A Randomized Placebo-Controlled Pilot Trial of Early Targeted Nonsteroidal Anti-Inflammatory Drugs in Preterm Infants with a Patent Ductus Arteriosus

Waal, Koert de; Phad, Nilkant; Stubbs, Michelle; Chen, Yan; Kluckow, Martin

doi:10.1016/j.jpeds.2020.08.062

Cited by 31 publications

(23 citation statements)

References 38 publications

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“…The median age at the time of death did not differ between the groups (►Table 2), and the survival curves were almost identical (Cox's F-test, p ¼ 0.377). In the expectant management group, infants who died had a significantly lower gestational age than in the treatment group (25 [range: [24][25] weeks vs. 27 [25][26][27] weeks, respectively, p ¼ 0.04). Infants with a lower gestational age had a significantly higher mortality (r S ¼ -0.52; p ¼ 0.000).…”

Section: Resultsmentioning

confidence: 98%

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Randomized Noninferiority Trial of Expectant Management versus Early Treatment of Patent Ductus Arteriosus in Preterm Infants

et al. 2022

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Objective The study aimed to investigate, whether expectant management is non-inferior to early patent ductus arteriosus (PDA) treatment with regard to the composite of mortality and/or incidence of bronchopulmonary dysplasia (BPD) in very preterm infants. Study design 208 very preterm infants of the gestational age <32 weeks, birth weight <1500 g, chronological age <72 h, and PDA >1.5 mm were randomized between the treatment or expectant management group. Both, the intention-to-treat and per-protocol analyses were performed. Results 104 (50%) patients received rectal ibuprofen (n=52) or intravenous acetaminophen (n=52) within first 72 h of life. In 104 (50%) infants expectant management was used. Eight of them (8%) received rescue treatment at the median age of 7 (6-13) days. PDA closure rates by the 10th day of life were 81% (n=84) in the treatment arm, and 58% (n=60) in the expectant management arm (p<0.01). The median age at the time of ductus closure was 5 (5-6) days in the treatment arm, and 8 (6-11) days in the expectant management arm (p<0.01). At the time of discharge, ductus was closed in 83% of treated infants and in 78% of patients who were managed expectantly (p>0.05). No significant difference between the groups was found for the primary clinical outcomes, BPD/death, or the secondary outcomes at a postmenstrual age of 36 weeks or discharge. Conclusion Expectant management is non-inferior to early PDA treatment for reducing the incidence of death/BPD. Compared with the expectant management, early pharmacological treatment provides more frequent and faster PDA closure in preterm infants with gestational age <32 weeks, but neither reduces morbidity nor improves survival rates.

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Section: Resultsmentioning

confidence: 98%

“…The lower rate of spontaneous PDA closure in the study by de Waal et al could be associated with the involvement of only extremely preterm infants (gestational age <28 weeks). 27…”

Section: Discussionmentioning

confidence: 99%

Randomized Noninferiority Trial of Expectant Management versus Early Treatment of Patent Ductus Arteriosus in Preterm Infants

et al. 2022

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“…Several recent RCTs have attempted to determine whether exposures to moderate-large PDA shunt that persist for more than a week affect morbidity. 3 , 76 - 78 These trials enrolled infants <28-29 weeks’ gestation with moderate-large PDA shunts which were likely to persist for several weeks. Two trials compared early routine treatment starting at 8 days with a conservative, expectant management approach.…”

Section: Management Of Pdamentioning

confidence: 99%

“…Similar problems (either unexpectedly low rates of drug-induced PDA closure or high rates of spontaneous closure) existed in 2 additional pilot RCTs, that enrolled infants within 72 hours of birth. 77 , 78 Future RCTs will clearly need more effective PDA closure strategies.…”

Section: Management Of Pdamentioning

confidence: 99%

An Update on Patent Ductus Arteriosus and What is Coming Next

Erdeve

Okulu

Singh

et al. 2022

Turk Arch Pediatrics

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Patent ductus arteriosus is the most common cardiovascular condition in preterm infants. There is a significant uncertainty about when and how to close ductus arteriosus in preterm infants due to a high spontaneous closure rate even in very immature preterm infants. Diagnosis and management of patent ductus arteriosus remain a challenge for both neonatologists and pediatric cardiologists. Researchers have tried to define a balance between an expectant approach and active treatment in selected infants. This review aimed to focus on the pathophysiology and management of patent ductus arteriosus and to make suggestions about approaches that might eliminate the association of morbidities with patent ductus arteriosus.

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“…PDA closure can be performed pharmacologically or, in case of failure or contraindication, with surgical ligation or transcatheter closure (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Early Urinary Metabolomics in Patent Ductus Arteriosus Anticipates the Fate: Preliminary Data

et al. 2020

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Introduction: In premature neonates, the persistence of hemodynamically significant ductus arteriosus (hsPDA) can be associated with short- and long-term consequences, impairing their outcome. The correct strategy of management for such condition is under debate, especially regarding contraindications and/or side effects. In recent years, metabolomics was applied to several perinatal, pediatric, and adult conditions to investigate potential biomarkers of disease, which have become useful for early diagnosis and/or therapeutic management.Aim of the Study: The main purpose of our exploratory study was to asses, through 1H-NMR metabolomics analysis of urinary samples at birth, possible metabolic pathways differentiating, with a significant predictive power, those preterm neonates who will subsequently develop hsPDA and neonates of comparable gestational age (GA) who will undergo spontaneous ductal closure or the persistence of an irrelevant PDA (no-hsPDA). Moreover, we investigated potential prenatal or perinatal clinical factors potentially influencing the development of hsPDA.Materials and Methods: We enrolled n = 35 preterm neonates with GA between 24 and 32 weeks; urinary samples were collected within the first 12 h of life. Patients were closely monitored regarding intensive care, respiratory support, fluid balance and administered drugs; an echocardiogram was performed at 48–72 h.Results: Our results reported a significant correlation between lower GA at birth and the development of hsPDA. Moreover, neonates with GA ≤ 30w developing hsPDA were characterized by lower Apgar scores at 1′ and 5′, higher rates of perinatal asphyxia, higher need of delivery room resuscitation and subsequent surfactant administration. Interestingly, metabolomics analysis at birth detected a clear separation between the 1H-NMR urinary spectra of subjects GA ≤ 30w not developing hsPDA (n = 19) and those of subjects born at GA ≤ 30w in which hsPDA was confirmed at 48–72 h of life (n = 5).Conclusions: This is the first study applying metabolomics to investigate the PDA condition. Although preliminary and conducted on a limited sample, our results reveal that metabolomics could be a promising tool in the early identification of hsPDA, potentially superior to the clinical or laboratory predictive tools explored to date and even to the clinical observations and correlations in our sample, through the detection of specific urinary metabolites.

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A Randomized Placebo-Controlled Pilot Trial of Early Targeted Nonsteroidal Anti-Inflammatory Drugs in Preterm Infants with a Patent Ductus Arteriosus

Cited by 31 publications

References 38 publications

Randomized Noninferiority Trial of Expectant Management versus Early Treatment of Patent Ductus Arteriosus in Preterm Infants

Randomized Noninferiority Trial of Expectant Management versus Early Treatment of Patent Ductus Arteriosus in Preterm Infants

An Update on Patent Ductus Arteriosus and What is Coming Next

Early Urinary Metabolomics in Patent Ductus Arteriosus Anticipates the Fate: Preliminary Data

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