Kajsa Bohlin - Academia.edu (original) (raw)
Papers by Kajsa Bohlin
Pediatric Research, May 1, 2005
In preterm infants with respiratory distress syndrome, surfactant administration followed by imme... more In preterm infants with respiratory distress syndrome, surfactant administration followed by immediate extubation to spontaneous breathing with nasal continuous positive airway pressure reduces the need for mechanical ventilation. With this treatment approach, repeated doses of surfactant are rarely indicated. We used a rabbit model to test the hypothesis that exogenous surfactant therapy followed by spontaneous breathing results in a more sustained initial treatment response compared with treatment followed by mechanical ventilation. Preterm rabbits (gestational age 28.5 d) were treated with pharyngeal deposition of 200 mg/kg radiolabeled surfactant ( 14 C-Curosurf) and randomized to 4 h of spontaneous breathing or mechanical ventilation or to a control group, killed immediately after surfactant administration. With pharyngeal deposition, 46 Ϯ 10% (mean Ϯ SEM) of the administered surfactant reached the lungs. The dynamic lung-thorax compliance was higher in spontaneously breathing compared with mechanically ventilated animals (median, 9.9 and 0.75 ml ⅐ cm H 2 O Ϫ1 ⅐ kg Ϫ1 , respectively; p Ͻ 0.05). The relative distribution of 14 C-Curosurf in bronchoalveolar lavage fluid and homogenized lung tissue showed a higher degree of tissue association in the spontaneously breathing animals [53 Ϯ 4 versus 26 Ϯ 3% (mean Ϯ SEM)] than in mechanically ventilated animals (p Ͻ 0.01), the latter figure being very similar to that of the control group (25 Ϯ 5%). There was a higher degree of lipid peroxidation and fewer microbubbles in bronchoalveolar lavage fluid from mechanically ventilated animals. We conclude that the initial lung tissue association of exogenous surfactant is impaired by mechanical ventilation. This is associated with a reduction of dynamic compliance and evidence of increased surfactant inactivation. (Pediatr Res 57: 624-630, 2005) Abbreviations BAL, bronchoalveolar lavage MDA, malondialdehyde MST, microbubble stability test nCPAP, nasal continuous positive airway pressure PEEP, positive end expiratory pressure RDS, respiratory distress syndrome 4-HNE, 4-hydroxyalkenals
Europe PMC (PubMed Central), 2016
Pediatric Research, Aug 1, 2003
Studies using stable isotopically labeled glucose and palmitate as precursors of pulmonary surfac... more Studies using stable isotopically labeled glucose and palmitate as precursors of pulmonary surfactant synthesis have demonstrated slow surfactant turnover in premature infants with respiratory distress syndrome (RDS). However, only limited data about surfactant turnover are available for term infants. Because acetate is a direct precursor of de novo synthesized surfactant fatty acid, we measured [1-13 C 1 ]acetate incorporation into surfactant of term infants without respiratory dysfunction (control group), preterm infants with RDS, and term infants with primary respiratory failure to determine whether stable isotopically labeled acetate would yield similar results to previous studies of preterm infants with RDS and, furthermore, would distinguish normal from abnormal surfactant turnover. Despite similar amounts of phospholipids and acetate precursor enrichment, the control group had higher fractional synthetic rate and shorter half-life of clearance than preterm infants with RDS, (fractional synthetic rate, 15.4 Ϯ 2.4 versus 2.2 Ϯ 0.4%/d, p Ͻ 0.001; half-life of clearance, 27 Ϯ 3 versus 105 Ϯ 11 h, p Ͻ 0.001). Term infants with severe respiratory failure had a lower fractional synthetic rate than those with mild disease (2.9 Ϯ 0.6 versus 13.8 Ϯ 3.5%/d, p ϭ 0.014) and a reduced amount of phospholipids recovered from tracheal aspirates (54 Ϯ 17 versus 300 Ϯ 28 nmol, severe versus mild disease, respectively, p Ͻ 0.001). The amount of phospholipids in tracheal aspirates correlated inversely with disease severity, (r ϭ Ϫ0.75, p ϭ 0.01). We conclude that normal surfactant turnover in term infants is faster than in preterm infants with RDS. Surfactant turnover in term infants with severe respiratory failure is similar to that of preterm infants with RDS, suggesting either delayed maturity of the surfactant system or disruption from the underlying disease process. (Pediatr Res 54: 185-191, 2003) Abbreviations DPPC, dipalmitoylphosphatidylcholine E max , maximum enrichment FSR, fractional synthetic rate FiO 2 , fraction of inspired oxygen GC/MS, gas chromatography/mass spectrometry MIDA, mass isotopomer distribution analysis RDS, respiratory distress syndrome T1/2, half-life of clearance TA, tracheal aspirate T app , time of appearance T max , time of maximum enrichment TTR, tracer to tracee ratio
Pediatric Research, Jan 11, 2020
This review summarizes the current knowledge on the physiological action of endogenous and exogen... more This review summarizes the current knowledge on the physiological action of endogenous and exogenous pulmonary surfactant, the role of different types of animal-derived and synthetic surfactants for RDS therapy, different modes of administration, potential risks and strategies of ventilation, and highlights the most promising aims for future development. Scientists have clarified the physicochemical properties and functions of the different components of surfactant, and part of this successful research is derived from the characterization of genetic diseases affecting surfactant composition or function. Knowledge from functional tests of surfactant action, its immunochemistry, kinetics and homeostasis are important also for improving therapy with animal-derived surfactant preparations and for the development of modified surfactants. In the past decade newly designed artificial surfactants and additives have gained much attention and have proven different advantages, but their particular role still has to be defined. For clinical practice, alternative administration techniques as well as postsurfactant ventilation modes, taking into account alterations in lung mechanics after surfactant placement, may be important in optimizing the potential of this most important drug in neonatology.
Pediatric Research, Nov 1, 2011
Current evidence indicates that a strategy of early CPAP in very preterm infants is as safe as ro... more Current evidence indicates that a strategy of early CPAP in very preterm infants is as safe as routine intubation in the DR. There appears to be no serious side effects and a tendency towards improved outcome, at least in the short term. Prophylactic surfactant no longer gives any clear benefits over selective treatment, but surfactant should be given early in the course of RDS and a strategy for surfactant administration is imperative for a practice of early CPAP. Predicting which infants will fail CPAP and decide the optimal time and mode for surfactant administration are important future goals. In a situation of equipoise, the least invasive approach should be chosen. Thus, early CPAP could now be considered as the recommended intitial ventilation support for preterm infants, leaving the burden of proving superiority to those still advocating primary intubation. The overall evidence and experiences from Scandinavia will be discussed.
Pediatric Research, May 1, 2005
In preterm infants with respiratory distress syndrome, surfactant administration followed by imme... more In preterm infants with respiratory distress syndrome, surfactant administration followed by immediate extubation to spontaneous breathing with nasal continuous positive airway pressure reduces the need for mechanical ventilation. With this treatment approach, repeated doses of surfactant are rarely indicated. We used a rabbit model to test the hypothesis that exogenous surfactant therapy followed by spontaneous breathing results in a more sustained initial treatment response compared with treatment followed by mechanical ventilation. Preterm rabbits (gestational age 28.5 d) were treated with pharyngeal deposition of 200 mg/kg radiolabeled surfactant ( 14 C-Curosurf) and randomized to 4 h of spontaneous breathing or mechanical ventilation or to a control group, killed immediately after surfactant administration. With pharyngeal deposition, 46 Ϯ 10% (mean Ϯ SEM) of the administered surfactant reached the lungs. The dynamic lung-thorax compliance was higher in spontaneously breathing compared with mechanically ventilated animals (median, 9.9 and 0.75 ml ⅐ cm H 2 O Ϫ1 ⅐ kg Ϫ1 , respectively; p Ͻ 0.05). The relative distribution of 14 C-Curosurf in bronchoalveolar lavage fluid and homogenized lung tissue showed a higher degree of tissue association in the spontaneously breathing animals [53 Ϯ 4 versus 26 Ϯ 3% (mean Ϯ SEM)] than in mechanically ventilated animals (p Ͻ 0.01), the latter figure being very similar to that of the control group (25 Ϯ 5%). There was a higher degree of lipid peroxidation and fewer microbubbles in bronchoalveolar lavage fluid from mechanically ventilated animals. We conclude that the initial lung tissue association of exogenous surfactant is impaired by mechanical ventilation. This is associated with a reduction of dynamic compliance and evidence of increased surfactant inactivation. (Pediatr Res 57: 624-630, 2005) Abbreviations BAL, bronchoalveolar lavage MDA, malondialdehyde MST, microbubble stability test nCPAP, nasal continuous positive airway pressure PEEP, positive end expiratory pressure RDS, respiratory distress syndrome 4-HNE, 4-hydroxyalkenals
Archives of Disease in Childhood, 2014
Archives of Disease in Childhood, Oct 1, 2014
Background and aims Nasal high frequency oscillation ventilation (nHFOV) is a non-invasive ventil... more Background and aims Nasal high frequency oscillation ventilation (nHFOV) is a non-invasive ventilation mode that applies an oscillatory pressure waveform to the airways using a nasal interface. NHFOV has been shown to facilitate carbon dioxide expiration, but there are little data about its use in neonates. Therefore, the aim of this survey was to collect data about nHFOV use in neonatal intensive care units (NICUs). Methods From June 2013 to February 2014, we conducted a prospective survey in Austria, Switzerland, Germany, the Netherlands and Sweden. A 26-item questionnaire was sent to NICUs who provide the highest level of care. We asked for indications to start nHFOV, equipment used, nHFOV settings and observed side effects. Results Of all contacted NICUs, 172/186 (92%) participated. Among those responding, 30/172 (17%) used nHFOV, most frequently in premature infants O 2 , the maximum pressure 10[7-18] cm H 2 O, and pressure before switching to nCPAP 7,5 [5][6][7][8][9][10][11][12][13][14][15] cm H 2 O. The typical nHFOV frequency was 10[6-13] Hz. Abdominal distension (11/30), highly viscous secretions (7/30) and upper airway obstruction due to such secretions (8/30) were the most common nHFOV side effects. Conclusion Based on individual experience, a number of European NICUs use nHFOV. There are substantial differences in nHFOV equipment, indications and settings. New clinical studies are needed to further investigate the risks and benefits of nHFOV in neonates.
Archives of Disease in Childhood, Oct 1, 2012
perfusion was measured using laser Doppler. Local cerebral bloodflow was measured by iodo[ 14 C]a... more perfusion was measured using laser Doppler. Local cerebral bloodflow was measured by iodo[ 14 C]antipyrine autoradiography. None of the procedures of serial mechanical interruptions of blood flow applied at reperfusion induced a reduction of infarct volume after 72 hours. In contrast to adult ischemia, a gradual perfusion was found during early re-flow both in the left internal carotid artery and in the cortical penumbra. No hyperemia was detected on autoradiograms. In addition, vasodilation to hypercapnia remained unchanged. Absence of acute hyperemia during early CCA re-flows and absence of increased cerebrovascular reactivity could at least in part explain the inefficiency of ischemic postconditioning in the developing brain.
Pediatric Research, Mar 13, 2020
BACKGROUND: Prematurity in itself and exposure to neonatal intensive care triggers inflammatory p... more BACKGROUND: Prematurity in itself and exposure to neonatal intensive care triggers inflammatory processes and oxidative stress, leading to risk for disease later in life. The effects on cellular aging processes are incompletely understood. METHODS: Relative telomere length (RTL) was measured by qPCR in this longitudinal cohort study with blood samples taken at birth and at 2 years of age from 60 children (16 preterm and 44 term). Viral respiratory infections the first year were evaluated. Epigenetic biological DNA methylation (DNAm) age was predicted based on methylation array data in 23 children (11 preterm and 12 term). RTL change/year and DNAm age change/year was compared in preterm and term during the 2 first years of life. RESULTS: Preterm infants had longer telomeres than term born at birth and at 2 years of age, but no difference in telomere attrition rate could be detected. Predicted epigenetic DNAm age was younger in preterm infants, but rate of DNAm aging was similar in both groups. CONCLUSIONS: Despite early exposure to risk factors for accelerated cellular aging, children born preterm exhibited preserved telomeres. Stress during the neonatal intensive care period did not reflect accelerated epigenetic DNAm aging. Early-life aging was not explained by preterm birth.
Scientific Reports, Sep 2, 2022
Preterm newborns are more likely to suffer from infectious diseases at birth compared to children... more Preterm newborns are more likely to suffer from infectious diseases at birth compared to children delivered at term. Whether this is due to compromised cellular, humoral, or organ-specific development remains unclear. To begin to define whether maternal-fetal antibody transfer profiles differ across preterm (PT) and fullterm (FT) infants, the overall quantity and functional quality of an array of 24 vaccine-, endemic pathogen-, and common antigen-specific antibodies were assessed across a cohort of 11 PT and 12 term-delivered maternal:infant pairs from birth through week 12. While total IgG levels to influenza, pneumo, measles, rubella, EBV, and RSV were higher in FT newborns, selective Fc-receptor binding antibodies was noted in PT newborns. In fact, near equivalent antibody-effector functions were observed across PT and FT infants, despite significant quantitative differences in transferred antibody levels. Moreover, temporal transfer analysis revealed the selective early transfer of FcRn, FcγR2, and FcγR3 binding antibodies, pointing to differential placental sieving mechanisms across gestation. These data point to selectivity in placental transfer at distinct gestational ages, to ensure that children are endowed with the most robust humoral immunity even if born preterm. In the US alone, more than 10% of babies are born at less than 37 weeks of gestation, with 2.75% born at less than 34 weeks of gestation 1 . Babies born earlier than 39 weeks have a greater incidence of respiratory complications, low blood sugar, feeding problems, as well as an elevated risk of developing diseases over time . While rates of preterm (PT) births are declining in the developed world, PT births are on the rise in the developing world 4 , with 15 million PT births world-wide each year 5 , with premature birth representing the second leading cause of death among children under 5 years of age across the globe 6 . In the last weeks of pregnancy, significant development of the brain, lungs, liver, and skin occur in parallel to significant weight gain, that collectively ensure the survival of the neonate outside the uterus. Significant changes also occur in immune cellular maturation and function, in the last weeks of gestation and first months of life, pointing to a rapid evolution of the immune system in preparation for exposure to the non-sterile world 7,8 . However, even when fully developed, neonates are born with a largely naïve immune system, that must quickly adapt to the new environment and prevent infections 7,8 . To help their offspring, mothers actively transfer copious levels of IgG antibodies to infants in utero, to passively immunize the neonates against pathogens previously encountered by the mother. Thus, the final months/weeks of gestation are critical for final developmental events and to fully immunologically arm the neonate to prepare for the non-sterile life outside utero. Commonly attributed to developmental and immune prematurity, PT babies are more susceptible to infections 2 . This includes infections in the lungs, skin, kidneys, eyes, bladder, and gastrointestinal tract. Specifically, higher susceptibility in PT infants has been reported for Varicella-Zoster virus 9 and viral respiratory infections 2 even when transferred antibody levels are comparable. However, whether this increased susceptibility of PT children is related to an impairment in the immune system or due to incomplete transfer of protective
Pediatric Research, Sep 1, 2004
Journal of Perinatology, May 3, 2007
Objective: To study the effects of implementing a method for surfactant administration by transie... more Objective: To study the effects of implementing a method for surfactant administration by transient intubation, INSURE (i.e. INtubation SURfactant Extubation) during nasal continuous positive airway pressure (nCPAP) for moderately preterm infants with respiratory distress syndrome (RDS). Study design: A descriptive, retrospective, bi-center study in Stockholm, Sweden, comparing mechanical ventilation (MV) rates, surfactant use, treatment response and outcome of all inborn infants with gestational age 27 to 34 weeks and RDS, (n ¼ 420), during the 5-year periods before and after the introduction of the INSURE-strategy at one of the centers (Karolinska Huddinge) in 1998. The other center (Karolinska Solna) continued conventional surfactant therapy in conjunction with MV throughout the study. Results: Implementation of INSURE at Karolinska Huddinge reduced the number of infants requiring MV by 50% (P<0.01), resulted in earlier surfactant administration and increased overall surfactant use. INSURE-treatment improved oxygenation and the treatment response was sustained over time with only 17% of the infants requiring >1 dose of surfactant. At Karolinska Solna, the MV rates were unaltered between the first and second 5-year period. Implementing a strategy of surfactant administration by transient intubation during nCPAP reduces the need for MV without adverse effects on outcome and may be an option to more effectively treat RDS, particularly in a care setting where transfer is necessary to provide MV.
Journal of Perinatology, Feb 22, 2022
To estimate the incidence of cholestasis in neonates with hemolytic disease of the fetus and newb... more To estimate the incidence of cholestasis in neonates with hemolytic disease of the fetus and newborn (HDFN) and investigate risk factors and long-term liver disease. STUDY DESIGN: A population-based cohort study of all infants born with HDFN within the Stockholm region between 2006 and 2015. The study period was the first 90 days of life, and presence of any chronic liver disease was evaluated at two years of age. RESULTS: Cholestasis occurred in 7% (11/149). Median age at detection was 1.1 days. Intrauterine blood transfusions and maternal alloimmunization with multiple red blood cell antibodies including D-, c-or K-antibodies were independent risk factors for cholestasis. No infant had chronic liver disease at two years of age. CONCLUSIONS: Infants with severe HDFN have increased risk for cholestasis, particularly those requiring multiple intrauterine transfusions. Early and repeated screening for conjugated hyperbilirubinemia in the first week of life is needed to ensure adequate management.
Research Square (Research Square), Dec 1, 2021
Preterm newborns are more likely to suffer from infectious diseases at birth compared to children... more Preterm newborns are more likely to suffer from infectious diseases at birth compared to children delivered at term. Whether this is due to compromised cellular, humoral, or organ-speci c development remains unclear. Recent studies have shown that while preterm children have an aberrant cellular immune response, these infants receive similar maternal anti-viral IgG repertoires compared to term children, albeit at lower concentrations. These data point to selectivity in placental transfer at distinct gestational ages, to ensure that children are endowed with the most robust humoral immunity even if born preterm. To begin to de ne the mechanism by which preterm selective transfer may occur, the overall quantity and functional quality of an array of vaccine-, endemic pathogen-, and common antigen-speci c antibodies were assessed across a cohort of 11 preterm and 12 term-delivered mother:infant pairs from birth through week 12. Although higher antibody levels were present in term infants, the overall functional pro les of antigen-speci c antibodies were very similar. Temporal transfer differences were ascertained across distinct antibody subpopulations, with early transfer of functional antibodies capable of binding to FcRn and FcγR2-3 receptors followed by the transfer of distinct IgG subclasses. These results provide new insights on maternal:fetal immunity, highlighting novel immune axes that may be manipulated to enhance neonatal immune transfer of antibodies through gestation.
Journal of Human Lactation, Jun 1, 2021
Background Preterm infants are more susceptible to inflammatory complications than term infants. ... more Background Preterm infants are more susceptible to inflammatory complications than term infants. Human milk contains numerous bioactive components protecting the newborn infant. Antisecretory factor, a protein regulating secretory and inflammatory processes by complex binding with complement factors, is present in human milk. Research Aims To describe antisecretory factor (1) in mother’s own milk in term and preterm infants; and (2) in donor milk before and after Holder pasteurization. Methods The study was prospective, longitudinal, explorative, and descriptive. Antisecretory factor-compleasome was determined using sandwich enzyme-linked immunosorbent assay in longitudinal human milk samples over 12 weeks from mothers ( N = 87) of term ( n = 41) and of preterm ( n = 46) infants and 20 anonymized donor human milk samples before and after Holder pasteurization. Results Antisecretory factor-compleasome was overall higher in colostrum versus mature milk ( p < .001) and no difference was found in term or preterm colostrum ( p = .82). In mature milk, compleasome was higher and more variable in the preterm group ( p = .01). After Holder pasteurization, compleasome levels increased ( p < .001). Conclusion Antisecretory factor followed the pattern of other immunological factors with high levels in colostrum. After preterm birth, levels of antisecretory factor were higher and more variable in mature milk. Holder pasteurization did not degrade antisecretory factor, indicating preserved anti-inflammatory properties in donor human milk.
Acta Paediatrica, Jun 29, 2020
Aim: To describe outcome linked to neonatal cholestasis in a defined cohort of very preterm infan... more Aim: To describe outcome linked to neonatal cholestasis in a defined cohort of very preterm infants. Methods: Population-based retrospective case-control study of preterm infants, gestational age <30 weeks, surviving for 28 days, in Stockholm County. Cholestasis was defined as conjugated bilirubin ≥30 μmol/L exceeding 20% of total level at least twice, and graded as high if exceeding 100 μmol/L. Cholestatic cases were matched on gestational week with two non-cholestatic controls. The incidence rate of cholestasis was 37/250 (14.8%), with increasing rates in lower gestational weeks. Perinatal factors associated with cholestasis were preeclampsia and being born small for gestational age. Cholestatic infants had three times more bronchopulmonary dysplasia and eight times more retinopathy of prematurity. The mortality was 13.5% in cholestatic infants versus 2.7% in controls (p=0.040). All deceased cholestatic infants had high-grade cholestasis. No surviving infants developed chronic liver disease by 10 years of age. Cholestasis was common in very preterm infants and linked to disease severity and adverse outcome. Cholestasis may be an independent risk factor for bronchopulmonary dysplasia and retinopathy of prematurity and more severe cholestasis associated with increased mortality. Cholestasis was not associated with chronic liver disease later in childhood. Cholestasis in very preterm infants is a common clinical problem, but the long-term effects are poorly known. In this population-based case-control study of very preterm infants, cholestasis developed in 14.8% of infants and was associated with higher rates of retinopathy of prematurity, bronchopulmonary dysplasia and death, but not associated with chronic liver-disease at ten years of age.
Pediatric Research, Nov 1, 2011
Background and aims: Oxidative stress, as a result of inflammation and oxygen toxicity, may affec... more Background and aims: Oxidative stress, as a result of inflammation and oxygen toxicity, may affect lung growth and contribute to the development of bronchopulmonary dysplasia (BPD) in preterm infants. Preterm infants have longer telomeres than term infants at birth. In adults, chronic obstructive lung disease has been related to shorter telomeres. Telomere length in relation to prematurity and lung function therefore was studied. Methods: Relative telomere length (RTL) was measured using real-time PCR on extracted DNA in children born preterm with a history of BPD at the age of 10 years and a control group of children born healthy at term with a history of asthma. Lung function as dynamic spirometry and inflammation examined as fractional exhaled nitric oxygen (NO) was performed. Results: Children with BPD (n= 23) compared to children with asthma (n=19) had shorter telomeres (RTL 1,43 vs 1,61, p< 0,05) and reduced lung function (Forced Expiratory Fraction (FEF 25-75%), 1,55 vs 1,88, p< 0,05) but lower levels of exhaled NO (NO 12,6 ppb vs 22,3 ppb, p< 0,05). Lung function and levels of NO were not independently correlated to RTL. Preterm birth and lung disease in infancy resulted in shorter telomere length and reduced lung function at 10 years of age compared to controls with asthma. This may indicate faster telomere attrition in preterm infants with BPD. The influence of oxidative stress and inflammation in the neonatal period and beyond needs to be further studied in relation to intra-individual telomere shortening rate and long term outcome.
Pediatric Research, May 1, 2005
In preterm infants with respiratory distress syndrome, surfactant administration followed by imme... more In preterm infants with respiratory distress syndrome, surfactant administration followed by immediate extubation to spontaneous breathing with nasal continuous positive airway pressure reduces the need for mechanical ventilation. With this treatment approach, repeated doses of surfactant are rarely indicated. We used a rabbit model to test the hypothesis that exogenous surfactant therapy followed by spontaneous breathing results in a more sustained initial treatment response compared with treatment followed by mechanical ventilation. Preterm rabbits (gestational age 28.5 d) were treated with pharyngeal deposition of 200 mg/kg radiolabeled surfactant ( 14 C-Curosurf) and randomized to 4 h of spontaneous breathing or mechanical ventilation or to a control group, killed immediately after surfactant administration. With pharyngeal deposition, 46 Ϯ 10% (mean Ϯ SEM) of the administered surfactant reached the lungs. The dynamic lung-thorax compliance was higher in spontaneously breathing compared with mechanically ventilated animals (median, 9.9 and 0.75 ml ⅐ cm H 2 O Ϫ1 ⅐ kg Ϫ1 , respectively; p Ͻ 0.05). The relative distribution of 14 C-Curosurf in bronchoalveolar lavage fluid and homogenized lung tissue showed a higher degree of tissue association in the spontaneously breathing animals [53 Ϯ 4 versus 26 Ϯ 3% (mean Ϯ SEM)] than in mechanically ventilated animals (p Ͻ 0.01), the latter figure being very similar to that of the control group (25 Ϯ 5%). There was a higher degree of lipid peroxidation and fewer microbubbles in bronchoalveolar lavage fluid from mechanically ventilated animals. We conclude that the initial lung tissue association of exogenous surfactant is impaired by mechanical ventilation. This is associated with a reduction of dynamic compliance and evidence of increased surfactant inactivation. (Pediatr Res 57: 624-630, 2005) Abbreviations BAL, bronchoalveolar lavage MDA, malondialdehyde MST, microbubble stability test nCPAP, nasal continuous positive airway pressure PEEP, positive end expiratory pressure RDS, respiratory distress syndrome 4-HNE, 4-hydroxyalkenals
Europe PMC (PubMed Central), 2016
Pediatric Research, Aug 1, 2003
Studies using stable isotopically labeled glucose and palmitate as precursors of pulmonary surfac... more Studies using stable isotopically labeled glucose and palmitate as precursors of pulmonary surfactant synthesis have demonstrated slow surfactant turnover in premature infants with respiratory distress syndrome (RDS). However, only limited data about surfactant turnover are available for term infants. Because acetate is a direct precursor of de novo synthesized surfactant fatty acid, we measured [1-13 C 1 ]acetate incorporation into surfactant of term infants without respiratory dysfunction (control group), preterm infants with RDS, and term infants with primary respiratory failure to determine whether stable isotopically labeled acetate would yield similar results to previous studies of preterm infants with RDS and, furthermore, would distinguish normal from abnormal surfactant turnover. Despite similar amounts of phospholipids and acetate precursor enrichment, the control group had higher fractional synthetic rate and shorter half-life of clearance than preterm infants with RDS, (fractional synthetic rate, 15.4 Ϯ 2.4 versus 2.2 Ϯ 0.4%/d, p Ͻ 0.001; half-life of clearance, 27 Ϯ 3 versus 105 Ϯ 11 h, p Ͻ 0.001). Term infants with severe respiratory failure had a lower fractional synthetic rate than those with mild disease (2.9 Ϯ 0.6 versus 13.8 Ϯ 3.5%/d, p ϭ 0.014) and a reduced amount of phospholipids recovered from tracheal aspirates (54 Ϯ 17 versus 300 Ϯ 28 nmol, severe versus mild disease, respectively, p Ͻ 0.001). The amount of phospholipids in tracheal aspirates correlated inversely with disease severity, (r ϭ Ϫ0.75, p ϭ 0.01). We conclude that normal surfactant turnover in term infants is faster than in preterm infants with RDS. Surfactant turnover in term infants with severe respiratory failure is similar to that of preterm infants with RDS, suggesting either delayed maturity of the surfactant system or disruption from the underlying disease process. (Pediatr Res 54: 185-191, 2003) Abbreviations DPPC, dipalmitoylphosphatidylcholine E max , maximum enrichment FSR, fractional synthetic rate FiO 2 , fraction of inspired oxygen GC/MS, gas chromatography/mass spectrometry MIDA, mass isotopomer distribution analysis RDS, respiratory distress syndrome T1/2, half-life of clearance TA, tracheal aspirate T app , time of appearance T max , time of maximum enrichment TTR, tracer to tracee ratio
Pediatric Research, Jan 11, 2020
This review summarizes the current knowledge on the physiological action of endogenous and exogen... more This review summarizes the current knowledge on the physiological action of endogenous and exogenous pulmonary surfactant, the role of different types of animal-derived and synthetic surfactants for RDS therapy, different modes of administration, potential risks and strategies of ventilation, and highlights the most promising aims for future development. Scientists have clarified the physicochemical properties and functions of the different components of surfactant, and part of this successful research is derived from the characterization of genetic diseases affecting surfactant composition or function. Knowledge from functional tests of surfactant action, its immunochemistry, kinetics and homeostasis are important also for improving therapy with animal-derived surfactant preparations and for the development of modified surfactants. In the past decade newly designed artificial surfactants and additives have gained much attention and have proven different advantages, but their particular role still has to be defined. For clinical practice, alternative administration techniques as well as postsurfactant ventilation modes, taking into account alterations in lung mechanics after surfactant placement, may be important in optimizing the potential of this most important drug in neonatology.
Pediatric Research, Nov 1, 2011
Current evidence indicates that a strategy of early CPAP in very preterm infants is as safe as ro... more Current evidence indicates that a strategy of early CPAP in very preterm infants is as safe as routine intubation in the DR. There appears to be no serious side effects and a tendency towards improved outcome, at least in the short term. Prophylactic surfactant no longer gives any clear benefits over selective treatment, but surfactant should be given early in the course of RDS and a strategy for surfactant administration is imperative for a practice of early CPAP. Predicting which infants will fail CPAP and decide the optimal time and mode for surfactant administration are important future goals. In a situation of equipoise, the least invasive approach should be chosen. Thus, early CPAP could now be considered as the recommended intitial ventilation support for preterm infants, leaving the burden of proving superiority to those still advocating primary intubation. The overall evidence and experiences from Scandinavia will be discussed.
Pediatric Research, May 1, 2005
In preterm infants with respiratory distress syndrome, surfactant administration followed by imme... more In preterm infants with respiratory distress syndrome, surfactant administration followed by immediate extubation to spontaneous breathing with nasal continuous positive airway pressure reduces the need for mechanical ventilation. With this treatment approach, repeated doses of surfactant are rarely indicated. We used a rabbit model to test the hypothesis that exogenous surfactant therapy followed by spontaneous breathing results in a more sustained initial treatment response compared with treatment followed by mechanical ventilation. Preterm rabbits (gestational age 28.5 d) were treated with pharyngeal deposition of 200 mg/kg radiolabeled surfactant ( 14 C-Curosurf) and randomized to 4 h of spontaneous breathing or mechanical ventilation or to a control group, killed immediately after surfactant administration. With pharyngeal deposition, 46 Ϯ 10% (mean Ϯ SEM) of the administered surfactant reached the lungs. The dynamic lung-thorax compliance was higher in spontaneously breathing compared with mechanically ventilated animals (median, 9.9 and 0.75 ml ⅐ cm H 2 O Ϫ1 ⅐ kg Ϫ1 , respectively; p Ͻ 0.05). The relative distribution of 14 C-Curosurf in bronchoalveolar lavage fluid and homogenized lung tissue showed a higher degree of tissue association in the spontaneously breathing animals [53 Ϯ 4 versus 26 Ϯ 3% (mean Ϯ SEM)] than in mechanically ventilated animals (p Ͻ 0.01), the latter figure being very similar to that of the control group (25 Ϯ 5%). There was a higher degree of lipid peroxidation and fewer microbubbles in bronchoalveolar lavage fluid from mechanically ventilated animals. We conclude that the initial lung tissue association of exogenous surfactant is impaired by mechanical ventilation. This is associated with a reduction of dynamic compliance and evidence of increased surfactant inactivation. (Pediatr Res 57: 624-630, 2005) Abbreviations BAL, bronchoalveolar lavage MDA, malondialdehyde MST, microbubble stability test nCPAP, nasal continuous positive airway pressure PEEP, positive end expiratory pressure RDS, respiratory distress syndrome 4-HNE, 4-hydroxyalkenals
Archives of Disease in Childhood, 2014
Archives of Disease in Childhood, Oct 1, 2014
Background and aims Nasal high frequency oscillation ventilation (nHFOV) is a non-invasive ventil... more Background and aims Nasal high frequency oscillation ventilation (nHFOV) is a non-invasive ventilation mode that applies an oscillatory pressure waveform to the airways using a nasal interface. NHFOV has been shown to facilitate carbon dioxide expiration, but there are little data about its use in neonates. Therefore, the aim of this survey was to collect data about nHFOV use in neonatal intensive care units (NICUs). Methods From June 2013 to February 2014, we conducted a prospective survey in Austria, Switzerland, Germany, the Netherlands and Sweden. A 26-item questionnaire was sent to NICUs who provide the highest level of care. We asked for indications to start nHFOV, equipment used, nHFOV settings and observed side effects. Results Of all contacted NICUs, 172/186 (92%) participated. Among those responding, 30/172 (17%) used nHFOV, most frequently in premature infants O 2 , the maximum pressure 10[7-18] cm H 2 O, and pressure before switching to nCPAP 7,5 [5][6][7][8][9][10][11][12][13][14][15] cm H 2 O. The typical nHFOV frequency was 10[6-13] Hz. Abdominal distension (11/30), highly viscous secretions (7/30) and upper airway obstruction due to such secretions (8/30) were the most common nHFOV side effects. Conclusion Based on individual experience, a number of European NICUs use nHFOV. There are substantial differences in nHFOV equipment, indications and settings. New clinical studies are needed to further investigate the risks and benefits of nHFOV in neonates.
Archives of Disease in Childhood, Oct 1, 2012
perfusion was measured using laser Doppler. Local cerebral bloodflow was measured by iodo[ 14 C]a... more perfusion was measured using laser Doppler. Local cerebral bloodflow was measured by iodo[ 14 C]antipyrine autoradiography. None of the procedures of serial mechanical interruptions of blood flow applied at reperfusion induced a reduction of infarct volume after 72 hours. In contrast to adult ischemia, a gradual perfusion was found during early re-flow both in the left internal carotid artery and in the cortical penumbra. No hyperemia was detected on autoradiograms. In addition, vasodilation to hypercapnia remained unchanged. Absence of acute hyperemia during early CCA re-flows and absence of increased cerebrovascular reactivity could at least in part explain the inefficiency of ischemic postconditioning in the developing brain.
Pediatric Research, Mar 13, 2020
BACKGROUND: Prematurity in itself and exposure to neonatal intensive care triggers inflammatory p... more BACKGROUND: Prematurity in itself and exposure to neonatal intensive care triggers inflammatory processes and oxidative stress, leading to risk for disease later in life. The effects on cellular aging processes are incompletely understood. METHODS: Relative telomere length (RTL) was measured by qPCR in this longitudinal cohort study with blood samples taken at birth and at 2 years of age from 60 children (16 preterm and 44 term). Viral respiratory infections the first year were evaluated. Epigenetic biological DNA methylation (DNAm) age was predicted based on methylation array data in 23 children (11 preterm and 12 term). RTL change/year and DNAm age change/year was compared in preterm and term during the 2 first years of life. RESULTS: Preterm infants had longer telomeres than term born at birth and at 2 years of age, but no difference in telomere attrition rate could be detected. Predicted epigenetic DNAm age was younger in preterm infants, but rate of DNAm aging was similar in both groups. CONCLUSIONS: Despite early exposure to risk factors for accelerated cellular aging, children born preterm exhibited preserved telomeres. Stress during the neonatal intensive care period did not reflect accelerated epigenetic DNAm aging. Early-life aging was not explained by preterm birth.
Scientific Reports, Sep 2, 2022
Preterm newborns are more likely to suffer from infectious diseases at birth compared to children... more Preterm newborns are more likely to suffer from infectious diseases at birth compared to children delivered at term. Whether this is due to compromised cellular, humoral, or organ-specific development remains unclear. To begin to define whether maternal-fetal antibody transfer profiles differ across preterm (PT) and fullterm (FT) infants, the overall quantity and functional quality of an array of 24 vaccine-, endemic pathogen-, and common antigen-specific antibodies were assessed across a cohort of 11 PT and 12 term-delivered maternal:infant pairs from birth through week 12. While total IgG levels to influenza, pneumo, measles, rubella, EBV, and RSV were higher in FT newborns, selective Fc-receptor binding antibodies was noted in PT newborns. In fact, near equivalent antibody-effector functions were observed across PT and FT infants, despite significant quantitative differences in transferred antibody levels. Moreover, temporal transfer analysis revealed the selective early transfer of FcRn, FcγR2, and FcγR3 binding antibodies, pointing to differential placental sieving mechanisms across gestation. These data point to selectivity in placental transfer at distinct gestational ages, to ensure that children are endowed with the most robust humoral immunity even if born preterm. In the US alone, more than 10% of babies are born at less than 37 weeks of gestation, with 2.75% born at less than 34 weeks of gestation 1 . Babies born earlier than 39 weeks have a greater incidence of respiratory complications, low blood sugar, feeding problems, as well as an elevated risk of developing diseases over time . While rates of preterm (PT) births are declining in the developed world, PT births are on the rise in the developing world 4 , with 15 million PT births world-wide each year 5 , with premature birth representing the second leading cause of death among children under 5 years of age across the globe 6 . In the last weeks of pregnancy, significant development of the brain, lungs, liver, and skin occur in parallel to significant weight gain, that collectively ensure the survival of the neonate outside the uterus. Significant changes also occur in immune cellular maturation and function, in the last weeks of gestation and first months of life, pointing to a rapid evolution of the immune system in preparation for exposure to the non-sterile world 7,8 . However, even when fully developed, neonates are born with a largely naïve immune system, that must quickly adapt to the new environment and prevent infections 7,8 . To help their offspring, mothers actively transfer copious levels of IgG antibodies to infants in utero, to passively immunize the neonates against pathogens previously encountered by the mother. Thus, the final months/weeks of gestation are critical for final developmental events and to fully immunologically arm the neonate to prepare for the non-sterile life outside utero. Commonly attributed to developmental and immune prematurity, PT babies are more susceptible to infections 2 . This includes infections in the lungs, skin, kidneys, eyes, bladder, and gastrointestinal tract. Specifically, higher susceptibility in PT infants has been reported for Varicella-Zoster virus 9 and viral respiratory infections 2 even when transferred antibody levels are comparable. However, whether this increased susceptibility of PT children is related to an impairment in the immune system or due to incomplete transfer of protective
Pediatric Research, Sep 1, 2004
Journal of Perinatology, May 3, 2007
Objective: To study the effects of implementing a method for surfactant administration by transie... more Objective: To study the effects of implementing a method for surfactant administration by transient intubation, INSURE (i.e. INtubation SURfactant Extubation) during nasal continuous positive airway pressure (nCPAP) for moderately preterm infants with respiratory distress syndrome (RDS). Study design: A descriptive, retrospective, bi-center study in Stockholm, Sweden, comparing mechanical ventilation (MV) rates, surfactant use, treatment response and outcome of all inborn infants with gestational age 27 to 34 weeks and RDS, (n ¼ 420), during the 5-year periods before and after the introduction of the INSURE-strategy at one of the centers (Karolinska Huddinge) in 1998. The other center (Karolinska Solna) continued conventional surfactant therapy in conjunction with MV throughout the study. Results: Implementation of INSURE at Karolinska Huddinge reduced the number of infants requiring MV by 50% (P<0.01), resulted in earlier surfactant administration and increased overall surfactant use. INSURE-treatment improved oxygenation and the treatment response was sustained over time with only 17% of the infants requiring >1 dose of surfactant. At Karolinska Solna, the MV rates were unaltered between the first and second 5-year period. Implementing a strategy of surfactant administration by transient intubation during nCPAP reduces the need for MV without adverse effects on outcome and may be an option to more effectively treat RDS, particularly in a care setting where transfer is necessary to provide MV.
Journal of Perinatology, Feb 22, 2022
To estimate the incidence of cholestasis in neonates with hemolytic disease of the fetus and newb... more To estimate the incidence of cholestasis in neonates with hemolytic disease of the fetus and newborn (HDFN) and investigate risk factors and long-term liver disease. STUDY DESIGN: A population-based cohort study of all infants born with HDFN within the Stockholm region between 2006 and 2015. The study period was the first 90 days of life, and presence of any chronic liver disease was evaluated at two years of age. RESULTS: Cholestasis occurred in 7% (11/149). Median age at detection was 1.1 days. Intrauterine blood transfusions and maternal alloimmunization with multiple red blood cell antibodies including D-, c-or K-antibodies were independent risk factors for cholestasis. No infant had chronic liver disease at two years of age. CONCLUSIONS: Infants with severe HDFN have increased risk for cholestasis, particularly those requiring multiple intrauterine transfusions. Early and repeated screening for conjugated hyperbilirubinemia in the first week of life is needed to ensure adequate management.
Research Square (Research Square), Dec 1, 2021
Preterm newborns are more likely to suffer from infectious diseases at birth compared to children... more Preterm newborns are more likely to suffer from infectious diseases at birth compared to children delivered at term. Whether this is due to compromised cellular, humoral, or organ-speci c development remains unclear. Recent studies have shown that while preterm children have an aberrant cellular immune response, these infants receive similar maternal anti-viral IgG repertoires compared to term children, albeit at lower concentrations. These data point to selectivity in placental transfer at distinct gestational ages, to ensure that children are endowed with the most robust humoral immunity even if born preterm. To begin to de ne the mechanism by which preterm selective transfer may occur, the overall quantity and functional quality of an array of vaccine-, endemic pathogen-, and common antigen-speci c antibodies were assessed across a cohort of 11 preterm and 12 term-delivered mother:infant pairs from birth through week 12. Although higher antibody levels were present in term infants, the overall functional pro les of antigen-speci c antibodies were very similar. Temporal transfer differences were ascertained across distinct antibody subpopulations, with early transfer of functional antibodies capable of binding to FcRn and FcγR2-3 receptors followed by the transfer of distinct IgG subclasses. These results provide new insights on maternal:fetal immunity, highlighting novel immune axes that may be manipulated to enhance neonatal immune transfer of antibodies through gestation.
Journal of Human Lactation, Jun 1, 2021
Background Preterm infants are more susceptible to inflammatory complications than term infants. ... more Background Preterm infants are more susceptible to inflammatory complications than term infants. Human milk contains numerous bioactive components protecting the newborn infant. Antisecretory factor, a protein regulating secretory and inflammatory processes by complex binding with complement factors, is present in human milk. Research Aims To describe antisecretory factor (1) in mother’s own milk in term and preterm infants; and (2) in donor milk before and after Holder pasteurization. Methods The study was prospective, longitudinal, explorative, and descriptive. Antisecretory factor-compleasome was determined using sandwich enzyme-linked immunosorbent assay in longitudinal human milk samples over 12 weeks from mothers ( N = 87) of term ( n = 41) and of preterm ( n = 46) infants and 20 anonymized donor human milk samples before and after Holder pasteurization. Results Antisecretory factor-compleasome was overall higher in colostrum versus mature milk ( p < .001) and no difference was found in term or preterm colostrum ( p = .82). In mature milk, compleasome was higher and more variable in the preterm group ( p = .01). After Holder pasteurization, compleasome levels increased ( p < .001). Conclusion Antisecretory factor followed the pattern of other immunological factors with high levels in colostrum. After preterm birth, levels of antisecretory factor were higher and more variable in mature milk. Holder pasteurization did not degrade antisecretory factor, indicating preserved anti-inflammatory properties in donor human milk.
Acta Paediatrica, Jun 29, 2020
Aim: To describe outcome linked to neonatal cholestasis in a defined cohort of very preterm infan... more Aim: To describe outcome linked to neonatal cholestasis in a defined cohort of very preterm infants. Methods: Population-based retrospective case-control study of preterm infants, gestational age <30 weeks, surviving for 28 days, in Stockholm County. Cholestasis was defined as conjugated bilirubin ≥30 μmol/L exceeding 20% of total level at least twice, and graded as high if exceeding 100 μmol/L. Cholestatic cases were matched on gestational week with two non-cholestatic controls. The incidence rate of cholestasis was 37/250 (14.8%), with increasing rates in lower gestational weeks. Perinatal factors associated with cholestasis were preeclampsia and being born small for gestational age. Cholestatic infants had three times more bronchopulmonary dysplasia and eight times more retinopathy of prematurity. The mortality was 13.5% in cholestatic infants versus 2.7% in controls (p=0.040). All deceased cholestatic infants had high-grade cholestasis. No surviving infants developed chronic liver disease by 10 years of age. Cholestasis was common in very preterm infants and linked to disease severity and adverse outcome. Cholestasis may be an independent risk factor for bronchopulmonary dysplasia and retinopathy of prematurity and more severe cholestasis associated with increased mortality. Cholestasis was not associated with chronic liver disease later in childhood. Cholestasis in very preterm infants is a common clinical problem, but the long-term effects are poorly known. In this population-based case-control study of very preterm infants, cholestasis developed in 14.8% of infants and was associated with higher rates of retinopathy of prematurity, bronchopulmonary dysplasia and death, but not associated with chronic liver-disease at ten years of age.
Pediatric Research, Nov 1, 2011
Background and aims: Oxidative stress, as a result of inflammation and oxygen toxicity, may affec... more Background and aims: Oxidative stress, as a result of inflammation and oxygen toxicity, may affect lung growth and contribute to the development of bronchopulmonary dysplasia (BPD) in preterm infants. Preterm infants have longer telomeres than term infants at birth. In adults, chronic obstructive lung disease has been related to shorter telomeres. Telomere length in relation to prematurity and lung function therefore was studied. Methods: Relative telomere length (RTL) was measured using real-time PCR on extracted DNA in children born preterm with a history of BPD at the age of 10 years and a control group of children born healthy at term with a history of asthma. Lung function as dynamic spirometry and inflammation examined as fractional exhaled nitric oxygen (NO) was performed. Results: Children with BPD (n= 23) compared to children with asthma (n=19) had shorter telomeres (RTL 1,43 vs 1,61, p< 0,05) and reduced lung function (Forced Expiratory Fraction (FEF 25-75%), 1,55 vs 1,88, p< 0,05) but lower levels of exhaled NO (NO 12,6 ppb vs 22,3 ppb, p< 0,05). Lung function and levels of NO were not independently correlated to RTL. Preterm birth and lung disease in infancy resulted in shorter telomere length and reduced lung function at 10 years of age compared to controls with asthma. This may indicate faster telomere attrition in preterm infants with BPD. The influence of oxidative stress and inflammation in the neonatal period and beyond needs to be further studied in relation to intra-individual telomere shortening rate and long term outcome.