Surgical Ligation Of Patent Ductus Arteriosus Research Articles

G145(P) Indomethacin vs ibuprofen to treat patent ductus arteriosus (pda) in neonates

Aims To compare gastrointestinal pathology, mortality and surgical ligation of PDA in infants treated for PDA with Ibuprofen and Indomethacin. Background PDA affects 60% of infants NSAIDs are effective pharmacological agents used to treat PDA. They inhibit prostaglandin synthesis via non-selective inhibition COX-1 and COX-2. COX-1 inhibition reduces cerebral, mesenteric and renal blood flow and alters platelet function. Ibuprofen has less COX1 inhibition, therefore may have reduced side effect profile. In our unit PDA treatment changed in 2010 from Indomethacin to Ibuprofen because of unavailability of Indomethacin. Methods Demographics and outcomes from babies Results Conclusion There was a significant reduction in early NEC during the Ibuprofen epoch compared to Indomethacin epoch. These results are similar to the reduction of NEC with Ibuprofen compared to Indomethacin (RR 0.68 (95% CI 0.47 to 0.99)) reported in a recent meta-analysis (Cochrane Database Syst Rev. 2013 Apr 30; 4:CD003481). As with all cohort studies there are confounding factors including demographics factors and potential alterations in clinical practice including feeding practices between the two epochs.

PO-0775 Respiratory Morbidities In Very Low Birth Weight Infants In A Tertiary Level Hospital, Saudi Arabia

<h3>Background and aims</h3> The improvement of perinatal care has led to significant reduction in perinatal mortality. In our region, there is limited data about prematurity-related outcomes. Therefore, we designed this study to report the in-hospital respiratory morbidities and interventions in VLBWI. <h3>Methods</h3> This is a retrospective study of all inborns (Prince Sultan Military Medical City (2004–2012), Riyadh-Saudi Arabia) with a birth weight (b.wt) of &lt;1500 g and gestational age (GA) &lt;34 wks, with no major anomaly. In-hospital respiratory morbidities and interventions were reported. Chronic lung disease (CLD) was defined as requirement of O₂ at 36 wks post-conception. <h3>Results</h3> 1262 were included (GA: 28 ± 3 wks, b.wt: 1016 ± 298 g, median length of stay (IQR) was 48d (30–74), survival: 83% and exposure to any antenatal steroid: 79%). Respiratory distress syndrome (RDS), CLD and pneumothorax were diagnosed in 87, 16.3 and 5.9%, respectively. Surfactant, indomethacin and post-natal dexamethasone were used in 67, 23 and 7%, respectively. Surgical ligation of PDA was required in 3% and iNO was used in 9%. The median days on mechanical ventilation, CPAP and O₂ were 2 (0–14),5 (1–21) and 6 (1–36). Males were more likely to have worse RDS, pulmonary haemorrhage and also required longer days on O₂ and received more surfactant (all p &lt; 0.05). <h3>Conclusions</h3> The findings of this study suggest that our population is comparable to that reported in the literature and males are at higher risk. These data would set a baseline for further clinical trials and quality improvement projects in our region.

Sensorineural hearing loss in very low birth weight infants with histological chorioamnionitis

Objective: Histological chorioamnionitis (HCAM) has been associated with inflammatory diseases of preterm infants. Recently we have observed that it increased the risk of speech delay and hearing loss. So the aim of this study was to evaluate the relationship between sensorineural hearing loss (SNHL) of VLBW infants and HCAM.Methods: We performed an observational study on VLBW infants admitted to the NICU of Padua. Each patient with HCAM was matched with one control without HCAM. All infants underwent hearing screening before discharge by means of automated transient–evoked otoacustic emissions and automated auditory brainstem responses, which were repeated at 3 and 6 months of age with tympanometry measurement. Incidence of SNHL at 6 months of age was compared in the 2 groups and risk factors for hearing loss were studied.Results: Two of 77 (2.6%) newborns with HCAM e 6/73 (8.2%) without it presented SNHL at 6 months of corrected age (p = 0.16). Multivariable logistic regression analysis identified surgical ligation of patent ductus arteriosus (PDA) as independent predictors of SNHL (OR: 5.75, 95% CI 1.34–24.84, p = 0.02), whereas the effect of HCAM on SNHL was only near to statistical significance level.Conclusions: Surgical ligation of PDA is associated with an increased risk of SNHL in VLBW infants, regardless of HCAM.

PDA Ligation and Health Outcomes: A Meta-analysis

Patent ductus arteriosus (PDA) ligation has been variably associated with neonatal morbidities and neurodevelopmental impairment (NDI). The objective was to systematically review and meta-analyze the impact of PDA ligation in preterm infants at <32 weeks' gestation on the risk of mortality, severe neonatal morbidities, and NDI in early childhood. Medline, Embase, Cochrane Central Register of Controlled Trials, Education Resources Information Centre (ERIC), Cumulative Index to Nursing and Allied Health (CINAHL), PsycINFO, and the Dissertation database were searched (1947 through August 2013). Risk of bias was assessed by using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool. Meta-analyses were performed by using a random-effects model. Unadjusted and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were pooled when appropriate. Thirty-nine cohort studies and 1 randomized controlled trial were included. Nearly all cohort studies had at least moderate risk of bias mainly due to failure to adjust for survival bias and important postnatal preligation confounders such as ventilator dependence, intraventricular hemorrhage, and sepsis. Compared with medical treatment, surgical ligation was associated with increases in NDI (aOR: 1.54; 95% CI: 1.01-2.33), chronic lung disease (aOR: 2.51; 95% CI: 1.98-3.18), and severe retinopathy of prematurity (aOR: 2.23; 95% CI: 1.62-3.08) but with a reduction in mortality (aOR: 0.54; 95% CI: 0.38-0.77). There was no difference in the composite outcome of death or NDI in early childhood (aOR: 0.95; 95% CI: 0.58-1.57). Surgical ligation of PDA is associated with reduced mortality, but surviving infants are at increased risk of NDI. However, there is a lack of studies addressing survival bias and confounding by indication.

The timing of surgical ligation for patent ductus arteriosus is associated with neonatal morbidity in extremely preterm infants born at 23-25 weeks of gestation.

The purpose of this study was to evaluate prognostic factors associated with surgical ligation for patent ductus arteriosus (PDA) in extremely preterm infants born at the limits of viability. Ninety infants who were born at 23-25 weeks of gestation and who received surgical ligation were included and their cases were retrospectively reviewed. Infants were classified into two different groups: survivors with no major morbidity (N), and non-survivors or survivors with any major morbidity (M). Clinical characteristics were compared between the groups. Possible prognostic factors were derived from this comparison and further tested by logistic regression analysis. The mean gestational age and the mean birth weight of M were significantly lower than those of N. Notably, the mean postnatal age at time of ligation in N was significantly later than that of the other group (17 ± 12 vs 11 ± 8 days in N and M, respectively). An adjusted analysis showed that delayed ligation (>2 weeks) was uniquely associated with a significantly decreased risk for mortality or composite morbidity after surgical ligation (OR, 0.105; 95% CI, 0.012-0.928). In conclusion, delayed surgical ligation for PDA (>2 weeks) is associated with decreased mortality or morbidities in extremely preterm infants born at 23-25 weeks of gestation.

The Aristotle Score Predicts Mortality After Surgery of Patent Ductus Arteriosus in Preterm Infants

Outcomes after surgical ligation of patent ductus arteriosus (PDA) in preterm infants are often complicated by prematurity associated comorbidities. The Aristotle comprehensive complexity score (ACCS) has been proposed as a useful tool for complexity adjustment in the analysis of outcome after congenital heart surgery. The aims of this study were to define preoperative risk factors for mortality and to demonstrate the usefulness of ACCS to predict mortality after surgical ligation of PDA in the preterm. Included were 49 preterm babies (≤35 weeks of gestation) who had surgical ligation of PDA between May 2009 and July 2012. Median gestational age was 27.6 weeks (range, 23 to 35 weeks) and median birth weight was 1,040 g (range, 520 to 2,280 g). Median age at operation was 15 days (range, 4 to 44 days) and median weight was 1,120 g (range, 400 to 2,880 g). Initial oral ibuprofen was ineffective in 24 patients and contraindicated in 25. All surgical ligations were done at bedside in the neonatal intensive care unit. Preoperative clinical and laboratory profiles were reviewed and ACCS was derived. Eight of 49 patients (16.3%) died at a median of 14 days (range, 2 to 73 days) after PDA ligation. Patients who had contraindications for oral ibuprofen (odds ratio [OR] 8.94; p=0.049), coagulopathy (OR 12.13; p=0.025), renal dysfunction (OR 28.88; p=0.003), intraventricular hemorrhage greater than grade II or seizure (OR 34.00; p=0.002), and ACCS points (OR 29.594; p<0.05) were significantly associated with an increased risk for mortality. Among the risk factors, ACCS showed the largest area under curve (0.991) by receiver-operating characteristic curve analysis. Optimal cutoff value of ACCS for mortality were 15 or greater, with sensitivity of 87.5%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 97.6%. The ACCS, especially for procedure-independent complexity factors, is a useful tool to predict mortality after ligation of PDA in preterm infants.

Amplitude Electroencephalogram Characterization in Preterm Infants Undergoing Patent Ductus Arteriosus Ligation

Recent studies suggest an increased risk of neurodevelopmental impairment following patent ductus arteriosus surgical ligation. The mechanisms are unclear, but intraoperative stress or pain may contribute. The objectives of this study were to determine if pain, evidenced by an increase in heart rate and blood pressure, during patent ductus arteriosus ligation would be accompanied by an increase in amplitude-integrated electroencephalogram (aEEG) voltage. This was an observational, pilot study of infants born at 22.6-35.1 weeks with patent ductus arteriosus requiring surgical ligation. The aEEG was recorded prior to, during surgery, and for 2 hours following surgery. Mean heart rate, blood pressure, and aEEG voltage were analyzed for each recording period. Seventeen preterm infants were studied at a mean postmenstrual age of 26.6 weeks. Following anesthetic induction, aEEG became suppressed and remained suppressed during the postoperative period. Heart rate and blood pressure increased significantly intraoperatively. The aEEG voltage did not increase with an increase in heart rate. Infants received between 3.7-47 μg/kg of fentanyl. There was no correlation between aEEG voltage and vital sign changes. aEEG is not a useful tool as a marker of pain during patent ductus arteriosus ligation, rather a more standardized approach to pain management should be considered.

Surgical versus medical treatment with cyclooxygenase inhibitors for symptomatic patent ductus arteriosus in preterm infants

A patent ductus arteriosus (PDA) with significant left to right shunt increases morbidity and mortality in preterm infants. Early closure of the ductus arteriosus may be achieved pharmacologically or by surgery. The preferred initial treatment of a symptomatic PDA, surgical ligation or treatment with indomethacin, is not clear. To compare the effect of surgical ligation of PDA versus medical treatment with cyclooxygenase inhibitors (indomethacin, ibuprofen or mefenamic acid), each used as the initial treatment, on neonatal mortality in preterm infants with a symptomatic PDA. For this update we searched The Cochrane Library 2012, Issue 2, MEDLINE, EMBASE, CINAHL, Clinicaltrials.gov, Controlled-trials.com, Proceedings of the Annual Meetings of the Pediatric Academic Societies (2000 to 2011) (Abstracts2View(TM)) and Web of Science on 8 February 2012. Randomised or quasi-randomised trials in preterm or low birth weight neonates with symptomatic PDA and comparing surgical ligation with medical treatment with cyclooxygenase inhibitors, each used as the initial treatment for closure of PDA. The authors independently assessed methodological quality and extracted data for the included trial. We used RevMan 5.1 for analyses of the data. One study reporting on 154 neonates was found eligible. No significant difference between surgical closure and indomethacin treatment was found for in-hospital mortality, chronic lung disease, necrotising enterocolitis, sepsis, creatinine level or intraventricular haemorrhage. There was a significant increase in the surgical group in the incidence of pneumothorax (risk ratio (RR) 2.68; 95% confidence interval (CI) 1.45 to 4.93; risk difference (RD) 0.25; 95% CI 0.11 to 0.38; number needed to treat to harm (NNTH) 4 (95% CI 3 to 9)) and retinopathy of prematurity stage III and IV (RR 3.80; 95% CI 1.12 to 12.93; RD 0.11; 95% CI 0.02 to 0.20; NNTH 9 (95% CI 5 to 50)) compared to the indomethacin group. There was a statistically significant decrease in failure of ductal closure rate in the surgical group as compared to the indomethacin group (RR 0.04; 95% CI 0.01 to 0.27; RD -0.32; 95% CI -0.43 to -0.21, number needed to treat to benefit (NNTB) 3 (95% CI 2 to 4)). No new trials were identified for inclusion in the 2012 update. There are insufficient data to conclude whether surgical ligation or medical treatment with indomethacin is preferred as the initial treatment for symptomatic PDA in preterm infants.

Ligation of the Patent Ductus Arteriosus in Preterm Infants: Understanding the Physiology

T he diagnosis and management of preterm neonates with a patent ductus arteriosus (PDA) that fails to close after medical management poses a major challenge. The association of prolonged ductal patency withmorbidities including feeding intolerance, necrotizing enterocolitis (NEC), severe intraventricular hemorrhage (IVH), metabolic acidosis, renal failure, increased ventilator dependence, bronchopulmonary dysplasia (BPD), and pulmonary hemorrhage are well recognized. In addition, a PDA failing medical treatment is associated with a 4to 7-fold increase in mortality. This association remains significant after adjustment for gestation, birth weight, disease severity, and other comorbidities, including IVH, NEC, and sepsis. The decision to perform surgical PDA ligation has been challenged recently, owing to its possible association with adverse neurologic outcomes. Themagnitude of postoperative instability in some patients often dissuades neonatologists from choosing surgery. Neonatologists face uncertainty regarding the optimal approach to this patient population. In this article, we outline the concerns surrounding PDA ligation, review the selection process for intervention, and discuss the perioperative physiological changes that may explain the link between ligation and adverse neurodevelopmental outcomes. In addition, we propose a postoperative management strategy aimed at minimizing hemodynamic compromise after PDA ligation.

Response to Dr Egan’s letter

Thank you for the opportunity to respond to the letter from Dr Edmund A Egan, Chief Medical Officer of ONY, Inc., manufacturer of Infasurf (Calfactant, (CA)). In the letter by Dr Egan, he refers to the studies presented as abstracts in 2007 (ref. 1,2 in his letter) and our study published electronically as a peer reviewed manuscript in 2011 and included in this print issue. These are different studies, in which different protocols, different timeframes (abstract 2007: Jan 2003 to June 2006; full publication 2011:Jan 2005 to Dec 2009) different infants, different number of patients and different statistical models were used. Dr Egan discusses the increased length of stay (LOS) resulting from improvement in mortality due to surfactant therapy in studies comparing surfactant vs placebo. Based on evidence, the introduction of surfactant therapy has led to significantly decreased mortality and morbidity without increasing resource utilization. The statements of Dr Egan regarding inverse correlation between mortality and LOS are based on a very old study (ref. 3 in his letter) comparing surfactant with placebo in a different ‘era’ of neonatology, where respiratory distress syndrome (RDS) was the major cause of death and had a major influence on LOS. Most important is the fact that surfactant therapy compared with placebo has shown decrease in cost both in infants who survived as well as in infants who died. Subsequent studies on resource utilization are clearly different and these have reported LOS in patients who received one of the three animal-derived surfactants.1, 2 Baroutis et al.3 reported decreased mortality and significantly shorter LOS with poractant alfa (PA), when compared to alveofact or beractant (BE) in a randomized, controlled trial. Fujii et al.4 reported a nonsignificant decrease in mortality (8 vs 19%) and shorter LOS in a PA-treated group compared with that in the BE-treated group (87 vs 97 days, P=0.179). In two randomized, controlled trials comparing PA and BE, incidence of patent ductus arteriosus (PDA), as well as the need for medical or surgical ligation of PDA, were significantly less in patients treated with PA,4, 5 which might therefore contribute to shorter LOS. In a study comparing high vs low dose surfactant therapy, LOS was shorter in the high dose group when compared with low dose group (82 vs 99 days).6 A recently published systematic review and meta-analysis,7 demonstrated a good correlation between higher surfactant efficacy (mortality reduction) and reduced LOS with poractant alfa (PA). Indeed, in the meta-analysis, PA was associated with both a significant reduced risk of death vs BE (P=0.02) and a significantly shorter LOS (weighted mean difference: −26.3 [95% CI: −36.5 to −16.07]; P<0.00001). In the most recent randomized trial comparing PA with BE, LOS was not increased in PA group despite a 50% reduction in mortality rate in the PA-treated group (9.8 vs 20%).8

Effectiveness and Safety of Indomethacin versus Ibuprofen for the Treatment of Patent Ductus Arteriosus in Preterm Infants

To compare the incidence of medical closure of patent ductus arteriosus (PDA) and adverse events (acute renal dysfunction, necrotizing enterocolitis, spontaneous intestinal perforation, and gastrointestinal bleeding) between preterm infants who received indomethacin and ibuprofen for the treatment of PDA. A retrospective comparative effectiveness evaluation study was conducted on preterm infants (≤32 weeks) who received indomethacin or ibuprofen for treatment of symptomatic PDA. Of the 124 eligible infants, 54 received indomethacin and 70 received ibuprofen. The overall incidence of medical PDA closure with indomethacin was 37/54 (68.5%) as compared with 42/70 (60%) in the ibuprofen group (p = 0.32). The proportion of infants with surgical PDA ligation was similar between the two groups (18.5% in both the groups). There was no difference in the incidences of acute renal dysfunction, necrotizing enterocolitis stage ≥ 2, spontaneous intestinal perforation, and gastrointestinal bleeding between indomethacin and ibuprofen groups. Ibuprofen is as effective as indomethacin in the treatment of symptomatic PDA in preterm infants. This study also shows that both agents have similar adverse effects and the choice of one agent over the other should be based on local availability and dosing preference.

Patent Ductus Arteriosus in Preterm Infants: Do We Have the Right Answers?

Patent ductus arteriosus (PDA) is a common clinical condition in preterm infants. Preterm newborns with PDA are at greater risk for several morbidities, including higher rates of bronchopulmonary dysplasia (BPD), decreased perfusion of vital organs, and mortality. Therefore, cyclooxygenase (COX) inhibitors and surgical interventions for ligation of PDA are widely used. However, these interventions were reported to be associated with side effects. In the absence of clear restricted rules for application of these interventions, different strategies are adopted by neonatologists. Three different approaches have been investigated including prophylactic treatment shortly after birth irrespective of the state of PDA, presymptomatic treatment using echocardiography at variable postnatal ages to select infants for treatment prior to the duct becoming clinically significant, and symptomatic treatment once PDA becomes clinically apparent or hemodynamically significant. Future appropriately designed randomized controlled trials (RCTs) to refine selection of patients for medical and surgical treatments should be conducted. Waiting for new evidence, it seems wise to employ available clinical and echocardiographic parameters of a hemodynamically significant (HS) PDA to select patients who are candidates for medical treatment. Surgical ligation of PDA could be used as a back-up tool for those patients who failed medical treatment and continued to have hemodynamic compromise.

Anomalous Left Coronary Artery from the Pulmonary Artery with a Large Patent Ductus Arteriosus: Aversion of a Catastrophe

We present an infant who had an anomalous left coronary artery arising from the pulmonary artery (ALCAPA) and a large patent ductus arteriosus (PDA), who was diagnosed before a potentially catastrophic closure of PDA. In the presence of normal left ventricular function and the absence of coronary artery collaterals, it is difficult to diagnose ALCAPA. A disproportionate degree of left ventricular dilation and severity of mitral valve regurgitation relative to the degree of PDA shunt, and echogenic papillary muscles on an echocardiogram should raise a suspicion of coronary artery anomalies. The infant underwent surgical ligation of PDA with translocation of coronary arteries and had an uneventful recovery.

1129 Surgical Treatment of Patent Ductus Arteriosus in Preterm Infants. Ten-Year Experience with Ligation in the Newborn Intensive Care Unit

Background and Aim of studyFrequently in low-birth-weight infants, ductus arteriosus fails to close spontaneously. This study evaluates the results of surgical ligation of symptomatic PDA in low birth weights preterms.MethodsWe...

Acute Changes in Myocardial Systolic Function in Preterm Infants Undergoing Patent Ductus Arteriosus Ligation: A Tissue Doppler and Myocardial Deformation Study

Ligation of a patent ductus arteriosus (PDA) in preterm infants causes profound hemodynamic changes that can result in low cardiac output syndrome and hypotension. The effect of PDA ligation on left ventricular myocardial function has not been studied using tissue Doppler and myocardial deformation imaging, mainly because of the limited validation of these methods in preterm infants. The primary objective of the present study was to determine the feasibility and reliability (intraobserver and interobserver variability) of tissue Doppler and myocardial deformation imaging for evaluating myocardial function in preterm infants undergoing surgical PDA ligation. Additionally, we sought to study the immediate effect of surgical ligation on the left ventricular tissue Doppler and strain measurements in the first 24 hours after surgery. Echocardiography was performed in 19 preterm infants before, 1 hour after, and 18 hours after PDA ligation born at 24-29 weeks of gestation. The tissue Doppler velocities of the lateral tricuspid and lateral and septal mitral valve annuli were obtained. The global and regional longitudinal peak systolic strain values were determined using two-dimensional speckle tracking echocardiography. The results of the three measurement points were compared using repeated measures analysis of variance. The intra- and interobserver variability was assessed using the intraclass correlation coefficient and Bland-Altman analysis. The median gestational age was 25.0 weeks (interquartile range 24.9-25.9) and the birth weight was 750 g (interquartile range 600-810). For the global longitudinal strain, the intraobserver intraclass correlation coefficient was 0.92 (95% CI, 0.78-0.97, P < .001), and the interobserver intraclass correlation coefficient was 0.93 (95% CI, 0.66-0.98, P < .001). Bland-Altman analysis showed no significant bias between the two observers, with good agreement. The systolic and diastolic tissue Doppler velocities of the mitral valve decreased significantly immediately after ligation and remained significantly lower than the preoperative levels at 18 hours. Also, the global longitudinal strain values significantly decreased 1 hour after the procedure (global longitudinal strain before -19.7% ± -3.8% vs -11.5% ± -3.5%; P= .001) but had significantly improved 18hours after the procedure (-15.1% ± -2.9%, P= .01). The present study has shown the feasibility and reliability of using tissue Doppler and strain imaging in premature infants with a hemodynamically significant PDA. Significant changes in myocardial function were observed immediately after PDA ligation, suggesting important changes in myocardial performance immediately after ductal ligation.

Coronary artery perfusion and myocardial performance after patent ductus arteriosus ligation

To study coronary artery (CA) perfusion and myocardial performance after patent ductus arteriosus (PDA) ligation. The postoperative course in premature infants undergoing surgical ligation of PDA is often complicated by cardiorespiratory instability secondary to impaired left ventricular performance. Serial echocardiography was performed before and after (1, 8, and 24 hours) PDA ligation to assess systolic (left ventricular output [LVO]) and diastolic (isovolumic relaxation time, E and A wave peak velocity) myocardial performance, and CA diastolic flow (CA velocity time integral and flow). The ratio of CA flow to LVO was calculated as a surrogate of coronary flow. A total of 20 infants (gestational age at birth, 26.3 ± 0.7 weeks) requiring PDA ligation at a median of 28.5 days (range, 9-40) after birth and weight of 780 g (range, 570-2840) were studied. A postoperative increase in the CA flow/LVO ratio was demonstrated. An early decrease in E and A wave peak velocity (P < .05) and increase in isovolumic relaxation time (P < .05) were demonstrated at 1 hour, before any clinical deterioration. A low baseline CA velocity time integral was associated with a low E/A ratio (r = 0.63, P = .01) at 1 hour and lower systolic blood pressure at 8 hours (r = 0.5, P = .05). The postoperative need for inotropes (n = 8) was associated with a low baseline CA velocity time integral at 1 hour (r = 0.52, P < .05), low LVO at 1 and 8 hours (P < .05), and increased oxygen requirement at 24 hours (P < .05). PDA ligation is followed by altered CA perfusion. Perioperative evaluation of the CA perfusion can help identify neonates at risk of impaired myocardial performance, systolic hypotension, and the need for inotropes.

Peri-Operative Nutrition for Extremely Preterm Infants Undergoing Surgical Treatment for PDA

Background and Aim: In Sweden, 24% of extremely preterm infants are surgically treated for patent ductus arteriosus (PDA). The aim of this study was to evaluate the peri-operative nutrition. Methods: Population-based cohort1, 2 of 118 extremely preterm infants (gestational age < 27 weeks, birth weight 719±161g[mean±SD], 63(53%) boys, 19 multiplets) treated with surgical ligation of PDA (mean postnatal age 22[range 3-82] days) and surviving to 1 year-of-age. Nutrition was collected from hospital charts (24 infants with incomplete records). Daily intakes of total enteral and parenteral nutrients, including blood products, were entered into a computer based tool for nutrition analysis. Provision of energy, protein, fat and carbohydrate was calculated three days before (day-3), on the day of surgery (day0) and three days after surgery (day+3). Data were compared to minimal requirements according to international recommendations.3 Results: The fluid volume day0 was 166±44 ml/kg/d and was the same as day-3(165±31) and day+3(164±36, mean±SD). Table1 Conclusions: Peri-operative nutrition for extremely preterm infants undergoing surgical treatment for PDA is suboptimal and needs to be improved. The significance of malnutrition for outcome after PDA surgery is still unclear and will be investigated.

Natural History of the Ductus Arteriosus in Extremely Low Gestational Age Neonates with Minimal Intervention

Background: Despite little evidence of benefit and significant potential for harm, patent ductus arteriosus (PDA) treatment is widespread. Trials comparing treatment with observation are absent. The rate of spontaneous closure in extremely low gestational age neonates (ELGANs) is unknown. We aimed to identify the spontaneous duct closure rate and clinical outcomes of a population of ELGANs when PDA treatment is rarely employed.Methods: The outcomes of all infants, inborn or outborn before 28 weeks, and admitted on their day of birth to the NICU of the Simpson Centre for Reproductive Health, Edinburgh, during the 5 years 2006-2010 were ascertained. PDA treatment was recorded. Outcomes of infants with a murmur at discharge were ascertained.Results: 163 ELGANs were admitted. 27 (16.6%) died before discharge. No infant received COX inhibitors. 2 infants had surgical ligation of PDA before discharge. Of 136 infants discharged alive, 31 had a murmur at discharge. 1 of these had PDA treated with COX inhibitors and 1 surgically in other units. 1 infant had surgical closure in infancy after discharge home. 19 murmurs resolved on follow up. 7 infants still have murmurs on follow up. 2 infants have unknown status. Other outcomes were: grade III/IV IVH: 17 (10.4%), NEC= stage 2: 26 (16%), Laser-treated ROP: 30/131 (22.9%), BPD at 36 weeks in survivors 80/129 (62%).Conclusions: In a population of 163 ELGAN infants with 83.4% survival to discharge, spontaneous duct closure occurred eventually in 89.7%. Trials of treatment versus observation are needed to determine whether treatment is advantageous.

Indomethacin prophylaxis revisited: changing practice and supportive evidence

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.

Indomethacin Tocolysis and Neurodevelopmental Outcome

To compare the neurodevelopmental outcomes, at 30-42 months adjusted age, between infants exposed to antenatal indomethacin and those unexposed to antenatal indomethacin. This was a retrospective cohort study. The study cohort consisted of all nonanomalous infants with birth weight ≤ 1250 g and/or gestational age ≤ 28 wks born between 2000 and 2003, who completed neurodevelopmental assessments between 30-42 months adjusted age. The authors compared the neurodevelopmental outcomes of infants exposed and unexposed to antenatal indomethacin. Of the 321 infants, 75 infants (23%) exposed to antenatal indomethacin were lower in gestational age (26.4 vs 27.8 wks). In univariate analysis, infants exposed to antenatal indomethacin had significantly increased incidence of patent ductus arteriosus (PDA) (60% vs. 39%), surgical PDA ligation (40% vs. 18%) and bronchopulmonary dysplasia (81% vs. 60%). There was no significant difference in cerebral palsy, cognitive delay, deafness, blindness and major disability between the two groups. In multivariable logistic regression analysis, antenatal indomethacin exposure was not associated with cerebral palsy (OR, 0.70; 95% CI, 0.22-2.18), cognitive delay (OR, 0.56; 95% CI, 0.28-1.12) or neurodevelopmental disability (OR, 0.50; 95% CI, 0.21-1.19). Neurodevelopmental outcome of preterm infants exposed to antenatal indomethacin is equivalent to those unexposed to antenatal indomethacin, despite being born earlier.