Ibuprofen Use to Reduce the Incidence and Severity of Bronchopulmonary Dysplasia: A Pilot Study

Raju, N.V.S. Lakshmipathi; Bharadwaj, R.; Thomas, Ronald; Konduri, Girija G.

doi:10.1038/sj.jp.7200296

Cited by 24 publications

(17 citation statements)

References 13 publications

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“…In the study by Raju et al, 32 in which ibuprofen was administered orally or intravenously to 9 preterm infants for the prevention of bronchopulmonary dysplasia, the study drug was withdrawn in 1 infant after 8 days (15 doses) of treatment because of gastrointestinal hemorrhage that occurred 6 hours after the last dose. However, this infant also received steroids and aminophylline, which potentially can cause gastrointestinal bleeding, and it is not clear whether this infant received intravenous or oral ibuprofen.…”

Section: Discussionmentioning

confidence: 99%

“…However, this infant also received steroids and aminophylline, which potentially can cause gastrointestinal bleeding, and it is not clear whether this infant received intravenous or oral ibuprofen. 32 Furthermore, gastrointestinal adverse reactions have been observed among preterm and term infants whose mothers were treated with antenatal indomethacin without direct contact of the nonsteroidal anti-inflammatory drugs with the gastrointestinal tract of the newborn. [35][36][37] Serum creatinine levels in our patients were within normal range at all times, so there was no contraindication for a second or third dose of ibuprofen when it was needed.…”

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confidence: 99%

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Closure of Patent Ductus Arteriosus With Oral Ibuprofen Suspension in Premature Newborns: A Pilot Study

et al. 2003

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ABSTRACT. Objective. Patent ductus arteriosus (PDA), a common finding among premature infants, is conventionally treated by intravenous indomethacin. Intravenous ibuprofen was recently shown to be as effective and to have fewer adverse reactions in preterm infants. If equally effective, then oral ibuprofen for PDA closure would have several important advantages over the intravenous route. This study was designed to determine whether oral ibuprofen treatment is efficacious and safe in closure of a PDA in premature infants with respiratory distress syndrome.Methods. Twenty-two preterm newborns (gestational age: 27.5 ؎ 1.75 [range: 23.9 -31 weeks]; weight: 979 ؎ 266 [range: 380-1500 g]) with PDA and respiratory distress syndrome were studied prospectively. They received oral ibuprofen suspension 10 mg/kg/body weight for the first dose, followed at 24-hour intervals by 2 additional doses of 5 mg/kg each, if needed, starting on the second day of life. Echocardiography was performed before treatment and 24 hours after each dose. Every child underwent cranial ultrasonography before and after each ibuprofen dose. The rate of ductal closure, the need for additional treatment, side effects, complications, and the infants' clinical courses were recorded.Results. Ductal closure was achieved in all newborns except for 1 (95.5%), in whom clinically nonsignificant ductal shunting persisted. No infant required surgical ligation of the ductus. There was no reopening of the ductus after closure had been achieved. Fourteen newborns were treated with 1 dose of ibuprofen, 6 were treated with 2 doses, and the remaining 2 were treated with 3 doses. The survival rate at 1 month was 86.4% (19 of 22). Three (13.6%) infants died from the following causes: 1 who was born at 24 weeks' gestation with a birth weight of 380 g died as a result of extreme prematurity complications, necrotizing enterocolitis, and low birth weight; 1 died as a result of Candida sepsis; and the third died as a result of Klebsiella sepsis. Intraventricular hemorrhage was observed in 7 infants. The classification was changed from grade 2 to grade 3 in 1 and from grade 0 to grade 1 or higher in 3 others. The rate of survival to discharge was 86.4% (19 of 22). No bronchopulmonary dysplasia was observed in the study group, and there was no case of tendency to bleed. There were no significant differences in the levels of serum creatinine before and after treatment with oral ibuprofen.Conclusions. Oral ibuprofen suspension may be an effective and safe alternative for PDA closure in premature infants with PDA. However, larger comparative studies are warranted. Pediatrics 2003;112:e354 -e358. URL: http://www.pediatrics.org/cgi/content/full/112/5/ e354; oral ibuprofen, patent ductus arteriosus, premature newborns.ABBREVIATIONS. PDA, patent ductus arteriosus; RDS, respiratory distress syndrome; IVH, intraventricular hemorrhage; NEC, necrotizing enterocolitis.T he incidence of patent ductus arteriosus (PDA) in premature infants who weigh between 500 and 1500 g at birth is appr...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Closure of Patent Ductus Arteriosus With Oral Ibuprofen Suspension in Premature Newborns: A Pilot Study

et al. 2003

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“…Meta-analysis has confi rmed that ibuprofen use in preterm infants is associated with an increased incidence of CLD [1] . Also, in a recent small trial of ibuprofen in infants with CLD, the incidence of NEC was increased in the test group [2] .…”

Section: Discussionmentioning

confidence: 93%

“…However, some recent studies have suggested that ibuprofen may be associated with the development of infl ammatory diseases, including necrotizing enterocolitis (NEC) and chronic lung disease (CLD), in premature infants [1,2] . These conditions are preceded by infection and/or tissue hypoxia, and are characterized by elevated levels of infl ammatory mediators that reduce the rate of neutrophil apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Effects of Ibuprofen and Hypoxia on Neutrophil Apoptosis in Neonates

Hanna

Graboski

Laskin³

et al. 2004

Neonatology

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Background: Ibuprofen is a cyclooxygenase inhibitor that is effective in treating patent ductus arteriosus in preterm infants. However, recent trials have suggested that it may increase the risk of developing necrotizing enterocolitis and chronic lung disease. Apoptosis of neutrophils is impaired in newborns, leading to reduced clearance of activated cells and possibly contributing to the susceptibility of infants to these inflammatory diseases. Objectives: In the present studies, we investigated the hypothesis that ibuprofen reduces neonatal neutrophil apoptosis in the setting of hypoxia or lipopolysaccharide (LPS). Methods: Neutrophils and peripheral blood mononuclear cells were isolated from adult and cord blood and cultured in the presence or absence of ibuprofen (1.5 mM), hypoxia (<5% O₂), and bacterial LPS (100 ng/ml). Apoptosis was quantified by measuring binding of FITC-Annexin V using flow cytometry. Cytokine concentrations in cell supernatants were measured by ELISA. Results: After 24 h, 20% of adult and 14% of neonatal neutrophils were apoptotic. Apoptosis was reduced by hypoxia in both adult and neonatal cells. Ibuprofen further reduced neutrophil apoptosis, but only when the cells were cultured in the presence of mixed leukocytes. This suggests that the effects of ibuprofen on apoptosis are dependent on soluble products secreted by peripheral blood mononuclear cells. We found that production of tumor necrosis factor (TNF)-α by neonatal leukocytes was significantly increased by ibuprofen, and was further increased following exposure to ibuprofen in the presence of LPS and hypoxia. In contrast, production of macrophage inflammatory protein (MIP)-1α was not affected by treatment with ibuprofen, and ibuprofen blocked induction of this chemokine by LPS. Conclusion: We conclude that the net effect of ibuprofen on neutrophils is antiapoptotic, especially in the presence of hypoxia or LPS. This effect may be mediated, in part, by increased production of TNF-α by peripheral blood mononuclear cells. These data suggest that treatment of infants with ibuprofen, in the presence of infection and/or tissue hypoperfusion/hypoxia, may contribute to the development of inflammatory diseases.

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“…Apart from steroids, ibuprofen and cromolyn have been assessed for the prevention and treatment of BPD; however clinical studies have shown them to be ineffective [8,9]. Experimental studies using pentoxifylline have demonstrated suppressed synthesis of tumor necrosis factor (TNF) and granulocyte-macrophage colony stimulating factor (GM-CSF) by human monocytes and lung macrophages [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Nebulized pentoxifylline for prevention of bronchopulmonary dysplasia in very low birth weight infants: A pilot clinical study

Lauterbach

Szymura-Oleksiak

Pawlik

et al. 2006

The Journal of Maternal-Fetal & Neonatal Medicine

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Ibuprofen Use to Reduce the Incidence and Severity of Bronchopulmonary Dysplasia: A Pilot Study

Cited by 24 publications

References 13 publications

Closure of Patent Ductus Arteriosus With Oral Ibuprofen Suspension in Premature Newborns: A Pilot Study

Closure of Patent Ductus Arteriosus With Oral Ibuprofen Suspension in Premature Newborns: A Pilot Study

Effects of Ibuprofen and Hypoxia on Neutrophil Apoptosis in Neonates

Nebulized pentoxifylline for prevention of bronchopulmonary dysplasia in very low birth weight infants: A pilot clinical study

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