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In this article, we will review major therapeutic advances in neonatology over the past ten years. We will discuss the antenatal administration of magnesium sulfate, the interest of hypothermia in the context of hypoxic ischaemic encephalopathy, the benefits and modalities of placental transfusion, less invasive techniques for ventilation and administration of the surfactant, possibilities to fortify breast milk and the concept of developmental care. These therapeutic advances are sometimes based on new therapeutics, sometimes on new concepts and, sometimes, on new less invasive techniques. They have made it possible to optimize the care of premature babies but also of term newborns.Dans cet article, nous allons passer en revue les grandes avancées thérapeutiques dans le domaine de la néonatologie au cours des dix dernières années. Nous traiterons de l’administration anténatale du sulfate de magnésium, de l’intérêt de l’hypothermie contrôlée dans le cadre de l’encéphalopathie d’origine hypoxo-ischémique, des bénéfices et modalités de la transfusion placentaire, des techniques moins invasives pour la ventilation et pour l’administration du surfactant, de la fortification du lait maternel et du concept de soins de développement. Ces avancées thérapeutiques reposent tantôt sur des nouveautés thérapeutiques, tantôt sur de nouveaux concepts et, parfois, sur de nouvelles techniques moins invasives. Elles ont permis d’optimiser la prise en charge des prématurés, mais aussi des nouveau-nés à terme.

Hypothermia therapy is a protocol put in place to treat neonatal hypoxic ischemic encephalopathy in the first six hours after birth in order to prevent irreversible brain damage. The parents are therefore immediately separated from the newborn and endure an interminable 72-hour wait before being able to really meet their baby. Psychological support is therefore necessary to be able to think the unthinkable.

According to the French High Authority for Health, sudden unexpected death in infants (SUDI) is defined as "a sudden death that occurs in an infant, whereas nothing in its known history could have predicted it". This is an exclusion diagnosis. There are great interregional disparities despite the professional recommendations established in February 2007. For the examination of the brain, instructions are not adapted to current and research practice. The role of the pathologist, like anyone involved in SUDI, is to eliminate an abuse head trauma and to determine the cause of death. Major neuropathological lesions by definition do not exist. Lesions of hypoxia/ischemia are the most frequent but not specific. The accessibility of anti-APP immunoblotting has highlighted the role of anoxia in the development of axonal diffuse damages. Many studies are looking for a neurological substratum of the SUDI (neuropathological and/or neurobiochinic). This article aims to define a detailed sampling protocol based on foreign consensus and current data of science in order to assist pathologists and to promote a homogeneous data bank in France.

To describe neonatal complications related to shoulder dystocia.This systematic evidence review is based on PubMed search, Cochrane library and experts' recommendations.The risks of brachial plexus birth injury, clavicle and humeral fracture, perinatal asphyxia, hypoxic-ischemic encephalopathy and perinatal mortality are increased after shoulder dystocia. The medical team should be able to provide neonatal resuscitation in the delivery room in case of perinatal asphyxia following shoulder dystocia, according to national and international guidelines. The initial clinical examination should search for complications such as brachial plexus birth injury or clavicle fracture.The risk of perinatal complications is increased in newborn after shoulder dystocia. The medical team should be able to manage these complications.

Intrapartum asphyxia is a rare yet serious complication during labor with immediate consequences and possible long-term neurological impairment. The international Cerebral Palsy Task Force established criteria that attribute a cerebral palsy to intrapartum asphyxia: metabolic acidemia measured at birth with pH7 and base deficit≥12mmol/L.To determine the risk factors of an intrapartum asphyxia occurring in term live births, to evaluate the short-term consequences.Our retrospective study included all births between 2002 and 2010 in a level 3 maternity of a university hospital center. Inclusion criteria were those of the Cerebral Palsy Task Force associated with a gestational age≥34weeks of gestation. We studied the conventional markers of intrapartum asphyxia: Apgar score at 5minutes, abnormal cardiotogographic recordings whether they occurred after a sentinel hypoxic event or not before and during labor. The duration of expulsive efforts, the amniotic fluid aspects, the delivery mode as well as the preexisting pregnancy pathologies were also evaluated. On the other hand, we studied the short-term consequences at the newborns: death, multiorgan failure and especially the occurring of a neonatal encephalopathy using Sarnat and Sarnat staging.One hundred and twenty-nine newborns (0.43%) out of 29,416 live births had a pH7 of whom only 82 (0.27%) presented a real intrapartum asphyxia and were included in this study. A preexisting pregnancy pathology was found in 22% of the women. Hypoxic events were noted in only 9/82 of the cases. Abnormal cardiotocographic recordings were present in 97.6% of the cases. The duration of expulsive efforts as well as the amniotic fluid aspects did not interfere with the occurring of a metabolic acidemia. Caesarean rate was at 46.3% and instrumental extraction rate was at 34.1%. Thity-eight newborns (46.3%) were admitted in neonatal intensive care in which we noted 3 deaths (3.65%), 2 multiorgan failures (2.4%) and 17 neonatal encephalopathy (20.7%). The pH value seemed to influence the occurring of an encephalopathy: 50% when pH6.9 vs. 13.6% when pH≥6.9 (P=0.0013), as well as for the base deficit: 50% when BD-18 vs. 15.7% when BD≥-18 (P=0.0068). Apgar score at 5minutes also seemed predictive for a neonatal encephalopathy: 100% when4, 46% between 4 and 6 and 11% when6 (P0.001).Our results showed an intrapartum asphyxia rate half the one widely recorded of 0.5% of total live births. Our study also validates the commonly used markers to evaluate a high risk of an early neonatal encephalopathy. This study should be continued with the evaluation of hypoxia long-term consequences on the psychomotor development of these kids and especially the occurring of cerebral palsy.

Criteria defining the involvement of severe perinatal anoxia in neonatal encephalopathy in at-term newborns at birth are stringent and are rarely all present. The simultaneous action of pre- and intrapartum factors preceding neonatal hypoxic-ischemic encephalopathy are often observed. Cooling is recommended as there is evidence that it reduces mortality without increasing major disability in survivors. It must be conducted following strict clinical and electroencephalographic criteria. Other strategies for brain protection remain difficult to establish. Follow-up must be long enough to detect cognitive deficiencies, which are frequent, even if cerebral palsy is not observed.

In Western populations, especially in France, most severe influenza cases are observed in adults. Some cases are also recorded in children, especially influenza-associated encephalitis. This is contrary to what occurs in Japan where influenza-associated encephalitis is frequent and severe in children. We describe three cases of influenza-associated encephalitis in children who were hospitalized in the pediatric intensive care unit (PICU) during the winter of 2012-2013. The patients did not necessarily show the usual symptoms of influenza and were admitted to the PICU because of their severe neurological symptoms. Two children showed multiple-organ failure, as in the cases reported in Japan. The outcomes ranged from small residual signs to death. These cases remind us that the severe influenza complications that are common in Japan are also seen in France.

Sudden postnatal collapse of a full-term newborn is uncommon but may result in severe consequences: these include death; epilepsy; and motor, cognitive, or sensory impairment. Most authors suggest applying a therapeutic hypothermia approach when a previously healthy newborn develops moderate or severe encephalopathy after a sudden postnatal collapse occurring within the first hours or days after birth. However, this technique has still not been validated by randomized trials. Only a few cases have been reported in the literature. This article describes five apparently healthy newborns, born between 2007 and 2012, who suffered moderate to severe encephalopathy following a postnatal collapse on their first day of life. It describes their clinical history as well as their treatment and follow-up. The article focuses on the implementation of hypothermia in this indication and its limitations. Two newborns underwent classic therapeutic hypothermia, two others underwent temperature regulation (one at 34.5 °C, the other one for only 15 h because she quickly improved). One newborn, with severe pulmonary arterial hypertension, did not receive therapeutic hypothermia. Two newborns died (one had classic hypothermia and the other hypothermia at 34.5 °C), the outcome of the three survivors at three years, 18 months, and 15 months is good with only transient postural anomalies. Follow-up must be continued to assess their cognitive development and particularly their memorization processes. Additional research and centralization of the cases is required to evaluate the feasibility, safety, and benefits of therapeutic hypothermia in this situation.

Neonatal hypoxic-ischemic encephalopathy is a major cause of death and neurodevelopmental delay. Brain cooling by mild controlled hypothermia is currently the most promising therapy.

To estimate the modalities of management of post-term neonates.This study is based on PubMed search, Cochrane library and HAS recommendations.Medical team should be able to provide neonatal resuscitation in delivery room in case of meconium-stained fluid or perinatal asphyxia according to the international guidelines ILCOR 2010. The glycaemia of the post-term newborn with macrosomia should be evaluated. The initial clinical examination should search complications such as shoulder dystocia or clavicular fracture. Full blood count should be performed in symptomatic newborn post-term. Developmental assessment should be performed in post-term newborn in case of associated pathology.The risk of perinatal complications is increased in newborn post-term in delivery room and during hospitalization. Medical team should be able to manage these complications.

The newborn infant is prone to motor phenomena of various physiological mechanisms and pathological significance whereas they can share close clinical patterns. A detailed clinical analysis, that should be supported by a video EEG recording, is necessary. That may help to distinguish myoclonus, jitteriness or seizures. Some rare phenomenom such as hyperekplexia or myotonia have also to be known. The pregnancy and birth history, the clinical examination and the search for association of various motor phenomena give essential clues for the diagnosis. Misdiagnosing non epileptic phenomona as seizures has to be avoided as it leads to unnecessary anticonvulsivant therapy with potential harmful effects.

Sneddon's syndrome is a particular and rare entity that mostly affects young women and whose diagnosis is based on the coexistence of a cuteaneous livedo and a cerebrovascular ischemic attack. It had be considered as being an expression of an occlusive vasculitis or of antiphospholipid antibody syndrome. We report the case of a 20-year-old female, who had developed a left homonymous hemianopia after ischemic encephalopathy. Visual field examination confirmed the presence of a complete left homonymous hemianopia. Cerebral Magnetic Resonance Imaging revealed right occipital cerebrovascular ischemic lesions. Sneddon's syndrome diagnosis was considered on the presence of cutaneous livedo reticularis and associated cerebral ischemic events. With medical treatment, a small functional improvement could be noticed but without net improvement in the visual field defect.

The main causes of epilepsy in children are cortical malformations (hemimegalencephaly, cortical dysplasia, lissencephaly, etc.) and phakomatosis (tuberous sclerosis, Sturge-Weber disease, neurofibromatosis type 1, etc.), perinatal ischemia, traumatisms, infections, mesial temporal sclerosis, metabolic diseases, and tumors. Imaging indications are precise, including partial seizures and a pathological electroencephalogram. Twenty-five percent of these epilepsy cases are pharmacoresistant. Indeed, MRI is essential to consider surgical treatment, allowing one to localize potential epileptogenic anatomic lesions. The protocol includes sequences in three planes of space, weighted in T1, T2, Flair, T1 inversion-recovery, and T1 after gadolinium injection. MRI findings are characteristic for some tumors, but most malformations are subtle. Consequently recent techniques (spectroscopy, diffusion, etc.) are crucial when conventional MRI is not sufficient. The aim of this article is to illustrate, with a substantive image revue, this wide diversity of etiologies in pediatric epilepsy, in order to help the attendee recognize MRI findings, also discussing the role of newer imaging modalities in this field.

Hypoxic-ischemic encephalopathy (HIE) is an important cause of acute neurologic injury at birth, affecting approximately two to three cases per 1000 full-term live births. Despite advancements in many aspects of neonatal intensive care, the outcome for infants with HIE remains poor. Interventions to improve outcomes in this population have been disappointing. The treatment of infants who have HIE is generally supportive and includes fluid and electrolytes homeostasis, correction of hypotension, and treatment of seizures. It is now known that severe hypoxia-ischemia may not necessarily cause immediate cell death, but can precipitate a complex biochemical cascade leading to the delayed neuronal loss. The key phases of injury include a latent phase after reperfusion, with initial recovery of cerebral energy metabolism, followed by a secondary phase characterized by accumulation of cytotoxins, seizures, cytotoxic edema, and failure of cerebral oxidative metabolism starting 6 to 15 h post insult. Studies designed around this conceptual framework have shown that moderate cerebral hypothermia initiated as early as possible before the onset of secondary deterioration, and continued for a sufficient duration has been associated with long-lasting neuroprotection. Three large controlled trials have demonstrated that post resuscitation cooling is generally safe and reduces death or disability at 18 months of age after neonatal encephalopathy. Hypothermia is now widely recommended as a standard of care for infants with HIE. However, national guidelines concerning regional organization and supportive care are necessary. A developmental follow-up must be organized. Neonatologists involved in this procedure must be encouraged joining a national data collection and registry.

The objective of this work is to specify, by reference to the normal newborn, the current contribution of the electroencephalogram in the hypoxic-ischemic encephalopathy of the full-term newborn. Both digitized traditional EEG and cerebral function monitoring (CFM) will be considered. We first describe the main features of normal and pathological EEGs. A good knowledge of the organization of the sleep-wakefulness cycles, in relationship with the EEG, is essential. Very early recordings (before 6 hours of life) are needed to put the indications of neuroprotective treatments (hypothermia). Between the normal or near-normal tracings, which are associated with a good prognosis, and the very pathological tracings (inactive, paroxysmal), which are associated with a poor vital or functional prognosis, the interpretation of "intermediate" tracings - mainly represented by other types of discontinuous tracings - must take into account characteristics of bursts and discontinuities, postnatal age, the evolution of successive tracings, and pharmacological treatments. A flowchart is used to illustrate our strategy of EEG watching over a full-term newborn after an acute fetal distress.

A whole-body hypothermia protocol for term infants with hypoxic-ischemic encephalopathy (HIE) was implemented in our network in May 2004. The main objective of this study was to assess the feasibility of the protocol. The impact on the outcome was also assessed.Monocentric retrospective study of all term infants admitted for HIE after the implementation of the protocol. The feasibility of the protocol was evaluated by its observance during the first 72 h. The neurodevelopmental outcome at 12 months of age of this population was compared with a historical control group.Twenty-five children were included. The protocol was not correctly applied for 8 children. The target temperature (33-34°C) was not reached for 3 infants. Four infants were admitted after 6h of age. In 1 infant, HIE was not diagnosed at admission. In the 17 patients with a good protocol observance, rectal temperature fell to the target temperature on average at 6.4h of age. The long-term follow-up rate was improved after the implementation of the protocol (100 % versus 92 % before protocol implementation). Death or neurodevelopmental disability occurred in 40 % during the protocol period versus 87 % before protocol implementation (p0.01).The main limiting factor for implementation of whole-body hypothermia in infants with HIE is admission delay. The follow-up and the rate of death or disability in infants with HIE improved after implementing the protocol.

Most of the contemporary guidelines on newborn resuscitation are based on experience but lack scientific evidence. The use of 100% oxygen is one of the more evident. Today, these practices are questioned, particularly for the resuscitation of moderately depressed full-term or near-term newborns. Results of recent meta-analysis of trials that compared ventilation with room air versus pure oxygen at birth suggest current practices should be revisited. On the basis of these data, air can be the initial gas to use for these babies. Large-scale trials, including preterm and cause and/or severity of initial asphyxia, must now be undertaken before the publication of new guidelines for these populations.

The hypothermia treatment for neonatal hypoxic ischemic encephalopathy is a concept revisited for more than 10 years. With this strategy, animal studies have shown an 80% reduction of brain damage. Conditions for the practice of hypothermia, to obtain neuroprotection, have been described in these studies: rapidity of the onset of cooling after the hypoxic ischemic event, prolonged duration during several hours, ability to obtain neuroprotection with two methods of cooling, selective head cooling or whole body hypothermia. Pilot studies in human newborns have demonstrated the feasibility of these strategies without immediate adverse effects. Two large randomised trials have been conducted in 2005 to test the efficacy. Only with the strategy of whole body cooling, the incidence of poor outcome at 18 months (death or severe disability) was statistically decreased (44% versus 66% in the control group). This reduction seems especially significant in the sub group of intermediate severity (48% versus 66%), whereas severe forms (Grade III in the Sarnat and Sarnat classification) were probably not ameliorated with this treatment. Now, the major problem is to determine the best indications for hypothermia with an early and precise assessment of the grade of the encephalopathy.

To evaluate the validity and the feasibility of fetal scalp lactate sampling during labour in the assessment of non reassuring fetal status.A prospective observational study was conducted on 129 fetal scalp blood samplings. Scalp lactate measurements were compared to scalp pH (gold standard procedure), neonatal cord blood gas (pH and lactates) and Apgar score. Pathological values taken were for scalp lactates5 mmol/l, scalp pH7.20, cord arterial pH7.10, cord arterial lactates6,35 mmol/l, and Apgar score7 at one and five minutes. All measurements were performed using the Rapid Lab 860 device from Bayer.Scalp lactate correlated significantly with scalp pH (R=-0.54, P=0.001), with umbilical artery pH (R=-0.46, P=0,01), with umbilical artery lactate (P=0.49, P=0.01), but with neither Apgar score at one minute (R=-0.21, ns) nor at 5 minutes (R=-0.11, ns). Scalp lactate at a cut-off value of 5 mmol/l had the same predictive values than scalp pH at 7.20 to predict neonatal acidosis. Sampling failure with scalp lactate was inferior to 1 vs 18% for scalp pH.The measurement of lactate in fetal blood scalp seems correlated to the fetal scalp pH. It may be an attractive alternative to pH analysis and a useful tool for monitoring fetal asphyxia, especially with the advent of handheld devices requiring small sample volumes.

Neonatal brain disorders consist of a wide chapter including brain malformations, hypoxic-ischemic encephalopathy, intracranial infections, perinatal trauma and metabolic encephalopathies. The aim of this review paper is to describe the main imaging modalities (ultrasonography, CT, MRI) that are used extensively for the diagnosis of neonatal brain disorders, with their respective advantages and limitations, to illustrate and describe the main brain lesions encountered in the neonatal period, particularly with MRI since its role has increased over the recent years. We will focus on hypoxic-ischemic encephalopathy, materno-fetal infections, metabolic encephalopathies and stroke, those four conditions being the most frequent so far. Imaging modalities, especially MRI, by showing the extent of brain damage, are part of the prognostic factors in cases of infective causes and of hypoxic-ischemic origin. MRI is also very efficient in showing brain damage as atrophy and white matter abnormalities suggestive of an underlying abnormal brain of metabolic origin.

Recruitment, work load and morbidity linked to newborn asphyxia during delivery at term: a study from Pediatric Mobile Intensive Care Units.In a population of term neonates transported by the mobile intensive care units (MICU), we aimed to determine the incidence of neonates with anoxic-ischemic encephalopathy related to asphyxia, to analyze in this population the difficulties of management, and to try to identify which of these newborns require new therapeutic strategies.This retrospective study was performed over a 2-year period (2000 and 2001) in 3 paediatric MICU from the Ile de France area. During this period, 7,648 infants were transported including 3,301 newborns of more than 36 weeks of gestational age and less than 72 hours of life. These neonates came from 73 different hospitals. Among these 3,301 infants, 237 neonates (124 boys and 113 girls) with anoxic-ischemic encephalopathy related to asphyxia were selected in the present study. Inclusion criteria were association of one obligatory criterion of fetal distress during delivery and at least one criterion of neonatal asphyxia or one criterion of anoxic-ischemic encephalopathy. Data were compiled and analyzed with Epidata package and Epi info package, respectively.These 237 neonates with anoxic-ischemic represented 12% of MICU activity at the same gestational and postnatal ages. The mean gestational age was 39.5 + 1.5 weeks. The mean birth weight was 3,188 + 559 g. More than 50% of these neonates were born in level I maternities. Fifty-three percent of the infants were born by caesarean section. Eighty-three percent of the neonates had an Apgar score at 1 minute3. Eighty-eight percent of the neonates received resuscitation care at 5 minutes of life and 34% of these had an Apgar score at 10 minutes5. In 50% of the cases, the MICUs arrived at the maternity of delivery within 1 h 45 min of life and transportation of the neonates was completed after 3 hours of life. The neonates were transported to an intensive care unit in 88% of the cases (half to a polyvalent intensive care unit and half to a neonatal intensive care unit). Forty-four percent of transported neonates had no encephalopathy, 30% had a severe encephalopathy or seizures, 27% had multiple organ failure. Mortality reached 28% and encephalopathy accounted for two thirds of these deaths. Neonates who arrived in pediatric care units after 3 hours of life had more severe morbidity than neonates who arrived before 3 hours of life.Pediatric MICUs transport the most severely affected neonates. The initial clinical state is critical, and systemic and neurological complications are frequent and severe. Calls to the MICU should be made earlier in order to enable a better impact of new neuroprotective strategies.

Perinatal asphyxia complicated by hypoxic ischemic brain injury still remains the source of neurological lesions often serious and definitive. A major aim of neonatologists is to appreciate the severity of the hypoxic ischemic brain injury in the first days of life and to evaluate the forecast. The purpose of this work is to establish a relation between clinical signs, EEG, neuroimaging (MRI and CTS) and neuro-development.26 neonates from paediatric resuscitation unit (Hospital North, Marseille) were enrolled in a retrospective study since February 1994 to December 1997. All the newborns had at least one anamnestic criteria of perinatal asphyxia, an early electroencephalogram in the first two days of life and another between the third and the seventh day of life, and neuroimaging in the first 15 days of life: CTS in five cases and MRI in 21 cases.There was a good electro-clinic (P: 0.01) and prognostic (P: 0.03) correlation in patients within stage 3 of the "Sarnat classification". In the stage 2, the EEG did not provide valuable information about severity of the injury, and neuroimaging (especially MRI) allowed better prognosis. Diffuse brain injury or lesions of basal ganglia in MRI were associated, independently of clinical settings and EEG tracings, with a poor neurodevelopmental outcome (P: 0.02). The MRI was diagnostic in four cases of congenital encephalopathy complicated with neonatal suffering.Our study confirms the interest of the association of clinical settings, EEG tracings and MRI in the diagnosis and the prognostic of the hypoxic-ischemic encephalopathy in term neonate.