Early Patent Ductus Arteriosus Research Articles

Outcomes and Determinant Factors of Percutaneous Transcatheter Occlusion among Children with Patent Ductus Arteriosus in the East Coast Malaysia: A 10 Year Experience

Introduction: Transcatheter closure was a well-established procedure in patent ductus arteriosus (PDA). The aim of the study was to determine the outcomes, median time and PDAs closure from diagnosis and the predictive factors which influenced the decision for PDA closure. Material and methods: A 10-year retrospective record review was performed involving patients who had undergone transcatheter closure of PDA from January 2007 to January 2017 at a single centre in the North-eastern of Peninsular Malaysia. Descriptive statistics were used to examine all variables. Kaplan-Meier survival analysis was applied to determine median time for diagnosis and transcatheter closure of PDA. Multiple Cox regression analysis was used to identify predictors for early intervention of PDA closure. Results: A total of 123 patients were recruited with 65.9% of them were predominantly female. The age at the time of diagnosis was between 4-day to 14.5-year-old and median age for undergoing the procedure was 2.6-year-old (range:3-month to 15.8-year-old). The PDA size ranged between 0.2-12mm with 59% of the patients had large size PDA. Successful closure rate was achieved in 96.2 % with 3.8 % having very minimal residual shunt at 2 years post procedure. Complications were noted in 17 patients (4.0% major, 9.8% minor). Overall, the median time to diagnose and to close PDA were 6 months and 16.9 months respectively. Earlier intervention was likely to be performed in younger children (p<0.001) with weight of less than 10 kg (p<0.001). Conclusions: Transcatheter device closure was safe and effective in children with PDA with excellent outcome and minimal complication. Age and weight were the determinant factors for early PDA closure.

A simple noninvasive biomarker can reflect both the acute and chronic pulmonary impact of patent ductus arteriosusshunting.

The SFR (SpO2 /FiO2 ratio) offers a continuous, noninvasive reflection of pulmonary function regardless of whether the baby is ventilated or breathing spontaneously. We hypothesized that significant patent ductus arteriosus (PDA) shunting would impair pulmonary oxygen diffusion, reflected by decreased SFR; and that early PDA related decreases in SFR predict subsequent chronic lung disease (CLD). We retrospectively examined records from preterm neonates ≤30 weeks gestational age. Ductal shunting was graded for severity by first week echocardiogram. SFR was calculated as SpO2 /FiO2 and recorded on Day 7 of life and 36 weeks postmenstrual age (PMA). We studied 104 infants: 65 with closed duct,17 with hemodynamically insignificant PDA, and 22 with hemodynamically significant (hsPDAs). CLD developed in 9 (14%) of those with closed ducts; 6 (35%) of those with hisPDA; and in 12 (55%) of those with hsPDA (p = 0.005). SFR values at 1 week postnatally were decreased in those with hsPDA and with hisPDA as compared with those with closed ducts(closed ducts 452 [448-457]vs.hisPDA 396 [294-442]vs.hsPDA 327 [235-369]; p = 0.00001). However, at 36 weeks only SFRs of babies with hsPDA remained significantly lower (467 [461-467]vs.467 [413-471]vs.369 [262-436]for closed vs.hisPDA vs.hsPDA respectively; p = 0.000148). Using ROC curve analysis, Week 1 SFR was strongly associated with hsPDA (area under curve [AUC] = 0.770; p < 0.0001) and highly predictive (AUC = 0.801; p < 0.0001) of CLD at 36 weeks PMA. Early decreases in SFR reflect both the acute and chronic pulmonary impact of PDA shunting, possibly providing the missing link supporting an association between hemodynamically significant PDA and subsequent CLD.

Is early patent ductus arteriosus ligation helpful in premature neonates? A 10-year retrospective study.

To compare short and long outcomes between early (≤ 28days) (EL) and late ligation (LL) groups. To explore factors predicting early extubation (≤ 7days) after patent ductus arteriosus (PDA) ligation. We conducted a single center, retrospective cohort study of preterm infants < 32weeks who underwent surgical ligation over a 10-year period (2009-2019). A total of 133 infants underwent PDA ligation, in the study period. Both groups had similar short-term outcome such as bronchopulmonary dysplasia (BPD) or death (96% vs. 98%, P = 0.64) and long-term clinical outcomes including Bayley's assessment at 2 years corrected age. Fewer infants in the EL group developed severe BPD (63% vs. 81%, P = 0.02). Age at ligation had adjusted odds ratio of 1.04 with over lapping confidence interval (95% CI 1.0-1.1, P = 0.02) for severe BPD/death. There was no difference in day of extubation between the EL and LL group (8days vs. 7days, P = 0.85). Left atrium/aortic root ratio of ≥ 1.75 would give sensitivity of 41% and 80% specificity for early extubation (area under the curve of 0.61). There was marginal reduction of hospital stay in the EL group [113 (105-121) days vs. 115 (107-123) days; log rank P = 0.026]. EL can be delivered safely with a clinically important lower incidence of severe BPD and shorter duration of hospital stay compared to LL.

Early targeted patent ductus arteriosus treatment in premature neonates using a risk based severity score: study protocol for a randomised controlled trial (PDA RCT)

A patent ductus arteriosus (PDA) in preterm infants is associated with increased ventilator dependence and chronic lung disease, necrotizing enterocolitis, intraventricular haemorrhage, and poor neurodevelopmental outcome. Randomised controlled trials of early PDA treatment have not established a drop in the aforementioned morbidities. Those trials did not physiologically categorise PDA severity. Incorporating the specific physiological features of a haemodynamic significant PDA may evolve our understanding of this phenomenon, allowing accurate triaging using echocardiography and targeted treatment. Our group has recently demonstrated that a PDA severity score (PDAsc) derived at 36-48 hours of age can accurately predict the later occurrence of chronic lung disease or death (CLD/Death). Using echocardiography, we assessed PDA characteristics, as well as left ventricular diastolic function and markers of pulmonary overcirculation, and from this formulated a PDAsc. Gestation was also incorporated into the score. We hypothesise that in preterm infants at high risk of developing CLD/Death based on a PDAsc, early treatment with Ibuprofen compared with placebo will result in a reduction in CLD/Death. This is a single centre double-blind two arm randomised controlled trial conducted in the neonatal intensive care unit in the Rotunda Hospital, Dublin. Echocardiogram is carried out in the first 36-48 hours of life to identify preterm infants with a PDAsc ≥ 5.0 and these infants are randomised to Ibuprofen or placebo. Primary outcomes are assessed at 36 weeks post menstrual age. This pilot study’s purpose is to assess the feasibility of performing the trial and to obtain preliminary data to calculate a sample size for a definitive multi-centre trial of early PDA treatment using a PDAsc. We aim to recruit a total of 60 infants with a high risk PDA over three years.Trial Registration: ISRCTN ISRCTN13281214 (26/07/2016) and the European Union Drug Regulating Authorities Clinical Trials Database 2015-004526-33 (03/12/2015).

Ductal ligation timing and neonatal outcomes: a 12-year bicentric comparison

Patent ductus arteriosus (PDA) is common among extremely preterm infants. In selected cases, surgical PDA ligation may be required. The timing for PDA ligation may depend upon a variety of factors, with potential clinical implications. We aimed to investigate the impact of different surgical PDA managements on ligation timing and neonatal outcomes. Inborn infants < 32 weeks of gestation and < 1500 g admitted at two tertiary Neonatal Intensive Care Units that underwent PDA ligation between 2007 and 2018 were enrolled in this retrospective cohort study and split into the following groups based on their surgical management: on-site bedside PDA ligation (ONS) vs. referral to an off-site pediatric cardiac surgery (OFS). Neonatal characteristics, surgical timing, and clinical outcomes of the enrolled infants were compared between the groups. Multivariate analysis was performed to evaluate the impact of PDA ligation timing on significantly different outcomes. Seventy-eight neonates (ONS, n = 39; OFS, n = 39) were included. Infants in the ONS group underwent PDA ligation significantly earlier than those in the OFS group (median age 12 vs. 36 days, p < 0.001) with no increase in postoperative mortality and complications. The multivariate analysis revealed a significant association between PDA ligation timing, late-onset sepsis prevalence (OR 1.045, 0.032), and oxygen need at discharge (OR 1.037, p = 0.025).Conclusions: Compared with off-site surgery, on-site bedside ligation allows an earlier surgical closure of PDA, with no apparent increase in mortality or complications. Earlier PDA ligation may contribute to reduced rates of late-onset sepsis and post-discharge home oxygen therapy, with possible cost-benefit implications.What is known:• Ineffective or contraindicated pharmacological closure of a hemodynamically significant PDA may require a surgical ligation.• Available literature comparing the effect of early vs. late PDA ligation on the main neonatal morbidities has yield contrasting results.What is new:• The availability of a cardiac surgery service performing bedside PDA ligation allows an earlier intervention compared to patient referral to an off-site center, with no difference in postoperative mortality and complications compared to off-site surgery.• Earlier PDA ligation was associated with a lower prevalence of late-onset sepsis and of oxygen need at discharge, with possible cost-benefit implications.

Patent ductus arteriosus shunt elimination results in a reduction in adverse outcomes: a post hoc analysis of the PDA RCT cohort.

A post hoc appraisal of the PDA RCT to assess the relationship between early patent ductus arteriosus (PDA) shunt elimination and chronic lung disease or death (CLD/Death). Infants <29 weeks were divided into four groups: intervention arm in whom PDA closure was achieved (n = 17); intervention arm in whom PDA closure was not achieved (n = 13); placebo arm (n = 30); low risk infants (n = 13). The main outcome measure was CLD/Death. The rates of CLD/Death were lower in the Intervention Success Group (29%) when compared to the Intervention Failure Group (85%) or the Placebo Group (60%, all p < 0.05). There was no difference in CLD/Death between the Intervention Success and Low Risk Groups (8%, p > 0.05). A persistent PDA beyond Day 8 was associated with CLD/Death (aOR 6.5 [1.7-25.5]). Early shunt elimination in preterm infants with a PDA may reduce respiratory morbidity when compared to infants with prolonged shunt exposure.

Predictive Model of Early Spontaneous Ductus Arteriosus Closure Based on Neonatologist Performed Echocardiography in Preterm Infants.

Background: Patent ductus arteriosus (PDA) treatment remains controversial. Modeling on the predictive capacity of early spontaneous PDA closure would help in decision-making.Aim: To design a predictive model of early spontaneous PDA closure.Methods: As part of a trial to assess efficacy and safety of two ibuprofen treatment schemes for PDA, infants below 29 weeks' gestation were scanned between 18 and 72 h of birth, and serially if indicated. PDA treatment was decided based on echocardiography signs of lung overflow or systemic hypoperfusion and clinical criteria. A PDA score that included the echocardiographic parameters significantly associated with treatment prescription was retrospectively applied. Perinatal variables and screening score were included in a backwards elimination model to predict early spontaneous closure.Results: Among 87 eligible infants (27 weeks' gestation; age at screening 45 h), 21 received ibuprofen at 69 h of life [screening score = 7 (IQR = 5–8.5); score at treatment = 9 (IQR = 8–9)], while 42 infants had conservative management, [screening score = 1 (IQR = 0–4)]. Twenty four infants were excluded (ibuprofen contraindication, declined consent or incomplete echocardiography). Screening score showed an AUC = 0.93 to predict early spontaneous PDA closure, [cut-off value = 4.5 (sensitivity = 0.90, specificity = 0.86)]. The predictive model for early spontaneous PDA closure followed the equation: Log (p/1-p) = −28.41 + 1.23* gestational age −0.87* PDA screening score.Conclusions: A predictive model of early spontaneous PDA closure that includes gestational age and the screening PDA score is proposed to help clinicians in the decision- making for PDA treatment. In addition, this model could be used in future intervention trials aimed to prevent PDA related morbidities to improve the eligibility criteria.

Predictive Value of Blood N-Terminal Pro-Brain Natriuretic Peptide Concentrations for Early Patent Ductus Closure in Very Preterm Infants.

ObjectivesIt has been shown that blood concentrations of NT-proBNP may be useful in identifying preterm infants at risk of hemodynamically significant patent ductus arteriosus and its complications. The aim of the study was to assess predictive value of serum NT-proBNP levels for early ductus arteriosus (DA) closure in very preterm newborns.MethodsFifty-two infants <32 weeks’ gestation aged <72 hours with patent ductus arteriosus (PDA) diameter >1.5 mm were involved in a randomized study. Twenty-seven (52%) of them were treated with ibuprofen or paracetamol starting within the first 3 days of life. Expectant management was applied to 25 (48%) infants. All patients underwent planned echocardiographic (daily) and two serum NT-proBNP measurements within the first 10 days after birth. Depending on the DA closure within the first 10 days of life, 2 groups of patients were formed retrospectively, with closed (n = 30) or patent (n = 22) DA by this age.ResultsIn the first 10 days of life, DA closure occurred in 19 (70%) treated infants and in 11 (44%) infants managed expectantly (p > 0,05). Initial concentrations of NT-proBNP were significantly higher in infants that had patent ductus arteriosus (PDA) at 10 days of life. By the eighth day, median NT-proBNP values in both groups significantly decreased but remained considerably higher in newborns with PDA. NT-proBNP serum concentrations on the second day of life could reliably predict DA closure within the first 10 days after birth in treated babies (the AUC was significant 0.81 [95% CI: 0.58–1.03], p < 0.05) but not in infants who were managed expectantly.ConclusionsSerum NT-proBNP concentrations on the second day of life could reliably predict early PDA closure in treated but not in expectantly managed very preterm infants.

Early targeted patent ductus arteriosus treatment in premature neonates using a risk based severity score: study protocol for a randomised controlled trial (PDA RCT).

A patent ductus arteriosus (PDA) in preterm infants is associated with increased ventilator dependence and chronic lung disease, necrotizing enterocolitis, intraventricular haemorrhage, and poor neurodevelopmental outcome. Randomised controlled trials of early PDA treatment have not established a drop in the aforementioned morbidities. Those trials did not physiologically categorise PDA severity. Incorporating the specific physiological features of a haemodynamic significant PDA may evolve our understanding of this phenomenon, allowing accurate triaging using echocardiography and targeted treatment. Our group has recently demonstrated that a PDA severity score (PDAsc) derived at 36-48 hours of age can accurately predict the later occurrence of chronic lung disease or death (CLD/Death). Using echocardiography, we assessed PDA characteristics, as well as left ventricular diastolic function and markers of pulmonary overcirculation, and from this formulated a PDAsc. Gestation was also incorporated into the score. We hypothesise that in preterm infants at high risk of developing CLD/Death based on a PDAsc, early treatment with Ibuprofen compared with placebo will result in a reduction in CLD/Death. This is a single centre double-blind two arm randomised controlled trial conducted in the neonatal intensive care unit in the Rotunda Hospital, Dublin. Echocardiogram is carried out in the first 36-48 hours of life to identify preterm infants with a PDAsc ≥ 5.0 and these infants are randomised to Ibuprofen or placebo. Primary outcomes are assessed at 36 weeks post menstrual age. This pilot study's purpose is to assess the feasibility of performing the trial and to obtain preliminary data to calculate a sample size for a definitive multi-centre trial of early PDA treatment using a PDAsc. We aim to recruit a total of 60 infants with a high risk PDA over three years. Trial Registration: ISRCTN ISRCTN13281214 (26/07/2016) and the European Union Drug Regulating Authorities Clinical Trials Database 2015-004526-33 (03/12/2015).

Left ventricular dysfunction postsurgical patent ductus arteriosus ligation in children: predictor factors analysis

ObjectiveTo identify the predictor factors of left ventricular (LV) dysfunction following patent ductus arteriosus (PDA) surgical ligation.BackgroundPDA is viewed as a noticeable amongst the most widely recognized congenital heart defects in children and its closure is responsible for many hemodynamic changes that require intervention and care.MethodsA retrospective study included fifty children with isolated PDA treated by surgical ligation from June 2015 to June 2018. The LV dimensions and systolic function were assessed by two-dimensional echocardiography pre and post PDA ligation. All cases were followed-up on the first-day, 1 month and 6 months post ligation.ResultsThe mean age of cases was 15.78 ± 7.58 months and 72% were females. The mean duct size was 4.08 ± 1.25 mm. There was a marked decrease in LVEDd, LA/Ao, EF and FS in the first-day post ligation contrasted with pre ligation values. Moreover, an amazing decline in LVEDd and LA/Ao ratio was observed 1 month post ligation contrasted with the early post ligation status with asynchronous improvement of FS and EF at one and 6 months postoperatively.ConclusionPDA ligation is associated with a noteworthy LV systolic dysfunction within the first day post ligation; that in a significant number of patients may require anti-failure measures, prolong the hospital stay and necessitate a regular follow up and monitoring of LV function. PDA size, age, preoperative LVEDd and FS can be considered as predictor factors for suspicion of acute decrease in the LV systolic function early post PDA ligation.Trial registrationClinTrial.Gov NCT04018079.

Early prediction of spontaneous Patent Ductus Arteriosus (PDA) closure and PDA-associated outcomes: a prospective cohort investigation

BackgroundPatent ductus arteriosus (PDA), the most commonly diagnosed cardiovascular condition in preterm infants, is associated with increased mortality and harmful long-term outcomes (chronic lung disease, neurodevelopmental delay). Although pharmacologic and/or interventional treatments to close PDA likely benefit some infants, widespread routine treatment of all preterm infants with PDA may not improve outcomes. Most PDAs close spontaneously by 44-weeks postmenstrual age; treatment is increasingly controversial, varying markedly between institutions and providers. Because treatment detriments may outweigh benefits, especially in infants destined for early, spontaneous PDA closure, the relevant unanswered clinical question is not whether to treat all preterm infants with PDA, but whom to treat (and when). Clinicians cannot currently predict in the first month which infants are at highest risk for persistent PDA, nor which combination of clinical risk factors, echocardiographic measurements, and biomarkers best predict PDA-associated harm.MethodsProspective cohort of untreated infants with PDA (n=450) will be used to predict spontaneous ductal closure timing. Clinical measures, serum (brain natriuretic peptide, N-terminal pro-brain natriuretic peptide) and urine (neutrophil gelatinase-associated lipocalin, heart-type fatty acid-binding protein) biomarkers, and echocardiographic variables collected during each of first 4 postnatal weeks will be analyzed to identify those associated with long-term impairment. Myocardial deformation imaging and tissue Doppler imaging, innovative echocardiographic techniques, will facilitate quantitative evaluation of myocardial performance. Aim1 will estimate probability of spontaneous PDA closure and predict timing of ductal closure using echocardiographic, biomarker, and clinical predictors. Aim2 will specify which echocardiographic predictors and biomarkers are associated with mortality and respiratory illness severity at 36-weeks postmenstrual age. Aim3 will identify which echocardiographic predictors and biomarkers are associated with 22 to 26-month neurodevelopmental delay. Models will be validated in a separate cohort of infants (n=225) enrolled subsequent to primary study cohort.DiscussionThe current study will make significant contributions to scientific knowledge and effective PDA management. Study results will reduce unnecessary and harmful overtreatment of infants with a high probability of early spontaneous PDA closure and facilitate development of outcomes-focused trials to examine effectiveness of PDA closure in “high-risk” infants most likely to receive benefit.Trial registrationClinicalTrials.gov NCT03782610. Registered 20 December 2018.

Does Early PDA Screening Benefit Extremely Premature Babies

The optimal management of patent ductus arteriosus (PDA) is still under debate, because the benefit of treatment on survival or long-term outcomes is

Antioxidants and Biomarkers of Oxidative Stress in Preterm Infants with Symptomatic Patent Ductus Arteriosus.

Immature antioxidant and oxygen-sensing mechanisms are involved in the pathogenesis of the patent ductus arteriosus (PDA). We conducted a prospective, observational, pilot study to test the hypothesis that antioxidant activity is low at birth in preterm infants at risk for symptomatic PDA. Blood and urine samples were collected within 24 to 48 hours of life in 53 preterm infants (≤32 weeks' gestation) who developed early PDA symptoms and in 30 term (≥37 weeks' gestation) control infants. Thirty preterm infants developed hemodynamically significant PDA (hsPDA) and required pharmacologic treatment and/or PDA ligation. For these infants, blood and urine samples were also collected at 24 hours posttreatment. Samples were analyzed for biomarkers of antioxidant activity, oxidative stress, and lipid peroxidation. At 24 to 48 hours after birth, plasma superoxide dismutase (SOD), urinary catalase, and plasma and urinary 8-isoPGF2α were significantly lower in preterm infants who developed hsPDA. Plasma 8-isoPGF2α levels rebounded post-PDA treatment, while urinary prostaglandin E2, plasma and urinary thromboxane B2, and plasma SOD declined. The antioxidant status is low in preterm infants at risk for developing hsPDA. SOD may be a key antioxidant regulating functional ductus arteriosus closure. Therefore, low levels may result in persistence of a hsPDA.

The effect of histological chorioamnionitis on the short-term outcome of preterm infants ≤32 weeks: a single-center study

Background and objectives: Chorioamnionitis (CA) is an acute inflammation of the membranes and chorion of the placenta. The aim of this study was to determine the effect of histological CA on the short-term outcome of preterm infants.Subjects and methods: The clinical characteristics and outcomes of the preterm infant including respiratory distress syndrome, duration of mechanical ventilation, patent ductus arteriosus (PDA) requiring medical treatment or ligation, necrotizing enterocolitis, bronchopulmonary dysplasia, death and intraventricular hemorrhage (IVH; grade III–IV) were analyzed.Results: Two hundred and eighty-one infants born at ≤32 weeks gestational ages were included. Infants were divided into two groups: one with histological CA (n = 145) and without histological CA (n = 136). Mean gestational age was 28.8 ± 2.6 weeks and 29.1 ± 2.5 weeks, and mean birth weight was 1138 ± 350 g and 1210 ± 299 g, respectively. There were no differences in gestational age and birth weight among the groups. Compared with the group, histological CA was associated with early onset sepsis (p = 0.007), PDA (p = 0.003), IVH (p = 0.03), and death (p = 0.04).Conclusion: Maternal histological CA is an important risk factor for preterm deliveries and associated with serious morbidities such as early onset sepsis, IVH, PDA and increased mortality.

Preoperative left ventricular internal dimension in end-diastole as earlier identification of early patent ductus arteriosus operation and postoperative intensive care in very low birth weight infants

Patent ductus arteriosus (PDA) is common in premature infants. In very low birth weight infants (VLBWI), PDA requires surgical therapy in many cases. It is unclear to know at-risk infants showing cardio-dysfunction after PDA surgery. The purpose of this study was to identify at-risk infants showing cardio-dysfunction after surgery for patent ductus arteriosus (PDA). We examined the relationship between left ventricular (LV) performance before and after PDA ligation in a retrospective observational cohort study. We studied 64 preterm neonates with symptomatic PDA before and after surgical ligation. Echocardiographic examinations were performed pre- and postoperatively. M-mode measurements included left ventricular internal dimension in end-diastole (LVIDd) and LV fractional shortening (FS). All cases showed decreased LVFS after PDA closure. Most cases (49/64, 77%) showed postoperative FS decreased to below normal (<28%). Preoperative relative LVIDd was significantly larger in abnormal FS infants (137±18%) than in normal FS infants (118±11%; p<0.01). A cut-off value of preoperative relative LVIDd (absolute LVIDd/normal value) for predicting postoperative cardio-dysfunction was 127.4% (sensitivity, 0.735; specificity, 0.933; area under curve, 0.817). Determination of preoperative LVIDd might facilitate earlier identification of infants needing early PDA surgery and postoperative intensive care.

Early colour Doppler duct diameter and symptomatic patent ductus arteriosus in a cyclo‐oxygenase inhibitor naïve population

To examine the relationship between early duct diameter and patent ductus arteriosus (PDA) symptoms. A retrospective study of infants <29weeks of gestation with early colour Doppler assessment of PDA diameter, in whom PDA was managed conservatively, without cyclo-oxygenase inhibitor (COI) treatment. Gestation and birthweight, [median (range)], were 26 (23-28) weeks and 865 (500-1440) g, respectively. Symptomatic PDA developed in 20 (68.9%) infants, with 11 (37.9%) referred for PDA ligation at 24 (17-30) days. Symptoms resolved spontaneously in 7 infants (24.1%) at 19 (7-32) days. There were 6 (20.7%) deaths, including four early neonatal deaths with large PDA. Early colour Doppler PDA diameter >1.5mm (n=20) predicted development of symptomatic PDA (sensitivity 91%, specificity 100%), but symptoms resolved spontaneously without treatment in 30%. There was a significant linear correlation (p<0.001) with increasing early PDA diameter and the development of more persistent PDA symptoms, early neonatal mortality and morbidity. In our (COI)-naïve population, the mortality and morbidity associated with prolonged exposure to unrestricted ducts are high. Not all infants with early PDA diameter >1.5mm have persistent symptomatic PDA, but early PDA diameter could be utilized to identify those infants at greatest risk of adverse outcome associated with PDA.

Timing of surgical closure of patent ductus arteriosus in preterm neonates?

A retrospective cohort study was conducted on 115 preterm neonates who underwent patent ductus arteriosus ligation after failure of medical treatment, at Chiang Mai University Hospital between January 2003 and December 2010. Two groups were defined: an early surgery group (39.1%) treated with surgical closure within 21 days, and a late surgery group (60.9%) operated on >21 days after birth. There were significant differences between the 2 groups in terms of weight at surgery, birth weight, duration of intubation, ductal size, and preoperative indomethacin usage. The early surgery group had a longer intensive care unit stay, but differences in postoperative chronic lung disease, ductal size, and surfactant use were not significant. Babies with a low birth weight (<1,500 g) and those with a higher ductal gradient were more susceptible to chronic lung disease, but multivariate analysis showed no difference between early and late surgery patients in either early extubation or chronic lung disease. It was concluded that early patent ductus arteriosus ligation did not show more benefits than late surgery.

Timing of Patent Ductus Arteriosus Treatment and Respiratory Outcome in Premature Infants: A Double-Blind Randomized Controlled Trial

To determine whether "early" ibuprofen treatment, at the onset of subtle patent ductus arteriosus (PDA) symptoms, would improve respiratory outcome in premature infants compared with "expectant" management, with ibuprofen treatment only when the PDA becomes hemodynamically significant (HS). We conducted a randomized double-blind controlled trial of infants with gestational ages 23 to 32 weeks and birth weights 500 to 1250 g who had echocardiography for subtle PDA symptoms (metabolic acidosis, murmur, bounding pulses). Infants were then randomized to "early" treatment (blinded ibuprofen; n = 54) or "expectant management" (blinded placebo, n = 51). If the PDA became HS (pulmonary hemorrhage, hypotension, respiratory deterioration), infants received open label ibuprofen. Infants with HS PDA at enrollment were excluded from the study. Respiratory outcomes and mortality and major morbidities were determined. "Early" treatment infants received ibuprofen at median age of 3 days; infants in the "expectant group" in whom HS symptoms developed (20%) received ibuprofen at median of 11 days. A total of 49% of "expectant" infants never required ibuprofen or ligation. No significant differences were found in the primary outcome (days on oxygen [O(2)] during the first 28 days), death, O(2) at 36 weeks, death or O(2) at 36 weeks, intestinal perforation, surgical necrotizing enterocolitis, grades III and IV intracranial hemorrhage, periventricular leukomalacia, sepsis or retinopathy of prematurity. Infants with mild signs of PDA do not benefit from early PDA treatment compared with delayed treatment.

Early Surgical Ligation Versus a Conservative Approach for Management of Patent Ductus Arteriosus That Fails to Close after Indomethacin Treatment

To examine whether a more conservative approach to treating patent ductus arteriosus (PDA) is associated with an increase or decrease in morbidity compared with an approach involving early PDA ligation. In January 2005, we changed our approach to infants born at age<or=27 weeks gestation who failed indomethacin treatment. We changed from an early surgical approach, in which feedings were stopped and all PDAs were ligated (period 1: January 1999 to December 2004; n=216) to a more conservative approach in which feedings continued and PDAs were ligated only if cardiopulmonary compromise developed (period 2: January 2005 to August 2009; n=180). All infants in both periods received prophylactic indomethacin therapy. The 2 periods had similar rates of perinatal/neonatal risk factors and indomethacin failure (24%), as well as ventilator management and feeding advance protocols. The conservative approach (period 2) was associated with decreased rates of duct ligation (72% vs 100%; P<.05). Even though infants subjected to this approach were exposed to larger PDA shunts for longer durations, the rates of bronchopulmonary dysplasia, sepsis, retinopathy of prematurity, neurologic injury, and death were similar to those in period 1. The overall rate of necrotizing enterocolitis was significantly lower in period 2 compared with period 1. These findings support the need for new controlled, randomized trials to reexamine the benefits and risks of different approaches to PDA treatment.

A Randomized, Double-Blind, Placebo-Controlled Trial on Intravenous Ibuprofen L-Lysine for the Early Closure of Nonsymptomatic Patent Ductus Arteriosus within 72 Hours of Birth in Extremely Low-Birth-Weight Infants

A multicenter, double-blind, randomized, placebo-controlled trial was conducted to evaluate the efficacy and safety of intravenous (IV) ibuprofen (L-lysine) for the early closure of nonsymptomatic patent ductus arteriosus (PDA) within 72 hours of birth in extremely low-birth-weight (ELBW) infants with evidence of ductal shunting by echocardiogram. Eleven sites enrolled 136 infants with nonsymptomatic early PDA (gestational age < 30 weeks; body weight 500 to 1000 g) to receive a 3-day course (10 mg/kg, 5 mg/kg, and 5 mg/kg) of IV ibuprofen ( N = 68) or placebo ( N = 68). Cardiac echocardiogram was performed on study days 1 and 14, and with rescue. Infants were followed to 36 weeks postconceptional age. Patient demographics, mean (standard deviation), were similar between ibuprofen and placebo: birth weight: 798.5 g (128.7) versus 797.3 g (132.8); gestational age: 26.1 weeks (1.3) versus 26.2 weeks (1.4); and age at first dose: 1.5 days (0.7). The intent-to-treat analysis of the primary endpoint, subjects rescued, died, or dropped through study day 14, was 21/68 (30.9%) with ibuprofen and 36/68 (52.9%) for placebo ( P = 0.005). Death, intraventricular hemorrhage, necrotizing enterocolitis, daily fluid intake/output, liver function, bronchopulmonary dysplasia, and retinopathy of prematurity did not differ. A trend toward decreased periventricular leukomalacia by ibuprofen was noted. IV ibuprofen was effective and safe in the early closure of PDA in preterm neonates.