Hemolytic specimens in complete blood cell count: Red cell parameters could be revised by plasma free hemoglobin.

INTRODUCTION: Hemolysis is the main cause of unqualified clinical samples. In this study, we established a method for detecting and evaluating hemolysis in whole blood test. We used a mathematical formula for correcting the influence of hemolysis on complete blood cell count (CBC) so as to avoid re-venipuncture and obtain more accurate parameters of red blood cell detection, reduce the burden of patients, and improve the efficiency of diagnosis and treatment. METHODS: Hemolytic samples were selected and then corrected using the new formula. Plasma free hemoglobin (fHB) was used as the criterion to determine the degree of hemolysis; the uncertainty of measurement is acceptable as the limit value of deviation between the measured value and the revised value. Hemolysis simulation analysis in vitro and continuous monitoring of clinical patients were used to verify the correction effect. RESULTS: A total of 83 clinical samples with hemolysis were collected and analyzed; fHB 1.4 g/L was selected as the unacceptable value for clinical hemolysis detection. In hemolytic samples, the red blood cell parameters corrected by formula are significantly different from those uncorrected and had a good consistency with those before hemolysis. CONCLUSION: The results show that the hemolysis phenomenon of CBC has a significant impact on routine blood testing. By using the new formula, the influence of hemolysis on erythrocyte and related parameters can be quickly and easily corrected, thus avoiding venipuncture again for re-examination, reducing diagnostic errors, and saving medical resources.

Mature and immature platelets during the first week after birth and incidence of patent ductus arteriosus.

BACKGROUND: Thrombocytopenia is a risk factor for patent ductus arteriosus. Immature and mature platelets exhibit distinct haemostatic properties; however, whether platelet maturity plays a role in postnatal, ductus arteriosus closure is unknown. METHODS: In this observational study, counts of immature and mature platelets (=total platelet count - immature platelet count) were assessed on days 1, 3, and 7 of life in very low birth weight infants (<1500 g birth weight). We performed echocardiographic screening for haemodynamically significant patent ductus arteriosus on day 7. RESULTS: Counts of mature platelets did not differ on day 1 in infants with (n = 24) and without (n = 45) haemodynamically significant patent ductus arteriosus, while infants with significant patent ductus arteriosus exhibited lower counts of mature platelet on postnatal days 3 and 7. Relative counts of immature platelets (fraction, in %) were higher in infants with patent ductus arteriosus on day 7 but not on days 1 and 3. Receiver operating characteristic curve analysis unraveled associations between both lower mature platelet counts and higher immature platelet fraction (percentage) values on days 3 and 7, with haemodynamically significant ductus arteriosus. Logistic regression analysis revealed that mature platelet counts, but not immature platelet fraction values, were independent predictors of haemodynamically significant patent ductus arteriosus. CONCLUSION: During the first week of postnatal life, lower counts of mature platelets and higher immature platelet fraction values are associated with haemodynamically significant patent ductus arteriosus. Lower counts of mature platelet were found to be independent predictors of haemodynamically significant patent ductus arteriosus.

Exploration of potential biochemical markers for persistence of patent ductus arteriosus in preterm infants at 22-27 weeks' gestation.

BACKGROUND: Early identification of infants at risk for complications from patent ductus arteriosus (PDA) may improve treatment outcomes. The aim of this study was to identify biochemical markers associated with persistence of PDA, and with failure of pharmacological treatment for PDA, in extremely preterm infants. METHODS: Infants born at 22-27 weeks' gestation were included in this prospective study. Blood samples were collected on the second day of life. Fourteen biochemical markers associated with factors that may affect PDA closure were analyzed and related to persistent PDA and to the response of pharmacological treatment with ibuprofen. RESULTS: High levels of B-type natriuretic peptide, interleukin-6, -8, -10, and -12, growth differentiation factor 15 and monocyte chemotactic protein 1 were associated with persistent PDA, as were low levels of platelet-derived growth factor. High levels of erythropoietin were associated with both persistent PDA and failure to close PDA within 24 h of the last dose of ibuprofen. CONCLUSIONS: High levels of inflammatory markers were associated with the persistence of PDA. High levels of erythropoietin were associated with both the persistence of PDA and failure to respond to pharmacological treatment.

Predicting the serum digoxin concentrations of infants in the neonatal intensive care unit through an artificial neural network.

BACKGROUND: Given its narrow therapeutic range, digoxin's pharmacokinetic parameters in infants are difficult to predict due to variation in birth weight and gestational age, especially for critically ill newborns. There is limited evidence to support the safety and dosage requirements of digoxin, let alone to predict its concentrations in infants. This study aimed to compare the concentrations of digoxin predicted by traditional regression modeling and artificial neural network (ANN) modeling for newborn infants given digoxin for clinically significant patent ductus arteriosus (PDA). METHODS: A retrospective chart review was conducted to obtain data on digoxin use for clinically significant PDA in a neonatal intensive care unit. Newborn infants who were given digoxin and had digoxin concentration(s) within the acceptable range were identified as subjects in the training model and validation datasets, accordingly. Their demographics, disease, and medication information, which were potentially associated with heart failure, were used for model training and analysis of digoxin concentration prediction. The models were generated using backward standard multivariable linear regressions (MLRs) and a standard backpropagation algorithm of ANN, respectively. The common goodness-of-fit estimates, receiver operating characteristic curves, and classification of sensitivity and specificity of the toxic concentrations in the validation dataset obtained from MLR or ANN models were compared to identify the final better predictive model. RESULTS: Given the weakness of correlations between actual observed digoxin concentrations and pre-specified variables in newborn infants, the performance of all ANN models was better than that of MLR models for digoxin concentration prediction. In particular, the nine-parameter ANN model has better forecasting accuracy and differentiation ability for toxic concentrations. CONCLUSION: The nine-parameter ANN model is the best alternative than the other models to predict serum digoxin concentrations whenever therapeutic drug monitoring is not available. Further cross-validations using diverse samples from different hospitals for newborn infants are needed.

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

BACKGROUND: Patent 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. METHODS: Prospective 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. DISCUSSION: The 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 REGISTRATION: ClinicalTrials.gov NCT03782610. Registered 20 December 2018.

Can lactate levels be used as a marker of patent ductus arteriosus in preterm babies?

OBJECTIVE: Serum lactate levels provide information on metabolic capacity at the cellular level. In addition, lactate reflects tissue perfusion and oxygenation status. The aim of this study was to determine the usefulness of high lactate levels as a marker in hemodynamically significant patent ductus arteriosus (hsPDA), which may lead to tissue perfusion defects. METHODS: Preterm infants with gestational age ≤32 weeks and birthweight ≤1500 g were included. Lactate levels were determined at postnatal 48-72 hours before echocardiographic evaluation. Eligible infants were divided into two groups as infants with and without hsPDA. Cut-off values for lactate were taken as lactate >4 mmol/L, identified as a high lactate level. Infants were also divided into two groups according to lactate levels as group I: lactate levels >4 mmol/L and group II: lactate levels ≤4 mmol/L. Haemodynamic PDA and lactate levels were compared. RESULTS: A total of 119 patients with gestational age ≤32 weeks and birthweight ≤1500 g were included in the study. Fifty patients had echocardiographic hsPDA and 69 patients had no PDA. Twelve (24%) of the patients with hsPDA and 22 (31.9%) of the non-hsPDA patients had a lactate level of 4 mmol/L (P = 0.392). There was no correlation between hsPDA presence and lactate levels (P = 0.35). CONCLUSION: High lactate levels are multifactorial and usually indicate impairment of tissue perfusion. There are a number of factors that can lead to impaired tissue perfusion in preterm infants. For the first time in this study, it was shown that lactate levels did not significantly increase in the presence of hemodynamically significant PDA. This may be due to the fact that peripheral tissue perfusion in the presence of hemodynamic PDA does not deteriorate enough to cause an increase in anaerobic metabolism.

Useful Platelet Indices for the Diagnosis and Follow-Up of Patent Ductus Arteriosus.

OBJECTIVE: The aim of this study was to assess the utility of early postnatal platelet indices in the prediction of hemodynamically significant patent ductus arteriosus (hsPDA) and its response to pharmacological treatment in preterm infants. STUDY DESIGN: The medical records of 971 infants with gestational age < 30 weeks and birth weight < 1,500 g were analyzed retrospectively. Infants with hsPDA comprised the study group and those without hsPDA comprised the control group. Complete blood count results were recorded, and red cell distribution width-to-platelet ratio (RPR) and platelet mass were calculated. RESULTS: A total of 481 infants, 169 in the hsPDA group and 312 in the control group, were included. In terms of platelet indices, the hsPDA group showed significantly lower mean platelet volume (MPV) and platelet mass, whereas RPR was significantly higher (p < 0.05, respectively). Multiple logistic regression analysis showed that RDS (relative ratio [RR]: 2.39; 95% confidence interval [CI]: 1.45-3.93; p < 0.001), MPV < 7.85 (RR: 3.71; 95% CI: 2.29-6.01; p < 0.001), and RPR > 0.070 (RR: 5.33; 95% CI: 3.28-8.65; p < 0.001) were independent risk factors for hsPDA. CONCLUSION: Low MPV and platelet mass and high RPR in the first hours of life are risk factors for hsPDA and hsPDA refractive to pharmacological treatment with ibuprofen in preterm infants.

Paracetamol Serum Concentrations in Neonates Treated Enterally for Ductal Closure: A Pilot Study.

We determined serum paracetamol concentrations 4 hours after the eighth dose in infants treated enterally for ductal closure. Serum paracetamol concentrations correlated (P = .0026) with ductal response. No patent ductus arteriosus in a baby with paracetamol levels <20 mg/L closed in response to treatment. Paracetamol levels also correlated (P = .046) with postnatal age.

Maturation of Platelet Function During Murine Fetal Development In Vivo.

OBJECTIVE: Platelet function has been intensively studied in the adult organism. However, little is known about the function and hemostatic capacity of platelets in the developing fetus as suitable in vivo models are lacking. APPROACH AND RESULTS: To examine fetal platelet function in vivo, we generated a fetal thrombosis model and investigated light/dye-induced thrombus formation by intravital microscopy throughout gestation. We observed that significantly less and unstable thrombi were formed at embryonic day (E) 13.5 compared with E17.5. Flow cytometry revealed significantly lower platelet counts in E13.5 versus E17.5 fetuses versus adult controls. In addition, fetal platelets demonstrated changed activation responses of surface adhesion molecules and reduced P-selectin content and mobilization. Interestingly, we also measured reduced levels of the integrin-activating proteins Kindlin-3, Talin-1, and Rap1 during fetal development. Consistently, fetal platelets demonstrated diminished spreading capacity compared with adults. Transfusion of adult platelets into the fetal circulation led to rapid platelet aggregate formation even in young fetuses. Yet, retrospective data analysis of a neonatal cohort demonstrated no correlation of platelet transfusion with closure of a persistent ductus arteriosus, a process reported to be platelet dependent. CONCLUSIONS: Taken together, we demonstrate an ontogenetic regulation of platelet function in vivo with physiologically low platelet numbers and hyporeactivity early during fetal development shedding new light on hemostatic function during fetal life.

Increase of prostaglandin E2 in the reversal of fetal ductal constriction after polyphenol restriction.

OBJECTIVE: Anti-inflammatory substances that inhibit the synthesis of prostaglandins, such as non-steroidal anti-inflammatory drugs (NSAIDs) and polyphenol-rich foods, can cause constriction of the fetal ductus arteriosus. This study aimed to test the hypothesis that reversal of fetal ductal constriction after maternal restriction of polyphenol-rich foods, in the third trimester of pregnancy, is accompanied by increased plasma levels of prostaglandin E2 (PGE2). METHODS: This was a controlled clinical trial of women with singleton pregnancy ≥ 28 weeks undergoing fetal echocardiography. The intervention group included pregnancies with diagnosis of fetal ductal constriction and not exposed to NSAIDs. The control group consisted of third-trimester normal pregnancies. Both groups answered a food frequency questionnaire to assess the amount of total polyphenols in their diet, underwent Doppler echocardiographic examination and had blood samples collected for analysis of plasma levels of PGE2. Intervention group participants received dietary guidance to restrict the intake of polyphenol-rich foods. The assessments were repeated after 2 weeks in both groups. RESULTS: Forty normal pregnancies were assessed in the control group and 35 with fetal ductal constriction in the intervention group. Mean maternal age (26.6 years) and mean body mass index (30.12 kg/m2 ) were similar between the two groups. Intragroup analysis showed that dietary guidance reduced the median consumption of polyphenols (from 1234.82 to 21.03 mg/day, P < 0.001), increasing significantly the plasma concentration of PGE2 (from 1091.80 to 1136.98 pg/mL, P < 0.05) in the intervention group after 2 weeks. In addition, Doppler echocardiography showed reversal of fetal ductal constriction in the intervention group. No significant changes were observed in the control group. CONCLUSIONS: Dietary intervention for maternal restriction of polyphenol-rich foods in the third trimester of pregnancy is accompanied by increase in plasma levels of PGE2 and reversal of fetal ductal constriction. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Factors affecting N-terminal pro-B-type natriuretic peptide levels in preterm infants and use in determination of haemodynamic significance of patent ductus arteriosus.

This study aimed to investigate factors affecting N-terminal pro-B-type natriuretic peptide (NTproBNP) in preterm infants and the ability of NTproBNP to predict haemodynamically significant patent ductus arteriosus (HsPDA). Prospective cohort study of 51 infants < 30 weeks gestation. Blood NTproBNP and heart ultrasound were performed on day of life 3, 10, 28 and 36 weeks corrected age. NTproBNP levels analysed for prediction of HsPDA. The effect of gestational age, ventilation, hypoxia, bronchopulmonary dysplasia (BPD), creatinine and haemoglobin levels on NTproBNP levels were investigated. Infants with HsPDA had higher mean (SD) day 3 NTproBNP (1840 pmol/L (1058) versus 178 pmol/L (140) p < 0.001). Receiver operator curves of day 3 NTproBNP for prediction of day 3 and day 10 HsPDA had an area under the curve of 0.98 and 0.94, respectively. A chosen day 3 NTproBNP value of ≥ 287 pmol/L for the prediction of day 3 HsPDA correctly classified 92% (sensitivity 92%, specificity 92%). NTproBNP demonstrated only modest ability to predict severe BPD. Chronological but not gestational age affected NTproBNP. Ventilation, hypoxia and haemoglobin levels did not influence NTproBNP but creatinine level was positively correlated. CONCLUSION: Day 3 NTproBNP is a useful biomarker to predict HsPDA and may be a valuable tool in future trial design. What is Known: • NTproBNP is a cardiac hormone used to diagnose and monitor cardiac dysfunction in adults and has been shown to be higher in premature infants with haemodynamically significant ductus arteriosus (HsPDA). What is new: • NTproBNP is highly predictive of ultrasound-defined HsPDA and may be a useful tool for further triage • Early NTproBNP higher in infants who develop severe BPD and with renal impairment but not affected by gestational age, recent exposure to hypoxia or haemoglobin levels while late levels unexpectedly higher in those without BPD or HsPDA.

A promising, novel index in the diagnosis and follow-up of patent ductus arteriosus: Red cell distribution width-to-platelet ratio.

BACKGROUND: The role of red cell distribution width-to-platelet ratio (RPR) has not previously been mentioned in reports on patent ductus arteriosus (PDA). Our objective was to evaluate whether RPR would have a role in the diagnosis and/or prediction of pharmacological closure of PDA. METHODS: Preterm infants' gestational age ≤30 weeks and ≤1500 g who were given first ibuprofen treatment in the first week of life for hemodynamically significant PDA (hsPDA) were included in the study. The patients were matched for gestational age, birthweight, and sex. Patients were subdivided into two groups based on the response to medical treatment (open and closed PDA). Hemogram parameters were recorded before and after medical therapy. Groups were compared with regard to demographic and clinical characteristics and for three sequential hematological parameters. RPR was calculated. Patients with sepsis, anemia, perinatal asphyxia, and congenital/chromosomal anomaly were not included in the study. RESULTS: A total of 112 infants had medically treated hsPDA. Of those, ductus closed in 70 neonates (closed PDA). A total of 96 infants constituted the control group. Mean gestational age and birthweight of the patients were 28.9 ± 2.4 weeks and 1207 ± 372 g. While RPR was significantly increased, PCT was lower in both hsPDA and open PDA groups (P < 0.05 and P < 0.05, respectively). In multivariate analysis, high RPR (OR 3.3, 95% CI 1.438-5.872, P < 0.05) and RDS (OR 2.9, 95% CI 1.903-4.811, P < 0.01) were detected as independent risk factors for hsPDA. CONCLUSION: Red cell distribution width-to-platelet ratio and PCT may be promising supportive tools for the diagnosis and prediction of pharmacotherapy success.

Relationship between perfusion index and patent ductus arteriosus in preterm infants.

BACKGROUND: Perfusion index (PI) is a noninvasive measure of perfusion. ΔPI (difference between pre- and postductal PI) may identify hemodynamically significant PDA. However, studies are limited to brief and intermittent ΔPI sampling. Our objective is to assess the value of continuous high resolution ΔPI monitoring in the diagnosis of PDA. METHODS: Continuous ΔPI monitoring in preterm infants was prospectively performed using two high-resolution pulse oximeters. Perfusion Index measures (ΔPI mean and variability, pre- and postductal PI) were analyzed over a 4-h period prior to echocardiography. A cardiologist blinded to the results evaluated for PDA on echocardiography. Linear mixed regression models were utilized for analyses. RESULTS: We obtained 31 echocardiography observations. Mean ΔPI (-0.23 vs. 0.16; P < 0.05), mean pre-PI (0.86 vs. 1.26; P < 0.05), and ΔPI variability (0.39 vs. 0.61; P = 0.05) were lower in infants with PDA compared to infants without PDA at the time of echocardiography. CONCLUSION: Mean ΔPI, ΔPI variability, and mean pre-PI measured 4 h prior to echocardiography detect PDA in preterm infants. PI is dynamic and should be assessed continuously. Perfusion index is a promising bedside measurement to identify PDA in preterm infants.

Patent Ductus Arteriosus in the Preterm Infant: Diagnostic and Treatment Options.

BACKGROUND: The incidence of hemodynamically significant patent ductus arteriosus (hsPDA) increases with decreasing gestational age and is associated with many common morbidities of extreme prematurity. Controversies remain surrounding the definition of hsPDA, the population of infants requiring treatment, the appropriate timing and method of treatment, and the outcomes associated with PDA and its therapies. PURPOSE: This integrative literature review focuses on diagnostic and treatment recommendations derived from the highest levels of evidence. SEARCH STRATEGY: PubMed and CINAHL were searched using key words "neonatal" and "patent ductus arteriosus" to discover the highest levels of evidence surrounding diagnosis, treatment methods, and outcomes. FINDINGS/RESULTS: The lack of consensus surrounding the diagnosis and clinical significance of PDA hinders meta-analysis across studies and confounds understanding of appropriate management strategies. Novel biomarkers, pharmaceutical choices, and transcatheter closure methods are expanding diagnostic and treatment options. IMPLICATIONS FOR PRACTICE: Infants weighing less than 1000 g are at highest risk. Prophylactic closure is no longer recommended, although early asymptomatic therapy is still preferred by some to avoid prolonged pulmonary overcirculation or decreased renal and gut perfusion. Conservative treatment measures such as fluid restriction and diuretic administration have not consistently proven effective and are in some instances detrimental. Cyclooxygenase inhibitors are effective but have adverse renal and mesenteric effects. Oral ibuprofen is associated with lower instance of necrotizing enterocolitis. IMPLICATIONS FOR RESEARCH: Well-defined staging criteria would aid in comparison and meta-analysis. Trials that include a control group that receives no therapy may help separate the outcomes associated with prematurity from those associated with PDA.

Does ibuprofen treatment in patent ductus arteriosus alter oxygen free radicals in premature infants?

Introduction Ibuprofen is used widely to close patent ductus arteriosus in preterm infants. The anti-inflammatory activity of ibuprofen may also be partly due to its ability to scavenge reactive oxygen species and reactive nitrogen species. We evaluated the interaction between oxidative status and the medical treatment of patent ductus arteriosus with two forms of ibuprofen. Materials and methods This study enrolled newborns of gestational age ⩽32 weeks, birth weight ⩽1500 g, and postnatal age 48-96 hours, who received either intravenous or oral ibuprofen to treat patent ductus arteriosus. Venous blood was sampled before ibuprofen treatment from each patient to determine antioxidant and oxidant concentrations. Secondary samples were collected 24 hours after the end of the treatment. Total oxidant status and total antioxidant capacity were measured using Erel's method. RESULTS: This prospective randomised study enrolled 102 preterm infants with patent ductus arteriosus. The patent ductus arteriosus closure rate was significantly higher in the oral ibuprofen group (84.6 versus 62%) after the first course of treatment (p=0.011). No significant difference was found between the pre- and post-treatment total oxidant status and total antioxidant capacity in the groups. Discussion Ibuprofen treatment does not change the total oxidant status or total antioxidant capacity. We believe that the effect of ibuprofen treatment in inducing ischaemia overcomes the scavenging effect of ibuprofen.

Association between neutrophil/lymphocyte ratio with ductus arteriosus patency in preterm newborns.

OBJECTIVE: The aim of this study was to assess the influence of neutrophil to lymphocyte (N/L) ratio and platelet indices on patent ductus arteriosus (PDA) in preterm infants. BACKGROUND: PDA is a common problem with potentially serious associated morbidities in preterm neonates. METHODS: Premature infants with hemodynamically significant PDA (n = 47) and a control group without PDA (n = 50) who were hospitalized in the neonatal intensive care unit were retrospectively evaluated. The characteristics, perinatal factors, N/L ratio, platelet counts and other platelet indices of the infants in both groups during the first 3 days of life were recorded. RESULTS: Platelet counts were significantly lower in the patient group than in the control group (p = 0.0343). There was a marked positive correlation between body weight and N/L ratio in preterm infants with PDA (p = 0.0001). PDA was associated with low platelet count. CONCLUSION: Our results showed that N/L ratio is positively correllated with body weight in PDA group. These data suggest that platelet counts and N/L ratio might be useful predictors for the early diagnosis and evaluation of the clinical course of PDA in preterm infants (Tab. 2, Ref. 28).

Elevated Nucleated Red Blood Cells at Birth Predict Hemodynamically Significant Patent Ductus Arteriosus.

We hypothesized that postnatal absolute nucleated red blood cell (aNRBC) counts would be elevated in premature infants with hemodynamically significant patent ductus arteriosus (PDA), reflecting intrauterine hypoxia. PDA severity was assessed and categorized echocardiographically. aNRBC counts were significantly correlated with ductal severity (Pearson correlation: P = .007). At the extremes, aNRBC levels were 3770 (728, 6015) hemodynamically significant PDA vs 865 (483, 2528) closed ductus.

C-reactive protein, platelets, and patent ductus arteriosus.

The association between inflammation, platelets, and patent ductus arteriosus (PDA) has not been studied so far. The purpose of this study was to evaluate whether C-reactive protein (CRP) is related to low platelet count and PDA. This was a retrospective study of 88 infants with a birth weight ≤1500 g and a gestational age ≤30 weeks. Platelet count, CRP, and an echocardiogram were assessed in all infants. The subjects were matched by sex, gestational age, and birth weight. Differences were compared using the χ2, t-test, or Mann-Whitney U-test, as appropriate. Significant variables were entered into a logistic regression model. The association between CRP and platelets was evaluated by correlation and regression analysis. Platelet count (167 000 vs. 213 000 µl-1, p = 0.015) was lower and the CRP (0.45 vs. 0.20 mg/dl, p = 0.002) was higher, and the platelet count correlated inversely with CRP (r = -0.145, p = 0.049) in the infants with vs. without PDA. Only CRP was independently associated with PDA in a logistic regression model (OR 64.1, 95% confidence interval 1.4-2941, p = 0.033).

Lower early postnatal oxygen saturation target and risk of ductus arteriosus closure failure.

BACKGROUND: Early postnatal hyperoxia is a major risk factor for retinopathy of prematurity (ROP) in extremely premature infants. To reduce the occurrence of ROP, we adopted a lower early postnatal oxygen saturation (SpO2 ) target range (85-92%) from April 2011. Lower SpO2 target range, however, may lead to hypoxemia and an increase in the risk of ductus arteriosus (DA) closure failure. The aim of this study was therefore to determine whether a lower SpO2 target range, during the early postnatal stage, increases the risk of DA closure failure. METHODS: Infants born at <28 weeks' gestation were enrolled in this study. Oxygen saturation target range during the first postnatal 72 h was 84-100% in study period 1 and 85-92% in period 2. RESULTS: Eighty-two infants were included in period 1, and 61 were included in period 2. The lower oxygen saturation target range increased the occurrence of hypoxemia during the first postnatal 72 h. Prevalence of DA closure failure in period 2 (21%) was significantly higher than that in period 1 (1%). On multivariate logistic regression analysis, the lower oxygen saturation target range was an independent risk factor for DA closure failure. CONCLUSION: Lower early postnatal oxygen saturation target range increases the risk of DA closure failure.

Indomethacin vs ibuprofen: comparison of efficacy in the setting of conservative therapeutic approach.

UNLABELLED: Indomethacin has been the mainstay for medical closure of patent ductus arteriosus. With its discontinuation, many units shifted to the use ibuprofen. We compared the therapeutic efficacy (successful closure, a priori defined as complete closure or >50% reduction in size) and the impact of the two drugs on neonatal morbidities. Two time epochs were analysed (IV indomethacin, January 2008 to November 2010, and IV ibuprofen lysine, November 2010 to September 2013). Demographic, clinical and echocardiographic data was compared. A total of 101 infants formed the study population, 58 (57.4%, indomethacin epoch) and 43 (42.6%, ibuprofen epoch). The gestational age, birth weight and postnatal age at initial treatment respectively were comparable [26 ± 1.8 vs 26.5 ± 1.9 weeks, 806 ± 183 vs 862 ± 234 g and median 12 (6, 17) vs 11 days (8, 18)]. Successful closure was significantly higher in the indomethacin group [26 (45%) vs 6 (14%), p < 0.01]. The incidence of bronchopulmonary dysplasia (BPD) and discharge in oxygen was comparable. Four infants (all in the ibuprofen group) developed pulmonary hypertension; one required pulmonary vasodilator therapy. Posttreatment serum creatinine was significantly lower in the ibuprofen group. Mortality was higher during the indomethacin epoch. On univariate analysis, the choice of the drug and higher gestational age were associated with successful closure. CONCLUSION: Indomethacin was more efficacious for ductal closure although did not impact outcomes. Use of staging schema may help understand 'need to treat' and refine therapy.