Prophylactic ibuprofen versus placebo in very premature infants: a randomised, double-blind, placebo-controlled trial

Gournay, Véronique; Rozé, J. C.; Küster, Alice; Daoud, Patrick; Cambonie, Gilles; Hascoët, J.-M.; Chamboux, C.; Blanc, Thierry; Fichtner, Christopher G.; Savagner, C.; Jb, Gouyon; Flurin, V.; Thiriez, Gérard

doi:10.1016/s0140-6736(04)17476-x

Cited by 143 publications

(112 citation statements)

References 22 publications

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“…36 Of 25 studies reporting the combined outcome of death or BPD, only one showed a reduction. 78 A single trial of prophylactic ligation described a decrease in NEC, 64 and one trial of ibuprofen prophylaxis found more NEC, 87 but most found no effect. IVH rates were lower in 3 trials of prophylactic indomethacin, 91,96,98 2 trials reported lower rates of IVH>grade 2, 100,106 and 30 found no effect.…”

Section: Findings From Individual Randomized-controlled Trialsmentioning

confidence: 99%

Treatment of persistent patent ductus arteriosus in preterm infants: time to accept the null hypothesis?

2010

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Section: Findings From Individual Randomized-controlled Trialsmentioning

confidence: 99%

Treatment of persistent patent ductus arteriosus in preterm infants: time to accept the null hypothesis?

2010

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“…5,6 Although prophylactic treatment with indomethacin reduces incidence of PDA and severe intraventricular hemorrhage in preterm infants, 7,8 there are no differences in mortality and long-term neurodevelopment. 9,10 Recent studies have shown that only one-third of very low birth weight infants develops significant PDA. 10,11 Therefore, a number of infants, whose PDA would otherwise close spontaneously, will be exposed to the treatment unnecessarily if prophylaxis strategy is used.…”

Section: Introductionmentioning

confidence: 99%

“…9,10 Recent studies have shown that only one-third of very low birth weight infants develops significant PDA. 10,11 Therefore, a number of infants, whose PDA would otherwise close spontaneously, will be exposed to the treatment unnecessarily if prophylaxis strategy is used. Clinical assessment for the diagnosis of PDA has been shown to be specific, but not sensitive.…”

Section: Introductionmentioning

confidence: 99%

N-terminal probrain natriuretic peptide and patent ductus arteriosus in preterm infants

Nuntnarumit

Khositseth

2008

J Perinatol

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Objective: To determine whether plasma N-terminal probrain natriuretic peptide (NT-proBNP) in premature infants could identify hemodynamically significant patent ductus arteriosus (HsPDA) and to determine the correlation between serial plasma NT-proBNP and echocardiographic assessment of ductal shunting.Study Design: An observational study involving 35 preterm infants who underwent echocardiographic assessment for PDA on day 2, 4 and 7 of life with simultaneous blood sampling for determination of NT-proBNP concentrations. HsPDA was diagnosed by left-to-right ductal shunt on color Doppler, measuring diameter >1.5 mm on two-dimensional echocardiography plus X2 clinical features of PDA.Result: Plasma NT-proNBP levels on day 2 in the HsPDA group (n ¼ 12) were significantly higher than in non-HsPDA group (n ¼ 23) with a median of 16 353 pg ml À1 (interquartile range (IQR), 12 360-33 459; range, 10 316-104 998) vs 3914 pg ml À1 (IQR, 2601-5782; range, 1535-19 516) (P<0.001), respectively. Eight infants (67%) in the HsPDA group responded to an initial course of indomethacin or ibuprofen and their NT-proBNP levels significantly decreased within 48 h after treatment compared with non-responders (P ¼ 0.007). NT-proBNP concentrations were significantly correlated with left atrial to aortic root ratio. A cut-off NT-proBNP on day 2 of 10 180 pg ml À1 offered the best predictive values for HsPDA with a sensitivity of 100% and a specificity of 91%.Conclusion: Plasma NT-proBNP on day 2 was found as a sensitive marker for predicting HsPDA in preterm infants. Successful closure of PDA was also correspondent with the decline in plasma NT-proBNP. Journal of Perinatology (2009) 29, 137-142; doi:10.1038/jp.2008 published online 20 November 2008 Keywords: preterm infant; patent ductus arteriosus; NT-proBNP Introduction It is of vital importance to recognize and properly treat hemodynamically significant patent ductus arteriosus (HsPDA) in preterm infants. PDA has been reported to be associated with morbidities in preterm infants as a result of ductal steal from systemic circulation, for example, pulmonary congestion, pulmonary hemorrhage, bronchopulmonary dysplasia, intraventricular hemorrhage and necrotizing enterocolitis. [1][2][3][4] Strategies for PDA closure involve prophylactic treatment, presymptomatic treatment for non-HsPDA, and treatment for HsPDA. 5,6 Although prophylactic treatment with indomethacin reduces incidence of PDA and severe intraventricular hemorrhage in preterm infants, 7,8 there are no differences in mortality and long-term neurodevelopment. 9,10 Recent studies have shown that only one-third of very low birth weight infants develops significant PDA. 10,11 Therefore, a number of infants, whose PDA would otherwise close spontaneously, will be exposed to the treatment unnecessarily if prophylaxis strategy is used. Clinical assessment for the diagnosis of PDA has been shown to be specific, but not sensitive. [12][13][14] Echocardiography is used to detect PDA and to assess the degree of shunting through vario...

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“…Two studies reported using prophylactic intravenous ibuprofen within 6 to 8 h after birth, with bowel perforation occurring in 8.0 to 8.3% of the infants, 8,21 whereas another study reported bowel perforation in 8.0% when ibuprofen (treatment) was used at a median age of 6 days. 22 Bowel perforation has also been reported in isolated infants within 48 h of oral ibuprofen prophylaxis, or with treatment of PDA.…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal complications associated with ibuprofen therapy for patent ductus arteriosus

Rao

Bryowsky

Mao³

et al. 2011

J Perinatol

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Objective: To review intestinal complications associated with ibuprofen treatment of patent ductus arteriosus (PDA).Study Design: Data from preterm infants treated with ibuprofen were retrospectively reviewed. w 2 test and Fischer's exact test were used for univariate analyses. Multivariate analyses with logistic regression modeling were used to identify risk factors.Result: One hundred and two infants were treated with ibuprofen for PDA. Nine (9/102, 8.8%) infants developed spontaneous intestinal perforation (SIP), whereas 93/102 (91.2%) did not. The mean (±s.d.) gestational age (GA) at birth in infants with and without SIP was 25.2 ( ± 1.3) vs 27.6 ( ± 2.4) weeks (P ¼ 0.02) and the median (interquartile) length of stay (LOS) was 109.5 (91.0 to 116.5) vs 75.0 (53.0 to 94.5) days (P ¼ 0.002), respectively. The mean ( ± s.d.) age at starting ibuprofen was 3.3 ( ± 1.3) vs 5.8 (±3.5) days in infants with and without SIP, respectively (P ¼ 0.03). In logistic regression analyses, increasing GA and later initiation of ibuprofen treatment were protective against risk of SIP; odds ratio, 95% confidence interval (OR, 95% CI) ¼ 0.26 (0.09 to 0.75), P ¼ 0.01 and 0.63 (0.41 to 0.95), P ¼ 0.03, respectively.Conclusion: Infants at lower GA are at risk of SIP when treated early with ibuprofen for symptomatic PDA.

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Prophylactic ibuprofen versus placebo in very premature infants: a randomised, double-blind, placebo-controlled trial

Cited by 143 publications

References 22 publications

Treatment of persistent patent ductus arteriosus in preterm infants: time to accept the null hypothesis?

Treatment of persistent patent ductus arteriosus in preterm infants: time to accept the null hypothesis?

N-terminal probrain natriuretic peptide and patent ductus arteriosus in preterm infants

Gastrointestinal complications associated with ibuprofen therapy for patent ductus arteriosus

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