cardiovascular-agents and Ductus-Arteriosus--Patent

Patent ductus arteriosus (PDA) poses a diagnostic and therapeutic dilemma for clinicians. Diagnosis of persistent PDA and determination of its clinical and hemodynamic significance are challenging. Although the condition has been associated with substantial neonatal morbidities such as intraventricular hemorrhage, bronchopulmonary dysplasia, and necrotizing enterocolitis, most therapeutic approaches have failed to show improvement in these outcomes. As such, clinicians have tended toward conservative management strategies; however, the benefits and risks of such an approach are unclear. In this review, we explore various clinical diagnostic modalities, echocardiographic parameters for assessment of shunt presence, shunt volume and its effect on cardiovascular and hemodynamic status, and challenges in determining if a PDA is hemodynamically significant and clinically relevant. From the therapeutic aspect, we review current evidence on conservative, pharmacological, and mechanical (surgical or nonsurgical ligation) approaches to PDA closure. Dose, route, duration, and comparison of pharmacological strategies are reviewed, with implications for future research.

Topics: Biomarkers; Cardiovascular Agents; Ductus Arteriosus, Patent; Hemodynamics; Humans; Infant, Newborn; Infant, Premature; Ligation

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Intracranial Hemorrhages; Severity of Illness Index

Although a moderate-sized patent ductus arteriosus (PDA) needs to be closed by the time a child is 1-2 years old, there is great uncertainty about whether it needs to be closed during the neonatal period. Although 95% of neonatologists believe that a moderate-sized PDA should be closed if it persists in infants (born before 28 weeks) who still require mechanical ventilation, the number of neonatologists who treat a PDA when it occurs in infants who do not require mechanical ventilation varies widely. Both the high likelihood of spontaneous ductus closure and the absence of randomized controlled trials, specifically addressing the risks and benefits of neonatal ductus closure, add to the current uncertainty. New information suggests that early pharmacologic treatment has several important short-term benefits for the preterm newborn. By contrast, ductus ligation, while eliminating the detrimental effects of a PDA on lung development, may create its own set of morbidities that counteract many of the benefits derived from ductus closure.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Ligation; Male; Pregnancy; Respiration, Artificial; Unnecessary Procedures

To evaluate the effects of indomethacin or ibuprofen compared with placebo on closure, morbidity and mortality in preterm infants <37 weeks' gestation with echocardiographically and/or clinically important patent ductus arteriosus (PDA) at >24 h of life.. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, Cochrane Library, clinicaltrials.gov, controlled-trials.com, American Pediatric and European Paediatric Research Societies and Effective Care of the Newborn Infant.. Systematic review with network meta-analysis of randomised studies comparing intravenous indomethacin, ibuprofen or placebo for PDA in preterm infants at >24 h of life.. Ten trials compared intravenous indomethacin versus intravenous ibuprofen, nine intravenous indomethacin versus placebo and one intravenous ibuprofen versus placebo. Both intravenous indomethacin (pooled RR 2.39 (95% CI 2.05 to 2.78)) and intravenous ibuprofen (RR 2.40 (95% CI 2.03 to 2.84)) closed a PDA more effectively than placebo. Intravenous ibuprofen was associated with approximately 30% greater risk of chronic lung disease than intravenous indomethacin (RR 1.28 (95% CI 1.03 to 1.60)) or placebo (RR 1.29 (95% CI 0.99 to 1.70)). Differences in risk or benefit were not significant between any combination of intravenous indomethacin, intravenous ibuprofen or placebo groups for intraventricular haemorrhage, necrotising enterocolitis and death. Reporting on neurological outcomes was insufficient for pooling.. Intravenous indomethacin or ibuprofen administered to preterm infants for PDA at >24 h of life promoted ductal closure, but other short-term benefits were not seen. Treatment with intravenous ibuprofen may increase the risk of chronic lung disease. Good-quality evidence of treatment effect on morbidity, mortality and improved neurodevelopment is urgently needed.

Topics: Cardiovascular Agents; Cyclooxygenase Inhibitors; Ductus Arteriosus, Patent; Female; Humans; Ibuprofen; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Randomized Controlled Trials as Topic; Treatment Outcome

Over the last three decades, knowledge about fundamental and clinical aspects of the ductus arteriosus has substantially improved, leading to considerable progress in the management of various cardiac diseases involving the ductus. The identification of the mechanisms regulating ductal patency led to design pharmacological drugs to achieve medical closure of PDA in premature infants, or inversely to maintain patency in neonates with duct-dependent congenital heart diseases. Concurrently, widespread availability of echocardiography has improved the detection of congenital PDA, resulting in earlier treatment. Closure of PDA, by either surgery or transcatheter techniques, can now be achieved safely, resulting in a decrease in the incidence of severe complications of PDA.

Topics: Cardiac Catheterization; Cardiac Surgical Procedures; Cardiovascular Agents; Ductus Arteriosus; Ductus Arteriosus, Patent; Echocardiography, Doppler, Color; Electrocardiography; Hemodynamics; Humans; Infant, Newborn; Infant, Premature; Predictive Value of Tests; Treatment Outcome

Persistent patent ductus arteriosus (PDA) is associated with mortality and morbidity in preterm infants. Prostaglandin synthetase inhibitors such as indomethacin promote PDA closure but also have potential side effects. The effect of the prophylactic use of indomethacin, where infants who may not have gone on to develop a symptomatic PDA would be exposed to indomethacin, warrants particular scrutiny.. To determine the effect of prophylactic indomethacin on mortality and morbidity in preterm infants.. The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 5, 2010), MEDLINE, EMBASE and CINAHL (until April 2010), conference proceedings, and previous reviews.. Randomised or quasi-randomised controlled trials that compared prophylactic indomethacin versus placebo or no drug in preterm infants.. The standard methods of the Cochrane Neonatal Review Group were used, with separate evaluation of trial quality and data extraction by two review authors.. Nineteen eligible trials in which 2872 infants participated were identified. Most participants were very low birth weight, but the largest single trial restricted participation to extremely low birth weight infants (N = 1202). The trials were generally of good quality.The incidence of symptomatic PDA [typical relative risk (RR) 0.44, 95% confidence interval (CI) 0.38 to 0.50] and PDA surgical ligation (typical RR 0.51, 95% CI 0.37,0.71) was significantly lower in treated infants. Prophylactic indomethacin also significantly reduced the incidence of severe intraventricular haemorrhage (typical RR 0.66, 95% CI 0.53 to 0.82). Meta-analyses found no evidence of an effect on mortality (typical RR 0.96, 95% CI 0.81 to 1.12) or on a composite of death or severe neurodevelopmental disability assessed at 18 to 36 months old (typical RR 1.02, 95% CI 0.90, 1.15).. Prophylactic indomethacin has short-term benefits for preterm infants including a reduction in the incidence of symptomatic PDA, PDA surgical ligation, and severe intraventricular haemorrhage. However, there is no evidence of effect on mortality or neurodevelopment.

Topics: Cardiovascular Agents; Cerebral Hemorrhage; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Injections, Intravenous; Randomized Controlled Trials as Topic

Patent ductus arteriosus (PDA) in preterm newborns prior to 28 weeks of gestation has led to many challenges regarding the type and timing of treatment regimens. A PDA results in increased pulmonary blood flow and redistribution of flow to other organs. Several co-morbidities (i.e., necrotizing enterocolitis, intracranial hemorrhage, pulmonary edema/hemorrhage, bronchopulmonary dysplasia, and retinopathy) are associated with the presence of a PDA, but whether or not a PDA is responsible for their development is still unclear. The prostaglandin inhibitor, indomethacin, is effective in the treatment of PDA. Questions regarding the optimal timing of the intervention--early prophylaxis or treatment, once signs and symptoms become evident--have challenged physicians for decades. Both evidence and experience are explored in this article. Comparative physiology between the full-term and preterm newborn and the barriers preventing the necessary cascade of events leading to permanent constriction of the PDA are reviewed.

Topics: Cardiac Surgical Procedures; Cardiovascular Agents; Comorbidity; Ductus Arteriosus, Patent; Gestational Age; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Treatment Outcome

Botallo's duct connects the systemic and pulmonary circulation. It can play a crucial hemodynamic role in some cardiac and respiratory diseases of the newborn, and strongly influences the outcome if it remains patent after birth or if it closes rapidly. The recently acquired in-depth knowledge on the genesis of these events have advanced the so called ''pharmacological manipulation of Botallo's duct'', i.e. pharmacological treatment to regulate the opening or closure of the ductus depending on clinical requirements and that, as will be described, is a key issue in managing newborns with severe cardiac and/or respiratory distress. This study illustrates the main underlying mechanisms of duct patency during intrauterine life and its closure after birth, and then describes the clinical conditions of the newborn where Botallo's duct must be kept patent after birth (duct-dependent cardiac malformations) and where its closure must be accelerated (patent duct associated idiopathic respiratory syndrome). It also reports the recent findings on the use of prostaglandins (PGE1) and prostaglandin synthesis inhibitors (indomethacin, ibuprofen) and the potential use of drugs capable of favouring or inhibiting nitric oxide in the duct endothelium.

Topics: Alprostadil; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Agents; Cerebral Angiography; Cyanosis; Cyclooxygenase Inhibitors; Ductus Arteriosus; Ductus Arteriosus, Patent; Heart Defects, Congenital; Heart Failure; Hemodynamics; Humans; Ibuprofen; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Respiratory Distress Syndrome, Newborn; Vasodilator Agents

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Agents; Ductus Arteriosus, Patent; Humans; Ibuprofen; Indomethacin; Infant, Newborn

Patent ductus arteriosus (PDA) continues to be one of the most common problems found in premature infants. The incidence is inversely related to gestation, but may be reduced by use of antenatal steroids, lower volume fluid regimen and judicious use of phototherapy. However, there continues to be controversy as to the appropriate indications for treatment, varying from prophylaxis on the basis of gestation to treatment only when a PDA is demonstrably significant. The situation is further complicated by differing diagnostic criteria for ductal patency or significance. Prophylactic treatment is likely to result in up to 64% of babies being treated unnecessarily. Early treatment of significant or symptomatic PDA depends upon accurate diagnosis. PDA closure can then be achieved using medical means, with surgery reserved for patients in whom this fails or in whom there are contra-indications. However, the optimum timing for intervention remains unknown.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Atrial Function, Left; Blood Flow Velocity; Blood Vessel Prosthesis; Cardiovascular Agents; Diagnosis, Differential; Ductus Arteriosus, Patent; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Prognosis; Time Factors

Patent ductus arteriosus (PDA) and intraventricular haemorrhage (IVH) are both associated with increased mortality and morbidity in preterm infants. Indomethacin has been used successfully to treat symptomatic PDA and may also prevent or limit IVH in the neonatal period. There are however potential unwanted side effects of indomethacin, in particular a potential for reduced organ perfusion that might outweigh any clinical benefits. The prophylactic use of indomethacin, where infants who may not have gone on to develop a symptomatic PDA or IVH would be exposed to indomethacin, warrants particular scrutiny.. This review examines the effectiveness of prophylactic intravenous indomethacin in reducing the mortality and morbidity associated with PDA and IVH in preterm infants.. An initial literature search was conducted in three computerised databases: MEDLINE; EMBASE; and the Oxford Database of Perinatal Trials in October 1994. The search was updated in February 1997 and October 2001.. Strict selection criteria were applied to clinical trials: the population had to be newborn preterm infants (less than 37 completed weeks gestation); the intervention had to be prophylactic intravenous indomethacin; the trial had to be randomised and controlled; and at least one of several prespecified outcomes had to be reported in the results.. The methodological quality of each study was assessed using explicit criteria. Data on relevant outcome measures were extracted and, where appropriate, the results of individual trials were combined using meta-analysis techniques to provide a pooled estimate of effect.. Nineteen eligible trials randomising 2872 infants were identified. There is no evidence of difference in mortality at latest follow-up between infants receiving prophylactic indomethacin and controls, pooled relative risk (RR) = 0.96 [95% CI 0.81 to 1.12]. There is no evidence to suggest prophylactic indomethacin is associated with any reduction in long-term neurosensory impairment, ie no significant difference in rates of cognitive delay, cerebral palsy, blindness or deafness. The incidence of symptomatic patent ductus arteriosus is significantly reduced in treated infants, pooled RR = 0.44 [0.38 to 0.50] but there is no evidence that treatment affects respiratory outcomes. Prophylactic indomethacin reduces the need for surgical PDA ligation [RR = 0.51 (0.37,0.71)]. Prophylactic indomethacin significantly reduces the incidence of Grade 3 and 4 intraventricular haemorrhage, pooled RR = 0.66 [0.53 to 0.82]. There is no evidence of difference in rates of necrotising enterocolitis, excessive clinical bleeding or sepsis. Increased incidence of oliguria is seen with prophylactic indomethacin [RR = 1.90 (1.45,2.47] but this is not associated with major renal impairment.. Prophylactic treatment with indomethacin has a number of immediate benefits, in particular a reduction in symptomatic patent ductus arteriosus, the need for duct ligation and severe intraventricular haemorrhage. There is no evidence to suggest either benefit or harm in longer term outcomes including neurodevelopment. Depending on clinical circumstances and personal preferences, there may be a role for prophylactic indomethacin in some infants on some neonatal units.

Topics: Cardiovascular Agents; Cerebral Hemorrhage; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Randomized Controlled Trials as Topic

Indomethacin therapy for closure of patent ductus arteriosus frequently causes oliguria, and occasionally more serious renal dysfunction. Low dose dopamine has been suggested as a means for preventing this side effect.. To determine whether dopamine therapy may prevent indomethacin-mediated deterioration in renal function in the preterm newborn infant without serious adverse effects.. To assess the effects of dopamine on the above variables in two subgroups: (1) patients given indomethacin as prophylaxis of intraventricular hemorrhage, and (2) patients given indomethacin as treatment of patent ductus arteriosus. Standard methods of the Cochrane Neonatal Review Group (CNRG) were used. We searched MEDLINE (1966-2001) using PubMed as the search engine, EMBASE (1974-2001) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (Issue 3, 2001). In addition we contacted the principal investigators if necessary to ascertain the required information.. Randomized or quasi-randomized studies of the effects of dopamine on urine output, glomerular filtration rate, fluid balance or incidence of renal failure, in preterm newborn infants receiving indomethacin. The comparison group should have received no dopamine.. We used the standard methods of the Cochrane Collaboration and those of the CNRG. The primary outcomes of interest were: mortality before discharge; intraventricular hemorrhage, grade three or four; cystic periventricular leukomalacia; renal failure (either oliguria, defined as a urine output less than 1 ml/kg/hour or an elevation in creatinine by more than 40 micromoles/L); failure to close the ductus arteriosus; need for surgical PDA ligation. For categorical outcomes, we calculated typical estimates for relative risk and risk difference. For continuous outcomes the weighted mean difference (WMD) was calculated. Fixed effect models were assumed for meta-analysis.. Three studies were found (total number randomized patients, 75) which fulfilled the entry criteria for this review. All were single center trials which enrolled NICU patients receiving indomethacin for symptomatic patent ductus arteriosus. There are no (or only partial) results for effects of dopamine on several of the primary outcomes, including death before discharge, serious intraventricular hemorrhage, cystic periventricular leukomalacia, or renal failure. There has been inadequate investigation of the effects of dopamine on cerebral perfusion or cardiac output, or GI complications, or endocrine toxicity. Dopamine improved urine output [WMD 0.68 ml/kg/hour (95% CI 0.22, 1.44)], but there was no evidence of effect on serum creatinine (WMD 2.04 micromoles/liter, CI -17.90, 21.97) or the incidence of oliguria (urine output < 1 ml/kg/hour) (RR 0.73, CI 0.35, 1.54). There was no evidence of effect of dopamine on the frequency of failure to close the ductus arteriosus (RR 1.11, CI 0.56, 2.19).. There is no evidence from randomized trials to support the use of dopamine to prevent renal dysfunction in indomethacin-treated preterm infants.

Topics: Cardiovascular Agents; Dopamine; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Renal Agents; Renal Insufficiency

This section is under preparation and will be included in the next issue.. Indomethacin is used to treat symptomatic patent ductus arteriosus and may prevent or limit intraventricular haemorrhage in the neonatal period. This review examines the effectiveness of prophylactic intravenous indomethacin in reducing the mortality and morbidity associated with these conditions in infants weighing less than 1750 grams at birth.. A literature search from January 1980 to October 1994 was made in three computerised data bases: Medline; Embase; and the Oxford Database of Perinatal Trials. The search was updated in February 1997.. Strict selection criteria were applied to clinical trials: the population had to be newborn infants of birth weight < 1751 grams; the intervention had to be prophylactic intravenous indomethacin; the trial had to be randomised and controlled; and at least one of several prespecified outcomes had to be reported in the results.. The methodological quality of each study was assessed using explicit criteria. Data on relevant outcome measures were extracted on two separate occasions and, where appropriate, the results of individual trials were combined using meta-analysis techniques to provide a pooled estimate of effect.. There is a trend towards reduced neonatal mortality in infants receiving prophylactic indomethacin, pooled relative risk (RR) = 0. 85 [95% CI 0.66 to 1.09]. The incidence of symptomatic patent ductus arteriosus is significantly reduced in treated infants, pooled RR = 0.35 [0.26 to 0.47] but there is no evidence that treatment affects respiratory outcomes. Prophylactic indomethacin significantly reduces the incidence of Grade 3 and 4 intraventricular haemorrhage in treated infants, pooled RR = 0.60 [0.43 to 0.83]. There is no evidence to suggest prophylactic indomethacin is associated with any long term adverse effect although there is a trend in treated infants towards an increased incidence of necrotizing enterocolitis, and some evidence that treatment may transiently impair renal function. There is no evidence that haemostasis is disturbed.. Prophylactic treatment with indomethacin has a number of immediate benefits, in particular a reduction in symptomatic patent ductus arteriosus and severe intraventricular haemorrhage. There is no evidence at present of long-term harm. Further trials are needed to assess more precisely the effects, both beneficial and harmful, on short and long-term outcomes.

Topics: Cardiovascular Agents; Cerebral Hemorrhage; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Randomized Controlled Trials as Topic

In low- and middle-income countries (LMIC), haemodynamically significant patent ductus arteriosus (hsPDA) is treated with oral indomethacin (IDC) and ibuprofen (IB) instead of intravenous formulations. No significant differences in efficacy have been reported. However, previous studies had small numbers of VLBW infants (<1500 g).. To evaluate the efficacy of oral IDC and IB for closing PDA in VLBW infants with a gestational age of 24-32 weeks.. This randomised controlled study enrolled 32 infants with hsPDA for treatment with either three doses of oral IDC or oral IB. Echocardiography was performed before and after treatment.. Oral IDC was more effective than oral IB (65% vs. 27%, p = 0.03). This difference was attributable to the subset of extremely low-birthweight infants (<1000 g) in whom an hsPDA closed 78% of the time after oral IDC compared with 13% of those treated with oral IB (p = 0.01). In contrast, there was no difference in hsPDA closure rates between the study groups of infants with birthweights of 1000-1499 g. There was no significant difference between the drugs in clinical and laboratory measures of adverse effects, nor of other clinical outcomes Conclusion: Oral IDC was more effective than oral IB for closing PDA in VLBW infants, without significant differences in side-effects or short-term outcomes.

Topics: Administration, Oral; Cardiovascular Agents; Ductus Arteriosus, Patent; Echocardiography; Female; Humans; Ibuprofen; Indomethacin; Infant, Newborn; Infant, Very Low Birth Weight; Male; Treatment Outcome

To determine whether extremely low birth weight infants who receive enteral sterile water have a reduction in treated patent ductus arteriosus or death by 28 days compared to infants with routine management.. A total of 214 infants were enrolled and randomized by 36 h of age to receive up to 50 ml kg(-1) per day of enteral sterile water (n=109) for 7 days or routine fluid management (n=104). Patent ductus arteriosus treatment was defined as either indomethacin treatment or surgical ligation.. The proportion of infants with a treated patent ductus arteriosus or death at <28 days of age was 63% in the sterile water group vs 64% in the control group (relative risk 0.99, 95% confidence interval 0.81 to 1.22). There were no differences in the proportion of infants in the sterile water group vs control group with a treated patent ductus arteriosus (55 vs 48%), death (21 vs 28%), necrotizing enterocolitis or death (24 vs 32%), or bronchopulmonary dysplasia or death at <28 days (80 vs 77%). Daily mean glucose levels were significantly higher (P=0.04) in control infants than sterile water infants.. The use of sterile water did not decrease the incidence of patent ductus arteriosus or other adverse clinical outcomes. The role of enteral sterile water in the fluid management of extremely low birth weight infants remains uncertain.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Enteral Nutrition; Female; Fluid Therapy; Gestational Age; Humans; Indomethacin; Infant, Extremely Low Birth Weight; Infant, Newborn; Infusions, Intravenous; Male; Water

A population pharmacokinetic model was developed after administration of orogastric and/or intravenous indomethacin for the treatment of patent ductus arteriosus in preterm infants. Plasma indomethacin concentrations (n=227) were obtained from 90 preterm infants of median gestational age 27 weeks, mean postnatal age of 12 days, and a mean current weight (WT) of 1010 g. Infants received one to three courses of indomethacin (0.1 mg/kg per day for 6 days). A one-compartment model was fitted to the data to obtain estimates of clearance (CL), volume of distribution (V), absorption rate constant (Ka) and orogastric bioavailability (F), using NONMEM. Model robustness was assessed by bootstrapping with replacement (500 samples). The structural model was: CL (L/h)=0.0166 (WT / 0.936)1.54; V (L)=0.484 (WT / 0.936)1.41; F=0.986; Ka (h(-1))=0.786. The interindividual variability for CL and V was 57.7% and 45.6%, respectively. There remained considerable residual unexplained variability (45.4%). Mean (range) conditional estimates from individual infants for CL, V, and elimination half-life were 18.9 (4.7-45.5) mL/h/kg, 509 (191-1120) mL/kg, and 20.0 (12.0-37.3) hours, respectively. Complete ductus closure occurred in 67% of patients. Infants of lower gestational age or birth weight had less chance of successful ductal closure. There was no obvious dose-response relationship between systemic exposure to varying plasma indomethacin concentrations and ductus closure, which does not support individualized indomethacin dosing based on monitoring to a target plasma concentration.

Topics: Administration, Oral; Biological Availability; Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Injections, Intravenous; Male; Treatment Outcome

In the present study, 0.2-0.6 mg/kg (0.4+/-0.2, mean +/- standard deviation) indomethacin was administered intravenously to close a patent ductus arteriosus in 13 infants with co-existing congenital heart defects whose ages ranged from 3 to 48 (14+/-14) days. All of them were hemodynamically ductus-independent and symptomatic. Echocardiography demonstrated that the ductus had closed in 8 infants, aged 3-33 (12+/-10) days (responders), but had not closed in 5 infants aged 6-48 (19 +/-19) days (non-responders). There was no significant difference between the responders and non-responders in their age, body weight, minimal diameter of the duct, dose of indomethacin, gestational age, birthweight, or Apgar score. One possible major complication might be associated with indomethacin. However, intravenous indomethacin should be considered prior to surgical ligation as one option for infants with a symptomatic patent ductus arteriosus complicated by other congenital heart defects.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Echocardiography; Female; Heart Defects, Congenital; Humans; Indomethacin; Infant; Infant, Newborn; Infant, Premature; Injections, Intravenous; Male; Retreatment

Permanent closure of the ductus arteriosus (DA) requires both effective muscular constriction to block luminal blood flow and anatomic remodeling to prevent later reopening.. We examined the role of prophylactic indomethacin in producing permanent DA closure and the mechanism by which this occurs.. We studied 2 separate approaches to managing a patent DA in 257 preterm infants (gestation 24 to 27 weeks): (1) prophylactic indomethacin (all infants treated during the first 15 hours after birth) or (2) symptomatic treatment (infants in this group received indomethacin only if clinical symptoms appeared; infants whose ductus closed spontaneously and never received indomethacin were included in this group). Echocardiography was performed 24 to 36 hours after the last dose of indomethacin was administered or by age 5 days if spontaneous closure occurred. Infants were monitored for the development of ductus reopening.. The prophylactic treatment group had a greater degree of initial ductus constriction, a higher rate of permanent anatomic closure, and a decreased need for surgical ligation than did the symptomatic treatment group. The degree of initial ductus constriction was the most important factor determining the rate of ductus reopening. Post-treatment echocardiography proved to be the best test for predicting eventual reopening.. Prophylactic indomethacin improved the rate of permanent ductus closure by increasing the degree of initial constriction. Prophylactic indomethacin did not affect the remodeling process, nor did it alter the inverse relationship between infant maturity and subsequent reopening. Even when managed with prophylactic indomethacin, the rate of ductus reopening remained unacceptably high in the most immature infants.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Male

Previous reports have suggested that prophylactic indomethacin decreases cerebral blood flow and may play a role in the development of ischemic brain injury and developmental handicaps.. To assess the neurodevelopmental outcome of subjects at 36 months' corrected age (CA) who, as low-birth-weight infants, received prophylactic low-dose indomethacin within the first 24 hours of life to prevent patent ductus arteriosus.. Newborn intensive care nursery and outpatient follow-up clinic at Children's Hospitals and Clinics of Minneapolis, Minneapolis, Minn.. Ninety infants with birth weights of 600 to 1250 g were entered into a prospective, randomized, controlled trial to receive either prophylactic indomethacin, 0.1 mg/kg, or placebo in the first 24 hours and again every 24 hours for 6 doses to prevent patent ductus arteriosus. Nonresponders were treated with standard therapeutic indomethacin or ligation. Neurodevelopmental assessment at approximately 36 months' CA included medical and developmental histories, physical examinations, and developmental testing using the Bayley II Scales of Infant Development on subjects up to 42 months' CA. Subjects were classified as (1) normal, (2) mildly to moderately abnormal, or (3) severely impaired.. Forty-two (98%) of 43 subjects who received prophylactic indomethacin survived compared with 46 (98%) of 47 who received placebo. Sixty-six (75%) of 88 survivors were seen for neurodevelopmental assessment at 36 months' CA. This group included 29 (69%) of 42 who received prophylactic indomethacin and 37 (80%) of 46 who received placebo. Twenty-three (79%) of 29 infants in the prophylactic indomethacin group had normal neurodevelopmental assessments at 36 months' CA compared with 26 (70%) of 37 placebo-treated subjects (P = .68). Of 4 significantly impaired subjects treated with prophylactic indomethacin, 1 had spastic diplegia; 1, spastic quadriplegia; 1, cognitive delay; and 1, significant motor delay. Of 8 significantly impaired placebo-treated subjects, 7 had spastic diplegia; 1, microcephaly.. The use of prophylactic low-dose indomethacin when initiated in the first 24 hours of life in low-birth-weight infants to prevent patent ductus arteriosus is not associated with adverse neurodevelopmental outcome at 36 months' CA.

Topics: Cardiovascular Agents; Child Development; Ductus Arteriosus, Patent; Female; Follow-Up Studies; Humans; Indomethacin; Infant; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Male; Nervous System; Prospective Studies

Extremely preterm infants are peculiar in regard to their risk of retinopathy of prematurity (ROP). In this study, we aim to study insults that may affect extremely preterm infants, including prenatal, at birth, and postnatal insults and their effect on the development of ROP.. This study used the data from Prematurity and Respiratory Outcomes Program (PROP). All included infants with a gestational age of 23 0/7 to 28 6/7 weeks using best obstetrical estimate. We included stressful events and/or modifiable variables that may affect the normal development. We used multiple regression analysis in our statistical analysis.. We included a total of 751 infants in our study. The mean birth weight for the included sample was 915.1 (±232.94) grams. 391 (52.1%) Infants were diagnosed with ROP. We found a significant negative correlation between ROP development and birth weight (p < 0.001), with a correlation coefficient of - 0.374. We found that the need for prophylactic indomethacin (OR 1.67), the occurrence of air leaks (OR: 2.35), ventilator-associated pneumonia (OR: 2.01), isolated bowel perforations (OR: 3.7), blood culture-proven sepsis (OR: 1.5), other infections (OR: 1.44), and receiving ventricular shunt (OR: 2.9) are significantly associated with the development of ROP.. We believe this study included the largest number of factors studied in the largest sample of extremely premature infants. We recommend a screening program for extremely preterm infants that takes into account a scoring system with higher scores for complicated condition.

Topics: Birth Weight; Cardiovascular Agents; Cellulitis; Cerebrospinal Fluid Shunts; Continuous Positive Airway Pressure; Ductus Arteriosus, Patent; Embolism, Air; Female; Humans; Indomethacin; Infant, Extremely Low Birth Weight; Infant, Extremely Premature; Infant, Newborn; Infant, Very Low Birth Weight; Intestinal Perforation; Male; Mediastinal Emphysema; Meningitis; Neonatal Sepsis; Pneumonia, Ventilator-Associated; Pneumopericardium; Pneumoperitoneum; Pneumothorax; Protective Factors; Retinopathy of Prematurity; Subcutaneous Emphysema; Urinary Tract Infections

The treatment of patent ductus arteriosus (PDA) in very low birth weight (VLBW) infants remains a challenge. The ability to predict which infants will respond to indomethacin could spare some from the risks of unnecessary medications. Our objective was to determine if indicators of acid-base homeostasis could predict response to indomethacin treatment for ductal closure, and thus help guide treatment decisions.. We performed a retrospective analysis of medical records of VLBW (< 1500 g) neonates with hemodynamically significant PDA born at our institution between January 2009 and December 2012; all infants included in the study were treated with indomethacin for ductal closure within the first 2 weeks of life. We extracted data for a number of clinical variables including gestational age, birth weight, blood chemistries, surfactant use, hematocrit, and blood gas parameters. Our primary outcome measure was successful closure of PDA following the first round of indomethacin. Using variables that were significant on initial testing, we created multivariable regression models to determine the independent association of selected variables with indomethacin response.. Of the 91 infants included in the study, 62 (68%) responded to the first course of indomethacin with successful ductal closure. Multivariable regression modeling revealed that both base excess and hematocrit were independently associated with indomethacin response; odds of PDA closure increased with increasing base excess (OR [odds ratio]: 1.81; 95% confidence interval [CI]: 1.36-2.60) and increasing hematocrit (OR: 1.21; 95% CI: 1.01-1.45). The optimal cutoff value for base excess was - 4.56, with a sensitivity of 96.8% (95% CI: 89-100) and specificity of 79.3% (95% CI: 60-92); optimal cutoff value for hematocrit was 40, with 69.4% sensitivity (95% CI: 56-80) and 65.5% specificity (95% CI: 46-82).. Base excess and hematocrit may be independent predictors of indomethacin response in VLBW infants with PDA. Low-cost and readily accessible, acid-base indicators such as base excess could help guide treatment decisions.

Topics: Acid-Base Equilibrium; Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Hematocrit; Humans; Indomethacin; Infant, Newborn; Infant, Very Low Birth Weight; Male; Predictive Value of Tests; Retrospective Studies; Treatment Outcome

Serum creatinine (SCr)- or urine output-based definitions of acute kidney injury (AKI) have important limitations in neonates. This study evaluates the diagnostic value of urinary biomarkers in very low-birth-weight (VLBW) infants receiving indomethacin for closure of a patent ductus arteriosus (PDA).. Prospective cohort study in 14 indomethacin-treated VLBW infants and 18 VLBW infants without indomethacin as controls. Urinary biomarkers were measured before, during, and after indomethacin administration.. Indomethacin therapy was associated with significantly higher SCr concentrations at 36, 84, and 120 h compared to controls. At 36 h, three indomethacin-treated patients met the criteria for neonatal modified Kidney Disease: Improving Global Outcomes (KDIGO) AKI. The product of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2]•[IGFBP7]) was significantly elevated in the AKI subgroup at 12 h (P < 0.05), hence 24 h earlier than the increase in SCr. Urinary neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin were significantly increased in the indomethacin group at 12 h (P < 0.05), irrespective of fulfillment of the AKI criteria. Urinary kidney injury molecule-1 (KIM-1) was not significantly altered.. While urinary [TIMP-2]•[IGFBP7] proves valuable for the early diagnosis of neonatal modified KDIGO-defined AKI, elevated urinary NGAL and calprotectin concentrations in indomethacin-treated VLBW infants not fulfilling the AKI criteria may indicate subclinical kidney injury.

Topics: Acute Kidney Injury; Biomarkers; Cardiovascular Agents; Case-Control Studies; Creatinine; Cross-Sectional Studies; Ductus Arteriosus, Patent; Female; Humans; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Infant, Very Low Birth Weight; Insulin-Like Growth Factor Binding Proteins; Leukocyte L1 Antigen Complex; Lipocalin-2; Male; Prospective Studies; Tissue Inhibitor of Metalloproteinase-2; Treatment Outcome

Video-assisted thoracoscopic surgery for patent ductus arteriosus (VATS-PDA) is an alternative surgical procedure to open chest surgery, even in premature infants. This study investigated whether the timing of VATS-PDA has a prognostic impact in premature infants whose operative indication was determined according to the symptomatic PDA and the ineffectiveness of or contraindication to indomethacine therapy.. We studied 49 infants born at or before 28 weeks of gestation who were admitted to the neonatal intensive care unit between January 2004 and June 2016, and who underwent VATS-PDA. The patients were divided into two groups according to median age at the time of surgery (early group, 24 infants who underwent surgery at ≤ 24 days of life; late group, 25 infants who underwent surgery at ≥ 25 days of life).. No significant differences were found in bodyweight at 30 days of age and 40 weeks of corrected gestational age between the groups. The timing of surgery did not affect the operative procedure or postoperative complications. In addition, no differences were observed between the early and late groups in terms of complications associated with prematurity, including intraventricular hemorrhage, incidence and severity of bronchopulmonary dysplasia, and necrotizing enteropathy.. Video-assisted thoracoscopic surgery for patent ductus arteriosus can be safely performed in premature infants without a preferential timing for the intervention, suggesting that this procedure allows for an elective basis approach after heart failure management with conservative and/or drug therapy in premature infants with PDA.

Topics: Age Factors; Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Humans; Indomethacin; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases; Male; Prognosis; Retrospective Studies; Thoracic Surgery, Video-Assisted; Treatment Outcome

Failure of first course of indomethacin (FCI) for patent ductus arteriosus (PDA) treatment in preterm neonates often prompts clinicians to consider a second course (SCI).. To identify factors including baseline characteristics and response to FCI that are associated with non-response to SCI for PDA treatment in preterm neonates.. In this retrospective observational study, neonates ≤32 weeks admitted to a tertiary NICU over 5 years who received two indomethacin courses for PDA treatment were reviewed. Only neonates with echocardiograms (ECHO) immediately before and after receipt of each indomethacin course were included. Primary outcome was non-response to SCI. Baseline characteristics and response to FCI were compared between responders and non-responders of SCI.. Of the 98 neonates enrolled, 47 (48%) had non-response to SCI. Of them, 27 patients (57%) had prior non-response to FCI, while of the 51 neonates who responded to SCI, 24 neonates (47%) had prior non-response to FCI. The adjusted risk of non-response to SCI in patients who had non-response to FCI was 37% higher (relative risk = 1.37, 95%CI: 0.87-1.80; p = .07) compared to those who had response to FCI. Multivariable analysis showed that increasing gestational age (AOR: 1.6, 95%CI: 1.1-2.3, p = .03) was associated with a higher odds of non-response to SCI while the odds of non-response to SCI increased by 90% in patients with non-response to FCI (AOR: 1.9, 95%CI: 0.8-4.5; p = .15) compared to those with success of FCI, although no statistical significance was observed.. Advanced gestational age was the predictor of non-response to SCI in preterm neonates.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Male; Retrospective Studies; Treatment Failure

The primary objective of this study was to evaluate early postnatal serum gut hormone concentrations in preterm infants as predictors of time to full enteral feedings. The secondary objective was to identify infant characteristics and nutritional factors that modulate serum gut hormone concentrations and time to full enteral feedings.. Sixty-four preterm infants less than 30 weeks of gestation were included in this retrospective cohort study. Serum gut hormone concentrations at postnatal days 0 and 7 were measured using enzyme-linked immunosorbent assays. Linear regression and mediation analyses were performed.. Median (interquartile range) serum concentrations of glucose-dependent insulinotropic peptide (GIP) and peptide YY (PYY) on postnatal day 7 were 31.3 pg/mL (18.2, 52.3) and 1181.7 pg/mL (859.0, 1650.2), respectively. GIP and PYY concentrations on day 7 were associated with days to full enteral feedings after adjustment for confounders (β = -1.1, P = 0.03; and β = -0.002, P = 0.02, respectively). Nutritional intake was correlated with serum concentrations of GIP and PYY on postnatal day 7 and time to full enteral feedings. Mediation analysis revealed that the effect of serum gut hormone concentrations on time to full enteral feedings was not fully explained by nutritional intake. Intrauterine growth restriction, mechanical ventilation on postnatal day 7, and patent ductus arteriosus treated with indomethacin were associated with longer time to full enteral feedings.. Serum concentrations of GIP and PYY on postnatal 7 are independently associated with time to full enteral feedings. The link between serum gut hormone concentrations and time to full enteral feedings is not fully mediated by nutritional factors, suggesting an independent mechanism underlying the influence of gut hormones on feeding tolerance and time to full enteral feedings.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Enteral Nutrition; Female; Fetal Growth Retardation; Gastric Inhibitory Polypeptide; Gastrointestinal Tract; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Male; Nutritional Physiological Phenomena; Peptide YY; Respiration, Artificial; Retrospective Studies; Time Factors

To determine whether a moderate-to-large patent ductus arteriosus (PDA) is responsible for vasopressor-dependent hypotension, occurring at the end of the first postnatal week.. As expected, the incidence of moderate-to-large PDA at the end of the first week differed significantly between epochs (PINDO = 8%; conservative = 64%). In multivariate analyses, infants in the PINDO epoch had a significantly lower incidence of vasopressor-dependent hypotension (11%) than infants in the conservative epoch (21%; OR = 0.40, 95% CI 0.20-0.82). Infants in the PINDO epoch also required less mean airway pressure, had a lower respiratory severity score, and lower mode of ventilation score than infants in the conservative epoch during postnatal days 4-7. The effects of PINDO on both the incidence of vasopressor-dependent hypotension and the need for respiratory support were no longer significant when analyses were adjusted for "presence or absence of a moderate-to-large PDA.". PINDO decreases vasopressor-dependent hypotension and the need for respiratory support at the end of the first postnatal week. These effects are mediated by closure of the PDA.

Topics: Cardiovascular Agents; Cohort Studies; Dopamine; Ductus Arteriosus, Patent; Echocardiography; Female; Humans; Hypotension; Incidence; Indomethacin; Infant, Extremely Premature; Infant, Newborn; Male; Retrospective Studies

PDA(Patent ductus arteriosus) is a common and clinically important condition which is presented with a number of hemodynamic and respiratory problems such as intraventricular hemorrhage, pulmonary hemorrhage and necrotizing enterocolitis due to increased pulmonary blood flow and stealing from systemic circulation. The incidence of PDA among the infants that were born before the 28th gestational week is as high as 70 %; and spontaneous closure rates in very-low-birth-weight premature neonates(VLBWPN) is around 34 %. The onset, duration, and repeat number of consecutive courses of the prostaglandin synthesis inhibitor medication for PDA closure are still issues of debate. Bed-side PDA closure is a safe surgical procedure in both mature and premature babies. Here we aim to retrospectively present our 26 cases which were less than 28 weeks and 1000 grams that underwent bed-side PDA ligation.. This retrospective study included 26 VLBWPN with PDA that underwent bed-side ligation between 2012 and 2015. Babies were born before the 28th gestational week (23-27 weeks) and less than 1000 grams (489-970 gr). Of the 26, 15 were female and 11 were male. Indomethacin was administered to all of the cases as the medical closing agent. The medication was stopped due to unwanted effects in 6 cases. All of the patients took medical treatment before surgery.. No surgical mortality occurred during our study. One case of pneumothorax was recorded as late surgical complication. Five of the 26 patients were lost, and the most common cause of mortality was sepsis (in 3 cases). The remaining 21 cases were discharged on days 86-238. The follow-up periods of the patients were 2 moths - 3 years. The most frequent problems encountered after discharge was chronic lung problems.. Bed side PDA ligation surgery in the ICU is a safe method for VLBWPN with clinically significant PDA.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Gestational Age; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Ligation; Male; Retrospective Studies; Treatment Outcome; Vascular Surgical Procedures

The management of a patent ductus arteriosus in preterm infants continues to be debated among neonatologists due to the absence of concrete evidence that precisely weighs the long term outcomes of active, early intervention against a conservative approach. In the majority of institutions, parents are encouraged to play an active role in the complex, decision -making processes with regard to the care of their infants. The objective of this study is to elicit maternal preferences for indomethacin prophylaxis versus treatment of a patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants, utilizing a decision aid instrument (DAI).. Healthy and high risk pregnant women at 23-28 weeks gestation, and mothers of admitted ELBW infants were enrolled. A computer based, validated DAI was utilized during interviews. The DAI first provides information about prematurity and concurrent morbidities with comprehensive facts of the pros and cons about prophylactic versus treatment options. It subsequently coaches participants how to select values and preferences based on their decisions. A 17-item questionnaire assessed and valued each short and long term morbidity of extreme prematurity and preferred choice for PDA management.. Two hundred ninety nine subjects were enrolled; 75% were healthy women at 23-28 weeks gestation, 19% were high risk and 6% recently delivered an ELBW infant. Eighty-two percent preferred a prophylactic indomethacin strategy versus symptomatic treatment for the management of PDA. Across a spectrum of potential morbidities, the occurrence of severe intraventricular hemorrhage was viewed by mothers as the most un-wanted outcome irrespective of the two proposed options.. In contrast to neonatal practitioners, mothers who used this particular DAI strongly endorsed prophylactic indomethacin versus a treatment intervention for the management of PDA in preterm infants.

Topics: Cardiovascular Agents; Decision Support Techniques; Ductus Arteriosus, Patent; Female; Humans; Indomethacin; Infant, Extremely Low Birth Weight; Mothers; Patient Participation; Pregnancy; Prospective Studies

Patent ductus arteriosus (PDA) is common in extremely premature infants and associated with increased morbidity and mortality. Medical management of PDA uses either indomethacin or ibuprofen. Despite numerous studies, uncertainty exists as to which drug is safer or more effective; we sought to fill this knowledge gap.. We identified infants <28weeks gestational age discharged from neonatal intensive care units included in the Pediatrix Medical Group Clinical Data Warehouse between 2006 and 2012 who were treated with indomethacin or ibuprofen between postnatal days 2 and 14. Infants treated with both drugs or infants with a congenital malformation were excluded. We used multivariable logistic regression to determine the association of indomethacin versus ibuprofen on clinical outcomes.. Of 6349 patients who met study criteria, 1177 (19%) received ibuprofen and 5172 (81%) received indomethacin. The median gestational age was 25weeks (interquartile range 24-26), and 2894 (46%) infants were <750g at birth. On unadjusted analysis, infants who received ibuprofen had significantly higher incidences of death prior to discharge, surgical ligation of the PDA prior to discharge, death or spontaneous intestinal perforation within 7days of therapy, death or surgical ligation of the PDA prior to discharge, and an elevated creatinine within 7days of treatment. However, on multivariable analysis, no significant differences in outcomes were observed (odds ratio for death/PDA ligation for ibuprofen vs. indomethacin=1.12 [95% CI 0.91-1.39]).. We observed similar effectiveness and safety profiles for indomethacin and ibuprofen in the medical management of PDA in premature infants.

Topics: Cardiovascular Agents; Databases, Factual; Ductus Arteriosus, Patent; Female; Gestational Age; Humans; Ibuprofen; Indomethacin; Infant; Infant, Extremely Premature; Infant, Newborn; Intensive Care Units, Neonatal; Male; Treatment Outcome

To compare the effects of prophylactic indomethacin versus expectant management on short-term respiratory outcomes in extremely low-birth-weight (ELBW) infants.. This was a retrospective cohort study of ELBW infants with gestational age less than 28 weeks, born at a level III neonatal intensive care unit from 2004 to 2009. Patients were grouped based on whether they received prophylactic indomethacin or expectant treatment. The key outcome was the cumulative number of days of mechanical ventilation. Other outcomes were cumulative number of days supplemental oxygen and continuous positive airway pressure (CPAP) were required; duration of hospital stay; mortality; and other morbidities such as necrotizing enterocolitis and intraventricular hemorrhage. Multivariable linear regression was performed with treatment group and seven covariates, defined a priori, as predictor variables and cumulative number of days of mechanical ventilation as the outcome.. There were 144 infants in the prophylaxis group and 221 infants in the expectant treatment group. At baseline, the Score for Neonatal Acute Physiology-Perinatal Extension, incidence of respiratory distress syndrome, and usage of antenatal corticosteroids were significantly higher in the prophylaxis group. The cumulative number of days of mechanical ventilation, supplemental oxygen, and CPAP were significantly higher in the prophylaxis group. On multivariable linear regression, after adjusting for confounders, use of prophylactic indomethacin (unstandardized β coefficient = 12.4; 95% confidence interval [CI]: 6.6, 18.1; p < 0.001), birth weight (β =  -0.025; 95% CI: -0.05, -0.001; p = 0.043), and gestation (β =  -4.5; 95% CI: -7.24, -1.8; p = 0.001) were the independent predictors of cumulative number of days of mechanical ventilation.. ELBW infants who received prophylactic indomethacin had significantly longer cumulative number of days of mechanical ventilation, supplemental oxygen, and CPAP. Prophylactic indomethacin is an independent predictor of cumulative number of days of mechanical ventilation.

Topics: Cardiovascular Agents; Cerebral Hemorrhage; Continuous Positive Airway Pressure; Ductus Arteriosus, Patent; Female; Gestational Age; Humans; Indomethacin; Infant, Extremely Low Birth Weight; Infant, Newborn; Length of Stay; Male; Oxygen Inhalation Therapy; Respiration, Artificial; Retrospective Studies; Time Factors; Watchful Waiting

Pediatric studies have found a correlation between the clinical heart failure score and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. However, the clinical usefulness of this marker remains unclear in neonates. At hospitals without pediatric cardiologists, neonatologists or general pediatricians must judge whether surgery is indicated and transfer patients to a specialized hospital in a timely fashion as required. Thus, we tested the hypothesis that increased NT-proBNP levels predict short-term outcomes in neonates with congenital heart diseases (CHDs) and are thus a useful tool for evaluating clinical status and guiding treatment. Subjects were term or near-term newborns (≥36 weeks' gestation) with CHDs confined to left-to-right shunt lesions. Clinical parameters and NT-proBNP levels were measured on the first 7, 14, 21, and 28 days of life (DOL). We divided patients into a surgical (n = 7) and a conservative-treatment group (n = 21), and then compared clinical variables and outcomes between the groups. In the surgical group, NT-proBNP levels had a tendency to increase during the first 14 postnatal days and were significantly greater than in the conservative-treatment group on 7 DOL [median (range), 13,983 pg/mL (4,732-26,524) vs. 1,954 pg/mL (671-10,881); p = 0.0028] and on 14 DOL [29,274 pg/mL (14,006-33,740) vs. 2,050 pg/mL (1,304-9,250); p = 0.0055]. In contrast, NT-proBNP levels tended to decrease sequentially in the conservative-treatment group. The values of additional markers, such as mean NT-proBNP level on 7 and 14 DOLs (M7-14) and NT-proBNP level on 14 DOL minus that on 7 DOL (Δ7-14), were both significantly greater in the surgical group than in the conservative-treatment group. To examine the usability of M7-14 and Δ7-14 when the difference and mean cut-off levels were set at 10,000 and 3,000 pg/mL, respectively, the sensitivity and specificity were both 100 %. In neonates who had CHDs with left-to-right shunt, analysis of the association between clinical variables and short-term outcomes showed that NT-proBNP, especially M7-14 and Δ7-14, is a useful predictor of early surgery.

Topics: Biomarkers; Cardiac Catheterization; Cardiac Surgical Procedures; Cardiovascular Agents; Dimensional Measurement Accuracy; Ductus Arteriosus, Patent; Echocardiography; Female; Heart Septal Defects; Humans; Infant, Newborn; Japan; Male; Natriuretic Peptide, Brain; Outcome Assessment, Health Care; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Statistics as Topic; Term Birth; Time-to-Treatment

The indications for ductus arteriosus ligation in very-low-birth-weight infants (VLBWIs) with persistent ductus arteriosus (PDA) are unclear. Increased left ventricular end-diastolic dimension (LVDd) is commonly found in patients with PDA. Here, the enlargement of LVDd in term and preterm neonates without congenital heart disease was estimated by two-dimensional echocardiography.. The value of the measured LVDd was divided by the normal LVDd as an index (LVDd ratio) to compare 30 patients who underwent PDA ligation with 30 patients treated with indomethacin and 30 patients who did not undergo radical therapy.. An LVDd ratio between 122% and 197% (mean, 142%) was considered to be an indication for the ligation procedure. The proportion of patients exceeding 130% in the LVDd ratio was 87% (26/30) in those patients who underwent ligation. Catecholamines and/or vasodilators were required in 83% patients for the treatment of low ejection fraction or hypertension after operations, suggesting that patients had been in preload and/or afterload remodeling failure during the operation. The percentage of patients with less than 115% in the LVDd ratio was 90% in the non-radical-therapy patients. The LVDd ratios of 130% and 115% were regarded as cut-off values for surgical ligation and indomethacin treatment.. The LVDd ratio is a useful measure to determine the treatment of VLBWIs with PDA.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Echocardiography; Female; Heart Ventricles; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Ligation; Male

Topics: Acetaminophen; Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Humans; Infant, Low Birth Weight; Male

Topics: Acetaminophen; Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Humans; Infant, Low Birth Weight; Male

Topics: Acetaminophen; Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Humans; Infant, Low Birth Weight; Male

After the introduction of a new protocol based on the early treatment with indomethacin for patent ductus arteriosus, the objective of this study was to assess the safety and efficacy of this new practice in comparison with the safety and efficacy of the conventional treatment in a high-risk population.. We conducted a retrospective cohort study including 154 newborns with an average gestational age of 26.4 weeks (1.37 standard deviation) and an average birth weight of 855 g (201.5 standard deviation). A statistically descriptive analysis was performed with SPSS Statistics Pack version 17.0.. We did not find any statistically significant differences in the clinical features of the two treatment groups, nor in the main efficacy, morbidity, and mortality results.

Topics: Cardiovascular Agents; Chi-Square Distribution; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Ductus Arteriosus, Patent; Echocardiography, Doppler; Female; Follow-Up Studies; Gestational Age; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Male; Retrospective Studies; Risk Assessment; Survival Rate; Time Factors; Treatment Outcome

Treatment options for the closure of a hemodynamically significant patent ductus arteriosus (hsPDA) include medical therapy such as ibuprofen and indomethacin and surgical ligation.. To evaluate the efficacy of intravenous paracetamol in preterm infants with hsPDA whose feeding was contraindicated or had feeding intolerance.. Preterm infants with hsPDA were started on intravenous paracetamol treatment with parental consent. Paracetamol was administered at a dose of 60 mg/kg/day, in four divided doses, for a period of 3 days. In the absence of closure of hsPDA, treatment was extended up to 6 days, after which echocardiographic examination was performed.. A total of 10 preterm infants were included in the study with a median gestational age of 27(4/7) weeks (minimum-maximum: 24-29) and a median birth weight of 775 g (590-990). The first dose of intravenous paracetamol was given after a median of 6 days (2-15). On echocardiographic examination, median internal ductal diameter was 2 mm (1.5-3), with a median left atrium-to-aortic root ratio of 1.95 (1.6-2.2). Intravenous paracetamol resulted in successful closure of hsPDA in all patients.. This study is the first case series in the literature which used intravenous paracetamol treatment for hsPDA. We believe that intravenous paracetamol could be used as an alternative drug for infants. Further prospective randomized-controlled trials are needed to evaluate the efficacy of intravenous paracetamol for the closure of hsPDA.

Topics: Acetaminophen; Cardiovascular Agents; Chi-Square Distribution; Drug Administration Schedule; Ductus Arteriosus, Patent; Female; Gestational Age; Humans; Infant, Low Birth Weight; Infant, Newborn; Injections, Intravenous; Male; Time Factors; Treatment Outcome; Ultrasonography

To determine Patent ductus arteriosus (PDA) closure rates for extremely preterm infants in a tertiary care centre, factors affecting response to indomethacin and outcomes of these infants relative to their PDA status.. Neonatal intensive care unit in tertiary-care children's hospital.. Retrospective medical record review.. A retrospective chart review of all infants <29 weeks gestation between 1st Jan 2003 and 30th June 2006 was carried out. Multiple courses of standard intravenous indomethacin (dose: 0.2 mg/kg 12 hourly; 3 doses) followed by a tail course (0.1 mg/kg/day; 3 doses) were used to treat PDA depending on clinical and hemodynamic status. Data on demographic characteristics, PDA status, use of indomethacin, and outcome factors such as chronic lung disease and mortality were collected.. A total of 166 infants were identified in the study period, of which 15 were excluded. The median gestation was 27 weeks [IQR (25, 28)] and the mean (SD) birthweight was 950 (244) grams. The remaining infants (n=151) were divided into three groups. Group1 (n=47): no or non-significant PDA, Group 2 (n=91): significant PDA closed after indomethacin treatment (= 1 course) and Group 3 (n=13): significant PDA not responding to indomethacin. The closure rate of PDA with indomethacin treatment (group 2) was 87%. A low gestational age < 26 weeks (OR 5.6, 95% CI 1.6-19.9) and female sex (OR 5.8, 95% CI 1.5-22.8) was associated with poor response to indomethacin in our study population.. Multiple indomethacin courses using the standard dosing approach result in high PDA closure rates for infants < 29 weeks gestation.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Humans; Indomethacin; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases; Intensive Care Units, Neonatal; Male; Retrospective Studies; Treatment Outcome

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Echocardiography; Female; History, 16th Century; History, 17th Century; History, 21st Century; History, Ancient; Humans; Indomethacin; Pregnancy

Preterm infants are delivered while glomerulogenesis is ongoing and may be exposed to insults, including medications that may affect renal development. Podocytes detected in the urine are an indicator of glomerular injury. The aims of this study were to determine whether preterm and term infants excrete podocytes in their urine and whether exposure to gentamicin and indomethacin increase podocyte excretion in their urine.. Preterm infants <33 weeks gestation had urine collected each day while receiving either gentamicin or indomethacin. Preterm and term control infants had urine collected for 3 days. The number of casts and podocytes present in the urine of infants receiving indomethacin and gentamicin were compared with preterm and term control infants.. Forty-two neonates were included in the study. Podocytes were present in small numbers (< 2) in the urine of both preterm and term control neonates. The number of podocytes in the preterm group receiving indomethacin was significantly higher than in all other groups (p=0.02) ,as was urinary albumin (p=0.02).. Increased number of podocytes in preterm neonates receiving indomethacin and higher excretion of albumin suggest glomerular injury is occurring. It is unknown whether injury to glomeruli during glomerulogenesis in preterm neonates has long-term sequelae for renal development and function into adulthood.

Topics: Anti-Bacterial Agents; Cardiovascular Agents; Drug Therapy, Combination; Ductus Arteriosus, Patent; Female; Gentamicins; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Kidney Diseases; Kidney Glomerulus; Male; Podocytes

To examine whether a change in the approach to managing persistent patent ductus arteriosus (PDA) from early ligation to selective ligation is associated with an increased risk of abnormal neurodevelopmental outcomes.. In 2005, we changed our PDA treatment protocol for infants born at ≤27 6/7 weeks' gestation from an early ligation approach, with prompt PDA ligation if the ductus failed to close after indomethacin therapy (period 1: January 1999 to December 2004), to a selective ligation approach, with PDA ligation performed only if specific criteria were met (period 2: January 2005 to May 2009). All infants in both periods received prophylactic indomethacin. Multivariate analysis was used to compare the odds of a composite abnormal neurodevelopmental outcome (Bayley Mental Developmental Index or Cognitive Score <70, cerebral palsy, blindness, and/or deafness) associated with each treatment approach at age 18-36 months (n = 224).. During period 1, 23% of the infants in follow-up failed indomethacin treatment, and all underwent surgical ligation. During period 2, 30% of infants failed indomethacin, and 66% underwent ligation after meeting prespecified criteria. Infants treated with the selective ligation strategy demonstrated fewer abnormal outcomes than those treated with the early ligation approach (OR, 0.07; P = .046). Infants who underwent ligation before 10 days of age had an increased incidence of abnormal neurodevelopmental outcome. The significant difference in outcomes between the 2 PDA treatment strategies could be accounted for in part by the earlier age of ligation during period 1.. A selective ligation approach for PDAs that fail to close with indomethacin therapy is not associated with worse neurodevelopmental outcomes at age 18-36 months.

Topics: Age Factors; Blindness; Cardiovascular Agents; Cerebral Palsy; Child, Preschool; Combined Modality Therapy; Deafness; Developmental Disabilities; Ductus Arteriosus, Patent; Female; Follow-Up Studies; Humans; Indomethacin; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Ligation; Logistic Models; Male; Multivariate Analysis; Risk Factors; Treatment Outcome

Water channel AQP2 is the target for vasopressin (AVP) and a major determinant of urinary concentrating capacity. In mature kidneys, prostaglandins counteract the effect of AVP on AQP2 expression at functional sites. We investigated whether disturbances in water homeostasis in infants with patent ductus arteriosus (PDA) treated with prostaglandin inhibitors can be attributed to activation of AQP2.. In 53 infants with symptomatic PDA (gestational age 24-33 weeks), 30 receiving ibuprofen and 23 indomethacin starting at 2-15 days of life, clinical and biochemical data were collected before treatment and after each dose of the drugs. Urinary AQP2 was determined by dot immunoblotting.. Urinary AQP2 level and osmolality were decreased in both groups. Urinary osmolality was overall low and correlated inversely with fluid uptake. In ibuprofen group, there was no correlation of AQP2 level with urinary osmolality.. There was no AQP2 upregulation in the infants. The low urinary osmolality and dissociation between urinary osmolality and urinary AQP2 level indicate that the fluid retention sometimes observed in PDA infants treated with prostaglandin inhibitors is not caused by increased levels of functional AQP2. Thus, knowledge about the renal physiology of the adult cannot always be transferred to the infant kidney.

Topics: Aquaporin 2; Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Gestational Age; Humans; Ibuprofen; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Osmolar Concentration

To determine whether low platelet counts are related to the incidence of patent ductus arteriosus (PDA) after indomethacin treatment in preterm human infants.. Multivariable logistic regression modeling was used for a cohort of 497 infants, who received indomethacin (within 15 hours of birth).. Platelet counts were not related to the incidence of permanent closure after indomethacin constriction. There was a relationship between platelet counts and the initial degree of constriction; however, this relationship appeared to be primarily influenced by the high end of the platelet distribution curve. PDA incidence was similar in infants with platelet counts < 50 × 10⁹/L and those with platelet counts above this range. Only when platelet counts were consistently >230 ×10⁹/L was there a decrease in PDA incidence.. In contrast to the evidence in mice, low circulating platelet counts do not affect permanent ductus closure (or ductus reopening) in human preterm infants.

Topics: Cardiovascular Agents; Cohort Studies; Ductus Arteriosus; Ductus Arteriosus, Patent; Echocardiography; Female; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Male; Platelet Count; Regression Analysis; Time Factors; Treatment Outcome

Important short-term intermediate outcomes such as patent ductus arteriosus (PDA), severe intraventricular haemorrhage, surgical ligation of PDA and serious pulmonary haemorrhage correlate with worse neurosensory outcomes in extreme low birth weight infants. Indomethacin prophylaxis has been shown to significantly prevent such outcomes. However, this positive effect did not translate into neither prevention of bronchopulmonary dysplasia nor long-term neurosensory outcome. The indomethacin prophylaxis story is indeed a puzzling one to neonatal practitioners. We present a summary of evidence and possible explanations to the lack of appreciated long-term effect of indomethacin prophylaxis. As the trial of indomethacin prophylaxis for preterms trial is a major contributor to current evidence, a detailed critical analysis of its methodology is presented. Methodological concerns such as the use of a composite outcome, statistical power, anticipated side effects of indomethacin prophylaxis and lack of predictive validity of cognitive delay measurements are presented.. Conclusive evidence of indomethacin prophylaxis use in extreme low birth weight infants is still lacking. Future research should put more emphasis on parental preferences, synergistic effect of indomethacin prophylaxis and fluid restriction and early targeted approach to PDA management.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Agents; Clinical Trials as Topic; Ductus Arteriosus, Patent; Evidence-Based Medicine; Humans; Indomethacin; Infant, Extremely Low Birth Weight; Infant, Newborn; Practice Patterns, Physicians'

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Echocardiography; Enterocolitis, Necrotizing; Humans; Indomethacin; Infant, Newborn; Ligation; Pediatrics; Treatment Outcome

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Agents; Clinical Trials as Topic; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Practice Patterns, Physicians'

To determine whether N-terminal-pro-brain natriuretic peptide (NT-proBNP) level could be an effective guide for early targeted indomethacin therapy for patent ductus arteriosus (PDA) in preterm infants.. An interventional study involved preterm infants, born at <33 weeks of gestation, who had plasma NT-proBNP levels obtained at day 2 of life. Indomethacin therapy was given if plasma NT-proBNP level was ≥10,180 pg/mL, the cut-off for predicting hemodynamic significant PDA (hsPDA). Echocardiograms were performed within 6 h at the time of plasma NT-proBNP collection and again at day 7, or whenever clinical hsPDA was suspected. Primary outcomes were the incidence of later hsPDA and unnecessary exposure rate to indomethacin.. Fifty infants were enrolled. On day 2, 19 (38%) infants had plasma NT-proBNP above the cut-off and received indomethacin therapy; none of them developed later hsPDA, while 1 of 31 infants with NT-proBNP below the cut-off level developed clinical hsPDA. Unnecessary exposure to indomethacin occurred in two infants (11%). Overall, no enrolled infants had either reopening of ductus or PDA ligation.. Using NT-proBNP level on day 2 as a guide for early targeted indomethacin therapy reduced later onset of hsPDA and the number of unnecessary exposures to indomethacin.

Topics: Bronchopulmonary Dysplasia; Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Humans; Indomethacin; Infant; Infant, Newborn; Infant, Premature; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Statistics as Topic; Time Factors

Decision Aids (DA) are well established in various fields of medicine. It can improve the quality of decision-making and reduce decisional conflict. In neonatal care, and due to scientific equipoise, neonatologists caring for extreme low birth weight (ELBW) infants are in need to elicit parents' preferences with regard to the use of indomethacin therapy in ELBW infants. We aimed to develop a DA that elicits parents' preferences with regard to indomethacin therapy in ELBW infants.. We developed a DA for the use of the indomethacin therapy in ELBW infants according to the Ottawa Decision Support Framework. The development process involved parents, neonatologists, DA developers and decision making experts. A pilot testing with healthy volunteers was conducted through an evaluation questionnaire, a knowledge scale, and a validated decisional conflict scale.. The DA is a computer-based interactive tool. In the first part, the DA provides information about patent ductus arteriosus (PDA) as a disease, the different treatment options, and the benefits and downsides of using indomethacin therapy in preterm infants. In the second part, it coaches the parent in the decision making process through clarifying values and preferences. Volunteers rated 10 out of 13 items of the DA positively and showed significant improvement on both the knowledge scale (p = 0.008) and the decisional conflict scale (p = 0.008).. We have developed a computer based DA to assess parental preferences with regard to indomethacin therapy in preterm infants. Future research will involve measurement of parental preferences to guide and augment the clinical decisions in current neonatal practice.

Topics: Adult; Bronchopulmonary Dysplasia; Cardiovascular Agents; Decision Support Techniques; Ductus Arteriosus, Patent; Female; Hemorrhage; Humans; Indomethacin; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature; Intracranial Hemorrhages; Lung Diseases; Parents; Pilot Projects; Severity of Illness Index

Prostaglandin E(2) (PGE(2)) plays a major role both in maintaining patency of the fetal ductus arteriosus and in closure of the ductus arteriosus after birth. The rate-limiting step in PGE(2) signal termination is PGE(2) uptake by the transporter PGT.. To determine the role of PGT in ductus arteriosus closure, we used a gene-targeting strategy to produce mice in which PGT exon 1 was flanked by loxP sites. Successful targeting was obtained because neither mice hypomorphic at the PGT allele (PGT Neo/Neo) nor global PGT knockout mice (PGT(-/-)) exhibited PGT protein expression; moreover, embryonic fibroblasts isolated from targeted mice failed to exhibit carrier-mediated PGE(2) uptake. Although born in a normal mendelian ratio, no PGT(-/-) mice survived past postnatal day 1, and no PGT Neo/Neo mice survived past postnatal day 2. Necropsy revealed patent ductus arteriosus with normal intimal thickening but dilated cardiac chambers. Both PGT Neo/Neo and PGT(-/-) mice could be rescued through the postnatal period by giving the mother indomethacin before birth. Rescued mice grew normally and had no abnormalities by gross and microscopic postmortem analyses. In accordance with the known role of PGT in metabolizing PGE(2), rescued adult PGT(-/-) mice had lower plasma PGE(2) metabolite levels and higher urinary PGE(2) excretion rates than wild-type mice.. PGT plays a critical role in closure of the ductus arteriosus after birth by ensuring a reduction in local and/or circulating PGE(2) concentrations.

Topics: Animals; Cardiovascular Agents; Cells, Cultured; Dinoprostone; Disease Models, Animal; Ductus Arteriosus; Ductus Arteriosus, Patent; Female; Fibroblasts; Indomethacin; Lung; Mice; Mice, Knockout; Organic Anion Transporters; Pregnancy; Receptors, Prostaglandin E; Signal Transduction

To determine whether B-type natriuretic peptide (BNP) predicts indomethacin responsiveness in premature neonates with patent ductus arteriosus (PDA).. Premature neonates receiving indomethacin for an echocardiograhically large (diameter>1.5 mm) and clinically significant PDA were prospectively studied. All neonates underwent paired echocardiography and BNP measurements at baseline and 24 hours after each dose of indomethacin. After treatment, neonates who responded (with closed or insignificant PDA) and neonates who did not respond (with persistent significant PDA requiring surgical ligation) were compared.. Thirty-one premature neonates (mean gestational age, 30 weeks) underwent 119 paired echocardiography and BNP determinations. Mean BNP levels (1286+/-986 pg/mL) associated with significant PDA (n=96) were higher than those associated with closed or insignificant PDA (n=23; 118+/-124 pg/mL; P<.001). Twenty-three neonates responded and 8 neonates did not respond to indomethacin. Mean baseline BNP levels were higher in neonates who were non-responders (2234+/-991 pg/mL) than neonates who were responders (983+/-814 pg/mL; P=.001). A baseline BNP level>1805 pg/mL had a sensitivity rate of 88% and a specificity rate of 87% for predicting indomethacin non-responsiveness (P=.003).. High baseline BNP levels predict poor responses to indomethacin and the need for surgery in premature neonates with PDA.

Topics: Cardiovascular Agents; Cyclooxygenase Inhibitors; Ductus Arteriosus, Patent; Female; Gestational Age; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Pregnancy; Severity of Illness Index; Treatment Outcome; Ultrasonography

Although B-type natriuretic peptide (BNP) concentrations seem to be useful for detecting the presence of patent ductus arteriosus, there is no information about their usefulness for monitoring changes in PDA shunt magnitude.. We performed a retrospective analysis of paired BNP-echocardiogram measurements (obtained from infants (24 to 32 weeks gestation) with clinical suspicion of PDA).. Individual BNP concentrations (n=146, from 88 infants) were significantly related to shunt magnitude at the time of measurement and had good discriminating power for detecting a moderate-or-large shunt (area under receiver-operator characteristic curves (ROC-AUC)=0.85). In total, 36 infants had serial BNP-echocardiogram pairs (n=91) measured during their hospitalization. Changes (either increases or decreases) in BNP concentrations over time had only fair discriminating power (ROC-AUC=0.76) for detecting increases or decreases, respectively, in shunt magnitude.. The high degree of variability in the BNP measurements made them less useful for monitoring changes in magnitude.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Echocardiography; Female; Gestational Age; Humans; Indomethacin; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Male; Natriuretic Peptide, Brain; Predictive Value of Tests

Topics: Cardiac Surgical Procedures; Cardiotonic Agents; Cardiovascular Agents; Diuretics; Ductus Arteriosus, Patent; Gestational Age; Humans; Indomethacin; Infant, Newborn; Risk Factors

Respiratory distress and patent ductus arteriosus (PDA) in neonates are mutually perpetuating. Contrary to the situation in premature infants, the recognition, clinical relevance and optimal management of PDA in full-term neonates are unclear. The present study aimed to identify PDA as a possible cause of respiratory distress in term and near-term neonates, and to examine the clinical responsiveness of PDA to different treatment modalities in mature-gestational-age neonates.. Patients with gestational ages of over 34 weeks were included in this retrospective chart review; they had PDA as the sole recognizable cause of respiratory distress and were free of all other diseases. Clinical responsiveness to different regimens, including conservative treatment, drug therapy with preload reduction and inotropic agent with or without the addition of indomethacin, and surgical intervention were analyzed.. Forty-four neonates qualified for this study. Six received no treatment and their cardiorespiratory symptoms resolved within 1 week (regimen A). Symptoms in 11 neonates were relieved after use of diuretic and inotropic agents (regimen B). Twelve neonates became asymptomatic without further intervention after indomethacin treatment in addition to preload reduction and inotropes (regimen C). A total of 15 of the 44 infants underwent PDA ligation (regimen D) due to persistent heart failure following regimens B or C, but had speedy resolution of respiratory symptoms following surgery. There were significant differences in birth body weight and hemodynamic variation based on left atrium to aortic root dimensional ratio between the treatment (regimens B, C and D) and non-treatment (regimen A) groups (p < 0.05).. PDA plays an important role in prolonging respiratory distress in term or near-term neonates. Although most infants respond to noninvasive medical treatment, surgical ligation during the neonatal period is warranted in certain mature infants. Surgical treatment should be considered in patients with smaller birth body weights and those with increased left atrium to aortic root dimensional ratios.

Topics: Analysis of Variance; Cardiac Surgical Procedures; Cardiotonic Agents; Cardiovascular Agents; Diuretics; Ductus Arteriosus, Patent; Female; Gestational Age; Humans; Indomethacin; Infant, Newborn; Male; Respiratory Distress Syndrome, Newborn; Retrospective Studies; Treatment Outcome

The ductus arteriosus is an arterial vessel that shunts blood flow away from the lungs during fetal life, but normally occludes after birth to establish the adult circulation pattern. Failure of the ductus arteriosus to close after birth is termed patent ductus arteriosus and is one of the most common congenital heart defects. Mice with smooth muscle cell-specific deletion of Jag1, which encodes a Notch ligand, die postnatally from patent ductus arteriosus. These mice exhibit defects in contractile smooth muscle cell differentiation in the vascular wall of the ductus arteriosus and adjacent descending aorta. These defects arise through an inability to propagate the JAG1-Notch signal via lateral induction throughout the width of the vascular wall. Both heterotypic endothelial smooth muscle cell interactions and homotypic vascular smooth muscle cell interactions are required for normal patterning and differentiation of the ductus arteriosus and adjacent descending aorta. This new model for a common congenital heart defect provides novel insights into the genetic programs that underlie ductus arteriosus development and closure.

Topics: Animals; Animals, Newborn; Calcium-Binding Proteins; Cardiovascular Agents; Cell Differentiation; Ductus Arteriosus, Patent; Embryo, Mammalian; Female; Fluorescent Antibody Technique; Indomethacin; Intercellular Signaling Peptides and Proteins; Jagged-1 Protein; Male; Membrane Proteins; Mice; Microscopy, Electron, Transmission; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Receptor, Notch1; Reverse Transcriptase Polymerase Chain Reaction; Serrate-Jagged Proteins

Indomethacin is accepted therapy for patent ductus arteriosus (PDA) in ELBW infants (<1000 g). We hypothesize that surgical ligation may provide comparatively superior outcomes in select ELBW infants.. Predischarge outcomes of 298 ELBW infants with echocardiography-proven PDA were retrospectively compared by treatment provided: no treatment (group 1, n = 54), indomethacin (group 2, n = 140), ligation (group 3, n = 46), and ligation after indomethacin failure (group 4, n = 58). chi(2) and Wilcoxon rank sum tests were used to test for significance. Institutional review board approval was obtained (IRB/05-00395).. Group 3 had significantly lower gestational age (P < .001), birth weight (P = .006), and 5-minute Apgar scores (P = .03) compared with group 2. Group 3 and group 1 had a higher rate of pretreatment intraventricular hemorrhage (IVH) compared with group 2 (P < .001). By contrast, posttreatment complications including acute renal failure, necrotizing enterocolitis, thrombocytopenia, and IVH occurred more frequently in groups 2 (P = .004) and 4 (P = .001) compared with group 3. Survival was 57.7% in group 1 compared with groups 2, 3, and 4 (82.4%, 86.0%, and 92.7% respectively; P = .001). Preoperative conditions associated with nonsurvival include gestational age (P = .009), birth weight (P = .002), maternal preeclampsia (P = .015), 5-minute Apgar score (P = .013), and sepsis (P = .018). Posttreatment complications associated with nonsurvival include acute renal failure (P = .002), thrombocytopenia (P = .002), and necrotizing enterocolitis (P = .034). Survival was not influenced by any congenital comorbidity, pre- or posttreatment IVH, diameter of the PDA, or recurrence of the PDA after indomethacin therapy.. (1) Patent ductus arteriosis requires treatment in ELBW infants to maximize survival. (2) Indomethacin and surgical ligation permit equivalent survival in low-risk ELBW infants, but indomethacin results in a high failure and complication rate requiring operative salvage in a number of patients. (3) Surgical ligation permits survival of high-risk ELBW infants with a low complication rate and is preferable to indomethacin in ELBW infants with the above risk factors.

Topics: Cardiovascular Agents; Chi-Square Distribution; Ductus Arteriosus, Patent; Echocardiography; Female; Gestational Age; Humans; Indomethacin; Infant, Extremely Low Birth Weight; Infant, Newborn; Ligation; Male; Postoperative Complications; Retrospective Studies; Risk Factors; Statistics, Nonparametric; Treatment Outcome

This study aimed to establish current management practice for patent ductus arteriosus (PDA) among individual consultant neonatologists in Australia and New Zealand, to examine the influences that drives practice and highlight the importance of future randomised controlled trials in the region.. Eligible subjects were identified from the Directory of Neonatal Intensive Care Units in Australia and New Zealand, 2007. A questionnaire was sent online to each consultant and was followed up with a letter and telephone call. Seven questions addressed management approach, the drug used and the treatment regimen, threshold for referral for surgical ligation and the literature influencing practice. Data were collected from 22 August 2007 to 22 November 2007.. The overall response rate was 95%. For infants < or =28 weeks or < or =1000 g, all consultants treat PDA by one of four distinct management approaches. Expectant management was favoured by 35%, echocardiographic targeted prophylaxis 32%, presymptomatic treatment 16% and prophylaxis by 17%. There were marked regional variations in practice. Within individual units, more than one approach is used in 14 out of 24 units. Long courses of indomethacin are used to treat PDA by 86%. For 22% of consultants, management is not influenced by published literature.. Differences of opinion in the literature are reflected by the heterogeneity in clinical practice across regions and within units. Crucial questions undergoing evaluation are whether data extrapolated from a previous area are relevant to PDA in modern neonatology and whether targeting treatment early can translate to improved clinical outcome.

Topics: Australia; Cardiovascular Agents; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Intensive Care, Neonatal; New Zealand; Practice Guidelines as Topic; Practice Patterns, Physicians'; Surveys and Questionnaires

To determine the incidence of spontaneous closure of the patent ductus arteriosus (PDA) and the use of medical therapies for treatment of PDA-related conditions among very low birth weight (VLBW) infants with ductal patency at the time of initial hospital discharge.. We conducted a single-centre, retrospective, observational study of VLBW infants (birth weight <1500 g) born during 2004 and 2005 and discharged with a PDA. PDA was defined by echocardiographic and/or clinical criteria. We identified the related discharge needs, subsequent interventions, and the post-menstrual age (PMA) at which there was no longer evidence of a PDA.. Three hundred and ninety one VLBW infants were admitted; 310 survived to discharge. Ninety five were diagnosed with a PDA during their hospitalisations; 21 had a PDA at discharge (10 received indomethacin, 11 were never treated). Among these, mean gestational age was 28 weeks, mean birth weight was 998 g, and median duration of hospitalisation was 73 days. Two infants were discharged on oxygen, two on diuretics, and two on both. None had congestive heart failure, and none died during infancy. Spontaneous closure occurred in 18 of 21 infants at a median PMA of 48 weeks (range 34-76; interquartile range 46-56). Two infants had coil occlusion at 11 months of age. One patient had a PDA at 14 months of age.. Among a select group of VLBW infants with a PDA at initial hospital discharge, spontaneous closure during early infancy occurred in most infants.

Topics: Cardiac Catheterization; Cardiovascular Agents; Ductus Arteriosus, Patent; Electrocardiography; Epidemiologic Methods; Female; Gestational Age; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Male; Patient Discharge; Pregnancy; Remission, Spontaneous; Treatment Outcome; Ultrasonography

To describe factors associated with failure of patent ductus arteriosus closure and development of gastrointestinal complications in subjects treated with indomethacin.. Infants

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Enterocolitis, Necrotizing; Female; Humans; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Intestinal Perforation; Logistic Models; Male; Multivariate Analysis; Predictive Value of Tests; Retrospective Studies; Risk Factors; Severity of Illness Index; Treatment Outcome

Failure of the ductus arteriosus to close within 48-96 hours of postnatal age results in a left to right shunt across the ductus and overloading of the pulmonary circulation. This is more likely to happen in premature neonates with respiratory distress syndrome. Deterioration in the respiratory status on day 3-4 in a ventilated neonate and unexplained metabolic acidosis may be the earliest indicators of a patent ductus arteriosus (PDA). Indomethacin is the main stay of medical management of PDA in preterm neonates. Guidelines for administration of indomethacin have been described in the protocol. Restricted fluid therapy may be beneficial in the prevention of PDA in preterm neonates. Presence of PDA in a term neonate should be investigated to rule out an underlying congenital heart disease.

Topics: Cardiovascular Agents; Diagnosis, Differential; Ductus Arteriosus, Patent; Fluid Therapy; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Risk Factors

Patent ductus arteriosus (PDA), especially PDA with sepsis, has been reported as a risk factor for feed intolerance in preterm neonates. In this study, the start to full feeds interval was found to be longest in preterm neonates (

Topics: Age Factors; Analysis of Variance; Cardiovascular Agents; Ductus Arteriosus, Patent; Enteral Nutrition; Enterocolitis, Necrotizing; Female; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Male; Prognosis; Risk Factors; Sepsis

We report a clinical observation showing that continuous exposure to heparin via a central venous catheter is associated with patent ductus arteriosus treatment failure with indomethacin in very low birthweight infants.. A clinical observational case report in infants weighting <1501 g.. This study compares the rates of patent ductus arteriosus treatment failure during a) the index period from June 2, 2003, to August 22, 2003, when all very low birthweight infants with a peripherally inserted central venous catheter received continuous infusion of heparinized parenteral nutrition; b) the baseline period of 1 yr before the index period; and c) the postindex period of 1 yr after the index period.. The rate of patent ductus arteriosus treatment failure with indomethacin increased significantly during the index period compared with the baseline (odds ratio, 7.0; 95% confidence interval, 1.41-34.7; p = .017) and postindex periods (odds ratio, 33.8; 95% confidence interval, 4.72-243; p = .0005). The result was confirmed in logistic multivariable regression analysis.. This observation, based on a case series and their controls, serves as a basis for a new hypothesis suggesting that continuous exposure to heparin through heparinized central venous infusion significantly increases patent ductus arteriosus treatment failure with indomethacin. This hypothesis needs to be tested in a randomized controlled trial.

Topics: Anticoagulants; Cardiovascular Agents; Catheterization, Central Venous; Drug Antagonism; Ductus Arteriosus; Ductus Arteriosus, Patent; Heparin; Humans; Indomethacin; Infant, Newborn; Infant, Very Low Birth Weight; Treatment Failure

Caffeine and other methyl xanthines are widely used in the neonatal period. A recent, randomized, placebo-controlled, multicenter trial found that infants who were randomly assigned to caffeine treatment had less need for pharmacologic and/or surgical closure of a patent ductus arteriosus (PDA). We hypothesized that the decreased need for pharmacologic and surgical closure of the PDA after caffeine treatment might be due to a direct effect of caffeine on ductus contractility. We examined preterm fetal lamb ductus arteriosus (from 24 fetuses, 105 +/- 4 d of gestation, term = 147 d), in vitro to determine the direct effects of caffeine on the isometric tension of the ductus arteriosus. Caffeine (0.003-0.3 mM) had no direct effect on ductus arteriosus tension, nor did it affect the contractile response of the ductus arteriosus to increasing oxygen concentrations. Caffeine's lack of effect was observed in both the presence and absence of indomethacin and NG-nitro-L-arginine methyl ester (L-NAME) (inhibitors of prostaglandin and nitric oxide production). In conclusion, we found no evidence of a direct effect of therapeutic caffeine concentrations on ductus contractility.

Topics: Animals; Caffeine; Cardiovascular Agents; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Ductus Arteriosus; Ductus Arteriosus, Patent; Female; Gestational Age; Indomethacin; Muscle, Smooth, Vascular; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Oxygen; Pregnancy; Prostaglandins; Sheep; Vasoconstriction

To evaluate the incidence of symptomatic patent ductus arteriosus (PDA) in preterm infants, and the results of the intravenous indomethacine treatment and surgery.. Among 394 preterm infants (<37 weeks), symptomatic PDA was diagnosed by echocardiography in 51 babies and they were examined retrospectively. All infants were managed conservatively and then IV indomethacine was given to non-responders (n=30). Surgical closure was performed in 12 babies.. The incidence of symptomatic PDA in preterm infants was 12.9%: median age: 3 days, mean birth weight: 1434+/-540 g (540-2900g) and mean gestational age (GA) 30.9+/-3.3 weeks (23-37 weeks). With indomethacine, ductal closure was achieved in 70% infants. Early clinical improvement was observed in all cases that underwent surgery and most of them had a low birth weight (<1500 g) and an early gestational age (<32 weeks). None of them died due to operation.. The incidence of symptomatic PDA is high in preterm infants. Treatment with indomethacine improves ductal closure and is associated with few reversible adverse effects. In the other hand, early clinical improvement and high success rate were achieved after surgery. If indomethacine fails to achieve ductal closure, decision of surgery must be made immediately.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Echocardiography, Doppler, Pulsed; Gestational Age; Humans; Incidence; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Ligation; Retrospective Studies; Treatment Outcome

A preterm male infant with a patent ductus arteriosus developed neutropenia during treatment with indomethacin. Afterward, the mother described her own history of indomethacin-associated neutropenia. During the recovery from the neutropenia, the infant became septic with bacteremia caused by Enterobacter cloacae. Although indomethacin-related neutropenia has been described in adults, no case in a neonate has been reported. If neutropenia occurs after indomethacin therapy in a neonate, a familial history of indomethacin-associated neutropenia should be sought and the increased risk of infection should be considered.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Enterobacter cloacae; Enterobacteriaceae Infections; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Male; Neutropenia; Sepsis

To identify factors related to indomethacin non-responsiveness for patent ductus arteriosus (PDA) closure in very-low-birthweight (VLBW) neonates.. A chart review of 107 VLBW neonates with a clinical diagnosis of PDA who received indomethacin, admitted to a tertiary neonatal intensive care unit in Toronto, Canada, was conducted (study period November 2001 to October 2003). Positive responders were those with no clinical evidence of PDA for 72 h after indomethacin.. Response to the first course of indomethacin was 75%, and to the second course 67% among initial responders. Higher CRIB score (OR 1.15, 95% CI 1.02-1.31) and early surfactant administration (OR 3.74, 95% CI 1.04-13.47) were associated with non-responsiveness to indomethacin.. Indomethacin is effective for PDA closure. The response rate diminished with subsequent courses. Early surfactant and severity of illness at admission were associated with non-responsiveness to indomethacin.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Male; Pulmonary Surfactants

Intracranial pathology is a common and important complication in extremely low birth weight babies. Lenticulostriate vasculopathy (LSV) is an abnormal finding on cranial ultrasounds of sick babies and has been associated with congenital infection, chromosomal aberration and twin-to-twin transfusion. We describe a previously unreported situation of LSV being detected in both donor and recipient twin. This pair of monochorionic, diamniotic twins was admitted to the Neonatal Intensive Care Unit at 28 weeks of gestation. The mother underwent an emergency caesarean section because ultrasound and Doppler studies showed stage III twin-to-twin transfusion syndrome. The first twin weighed 998 g and second twin weighed 600 g. The first twin had an uneventful stay, whereas the second twin needed prolonged continuous positive airway pressure and indomethacin for patent ductus arteriosus. Both of them developed LSV. The clinical significance of this condition on the neuro-developmental outcome of a neonate has not yet been fully determined.

Topics: Basal Ganglia Cerebrovascular Disease; Cardiovascular Agents; Continuous Positive Airway Pressure; Ductus Arteriosus, Patent; Female; Fetofetal Transfusion; Humans; Indomethacin; Infant, Newborn; Pregnancy; Thalamus; Twins, Monozygotic; Ultrasonography

Patent ductus arteriosus is a risk factor for the development of necrotizing enterocolitis. The use of indomethacin to treat patent ductus arteriosus in preterm infants may either decrease the incidence of necrotizing enterocolitis by stabilizing or closing the ductus arteriosus or increase its incidence by a direct constricting effect on mesenteric blood vessels. The authors sought to evaluate the interrelationship between patent ductus arteriosus, treatment with indomethacin and the risk of necrotizing enterocolitis in very low birth weight infants.. The Israel National database includes prospectively collected data on 99% of all very low birth weight infants in Israel. The study population comprised 6146 infants of 24-34 weeks' gestation born between 1995 and 2000. The effect of patent ductus arteriosus on necrotizing enterocolitis was assessed using multiple regression analysis.. Necrotizing enterocolitis occurred in 5.5% (n = 343) of all infants, in 9.4% of infants with patent ductus arteriosus and in 8.9% of infants who received indomethacin. The occurrence of necrotizing enterocolitis was independently associated with the presence of patent ductus arteriosus among infants not treated with indomethacin (odds ratio, 1.85) and those who received indomethacin therapy (odds ratio, 1.53). Indomethacin therapy in absence of patent ductus arteriosus was not associated with an increased risk of necrotizing enterocolitis (odds ratio, 0.72).. Patent ductus arteriosus is an independent risk factor for the development of necrotizing enterocolitis in very low birth weight infants. Therapy with indomethacin did not have a significant effect on the risk for necrotizing enterocolitis.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Enterocolitis, Necrotizing; Female; Humans; Indomethacin; Infant; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Male; Odds Ratio; Prevalence; Regression Analysis; Risk Factors

The effectiveness of continuous indomethacin (INDO) infusion versus bolus infusions for closure of patent ductus arteriosus (PDA) was investigated. The study design was an open-label case series (continuous INDO) with historic controls matched for gestational age (bolus INDO). Ductal closure rates were determined in two groups: 16 preterm infants with PDA treated with continuous INDO infusion (CONTIN group) and 16 control patients, matched for gestational age, who received bolus INDO infusions (BOLUS group). The total dosage was the same for both groups. PDA closed in seven of 16 preterm infants in the CONTIN group and in 13 of 16 in the BOLUS group ( p = 0.033, Fisher's exact test). In infants < 1000 g it was two of eight in the CONTIN group and 10 of 10 in the BOLUS group ( p = 0.002). Continuous INDO infusion was more likely than bolus infusion to be associated with failure of ductal closure (odds ratio, 19; 95% CI, 1.5 to 247; p = 0.023). This indicates that continuous infusion of INDO may be less effective in closing PDA than bolus infusions, especially in extremely low birth weight infants.

Topics: Cardiovascular Agents; Case-Control Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Ductus Arteriosus, Patent; Enterocolitis, Necrotizing; Female; Gestational Age; Humans; Indomethacin; Infant, Newborn; Infant, Very Low Birth Weight; Infusions, Intravenous; Logistic Models; Male; Oliguria; Retrospective Studies; Treatment Outcome

Surgical ligation of patent ductus arteriosus (PDA) is widely practised in preterm infants despite no clear evidence that this improves outcomes. Geographical isolation meant that ductal ligation was not an option in King Edward Memorial Hospital until recently.. A retrospective data analysis to test the hypothesis that outcomes of infants with persistent PDA were no worse than those of infants with no significant duct or a duct that closed after medical treatment.. A total of 252 infants (gestation < or =28 weeks) born between 1 January 2000 and 30 June 2002 were divided into three groups: group 1, no significant PDA (n = 154); group 2, significant PDA which closed after medical treatment (n = 65); group 3, significant PDA remaining patent after medical treatment (n = 33). A significant PDA was defined by a left atrium to aortic root ratio of >1.4 or a ductal diameter >1.5 mm with a left to right shunt.. Twenty four (10%) infants died at median (interquartile range) 15.5 (9-35) days. After adjustment for gestational age, relative to group 1, the infants from group 3 were at a 4.02 times increased risk of death (95% confidence interval 1.12 to 14.51). There was no significant difference between groups in the incidence of chronic lung disease, chronic lung disease or death, necrotising enterocolitis, intraventricular haemorrhage, duration of oxygen, or hospital stay.. Mortality was higher in infants with a persistent PDA, but other morbidities were not significantly different. A randomised trial is needed to determine whether surgical ligation will reduce mortality in such infants.

Topics: Cardiovascular Agents; Cause of Death; Ductus Arteriosus, Patent; Female; Gestational Age; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Ligation; Male; Prognosis; Retrospective Studies; Treatment Outcome; Unnecessary Procedures; Western Australia

The objective of this study was to determine the rate of patent ductus arteriosus (PDA) closure in premature infants using an adjustable indomethacin (INDO) dosing strategy, based on a second-dose peak plasma INDO level. We conducted a retrospective review of the medical records of premature infants that were treated with INDO for a PDA, had a second dose peak plasma NDO levels, and followed predetermined guidelines for INDO dosing adjustments, over a 4-year period (1995 to 1998). Of 103 infants treated with the adjustable INDO dosing strategy, 66 (64%) achieved PDA closure whereas 37 (36%) did not. No differences in the second-dose peak plasma INDO levels (830 +/- 339 versus 702 +/- 381 ng/mL), day of life treatment was started (4 +/- 3 versus 4 +/- 2 days), or the number of doses of INDO received (4 +/- 1 versus 5 +/- 2 dose) were observed between responders and nonresponders. However, fourth-dose peak plasma INDO levels, which were available from 38 of 66 (57%) of the responders and 20 of 37 (54%) of the nonresponders, were lower in nonresponders (1553 +/- 413 versus 1829 +/- 609 ng/mL, p < 0.05). Patient demographics, including birth weight and gestational age, were similar between these groups. Using an adjustable INDO dosing strategy, based on a second-dose peak plasma INDO level and estimated plasma levels, PDA closure rates of 64% can be achieved. Although a clear relationship between INDO plasma levels and PDA closure was evident form this study, the rate of PDA closure in our study was lower than has been observed in studies with serial plasma INDO level monitoring.

Topics: Cardiovascular Agents; Dose-Response Relationship, Drug; Ductus Arteriosus, Patent; Female; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Male; Retrospective Studies; Risk Factors; Treatment Outcome; United States

Wide pulse pressure is considered to be a sign of patent ductus arteriosus (PDA). We tested the hypothesis that, following indomethacin therapy, PDA closure is associated with a significant decrease in pulse pressure. Thirty-two ventilated preterm infants were echocardiographically diagnosed within the first 24 hours of life with PDA. Systolic, diastolic, and mean arterial blood pressures were measured prior to indomethacin treatment and after echocardiographically confirmed PDA closure. Following PDA closure, systolic and diastolic blood pressures and mean arterial pressure increased significantly without a significant change of pulse pressure (17 +/- 7 to 20 +/- 12 torr). We conclude that in preterm infants with PDA, systolic, diastolic, and mean arterial blood pressures increase significantly within first few days of life. Pulse pressure does not appear to be affected by early PDA closure. We speculate that high pulmonary resistance in the first days of life prevents significant diastolic aortic runoff and leaves pulse pressure unaffected by PDA, as well as by its closure.

Topics: Blood Pressure; Cardiovascular Agents; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Intensive Care Units, Neonatal; Predictive Value of Tests; Respiratory Distress Syndrome, Newborn; Retrospective Studies; Time Factors

With recent discussions in the literature regarding prophylactic use of early (within the first 12 h after birth), low-dose indomethacin to reduce the incidence and severity of intraventricular hemorrhage, knowledge pertaining to the cerebral hemodynamic effects of indomethacin in this age group is of significant interest. The cerebral circulation is known to undergo significant changes during the first few days of postnatal life. In the present study, we have investigated the hypothesis that postnatal adaptive changes influence the cerebral hemodynamic response to indomethacin in an age-dependent manner. Near-infrared spectroscopy with indocyanine green was used to measure cerebral hemodynamics, cerebral metabolic rate of oxygen, and cerebral oxygen extraction fraction in 39 newborn piglets. Piglets were grouped by age and received either 0.2 mg/kg indomethacin (14 were <13 h of age and 12 were >13 h of age) or saline (8 were <13 h of age and 5 were >13 h of age) infusions. In a subgroup of indomethacin-treated piglets (9 less than and 7 greater than 13 h of age), Doppler flow ultrasound was used to diagnose and monitor the presence and persistence of patent ductus arteriosus. Age was a significant factor in the cerebral hemodynamic response to indomethacin with piglets <13 h of age exhibiting delayed increases in cerebral blood flow and cerebral blood volume at 150 min post-indomethacin infusion.

Topics: Adaptation, Physiological; Aging; Animals; Animals, Newborn; Blood Volume; Brain; Cardiovascular Agents; Cerebrovascular Circulation; Coloring Agents; Ductus Arteriosus, Patent; Echocardiography, Doppler; Hemodynamics; Indocyanine Green; Indomethacin; Oxygen; Spectroscopy, Near-Infrared; Swine

To characterize the population pharmacokinetics of indometacin in preterm infants with symptomatic patent ductus arteriosus and to investigate the influence of various factors on the response to treatment.. Data were collected from 35 infants (gestational age 25-34 weeks; postnatal age 1-77 days) in neonatal units in Belfast and Copenhagen. Infants received an initial course of up to three doses of intravenous indometacin (0.1-0.2 mg kg(-1)) as considered appropriate by the treating physician. For those infants who did not respond to therapy or in whom the ductus reopened, a second course was sometimes given. Population analysis of the 185 plasma concentrations obtained was conducted using NONMEM and pharmacokinetic and demographic differences between responders and nonresponders were compared.. The concentration-time course of indometacin was best described by a one-compartment model. The final population parameter estimates of clearance (CL) and volume of distribution (V) (standardized to the median weight of 1.17 kg) were 0.00711 l h(-1) and 0.266 l, respectively. CL increased from birth by approximately 3.38% per day and V by approximately 1.47% per day. Concomitant digoxin therapy resulted in a 30% decrease in V. Interindividual variability in CL and V was 41% and 21%, respectively. Interoccasion variability for CL was 43%. Residual variability corresponded to a standard deviation of 0.148 mg l(-1). Closure occurred in 75% of infants with a plasma concentration > or = 0.4 mg l(-1) 24 h after the last dose.. Dosing regimens for indometacin should take into account the weight and postnatal age of the infant and any concomitant digoxin therapy. The population estimates can be used to determine typical values of CL and V allowing the prediction of individualized doses of indometacin that should increase the probability of achieving a 24 h plasma concentration > or = 0.4 mg l(-1). Although the pharmacokinetic estimates will be affected by both interindividual and within-individual variation, it is anticipated that this approach will decrease the variability of exposure and optimize treatment outcome.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Humans; Indomethacin; Infant; Infant, Newborn; Infant, Premature; Infusions, Intravenous; Male

Indomethacin is the most frequently used pharmacological agent for closure of a patent ductus arteriosus (PDA) in premature infants. However, reports of complications, particularly, necrotizing enterocolitis (NEC) and isolated gastrointestinal perforation have generated concerns about the use of this medication.. A retrospective study to compare the incidence of NEC, NEC-related gastrointestinal complications and isolated gastrointestinal perforation among premature infants treated for a PDA with either, indomethacin alone (I), surgical ligation alone (L), or indomethacin followed by surgical ligation (I-L).. The medical records of 224 infants that underwent treatment, either pharmacological or surgical, for a PDA, confirmed by echocardiography, over a 4-year period (1995 to 1998) were analyzed. Treatment history and gastrointestinal complications were reviewed.. Of the 224 infants, 108 (48.2%) were treated with I, 50 (22.3%) by L, 66 (29.5%) with I-L. The clinical characteristics of the three treatment groups were similar and no differences in the incidence of NEC were observed between groups. NEC occurred in 14 (13%) of the I group, seven (14%) of the L group, and eight (12%) of the I-L group. The rate of NEC related gastrointestinal complications and isolated gastrointestinal perforation were also similar among groups.. In this large retrospective study, indomethacin treatment for a significant PDA in premature infants was not associated with a greater risk for NEC or NEC-related gastrointestinal complications than surgical ligation.

Topics: Birth Weight; Cardiac Surgical Procedures; Cardiovascular Agents; Ductus Arteriosus, Patent; Enterocolitis, Necrotizing; Gastrointestinal Diseases; Gestational Age; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Intestinal Perforation; Ligation; Retrospective Studies

To determine the relative risk of severe intraventricular hemorrhage (IVH) between two very early indomethacin treatment strategies.. Retrospective chart review of infants <29 weeks gestation and <1350 g who received either indomethacin prophylaxis or very early echocardiography with indomethacin treatment only if the ductus arteriosus was patent.. A total of one hundred and two infants received prophylactic indomethacin (pINDO). Echochardiography was performed on 158 infants, of whom 117 received indomethacin. Infants receiving pINDO had lower gestational age, but similar birth weight, gender, race, antenatal steroid exposure, delivery mode, Apgar scores, and need for resuscitation as infants evaluated by echocardiography. Grades III to IV IVH was observed less frequently in infants who received pINDO (OR 0.27, 95% CI 0.10 to 0.77, p=0.014). Frequency of side effects and recurrent patent ductus arteriosus did not differ between treatment groups.. pINDO reduces severe IVH when compared to an early echocardiography strategy.

Topics: Cardiovascular Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Ductus Arteriosus, Patent; Echocardiography; Female; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Intracranial Hemorrhages; Male; Retrospective Studies; Severity of Illness Index; Time Factors

Altered pulmonary vascular resistance might be a factor for delayed closure of the ductus arteriosus (DA) in preterm infants. Angiotensin II plays a central role in the elevation of pulmonary vascular resistance. Angiotensin II exerts its vasoconstrictor effect on the angiotensin II type 1 receptor (AT1R). Homozygous carriers of the AT1R A1166C genetic variant present an exaggerated vasoconstrictor response to angiotensin II. We have investigated whether the presence of AT1R CC1166 influences the effect of prophylactic indomethacin treatment on the closure of DA until the fifth postnatal day in preterm infants. In this retrospective study detailed medical history of the first postnatal week was obtained in 159 infants born before the 33rd gestational week. All were treated by prophylactic indomethacin to induce permanent closure of the DA. On the sixth postnatal day the DA was still open in 56, whereas it was permanently closed in 103. The AT1R A1166C genotype of the infants was determined from Guthrie spots. Stepwise binary logistic regression analysis was used to assess the effect of medical conditions and genotype on the risk of patent DA (PDA). Birth weight, infantile respiratory distress, and severe hypotension were independent risk factors for PDA (p < 0.01, p < 0.05, p < 0.05, respectively). The carrier state of AT1R CC1166 was protective against PDA (p < 0.05; odds ratio, 0.067). AT1R AC1166 genotype was not associated with PDA. Our results indicate that the risk of PDA might be lower in infants of AT1R CC1166 than in those with AC or AA genotypes.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Genotype; Gestational Age; Humans; Indomethacin; Infant, Newborn; Infant, Very Low Birth Weight; Polymorphism, Genetic; Pregnancy; Receptor, Angiotensin, Type 1; Retrospective Studies

We evaluated the factors related to indomethacin responsiveness of the patent ductus arteriosus (PDA) and subsequent renal and electrolyte abnormalities in a large number of low birth weight infants.. The ductus was evaluated by Doppler echocardiogram or clinical signs after the last administration of indomethacin for 2538 low birth weight infants, through the use of postmarketing surveillance data.. Multivariate logistic regression analyses demonstrated that clinical closure of PDA was significantly associated with pregnancy-induced hypertension and respiratory distress syndrome. In contrast, a 1-point increase of cardiovascular dysfunction score or a 1-day increase in postnatal age at the first indomethacin treatment decreased the responsiveness of the ductus to indomethacin. Clinical ductal reopening was significantly less likely to occur for each week of increased gestational age. Ductal reopening was more likely for each day of postnatal life at the first administration of indomethacin. Infants with preexisting renal and electrolyte abnormalities and infants whose mothers had received indomethacin tocolysis or who had chorioamnionitis were at increased risk of development of renal impairment.. Both antenatal and postnatal factors predict good or poor response to indomethacin therapy for PDA.

Topics: Cardiovascular Agents; Chorioamnionitis; Ductus Arteriosus, Patent; Echocardiography, Doppler; Female; Humans; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Kidney Diseases; Male; Multivariate Analysis; Pregnancy; Pregnancy Complications; Water-Electrolyte Imbalance

Patent ductus arteriosus (PDA) is a frequent complication in premature infants. Intravenous indomethacin is the standard mode of medical therapy and has been shown to be efficacious in closing the ductus. In our setup, oral indomethacin is being regularly used for medical treatment of suspected or clinically diagnosed PDA. Non-availability of the parenteral preparation and lack of information regarding the pharmacokinetic disposition of indomethacin in the premature infants in north Indian population led us to conduct this pharmacokinetic study with oral indomethacin.. Twenty premature infants with gestational age 30.3 +/- 0.3 wk and birth weight, 1209.8 +/- 39.5 g; admitted to the neonatal unit of the Nehru Hospital, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh were enrolled in the study. Indomethacin was administered in a single oral dose of 0.2 mg/kg and blood samples were collected through an indwelling vascular catheter at 0 and 1, 2, 4, 8 and 12 h after administration of indomethacin. Plasma indomethacin concentrations were assayed by spectrofluorometric technique.. Large interindividual variability was observed for peak plasma concentrations (Cmax; 137.9 +/- 14.0 ng/ml), elimination half-life (t1/2 el; 21.4 +/- 1.7 h) and area under the plasma concentrations time curve (AUC0-infinity;4172 +/- 303 ng.h/ml) in these infants. Variables like birth weight, and sex did not have any sigiificant effect on indomethacin pharmacokinetics. However, the plasma t1/2 el of indomethacin was significantly (P < 0.01) larger in older infants (gestational age > 30 wk) in comparison to younger ones (gestational age < or = 30 wk). There was a negative correlation between gestational age and elimination t1/2 (r = -0.77).. In conclusion, indomethacin pharmacokinetics showed a wide variability in premature infants. In view of these findings it can be suggested that infants of smaller gestational age are at greater risk of cumulative toxicity if more than one dose of indomethacin is given. With advancing age, metabolism as well as elimination of drug is faster that may require modification in indomethacin dose to achieve therapeutic response. These preliminary results may be of use in designing future pharmacokinetic studies of oral indomethacin in preterm neonates on a larger sample.

Topics: Administration, Oral; Birth Weight; Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Humans; India; Indomethacin; Infant, Newborn; Infant, Premature; Male

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Agents; Cerebral Hemorrhage; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Postnatal Care

A prospective study was performed to evaluate the incidence, clinical manifestations and outcome of ductus arteriosus aneurysm (DAA) in full-term neonates.. Ductus arteriosus aneurysm has been considered to be a rare congenital lesion and a potentially fatal abnormality.. A total of 548 full-term neonates received echocardiographic screening.. There were 48 (8.8%) patients (28 boys and 20 girls) with DAA detected by echocardiography. The maximal diameter of the DAA ranged from 6.5 to 11.2 mm (8.2 +/- 1.2 mm). All cases were asymptomatic. There were no significant differences in gender, gestational age, maternal age or Apgar score between the newborns with or without DAA. Newborns with DAA had a higher birth body weight, higher incidence of maternal gestational diabetes mellitus and more mothers with blood group A, compared with newborns without DAA (p < 0.05). Follow-up echocardiograms showed spontaneous closure of the ductus arteriosus in all patients except those without DAA. The DAA became progressively smaller after ductal closure in 33 patients (70.2%) and completely disappeared by 7 to 35 days of life. The other 14 patients (29.8%) with DAA had echocardiographic evidence of progressive formation of thrombi between the third and tenth day of life. The DAA and thrombi spontaneously disappeared in all patients by one month after birth.. There is a higher incidence of DAA with a good outcome in our series compared with previous reports. We speculate that the presence of DAA may be a normal variant of the ductal bump and part of a normal process of spontaneous ductal closure in full-term neonates.

Topics: Aneurysm; Cardiovascular Agents; Ductus Arteriosus; Ductus Arteriosus, Patent; Echocardiography, Doppler, Color; Female; Humans; Imaging, Three-Dimensional; Indomethacin; Infant, Newborn; Magnetic Resonance Angiography; Male; Prospective Studies; Radiography

The aim of this study was to determine if it was possible to decrease the number of boluses of indomethacin for the treatment of patent ductus arteriosus. This retrospective study included 46 preterm neonates (<34 weeks' GA) who had had an ultrasound diagnosis predictive of subsequent symptomatic patent ductus arteriosus. All patients had received a daily intravenous doses of indomethacin, 0.1 mg/kg. Mean age at initiation of treatment was 4.5 +/- 3.1 days. Patency of the ductus arteriosus was controlled echocardiographically each day and treatment was discontinued as soon as the ductus arteriosus was closed. The initial success rate was 84.7%, of which 6.5% reopened. The mean cumulative dose of indomethacin was 0.35 mg/kg. There was no correlation between gestational age or birth weight and total cumulative dose. Overall tolerance was satisfactory with only one case of transient acute renal failure. A weak correlation between the cumulative dose of indomethacin and natremia (r = -0.43) or weight gain (r = 0.35) was noted, and none with serum creatinine or blood urea nitrogen levels. We confirm that lower indomethacin treatment of patent ductus arteriosus in premature neonates are as effective as standard protocols.

Topics: Cardiovascular Agents; Dose-Response Relationship, Drug; Ductus Arteriosus, Patent; Echocardiography; Female; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Male; Respiratory Distress Syndrome, Newborn; Retrospective Studies

To determine patent ductus arteriosus (PDA) closure rates, and indomethacin (INDO) toxicity rates in neonates dosed with INDO using an individualized pharmacokinetic/pharmacodynamic (PK/PD) dosing approach. In addition, develop PD curves evaluating dose-response and concentration-response relationships for closure and renal toxicity, especially in select subgroups historically known as "poor responders" (<1000 g and > or = 10 days postnatal age).. Prospective, cohort study.. Level III neonatal intensive care unit.. One hundred thirty-nine patients receiving 151 courses of INDO for PDA closure were evaluated.. Patients initially received 0.25 mg/kg of INDO, followed immediately by 1 mg/kg of furosemide. INDO concentrations were obtained 2 hrs and 8 hrs after the dose and were assayed using high-performance liquid chromatography. Individualized PK parameters were calculated with subsequent INDO dosing based on the individualized PK variables to increase trough serum concentrations by 0.3-0.5 mg/L.. Ductal closure was successful in 127 patients (91%). Renal toxicity occurred in 21 (15%) patients and was temporary and reversible. No significant differences in response rates based on treatment weight or postnatal age were observed. PD curves were similar for neonates <1000 g vs. > or = 1000 g. PD curves were also similar for neonates with postnatal age <10 days vs. > or = 10 days. Statistically significant differences were noted between neonates categorized for postnatal age <10 days vs. > or = 10 days in total days of therapy (1.8 vs. 2.3 days), total number of doses required to close PDA (3.5 vs. 5.6 doses), critical INDO dose (0.9 vs. 1.4 mg/kg), critical INDO concentration (1.9 vs. 1.4 mg/L), and critical dose/critical concentration ratio (0.52 vs. 2.2).. These findings support the hypothesis that the poor PDA closure rates with INDO for neonates >10 days postnatal age are the result of pharmacokinetic differences only and that weight does not impact response rates. Individualized pharmacokinetic/pharmacodynamic dosing of INDO continues to achieve higher closure rate than current dosing standards. Patients historically known as poor responders significantly benefit from this dosing approach.

Topics: Age Factors; Algorithms; Birth Weight; Cardiovascular Agents; Dose-Response Relationship, Drug; Ductus Arteriosus, Patent; Gestational Age; Humans; Indomethacin; Infant, Newborn; Prospective Studies; Reference Values; Treatment Outcome

Topics: Bronchopulmonary Dysplasia; Cardiovascular Agents; Ductus Arteriosus, Patent; High-Frequency Ventilation; Humans; Indomethacin; Infant Welfare; Infant, Newborn; Infant, Premature; Time Factors; Treatment Outcome

The most important factor determining anatomic remodeling and permanent closure of the ductus arteriosus is the degree of ductus constriction after indomethacin treatment. Muscular constriction produces a region of ischemic hypoxia in the middle of the ductus muscle media that initiates the process of permanent closure. Previous studies have shown that infants delivered before 28 weeks' gestation, who still have evidence of ductus flow on Doppler examination (performed after the standard 3-dose course of indomethacin), have a high likelihood (>85% chance) of reopening their ductus in the future. In contrast, if there is no evidence of luminal patency on the posttreatment Doppler examination, the incidence of ductus reopening is <20%. In the following study, we examined infants who still had a patent ductus on Doppler examination after a 3-dose course of indomethacin, to identify which factors might be associated with permanent ductus closure. We hypothesized that infants who received additional doses of indomethacin after the standard 3-dose course might develop an even tighter degree of ductus constriction and increase their chance of developing permanent closure.. We performed a retrospective cohort study of preterm infants (< or =26; weeks' gestation) who were treated with indomethacin. Between 12 and 24 hours after the third dose of indomethacin, infants were examined for the presence or absence of ductus-related signs, and an echocardiogram was performed. Infants responded to the initial 3 doses of indomethacin in 1 of 3 ways: 1) the ductus was closed clinically (absent clinical signs) with no evidence of luminal flow on Doppler examination ("clinically closed"; n = 214); 2) the ductus was closed clinically, but a small amount of left-to-right luminal flow was evident on Doppler examination ("partially closed"; n = 69); 3) or the ductus was open clinically and echocardiographically ("nonresponder"; n = 30). Nonresponders underwent surgical ligation (n = 30). Infants with a partially closed ductus formed our study population. We used a hierarchical regression model to identify which, if any, of the following factors might be associated with permanent anatomic closure in the 69 infants with a partially closed ductus: 1) gestational age, 2) exposure to antenatal steroids, 3) birth weight, 4) sex, 5) presence and severity of respiratory distress, 6) fluid administration during the first 96 hours after birth, 7) indomethacin treatment approach (prophylactic vs symptomatic), 8) year of birth, 9) use of surfactant, 10) preeclampsia, 11) chorioamnionitis, 12) bacterial septicemia, 13) necrotizing enterocolitis, or 14) duration of indomethacin treatment (standard 3-dose course vs prolonged 6-dose course). Infants who received the standard 3-dose course of indomethacin treatment were given 0.2, 0.1, and 0.1 mg/kg indomethacin during a 48-hour period. Infants who received the prolonged 6-dose course of indomethacin treatment were given a fourth, fifth, and sixth dose of 0.1 mg/kg at 24 hour-intervals, starting 24 hours after the third dose.. Sixty-eight of the 69 infants survived long enough to complete all of the study evaluations. Seventy-five percent (51/68) reopened their ductus and became symptomatic; 71% (48/68) were eventually ligated. Only gestational age and duration of indomethacin treatment were significantly and independently associated with permanent closure. A prolonged 6-dose course of indomethacin was more likely than the standard 3-dose course to be associated with an increased incidence of echocardiographic closure, a decreased incidence of symptomatic reopening (odds ratio: 0.19; 95% confidence interval: 0.04-0.96), and a decreased incidence of ductus ligation (odds ratio: 0.14; 95% confidence interval: 0.03-0.68).. Several older studies have suggested that a longer initial course of indomethacin therapy may be more effective in producing permanent ductus closure than the standard 3-dose course. In contrast, more recent studies have found that a longer course of indomethacin is no more effective than the standard 3-dose course in producing permanent closure. We hypothesize that the different outcomes among these studies may be attributable to differences in the degree of ductus constriction during the standard 3-dose course of indomethacin. Both the increased use of antenatal steroids and the earlier use of indomethacin has increased the effectiveness of the standard 3-dose course of indomethacin in recent years. We hypothesize that, in contrast with earlier studies, a significant proportion of the infants in the recent studies may have developed complete Doppler closure with just 3 doses of indomethacin (as occurred in 214 of the 313 infants treated with the standard 3-dose course in our study). Because the degree of ductus constriction seems to determine the rate of anatomic remodeling and permanent closure, daily echocardiographic evaluations of ductal patency may be the best way to decide when indomethacin therapy is no longer needed. Our study suggests that infants who still have evidence of luminal patency, after a standard 3-dose course of indomethacin, may be likely to benefit from a longer course of indomethacin. Future randomized trials that examine the benefits of different lengths of indomethacin treatment may wish to take this into consideration.. Despite the increased effectiveness of a prolonged course of indomethacin, the rates of ductus reopening and surgical ligation were still very high in infants with a partially closed ductus. Other therapeutic approaches will need to be developed before permanent closure is likely to occur in this group of immature infants.

Topics: Cardiovascular Agents; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Ductus Arteriosus; Ductus Arteriosus, Patent; Echocardiography; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Regression Analysis; Retrospective Studies; Time Factors

To define how often transient pulmonary branch stenosis (PBS) develops after closure of a patent ductus arteriosus (PDA) in babies born at less than 32 weeks gestation; to describe the natural history of PBS and the relation between PBS and a cardiac murmur.. Fifty three preterm infants born at a gestational age less than 32 weeks and who had PDA diagnosed on echocardiography were recruited. An echocardiogram was performed on alternate days until the ductus arteriosus closed. If PBS was diagnosed, the baby was followed up until PBS resolved.. In 59%, PBS developed in one or both branches after closure of the PDA. In 21%, both pulmonary branches were affected. In 79%, the left pulmonary artery alone was involved but the right side was never affected alone. PBS had resolved in 74% by the time the infants reached 40 weeks, in 95% at a corrected age of 6 weeks, and in 100% at a corrected age of 3 months. There is a better correlation between a cardiac murmur and PBS than between a murmur and PDA.. PBS in preterm infants is usually not present at birth but develops after closure of a PDA. PBS resolves by a corrected age of 3 months. The presence of a murmur after closure of a PDA is usually related to PBS and not to reopening of the ductus arteriosus.

Topics: Cardiovascular Agents; Disease Progression; Ductus Arteriosus, Patent; Female; Heart Murmurs; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Male; Pulmonary Valve Stenosis; Sensitivity and Specificity; Ultrasonography, Doppler

Cardiac troponin T (cTnT) represents a sensitive and specific marker of ischemic myocardial damage in adult and neonatal populations. The aim of this study was to detect the potential ischemic effect of persistent patent ductus arteriosus (PDA) and indomethacin treatment on the coronary vascular bed by measuring cTnT concentrations. cTnT levels were measured in 23 preterm infants (<32 weeks of gestational age) with respiratory distress syndrome (RDS), 11 with PDA and 12 without, at 2, 4, and 7 days after birth. cTnT concentrations (mean +/- SEM) significantly decreased (P<0.05) from the 2nd (0.63+/-0.09 microg/l) and the 4th (0.77+/-0.13 microg/l) to the 7th postnatal day (0.28+/-0.04 microg/l). At day 2 after birth, cTnT levels in preterm infants with RDS were significantly higher (P<0.05) than our reference values for healthy preterm neonates (0.63+/-0.09 microg/l vs. 0.18+/-0.04 microg/l). No differences were found between RDS infants with and without PDA at 2 (0.65+/-0.13 vs. 0.61+/-0.14 microg/l), 4 (0.71+/-0.21 vs. 0.87+/-0.16 microg/l), and 7 (0.26+/-0.05 vs. 0.29+/-0.07 microg/l) days of life. In infants with PDA, cTnT levels did not differ before the first dose of indomethacin was given (0.65+/-0.14 microg/l) or 2 h (0.65+/-0.15 microg/l) and 48 h (0.71+/-0.21 microg/l) afterwards.. In preterm infants with RDS the occurrence of PDA and indomethacin treatment are not associated with ischemic cardiac damage as detected by cTnT measurements.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Myocardial Ischemia; Respiratory Distress Syndrome, Newborn; Troponin T

Topics: Cardiovascular Agents; Drug Administration Schedule; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Recurrence; Time Factors

To determine in preterm infants with a patent ductus arteriosus (PDA) the effect of indomethacin treatment on spontaneous motor activity.. Motor activity was assessed from repeated videotape recordings in 32 preterm infants (

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Male; Movement; Prospective Studies; Reference Values

To evaluate the effects of indomethacin on blood glucose values in premature infants with patent ductus arteriosus (PDA).. Twenty-five very low birthweight infants with PDA were given 0.2 mg/kg, i.v., indomethacin for up to three doses. We examined the relationship between blood glucose values and glucose infusion rate before and after indomethacin therapy.. There was a significant reduction in blood glucose values between 12 and 96 h following i.v. indomethacin therapy. Eleven of 25 infants (44%) had blood glucose values below 40 mg/dL between 12 and 60 h (mean 32.7 h) after the initial dose. Although the glucose infusion rate during the first 12 h was constant (3.56 +/- 0.98 mg/kg per min), the blood glucose values decreased from 96 +/- 32 mg/dL at the starting point to 75 +/- 29 mg/dL at 12 h (P < 0.05). The maximum blood glucose reduction was 51.6 +/- 34.7 mg/dL and the maximum blood glucose reduction rate was 50.4 +/- 20.2%.. The results suggest that blood glucose values should be measured at least every 6 h for 72 h until they stabilize in order to prevent unexpected hypoglycemia.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Female; Humans; Hypoglycemia; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Male; Retrospective Studies; Statistics, Nonparametric

Topics: Arrhythmias, Cardiac; Cardiotonic Agents; Cardiovascular Agents; Ductus Arteriosus, Patent; Humans; Infant, Newborn

Topics: Alprostadil; Cardiovascular Agents; Ductus Arteriosus, Patent; Epoprostenol; Extracorporeal Circulation; Humans; Infant, Newborn; Ischemia; Prostaglandins E