[Enoxaparin and tinzaparin in pediatrics: Impact of recommendation on prescription quality and anti-Xa levels]. / Énoxaparine et tinzaparine en pédiatrie : impact de recommandations sur la qualité des prescriptions et l'activité anti-Xa.

OBJECTIVES: A protocol has been written and distributed in May 2017 to all prescribers in a pediatric hospital to standardize and to secure the prescriptions of enoxaparin and tinzaparin considered as two high risk medications. The aim of this study is to evaluate the impact of the protocol on those prescriptions in a pediatric population. METHODS: This is a monocentric retrospective study comparing prescriptions of this two low-molecular-weight heparins for patients under 18 years old in 2016 and 2018, thus before and after the protocol redaction. RESULTS: In 2016, 2246 prescriptions of enoxaparin and tinzaparin were analyzed for 627 patients. Among them, 142 (22.6%) patients have had at least one anti-Xa level dosed. On the other hand, in 2018, 2061 prescriptions were written for 628 patients including 96 (15.3%) who have had at least one anti-Xa level dosed. The conformity rate of the first dose in IU/kg/administration of the first enoxaparin prescription goes from 36.3% before protocol to 52.1% after (P=0.03*). Concerning tinzaparin, the conformity rate goes from 69.2% to 83.3%. (P=0.19). The rate of first anti-Xa level in the range 0.4 to 1.2 IU/ml increase between 2016 and 2018 from 27.7% to 43.8% (P<0.001*). CONCLUSION: This protocol enabled to improve the quality of prescriptions in terms of: dosage written in IU/kg/administration, frequency of administration, dilution conformity, and result of the first anti-Xa level. Some efforts must be made in writing the dose in IU not in mg or ml.

Pharmacokinetics of dolutegravir in a premature neonate after HIV treatment intensification during pregnancy.

We describe the pharmacokinetics of dolutegravir (DTG) in a premature neonate after maternal intensification of an antiretroviral (ARV) regimen by adding DTG. During the last 2 weeks of pregnancy, the ARV was tenofovir-emtricitabine, atazanavir-ritonavir, and DTG (50 mg once daily). From the interaction between atazanavir and DTG via CYP3A4 and UGT1A1 and placental efflux transporter inhibition and considering the infant's probable enzymatic immaturity, the DTG elimination half-life was estimated to be 4-fold longer in neonates than in adults.

[Epignathus teratoma: diagnostic and neonatal management; a case report]. / Tératome épignathe: diagnostic et prise en charge néonatale; à propos d'un cas.

Epignathus teratoma is a rare tumor whose prognosis essentially depends on its resectability and on neonatal care. When it is undiagnosed prenatally, mortality is close to 100 % at birth, because of obstruction of the upper airways. We present a case of epignathus teratoma detected during obstetrical ultrasound screening. Diagnosis enabled planning for a safe delivery in a suitable multidisciplinary unit and use of the EXIT procedure.

[Cerebellar injury in premature infants less than 30 weeks of gestation]. / Lésions acquises du cervelet chez le grand prématuré : prévalence, facteurs de risque et conséquences fonctionnelles.

UNLABELLED: Traditionally, the cerebellum has been regarded as a central component of the motor system. Recent studies suggest an important role played by the cerebellum in the development of cognitive and social functions. The objective of this study was to evaluate the incidence of cerebellar injury and to define the obstetrical, neonatal, and radiologic characteristics, as well as the functional outcomes in a population of very preterm infants. METHODS: This retrospective study included neonates born before 30 weeks of gestational age between March 2004 and July 2007. Infants underwent MRI studies at a term-adjusted age; for each preterm infant with cerebellar injury, we identified two infants for the control group with normal MRI, matched on the basis of gestational age. We collected pertinent demographic, prenatal, and acute postnatal data for all infants. Follow-up assessment was performed at 2 years, using the Brunet-Lezine scale. RESULTS: A total of 148 ex-preterm infants were studied. Cerebellar injury was present in 14 (9 %) cases and associated with supratentorial parenchymal injury in 90 %. Duration of ventilation was longer in children with cerebellar injury, compared to controls (19.5 days vs 16.5 days; P=0.03). The other neonatal criteria analyzed were comparable between the two groups. Global developmental, functional, and social-behavioral deficits were more common and profound in preterm infants with cerebellar injury, with no significant difference. CONCLUSION: This study confirms the high incidence of cerebellar injury in very preterm infants and the importance of a specific neurobehavioral follow-up.

[Implementing palliative care for newborns in various care settings. Part 3 of "Palliative care in the neonatal period"]. / La mise en oeuvre pratique des soins palliatifs dans les différents lieux de soins : 3(e) partie des réflexions et propositions autour des soins palliatifs en période néonatale.

Palliative care in newborns may take place in the delivery room and then continued either in maternity wards or in the neonatal unit. For babies developing a chronic condition, going home may be advantageous. The population concerned includes babies born with a severe intractable congenital malformation and certain extremely preterm newborn babies at the limits of viability. Care procedures as well as withholding and withdrawing treatments are reviewed.

[Premature rupture of membranes: pathophysiology of neurological impact]. / Rupture très prématurée des membranes: physiopathologie des conséquences neurologiques.

The premature rupture of membranes (PROM) is responsible for 30 % of the premature births because of a high risk of associated chorioamnionitis. PROM and the perinatal infection are recognized as 2 of the main risk factors of periventricular leukomalacia and white matter disease in very preterm neonates. Inflammation associated with PROM is likely to induce neuronal or glial cell death at a developmental stage of great vulnerability for the developing brain. Several mechanisms (release of cytokines, accumulation of free radicals, excitotoxicity, apoptosis...) account for this deleterious effect. The decision to actively extract a fetus subjected to a fetal inflammatory response syndrome should take account of the risks of a proved intrauterine infection for both the mother and the fetus and the risks for the neonate related to a very preterm birth per se. A reasonable attitude seems not to maintain a fetus in an undoubtful septic context in utero if a preterm birth in the very short term appears unevitable. Practically, no consensus gives a recommendation between aggressive or conservative management in case of PROM within 30 and 34 weeks'gestation. Expectant management seems to be indicated before 28 weeks'gestation and intentional delivery could be recommended beyond 34 weeks'gestation due to increased maternal risks compared to relatively low incidence of the complications of prematurity at this term.

[Two cases of Pseudomonas aeruginosa neonatal meningitis treated by ciprofloxacine]. / Infections néonatales a Pseudomonas aeruginosa et atteintes neuroméningées. Intérêt de la ciprofloxacine.

Two cases of Pseudomonas aeruginosa neonatal meningitis are reported. Case 1 occurred on day 6 of life, at home, in a full term newborn. Favourable outcome was obtained with a treatment associating ceftazidime, 21 days, gentamicin, 10 days and ciprofloxacin, 10 days. Case no 2 was a nosocomial meningitis in a 32 weeks and 4 days gestational age premature newborn. Despite in vitro effective antibiotherapy with ceftazidime, netilmicine and ciprofloxacine, six cerebral abscesses were observed during the second week of treatment. Ceftazidime was stopped after 6 weeks and ciprofloxacine prolonged until neuroradiological cure of cerebral lesions at one year of age. Normal outcome was observed at 3 and 4 and half year of age. Therapeutic indications and clinical tolerance of ciprofloxacine in neonatal meningitis are discussed.

[Ureaplasma urealyticum and Mycoplasma hominis infections in newborns: personal data and review of the literature]. / Ureaplasma urealyticum, Mycoplasma hominis et pathologies néonatales: Données personnelles et revue de la littérature.

Ureaplasma urealyticum and Mycoplasma hominis colonized 20-40% of newborns and are more frequent in premature. They are responsible for localized infections such as pleural effusion, pneumopathy, adenopathy, abscess or systemic sepsis. An important hyperleukocytosis is often associated with pulmonary infections. Their responsibility, as pathogen agents, is questionable in some non bacterial meningitis. There is large controversy for their role as cofactor, in chronic lung disease (bronchopulmonary dysplasia) and periventricular leukomalacia, because of a too low number of newborns in prospective trials. Genital mycoplamas are resistant to beta lactamines. Macrolides have a good sensitivity, particularly josamycine, but Mycoplasma hominis is resistant to erythromycin. For systemic sepsis, fluoroquinolones such as ciprofloxacine have less deleterious effects than IV erythromycin.

[Candida infections in newborns]. / Infections néonatales à Candida.

Candida infections in newborns are classified, as bacterial ones, in early onset or maternofoetal infections and late onset diseases, primitive and nosocomial. Candida infections are responsible of less than 1% of early onset sepsis. Their diagnosis is facilitated by suggestive cutaneous lesions which can be associated or not with systemic infection. Candida nosocomial infections are the most frequent, 7% in premature infants < 1500 g; they are associated with a central venous catheter or with cutaneous infection in extremely low birth weight infants. C. albicans is the predominant species in maternofoetal infections, contrary to nosocomial ones where C. parapsilosis is predominant, 60%. Both species are sensitive to fluconazole. Amphotericin B and its lipidic derivative Ambisome is the reference drug. Because of its lower toxicity and simplicity of administration, fluconazole is preferable for sensitive species. Its prophylactic use in colonized premature infants has been recently proposed.

[A case of atrial flutter after umbilical venous catheterization]. / Une observation de flutter auriculaire après pose de cathéter veineux ombilical.

UNLABELLED: Isolated atrial flutter is an extremely rare form of supraventricular tachycardia in the neonatal period. It may be initiated by central venous catheterization. CASE REPORT: A male infant was born at 35 weeks by cesarean section for placenta praevia. He was eutrophic. Apgar score was 10 at 1 and 5 minutes. He secondary developed a respiratory distress syndrome. He was then ventilated by nasal CPAP. Immediately after an umbilical venous catheterization, a tachycardia appeared without preexistent cardiac dysfunction. An intravenous dose of adenosine (Striadyne) showed a characteristic sawtooth pattern of P waves on inferior leads. The cardiac-US examination was normal. This atrial flutter was converted to normal sinus rhythm by transoesophageal pacing, without adjunction of antiarrhythmic drugs. The newborn was weaned from mechanical ventilation 48 hours later and discharged from hospital at seven days post natal age. His development and clinical examination were normal two months later. CONCLUSION: The isolated atrial flutter is rare in the neonate. It may be triggered by a venous catheterization. Transoesophageal atrial pacing is safe and effective for conversion.

[Severe neonatal bacterial infections]. / Infections bactériennes graves du nouveau-né.

The prognosis of septicemic forms of early and late neonatal sepsis is severe with a high rate of mortality especially in premature infants. The evaluation of severity is difficult because of the non specificity of the clinical signs and mortality seems to be a good means of evaluation. A study was conducted in France on the mortality due to infection in neonatal intensive care units and neonatology wards during the third trimester 2000. Among 18 units, the mortality rate was 9.3% of admissions, corresponding to 11 early onset sepsis and 17 nosocomial infections. Death in primitive infections is essentially due to group B streptococci and E. coli with a more important risk in low gestational age infants. The nosocomial infections arise almost only in premature infant. Prognosis of infections due to Staphylococcus coagulase negative staphylococci, most frequent pathogens is good but mortalities rate is higher for enterobacteriacae--40% and for Pseudomonas, 62%.

Dypiridamole, a cGMP phosphodiesterase inhibitor, transiently improves the response to inhaled nitric oxide in two newborns with congenital diaphragmatic hernia.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) remains a frustrating cause of respiratory failure associated with persistent pulmonary hypertension of the newborn (PPHN). Although inhaled nitric oxide (iNO) is effective in many infants with PPHN, it often fails to improve oxygenation in infants with CDH. As the increase in vascular smooth muscle cyclic guanosine monophosphate (cGMP) in response to iNO may be impeded by increased phosphodiesterase type-V (PDE-V) activity, it has been suggested that PDE-V blockade potentiates the efficiency of iNO. CASE REPORTS: We used dypiridamole (Persantine), a specific PDE-V inhibitor, in two patients with CDH. Prenatal diagnosis showed a left-sided CDH at 23 weeks of gestation (GA) with intrathoracic stomach and left heart underdevelopment in the one infant and a right-sided CDH at 26 weeks GA with intrathoracic liver in the other. After antenatal corticoids, planned delivery was performed by the vaginal route at 38 weeks GA. Preoperative stabilization was achieved by high frequency oscillation, iNO and inotropic support over 24 h. Both had early pneumothorax drained by a chest tube. Despite optimization of ventilatory and hemodynamic support with surfactant replacement, iNO and adrenaline, oxygenation worsened progressively. Dypiridamole was introduced intravenously at 27 and 40 h, respectively, and improved oxygenation over the next 12 h. However, oxygenation again deteriorated and both patients died. CONCLUSION: Dypiridamole enhanced the response to iNO in PPHN associated with CDH, although this effect was transient. Combined therapy of iNO with PDE-V inhibitors may improve pulmonary vasodilation in some forms of PPHN which do not respond to iNO, thereby reducing the need for extracorporeal membrane oxygenation (ECMO) and improving outcome.

[Congenital diaphragmatic hernia. II. Is pulmonary hypoplasia an indefinable obstacle?]. / Hernie diaphragmatique congénitale II. L'hypoplasie pulmonaire, obstacle incontournable?

Despite major insights into the pathogenesis and pathophysiology of congenital diaphragmatic hernia, and despite the availability of an antenatal diagnosis and continuous progress in neonatal intensive care, little improvement has been obtained in the prognosis of this malformation. Thus obstetricians, neonatologists and pediatric surgeons are still facing a several dilemma: dilemma before birth to predict the prognosis, i.e., to evaluate the severity of the associated pulmonary hypoplasia in order to decide whether or not to interrupt pregnancy; dilemma after birth in case of severe respiratory failure to decide how far to go in life support. Based on a review of the literature and their own experience, the authors attempt to recapitulate the perinatal management and outcome of this severe malformation.

[Neonatal alloimmune neutropenias. Importance of treatment with granulocyte colony-stimulating factor (G-CSF). Report of 2 new cases]. / Neutropénies allo-immunes néonatales. Intérêt du traitement par facteur de croissance granuleux (G-CSF). Deux nouvelles observations.

UNLABELLED: Alloimmune neonatal neutropenia is a rare event. Usually asymptomatic, it may however in some cases result in a severe sepsis. Treatment with recombinant granulocyte colony-stimulating factor (G-CSF) has been recently proposed. CASE REPORT: We report two new cases in infected newborns of a successful treatment of alloimmune neonatal neutropenia with G-CSF, resulting in complete neutrophil recovery in less than 72 hours. Moreover, the treatment was well tolerated. CONCLUSION: The analysis of these two cases and of those previously reported indicates that G-CSF represents the first-choice treatment in this affection when infectious signs are present in the neonate.

[Intracranial hypertension in a newborn treated with quinolone]. / Hypertension intracrânienne chez un nouveau-né traité par quinolones.

BACKGROUND: Fluoroquinolones have not received administrative authorization for use in children, but because of multiresistant pathogens in neonatal intensive care, floroquinolones may be the only alternative. CASE REPORT: A premature infant exclusively nourished by parenteral nutrition developed enterobacteria sepsis. Ceftazidine was given initially but resistance led to the prescription of fluoroquinolone. Signs of intracranial hypertension developed 3 days after onset of fluoroquinolone treatment and regressed 48 hours after its withdrawal. DISCUSSION: The main potential adverse effects with fluoroquinone in the newborn are arthropathy, photosensitivity, discoloration of the teeth and neurological disorders. Intracranial hypertension is a known complication of nalidixic acid both in adults and children, but to our knowledge has not been previously with floroquinolone in the newborn.

Recombinant tissue-type plasminogen activator therapy of thrombosis in 16 neonates.

We report 16 cases of neonatal vascular thrombosis treated with the same protocol for recombinant tissue-type plasminogen activator infusion. Flow restoration was complete in seven patients, partial in seven, and absent in two. Safety was satisfactory provided contraindications were respected.

Acute respiratory distress syndrome in children.

The adult (acute) respiratory distress syndrome is a significant cause of morbidity in children. The mortality rates remain elevated, greater than 50%, and even greater than 80% in patients with underlying malignancies. The therapeutic interventions remain mainly supportive. Strategies of conventional mechanical ventilation are directed toward the use of high positive end-expiratory pressures, low positive inspiratory pressure, and permissive hypercapnia. High-frequency oscillatory ventilation and tracheal insufflation are not yet used extensively, although they should contribute to less aggressive ventilation. Surfactant replacement, nitric oxide inhalation, and partial liquid ventilation seem to be promising technologies, but controlled clinical studies are necessary before their wide-spread use. Extracorporeal membrane oxygenation remains the alternative technology in case of failure of conventional support.

Prognostic factors of prenatally diagnosed gastroschisis.

OBJECTIVE: To evaluate the prognosis of prenatally diagnosed gastroschisis. STUDY DESIGN: In a retrospective study, we analyzed the clinical and echographic data of gastroschisis. These data were correlated with fetal outcome including delivery, surgical procedure, follow-up in the neonatal intensive-case unit and in the gastropediatric unit. RESULT: Twenty cases were analyzed. The overall survival rate was 85%. Classical criteria were analyzed (maximal bowel dilatation, thickening of bowel wall). Fetuses with both severe perivisceritis and meconium-stained amniotic fluid were born earlier than fetuses with mild perivisceritis and normal amniotic fluid (p < 0.01). CONCLUSION: Our data suggest that an inflammatory response could follow bowel exposure to amniotic fluid. This response could lead to perivisceritis and premature birth. This hypothesis is currently under investigation.

Can blood gas values predict pulmonary hypoplasia in antenatally diagnosed congenital diaphragmatic hernia?

The prognosis of antenatally diagnosed congenital diaphragmatic hernias (CDH) is clearly related to the degree of pulmonary hypoplasia (PH). After birth, controversies remain regarding the implementation of various therapies, especially the use of extracorporeal membrane oxygenation (ECMO). In the literature, the persistence of a Pao2 below 100 mm Hg and of Paco2 above 40 mm Hg despite optimal conventional therapy indicates poor prognosis. Therefore, since 1992, published and personal experiences led the authors to exclude CDH patients from ECMO when conventional therapy (including high-frequency oscillatory ventilation and nitric oxide) did not obtain Pao2 of above 80 mm Hg and Paco2 of below 60 mm Hg. The aim of this retrospective study is to determine whether blood gas results correlate with postmortem findings. Between July 1990 and July 1994, 32 cases of CDH were monitored antenatally and managed postnatally at the authors' institution. Six patients survived; 26 died, including one immediately at birth. Thirteen were treated by ECMO. Seventeen had a best Pao2 of above 80 mm Hg, including the six survivors. Fourteen did not reach this level, and none of them survived. Twenty-three infants underwent postmortem examination. PH was assessed using two criteria: (1) lung weight to body weight ratio (LW/BW) and (2) radial alveolar count (RAC). Two patients did not have hypoplasia (LW/BW > 0.018). Twenty-one patients had PH; 12 of them had an LW/BW ratio of less than .009; for 9, the LW/BW ratio was between .009 and .018, and the RAC (< 3.1) confirmed PH. All infants with a best Pao2 of less than 80 mm Hg had PH. Patients with a best Pao2 of greater than 80 mm Hg included two infants who died from complications without PH, eight infants with demonstrated PH, and the six survivors. In conclusion. (1) No infant with nonhypoplastic lungs has been deprived of ECMO by the authors' criteria. (2) Adequate values of blood gases may not eliminate PH. Therefore, this probably justifies starting ECMO when conventional therapy fails. (3) Conversely, permanent poor values of Pao2 allowed the prediction of PH in all cases. Such patients probably can be excluded from ECMO treatment.