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    A 2-day-old girl was admitted to surgery for repair of a left-sided diaphragmatic hernia (CDH). Preoperatively, an umbilical vein catheter (UVC) was inserted with the tip in the left hypochondrium. The UVC tip position was unchanged... more
    A 2-day-old girl was admitted to surgery for repair of a left-sided diaphragmatic hernia (CDH). Preoperatively, an umbilical vein catheter (UVC) was inserted with the tip in the left hypochondrium. The UVC tip position was unchanged radiographically peroperatively. At the fifth postopertive day abdominal distension and signs of gastric outlet obstruction appeared. Explorative laparotomy found liver necrosis at the site of the catheter tip and parenteral nutrition ascites.
    International guidelines recommend a compression to ventilation (C:V) ratio of 3:1 in neonates, and 15:2 for other paediatric age groups. The authors aimed to compare these two C:V ratios in a neonatal swine model of cardiac arrest... more
    International guidelines recommend a compression to ventilation (C:V) ratio of 3:1 in neonates, and 15:2 for other paediatric age groups. The authors aimed to compare these two C:V ratios in a neonatal swine model of cardiac arrest following asphyxia. Experimental animal study. Facility for animal research. 22 newborn pigs (age 12-36 h, weight 2.0-2.7 kg). Progressive asphyxia until asystole. Animals were randomised to receive C:V 3:1 (n=11) or 15:2 (n=11). Return of spontaneous circulation (ROSC) was defined as a heart rate ≥ 100 bpm. Also of interest were haemodynamic parameters, cerebral and systemic oxygen saturation and the proinflammatory cytokine interleukin-1β (IL-1β). Two animals in each group did not achieve ROSC. Mean (SD) increase in diastolic blood pressure (DBP; mm Hg) during compression cycles was significantly higher at a C:V ratio of 15:2 than 3:1 (7.1 (2.8) vs 4.8 (2.6)). Median time (IQR) to ROSC for the 3:1 group was 150 (140-180) s, and 195 (145-358) s for the 15:2 group. There were no significant differences in the temporal changes in haemodynamic parameters or oxygen saturation indices between the groups. IL-1β levels in cerebrospinal and bronchoalveolar lavage fluid was comparable between the groups. In neonatal pigs with asphyxia-induced cardiac arrest, the response to a C:V ratio of 15:2 is not better than the response to a C:V ratio of 3:1 despite better generation of DBP during resuscitation.
    To explore the possible effects of hyaluronan, an endogenous mediator of inflammation, on monocyte surface expression of Toll-like receptors 2 and 4 in human umbilical cord blood ex vivo, and in a model mimicking Gram-negative neonatal... more
    To explore the possible effects of hyaluronan, an endogenous mediator of inflammation, on monocyte surface expression of Toll-like receptors 2 and 4 in human umbilical cord blood ex vivo, and in a model mimicking Gram-negative neonatal sepsis. Term infant cord blood was obtained after elective caesarean sections, n = 15. Both unstimulated and lipopolysaccharide-stimulated (10 ng/mL) blood was incubated with 500 μg/mL high- or low-molecular-weight hyaluronan for 6 h. Expression of Toll-like receptors 2 and 4 on monocytes was measured using flow cytometry, and plasma concentrations of proinflammatory cytokines and matrix metalloproteinase 9 were analysed. RESULTS (MEAN ± SEM): We found a significant decrease in Toll-like receptor 4 expression in the presence of high-molecular-weight hyaluronan (HMW HA) in unstimulated blood (median fluorescence intensity 141 ± 7.3 vs. 163 ± 9.8, p = 0.019). There were no significant changes in Toll-like receptor 2 expression. Levels of cytokines and matrix metalloproteinase 9 increased in the presence of both forms of hyaluronan. Our results confirm that hyaluronan affects the neonatal immune response. The biological significance of these findings requires further clarification. More studies are needed to validate the possible down-modulation of Toll-like receptor 4 exerted by HMW HA.
    Microbiota development in (pre)term infants receiving various durations of postpartum antibiotic treatment. Determined through 16S rRNA gene amplicon sequencing (MiSeq, Illumina)
    Background: Recently, the International Liaison Committee on Resuscitation published a systematic review that concluded that routine suctioning of clear amniotic fluid in the delivery room might be associated with lower oxygen saturation... more
    Background: Recently, the International Liaison Committee on Resuscitation published a systematic review that concluded that routine suctioning of clear amniotic fluid in the delivery room might be associated with lower oxygen saturation (SpO2) and 10 min Apgar score. The aim of this study was to examine the effect of delivery room airway suctioning on the clinical appearance, including muscle tone and skin colour, of video-recorded term and preterm infants born through mainly clear amniotic fluid. Methods: This was a single-centre observational study using transcribed video recordings of neonatal stabilizations. All infants who received delivery room positive pressure ventilation (PPV) from August 2014 to November 2016 were included. The primary outcome was the effect of airway suctioning on muscle tone and skin colour (rated 0–2 according to the Apgar score), while the secondary outcome was the fraction of infants for whom airway suction preceded the initiation of PPV as a surroga...
    Very low birth weight infants (VLBW; birth weight < 1500 g) are treated with pharmaceuticals and medical equipment containing parabens and bisphenol A (BPA). Parabens are used in pharmaceuticals, whereas BPA in medical equipment where... more
    Very low birth weight infants (VLBW; birth weight < 1500 g) are treated with pharmaceuticals and medical equipment containing parabens and bisphenol A (BPA). Parabens are used in pharmaceuticals, whereas BPA in medical equipment where concentrations are rarely reported in hospitalised VLBW infants. We measured urinary concentrations of parabens and BPA and hypothesised high and increasing concentrations in infants born at lower gestational ages (GAs), and among infants with bronchopulmonary dysplasia (BPD) and late-onset septicaemia (LOS) due to higher exposure from pharmaceuticals and medical equipment. Urinary samples were collected during the first (n = 38) and fifth (n = 36) week of life. Methylparaben, ethylparaben, propylparaben, butylparaben, and BPA concentrations were measured using ultra high-performance liquid chromatography coupled to tandem mass spectrometry. VLBW infants had very high urinary concentrations of parabens and BPA compared to term infants and older children. The Σ paraben concentration was higher than detected in previous studies on premature infants. Lower GA at birth was associated with higher concentrations of parabens and BPA. Infants born before 28 weeks GA had higher first week concentrations of propylparaben (38.6 vs. 9.05 ng/mL, p = 0.007), butylparaben (0.28 vs. 0.09 ng/mL, p = 0.05) and fifth week concentrations of BPA (15.1 vs. 6.02 ng/mL, p = 0.02) than infants born after 28 weeks GA. Infants with LOS and BPD had higher fifth week concentrations of BPA than infants without LOS and BPD (LOS: 14.2 vs. 6.77 ng/mL, p = 0.07; BPD: 18.6 vs. 7.62 ng/mL, p = 0.05).
    Customized nutrient supply is vital to ensure optimal growth among very low birth weight infants (birth weight < 1500 g). The supply of amino acids is especially... more
    Customized nutrient supply is vital to ensure optimal growth among very low birth weight infants (birth weight < 1500 g). The supply of amino acids is especially important due to their impact on protein synthesis and growth. The objectives of this study were to evaluate the impact of enhanced nutrition on growth, blood concentrations of amino acids, and explore possible associations between amino acid concentrations and common neonatal morbidities. We hypothesized higher amino acids levels and growth velocity among infants on enhanced nutrient supply. This randomized controlled trial was performed in three university neonatal intensive care units in Oslo, Norway. Fifty very low birth weight infants were randomized to a control or intervention group. Within 24 h after birth, infants in the intervention group received enhanced supply of energy, amino acids, lipids, long-chain polyunsaturated fatty acids and vitamin A, whereas the control group received a standard nutrient supply. The intervention continued until 52 weeks postmenstrual age or until a body weight of 5.5 kg was reached. Amino acid analyses were performed at birth, day 3, 5 weeks of age and 5 months corrected age. Detailed information about nutrient intake, morbidities, blood amino acid concentrations and growth velocity were collected from 44 infants (6 infants excluded). High-performance liquid chromatography was used for amino acid analysis. The intervention group (n = 23) received higher supply of proteins, with higher blood concentrations of amino acids measured at 5 weeks of age, and improved growth velocity (mean 17.4 vs 14.3 g/kg/day, p < 0.001) at 36 weeks postmenstrual age, compared to the control group (n = 21). The correlation between concentrations of branched chain amino acids (leucine, isoleucine and valine) and growth was stronger and more positive among infants: a) in the control group (correlation coefficient ≥ 0.68, p ≤ 0.004); b) born with birth weight appropriate for gestational age (correlation coefficient ≥ 0.53, p ≤ 0.009) and c) not diagnosed with septicemia (correlation coefficient ≥ 0.63, p ≤ 0.005). Enhanced nutrient supply to very low birth weight infants led to higher blood amino acid concentrations and improved growth. The correlations between amino acid concentrations and growth velocity were weaker in the intervention group as compared to the control group. This could reflect an upper threshold for protein synthesis and growth with our intervention, whereas a potential for further growth with increasing amino acid supply was possible for the control group. NCT01103219.
    BackgroundAmbient heat exposure is increasing due to climate change and is known to affect the health of pregnant and postpartum women, and their newborns. Evidence for the effectiveness of interventions to prevent heat health outcomes in... more
    BackgroundAmbient heat exposure is increasing due to climate change and is known to affect the health of pregnant and postpartum women, and their newborns. Evidence for the effectiveness of interventions to prevent heat health outcomes in east Africa is limited. Codesigning and integrating local-indigenous and conventional knowledge is essential to develop effective adaptation to climate change.MethodsFollowing qualitative research on heat impacts in a community in Kilifi, Kenya, we conducted a two-day codesign workshop to inform a set of interventions to reduce the impact of heat exposure on maternal and neonatal health. Participants were drawn from a diverse group of purposively selected influencers, implementers, policy makers, service providers and community members. The key domains of focus for the discussion were: behavioral practices, health facilities and health system factors, home environment, water scarcity, and education and awareness. Following the discussions and group...
    IntroductionPulmonary hemorrhage (PH) is a life-threatening complication seen in very sick newborns with high morbidity and mortality. There is little data on the incidence, risk factors, and ultimate survival of newborns with pulmonary... more
    IntroductionPulmonary hemorrhage (PH) is a life-threatening complication seen in very sick newborns with high morbidity and mortality. There is little data on the incidence, risk factors, and ultimate survival of newborns with pulmonary hemorrhage in sub-Saharan countries, where the healthcare provision and facility differ in many ways compared to high-income countries. Hence, this study aimed to determine the incidence, identify the risk factors, and describe the outcome of pulmonary hemorrhage in newborns in a low middle income country setting.Methods and materialsA cohort study with prospective data collection was conducted in a public, tertiary-level hospital in Botswana, the Princess Marina Hospital (PMH). All newborns admitted to the neonatal unit from 1 January 2020 to 31 December 2021 were included in the study. Data were collected using a checklist developed on the RedCap database (https//:ehealth.ub.ac.bw/redcap). The incidence rate of pulmonary hemorrhage was calculated a...
    Adequate nutrient supply is essential for optimal postnatal growth in very low birth weight (VLBW, birth weight<1,500 g) infants. Early growth may influence the risk of metabolic syndrome later in life. To evaluate growth and blood... more
    Adequate nutrient supply is essential for optimal postnatal growth in very low birth weight (VLBW, birth weight<1,500 g) infants. Early growth may influence the risk of metabolic syndrome later in life. To evaluate growth and blood metabolic markers (adiponectin, leptin, and insulin-like growth factor-1 (IGF-1)) in VLBW infants participating in a randomized nutritional intervention study. Fifty VLBW infants were randomized to an enhanced nutrient supply or a standard nutrient supply. Thirty-seven infants were evaluated with growth measurements until 2 years corrected age (CA). Metabolic markers were measured at birth and 5 months CA. Weight gain and head growth were different in the two groups from birth to 2 years CA (weight gain: pinteraction=0.006; head growth: pinteraction=0.002). The intervention group improved their growth z-scores after birth, whereas the control group had a pronounced decline, followed by an increase and caught up with the intervention group after dischar...
    ObjectiveThe International Association of Diabetes and Pregnancy Study Groups (IADPSG) recently proposed new criteria for diagnosing gestational diabetes mellitus (GDM). We compared prevalence rates, risk factors, and the effect of... more
    ObjectiveThe International Association of Diabetes and Pregnancy Study Groups (IADPSG) recently proposed new criteria for diagnosing gestational diabetes mellitus (GDM). We compared prevalence rates, risk factors, and the effect of ethnicity using the World Health Organization (WHO) and modified IADPSG criteria.MethodsThis was a population-based cohort study of 823 (74% of eligible) healthy pregnant women, of whom 59% were from ethnic minorities. Universal screening was performed at 28±2 weeks of gestation with the 75 g oral glucose tolerance test (OGTT). Venous plasma glucose (PG) was measured on site. GDM was diagnosed as per the definition of WHO criteria as fasting PG (FPG) ≥7.0 or 2-h PG ≥7.8 mmol/l; and as per the modified IADPSG criteria as FPG ≥5.1 or 2-h PG ≥8.5 mmol/l.ResultsOGTT was performed in 759 women. Crude GDM prevalence was 13.0% with WHO (Western Europeans 11%, ethnic minorities 15%, P=0.14) and 31.5% with modified IADPSG criteria (Western Europeans 24%, ethnic mi...
    Very low birth weight infants (VLBW; birth weight<1500g) are exposed to potentially harmful phthalates from medical devices during their hospital stay. We measured... more
    Very low birth weight infants (VLBW; birth weight<1500g) are exposed to potentially harmful phthalates from medical devices during their hospital stay. We measured urinary phthalate concentrations among hospitalized VLBW infants participating in a nutritional study. Possible associations between different phthalates and birth weight (BW), septicemia and bronchopulmonary dysplasia (BPD) were evaluated. Forty-six VLBW infants were enrolled in this randomized controlled nutritional study. The intervention group (n=24) received increased quantities of energy, protein, fat, essential fatty acids and vitamin A, as compared to the control group (n=22). The concentrations of 12 urinary phthalate metabolites were measured, using high-performance liquid chromatography coupled to tandem mass spectrometry, at 3 time points during the first 5weeks of life. During this study, the levels of di (2-ethylhexyl) phthalate (DEHP) metabolites decreased, whereas an increasing trend was seen regarding metabolites of di-iso-nonyl phthalate (DiNP). Significantly higher levels of phthalate metabolites were seen in infants with lower BW and those diagnosed with late onset septicemia or BPD. A significant positive correlation between the duration of respiratory support and DEHP metabolites was observed (p≤0.01) at 2.9weeks of age. Birth weight was negatively associated with urinary phthalate metabolite concentrations. Infants with lower BW and those diagnosed with septicemia or BPD experienced prolonged exposure from medical equipment containing phthalates, with subsequent higher levels of phthalate metabolites detected. Clinical Trial Registration no.: NCT01103219.
    A 2-day-old girl was admitted to surgery for repair of a left-sided diaphragmatic hernia (CDH). Preoperatively, an umbilical vein catheter (UVC) was inserted with the tip in the left hypochondrium. The UVC tip position was unchanged... more
    A 2-day-old girl was admitted to surgery for repair of a left-sided diaphragmatic hernia (CDH). Preoperatively, an umbilical vein catheter (UVC) was inserted with the tip in the left hypochondrium. The UVC tip position was unchanged radiographically peroperatively. At the fifth postopertive day abdominal distension and signs of gastric outlet obstruction appeared. Explorative laparotomy found liver necrosis at the site of the catheter tip and parenteral nutrition ascites.
    Background Optimizing resuscitation is important to prevent morbidity and mortality from perinatal asphyxia. The metabolism of cells and tissues is severely disturbed during asphyxia and resuscitation, and metabolomic analyses provide a... more
    Background
    Optimizing resuscitation is important to prevent morbidity and mortality from perinatal asphyxia. The metabolism of cells and tissues is severely disturbed during asphyxia and resuscitation, and metabolomic analyses provide a snapshot of many small molecular weight metabolites in body fluids or tissues. In this study metabolomics profiles were studied in newborn pigs that were asphyxiated and resuscitated using different protocols to identify biomarkers for subject characterization, intervention effects and possibly prognosis.

    Methods
    A total of 125 newborn Noroc pigs were anesthetized, mechanically ventilated and inflicted progressive asphyxia until asystole. Pigs were randomized to resuscitation with a FiO2 0.21 or 1.0, different duration of ventilation before initiation of chest compressions (CC), and different CC to ventilation ratios. Plasma and urine samples were obtained at baseline, and 2 h and 4 h after return of spontaneous circulation (ROSC, heart rate >= 100 bpm). Metabolomics profiles of the samples were analyzed by nuclear magnetic resonance spectroscopy.

    Results
    Plasma and urine showed severe metabolic alterations consistent with hypoxia and acidosis 2 h and 4 h after ROSC. Baseline plasma hypoxanthine and lipoprotein concentrations were inversely correlated to the duration of hypoxia sustained before asystole occurred, but there was no evidence for a differential metabolic response to the different resuscitation protocols or in terms of survival.

    Conclusions
    Metabolic profiles of asphyxiated newborn pigs showed severe metabolic alterations. Consistent with previously published reports, we found no evidence of differences between established and alternative resuscitation protocols. Lactate and pyruvate may have a prognostic value, but have to be independently confirmed.
    Research Interests:
    Optimal nutrient supply to very low birth weight (VLBW: BW <1,500 g) infants is important for growth and neurodevelopment. Growth restriction is common among these infants and may be associated with neurocognitive impairments. To... more
    Optimal nutrient supply to very low birth weight (VLBW: BW <1,500 g) infants is important for growth and neurodevelopment. Growth restriction is common among these infants and may be associated with neurocognitive impairments. To compare an enhanced nutrient supply to a routine supply given to VLBW infants and to evaluate the effects on visual perception of global form and motion measured by visual event-related potentials (VERP). A total of 50 VLBW infants were randomized to an intervention group that received an increased supply of energy, protein, fat, essential fatty acids, and vitamin A or a control group that received standard nutritional care. At 5 months' corrected age the infants were examined using VERP to investigate the responses to global form and motion. VERP were analysed at the first (f1) and third (f3) harmonics of the stimulus frequency. Data from 31 subjects were eligible for analysis. The motion VERP responses for the f1 and f3 components were stronger in ...
    The COMFORT behavioural scale was developed to assess sedation, pain and distress in children unable to report pain. Our aims were to test construct validity of the scale in toddlers undergoing minor surgery and determine the inter-rater... more
    The COMFORT behavioural scale was developed to assess sedation, pain and distress in children unable to report pain. Our aims were to test construct validity of the scale in toddlers undergoing minor surgery and determine the inter-rater reliability of the scale. We consecutively enrolled 45 children aged 12-36 months from a Norwegian surgical outpatient care unit. The level of sedation, pain and distress was assessed before and after surgery with the COMFORT behavioural scale. Inter-rater reliability was estimated and construct validity was tested based on a priori defined hypotheses. A 2.5-point (15%) change in the scale was considered clinically important. We obtained 307 scores covering most of the scale's range, but a floor effect was clearly present. Inter-rater reliability was high between assessors (intraclass correlation coefficient = 0.96; 95% CI 0.92-0.98). Clinically important differences were seen between baseline and light sedation (3.1 points, p < 0.001) and between light and deep sedation (4.6 points, p = 0.002). The difference between baseline and our definition of a pain/distress state was not clinically important (1.5 points, p = 0.039). The COMFORT behavioural scale can provide one aspect of an overall clinical assessment of sedation, and probably pain and distress, in toddlers before and after surgery.
    In neonatal jaundice, phototherapy converts bilirubin to more polar photoisomers which can be excreted without conjugation. We measured changes in the concentration of bilirubin Z,E-photoisomer during the first four hours of intensive... more
    In neonatal jaundice, phototherapy converts bilirubin to more polar photoisomers which can be excreted without conjugation. We measured changes in the concentration of bilirubin Z,E-photoisomer during the first four hours of intensive phototherapy using single fluorescent lights as a reference, compared to double fluorescent lights, and a single unit of photodiodes. Neonates (N=42; BW 1200-4690G; GA 28-42W) were studied during phototherapy. Infants were randomized to: i) single, or ii) double fluorescent phototherapy; or iii) single unit photodiodes. Irradiance was measured. Serum bilirubin (by cooximetry) and Z,E bilirubin (by HPLC) were measured at 0,15, 30, 60, 120, and 240 minutes after the start of phototherapy. Data were analyzed with a linear mixed model. There was a highly significant increase of Z,E-bilirubin over time (p<0.0001), starting at 15 min. Photoisomers reached ~25% of total bilirubin concentration after four hours. However, there were no significant difference...
    To investigate whether intractable respiratory distress syndrome in three Norwegian term infants was due to mutations in the ABCA3 gene. The genes encoding SP-B (SFTPB), SP-C (SFTPC), and ABCA3 (ABCA3) were sequenced from the parents of... more
    To investigate whether intractable respiratory distress syndrome in three Norwegian term infants was due to mutations in the ABCA3 gene. The genes encoding SP-B (SFTPB), SP-C (SFTPC), and ABCA3 (ABCA3) were sequenced from the parents of one infant and two unrelated infants with fatal neonatal lung disease. Lung tissue was examined by histology, immunohistochemistry and electron microscopy. Novel ABCA3 mutations were identified in each family. One patient had a phenotype differing from previous descriptions of this disease with an initial uneventful period. The diagnosis was established 19 years after death by analysing DNA material from the parents, with an ABCA3 mutation identified on one allele in each parent. The other two infants had more typical clinical courses with the onset of respiratory symptoms immediately after birth. ABCA3 mutations were identified on both alleles from these two infants, and electron microscopy of alveolar type 2 cells demonstrated abnormal lamellar body formation characteristic of this disorder. ABCA3 mutations were the basis for lung disease in all three patients. Children with lung disease due to ABCA3 deficiency may not have symptoms at birth. The finding of five novel mutations indicates allelic heterogeneity for ABCA3 mutations within the Norwegian population.

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