cardiovascular-agents and Infant--Premature--Diseases

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

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

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

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

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

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

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

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

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

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

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'

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

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

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

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

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

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

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

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

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