Patent Ductus Arteriosus In Preterm Neonates Research Articles

Non-Invasive Electrical Cardiometry versus Echocardiography for Assessment of Patent Ductus Arteriosus Hemodynamic Response to Medical Treatment in Preterm Neonates

Abstract Background Patent ductus arteriosus (PDA) poses a diagnostic and a therapeutic dilemma for neonatologists. Although echocardiography (Echo) has been the gold standard diagnostic tool for PDA, it requires a trained cardiologist or neonatologist to perform and it is usually not available around the clock. Echo provides also a single rather than continuous assessment of the sick neonates, whose hemodynamic status changes quickly. Electrocardiometry (EC) is a new device for continuous hemodynamic monitoring of neonates. Aim of the Work To evaluate the accuracy and precision of EC in comparison to ECHO in assessment of PDA response to treatment in preterm neonates. Patients and Methods This diagnostic accuracy study was conducted in the neonatal intensive care units (NICUs) of Children’s Hospital of Ain Shams University, Cairo, between (1/5/2021 and 31/3/2022). The study was approved by the ethical committee of Ain Shams University. Preterm neonates<35weeks gestational age admitted during the study period were eligible for enrollment. Neonates with hemodynamically non-significant PDA and those with other congenital anomalies were excluded. A baseline echo and electrical cardiometry were done at the time of enrollment and on day 5. Results Forty neonates were enrolled (27 females, 13 males). Closure rate of oral ibuprofen was 100% (39/39) while paracetamol failed to close the PDA in one patient (closure success 0%). Echo and EC didn’t agree upon the tested parameters (stroke volume (SV), cardiac index (CI), ejection fraction (EF), cardiac output (CO) but agreed in measuring heart rate (HR). In patients with inotropes, Echo detected significant changes in CO (p = 0.044) and CI (p = 0.047) but no changes in SV, EF and HR (p = 0.41, 0.506 & 0.105 respectively). In patients who needed mechanical ventilation, Echo detected significant changes in CI (p = 0.008), CO (0.006) and SV (0.042). No changes were detected in any parameter by EC in patients who needed either inotropes or mechanical ventilation (p > 0.05 in all parameters). Conclusion While EC is safe and an easy to apply device, our results show that electrocardiometry is not as accurate as the echocardiography in predicting the hemodynamic changes that might correspond to the closure of PDA in preterm neonates with hemodynamically significant PDA.

Left Pulmonary Artery Occlusion Following Device Closure of Patent Ductus Arteriosus in Premature Infants

BackgroundDevice closure of a patent ductus arteriosus (PDA) is rapidly evolving, with the Amplatzer Piccolo Occluder (Abbott) receiving US Food and Drug Administration approval and becoming the first device approved for PDA closure in patients ≥700 g. We report on the first known cases of complete left pulmonary artery (LPA) occlusion following Piccolo closure of a PDA in premature infants. MethodsRetrospective chart analysis of PDA closures. ResultsWe have performed over 50 cases of Piccolo device closure of the PDA in preterm neonates in the past 2 years, with these 2 cases representing our only complications (4%). This represents a total complication rate similar to or lower than most centers that have published data for this procedure. ConclusionsAlthough rare, severe LPA obstruction can be seen in premature infants following device closure of the PDA. The Piccolo device is designed to ideally remain entirely intraductal. Although our device selection appeared to provide a device short enough for the given ductal length, we recommend, whenever possible, giving consideration to using the shortest possible device. We also recommend increasing the frequency of echocardiographic surveillance to weekly studies if at any time the imaging demonstrates an increase in the degree of obstruction/turbulence.

Patent Ductus Arteriosus Device Closure with AMPLATZER Duct Occluder-II in a Low Birth Weight Preterm Neonate- First Experience in Pakistan

We report a successful closure of large patent ductus arteriosus (PDA) in a low-birth weight preterm neonate using an ADO IIdevice for the first time in AFIC/NIHD Rawalpindi. A hemodynamically significant PDA in a preterm neonate carries anincreased risk of morbidity, including chronic lung disease, necrotizing enterocolitis and renal impairment. After the failure ofmedical therapy, successful, timely and safe transcatheter closure of PDA using appropriate equipment is a milestone inmanaging PDA in preterm neonates.

Clinical and echocardiographic characteristics associated with evolution of patent ductus arteriosus in preterm neonates: A prospective cohort study

In preterm infants, persistence of ductus arteriosus is an important medical condition. Functional echocardiography for patent ductus arteriosus (PDA) may guide clinical decision-making regarding treatment requirement strategies. Objectives of the study were to assess the trends of clinical and functional echocardiographic parameters with evolution of ductus arteriosus in babies≤1250 gm of birth weight and to evaluate whether there is any association of these parameters with persistence of ductus. In this prospective observational study, recruited babies were assessed serially for clinical events and functional echocardiography. Babies were classified into three groups: without PDA, with PDA but PDA spontaneously closed (within 7 days) and persistent PDA. We included 143 infants (Birth weight 1017±179 g, gestational age 30.8±2.7 weeks). Out of 60 babies with PDA, PDA failed to close spontaneously in first week in 32 (53.4 %) infants. PDA Doppler flow pattern on day 3 was found to be one of the most significant markers for future ductus. The highest frequency of growing pattern (37.5%) and pulsatile pattern (59.4%) was seen in persistence ductus group. PDA diameter and LA/Ao ratio were found strongly correlated with all other variables except E/A ratio. We noticed persistence of ductus in preterm infants had significant clinical and echocardiographic association. PDA doppler flow pattern on day 3 was found to be a significant marker for future behaviour of ductus. Significant correlation was found among individual functional echocardiographic parameters in babies with PDA. This would guide judicious treatment of PDA in preterm neonates.

Oral acetaminophen administration for patent ductus arteriosus (PDA) closure in preterm neonates

Background: Patent Ductus Arteriosus (PDA) is considered one of the most prevalent types of congenital heart disease. The closure of the ductus arteriosus physiologically occurs at the first 48-72 hours after the birth in healthy term infants. Different causes can result in the pathological opening of ductus arteriosus. This study aims to investigate the effect of oral acetaminophen on the closure of PDA in preterm neonates. Methods: The present study is a trial without control. Forty-five preterm neonates with a gestational age of <32 weeks were studied. Acetaminophen was orally administered with a dose of 10mg/kg every 6 hours for three days. Closure of ductus arteriosus was considered as the success of treatment. Data were analyzed using SPSS 15. Data were reported as )frequency-percent) and mean ± SD. To evaluate the normal distribution of data, we used a Kolmogorov-Smirnov test. Statistical significance was defined as P<0.05. Results: The study population consisted of 20 male and 25 female infants with the mean gestational age of 28.95 ± 1.66 weeks. Cesarean-born infants and vaginal-born infants consisted 17.8% and 82.2% of the study population, respectively. The proportion of PDA closure after administration of oralacetaminophen was 82.3%. Conclusion: The current study indicates that oral acetaminophen is highly effective in closing PDA. Considering its trivial side effects, it has the potency to be a convenient option for treating this condition.

Paracetamol for closure of patent ductus arteriosus in preterm babies born before 32-week gestational age: academic unit experience

Background: It remains unclear which treatment approach is most advantageous for closure of patent ductus arteriosus (PDA) in preterm infants. Despite the presence of previous trials and meta-analysis, a correct and univocal strategy for closure of PDA is still under debate. Till now, standard medical treatment for PDA closure has been indomethacin/ibuprofen, percutaneous transcatheter closure, or surgical ligation. Up to date, new strategies have been reported with paracetamol. The aim of this study was to present our experience with intravenous (IV) and oral paracetamol for closing PDA in preterm neonates born before 32-week gestational age (GA). Patients and Methods: We conducted a prospective study in a neonatal intensive care unit (NICU) from a tertiary hospital in Minia University; Egypt. Eighty-seven preterm neonates born before 32-week GA with hemodynamically significant PDA (hsPDA) were enrolled. They received 15 mg/kg/6 h for 5 days IV or oral paracetamol for ductal closure. Our NICU guidelines before the current study state that only hsPDA is treated with oral ibuprofen based on the decision of the neonatologist after discussion with pediatric cardiologist. The study aims to vary the practice to use IV or oral paracetamol instead of ibuprofen to avoid side effects of nonsteroidal drugs in preterm babies. Results: During the study period, 140 babies

Comparison of Oral Paracetamol with Oral Ibuprofen in Closing Patent Ductus Arteriosus in Premature Neonates: A Randomized Controlled Trial

Objectives: Patent ductus arteriosus (PDA) is one of the most common congenital heart diseases. Physiologically, the closure of the ductus arteriosus occurs within 48-72 hours after birth in healthy term neonates. This study aimed to compare oral paracetamol and oral ibuprofen in the closure of PDA in preterm neonates. Materials and Methods: This study is a single-blind randomized clinical trial. A total of 90 preterm neonates with a gestational age of less than 32 weeks were divided into two groups of oral ibuprofen and oral paracetamol. Oral ibuprofen was administered at a dose of 10 mg/kg on the first day and 5 mg/kg on the second and the third days. Oral paracetamol was administered at a dose of 10 mg/kg every 6 hours for 3 consecutive days. The primary outcome measure was the closure of the ductus arteriosus. The secondary outcome measure was the assessment of any type of complications following the administration of oral paracetamol. Results: The DA closure rate was 82.2% in the oral paracetamol group and it was 91.41% in the oral ibuprofen group P<0.65, (odds ratio [OR] = 2.22, 95% CI = 0.62-7.97). We did not see any unwanted complication during treatment with oral paracetamol. Conclusions: The present study showed that oral paracetamol is effective in the closure of PDA. On the other hand, it does not cause any unwanted side effects on the patient.

Diagnosis and Management of Patent Ductus Arteriosus.

Preterm infants are at increased risk for patent ductus arteriosus (PDA). Prolonged exposure to PDA may be deleterious and has been associated with neonatal morbidity and mortality. Although the molecular mechanisms underlying regulation of postnatal ductus arteriosus closure are not fully understood, clinical experience and research trials have informed recent changes in PDA management strategies and refocused treatment strategies on smaller subsets of infants who require intervention. This review examines current diagnostic and management approaches to PDA in preterm neonates.

Is Prophylactic Parenteral Paracetamol Effective to Diminish Incidence of PDA in Preterm Neonates? A Randomized Trial

Background: Patent ductus arteriosus (PDA) is a common cause of morbidity and mortality among preterm infants. This study aimed to assess the efficacy of prophylactic parenteral paracetamol dosage to decrease rate of ductus patency in preterm infants. Methods: The study was a randomized double-masked clinical trial that was conducted at Afzalipour tertiary medical center (Kerman, Iran) between Novembers 2015 and 2016, recruiting 160 neonates with gestational age less than 34 weeks who were equally divided into case and control arms. The neonates of case group received parenteral paracetamol with the loading dose of 20 mg/kg and maintenance dose of 7.5 mg/kg every 6 hours during first three postnatal days and the neonates of control group received nothing. Thereafter, echocardiography was done at the day 4 to detect any ductus patency. Results: Among the included infants and after intervention, 12 (15%) in case group and 57 (71.25%) in control group had PDA. Ductus patency incidence among the neonates of case group was significantly lower than in control group. Means of assisted ventilation requirement, cardiac shortening fraction and mortality rate were not significantly different comparing the two groups. Conclusions: This study showed that the prophylactic dosage of parenteral paracetamol can prevent ductus patency and accounts as a trustworthy alternative to the traditional drugs e.g. Ibuprofen or Indomethacin.

Closure of patent ductus arteriosus with oral acetaminophen in preterm neonates: A randomized trial

Introduction: Patent ductus arteriosus (PDA) is one of the most common cardiac problems in preterm neonates which could lead to morbidities, such as chronic lung disease, intraventricular hemorrhage and retinopathy. The aim of this study was to evaluate the effect of oral acetaminophen on closure of PDA in preterm neonates.
 Methods: Sixty-nine neonates with significant PDA (confirmed through echocardiography) were recruited in this study. Ibuprofen and indomethacin were contraindicated in these neonates These newborns were randomly divided into two groups of cases (n=36) and controls (n=33). The case group was treated with oral acetaminophen at a dose of 15 mg/kg/dose every 6 hours for 72 hours. The control group did not receive any intervention. After 72 hours, both groups were re-evaluated by echocardiography. In case of failed closure of PDA, the second course of treatment would be administration of acetaminophen. The main outcome of this study was to evaluate the rate of closure of PDA and the side effects of the acetaminophen.
 Results: The overall rate of PDA closure in the acetaminophen-receiving group was 94.4%; the ductus arteriosus was closed in 75% of patients with the first course of treatment. Moreover, 19.4% of patients did not respond to the first course of the treatment but their ductus arteriosus was closed with the second course of acetaminophen treatment. Of the patients, 5.6% did not respond to both courses of acetaminophen treatments. For the control group, the closure rate of PDA was 15.1%.
 Conclusion: The results of the study showed that oral acetaminophen is an effective alternative treatment for PDA in preterm neonates.

Efficacy of Paracetamol in Closure of Ductus Arteriosus in Infants under 32 Weeks of Gestation.

Standard medical treatment for patent ductus arteriosus (PDA) closure has been indomethacin/ibuprofen or surgical ligation. Up to date, new strategies have been reported with paracetamol. The aim of this study was to present our experience with intravenous paracetamol for closing PDA in preterm neonates presenting contraindication to ibuprofen or ibuprofen had failed and no candidates for surgical ligation because of huge instability. We conducted a retrospective case series study in a neonatal intensive care unit from a tertiary hospital. 9 preterm infants ≤32 weeks of gestational age with hemodynamically significant PDA (hsPDA) were enrolled. They received 15 mg/kg/6h intravenous paracetamol for ductal closure. Demographic data and transaminase levels before and after treatment were collected. 30 preterm babies were diagnosed of hsPDA. 11/30 received ibuprofen with closure in 81.1%. 9 received intravenous paracetamol mainly due to bleeding disorders or thrombocytopenia. Successful closure on paracetamol was achieved in seven of nine babies (77.7%). There was a significant increase in transaminase levels in two patients. They required no treatment for normalization. Paracetamol is an effective option in closure PDA. It should be a first-line therapeutic option when there are contraindications for ibuprofen treatment. Transaminases must be checked during treatment.

Efficacy of Indomethacin in Pharmacological Closure of PDA in Preterm Neonates: A Prospective Study from Tertiary Care Centre in Rural India

Background: Patent ductusarteriosus (PDA) is a fetal shunt necessary for intrauterine survival of the baby, however its closure at birth occurs as pulmonary vascular resistance drops and lungs get expanded for participating in ventilation. However, PDA remains patent in a large proportion of preterm babies and by day -7, 87% of babies <24 wk gestation have a PDA which hinders in ventilation and causes ductal steal to vital organs. Hence, we aimed to study pharmacological closure of ductus in preterm babies. Aims and Objectives: 1) To study the efficacy of COX inhibitor, Indomethacin in ductal closure in preterm babies <34 wk gestation. 2) To compare the symptomatology of PDA in different groups of preterm babies <34 wk GA. Methods: A Hospital-based prospective study was conducted in tertiary care NICU.A total of 104 consecutive, eligible preterm babies <34 wk with echocardiographically documented PDA. Indomethacin (COX inhibitor) was administered orally in a dose of 0.2 mg/kg 12 h for 3 doses and the babies underwent Echo study in first 48 h, after2 days, 7days, and weekly thereafter till PDA closure. A second cycle of indomethacin was repeated if PDA did not respond to the initial treatment. Results: 75/104 (72%) PDAs closed with indomethacin while 13(12.5%) did not respond, and 16(15.38%) showed a reduction in the calibre of PDA. 26–30 wk group showed a brisk response to ductal closure with indomethacin within 108.1±12.44 h, and a mean no. of cycles of indomethacin of 0.98±5.75. Conclusion: With indomethacin we achieved 72% (75/104) closure rates. The best response to indomethacin was noted in 30–32 wk GA group, while maximum nonresponders were in 32–34 wk; suggesting as gestation increases, response to PG inhibitors decreases. KEYWORDS: Patent ductusarteriosus, Cyclo-oxygenase, Indomethacin, Preterm Neonates, PG inhibitors, Ductus arteriosus, Ductal flow.

Comparison of Oral Acetaminophen Versus Ibuprofen in Premature Infants With Patent Ductus Arteriosus.

BackgroundPatent ductus arteriosus (PDA) is a common cause of morbidity. The aim of this study was to compare the efficacy of oral Acetaminophen and oral Ibuprofen for the closure of patent ductus arteriosus (PDA) in preterm infants.ObjectivesThis study demonstrated that, there was no significant difference between treatment of PDA with either oral Acetaminophen or oral Ibuprofen in preterm neonates.Patients and MethodsThis clinical trial, randomized study, enrolled 120 infants, with a gestational age of < 37 weeks, who were admitted in neonatal intensive care unit of Afzalipour hospital, Kerman, Iran, in 2014. PDA was confirmed echocardiographically. The trial was registered in Iranian registry of clinical trials (Reg. No. 25542). Sixty-seven infants received oral Acetaminophen (15mg/kg every six hours for three days) and 62 infants received Ibuprofen (an initial dose of 20 mg/kg, followed by 10 mg/kg at 24 and 48 hours). To evaluate the efficacy of the treatment, a second echocardiography was done after completing the treatment.ResultsAfter the first course of the treatment, PDA closed in 55 (82.1 %) patients who received oral Acetaminophen vs. 47 (75.8 %) of those given oral Ibuprofen (P = 0.38). After the second course of treatment, PDA closed in 50 % of oral Acetaminophen group and 73.3% of oral Ibuprofen group (P = 0.21).ConclusionsThis study demonstrated that, there was no significant difference between treatment of PDA with either oral Acetaminophen or oral Ibuprofen in preterm neonates. Oral Ibuprofen can effectively close PDA but is unfortunately associated with some adverse effects limiting its utility thus we studied an alternative drug with similar efficacy and less adverse effects. This study has recommends Acetaminophen with minimal complications for the treatment of PDA in preterm neonates instead of Ibuprofen.

Enteral paracetamol or Intravenous Indomethacin for Closure of Patent Ductus Arteriosus in Preterm Neonates: A Randomized Controlled Trial.

To compare the efficacy of enteral paracetamol and intravenous indomethacin for closure of patent ductus arteriosus (PDA) in preterm neonates. Randomized controlled trial. Level III neonatal intensive care unit. 77 preterm neonates with birth weight ?1500 g and PDA size ?1.5 mm, with left to right ductal flow with left atrium to aortic root ratio >1.5:1; diagnosed by 2D-Echo within first 48 hours of life. Paracetamol drops through the infant feeding tube (15 mg/kg/dose 6 hourly for 7 days) or intravenous indomethacin (0.2 mg/kg/dose once daily for 3 days). Primary: PDA closure rate assessed by echocardiography. Secondary: need for surgical closure of PDA, renal impairment, gastrointestinal bleed, necrotising enterocolitis, hepatotoxicity, pulmonary hemorrhage, sepsis, hypothermia, retinopathy of prematurity, intraventricular hemorrhage, bronchopulmonary dysplasia and mortality. PDA closure rate was 100% (36/36) in enteral paracetamol group as compared to 94.6% (35/37) in intravenous indomethacin group (P=0.13). The secondary outcomes were also similar between the two groups. There was no occurrence of hepatotoxicity. Enteral paracetamol is safe but not superior to intravenous indomethacin in the treatment of PDA in preterm neonates.

Comparison of Oral Ibuprofen with Oral Indomethacin for PDA Closure in Indian Preterm Neonates: A Randomized Controlled Trial

Oral ibuprofen is being used as an alternative to indomethacin in medical management of patent ductus arteriosus (PDA), but limited data exist on oral efficacy of these drugs for PDA closure in India. To assess and compare the efficacy of oral ibuprofen and oral indomethacin for PDA closure in preterm Indian neonates, we designed a randomized controlled study on clinically diagnosed and echocardiographically confirmed hemodynamically significant PDA in preterm neonates. Patients were assigned to receive either oral ibuprofen at a dosage of 10, 5, 5 mg/kg every 24 h or three doses of oral indomethacin (0.20-0.25 mg/kg every 24 h) starting on the third day of life or when diagnosed. A second course of ibuprofen/indomethacin was given, if PDA failed to close within 48 h after the first course. Patients were monitored for complications like oliguria, bleeding, necrotizing enterocolitis, intraventricular hemorrhage, oxygen dependency, and gastrointestinal side effects. The baseline characteristics were comparable in both groups. Of the 83 children enrolled, 57.8 % received oral ibuprofen and 42.1 % received oral indomethacin. The overall closure rate of PDA was 60 and 65.7 % in the ibuprofen and indomethacin groups, respectively. Closure rate was significantly higher when the drugs were administered at an early postnatal age (<8 days) (83.3 % [p = 0.02] in the indomethacin group and 75 % [p = 0.03] in the ibuprofen group) in neonates >28 weeks (ibuprofen group 66.7 % [p = 0.02]; indomethacin group 65.5 % [p = 0.04]) and in babies with birth weight >1,000 g (ibuprofen group 62.2 %; indomethacin group 70 % [p = 0.04 in both groups]). Complications were similar in both groups. The efficacy of both drugs was similar. Poor closure in our study could be because of genetic differences in pharmacokinetics of drug metabolism in the Indian population. Regimens with higher doses or increased duration of treatment may increase the frequency of closure. Studies with larger numbers of subjects with evaluation of pharmacokinetic parameters are therefore required.

Management of Patent Ductus Arteriosus in Preterm Infants-Where Do We Stand?

Patent ductus arteriosus (PDA) in preterm infants is a controversial topic in the management of preterm neonates. There are no generally accepted guidelines for diagnosis, treatment, and follow-up of PDA, and few publications have covered the whole topic or have been conclusively summarized to give a proper direction for the treating physician. Major issues remain to be clarified, both with respect to diagnosis and treatment. The definition of hemodynamic significance varies because of different use of echocardiographic criteria and uncertainty about the role of biomarkers. The detailed risks and benefits of available treatment alternatives are still under investigation. There has been a general shift in the management of PDA in preterm neonates from the "aggressive approach" to a more "conservative approach," but the effects of this strategy on morbidity in a longer time perspective are not fully known. An individualized therapeutic strategy with special emphasis on identification of hemodynamically significance seems to be the way forward. In this review we put forward the scientific background in favor of a seemingly growing body of evidence against active treatment, but we raise caution against shying away from all forms of treatment or instituting them too late. Finally, we try to integrate the current knowledge into suggestions for the management of PDA in premature infants.

Preservation of the metabolic rate of oxygen in preterm infants during indomethacin therapy for closure of the ductus arteriosus

The aim of this study was to assess and quantify the effects of indomethacin on cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) in preterm infants undergoing treatment for a patent ductus arteriosus (PDA). CBF and CMRO2 were measured before and after the first dose of a 3-d course of indomethacin to close hemodynamically significant PDA in preterm neonates. Indocyanine-green (ICG) concentration curves were acquired before and after indomethacin injection to quantify CBF and CMRO2. Eight preterm neonates (gestational age, 27.6 ± 0.5 wk; birth weight, 992 ± 109 g; 6 males:2 females) were treated at a median age of 4.5 d (range, 4-21 d). Indomethacin resulted in an average CBF decrease of 18% (pre- and post-CBF = 12.9 ± 1.3 and 10.6 ± 0.8 ml/100 g/min, respectively) and an OEF increase of 11% (pre- and post-OEF = 0.38 ± 0.02 and 0.42 ± 0.02, respectively) but no significant change in CMRO2 (pre- and post-CMRO2 = 0.83 ± 0.07 and 0.76 ± 0.07 ml O2/100 g/min, respectively). Corresponding mean blood pressure (BP), arterial oxygen saturation (SaO2), heart rate, and end-tidal carbon dioxide tension levels remained unchanged. Indomethacin resulted in significant reduction in CBF but did not alter CMRO2 because of a compensatory increase in OEF.

Perfusion index and its dynamic changes in preterm neonates with patent ductus arteriosus

The perfusion index (PI) and its dynamic change during respiration, and supressed the plethysmographic variability index (PVI), are calculated from pulse oximetry, and these indexes were recently proposed for continuous and noninvasive assessment of peripheral perfusion in neonates. We aimed to assess the effect of patent ductus arteriosus (PDA) on PI and PVI, according to ductal Doppler flow pattern. Forty-five neonates with median (Q25-75) gestational age (GA) and birthweight of 27 (25-28) weeks and 857 (750-1080) grams, respectively, were assessed prospectively using serial echocardiography and pulse oximetry during the first postnatal week. Perfusion index increased from 0.70 (0.50-1.05) at day 1 to 1.50 (1.0-2.00) at day 7 (p < 0.01) and was not influenced by ductal flow pattern. PVI was 22 (18-27) and did not vary during the study period but differed according to ductal flow pattern, with lower values in the growing and pulsatile groups compared with the pulmonary hypertension (p < 0.05), closing and closed groups (p < 0.01). Ductal persistence and flow pattern did not affect PI but did affect PVI in preterm neonates of less than 29 weeks of GA. Future studies are needed to establish the usefulness of PVI in the early detection and management of PDA in preterm neonates.

Treatment of Patent Ductus Arteriosus and Neonatal Mortality/Morbidities: Adjustment for Treatment Selection Bias

To examine the association between treatment for patent ductus arteriosus (PDA) and neonatal outcomes in preterm infants, after adjustment for treatment selection bias. Secondary analyses were conducted using data collected by the Canadian Neonatal Network for neonates born at a gestational age ≤ 32 weeks and admitted to neonatal intensive care units in Canada between 2004 and 2008. Infants who had PDA and survived beyond 72 hours were included in multivariable logistic regression analyses that compared mortality or any severe neonatal morbidity (intraventricular hemorrhage grades ≥ 3, retinopathy of prematurity stages ≥ 3, bronchopulmonary dysplasia, or necrotizing enterocolitis stages ≥ 2) between treatment groups (conservative management, indomethacin only, surgical ligation only, or both indomethacin and ligation). Propensity scores (PS) were estimated for each pair of treatment comparisons, and used in PS-adjusted and PS-matched analyses. Among 3556 eligible infants with a diagnosis of PDA, 577 (16%) were conservatively managed, 2026 (57%) received indomethacin only, 327 (9%) underwent ligation only, and 626 (18%) were treated with both indomethacin and ligation. All multivariable and PS-based analyses detected significantly higher mortality/morbidities for surgically ligated infants, irrespective of prior indomethacin treatment (OR ranged from 1.25-2.35) compared with infants managed conservatively or those who received only indomethacin. No significant differences were detected between infants treated with only indomethacin and those managed conservatively. Surgical ligation of PDA in preterm neonates was associated with increased neonatal mortality/morbidity in all analyses adjusted for measured confounders that attempt to account for treatment selection bias.

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.