Elke Kuypers

Elke Kuypers
Maastricht University | UM · Department of Paediatrics

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36
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Publications

Publications (36)
Article
Full-text available
Background Poractant alfa (Curosurf®) and Bovactant (Alveofact®) are two animal-derived pulmonary surfactants preparations approved for the treatment of neonatal respiratory distress syndrome (nRDS). They differ in their source, composition, pharmaceutical form, and clinical dose. How much these differences affect the acute pulmonary response to tr...
Article
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Term and near-term infants are at high risk of developing brain injury and life-long disability if they have suffered from severe perinatal asphyxia. We hypothesized that propofol administration to the maternal-fetal unit can diminish cerebral injury in term and near-term infant fetuses in states of progressive severe asphyxia. Forty-four late pret...
Article
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Hyperoxia and hypoxia influence morbidity and mortality of preterm infants. Automated closed-loop control of the fraction of inspired oxygen (FiO2) has been shown to facilitate oxygen supplementation in the NICU, but has not yet been tested during preterm resuscitation. We hypothesized that fully automated FiO2 control based on predefined oxygen sa...
Article
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Surfactant replacement therapy is the gold standard treatment of neonatal respiratory distress (RDS). Nebulization is a non-invasive mode of surfactant administration. We administered Poractant alfa (Curosurf) via a vibrating perforated membrane nebulizer (eFlow Neonatal Nebulizer) to spontaneously breathing preterm lambs during binasal continuous...
Article
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Objective: To better understand the inflammatory response in the central nervous system (CNS) after lipopolysaccharide (LPS)-induced chorioamnionitis. Study design: Fetal sheep were exposed to intra-amniotic LPS 2 or 14 days before preterm delivery at 125 days of gestation. mRNA levels of cytokines, TLRs and anti-oxidants were determined in diff...
Article
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Background Intra-uterine inflammation activates the fetal immune system and can result in organ injury and postnatal complications in preterm infants. As the spleen is an important site for peripheral immune activation, we asked how the fetal spleen would response to intra-uterine inflammation over time. We hypothesized that intra-amniotic lipopoly...
Article
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Background Oxygen under- and overexposure has detrimental effects on preterm infants. Controlling the oxygen saturation manually within strict targets is a notoriously difficult and time consuming task which can be facilitated by automated control. Aims To evaluate the performance of a closed loop fraction of inspired oxygen (FiO2) controller based...
Article
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Background and aims Preterm infants are prone to hypoxic-ischaemic encephalopathy. No therapy exists to treat this brain injury. The objective of this study was to assess the neuroprotective effect of exogenous administration of stem cells and the mobilisation of endogenous stem cells in the ovine preterm brain after global hypoxia-ischemia. Method...
Article
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Background: A new technique was proposed to administer surfactant to spontaneous breathing preterm infants by placing a thin catheter through the vocal cords. This technique was not studied with respect to oxygenation, gas exchange, surfactant distribution, and lung mechanics. We tested the technique of less-invasive surfactant administration (LIS...
Article
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Background: Intra-amniotic lipopolysaccharide (LPS) exposure may affect neonatal outcome by altering fetal lung and immune system development. We hypothesized that intra-amniotic LPS exposure would cause persistent fetal pulmonary responses as the lungs develop in utero. Methods: Fetal lambs were exposed to intra-amniotic LPS at 118 or at 118 an...
Article
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Chorioamnionitis and antenatal glucocorticoids are common exposures for preterm infants and can affect the fetal brain, contributing to cognitive and motor deficits in preterm infants. The effects of antenatal glucocorticoids on the brain in the setting of chorioamnionitis are unknown. We hypothesized that antenatal glucocorticoids would modulate i...
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Background Antenatal inflammation and maternal corticosteroids induce fetal lung maturation but interfere with late lung development. Canonical Wingless-Int (Wnt) signaling directs lung development and repair. We showed that intra-amniotic lipopolysaccharide (LPS) exposure disrupted developmental signaling pathways in the preterm lamb lungs. Theref...
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Hypoxic-ischemic encephalopathy (HIE) in preterm infants is a severe disease for which no curative treatment is available. Cerebral inflammation and invasion of activated peripheral immune cells have been shown to play a pivotal role in the etiology of white matter injury, which is the clinical hallmark of HIE in preterm infants. The objective of t...
Data
Detection of human specific β-2-microglobulin DNA sequences in preterm sheep brain. Genomic DNA was extracted from subcortical white matter of a MSC treated animal (MSC) and a saline treated animal (SAL) and analyzed by nested PCR for the presence of human β-2-microglobulin (B2M) DNA sequences. The presence of amplifiable DNA was evaluated by PCR...
Data
Correlation plots. (A) Density of immature preOLs was inversely related (Pearson r = -.83, P<0.001) to IBA-1 immunoreactivity in the SCWM. (B) MBP immunoreactivity was inversely related (Pearson r = -.71, P=0.002) to IBA-1 immunoreactivity in the SCWM. (C) The number of non-proliferating CD4-positive T cells harvested from the spleen was inversely...
Data
Gating strategy proliferation assay. (A–C) Dot plots illustrating gating strategy in the flow cytometry analysis of the proliferation assay. FSC = forward scatter, SSC = sideward scatter, 7-AAD = 7-Aminoactinomycin D (viability stain). (TIF)
Article
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Background: Bronchopulmonary dysplasia (BPD) is one of the most common complications after preterm birth and is associated with intrauterine exposure to bacteria. Transforming growth factor-β (TGFβ) is implicated in the development of BPD. Objectives: We hypothesized that different and/or multiple bacterial signals could elicit divergent TGFβ si...
Article
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Inflammation and antenatal glucocorticoids, the latter given to mothers at risk for preterm birth, affect lung development and may contribute to the development of bronchopulmonary dysplasia (BPD). The effects of the combined exposures on inflammation and antenatal glucocorticoids on transforming growth factor (TGF)β signaling are unknown. TGFβ and...
Article
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Rationale: Chorioamnionitis induces preterm delivery and acute involution of the fetal thymus which is associated with postnatal inflammatory disorders. We studied the immune response, cell composition, and architecture of the fetal thymus following intraamniotic lipopolysaccharide (LPS) exposure. Methods: Time-mated ewes received an intraamniot...
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In recent years, translational research with various animal models has been helpful to answer basic questions about the effect of antenatal inflammation on maturation and development of the fetal lung and immune system. The fetal lung and immune systems are very plastic and their development can be conditioned and influenced by both endogenous and/...
Article
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Respiratory distress syndrome in preterm babies is caused by a pulmonary surfactant deficiency, but also by its inactivation due to various conditions, including plasma protein leakage. Surfactant replacement therapy is well established, but clinical observations and in vitro experiments suggested that its efficacy may be impaired by inactivation....
Data
Minute and tidal volume. Recordings of the minute (A) and tidal volume (B) did not show any significantly difference between CHF 5633 treated animals and Poractant alfa treated animals for the duration of the experiment. Grey spheres = CHF 5633; Black cubes = Poractant alfa. Data expressed as mean±SEM. *p<0.05, two-way repeated-measures analysis of...
Article
Full-text available
Rationale Chorioamnionitis and antenatal corticosteroids mature the fetal lung functionally but disrupt late gestation lung development. Because Sonic Hedgehog (Shh) signaling is a major pathway directing lung development, we hypothesized that chorioamnionitis and antenatal corticosteroids modulated Shh signaling resulting in an altered fetal lung...
Article
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Infections during pregnancy can adversely affect the development of the fetal brain. This may contribute to disease processes such as schizophrenia in later life. Changes in the (cyto-) architecture of the anterior cingulate cortex (ACC), particularly in GABA-ergic interneurons, play a role in the pathogenesis of schizophrenia. We hypothesized that...
Article
Full-text available
Rationale: Chorioamnionitis is associated with preterm delivery and involution of the fetal thymus. Women at risk of preterm delivery receive antenatal corticosteroids which accelerate fetal lung maturation and improve neonatal outcome. However, the effects of antenatal corticosteroids on the fetal thymus in the settings of chorioamnionitis are la...
Article
Full-text available
The proinflammatory stimulus of chorioamnionitis is commonly associated with preterm delivery. Women at risk of preterm delivery receive antenatal glucocorticoids to functionally mature the fetal lung. However, the effects of the combined exposures of chorioamnionitis and antenatal glucocorticoids on the fetus are poorly understood. Time-mated ewes...
Article
Full-text available
Bronchopulmonary dysplasia is associated with chorioamnionitis and fetal lung inflammation. Ureaplasma species are the bacteria most frequently isolated from chorioamnionitis. Very chronic ureaplasma colonization of amniotic fluid causes low-grade lung inflammation and functional lung maturation in fetal sheep. Less is known about shorter exposures...

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