[Neonatal medicine, past and present].

This review deals with early neonatal medicine and its rapid development as a medical specialty, starting with the birth of neonatology in the early 19th century. Shaffer first used the term neonatology in 1963 to cover neonatal disorders and their treatment. Between the early 19th century and the 1950s, neonatal care was ensured by obstetricians, whose main goal was to reduce neonatal mortality.

[Folates and fetal programming: role of epigenetics and epigenomics].

Folates are needed for synthesis of methionine, the precursor of S-adenosyl methionine (SAM). They play therefore a key role in nutrition and epigenomics by fluxing monocarbons towards synthesis or methylation of DNA and RNA, and methylation of gene transregulators, respectively. The deficiency produces intrauterine growth retardation and birth dejects.

Non-injurious neonatal hypoxia confers resistance to brain senescence in aged male rats.

Whereas brief acute or intermittent episodes of hypoxia have been shown to exert a protective role in the central nervous system and to stimulate neurogenesis, other studies suggest that early hypoxia may constitute a risk factor that influences the future development of mental disorders. We therefore investigated the effects of a neonatal "conditioning-like" hypoxia (100% N₂, 5 min) on the brain and the cognitive outcomes of rats until 720 days of age (physiologic senescence). We confirmed that such a short hypoxia led to brain neurogenesis within the ensuing weeks, along with reduced apoptosis in the hippocampus involving activation of Erk1/2 and repression of p38 and death-associated protein (DAP) kinase.

Conditioning-like brief neonatal hypoxia improves cognitive function and brain tissue properties with marked gender dimorphism in adult rats.

Although recent studies have documented compensatory generation of neurons in adult brains in response to various insults, a noninjurious short episode of hypoxia in rat neonates has been shown to trigger neurogenesis within the ensuing weeks, without apparent brain lesions. Very little is known of the long-term consequences. We therefore investigated the effects of such a conditioning-like hypoxia (100% N(2), 5 min) on the brain and the cognitive outcomes of rats at 40 to 100 days of age.

[Infants of drug-addicted mothers: pitfalls of replacement therapy].

Maternal drug addiction can cause problems for the fetus and the newborn, and hamper long-term development. The prevalence of drug addiction during pregnancy varies from 1 % to more than 10 % depending on the country and the maternity unit. Management of these mothers can be further complicated by medical, social and psychological problems.

[Cell death and neurogenesis after hypoxia: a brain repair mechanism in the developing rat?].

Perinatal brain damage following hypoxia-ischemia has long been considered irreversible, but recent rodent studies show that various insults can induce de novo neurogenesis in the adult brain. Here we examined whether acute hypoxia could trigger neurogenesis in the developing rat brain. In vitro, we examined the impact of transient hypoxia on cultured embryonic rat neurons.

Apoptosis and neurogenesis after transient hypoxia in the developing rat brain.

Perinatal brain damage following a hypoxic-ischemic episode has been considered for a long time as an irreversible phenomenon. However, recent studies have shown that various insults may induce de novo neurogenesis in the adult rodent brain. The present study tested the hypothesis that acute hypoxia may trigger neurogenesis in the developing brain.

Differential neuronal fates in the CA1 hippocampus after hypoxia in newborn and 7-day-old rats: effects of pre-treatment with MK-801.

The brain displays an age-dependent sensitivity to ischemic insults. However, the consequences of oxygen deprivation per se in the developing brain remain unclear, and the role of glutamate excitotoxicity via N-methyl-D-aspartate (NMDA) receptors is controversial. To gain a better understanding of the mechanisms involved in the cerebral response to severe hypoxia, cell damage was temporally monitored in the CA1 hippocampus of rat pups transiently exposed to in vivo hypoxia (100% N2) at either 24 h or 7 days of age.

Neonatal hypoxia triggers transient apoptosis followed by neurogenesis in the rat CA1 hippocampus.

Continuous generation of new neurons has been demonstrated in the adult mammalian brain, and this process was shown to be stimulated by various pathologic conditions, including cerebral ischemia. Because brain oxygen deprivation is particularly frequent in neonates and represents the primary event of asphyxia, we analyzed long-term consequences of transient hypoxia in the newborn rat. Within 24 h after birth, animals were exposed to 100% N(2) for 20 min at 36 degrees C, and temporal changes in the vulnerable CA1 hippocampus were monitored.

Histopathological alterations and functional brain deficits after transient hypoxia in the newborn rat pup: a long term follow-up.

To assess temporal brain deficits consecutive to severe birth hypoxia, newborn rats were exposed for 20 min to 100% N2. This treatment induced a long-term growth retardation and a delayed, but only transient, neuronal loss (approximately 25%) in the CA1 hippocampus and parietal cortex, starting from 3 days and peaking at 6 days post-hypoxia. The expression profiles of various apoptosis-regulating proteins (including Bcl-2, Bax, p53 and caspase-3) were well correlated to the alterations of nuclear morphology depicted by 4,6-diamidino-2-phenylindole (DAPI).

Combined effects of bilirubin and hypoxia on cultured neurons from the developing rat forebrain.

Hyperbilirubinemia and hypoxia are common causes of brain injury in the newborn. To determine the effects of free bilirubin associated with transient hypoxia on developing rat neurons, the cells were exposed to bilirubin (0.25 to 5 micromol/L) and/or to hypoxia for 3 or 6 hours (95% N2-5% CO2).

[The toxicity of bilirubin to the central nervous system].

Whatever the causes of its accumulation, excessive production and/or insufficient elimination, unconjugated bilirubin when it reaches a certain concentration threshold, is responsible for neurones and astrocytes death. In this paper the mechanisms involved in this process of cellular death, from hemolysis to oxydation in neurons and neuroglial cells, are reviewed.

[Combined neuronal toxicity of bilirubin and hypoxia. Study of cultured rat neurons].

Unlabelled: Clinical observations suggest that bilirubin encephalopathy is often seen in newborn infants presenting not only with hyperbilirubinemia but also with alterations in oxygen transport like in severe anaemia. Since bilirubin and hypoxia have been shown to be detrimental to the central nervous system, the present study was designed to test the additional effects of the two insults on the outcome of cultured neurons from the forebrain of 14 day-old embryos. After 6 days in vitro, neurons were exposed either to bilirubin (0.

Intracellular generation of free radicals and modifications of detoxifying enzymes in cultured neurons from the developing rat forebrain in response to transient hypoxia.

To address the influence of oxidative stress and defense capacities in the effects of transient hypoxia in the immature brain, the time course of reactive oxygen species generation was monitored by flow cytometry using dihydrorhodamine 123 and 2',7'-dichlorofluorescein-diacetate in cultured neurons issued from the fetal rat forebrain and subjected to hypoxia/reoxygenation (6 h/96 h). Parallel transcriptional and activity changes of superoxide dismutases, glutathione peroxidase and catalase were analyzed, in line with cell outcome. The study confirmed hypoxia-induced delayed apoptotic death, and depicted increased mitochondrial and cytosolic productions of free radicals (+30%) occurring over the 48-h period after the restoration of oxygen supply, with sequential stimulations of superoxide dismutases.

Transcutaneous bilirubin measurement: a multicenter evaluation of a new device.

Objectives: The early discharge of neonates from hospitals makes transcutaneous measurement of total bilirubin concentration a useful tool to monitor neonatal jaundice. The objectives of this study were to determine whether 1) transcutaneous bilirubin (TcB) measurement, as performed using BiliCheck (BC), correlates with total serum bilirubin (TSB) levels, measured with standard laboratory methods and with high-pressure liquid chromatography (HPLC-B); 2) infant race, gestational age, postnatal age, or body weight interferes with the measurement of TcB levels in newborn infants; 3) the variability of the TcB measurement is comparable to the variability of TSB measurements; and 4) TcB measurements obtained from the forehead (BCF) and sternum (BCS) generate comparable results.

Study Design: Newborn infants who were <28 days and >30 weeks' gestational age and who underwent tests for TSB as part of their normal care in 6 different European hospitals were studied.

Bilirubin exerts additional toxic effects in hypoxic cultured neurons from the developing rat brain by the recruitment of glutamate neurotoxicity.

Both hypoxia and bilirubin are common risk factors in newborns, which may act synergistically to produce anatomical and functional disturbances of the CNS. Using primary cultures of neurons from the fetal rat brain, it was recently reported that neuronal apoptosis accounts for the deleterious consequences of these two insults. To investigate the influence of hypoxia, bilirubin, or their combination on the outcome of neuronal cells of the immature brain, and delineate cellular mechanisms involved, 6-d-old cultured neurons were submitted to either hypoxia (6 h), unconjugated bilirubin (0.

Bilirubin induces apoptosis via activation of NMDA receptors in developing rat brain neurons.

Increased amounts of bilirubin, the end product of heme degradation, are known to be detrimental to the central nervous system, especially in preterm newborns. In an attempt to delineate the cellular mechanisms by which unconjugated bilirubin exerts its toxic effects on neuronal cells in the developing brain, bilirubin (0.25-5 microM) was added to the extracellular medium of 6-day-old primary cultured neurons from the embryonic rat forebrain, and cell alterations were studied over the ensuing 96 h.

[Efficacy and limits of rescue high-frequency oscillatory ventilation in the treatment of hyaline membrane disease in preterm newborns].

Unlabelled: Conflicting reports of high-frequency oscillatory ventilation (HFOV) use as an alternative to conventional mechanical ventilation have been published. This retrospective study has evaluated the efficacy and safety of rescue HFOV in preterm infants with severe hyaline membrane disease (HMD) after the failure of conventional mechanical ventilation (CMV).

Population And Methods: All newborns hospitalized in our neonatal intensive care unit (NICU) from 10.

Severe side effects and drug plasma concentrations in preterm infants treated with doxapram.

A high-performance liquid chromatography method has been developed for simultaneous determination of doxapram and its metabolites including ketodoxapram, the main and only active metabolite. The aim of the study was to evaluate this microtechnique and to report the cases involving severe adverse effects to determine toxic plasma levels in neonates. The method was found to be selective, and showed a good baseline separation of doxapram and metabolites.

[Physiopathology of neonatal hyperbilirubinemia].

The most important steps of bilirubin metabolism involved in the pathophysiology of neonatal hyperbilirubinemia are: 1) hemoglobin degradation by heme oxygenase; 2) bilirubin binding to serum albumin; 3) bilirubin conjugation to acid glucoronic by glucoronyl transferase. Progress in the knowledge of these metabolic steps allows to understanding of why massive hemolysis, infections, hypoxia and prematurity increase the risk of kernicterus and therefore justify adapted preventive and therapeutic measures.

Cerebral metabolic consequences of neonatal pathologies in the immature rat.

The cerebral metabolic consequences of hypoxia, seizures and hyperbilirubinemia were explored in immature rates between the postnatal age of 10 (P10) and 21 days (P21) by the quantitative autoradiographic [14C]2-deoxyglucose technique. The effects of a previous bilirubin exposure on cerebral regional permeability to bilirubin were measured by autoradiography. Hypoxia was induced by breathing a 7% N2/93% O2 gas mixture and seizures were initiated by injections of pentylenetetrazol.