015; 13(11): 697–702. PMCID: PMC4695684

Papile LA, Burstein J, Burstein R, et al. Incidence and evolution of subsependymal and intraventricular hemorrhage. A study of infants with birth weights less than 1500 grams. J Pediatr 1978; 92: 529-534.

Khalessi N, Farahani Z, Shariat M, Rezaeizadeh G. Risk factors of intracranial hemorrhage in premature neonates. Acta Med Iran 2014;52(9):687-9.

Pishva N, Parsa G, Saki F, Saki M, Saki MR. Intraventricular hemorrhage in premature infants and its association with pneumothorax. Acta Med Iran 2012;50(7):473-6.

Jodeiry B, Heidarzadeh M, Sahmani-Asl S, Hoseini M, Javaherizadeh H, Eliasi S, Abedini K. Study of intraventricular hemorrhage in VLBW neonates admitted in Al-Zahra Hospital, Tabriz, Iran. Niger J Med 2012;21(1):92-7.

Garner RS, Miller C, Burchfield DJ. Prophylactic indomethacin infusion increases fractional cerebral oxygen extraction in ELBW neonates. J Perinatol 2012 Sep;32(9):695-8. doi: 10.1038/jp.2011.175. Epub 2012 Jan 5.

Mirza H, Laptook AR2, Oh W, Vohr BR, Stoll BJ, Kandefer S, Stonestreet BS. Effects of indomethacin prophylaxis timing on intraventricular haemorrhage and patent ductus arteriosus in extremely low birth weight infants. Arch Dis Child Fetal Neonatal Ed 2016. pii: fetalneonatal-2015-309112. doi: 10.1136/archdischild-2015-309112. [Epub ahead of print]

Schmidt B, Davis P, Moddemann D, et al. Trial of indomethacin prophylaxis in preterms investigators: long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants.NEngl J Med 2001; 344: 1966–72.

Johnston PG, Gillam-Krakauer M, Fuller MP, Reese J. Evidence-based use of indomethacin and ibuprofen in the neonatal intensive care unit. Clin Perinatol 2012 Mar;39(1):111-36. doi: 10.1016/j.clp.2011.12.002. Epub 2012 Jan 13.

Khalessi N, Farahani Z, Shariat M, Rezaeizadeh G. Risk factors of intracranial hemorrhage in premature neonates.Acta Med Iran 2014;52:687-9.

IssueVol 54, No 12 (2016) QRcode
Intraventricular hemorrhage Prophylaxis Indomethacin Ibuprofen

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Kalani M, Shariat M, Khalesi N, Farahani Z, Ahmadi S. A Comparison of Early Ibuprofen and Indomethacin Administration to Prevent Intraventricular Hemorrhage Among Preterm Infants. Acta Med Iran. 54(12):788-792.