[Management of patent ductus arteriosus in preterm infants: An evidence-based approach]. / Prise en charge du canal artériel du prématuré : une approche factuelle.

A patent ductus arteriosus, very common in the preterm infant (incidence up to 70% in infants less than 28 weeks gestational age), causes a left-to-right shunt leading to overload of the pulmonary circulation and low systemic blood flow. These hemodynamic anomalies are associated with a higher incidence of respiratory, neurological, and digestive complications of prematurity, as well as a higher mortality rate. Although growing knowledge about the natural history, the pathophysiology, and the mechanisms of closure of the ductus arteriosus has resulted in therapeutic progress, management of the patent ductus arteriosus in the preterm infant is still a subject of intense controversy. We describe here the different treatment modalities, their benefits and side effects, and the therapeutic strategies that have been tested in the last four decades. Based on this evidence, the current trend is a personalized approach to the patent ductus arteriosus, adapted to each preterm infant's individual characteristics and risk factors.

Preoperative Staphylococcus aureus Carriage and Risk of Surgical Site Infection After Cardiac Surgery in Children Younger than 1 year: A Pilot Cohort Study.

Surgical site infections (SSI) increase length of stay, morbidity, mortality and cost of hospitalization. Staphylococcus aureus (SA) carriage is a known risk factor of SSI in adults, but its role in pediatrics remains uncertain. The main objective of this pilot prospective monocentric cohort study was to describe the prevalence of SA colonization in children under 1 year old before cardiac surgery. The secondary objectives were to compare the incidence of SSI and other nosocomial infections (NI) between preoperative carriers and non-carriers. From May 2012 to November 2013, all children <1 year old undergoing cardiac surgery under cardiopulmonary bypass underwent preoperative methicillin-resistant (MRSA) and methicillin-sensitive SA (MSSA) screening using real-time PCR. The only exclusion criterion was invalid PCR. All patients were followed up to 1 year after the surgery regarding SSI and other nosocomial infections. Among the 68 studied patients, SA colonization prevalence was 26.5%, comprising 23.5% MSSA and 2.9% MRSA. There was no significant difference between colonized and non-colonized children regarding SSI rate (16.7 vs 20%; p = 0.53), but ventilator-associated pneumonia rate was significantly higher among the SA carriers (22.2 vs 2%; p < 0.05). The colonization rate was different depending on the age of the patients (p < 0.05). This pilot study highlights that colonization with MSSA is frequent whereas MRSA prevalence is low in our population. In this cohort, there was no association between SA colonization and SSI incidence but further studies are needed to analyze this association.

["Traffic lights" in pediatrics: what do residents beginning their family residency know about them?]. / Les « feux tricolores ¼ en pédiatrie : état des lieux des connaissances en début de 3e cycle de médecine générale.

OBJECTIVES: Pediatric practice is a difficult task requiring physicians to discriminate potentially serious situations among a variety of benign situations. The goal of this study was to assess the knowledge of students beginning their residency in family medicine on these situations. METHODS: One hundred and three students were evaluated on pediatric "traffic lights" using 103 true/false questions. Pediatric and family medicine teachers of the Nantes University Hospital defined "traffic lights" as the fundamentals of pediatrics, misleading situations, and diagnosis and treatment that should not to be missed. Emergency levels were defined by colors, with "red light" corresponding to life-threatening emergencies. RESULTS: Thirty-six percent of the questions (n=103) had a correct response rate below 75%. Thirty-two percent of the questions on emergency situations ("red lights") (n=37) had a response rate below 75%. Fifteen percent of the questions (n=103) had a correct response rate below 50%, half of which were "red light" (e.g., on meningitis, diabetic acidocytosis, or shock). Questions concerning infants (n=24) had significantly fewer correct answers (correct response rate below 50%: 29% versus 10%; P=0.047). All the students answered seven questions correctly. The students' mean score (percentage of good answers) was 76% (±6%). No student had 100% or less than 50% good answers. CONCLUSIONS: Some life-threatening situations or situations concerning infants had not been mastered by most of the students. It is therefore essential to optimize the teaching of pediatrics during the second cycle of medical studies.

[Evaluation of an educational program for oral anticoagulation in children with the INR home-monitoring CoaguChek XS(®)]. / Évaluation de l'éducation au traitement anticoagulant et au système d'auto-mesure de l'INR CoaguChek XS(®) chez l'enfant.

OBJECTIVE: To assesses the results of our education program relative to anticoagulation therapy and self-monitoring of INR. MATERIALS AND METHODS: All children treated with oral anticoagulation therapy and followed using INR self-monitoring in Tours and Nantes, France, were included. A questionnaire on the treatment and its management was sent to the patients and their family. We analyzed the quality of anticoagulation using the proportion of INR within the target range. RESULTS: Thirty-three children were included, with a mean age of 10.9years. Thirty-one questionnaires could be analyzed. Insufficient knowledge on the treatment objective and risks, the INR target range, and the interpretation of the INR was observed. We found 65.8% of INRs within the target range. The proportion of INRs within the target range was better with the INR self-testing than with the laboratory test (69.7% vs. 49.1%, P=0.003). There was no major complication observed during the study period. A moderate correlation (K=0.57) was noted between the INRs measured with the point-of-care monitor and the laboratory test on the same day. CONCLUSION: However, home-monitoring of oral anticoagulation therapy increases the quality of anticoagulation. Both education and the training program need improvement in order to provide patients and their families with better knowledge on anticoagulation therapy.

[Severe coarctation of the aorta in children revealed by high blood pressure: a case report]. / Hypertension artérielle révélant une coarctation aortique serrée chez l'enfant : à propos d'un cas.

Coarctation of the aorta is an obstructive aortic lesion that causes secondary hypertension. Diagnosis is sometimes difficult because patients could present no other symptom. An asymptomatic 20-month-old child was referred in the context of isolated high blood pressure. Echocardiography was not effective, but CT scan established the diagnosis of coarctation. This case report underlines the importance of blood pressure measurement in the detection of aortic obstructions in the pediatric population.

Population pharmacokinetics of domperidone in preterm neonates.

PURPOSE: A population pharmacokinetic analysis was performed to define domperidone pharmacokinetic parameters in preterm neonates, as no pharmacokinetic data are available in this population. METHODS: An oral domperidone solution was administered (0.75 mg/kg per day) in 32 preterm neonates (64 samples). Domperidone plasma concentration was measured by high-performance liquid chromatography (HPLC) assay, and a one-compartment model with first-order absorption was fitted to the data using NONMEM version V level 1.1. RESULTS: The mean peak and trough plasma concentration values of domperidone were, respectively, 25.3 +/- 20.5 ng/ml and 15.4 +/- 11.4 ng/ml (mean +/- standard deviation). The pharmacokinetic parameters (interindividual variability%) were clearance (Cl/F) = 0.92 L/h (51.6%), volume of distribution (Vd/F) = 0.405 L (68%), and absorption constant rate (Ka) = 0.0843 h(-1) (55.8%). The clearance is not lower than values reported in adults. No influence of covariates (postnatal age, prematurity, weight, gender) on domperidone pharmacokinetic parameters was found. CONCLUSION: This pilot study designed with a limited sampling strategy showed that domperidone plasma concentrations were consistent with those reported in adults, suggesting that domperidone dosage regimen currently used in preterm neonates is suitable.

[Septal alcoholisation of hypertrophic obstructive cardiomyopathy in childhood]. / Alcoolisation septale d'une cardiomyopathie hypertrophique obstructive de l'enfant.

The authors report a case of septal alcoholisation in a 6 year old child with hypertrophic obstructive cardiomyopathy responsible for congestive cardiac failure despite optimal betablocker therapy. The indication was retained in a context of mucoviscidosis complicated by multiresistant bacterial infection. At catheterisation, the dominant septal artery was identified and an alcoholisation was performed by the classic technique described in adults. The immediate result was satisfactory with regression of the signs of cardiac failure and reduction of 70 mmHg of the maximal instantaneous pressure gradient (from 160 to 90 mmHg). However, 10 months later, the signs of right heart failure reappeared with a partial increase in the maximal instantaneous pressure gradient (100 mmHg) leading to surgical myectomy while the patient's condition had considerably improved from the pulmonary point of view. Septal alcoholisation would appear to be a therapeutic alternative in children especially in cases with a temporary or permanent contraindication to conventional surgery.

Prophylactic ibuprofen versus placebo in very premature infants: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Patent ductus arteriosus is a common complication of prematurity that frequently requires surgical or medical treatment. The benefit of prophylactic treatment by indometacin, a cyclo-oxygenase inhibitor, remains uncertain compared with curative treatment. This benefit could be improved with ibuprofen, another cyclo-oxygenase inhibitor with fewer adverse effects than indometacin on renal, mesenteric, and cerebral perfusion. We aimed to compare prophylactic and curative ibuprofen in the treatment of this abnormality in very premature infants. METHODS: We did a randomised controlled trial in infants younger than 28 weeks of gestation, who were randomly assigned to receive either three doses of ibuprofen or placebo within 6 h of birth. After day 3, symptomatic patent ductus arteriosus was treated first by open curative ibuprofen, then back-up indometacin, surgery, or both. The primary endpoint was need for surgical ligation. Analysis was per protocol. FINDINGS: The study was stopped prematurely after 135 enrollments because of three cases of severe pulmonary hypertension in the prophylactic group. 65 infants received prophylactic ibuprofen, and 66 received placebo. Prophylaxis reduced the need for surgical ligation from six (9%) to zero (p=0.03), and decreased the rate of severe intraventricular haemorrhage from 15 (23%) to seven (11%) (p=0.10). However, survival was not improved (47 [71%] placebo vs 47 [72%] treatment, p=1.00), because of high frequency of adverse respiratory, renal, and digestive events. INTERPRETATION: In premature infants, prophylactic ibuprofen reduces the need for surgical ligation of patent ductus arteriosus, but does not reduce mortality or morbidity. Therefore, it should not be preferred to early curative ibuprofen.

Contamination of a milk bank pasteuriser causing a Pseudomonas aeruginosa outbreak in a neonatal intensive care unit.

An environmental investigation and a cohort study were carried out to analyse an outbreak of infection caused by a serotype O10 Pseudomonas aeruginosa in a neonatal intensive care unit. Thirty one cases of infection were recorded, including four lethal ones. The outbreak was stopped by eradicating the environmental sources: a contaminated milk bank pasteuriser and bottle warmer.

Partial anomalous pulmonary venous connection: correction by intra-atrial baffle and cavo-atrial anastomosis.

The creation of intracaval conduits to repair partial anomalous pulmonary venous connection of the right lung into the superior vena cava can be complicated by arrhythmias and superior vena cava and pulmonary vein obstruction. An intra-atrial baffle, combined with cavo-atrial anastomosis, has been proposed to avoid these complications. The authors report their recent experience with this operative technique. From January 1997 to December 2000, 7 patients with a mean age of 13.5 +/- 9 (2-31) years were operated according to this technique. Only one child did not have an associated atrial septal defect. The mean number of pulmonary veins connected to the superior vena cava was 2.5 +/- 0.5. The immediate postoperative course was uneventful for the seven patients. The mean follow-up was 20 +/- 17 months. No patient developed arrhythmia or superior vena cava or pulmonary vein obstruction at echocardiography. This surgical technique appears to constitute an attractive alternative when pulmonary veins drain abnormally into the superior vena cava above the cavo-atrial junction.

[Transient left myocardial dysfunction: a cause of neonatal hypoxemia]. / Incompétence myocardique gauche transitoire: une cause d'hypoxémie néonatale.

UNLABELLED: Refractory hypoxemia in the newborn requires an accurate diagnostic investigation for an optimal and prompt management. CASE REPORT: After a short delivery, a post-term newborn developed a severe hypoxemia with patchy pulmonary alveolar opacities and systolic right-to-left extrapulmonary shunting through the ductus arteriosus. Echocardiography ruled out a cardiac malformation and showed dilated left atrium with left-to-right shunting by the ovale foramen due to left ventricular dysfunction. Inotropic support associated with mechanical ventilation allowed a rapid improvement. CONCLUSION: A pathophysiological analysis is needed in case of severe neonatal hypoxemia. Doppler ultrasound is a non invasive and rapid method allowing the adjustment of the therapeutic strategy.

Pulmonary hypertension after ibuprofen prophylaxis in very preterm infants.

We report three cases of severe hypoxaemia after ibuprofen administration during a randomised controlled trial of prophylactic treatment of patent ductus arteriosus with ibuprofen in premature infants born at less than 28 weeks of gestation. Echocardiography showed severely decreased pulmonary blood flow. Hypoxaemia resolved quickly on inhaled nitric oxide therapy. We suggest that investigators involved in similar trials pay close attention to pulmonary pressure if hypoxaemia occurs after prophylactic administration of ibuprofen.

Development of baroreflex control of heart rate in preterm and full term infants.

AIM: To study baroreflex maturation by measuring, longitudinally, baroreflex sensitivity in preterm (gestational age 24-37 weeks) and full term infants. METHODS: Baroreflex sensitivity was quantified once a week, one to seven times, by a totally non-invasive method. RESULTS: Baroreflex sensitivity at birth was lower in the preterm infant and increased with gestational age. It also increased with postnatal age, but the values for the preterm infants at term still tended to be lower than the values for full term babies. CONCLUSION: Baroreflex control of heart rate is present in the premature infant, but is underdeveloped and increases with postnatal age. Ex utero maturation seems to be delayed compared with in utero maturation assessed by full term values. These results may reflect sympathovagal imbalance in preterm infants and could identify a population more vulnerable to stress.

[Osler endocarditis of a ventricular septal defect in a 21-month old child]. / Endocardite d'Osler sur communication interventriculaire chez un enfant de 21 mois.

The authors report a case of streptococcus mitis endocarditis of a ventricular septal defect in a 21 months old girl admitted for necrotic purpura of the lower limbs and a history of general ill health and pyrexia for two months. The severity of this case of endocarditis was illustrated by the importance of the vasculitis, the biological signs of infection (disseminated intravascular coagulation), and the size of the vegetation. The vegetation extended from the tricuspid valve as far as the pulmonary orifice which was partially obstructed, causing signs of right ventricular failure. The portal of entry was not found. Surgical ablation of the vegetation with tricuspid valvuloplasty was necessary after 48 hours of antibiotherapy. The outcome after one year's follow-up is good. The diagnosis of bacterial endocarditis must be considered even in very young children, especially those with congenital heart disease, and, in particular, ventricular septal defect.

[Preoperative mortality in transposition of the great vessels]. / Mortalité préopératoire de la transposition isolée des gros vaisseaux.

UNLABELLED: The aim of the study was to report the incidence and causes of preoperative deaths in isolated transposition of the great vessels and to describe the clinical findings in these neonates. PATIENTS AND METHODS: In five French centers of pediatric cardiology, data of all the neonates with isolated transposition of the great vessels who died before arterial switch operations between January 1986 and June 1996 were obtained from reviewing hospital files, echocardiography records and autopsy reports. RESULTS: Among 199 neonates with transposition of the great vessels, 20 (9.9%) died before surgery. The death was related to intracranial haemorrhage in one premature neonate, severe and early hypoxemia in 13 full-term patients (group A) and later sudden collapse in six patients (group B). In group A, the symptoms occurred within 20 minutes after the birth and included cyanosis (n = 12), acute respiratory distress (n = 8), and shock (n = 4). Despite assisted ventilation (n = 13), bicarbonate infusion (n = 12), prostaglandin E1 (n = 7), inotropic drugs (n = 5) and balloon atrioseptostomy (n = 7), death occurred at the median age of five hours. The patent foramen ovale was absent or tiny in ten patients, normal in one patient and not specified in two patients. The ductus arteriosus was patent in ten patients and not specified in three patients. In group B, the neonates were initially in a good hemodynamic condition. Unexplained death occurred between two and five days after the birth: one infant with a large patent foramen ovale did not receive prostaglandin E1, four patients died a few hours after an angiographic study or a balloon atrioseptostomy was performed in a catheterization laboratory, and one child suffered from a cerebral anoxia due to a tightened cord. CONCLUSION: We conclude that the high preoperative mortality rate in isolated transposition of the great vessels is mainly due to absent or small atrial shunt. These findings suggest that only prenatal diagnosis of transposition of the great vessels with immediate balloon atrioseptostomy could avoid a fatal outcome.

Perinatal myocardial DNA and protein changes in the lamb: effect of cortisol in the fetus.

Myocardial growth during fetal life is accomplished by proliferation of the number of myocytes (hyperplasia). Shortly after birth, normal growth of the heart is predominantly due to increase in cell size (hypertrophy), and myocytes largely lose the capability to replicate. This change is characterized by a decrease in myocardial DNA concentration and an increase in protein/DNA concentration ratio. Among many of the events associated with birth is an increase in plasma cortisol concentrations in the few days before delivery of the fetus. To determine the possible role of cortisol in the postnatal change in myocardial growth, we measured DNA and protein concentrations in the free walls of the left (LV) and right (RV) ventricles in normal fetal lambs, normal newborn lambs, and in fetal lambs in which cortisone was infused for 72-80 h into the left coronary artery, which we showed does not perfuse the RV free wall. Normally, fetal RV DNA is higher than LV DNA concentration, and DNA/protein ratio is lower in RV than in LV. It is suggested that this could be related to the greater load on the RV. Postnatally, protein concentrations increase progressively, but DNA remains the same in both ventricles, and protein/DNA ratios increase. Cortisol, infused to achieve normal prenatal levels in LV myocardium, markedly decreases LV DNA without affecting RV DNA concentrations. The present study indicates that cortisol inhibits myocyte replication and that cortisol simulates the change in myocardial growth pattern normally occurring after birth. It raises concerns regarding prenatal administration of glucocorticoids to mothers to mature the fetal lungs before preterm delivery.