Showing papers in "Neonatology in 2007"
TL;DR: Breast milk contains bifidobacteria and specific B ifidobacterium species that may promote healthy microbiota development that may predispose to disease later in life.
Abstract: Background: The establishment of gut microbiota is a stepwise process contributing to gut development and maturation of the immune system. Aberrant gut microbiota at an early age ma
252 citations
TL;DR: Normative cord serum ferritin data may permit a more precise assessment of infants who are at risk for abnormal iron status at birth, and have been implicated in neurodevelopmental impairments.
Abstract: Background: Serum ferritin measurements are used in clinical populations to estimate total body iron stores and the risk of subsequent iron deficiency or overload. The lack of norma
244 citations
TL;DR: It is suggested that lung sonography should become the first approach for imaging of neonatal respiratory distress although further prospective studies with good blinding need to be performed.
Abstract: Background: Transient tachypnea of the newborn (TTN) is a mild form of neonatal respiratory distress which early in its course needs to be differentiated from other severe respirato
203 citations
TL;DR: The measurement of TOI and FTOE by SRS correlated well with the cerebral venous saturation and FOE, respectively.
Abstract: Objective: To evaluate the relation between cerebral tissue oxygenation index (TOI), measured with spatially resolved spectroscopy (SRS), and the different oxygenation parameters. T
201 citations
TL;DR: Hair cortisol is influenced by days of ventilation in NICU term infants, a potentially valid outcome for chronic neonatal stress in these infants and warrants further investigation.
Abstract: Background: As preterm and term infants in the neonatal intensive care unit (NICU) undergo multiple stressful/painful procedures, research is required that addresses chronic stress.
171 citations
TL;DR: ABP is an age-specific phenomenon, however, more severe courses than expected for PMA or the resolution at a later PMA indicated an increased risk of neurodevelopmental disturbances at a corrected age of 13 months.
Abstract: Background: Apnea and bradycardia of prematurity (ABP) are possible risks towards damage of the developing brain. Objectives: To characterize the influence of neo
140 citations
TL;DR: A brief review focuses on the recently recognized role of angiogenic growth factors during normal alveolar development, injury and repair with a particular emphasis on the vascular endothelial growth factor.
Abstract: Since the initial description of bronchopulmonary dysplasia (BPD) 40 years ago, advances in perinatal care have allowed the survival of infants that are more immature. The disease has not disappeared, but it now affects infants with undeveloped distal airspaces, resulting in an arrest of alveolar development. The histological changes that occur during normal lung development are well described, but little is known about the signaling mechanisms that regulate saccular and alveolar development. Understanding how alveoli and the underlying capillary network develop and how these mechanisms are disrupted in preterm infants with BPD is critical to develop efficient and effective therapies for lung diseases characterized by alveolar damage. This brief review focuses on the recently recognized role of angiogenic growth factors during normal alveolar development, injury and repair with a particular emphasis on the vascular endothelial growth factor.
132 citations
TL;DR: The molecular basis and the genetic and tissue-based approaches to the evaluation of children suspected of having one of the Inherited disorders of pulmonary surfactant-associated proteins are discussed.
Abstract: Inherited disorders of pulmonary surfactant-associated proteins are rare but provide important insights into unique mechanisms of surfactant dysfunction. Recessive loss-of-function mutations in the surfactant protein-B and the ATP-binding cassette family member A3 (ABCA3) genes present as lethal surfactant deficiency in the newborn, whereas other recessive mutations in ABCA3 and dominant mutations in the surfactant protein-C gene result in interstitial lung disease in older infants and children. The molecular basis and the genetic and tissue-based approaches to the evaluation of children suspected of having one of these disorders are discussed.
114 citations
TL;DR: These laboratory studies suggest novel pharmacologic strategies for the treatment of refractory PPHN, including strategies to enhance NO-cGMP signaling.
Abstract: Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome characterized by failure of the lung circulation to achieve or sustain the normal drop in pulmonary vascular resistance (PVR) at birth. Past laboratory studies identified the important role of nitric oxide (NO)-cGMP signaling in the regulation of the perinatal lung circulation, leading to the development and application of inhaled NO therapy for PPHN. Although inhaled NO therapy has improved the clinical course and outcomes of many infants, pulmonary hypertension can be refractory to inhaled NO, suggesting the need for additional approaches to severe PPHN. To develop novel therapeutic strategies for PPHN, ongoing studies continue to explore basic mechanisms underlying the pathobiology of PPHN in experimental models, including strategies to enhance NO-cGMP signaling. Recent studies have demonstrated that impaired vascular endothelial growth factor (VEGF) signaling may contribute to the pathogenesis of PPHN. Lung VEGF expression is markedly decreased in an experimental model of PPHN in sheep; inhibition of VEGF mimics the structural and functional abnormalities of PPHN, and VEGF treatment improves pulmonary hypertension through upregulation of NO production. Other studies have shown that enhanced NO-cGMP activity through the use of cGMP-specific phosphodiesterase inhibitors (sildenafil), soluble guanylate cyclase activators (BAY 41-2272), superoxide scavengers (superoxide dismutase), and rho-kinase inhibitors (fasudil) can lead to potent and sustained pulmonary vasodilation in experimental PPHN. Overall, these laboratory studies suggest novel pharmacologic strategies for the treatment of refractory PPHN.
108 citations
TL;DR: Preliminary findings suggest that sildenafil may improve cardiac output by reducing pulmonary hypertension refractory to iNO in patients with CDH.
Abstract: Background: Pulmonary hypertension is a common problem in patients with congenital diaphragmatic hernia (CDH). In a subset of these patients, pulmonary hypertension persists despite
106 citations
TL;DR: There are sufficient data available to recommend that newborn resuscitation should not be carried out with 100% O2, and in ELBW infants, SaO2 levels should be kept between 85 and 93% or possibly between 88 and 95%, but should definitely not exceed 95%.
Abstract: Background: In recent years it has become clear that even a brief exposure to high oxygen concentration at birth and an oxygen saturation (SaO2) >93–95% in extremely low
TL;DR: The role of the blood vessels and the distinct cell populations, which are the mayor constitutive elements of the immature brain, in the pathophysiology of H-I lesion are discussed.
Abstract: Over the past decade, much has been learned about the cellular and molecular mechanisms underlying hypoxic-ischemic (H-I) injury in the preterm human brain. The pathogenesis of H-I brain injury is now
TL;DR: It is demonstrated here that LPS administration in pregnant rats at gestational day 18 and 19 induced WM injury in P7 progeny characterized by apoptosis, and especially prenatal maternal EPO treatment attenuates LPS-induced injury by reducing the expression of inflammatory cytokines and sparing MBP in the neonatal rat brain.
Abstract: Periventricular leukomalacia (PVL), a common neonatal brain white matter (WM) lesion, is frequently associated with cerebral palsy. Growing evidence has indicated that in addition to ischemia/reperfusion injury, cytokine-induced brain injury associated with maternal or fetal infection may also play an important role in the pathogenesis of PVL. Recent studies have shown that administration of lipopolysaccharide (LPS) to pregnant rats causes enhanced expression of the cytokines, i.e., IL-1 beta, TNF-alpha, and IL-6, in fetal brains. In recent years, it has been shown that erythropoietin (EPO) has a critical role in the development, maintenance, protection and repair of the nervous system. In the present study we investigated the effect of EPO on LPS-induced WM injury in Sprague-Dawley rats. LPS (500 microg/kg) suspension in pyrogen-free saline was administered intraperitoneally to pregnant rats at 18 and 19 days of gestation. The control group was treated with pyrogen-free saline. They were given 5,000 U/kg recombinant human EPO. Seven-day-old Sprague-Dawley rat pups were divided into four groups: control group, LPS-treated group, prenatal maternal EPO-treated group (5,000 U/kg, intraperitoneally given to pregnant rats at 18 and 19 days of gestation), and postnatal EPO-treated group (5,000 U/kg, intraperitoneally given to 1-day-old rat pups). Cytokine induction in the postnatal 7-day-old (P7) rat brain after maternal administration of LPS was determined by the ELISA method. The proinflammatory cytokine levels (IL-1 beta, TNF-alpha, and IL-6) in P7 rat pup brains were significantly increased in the LPS-treated group as compared with the control group. Prenatal maternal EPO treatment significantly reduced the concentration of TNF-alpha and IL-6 in the newborn rat brain following LPS injection. The concentration of IL-1 beta was decreased in the intrauterine EPO treatment group. Postnatal EPO treatment significantly decreased only the IL-6 concentration in the newborn rat brain following LPS injection. The concentration of cytokines, IL-1 beta and TNF-alpha, was reduced in the postnatal EPO treatment group. We demonstrated here that LPS administration in pregnant rats at gestational day 18 and 19 induced WM injury in P7 progeny characterized by apoptosis. Prenatal maternal and postnatal EPO treatment significantly reduced the number of apoptotic cells in the periventricular WM. Using immunohistochemistry techniques, we investigated the effects of maternal administration of LPS on myelin basic protein (MBP) staining, as a marker of myelination in the periventricular area in the neonatal rat brain. MBP staining was significantly less and weaker in the brains of the LPS-treated group as compared with the prenatal maternal EPO-treated group. However, the postnatal EPO treatment did not prevent LPS-stimulated loss of MBP-positive staining. In conclusion, especially prenatal maternal EPO treatment attenuates LPS-induced injury by reducing the expression of inflammatory cytokines and sparing MBP in the neonatal rat brain. While the postnatal EPO treatment prevented LPS-induced brain injury this effect was partial. To our knowledge, this is the first study that demonstrates a protective effect of EPO on LPS-induced WM injury in the developing brain. Regarding the wide use of EPO in premature newborns, this agent maybe potentially beneficial in treating LPS-induced brain injury in the perinatal period.
TL;DR: For the human newborn the innate immune system may have a broader significance; it may well be the key system determining the course of inflammatory events associated with premature birth, a notion that is emphasized by the recently described association between TLR polymorphisms and prematurity.
Abstract: The discovery of Toll-like receptors (TLRs) as essential components of the innate immune system has greatly advanced our knowledge and understanding of immune responses to infection and how these are regulated. Innate immunity in general and TLRs in particular play a crucial role in the front line of host defenses against microbes, but also are a key element in the proper functioning of the immune system at large in vertebrate animals. The innate immune system has been identified as a collection of factors, both cell-associated and cell-free, that comprises an impressively effective and well-organized system that is capable of immediate recognition of a whole array of microbes and microbial components. The cell-bound TLRs fulfill a central role in the process from pathogen recognition to activation of adaptive immunity. From the cell-free factors the plasma protein mannose-binding lectin (MBL) has been studied most extensively. Associations have already been documented between TLR polymorphisms in man and TLR deficiency in animals and an increased susceptibility to infection. The effect of MBL on infectious disease susceptibility only seems to emerge when host defenses are compromised by a severe underlying condition. The functional state of the various components of innate immunity at birth is largely unknown and only recently a number of studies have assessed this feature of the innate immune system. In addition, for the human newborn the innate immune system may have a broader significance; it may well be the key system determining the course of inflammatory events associated with premature birth, a notion that is emphasized by the recently described association between TLR polymorphisms and prematurity. However, there are still many open questions, particularly about the exact relation between individual TLRs and infectious disease susceptibility and how TLRs cooperate in resistance to infection and in initiating adaptive immune responses. With regard to the human newborn, the most relevant question that needs to be resolved is the precise role of innate immunity in the pathogenesis of prematurity.
TL;DR: A neonatal rat model simulates NICU stressors and enables measurement of acute physiological and long-term neurobehavioral indices and significantly increased the mortality.
Abstract: Background: During critical care in neonatal intensive care units (NICU), infants experience stressors and treatments that may produce lasting effects on adult health. An animal mod
TL;DR: Quantitative ultrasound (QUS) was first developed in 1984, as a non-ionising, portable and low cost method of assessing bone health, and preliminary studies suggest that this technique may be a useful technique of assessing changes in bone health in preterm infants, but the data need to be interpreted carefully.
Abstract: For a number of reasons there is a need to explore reliable non-invasive methods for assessing bone health in neonates and young infants. Epidemiological studies suggest that early events in life may predispose the adult to degenerative diseases such as osteoporosis. Preterm infants have an increased risk of low bone mass because of limited bone mass accretion in utero and a greater need for bone nutrients. Despite improvements in neonatal care fractures still occur. The diagnosis of osteopaenia of prematurity remains difficult as there is no screening test which is both sensitive and specific. Biochemical indices are non-diagnostic, and plain X-rays in the absence of fractures are poor at diagnosing bone disease. Although dual energy X-ray absorptiometry is increasingly used to assess bone mineral status in newborn infants, the size and immobility of the scanner, the length of time to perform the scan and use of ionising radiation make it unsuitable for routine use in the setting of the fragile very low birth weight infant. Quantitative ultrasound (QUS) was first developed in 1984, as a non-ionising, portable and low cost method of assessing bone health. The measurements obtained from QUS are thought to be related not only to the mineral density of the bone but also to reflect parameters of bone quality and strength. Preliminary studies suggest that this technique may be a useful method of assessing changes in bone health in preterm infants, but the data need to be interpreted carefully. This review will concentrate on the methodology of QUS and the studies that have already been performed in neonates.
TL;DR: Recent research developments with peptide analogues of SP-B and SP-C, designed using either the known primary sequence and three-dimensional (3D) structure of the native proteins or, alternatively, the known 3D structures of closely homologous proteins are reviewed.
Abstract: Lung surfactant is a complex mixture of phospholipids and four surfactant-associated proteins (SP-A, SP-B, SP-C and SP-D). Its major function in the lung alveolus is to reduce surface tension at the a
TL;DR: This pilot study of a portable NIRS device shows encouraging efficacy in identifying ELBW infants who were likely to benefit from early echocardiography and subsequent intervention to close a PDA.
Abstract: Background: Patent ductus arteriosus (PDA) is frequent and potentially pathologic in preterm infants. A simple bedside tool to screen for ductal patency would assist in the care of extremely low birth weight (ELBW) infants. Objective: To investigate the utility of near-infrared spectroscopy (NIRS) in identifying ELBW infants who would benefit from early echocardiography. Methods: Tissue oxygen saturation (StO2) was measured by NIRS in the lungs, brain, skeletal muscle and kidney of 20 ELBW infants. Comparisons were made between the StO2 in these organs and the need for intervention for a PDA. All studies were performed within the first 4 days of life. Similar measurements were performed following treatment with indomethacin in nine of the patients. Results: The StO2 of skeletal muscle (left deltoid) and kidney differed between the infants who were treated for PDA and those who were not (p = 0.01 for both). As a screen for a PDA requiring intervention, deltoid StO2 had sensitivity 77% and specificity 83%, and kidney StO2 had sensitivity 85% and specificity 83%. Following treatment with indomethacin, the low StO2 in the deltoid and kidney increased toward the range seen in patients who did not require treatment of a PDA. Inter- and intra-observer variability ranged from minimal to high. Conclusion: This pilot study of a portable NIRS device shows encouraging efficacy in identifying ELBW infants who were likely to benefit from early echocardiography and subsequent intervention to close a PDA. Further study is warranted.
TL;DR: PAV safely maintains gas exchange at lower mean airway pressures compared with PTV without adverse effects in this population of preterm infants, and conventional ventilation breaths must be provided to prevent apnea-related desaturations.
Abstract: Background: Refinement of ventilatory techniques remains a challenge given the persistence of chronic lung disease of preterm infants. Objective: To test the hypo
TL;DR: Repeated treatment of newborn rats with high-dose rEpo was safe under all conditions tested and prevented the learning impairment and dopamine neuron loss due to unilateral hypoxic-ischemic brain injury.
Abstract: Background: High-dose recombinant erythropoietin (rEpo) is neuroprotective in neonatal animal models of brain injury, but the long-term consequences of neonatal exposure have not be
TL;DR: High-dose hydrocortisone prophylaxis improved O2-free survival and early cardiocirculatory function in the population, without important short-term effects.
Abstract: Background: Several reports indicate a decreased cortisol response to adrenocorticotropic hormone in preterm infants developing chronic lung disease and in preterm infants with refr
TL;DR: It was shown that this breast milk mucin inhibits poxvirus activity by 100% using an inhibition assay with a viral concentration of 2.4 million plaque-forming units/ml.
Abstract: Human breast milk is known to contain numerous biologically active components which protect breast fed infants against microbes, viruses, and toxins. The purpose of this study was to purify and characterize the breast milk mucin and determine its anti-poxvirus activity. In this study human milk mucin, free of contaminant protein and of sufficient quantity for further analysis, was isolated and purified by Sepharose CL-4B gel filtration and cesiumchloride density-gradient centrifugation. Based on the criteria of size and appearance of the bands and their electrophoretic mobility on sodium dodecyl sulfate polyacrylamide-gel electrophoresis, Western blotting together with the amino acid analysis, it is very likely that the human breast milk mucin is MUC1. It was shown that this breast milk mucin inhibits poxvirus activity by 100% using an inhibition assay with a viral concentration of 2.4 million plaque-forming units/ml. As the milk mucin seems to aggregate poxviruses prior to their entry into host cells, it is possible that this mucin may also inhibit other enveloped viruses such as HIV from entry into host cells.
TL;DR: The induction of early meconium evacuation had a significantly positive effect on feeding tolerance and sepsis prevention in VLBWI.
Abstract: Background: A delay in reaching full enteral feeding is linked to poorer outcome in preterm neonates. Meconium retention has been viewed as a cause of bowel dysfunction in very low birth weight infants (VLBWI). Thus, adequate evacuation of meconium could help to promote feeding tolerance. Objectives: Our goal was to determine the effect of the induction of early meconium evacuation on feeding tolerance in VLBWI. Methods: An observational study involving two subsequent periods was performed in inborn infants with birth weights of Results: The study group achieved full enteral feeding significantly faster than the control group (hazard ratio (HR) = 2.9; 95% confidence interval (CI) = 1.8–4.8), and this effect was more definite in infants with a birth weight of Conclusions: The induction of early meconium evacuation had a significantly positive effect on feeding tolerance and sepsis prevention in VLBWI.
TL;DR: A 622-gram birth weight male infant of 23 weeks’ gestation who had sepsis-like syndrome and pneumonia is reported who had transient hearing impairment, and his neurodevelopmental outcome of 30 months of corrected age was normal.
Abstract: Several studies have reported that postnatally acquired cytomegalovirus (CMV) infection can cause sepsis-like syndrome in premature infants. We here report a 622-gram birth weight male infant of 23 we
TL;DR: Distressed fetuses delivered by emergency cesarean exhibited increased malondialdehyde concentrations, an indicative parameter for oxidative damage, and enhanced GPX activity an antioxidant enzyme, in amniotic fluid and umbilical cord blood compared to non-distressed fetus delivered by elective cesar section, probably an indication of higher fetal oxidative stress.
Abstract: Background: Several studies have addressed the influence of labor and mode of delivery on oxidative stress. Still it is unclear whether oxidative stress is related to delivery itself or whether it reflects a pre-existing fetal oxidative status. Objective: To investigate whether the degree of fetal oxidative stress is different between distressed fetuses that were delivered by emergent cesarean section and non-distressed fetuses that were delivered by elective cesarean section. Methods: The protocol of this prospective study was approved by the Institutional Review Board Committee. Amniotic fluid and umbilical artery blood were prospectively collected from 21 parturients who were delivered by an emergent cesarean section for non-reassuring fetal heart rate pattern and from 21 parturients who were delivered by an elective cesarean section in a tertiary care center. Oxidative stress was evaluated in amniotic fluid, umbilical cord plasma and erythrocytes by determining malondialdehyde concentration and glutathione peroxidase (GPX) activity. Results: Malondialdehyde concentration was higher in amniotic fluid (mean ± SEM) (2.2 ± 0.7 nmol/l vs. 0.6 ± 0.02 nmol/l, p Conclusion: Distressed fetuses delivered by emergency cesarean exhibited increased malondialdehyde concentrations, an indicative parameter for oxidative damage, and enhanced GPX activity an antioxidant enzyme, in amniotic fluid and umbilical cord blood compared to non-distressed fetuses delivered by elective cesarean section. This is probably an indication of higher fetal oxidative stress.
TL;DR: In preterm infants, with the administration of probiotics, 37% of the pre term infants had Lactobacillus colonized in the gastrointestinal tract and improved feeding tolerance with a tendency towards an increased incidence of sepsis.
Abstract: Background: Probiotics are live microbes that colonize the gastrointestinal tract and benefit the host. Preterm infants develop abnormal patterns of bowel colonization, and only a few clinical trials have reported the outcomes of preterm infants treated with probiotics. Purpose: We investigated the rate of colonization of Lactobacillus and the clinical variables affecting the colonization in preterm infants. Methods: Infants with gestational age less than 37 weeks treated at Ewha Womans University Hospital between March 2003 and July 2004 were eligible. Lactobacillus acidophilus (containing 108 CFU) was supplemented orally, mixed with breast milk or formula divided into three doses a day. Stool samples were collected before and 14 days after supplementation of the probiotic. Stool samples were anaerobically cultured on Rogosa agar and identified by Gram stain, catalase test and glucose fermentation test. Clinical characteristics were analyzed. Results: Seventy-three patients with an average gestational age of 33.0 ± 2.5 weeks were studied. Meconium was cultured in 46 patients and Lactobacillus was not detected. Probiotic supplementation began on 3.4 ± 6.8 days, and after 14 days of supplementation, Lactobacillus was cultured in an average of 3.01 × 108 CFU in the stool of 37.0% (27/73) of the patients. There was a tendency towards an increased incidence of sepsis in the Lactobacillus– group (p = 0.082). In the Lactobacillus+ group, a striking increase in feeding tolerance was detected. Conclusion: In preterm infants, with the administration of probiotics, 37% of the preterm infants had Lactobacillus colonized in the gastrointestinal tract and improved feeding tolerance. A double-blind study is in progress for further investigation into the effect on other systemic diseases in premature infants.
TL;DR: Minocycline 50 mg/kg 15 min prior to an intervention that normally produces acute bilirubin neurotoxicity is neuroprotective in jaundiced Gunn rat pups, and this model provides an efficient in vivomodel to screen and evaluate new agents that are neuroProtective against bilirUBin toxicity and kernicterus.
Abstract: Background: Extreme hyperbilirubinemia is treated with double volume exchange transfusion, which may take hours to commence. A neuroprotective agent that could be administered immed
TL;DR: It is suggested that intermittent hypoxia associated with hyperoxia-induced lung injury, but not lung injury itself, results in significant neurological handicap in neonatal mice with BPD.
Abstract: Bronchopulmonary dysplasia (BPD) is considered by many to be an independent risk factor for poor neurodevelopment in premature infants. However, infants with BPD experience intermittent hypoxic episodes. This study was undertaken to determine whether intermittent hypoxic stress associated with BPD contributes to the development of neurological deficit. The model of BPD was produced in neonatal mice by exposure to hyperoxia (65% O(2)) for 4 weeks. Arterial blood gases, pulmonary mechanics, and histopathology were used to define the degree of lung injury. The mice were subjected to brief (10 min/day) and intermittent (10 days) hypoxic stress (8% O(2)) at different stages of the development of hyperoxia-induced lung injury. At 8 weeks of life, the neurofunction was assessed by water maze and rota-rod tests followed by cerebral morphological analysis using Nissl, bromodeoxyuridine, and caspase-3 immunostaining. Data were compared to naive normoxic littermates and those mice that were exposed only to hyperoxia or intermittent hypoxia alone. Mice with BPD subjected to brief/intermittent hypoxia demonstrated a significantly poorer navigational memory performance as compared with normoxic mice and mice with BPD that were not subjected to intermittent hypoxia. The neurofunctional handicap in these mice was associated with significantly decreased brain weight and increased cerebral expression of caspase-3. Our results suggest that intermittent hypoxia associated with hyperoxia-induced lung injury, but not lung injury itself, results in significant neurological handicap in neonatal mice with BPD.
TL;DR: In newborns of low birthweight, high melatonin concentrations in the morning and during the first week of life are reported, which seem to derive from extrapineal sources, which mature to provide antioxidant protection in accordance with other elements of the antioxidant network to compensate for the high levels of oxidative stress that are present in the perinatal period.
Abstract: Aim: Melatonin is a potent free radical scavenger and an indirect antioxidant. Knowledge about the behavior of melatonin secretion in the early neonatal period, which may relate to
TL;DR: In SGA infants, hs-CRP concentrations are higher than in AGA neonates suggesting the presence of an inflammatory process in this group of patients during the fetal life, which could be involved in the previously reported relationship between low birth weight and cardiovascular disease in adult life.
Abstract: Background: Several epidemiological studies reported a significant correlation between low birth weight and cardiovascular disease in adult life. Recent studies showed that an infla