Early Closure Of Ductus Arteriosus Research Articles

Early closure mechanisms of the ductus arteriosus in immature infants.

According to experimental studies, cardiopulmonary distress decreases after closure of patent ductus arteriosus. However, early closure of the ductus using ibuprofen or indomethacin has failed to increase survival without serious morbidity. We review relevant data aiming to define optimal early management strategies that promote early closure of ductus arteriosus without serious adverse effects. Literature in English was searched selectively focusing on the potential of using acetaminophen for early closure of the ductus. Prophylactic ibuprofen or indomethacin intended to close the ductus, predisposes infants to ischaemia, bleeding and immune dysfunction. Acetaminophen appears to have a similar efficacy as indomethacin or ibuprofen, and all three dose-dependently constrict the ductus. Ibuprofen and indomethacin cause non-specific inhibition of prostaglandin synthesis, while acetaminophen predominantly inhibits prostaglandin E synthesis. Owing to low CYP450 activity in infancy, acetaminophen toxicity has been rarely evident. However, increasing the dosage increases the oxidative stress. We review prophylactic treatments that may increase the safety and efficacy of acetaminophen. These include vitamin A, cysteine and glutamine, and low-dose corticosteroid supplementation. The current challenge is to define a safe perinatal management practice that promotes cardiorespiratory adaptation in immature infants, particularly the seamless closure of the ductus before significant cardiopulmonary distress develops.

Non-immune Hydrops Fetalis: Retrospective Evaluation of Pathophysiological Mechanisms

Objective: Nonimmune hydrops fetalis (NIHF) is associated with abnormal fluid collections in fetal soft tissues and serous cavities due to nonimmunologic causes. It should be considered as a symptom, rather than a disorder. We aimed to investigate etiology and pathophysiology in cases with NIHF during a four-year time period. Methods: Eleven live-born infants with NIHF were evaluated retrospectively. Demographic data, laboratory values, and results of specified tests were recorded. Etiology and pathophysiological mechanisms were established. Results: The mean gestational age at birth was 32.8±2.6 weeks and the mean birth weight was 2545±809 grams. All cases presented with edema and ascites. Chromosomal disorders (5/11) were the leading etiology. Pathophysiological mechanisms were observed as fetal hypotonia, fetal hypoxia, lymphatic disorders, hypoalbuminemia, early closure of ductus arteriosus, anemia, and right-sided heart failure. Mortality was 72%. Conclusion: In the presented study NIHF occurred as a symptom which was presented in various conditions based on different mechanisms. Evaluations made in infants with NIHF should aim both diagnosis of the condition as well as finding out the underlying pathophysiological mechanisms. Mortality rate in infants with NIHF is high even though the improvements in neonatal care.

Paracetamol Accelerates Closure of the Ductus Arteriosus after Premature Birth: A Randomized Trial

To study the biologic effect of paracetamol, an inhibitor of prostaglandin synthase, on early closure of ductus arteriosus, and to evaluate possible adverse effects associated with the drug. In a controlled, double-blind, phase I-II trial, very low gestational age (<32weeks) infants requiring intensive care were randomly assigned to intravenous paracetamol or placebo (0.45% NaCl). A loading dose of 20mg/kg was given within 24hours of birth, followed by 7.5mg/kg every 6hours for 4days. Daily cardiac ultrasound examinations of ductal calibers were performed before the first dose, and until 1day after the last dose. The main outcome was a decrease in the ductal caliber without side effects. Of 63 screened infants, 48 were randomized: 23 were assigned to paracetamol and 25 to placebo. Before the intervention, their ductal calibers were similar. During the intervention, the ductus closed faster in the paracetamol group (hazard ratio 0.49, 95% CI 0.25-0.97, P=.016). The mean (95% CI) postnatal ages for ductal closure were 177hours (31.1-324) for the paracetamol-treated vs 338hours (118-557) for controls (P=.045). Paracetamol serum levels were within the therapeutic range, and no adverse effects were evident. Prophylactic paracetamol induced early closure of the ductus arteriosus without detectable side effects. Further trials are required to determine whether intravenous paracetamol may safely prevent symptomatic patent ductus arteriosus. ClinicalTrials.gov: NCT01938261; European Clinical Trials Database: EudraCT 2013-008142-33.

Early paracetamol treatment associated with lowered risk of persistent ductus arteriosus in very preterm infants

Objectives: Persistent ductus arteriosus (PDA) delays the recovery of very preterm infants (VLGA, gestation <32 weeks). Indomethacin/ibuprofen treatment and ligation of PDA have complications. As a prostaglandin synthase inhibitor paracetamol may also promote the closure of ductus arteriosus. We studied retrospectively whether early paracetamol therapy was associated with decreased incidence of PDA without adverse events.Methods: On June 2009, we introduced intravenous paracetamol during early respiratory therapy. We included 105 VLGA infants who received paracetamol before the age of 72 h. The loading dose was 20 mg/kg followed by 7.5 mg/kg every 6 hours. The 96 VLGA infants admitted from January 2008 to May 2009 without lethal congenital disease were controls. Infants dying very early were excluded, leaving 102 paracetamol-exposed and 88 controls for analysis.Results: After the introduction of paracetamol, the incidence of PDA decreased from 30.7% to 14.7% (p = 0.008). Ibuprofen treatment was given to 15 paracetamol-treated and to 26 control infants (p = 0.013). Three paracetamol-exposed and seven control infants required surgery. There was no detectable increase in adverse events.Conclusions: Annual incidence of PDA decreased after introduction of paracetamol. Efficacy and safety in promoting the early closure of ductus arteriosus remains to be established.