Malnutrition with hypoaminoacidemia in a 22-year-old pregnant patient masking a likely ornithine transcarbamylase deficiency.

BACKGROUND: Symptoms and clinical presentations of OTC deficiency vary widely according to the remaining activity of the enzyme. Three factors determine the residual enzyme activity. First, as the OTC gene is carried on the X chromosome, a complete inactivation of this enzyme in a newborn boy results an acute ammonia intoxication. Second, the female mosaicism due to lyonization (differential randomized X-inactivation) leads to differential OTC expression in hepatocytes. Third, the degree of severity depends on the mutation and the level of remaining activity it leaves to the protein. Published cases of OTC deficiency during pregnancy are scant. Most often, diagnosis of the metabolic disease is made before pregnancy or during the post-partum period. METHODS: We report the case of a 22-year-old woman's successful pregnancy with a moderate form of ornithine transcarbamylase (OTC) deficiency, unsuspected before pregnancy, biochemically consistent with plasma aminoacidogram and orotic acid analysis, and initially masked by malnutrition. RESULTS - CONCLUSION: Although maternal ammonia was subnormal and the neonate was safe, an OTC deficiency was revealed by stress factors such as the pregnancy itself and infection, and associated with uncontrollable maternal vomiting and psychiatric syndrome. However, this metabolic disease, revealed by aminoacidogram and urine orotic acid analysis, fortunately did not prevent a successful pregnancy. Even if infrequent, this situation deserves to be highlighted.

[In the case of premature live birth, is very early rupture of the membranes an additional risk factor for morbidity and mortality?] / En cas de naissance vivante prématurée, la rupture très précoce des membranes est-elle un facteur de risque supplémentaire de morbi-mortalité ?

OBJECTIVE: To describe survival rate after preterm premature rupture of membranes (PPROM) before 25 weeks of gestation and compare neonatal morbidity and mortality among those born alive with a control group of infants born at a similar gestational age without premature rupture of membranes. METHODS: We conducted a retrospective single-centre study at Port-Royal maternity, from 2007 to 2015, comparing neonatal outcomes between liveborninfants exposed to PPROM prior to 25 weeks of gestation (WG) and a control group not exposed to premature rupture of the membranes. For each live-born child, the next child born after spontaneous labor without PPROM was matched for gestational age at birth, sex, and whether or not they received antenatal corticosteroid therapy. The primary endpoint was severe neonatal complications assessed by a composite endpoint including neonatal deaths, grade 3-4 HIV, bronchopulmonary dysplasia, leukomalacia and stade 3-4 retinopathies. RESULTS: Among 77 cases of very premature rupture of the membranes, 55 children were born alive. Among these, the average gestational age at birth was 28 WG and 1 day. The rate of severe neonatal complications did not differ between the two groups (43.6% in the PPROM group vs. 36.4%, P=0.44) and the survival rate at discharge was also similar in the two groups (85.5% vs. 83.6%, P=0.98). CONCLUSIONS: In our cohort and among livebirths after 24 WG, PPROM before 25 WG was not associated with an increased risk of morbidity and mortality compared to children born at the same gestational age after a spontaneous labor with intact membranes.

Review shows that using surfactant a number of times or as a vehicle for budesonide may reduce the risk of bronchopulmonary dysplasia.

AIM: Bronchopulmonary dysplasia (BPD) remains the most common respiratory morbidity in immature infants. This review describes the diagnosis of BPD has evolved and summarises the therapeutic approaches that have made it possible to limit the incidence of BPD. METHOD: We reviewed the literature from the first definition of BPD by Northway in 1967 to the surfactant treatment policies that are currently in use, drawing on more than 50 papers up to 2017. RESULTS: Our review showed that improvements in neonatal survival have been associated with an increased risk of severe BPD, significant levels of long-term morbidity and the increased use of healthcare resources. These issues have encouraged researchers to explore potential new treatments that limit the incidence of BPD. Repeated surfactant instillation and the use of surfactant as a vehicle for budesonide are promising strategies for alleviating the burden of chronic lung disease. Ongoing research on surfactant or stem cell therapy may further improve the respiratory prognosis for prematurely born children. CONCLUSION: Considerable research has been carried out into the increase in BPD, which has resulted from improvements in neonatal survival. Key areas of research include repeated surfactant administration, using surfactant as a vehicle for budesonide and stem cell therapy.

[Perinatal care for extremely preterm infants. Considerations of the "risks in pregnancy" department]. / Prise en charge de la prématurité extrême. Réflexions du département hospitalo-universitaire (DHU) « risques et grossesse ¼.

Decisions regarding whether to initiate or forgo intensive care for extremely premature infants are often based on gestational age alone. However, other factors also affect the prognosis for these patients and must be taken into account. After a short review of these factors, we present the thoughts and proposals of the Risks and Pregnancy department. The proposals are to limit emergency decisions, to better take into account other factors than gestational age and prenatal predicted fetal weight in assessing the prognosis, to introduce multidisciplinary consultation in the evaluation and proposals that will be discussed with the parents, and to separate prenatal steroid therapy from decision-making regarding whether or not to administer intensive care.

[Recombinant human erythropoietin in neonates: guidelines for clinical practice from the French Society of Neonatology]. / L'érythropoïétine humaine recombinante chez le nouveau-né : recommandations pour la pratique clinique de la Société française de néonatologie.

OBJECTIVE: 1/To assess the effectiveness and safety of EPO in reducing red blood cell (RBC) transfusions in preterm infants. 2/To provide guidelines for clinical practice in France. METHODS: 1/This systematic evidence review is based on PubMed search, Cochrane library. 2/Using French National Authority for Health methods concerning guidelines for clinical practice. RESULTS: Early EPO reduced the risk of RBC transfusions, donor exposure, and the number of transfusions in very preterm infants (LE2). Late EPO reduced the risk of RBC transfusions and the number of transfusions in very preterm infants (LE2). There is no difference between the effectiveness of early and late EPO (LE2). There is no difference between high-dose and low-dose EPO (LE2). The level of evidence is too low to recommend the intravenous route. EPO has no impact on the rate of bronchopulmonary dysplasia, necrotizing enterocolitis (LE3), and retinopathy of prematurity (LE2). The level of evidence is too low to recommend EPO for neuroprotection in very preterm or term infants. CONCLUSIONS: EPO to reduce RBC transfusion in very preterm infants is recommended (Level A). The optimal time to start therapy is unknown (Level B). The recommended dose is 750IU/kg/week via three subcutaneous injections for 6weeks (Level B).

[Basic aspects of the potential toxicity of anesthetic drugs]. / Aspects fondamentaux de la toxicite éventuelle des drogues anesthésiques.

Brain development is a complex phenomenon in which several stages of production, maturation, and organization of neural cells in a network succeed each other. Various environmental factors can disrupt these stages. During the last decade, numerous in vitro and in vivo experimental studies in newborn animal models have established the neurotoxic effects of most anesthetic and sedative drugs used in pediatrics. These effects are essentially responsible for neuronal apoptosis and have been associated with learning disorders in adulthood. This neurotoxicity is time-varying: there is a vulnerability period during synaptogenesis. These toxic effects were attributed to agonist properties on GABA receptors or antagonist properties on NMDA receptors, which are characteristics of all implicated anesthetics. Excessive activation of the GABA pathway and/or excessive inhibition of the NMDA pathway activate cellular mechanisms leading to apoptosis. The intensity of neurotoxic effects is dose- and time-exposure-dependent. These numerous experimental data must be interpreted with caution with regard to their validity in humans, mainly because of interspecies differences as well as differences between experimental conditions and clinical practice. Today, these data are insufficient to change our practices, taking into account the indisputable benefits of the use of anesthetics and sedative drugs. However, progress in experimental research will help us identify the safest therapeutic strategies and neuroprotective treatments.

[Benefits and harms to the newborn of maternal attempt at trial of labor after prior caesarean versus elective repeat caesarean delivery]. / Bénéfices et risques néonataux de la tentative de voie basse comparée à la césarienne programmée en cas d'antécédent de césarienne.

OBJECTIVE: To evaluate neonatal outcome after elective repeat cesarean delivery (ERCD) versus trial of labor (TOL) after previous cesarean delivery. METHODS: This systematic evidence review is based on Pubmed search, Cochrane library and experts recommendations. RESULTS: The risks of fetal, perinatal and neonatal mortality are low after previous cesarean delivery but significantly higher for TOL as compared with ERCD. The risk of bag-and-mask ventilation and intubation for meconium-stained amniotic fluid are higher for TOL as compared with ERCD. Infants born after ERCD are more likely presented transient tachypnea. The risk of hypoxic encephalopathy/asphyxia is low after previous cesarean delivery but significantly higher for TOL as compared with ERCD. The risk of neonatal sepsis after previous cesarean delivery is significantly higher for TOL as compared with ERCD. There is no significant difference between TOL or ERCD regarding NICU admission. The strength of evidence is low to conclude about the impact of route of delivery upon birth trauma and Apgar score. CONCLUSIONS: The risk of the main neonatal complications is low whatever the route of delivery after previous caesarean delivery. However, the risk of perinatal mortality, bag-and-mask ventilation, perinatal asphyxia, is higher after TOL compared with ERCD. The risk of transient tachypnea is higher after ERCD compared with TOL.

Capnocytophaga species and preterm birth: case series and review of the literature.

Capnocytophaga, a genus of Gram-negative anaerobes that inhabit the oral cavity, has been reported to be an unusual cause of chorioamnionitis and neonatal infection. We report five cases of Capnocytophaga spp. infections in preterm infants (one proven infection and four probable infections) and review 14 previously reported cases. We suggest that Capnocytophaga sp. may be responsible for some occult causes of chorioamnionitis or preterm birth, and that the prevalence of this infection may be higher than previously reported.

[Oxygen weaning]. / Sevrage de l'oxygène.

Oxygen weaning is a controversial problem which can be summarized in three questions: what do we expect from oxygen supplementation? what are the optimal targets? with what sort of monitoring? We shall try to evaluate these different questions assuming the uncertainty of the proposed answers and the short-lived character of them.

Deleterious effects of IL-9-activated mast cells and neuroprotection by antihistamine drugs in the developing mouse brain.

Elevated mean IL-9 serum levels have been observed in human neonates who will later develop cerebral palsy. In earlier studies, using a newborn mouse model of excitotoxic lesions mimicking those described in human cerebral palsy, we found that IL-9 pretreatment exacerbated brain damage produced by intracerebral injections of the glutamatergic analog ibotenate. Among its different cell targets, the Th2 cytokine IL-9 is a mast cell growth and differentiation factor that can cause mast cells to release various substances including histamine. In the present study, we sought to determine whether the deleterious effects of IL-9 in our mouse model were mediated by mast cells through histamine release. All mouse pups were pretreated with intraperitoneal injections of IL-9 or saline between postnatal days (P) P1 and P5. Immunohistochemistry for murine mast cell protease-1 performed on P5 showed an increased density of labeled cells in the neopallium of IL-9-treated Swiss pups as compared with controls. Western blot analysis confirmed the increased murine mast cell protease-1 brain content of IL-9-treated Swiss mice. IL-9 pretreatment had no significant effect on ibotenate-induced excitotoxic brain lesions in mast cell-deficient P5 pups (WBB6F1/J kit(W/W-v)), whereas IL-9 exacerbated these lesions in the control littermates with normal mast cell populations. Finally, cromoglycate or antihistamine drugs significantly reduced ibotenate-induced brain lesions in IL-9-treated Swiss pups. Taken together, these data suggest that recruitment of cerebral mast cells with histamine release may contribute to the exacerbation of neonatal excitotoxic brain lesions produced by IL-9. Neuroprotective strategies targeting mast cells may be useful in some neonates at risk for cerebral palsy.

[Neonatal neurological impact of inflammation in the fetus]. / Conséquences neurologiques néonatales de l'inflammation sur le foetus.

With improvement of critical care of the newborn, perinatal mortality had decreased along the past decades. However, recent studies have shown that there is a slightly increase in the prevalence of cerebral palsy over the same period either for term or premature babies. Epidemiological data stress the multifactorial origins of cerebral palsy. Along with premature birth one of the predominant cause appears to be chorioamnionitis. Using data from a review of clinical and experimental studies the authors aim to clarify the link between infection, inflammation and fetal brain damage. The hypothesis that cytokines as mediators of inflammation can also mediate neurotoxicity is developed.

Proinflammatory cytokines and interleukin-9 exacerbate excitotoxic lesions of the newborn murine neopallium.

Many prenatal and perinatal factors are hypothesized to play a role in the cause of cerebral palsy (CP). Epidemiological data implicate maternal-fetal infection and associated increase in circulating cytokines. Murine model data suggest that excitotoxic damage can produce pathological change in brain tissue consistent with lesions observed in CP. Specifically, on day 5 after birth, mouse pups injected with ibotenate, a glutamatergic analogue, develop transcortical necrosis and white matter cysts mimicking some human perinatal lesions associated with CP. The present study builds on this murine model to assess the modulating role of several cytokines on the development of excitotoxic lesions. Pups pretreated with interleukin (IL)-1beta, IL-6, IL-9, or tumor necrosis factor-alpha developed significantly larger ibotenate-induced cortical and white matter damage than controls; IL-4 did not produce such an effect. In a similar manner, IL-9-overexpressing transgenic pups developed ibotenate-induced brain lesions, which were significantly larger than those induced in nontransgenic control pups. Pretreatment with proinflammatory cytokines significantly increased neopallial microglial density without affecting astrocytic density; IL-9 or IL-4 did not produce a similar effect. To our knowledge, this is the first in vivo study to demonstrate that systemically administered proinflammatory cytokines and IL-9 exacerbate brain lesions that are similar to those found in human infants with CP.

A new strategy for the surgical treatment of aortic coarctation associated with ventricular septal defect in infants using an absorbable pulmonary artery band.

OBJECTIVES: We propose a new strategy using coarctation repair together with a polidioxanone absorbable pulmonary artery banding to limit operative risk and to spare infants with aortic coarctation subsequent operations. BACKGROUND: The alternative for the surgical management of aortic coarctation associated with ventricular septal defect (VSD) is single-stage repair versus coarctation repair with or without banding of the pulmonary artery. METHODS: Eleven infants (mean weight 2,560 +/- 1,750 g, range 1,320 to 3,800 g) underwent a coarctation repair with a polydioxanone banding. Seven had a trabecular and four a perimembranous VSD. The mean size of the VSD was 5 +/- 0.7 mm (range 4 to 7 mm). The systolic pulmonary pressure was >80% of the aortic pressure in all. The pulmonary band was tightened until the systolic pulmonary pressure fell below 50% of the aortic pressure. RESULTS: There were no hospital deaths. The reabsorption of the banding was complete after 5.7 months in all patients (3 to 6.5 months). The VSD closed completely in four infants and partially in six, in whom the pulmonary artery pressure was normal without evidence for significant left-to-right shunt. One patient with a large trabecular VSD underwent surgical closure of his defect after four months. Finally, a subsequent open-heart surgery could be avoided in 91% (10/11) of patients. CONCLUSIONS: Provided the VSD belongs to types prone to close spontaneously, this policy may reduce the number of surgical procedures per infant as well as in-hospital mortality and morbidity rates. It should be proposed as an alternative to more complex procedures.

Continuous tracheal gas insufflation enables a volume reduction strategy in hyaline membrane disease: technical aspects and clinical results.

OBJECTIVE: Instrumental dead space wash-out can be used to improve carbon dioxide clearance. The aim of this study was to define, using a bench test, an optimal protocol for long-term use, and to assess the efficacy of this technique in neonates. DESIGN: A bench test with an artificial lung model, and an observational prospective study. Dead space wash-out was performed by continuous tracheal gas insufflation (CTGI), via six capillaries molded in the wall of a specially designed endotracheal tube, in 30 preterm neonates with hyaline membrane disease. SETTING: Neonatal intensive care unit of a regional hospital. RESULTS: The bench test study showed that a CTGI flow of 0.5 l/ min had the optimal efficacy-to-side-effect ratio, resulting in a maximal or submaximal efficacy (93 to 100%) without a marked increase in tracheal and CTGI circuit pressures. In the 30 newborns, 15 min of CTGI induced a significant fall in arterial carbon dioxide tension (PaCO2), from 45 +/- 7 to 35 +/- 5 mmHg (p = 0.0001), and in 14 patients allowed a reduction in the gradient between Peack inspirating pressure and positive end-expiratory pressure from 20.8 +/- 4.6 to 14.4 +/- 3.7 cmH2O (p < 0.0001) while keeping the transcutaneous partial pressure of carbon dioxide constant. As predicted by the bench test, the decrease in PaCO2 induced by CTGI correlated well with PaCO2 values before CTGI (r = 0.58, p < 0.002) and with instrumental dead space-to-tidal volume ratio (r = 0.54, p < 0.005). CONCLUSION: CTGI may be a useful adjunct to conventional ventilation in preterm neonates with respiratory disease, enabling an increase in CO2 clearance or a reduction in ventilatory pressure.