Pulmonary Arterial Hypertension after Ibuprofen Treatment for Patent Ductus Arteriosus in Very Low Birth Weight Infants

Kim, Sae Yun; Shin, Seung Han; Kim, Han Suk; Jung, Young Hwa; Kim, Ee Kyung; Choi, Jung Hwan

doi:10.1016/j.jpeds.2016.08.103

Cited by 15 publications

(8 citation statements)

References 22 publications

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“…Our experimental results show the inhibition of PDGF-BB, VEGF-A, and HIF-2α after ibuprofen treatment in premature infants. Considering the fundamental role of angiogenesis in the development of BPD, these findings could potentially explain the clinical observation that ibuprofen increases the risk of BPD and PAH shown in our and other studies ( 15 , 16 , 28 , 29 ). To our best knowledge, this is the first study to show the concentration change of angiogenesis-related growth factors after ibuprofen exposure, in paired blood samples from premature infants.…”

Section: Discussionsupporting

confidence: 75%

Decreased plasma levels of PDGF-BB, VEGF-A, and HIF-2α in preterm infants after ibuprofen treatment

et al. 2022

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IntroductionIbuprofen is one of the most common non-steroidal anti-inflammatory drugs used to close patent ductus arteriosus (PDA) in preterm infants. PDA is associated with bronchopulmonary dysplasia (BPD), while PDA closure by ibuprofen did not reduce the incidence of BPD or death. Previous studies have indicated an anti-angiogenesis effect of ibuprofen. This study investigated the change of angiogenic factors after ibuprofen treatment in preterm infants.MethodsPreterm infants with hemodynamically significant PDA (hsPDA) were included. After confirmed hsPDA by color doppler ultrasonography within 1 week after birth, infants received oral ibuprofen for three continuous days. Paired plasma before and after the ibuprofen treatment was collected and measured by ELISA to determine the concentrations of platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor A (VEGF-A), and hypoxia-inducible factor-2α (HIF-2α).Results17 paired plasma from infants with hsPDA were collected. The concentration of PDGF-BB and VEGF-A significantly decreased after ibuprofen treatment (1,908 vs. 442 pg/mL for PDGF-BB, 379 vs. 174 pg/mL for VEGF-A). HIF-2α level showed a tendency to decrease after ibuprofen treatment, although the reduction was not statistically significant (p = 0.077).ConclusionThis study demonstrated decreased vascular growth factors after ibuprofen exposure in hsPDA infants.

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Section: Discussionsupporting

confidence: 75%

Decreased plasma levels of PDGF-BB, VEGF-A, and HIF-2α in preterm infants after ibuprofen treatment

et al. 2022

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“…Unlike other studies in which ibuprofen was administered, [ 29 ] GI bleeding did not increase, GI function was not lowered, and the time to achieve a feeding of 50 mL/kg/day was significantly faster in the PT group than in the non-PT group. There have been some reports that ibuprofen administration is associated with persistent pulmonary hypertension of the newborn (PPHN), [ 30 , 31 ] but there were no cases of PPHN in this study.…”

Section: Discussioncontrasting

confidence: 67%

Single-dose prophylactic ibuprofen therapy for patent ductus arteriosus in preterm infants

Kim¹,

Chung²

2022

Medicine

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This study aimed to evaluate the short-term morbidities and efficacy of single-dose prophylactic intravenous ibuprofen for patent ductus arteriosus (PDA) on the first day of life in preterm infants.Data of 69 preterm infants with birth weight < 1250 g and gestational age < 30 weeks admitted to the neonatal intensive care unit were analyzed. Of these, 37 infants were assigned to the prophylactic treatment (PT) group and 32 were assigned to the nonprophylactic treatment (non-PT) group. Only the PT group administered intravenous ibuprofen (10 mg/kg) once within 6 hours after birth.Until postnatal day 7, ductal closure occurred in 11 (34.4%) infants in the non-PT group, and in 35 (94.6%) infants in the PT group, of which 30 (81.1%) infants had ductal closure on postnatal day 1. There were 2 (5.4%) infants in the PT group and 9 (28.1%) in the non-PT group who needed ibuprofen treatment due to moderate-to-large PDA after postnatal day 7. Preterm infants in the PT group were less likely to develop an intraventricular hemorrhage (≥grade 2) (adjusted odds ratio 0.007, 95% confidence interval 0.01-0.45), had a shorter duration of invasive ventilatory support and central venous catheter, and earlier postnatal age to achieve feeding of 50 and 100 mL/kg/day compared with those in the non-PT group.Single-dose prophylactic intravenous ibuprofen on the first day of life decreased the occurrence of a persistent PDA and intraventricular hemorrhage (≥grade 2), and reduced the duration of invasive ventilatory support, central venous catheter use, and hospital stay.

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“…In newborn rats, ibuprofen significantly diminishes neovascularization [15]. Clinical studies demonstrate a higher frequency of PAH after ibuprofen treatment in very low birth weight infants (<1500 g) [23]. Collectively, the anti-angiogenetic effect of ibuprofen might be the underlying mechanism of its effect on BPD, especially in extremely premature infants who are more vulnerable to blocked angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Neonatal ibuprofen exposure and bronchopulmonary dysplasia in extremely premature infants

et al. 2019

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ObjectiveTo evaluate the association of ibuprofen exposure with the risk of bronchopulmonary dysplasia (BPD) in extremely premature infants.Study designThis was a retrospective study of all extremely premature infants admitted to a tertiary unit from 2016 to 2018.ResultsA total of 203 extremely premature infants were included in this study. The rate of BPD was significantly higher in infants with early exposure to ibuprofen (42.5%) compared to infants with no exposure (21.6%, P = 0.001). After adjusting for covariates, the risk of BPD was associated independently with ibuprofen exposure (odds ratios (OR) 2.296, 95% confidence interval (CI): 1.166–4.522, p = 0.016). Further analysis showed a trend towards higher risk of BPD in infants with successful patent ductus arteriosus (PDA) closure after ibuprofen treatment (32.3%) compared to non-treated infants (20.2%, p = 0.162).ConclusionOur findings suggest that ibuprofen exposure may contribute to the occurrence of BPD in extremely preterm infants.

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Pulmonary Arterial Hypertension after Ibuprofen Treatment for Patent Ductus Arteriosus in Very Low Birth Weight Infants

Cited by 15 publications

References 22 publications

Decreased plasma levels of PDGF-BB, VEGF-A, and HIF-2α in preterm infants after ibuprofen treatment

Decreased plasma levels of PDGF-BB, VEGF-A, and HIF-2α in preterm infants after ibuprofen treatment

Single-dose prophylactic ibuprofen therapy for patent ductus arteriosus in preterm infants

Neonatal ibuprofen exposure and bronchopulmonary dysplasia in extremely premature infants

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