Biology of the Neonate

BACKGROUND: Tumor necrosis factor (TNF) is a central mediator of sepsis. The NcoI polymorphism within the TNF locus has been described as a prognostic marker for mortality in adult patients with sepsis. OBJECTIVES: The aim of our study was to investigate the genotype and allele distribution of 2 TNF gene polymorphisms in preterm infants <32 weeks of gestational age, who developed early-onset sepsis. METHODS: A double-blinded retrospective cohort study was carried out on stored Guthrie blood spot cards with group A including 67 premature infants <32 weeks of gestational age with proven early-onset sepsis and group B including 102 healthy newborn infants (>32 + 0 weeks of gestation)...

OBJECTIVE: To measure blood and cerebrospinal fluid (CSF) uric acid (UA) levels of neonates with intraventricular hemorrhage (IVH), and to examine whether or not UA can be used to differentiate traumatic tap from IVH. MATERIAL AND METHODS: The control group (n = 19, group I) consisted of neonates presenting with signs requiring analysis of CSF but whose CSF indices proved to be normal. Traumatic taps (n = 15, group II) were mimicked by adding 2 drops of homologous blood to normal CSF samples...

BACKGROUND: Allopregnanolone is a neurosteroid produced in the brain that can alter the excitability of the CNS. Neurosteroids have neuroprotective properties, and their elevation in response to stress may protect the newborn brain following infection or hypoxia. Infection, particularly of the respiratory tract, may lead to episodes of hypoxia. Infection and hypoxia have been identified as factors contributing to neonatal morbidity and mortality. OBJECTIVES: To determine the effect of acute episodes of hypoxia alone or in combination with lipopolysaccharide (LPS) exposure on plasma and brain allopregnanolone concentrations in lambs 10-21 days old...

BACKGROUND: Among newborns who die, those who have cerebral white matter damage are more likely than others to have thymus involution and low thymus weights. OBJECTIVE: We sought to evaluate in a population of preterm newborns who did not die if those who developed a cerebral white matter damage (as defined by an echolucency) are more likely than others to have thymus involution as assessed on chest radiographs. METHOD: The 89 infants whose data were evaluated were born before the 28th week of gestation, had at least one chest radiograph within the first 2 days of life (to determine thymus size), and at least one cranial ultrasonogram to assess for white matter echolucency...

BACKGROUND: Advances in neonatal intensive care have led to an increased survival of very low birth weight (VLBW, <1,500 g) and extremely low birth weight infants (ELBW, <1,000 g). Several abnormalities may occur in these children, e.g. esophageal atresia (EA), imperforate anus or abdominal wall defects. Correction of EA is often performed as a staged procedure in this group of patients. OBJECTIVES: To evaluate the feasibility of a primary correction of EA in 4 ELBW and VLBW infants...

This paper briefly reviews the systemic and pulmonary hemodynamic actions of the most frequently used vasopressor-inotropes and inotropes in the preterm and term neonate. It is important to note that very little is known about the medium- and long-term cardiovascular and neurodevelopmental benefits of the use of these medications in the neonate.

Animal-derived surfactant preparations are very effective in the treatment of premature infants with respiratory distress syndrome but they are expensive to produce and supplies are limited. In order to widen the indications for surfactant treatment there is a need for synthetic preparations, which can be produced in large quantities and at a reasonable cost. However, development of clinically active synthetic surfactants has turned out to be more complicated than initially anticipated. The hydrophobic surfactant proteins, SP-B and SP-C, which are involved in the adsorption of surface-active lipids to the air-liquid interface of the alveoli and increase alveolar stability, are either too big to synthesize, structurally complex or unstable in pure form...

A patent ductus arteriosus (PDA) results in increased pulmonary blood flow and redistribution of flow to other organs. Several co-morbidities (i.e., necrotizing enterocolitis, intracranial hemorrhage, pulmonary edema/hemorrhage, bronchopulmonary dysplasia, and retinopathy) are associated with the presence of a PDA, but whether or not a PDA is responsible for their development is still unclear. In this review, comparative physiology between the full term and preterm newborn and the barriers preventing the necessary cascade of events leading to permanent constriction of the PDA are reviewed...

OBJECTIVE: To search for recent clinical trials of neonatal surfactant treatment and report their findings. METHODS: Recent was defined as published between 2000 and 2005. An online search on PubMed was made on 30th December 2005 using the following terms: surfactant treatment, clinical trials and neonate, with limits of years 2000 to 2005 and age - newborn from birth to 1 month. Randomised clinical trials (RCTs) and systematic reviews of RCTs were prioritised and studies in children and animals were excluded from further analysis...

The human lung is born with a fraction of the adult complement of alveoli. The postnatal stages of human lung development comprise an alveolar stage, a stage of microvascular maturation, and very likely a stage of late alveolarization. The characteristic structural features of the alveolar stage are well known; they are very alike in human and rat lungs. The bases for alveolar formation are represented by immature inter-airspace walls with two capillary layers with a central sheet of connective tissue. Interalveolar septa are formed by folding up of one of the two capillary layers...

BACKGROUND: Recent improvements in the survival of extremely preterm infants have been accompanied by evolution in the pathogenesis and histopathology of bronchopulmonary dysplasia (BPD). Although oxygen and barotrauma-induced injury remain important contributing factors, pulmonary developmental arrest appears to play an equally important causal role in prolonged respiratory illness, especially among the most immature surviving preterm newborns. To date, clinical trials have failed to demonstrate a substantial benefit of a single treatment or preventive strategy for BPD...

Surfactant is now standard of care for infants with respiratory distress syndrome. Surfactant treatments are effective because of complex metabolic interactions between surfactant and the preterm lung. The large treatment dose functions as substrate; it is taken up by the preterm lung and is reprocessed and secreted with improved function. The components of the treatment surfactant remain in the preterm lung for days. If lung injury is avoided, then surfactant inhibition is minimized. Prenatal corticosteroids complement surfactant to further enhance lung function...

With the technical progress made in fetal and neonatal intensive care, perinatal mortality has decreased by 25% over the last decade and has expanded the surviving premature population. Prematurity drastically changes the environment of the developing organism. Striking evidence from a number of disciplines has focused attention on the interplay between the developing organism and the circumstances in which it finds itself. The environmental event during a sensitive period in development, induces injury and/or biological adaptations that lead to altered differentiation of tissues...

BACKGROUND AND OBJECTIVES: Different types of surfactant preparations were shown not to exert uniform response in preterm infants suffering from respiratory distress syndrome (RDS). Therefore, the effects of a recombinant surfactant protein C (rSP-C) based preparation and a natural surfactant were compared applying different levels of positive end-expiratory pressure (PEEP) in experimental RDS. METHODS: Preterm rabbits (n = 7-14 per group; 27 days gestation; term 30 days) were randomized for receiving either 100 mg/kg rSP-C or natural bovine surfactant and were compared with saline treated controls...

INTRODUCTION: An apparent re-emergence of kernicterus has been recently reported, with some cases occurring in otherwise healthy breastfed newborn. METHODS: We describe a case of kernicterus in a term Caucasian newborn. RESULTS: An exceptional polymorphism of UGT1A1 gene promoter co-existed with asymptomatic inherited spherocytosis, due to erythroid anion exchange (band-3) deficiency. Both concurred to the development of severe neonatal hyperbilirubinaemia...

BACKGROUND: Many neonatal diseases have been associated with oxidative stress and altered nitric oxide status. OBJECTIVE: To determine the effects of clinical interventions on the levels of urinary peroxides, a marker of oxidative stress, and urinary nitrate/nitrites, indices of nitric oxide production and metabolism, in the first 72 h of life in premature infants. METHODS: A single, spot urine sample was collected from 82 premature and 20 healthy term infants within the first 72 h of life...

BACKGROUND: Elevated blood lactate levels are common in the critically ill neonate; however, sometimes they are difficult to interpret. Persistent or recurrent lactic acidemia might point to an inborn error of metabolism, like disturbances of the oxidative phosphorylation. Chronic lactic acidemia results in increased serum alanine levels. Serum alanine levels in newborns with transient lactic acidemia have not yet been studied. OBJECTIVE: We designed a pilot study to evaluate the use of serum alanine levels as an additional metabolic marker to differentiate the transient effect of circulatory failure from a possible mitochondrial dysfunction...

The viability of the human fetus increases significantly beyond 25 weeks' gestation as the lung development progresses towards the 'saccular' stage. We report on a fetus of 22 weeks' gestation whose lung maturation was accelerated by 4 weeks, most likely due to the unintentional exposure to the retinoid isotretinoin (13-cis-retinoic acid) during pregnancy. Although retinoids are known to be stored within the lungs and to play a key role in lung differentiation and growth, their storage within the lung is limited during this critical developmental period...

BACKGROUND: Midazolam sedation and morphine analgesia are commonly used in ventilated premature infants. OBJECTIVES: To evaluate the effects of midazolam versus morphine infusion on cerebral oxygenation and hemodynamics in ventilated premature infants. METHODS: 11 patients (GA 26.6-33.0 weeks, BW 780-2,335 g) were sedated with midazolam (loading dose 0.2 mg/kg, maintenance 0.2 mg/kg/h) and 10 patients (GA 26.4-33.3 weeks, BW 842-1,955 g) were sedated with morphine (loading dose 0...

BACKGROUND: Tenascin-C (TN-C), an extracellular matrix glycoprotein, is crucial to cell-migration, proliferation, apoptosis and remodeling of tissues, with a potential role in pathobiology of pulmonary hypertension. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are crucial to the integrity of the extracellular matrix. TN-C and MMPs are counter-regulatory molecules, which influence the vascular integrity through modulations of elastin. We have a murine model of pulmonary hypoplasia with coexistent diaphragmatic hernia, vascular abnormalities and excessive arterial smooth muscle cell (SMC) proliferation...