Ductus Arteriosus of Extremely Preterm Twins is More Resistant to Cyclooxygenase Inhibitors Than Those of Singletons

Preterm birth has been associated with altered cardiac phenotype in adults. Our aim was to test the hypothesis that children surviving extremely preterm birth have important structural or functional changes of the right heart or pulmonary circulation. We also examined relations between birth size, gestational age, neonatal diagnoses of bronchopulmonary dysplasia (BPD) and patent ductus arteriosus (PDA) with cardiac outcomes. We assessed a population-based cohort of children born in Sweden before 27 weeks of gestation with echocardiography at 6.5 years of age (n = 176). Each preterm child was matched to a healthy control child born at term. Children born preterm had significantly smaller right atria, right ventricles with smaller widths, higher relative wall thickness and higher estimated pulmonary vascular resistance (PVR) than controls. In preterm children, PVR and right ventricular myocardial performance index (RVmpi’) were significantly higher in those with a PDA as neonates than in those without PDA, but no such associations were found with BPD. In conclusion, children born extremely preterm exhibit higher estimated PVR, altered right heart structure and function compared with children born at term.

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Molecular Mechanisms Underlying Remodeling of Ductus Arteriosus: Looking beyond the Prostaglandin Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms22063238 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3238

Author(s):

Ho-Wei Hsu ◽

Ting-Yi Lin ◽

Yi-Ching Liu ◽

Jwu-Lai Yeh ◽

Jong-Hau Hsu

Keyword(s):

Adverse Effect ◽

Clinical Management ◽

Vascular Remodeling ◽

Molecular Mechanisms ◽

Surgical Intervention ◽

Ductus Arteriosus ◽

Clinical Problem ◽

Cyclooxygenase Inhibitors ◽

Medical Patients ◽

Fetal Circulation

The ductus arteriosus (DA) is a physiologic vessel crucial for fetal circulation. As a major regulating factor, the prostaglandin pathway has long been the target for DA patency maintenance or closure. However, the adverse effect of prostaglandins and their inhibitors has been a major unsolved clinical problem. Furthermore, a significant portion of patients with patent DA fail to respond to cyclooxygenase inhibitors that target the prostaglandin pathway. These unresponsive medical patients ultimately require surgical intervention and highlight the importance of exploring pathways independent from this well-recognized prostaglandin pathway. The clinical limitations of prostaglandin-targeting therapeutics prompted us to investigate molecules beyond the prostaglandin pathway. Thus, this article introduces molecules independent from the prostaglandin pathway based on their correlating mechanisms contributing to vascular remodeling. These molecules may serve as potential targets for future DA patency clinical management.

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Cyclooxygenase Inhibitors in Preterm Infants With Patent Ductus Arteriosus: Effects on Cardiac and Vascular Indices

Pediatric Cardiology ◽

10.1007/s00246-014-0947-x ◽

2014 ◽

Vol 35 (8) ◽

pp. 1429-1436 ◽

Cited By ~ 8

Author(s):

Arvind Sehgal ◽

Tejas Doctor ◽

Samuel Menahem

Keyword(s):

Patent Ductus Arteriosus ◽

Preterm Infants ◽

Ductus Arteriosus ◽

Cyclooxygenase Inhibitors ◽

Patent Ductus

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Comparison of the effect of two drugs paracetamol with intravenous ibuprofen in patent ductus arteriosus treatment

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20201741 ◽

2020 ◽

Vol 9 (5) ◽

pp. 690

Author(s):

Mehrdad Mirzarahimi ◽

Ramin Emamzadeghan ◽

Afsaneh Enteshari Moghaddam ◽

Narges Falsafi

Keyword(s):

Patent Ductus Arteriosus ◽

Ductus Arteriosus ◽

Alternative Therapy ◽

Cyclooxygenase Inhibitors ◽

Arterial Duct ◽

Intravenous Paracetamol ◽

Liver Parameters ◽

Intravenous Ibuprofen ◽

Patent Ductus

Background: Patent ductus arteriosus (PDA) is a common cause of morbidity and mortality among premature infants that affects more than 40% of them. PDA treatment includes medical and surgical treatment. Most drugs used to block PDA are cyclooxygenase inhibitors (ibuprofen and indomethacin). The role of paracetamol as an alternative therapy in PDA ligation has been considered in recent years due to the potential side effects of cyclooxygenase inhibitors.Methods: Patients in the first group were treated with intravenous paracetamol at a dose of 15 mg/kg every 6 hours for three days and the second group was treated with intravenous ibuprofen at a daily dose of 10 mg/kg daily and 5 mg/kg for the second and third days. At the end of the treatment period (day 3), they underwent echocardiography again. If the echocardiographic findings indicated no closure of the arterial duct, patients were treated with the aforementioned drug for another period and rechecked at the end of the third day, and at each stage required information was collected.Results: Arterial duct closure in paracetamol group was 96.7% and in ibuprofen group was 100%. The effects of both paracetamol and ibuprofen were similar in terms of renal parameters but in terms of effects on liver parameters. The effect of paracetamol on all liver parameters except aspartate transaminase (AST) was significant, but ibuprofen was able to affect only bilirubin among liver parameters and had no significant effect on both AST and alanine aminotransferase, parameters.Conclusions: Results showed that both paracetamol and ibuprofen are effective in treating of PDA and had similar impact.

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Severe hypothyroidism following a single topical exposure to iodine in a premature neonate

BMJ Case Reports ◽

10.1136/bcr-2020-240006 ◽

2021 ◽

Vol 14 (2) ◽

pp. e240006

Author(s):

Catherine Mary Breen ◽

Monica Fahim Salama ◽

Michael A Boyle

Keyword(s):

Thyroid Function ◽

Ductus Arteriosus ◽

Urinary Iodine ◽

Premature Neonate ◽

Thyroid Stimulating Hormone ◽

Urinary Iodine Excretion ◽

Free T4 ◽

Delayed Treatment ◽

Extremely Preterm ◽

Extremely Preterm Infants

A neonate, born at 24 weeks, underwent a patent ductus arteriosus ligation, with previous normal thyroid stimulating hormone (TSH) levels, developed severe hypothyroidism from topical exposure to iodine following a single surgical procedure at 28 days of life. A low free T4 level of 0.05 ng/dL and a high TSH level of 228 mIU/L was detected with an increased urinary iodine excretion level of 178 mg/L (reference range 0.30–1.97 mg/L). The thyroid ultrasound was normal. Levothyroxine was started immediately but thyroid function did not recover fully during admission and levothyroxine was required beyond term corrected. This case highlighted how susceptible extremely preterm infants are to iodine induced hypothyroidism, even short-term topical exposure. Delayed treatment of hypothyroidism can lead to profound neurodevelopmental delay. As surgical advances allow for interventions at earlier gestations, the importance of early thyroid function testing postexposure to iodine is highlighted and ultimately topical iodine should be avoided in these susceptible infants.

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Hypertrophic cardiomyopathy in an extremely preterm infant

BMJ Case Reports ◽

10.1136/bcr-2020-239787 ◽

2021 ◽

Vol 14 (3) ◽

pp. e239787

Author(s):

Apoorva Aiyengar ◽

Claire Howarth ◽

Sujith Pereira

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Patent Ductus Arteriosus ◽

Preterm Infant ◽

Preterm Infants ◽

Ductus Arteriosus ◽

Careful Consideration ◽

Differential Diagnoses ◽

Cardiac Remodelling ◽

Extremely Preterm ◽

Patent Ductus

We present a case of an extreme preterm infant (Baby X) born at 24-week gestation. The echocardiogram showed evidence of hypertrophic cardiomyopathy (HCM) and a patent ductus arteriosus (PDA). There are a number of well-known causes of neonatal HCM including genetic, metabolic and endocrine. PDA is commonly present in preterm infants, and this can contribute to cardiac remodelling and result in cardiac changes mimicking HCM. Furthermore, medications such as steroids can also cause HCM through various mechanisms. A careful consideration of all the different aetiologies for HCM is important for appropriate management of such cases. This report examines the evidence in the literature for the above differential diagnoses and highlights the challenges in diagnosing the underlying cause of HCM in a preterm infant.

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Conservative Non-intervention Approach for Hemodynamically Significant Patent Ductus Arteriosus in Extremely Preterm Infants

Frontiers in Pediatrics ◽

10.3389/fped.2020.605134 ◽

2020 ◽

Vol 8 ◽

Author(s):

Se In Sung ◽

Yun Sil Chang ◽

So Yoon Ahn ◽

Heui Seung Jo ◽

Misun Yang ◽

...

Keyword(s):

Patent Ductus Arteriosus ◽

Preterm Infants ◽

Necrotizing Enterocolitis ◽

Ductus Arteriosus ◽

Intervention Approach ◽

Extremely Preterm ◽

Extremely Preterm Infants ◽

Surgical Treatments ◽

Minimal Evidence ◽

Patent Ductus

While persistent patent ductus arteriosus (PDA) in preterm infants has been known to be associated with increased mortality and morbidities including bronchopulmonary dysplasia, and necrotizing enterocolitis, there is minimal evidence supporting their causal relationships, and most traditional medical and/or surgical treatments have failed to show improvements in these outcomes. As such, the pendulum has swung toward the conservative non-intervention approach for the management of persistent PDA during the last decade; however, the benefits and risks of this approach are unclear. In this mini review, we focused on whom, when, and how to apply the conservative non-intervention approach for persistent PDA, especially in extremely preterm infants.

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