1. |
- Aburawi, Elhadi, et al.
(author)
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Coronary Flow in Neonates with Impaired Intrauterine Growth.
- 2012
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In: Journal of the American Society of Echocardiography. - : Elsevier BV. - 1097-6795 .- 0894-7317. ; 25:3, s. 313-318
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Journal article (peer-reviewed)abstract
- BACKGROUND: Subclinical myocardial injury has been reported in newborns with fetal weights < 2 SDs for gestational age. Intrauterine growth restriction might affect cardiac function and coronary flow (CF). METHODS: Seventeen newborns with intrauterine growth restriction and 15 age-matched healthy controls were enrolled in the study. Blood flow in the umbilical artery and maternal uterine artery was assessed using Doppler velocimetry. Cardiac function and left anterior descending coronary artery CF were measured using transthoracic Doppler echocardiography at 1 week of age. RESULTS: The mean growth deviation of the newborns from normal was -2.5 ± 0.2 SDs. Percentage left ventricular shortening fraction was 39 ± 4.3% in patients and 42 ± 4.1% in controls (P = .40), and the mean left ventricular mass index was 86.6 g/m(2) in patients and 73.7 g/m(2) in controls (P < .01). The mean left anterior descending coronary artery diameter was 0.99 ± 0.1 mm in patients and 0.8 ± 0.1 mm in controls (P = .002). The left anterior descending coronary artery flow velocity-time integral was correlated with left ventricular mass index (r = 0.31, P = .007) and with mitral peak E/A ratio (r = 0.74, P = .01). Intrauterine growth restriction was associated with increased peak flow velocity in diastole (34.5 ± 4 vs 19 ± 6 cm/sec in controls, P = .0001), as well as increased CF (37 ± 7.3 vs 8.2 ± 3.0 mL/min in controls, P = .001). CONCLUSIONS: CF is significantly increased in neonates with impaired intrauterine growth. Left ventricular mass index is increased, but systolic and diastolic function remains normal. The clinical significance of increased CF is unclear, but it might lead to decreased CF reserve.
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2. |
- Ahola, T., et al.
(author)
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Plasma 8-isoprostane is increased in preterm infants who develop bronchopulmonary dysplasia or periventricular leukomalacia
- 2004
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In: Pediatr Res. - 0031-3998. ; 56:1, s. 88-93
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Journal article (peer-reviewed)abstract
- Our aim was to assess the plasma free 8-epi-prostaglandin F(2alpha) (8-isoprostane) and ascorbyl radical as risk indicators for oxidative damage in extremely low birth weight infants (ELBWIs) and the effect of N-acetylcysteine (NAC) on these markers. Plasma samples were collected on days 3 and 7 of life from infants who were enrolled in a randomized, controlled trial in which i.v. NAC or placebo was administered to ELBWIs during the first week of life, with the aim of preventing bronchopulmonary dysplasia (BPD). Plasma 8-isoprostane was analyzed in 83 infants using an enzyme immunoassay kit. Ascorbyl radical concentration was measured in 61 infants with electron spin resonance spectroscopy. The 8-isoprostane concentrations were similar in the NAC and placebo groups. In infants who later developed BPD or died (n = 29), the median (range) 8-isoprostane concentration was significantly higher (p = 0.001) on day 3 and day 7 [50.0 pg/mL (19-360) and 57.0 pg/mL (14-460), respectively] than in survivors without BPD [n = 54; 34.5 pg/mL (5-240) and 39.5 pg/mL (7-400), respectively]. The 8-isoprostane levels increased significantly more (p < 0.05) in infants who later developed periventricular leukomalacia. NAC treatment or the later development of BPD was not related to the ascorbyl radical levels. The ascorbyl radical level decreased significantly in all groups from day 3 to day 7, but the difference between the groups was not significant. The mean (SD) ascorbyl radical level on day 3 was significantly higher (p < 0.01) in infants who later developed periventricular leukomalacia [287 (124) versus 194 (90)]. These data suggest that plasma 8-isoprostane could serve as a marker in assessing the risk for BPD development in ELBWIs.
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3. |
- Ahola, T, et al.
(author)
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Thiol metabolism in preterm infants during the first week of life
- 2004
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 64:7, s. 649-658
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Journal article (peer-reviewed)abstract
- Background: Oxidative stress is implicated in the pathogenesis of several complications of prematurity. The glutathione cycle is one of the most important intracellular antioxidant systems. The synthesis of glutathione may not be adequate in preterm neonates because of the low levels of cysteine available. The aim of this study was to evaluate cysteine and glutathione metabolism during the first week of life in preterm infants. Methods: Plasma and erythrocyte thiol concentrations were measured in 78 preterm infants with a birthweight of 500 1500 g, and erythrocyte glutamate-cysteine ligase (GCL), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferases (GST) and glucose 6-phosphatedehydrogenase (G6PDH) in 26 infants with a birthweight of 1000 - 1500 g. Results: The mean (SD) plasma glutathione concentration increased from day 0 to day 1 (14.9 (7.1) vs. 27.7 (11.9) mumol/L, p<0.001), and then decreased. The plasma cysteine concentration changed in the opposite direction ( 172 (59) vs. 129 (42) μmol/L, p<0.01). In infants with respiratory distress syndrome (RDS) the mean plasma glutathione concentration, but not cysteine, was lower on day 0 compared with infants without RDS (11.7 (5.2) vs. 21.4 (5.6) mumol/L, p<0.01). Erythrocyte glutathione concentration decreased during the first week of life, whereas erythrocyte cysteine concentration increased significantly from day 3 to day 7 (p<0.01). Erythrocyte cysteine and glutathione concentrations had a positive correlation. The GCL and GR activities did not change, but GST and G6PDH activities decreased during the first week (p<0.01). GPx activity decreased until day 3 (p<0.01) and was higher on day 0 and day 1 in infants with RDS. Conclusions: Very low birthweight infants have an initial increase in plasma glutathione and initial decrease in plasma cysteine level during the first week of life, and also a positive correlation between erythrocyte cysteine and glutathione levels.
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4. |
- Austeng, Dordi, et al.
(author)
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Incidence of and risk factors for neonatal morbidity after active perinatal care : extremely preterm infants study in Sweden (EXPRESS)
- 2010
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In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 99:7, s. 978-992
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Journal article (peer-reviewed)abstract
- Aims: The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors. Methods: Population based study of infants born before 27 gestational weeks and admitted for neonatal intensive care in Sweden during 2004-2007. Results: Of 638 admitted infants, 141 died. Among these, life support was withdrawn in 55 infants because of anticipation of poor long-term outcome. Of 497 surviving infants, 10% developed severe intraventricular haemorrhage (IVH), 5.7% cystic periventricular leucomalacia (cPVL), 41% septicaemia and 5.8% necrotizing enterocolitis (NEC); 61% had patent ductus arteriosus (PDA) and 34% developed retinopathy of prematurity (ROP) stage >= 3. Eighty-five per cent needed mechanical ventilation and 25% developed severe bronchopulmonary dysplasia (BPD). Forty-seven per cent survived to one year of age without any severe IVH, cPVL, severe ROP, severe BPD or NEC. Tocolysis increased and prolonged mechanical ventilation decreased the chances of survival without these morbidities. Maternal smoking and higher gestational duration were associated with lower risk of severe ROP, whereas PDA and poor growth increased this risk. Conclusion: Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long-term health of survivors are warranted.
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5. |
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6. |
- Bolk, J., et al.
(author)
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Perinatal risk factors for developmental coordination disorder in children born extremely preterm
- 2023
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In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 112:4, s. 675-685
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Journal article (peer-reviewed)abstract
- AimChildren born extremely preterm frequently have developmental coordination disorder (DCD). We aimed to evaluate perinatal risk factors for DCD. MethodsSwedish national cohort study including 226 children born before 27 gestational weeks without major neurodevelopmental disabilities at 6.5 years. Outcome was DCD, defined as <= 5th percentile on the Movement Assessment Battery for Children-Second Edition. Perinatal risk factors were evaluated using multivariable logistic regression. ResultsDCD was present in 84/226 (37.2%) children. Of the risk factors known at 40 weeks gestation, independent and significant risk factors for DCD were: mother's age at delivery (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.07-2.80); pre-eclampsia (2.79, 1.14-6.80); mother born in a non-Nordic country (2.23, 1.00-4.99); gestational age per week increase (0.70, 0.50-0.99) and retinopathy of prematurity (2.48, 1.26-4.87). Of factors known at discharge, postnatal steroids exposure (2.24, 1.13-4.46) and mechanical ventilation (1.76, 1.06-2.09) were independent risk factors when added to the model in separate analyses. ConclusionThe risk of DCD in children born extremely preterm was multifactorial and associated with gestational age largely mediated by ROP, maternal factors, pre-eclampsia, administration of postnatal steroids and mechanical ventilation. These risk factors are common among children born extremely preterm, contributing to their high risk of DCD.
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7. |
- Bonamy, Anna-Karin Edstedt, et al.
(author)
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Blood Pressure in 6-Year-Old Children Born Extremely Preterm
- 2017
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In: Journal of the American Heart Association. - : WILEY. - 2047-9980. ; 6:8
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Journal article (peer-reviewed)abstract
- Background-Advances in perinatal medicine have increased infant survival after very preterm birth. Although this progress is welcome, there is increasing concern that preterm birth is an emerging risk factor for hypertension at young age, with implications for the lifetime risk of cardiovascular disease. Methods and Results-We measured casual blood pressures (BPs) in a population-based cohort of 6-year-old survivors of extremely preterm birth (< 27 gestational weeks; n=171) and in age-and sex-matched controls born at term (n=172). Measured BP did not differ, but sex, age-, and height-adjusted median z scores were 0.14 SD higher (P=0.02) for systolic BP and 0.10 SD higher (P=0.01) for diastolic BP in children born extremely preterm than in controls. Among children born extremely preterm, shorter gestation, higher body mass index, and higher heart rate at follow-up were all independently associated with higher BP at 6 years of age, whereas preeclampsia, smoking in pregnancy, neonatal morbidity, and perinatal corticosteroid therapy were not. In multivariate regression analyses, systolic BP decreased by 0.10 SD (P=0.08) and diastolic BP by 0.09 SD (P=0.02) for each week-longer gestation. Conclusions-Six-year-old children born extremely preterm have normal but slightly higher BP than their peers born at term. Although this finding is reassuring for children born preterm and their families, follow-up at older age is warranted.
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8. |
- Carral, V, et al.
(author)
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A kind of auditory 'primitive intelligence' already present at birth
- 2005
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In: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 21:11, s. 3201-3204
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Journal article (peer-reviewed)abstract
- 'Primitive intelligence' in audition refers to the capacity of the auditory system to adaptatively model the acoustic regularity and react neurophysiologically to violations of such regularity, thus supporting the ability to predict future auditory events. In the present study, event-related brain potentials to pairs of tones were recorded in 11 human newborns to determine the infants' ability to extract an abstract acoustic rule, the direction of a frequency change. Most of the pairs (standard, P = 0.875) were of ascending frequency (i.e. the second tone higher than the first), while the remaining pairs (deviant, P = 0.125) were of descending frequency (the second tone being lower). Their frequencies varied among seven levels to prevent discrimination between standard and deviant pairs on the basis of absolute frequencies. We found that event-related brain potentials to deviant pairs differed in amplitude from those to standard pairs at 50-450 ms from the onset of the second tone of a pair, indicating the infants' ability to represent the abstract rule. This finding suggests the early ontogenetic origin of 'primitive intelligence' in audition that eventually may form a prerequisite for later language acquisition.
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9. |
- Cizmeci, Mehmet N, et al.
(author)
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Assessment of Brain Injury and Brain Volumes after Posthemorrhagic Ventricular Dilatation : A Nested Substudy of the Randomized Controlled ELVIS Trial
- 2019
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In: Journal of Pediatrics. - : Elsevier BV. - 1097-6833 .- 0022-3476. ; 208, s. 2-197
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To compare the effect of early and late intervention for posthemorrhagic ventricular dilatation on additional brain injury and ventricular volume using term-equivalent age-MRI.STUDY DESIGN: In the Early vs Late Ventricular Intervention Study (ELVIS) trial, 126 preterm infants ≤34 weeks of gestation with posthemorrhagic ventricular dilatation were randomized to low-threshold (ventricular index >p97 and anterior horn width >6 mm) or high-threshold (ventricular index >p97 + 4 mm and anterior horn width >10 mm) groups. In 88 of those (80%) with a term-equivalent age-MRI, the Kidokoro Global Brain Abnormality Score and the frontal and occipital horn ratio were measured. Automatic segmentation was used for volumetric analysis.RESULTS: The total Kidokoro score of the infants in the low-threshold group (n = 44) was lower than in the high-threshold group (n = 44; median, 8 [IQR, 5-12] vs median 12 [IQR, 9-17], respectively; P < .001). More infants in the low-threshold group had a normal or mildly increased score vs more infants in the high-threshold group with a moderately or severely increased score (46% vs 11% and 89% vs 54%, respectively; P = .002). The frontal and occipital horn ratio was lower in the low-threshold group (median, 0.42 [IQR, 0.34-0.63]) than the high-threshold group (median 0.48 [IQR, 0.37-0.68], respectively; P = .001). Ventricular cerebrospinal fluid volumes could be calculated in 47 infants and were smaller in the low-threshold group (P = .03).CONCLUSIONS: More brain injury and larger ventricular volumes were demonstrated in the high vs the low-threshold group. These results support the positive effects of early intervention for posthemorrhagic ventricular dilatation.TRIAL REGISTRATION: ISRCTN43171322.
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10. |
- Cizmeci, Mehmet N, et al.
(author)
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Randomized Controlled Early versus Late Ventricular Intervention Study in Posthemorrhagic Ventricular Dilatation : Outcome at 2 Years
- 2020
-
In: Journal of Pediatrics. - : Elsevier BV. - 1097-6833 .- 0022-3476. ; 226, s. 3-35
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To compare the effect of intervention at low vs high threshold of ventriculomegaly in preterm infants with posthemorrhagic ventricular dilatation on death or severe neurodevelopmental disability.STUDY DESIGN: This multicenter randomized controlled trial reviewed lumbar punctures initiated after either a low threshold (ventricular index of >p97 and anterior horn width of >6 mm) or high threshold (ventricular index of >p97 + 4 mm and anterior horn width of >10 mm). The composite adverse outcome was defined as death or cerebral palsy or Bayley composite cognitive/motor scores <-2 SDs at 24 months corrected age.RESULTS: Outcomes were assessed in 113 of 126 infants. The composite adverse outcome was seen in 20 of 58 infants (35%) in the low threshold group and 28 of 55 (51%) in the high threshold (P = .07). The low threshold intervention was associated with a decreased risk of an adverse outcome after correcting for gestational age, severity of intraventricular hemorrhage, and cerebellar hemorrhage (aOR, 0.24; 95% CI, 0.07-0.87; P = .03). Infants with a favorable outcome had a smaller fronto-occipital horn ratio (crude mean difference, -0.06; 95% CI, -0.09 to -0.03; P < .001) at term-equivalent age. Infants in the low threshold group with a ventriculoperitoneal shunt, had cognitive and motor scores similar to those without (P = .3 for both), whereas in the high threshold group those with a ventriculoperitoneal shunt had significantly lower scores than those without a ventriculoperitoneal shunt (P = .01 and P = .004, respectively).CONCLUSIONS: In a post hoc analysis, earlier intervention was associated with a lower odds of death or severe neurodevelopmental disability in preterm infants with progressive posthemorrhagic ventricular dilatation.TRIAL REGISTRATION: ISRCTN43171322.
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11. |
- Davoudi, Mina, et al.
(author)
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A mouse model of mitochondrial complex III dysfunction induced by myxothiazol.
- 2014
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In: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 446:4, s. 1079-1084
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Journal article (peer-reviewed)abstract
- Myxothiazol is a respiratory chain complex III (CIII) inhibitor that binds to the ubiquinol oxidation site Qo of CIII. It blocks electron transfer from ubiquinol to cytochrome b and thus inhibits CIII activity. It has been utilized as a tool in studies of respiratory chain function in in vitro and cell culture models. We developed a mouse model of biochemically induced and reversible CIII inhibition using myxothiazol. We administered myxothiazol intraperitoneally at a dose of 0.56mg/kg to C57Bl/J6 mice every 24h and assessed CIII activity, histology, lipid content, supercomplex formation, and gene expression in the livers of the mice. A reversible CIII activity decrease to 50% of control value occurred at 2h post-injection. At 74h only minor histological changes in the liver were found, supercomplex formation was preserved and no significant changes in the expression of genes indicating hepatotoxicity or inflammation were found. Thus, myxothiazol-induced CIII inhibition can be induced in mice for four days in a row without overt hepatotoxicity or lethality. This model could be utilized in further studies of respiratory chain function and pharmacological approaches to mitochondrial hepatopathies.
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12. |
- Davoudi, Mina, et al.
(author)
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Complex I Function and Supercomplex Formation Are Preserved in Liver Mitochondria Despite Progressive Complex III Deficiency.
- 2014
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:1
-
Journal article (peer-reviewed)abstract
- Functional oxidative phosphorylation requires appropriately assembled mitochondrial respiratory complexes and their supercomplexes formed mainly of complexes I, III and IV. BCS1L is the chaperone needed to incorporate the catalytic subunit, Rieske iron-sulfur protein, into complex III at the final stage of its assembly. In cell culture studies, this subunit has been considered necessary for supercomplex formation and for maintaining the stability of complex I. Our aim was to assess the importance of fully assembled complex III for supercomplex formation in intact liver tissue. We used our transgenic mouse model with a homozygous c.232A>G mutation in Bcs1l leading to decreased expression of BCS1L and progressive decrease of Rieske iron-sulfur protein in complex III, resulting in hepatopathy. We studied supercomplex formation at different ages using blue native gel electrophoresis and complex activity using high-resolution respirometry. In isolated liver mitochondria of young and healthy homozygous mutant mice, we found similar supercomplexes as in wild type. In homozygotes aged 27-29 days with liver disorder, complex III was predominantly a pre-complex lacking Rieske iron-sulfur protein. However, the main supercomplex was clearly detected and contained complex III mainly in the pre-complex form. Oxygen consumption of complex IV was similar and that of complex I was twofold compared with controls. These complexes in free form were more abundant in homozygotes than in controls, and the mRNA of complex I subunits were upregulated. In conclusion, when complex III assembly is deficient, the pre-complex without Rieske iron-sulfur protein can participate with available fully assembled complex III in supercomplex formation, complex I function is preserved, and respiratory chain stability is maintained.
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13. |
- Davoudi, Mina, et al.
(author)
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COX7A2L/SCAFI and pre-complex III modify respiratory chain supercomplex formation in different mouse strains with a Bcs1l mutation
- 2016
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:12
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Journal article (peer-reviewed)abstract
- The COX7A2L (Supercomplex Assembly Factor I, SCAFI) protein has been proposed to be a mitochondrial supercomplex assembly factor required for respirasome (supercomplex containing complexes I, III, and IV) formation. In the C57BL/6 mouse strain a homozygous in-frame 6-base-pair deletion in the COX7a2l/SCAF1 gene resulting in unstable protein and suggesting loss of function was previously identified. The loss of SCAFI was shown to impede respirasome formation, a major concern for the use of C57BL mouse strains in mitochondrial research. In contradiction, another recent study suggested that supercomplex formation is independent of SCAFI isoforms. We investigated whether SCAFI isoform status affected the disease severity and supercomplex formation in the liver of Bcs1lc.232A>G knock-in mice with incomplete complex III assembly. In homozygotes (Bcs1lG/G) of mixed (C57BL/6:129/Sv) genetic background, the lifespan was similar in mice with wild-type SCAFI allele and in those homozygous (SCAFIshort/short) for the deleted SCAF1 variant (34-3 days; n = 6 vs. 32-2 days; n = 7, respectively). SCAFI heterozygosity (SCAFIlong/short) resulted in decreased SCAFI protein but respirasome assembly was unaffected. Congenic (C57BL/6) mice were of the genotype SCAFIshort/short and had no detectable SCAFI protein. In their liver mitochondria, respirasome composition was altered as compared to mixed background mice. Complex IV was mainly present as monomers and dimers, and only low amounts were found in combination with complex I and complex III or with precomplex III. The main supercomplex in the liver mitochondria of C57BL/6 mice comprised only complexes I and III. In conclusion, in liver mitochondria of C57BL/6 mice, supercomplexes had markedly reduced amount of, but were not completely depleted of, complex IV, supporting a role for COX7A2L/SCAFI in supercomplex assembly. However, the disease progression of the Bcs1l mutant mice was unrelated to SCAFI isoforms and supercomplex composition, suggesting that other genetic factors contribute to the different survival in the different genetic backgrounds.
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14. |
- Diaz, Francisca, et al.
(author)
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Mitochondrial disorders caused by mutations in respiratory chain assembly factors
- 2011
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In: Seminars in Fetal & Neonatal Medicine. - : Elsevier BV. - 1878-0946 .- 1744-165X. ; 16:4, s. 197-204
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Journal article (peer-reviewed)abstract
- Mitochondrial diseases involve the dysfunction of the oxidative phosphorylation (OXPHOS) system. This group of diseases presents with heterogeneous clinical symptoms affecting mainly organs with high energy demands. Defects in the multimeric complexes comprising the OXPHOS system have a dual genetic origin, mitochondrial or nuclear DNA. Although many nuclear DNA mutations involve genes coding for subunits of the respiratory complexes, the majority of mutations found to date affect factors that do not form part of the final complexes. These assembly factors or chaperones have multiple functions ranging from cofactor insertion to proper assembly/stability of the complexes. Although significant progress has been made in the last few years in the discovery of new assembly factors, the function of many remains elusive. Here, we describe assembly factors or chaperones that are required for respiratory chain complex assembly and their clinical relevance. (C) 2011 Elsevier Ltd. All rights reserved.
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15. |
- Elens, Laure, et al.
(author)
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Genetic Predisposition to Poor Opioid Response in Preterm Infants : Impact of KCNJ6 and COMT Polymorphisms on Pain Relief after Endotracheal Intubation
- 2016
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In: Therapeutic Drug Monitoring. - 0163-4356 .- 1536-3694. ; 38:4, s. 525-533
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Journal article (peer-reviewed)abstract
- Background: Single-nucleotide polymorphisms in genes involved in pain control might predispose to exaggerated sensitivity or difference in opioid analgesic effect. The relevance of the KCNJ6 -1250G>A (rs6517442, c.-1787G>A) and the catecholamine-O-methyltransferase (COMT) c.472G>A (rs4680, Val 158 Met) single-nucleotide polymorphisms were studied in preterm infants needing intubation and randomized to a premedication strategy including remifentanil (n 17) or morphine (n 17). Methods: Pain was scored with Astrid Lindgren and Lund Children's Hospital Pain Assessment Scale every 30 minutes for 6 hours. The pain relief provided by the opioids was compared between the different KCNJ6 and COMT genotypes. Results: Infants homozygous for the KCNJ6 -1250A allele had an increased duration after intubation to achieve a score indicating no pain compared with infants with the A/G or G/G genotypes (182 ± 30, 109 ± 29, and 60 ± 21 minutes, respectively; Logrank 7.5, P 0.006). Similarly, the duration was increased in individuals with the COMT Val/Val alleles compared with Val/Met and Met/Met (285 ± 37, 137 ± 25, and 63 ± 15 minutes, respectively; Logrank 14.4, P 0.0021). Cox proportional hazards analysis confirmed that the variation in both genes was independently associated with susceptibility to respond to therapy. Conclusion: We conclude that the KCNJ6 -1250A and COMT 158 Val alleles are predisposing preterm newborns to diminished opioid-induced pain relief.
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21. |
- Fellman, Vineta, et al.
(author)
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Cortical auditory event-related potentials in newborn infants.
- 2006
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In: Seminars in Fetal & Neonatal Medicine. - : Elsevier BV. - 1878-0946 .- 1744-165X. ; 11:6, s. 452-458
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Journal article (peer-reviewed)abstract
- The possibility of recording changes in electroencephalography potentials following perception of sound was reported several decades ago. The recent expanding research on auditory cortical event-retated potentials (AERPs) for assessing sound discrimination abilities in children and infants has indicated that several methodological issues need to be addressed before it can be implemented in clinical practice. Latencies, polarities, and amplitudes of the responses change with gestational age and during infancy. Thus, the maturation of the infant must be considered when designing stimulus paradigms and interpreting the responses. Of healthy newborn infants, only about 80% will show mismatch negativity, the automatic change detection of the auditory stimuli. Currently, the AERP method cannot be applied in clinical practice in the neonatal period, although the findings in healthy newborns at risk for dyslexia are promising. Further research will elucidate the possibility of developing AERPs as a possible early screening method during infancy for later dyslexia or cognitive dysfunction.
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22. |
- Fellman, Vineta
(author)
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De GRACILA barnen
- 2006
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In: Finska Läkaresällskapets Handlingar. - 0015-2501. ; 166:2, s. 75-80
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Journal article (peer-reviewed)abstract
- GRACILE-syndromet (Fellmans syndrom, MIM 603358) hör till det fi nländska genetiska sjukdomsarvet. Sjukdomen är orsakad av en missens mutation (S78G) i BCS1L, ett protein som fungerar som en “chaperon” eller sammankopplande länk vid bildning av komplex III i andningskedjan. Syndromet uttrycker sig som en grav tillväxthämning redan under fostertiden, och efter födseln utvecklar barnet en uttalad metabolisk acidos pga. av nedsatt funktion i komplex III. Övriga symtom är proximal tubulopati, nedsatt leverfunktion med cirrhos och uttalad järnupplagring, störd järnmetabolism och tidig död. Diagnosen ställs med hjälp av mutationen, alla barn av fi nländskt ursprung har haft samma homozygota mutation S78G. I andra länder förekommer olika mutationer i BCS1L och fenotypen varierar. Behandlingen är än så länge enbart symtomatisk.
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23. |
- Fellman, Vineta
(author)
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GRACILE-oireyhtymä--vastasyntyneen vakava mitokondriotauti.
- 2012
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In: Duodecim; lääketieteellinen aikakauskirja. - 0012-7183. ; 128:15, s. 1560-1567
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Research review (peer-reviewed)abstract
- GRACILE syndrome belongs to the Finnish disease heritage, and is caused by a point mutation in the BCS1L-gene encoding a mitochondrial protein. This leads to dysfunction of the complex III in the respiratory chain. Significant fetal growth disturbance is the primary manifestation. Within the first day the newborn infant develops severe lactic acidosis. Hypoglycemia, elevated serum ferritin and conjugated bilirubin values and aminoaciduria imply mitochondrial liver disease and renal tubulopathy. In Finland, the diagnosis is based on the 232A>G mutation in the BCS1L-gene. No specific treatment is available. GRACILE syndrome leads to early death.
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24. |
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25. |
- Fellman, Vineta
(author)
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Mitochondrial complex III deficiencies in the newborn infant.
- 2006
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In: Drug Discovery Today: Disease Mechanisms. - : Elsevier BV. - 1740-6765. ; 3:4, s. 421-427
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Journal article (peer-reviewed)abstract
- New mechanisms for respiratory chain complex III diseases have recently been reported. Deletions, rearrangements and tRNA mutations of mitochondrial DNA cause deficiencies in several complexes. Mutations in the only complex III subunit encoded by mitochondrial DNA, cytochrome b, cause variable clinical phenotypes, such as cardiomyopathy or multisystemic dysfunction after birth. The homozygous serine78alanine mutation in the complex III assembling protein, BCS1L, causes a distinct phenotype, the GRACILE syndrome, whereas in other BCS1L mutations, the clinical picture is variable, but tubulopathy and liver dysfunction are typical.
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26. |
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27. |
- Fellman, Vineta, et al.
(author)
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Mitochondrial hepatopathies in the newborn period.
- 2011
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In: Seminars in Fetal & Neonatal Medicine. - : Elsevier BV. - 1878-0946 .- 1744-165X. ; 16, s. 222-228
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Journal article (peer-reviewed)abstract
- Mitochondrial disorders recognized in the neonatal period usually present as a metabolic crisis combined with one or several organ manifestations. Liver disorder in association with a respiratory chain deficiency may be overlooked since liver dysfunction is common in severely sick newborn infants. Lactacidosis, hypoglycemia, elevated serum transaminases and conjugated bilirubin are common signs of mitochondrial hepatopathy. Hepatosplenomegaly may occur in severe cases. A clinical picture with fetal growth restriction, postnatal lactacidosis, hypoglycemia, coagulopathy, and cholestasis, especially in combination with neurological symptoms or renal tubulopathy, should alert the neonatologist to direct investigations on mitochondrial disorder. A normal lactate level does not exclude respiratory chain defects. The most common liver manifestation caused by mutated mitochondrial DNA (deletion) is Pearson syndrome. Recently, mutations in several nuclear DNA genes have been identified that lead to mitochondrial hepatopathy, e.g. mitochondrial depletion syndrome caused by DGUOK, MPV17, SUCLG1, POLG1, or C10ORF2 mutations. A combination of lactacidosis, liver involvement, and Fanconi type renal tubulopathy is common when the complex III assembly factor BCS1L harbors mutations, the most severe disease with consistent genotype-phenotype correlation being the GRACILE syndrome. Mutations in nuclear translation factor genes (TRMU, EFG1, and EFTu) of the respiratory chain enzyme complexes have recently been identified. Diagnostic work-up of neonatal liver disorder should include assessment of function and structure of the complexes as well as mutation screening for known genes. So far, treatment is mainly symptomatic.
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28. |
- Fellman, Vineta
(author)
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More voice, less noise in NICUs
- 2017
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In: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253. ; 106:8, s. 1210-1211
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Journal article (other academic/artistic)
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29. |
- Fellman, Vineta, et al.
(author)
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One-year survival of extremely preterm infants after active perinatal care in Sweden.
- 2009
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In: JAMA : the journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 301:21, s. 2225-33
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Journal article (peer-reviewed)abstract
- Up-to-date information on infant survival after extremely preterm birth is needed for assessing perinatal care services, clinical guidelines, and parental counseling.
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30. |
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31. |
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32. |
- Fellman, Vineta, et al.
(author)
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Screening of BCS1L mutations in severe neonatal disorders suspicious for mitochondrial cause
- 2008
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In: Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1434-5161 .- 1435-232X. ; 53:6, s. 554-558
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Journal article (peer-reviewed)abstract
- The BCS1L gene encodes a chaperone responsible for assembly of respiratory chain complex III (CIII). A homozygous point mutation (232A -> G) has been found as the genetic etiology for fetal growth retardation, amino aciduria, cholestasis, iron overload, lactic acidosis, and early death (GRACILE) syndrome (MIM 603358). Variable phenotypes have been found with other mutations. Our aim was to assess whether 232A -> G or other BCS1L mutations were present in infants (n = 21) of Finnish origin with severe, lethal disease compatible with mitochondrial disorder. A further aim was to confirm the GRACILE genotype-phenotype constancy (n = 8). Three new cases with homozygous 232A -> G mutation were identified; all had the primary GRACILE characteristics. No other mutations were found in the gene in other cases. All infants with GRACILE syndrome had the typical mutation. In conclusion, the rather homogenous population of Finns seems to have a specific BCS1L mutation that, as homozygous state, causes GRACILE syndrome, whereas other mutations are rare or not occurring. Thus, the novel clinical implication of this study is to screen for BCS1L mutations only if CIII is dysfunctioning or lacking Rieske protein, and to assess 232A -> G mutation in cases with GRACILE syndrome.
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33. |
- Fellman, Vineta, et al.
(author)
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Severe neonatal MEGDHEL syndrome with a homozygous truncating mutation in SERAC1
- 2022
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In: Biochimica et Biophysica Acta - Molecular Basis of Disease. - : Elsevier BV. - 0925-4439. ; 1868:1
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Journal article (peer-reviewed)abstract
- In the diagnostic work-up of a newborn infant with a metabolic crisis, lethal multiorgan failure on day six of life, and increased excretion of 3-methylglutaconic acid, we found using whole genome sequencing a homozygous SERAC1 mutation indicating MEGDHEL syndrome (3-methylglutaconic aciduria with deafness-dystonia, hepatopathy, encephalopathy, and Leigh-like syndrome). The SERAC1 protein is located at the contact site between mitochondria and the endoplasmic reticulum (ER) and is crucial for cholesterol trafficking. Our aim was to investigate the effect of the homozygous truncating mutation on mitochondrial structure and function. In the patient fibroblasts, no SERAC1 protein was detected, the mitochondrial network was severely fragmented, and the cristae morphology was altered. Filipin staining showed uneven localization of unesterified cholesterol. The calcium buffer function between cytoplasm and mitochondria was deficient. In liver mitochondria, complexes I, III, and IV were clearly decreased. In transfected COS-1 cells the mutant protein with the a 45-amino acid C-terminal truncation was distributed throughout the cell, whereas wild-type SERAC1 partially colocalized with the mitochondrial marker MT-CO1. The structural and functional mitochondrial abnormalities, caused by the loss of SERAC1, suggest that the crucial disease mechanism is disrupted interplay between the ER and mitochondria leading to decreased influx of calcium to mitochondria and secondary respiratory chain deficiency.
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34. |
- Gram, Magnus, et al.
(author)
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The radical-binding lipocalin A1M binds to a Complex I subunit and protects mitochondrial structure and function.
- 2013
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In: Antioxidants & Redox Signaling. - : Mary Ann Liebert Inc. - 1557-7716 .- 1523-0864. ; 18:16, s. 2017-2028
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Journal article (peer-reviewed)abstract
- Aims: During cell death, energy-consuming cell degradation and recycling programs are performed. Maintenance of energy-delivery during cell death is therefore crucial but the mechanisms to keep the mitochondrial functions intact during these processes are poorly understood. We have investigated the hypothesis that the heme- and radical-binding ubiquitous protein A1M (α1-microglobulin) is involved in protection of the mitochondria against oxidative insult during cell death. Results: Using blood cells, keratinocytes and liver cells, we show that A1M binds with high affinity to apoptosis-induced cells and is localized to mitochondria. The mitochondrial Complex I subunit NDUFAB1 was identified as a major molecular target of the A1M-binding. Furthermore, A1M was shown to inhibit the swelling of mitochondria, and to reverse the severely abrogated ATP-production of mitochondria when exposed to heme and ROS. Innovation: Import of the radical- and heme-binding protein A1M from the extracellular compartment confers protection of mitochondrial structure and function during cellular insult. Conclusion: A1M binds to a subunit of Complex I and has a role in assisting the mitochondria to maintain its energy delivery during cell death. A1M may also, at the same time, counteract and eliminate the ROS generated by the mitochondrial respiration to prevent oxidative damage to surrounding healthy tissue.
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35. |
- Haavisto, Anu, et al.
(author)
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Latent class growth analysis identified different trajectories in cognitive development of extremely low birthweight children
- 2022
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In: BMJ Paediatrics Open. - : BMJ. - 2399-9772. ; 6:1
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Journal article (peer-reviewed)abstract
- Background Recent longitudinal studies suggest stable cognitive development in preterm children, although with great individual variation. This prospective neurocognitive follow-up study of extremely low birthweight (ELBW, <1000 g) children aimed to characterise groups with different developmental trajectories from preschool to preteen age. Methods ELBW children (n=115) born in Finland in 1996-1997 participated in cognitive assessments at a median age of 5.0 years and 11.3 years. A standardised test of intelligence (Wechsler Preschool and Primary Scale of Intelligence-Revised or Wechsler Intelligence Scale for Children-third edition) was administered at both ages. Results Three ELBW groups with different developmental trajectories over time were identified with latent class growth analysis. Children with average (Full-Scale IQ (FSIQ): 85-115) and below average (FSIQ: <85) intelligence at 5 years of age had significant decreases in intelligence scores by 11 years of age (-11.7 points and -14.9 points, respectively, both p<0.001), while those with above average intelligence (FSIQ: >115) showed stable development (-3.2 points, p=0.250). Multiple linear regression showed that neonatal complications (intraventricular haemorrhage grade 3-4 and blood culture positive sepsis) and maternal education significantly predicted lower intelligence at the second assessment (F(3,106)=7.27, p<0.001, adjusted R 2 =0.147). Conclusions ELBW children represent a heterogeneous patient population in which groups with different cognitive trajectories can be detected. Deterioration may occur particularly in children with initial average or below average cognitive performance at 5 years of age, with neonatal complications and lower maternal education presenting as risk factors. Catch-up in cognitive functions seems more uncommon in the ELBW population, which should be noted in clinical work.
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36. |
- Hansen-Pupp, Ingrid, et al.
(author)
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Postnatal Decrease in Circulating Insulin-Like Growth Factor-I and Low Brain Volumes in Very Preterm Infants.
- 2011
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 96:4, s. 1129-1135
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Journal article (peer-reviewed)abstract
- Context: IGF-I and IGF binding protein-3 (IGFBP-3) are essential for growth and maturation of the developing brain. Objective: The aim of this study was to evaluate the association between postnatal serum concentrations of IGF-I and IGFBP-3 and brain volumes at term in very preterm infants. Design: Fifty-one infants with a mean (sd) gestational age (GA) of 26.4 (1.9) wk and birth weight (BW) of 888 (288) g were studied, with weekly blood sampling of IGF-I and IGFBP-3 from birth until 35 gestational weeks (GW) and daily calculation of protein and caloric intake. Magnetic resonance images obtained at 40 GW were segmented into total brain, cerebellar, cerebrospinal fluid, gray matter, and unmyelinated white matter volumes. Main Outcome Measures: We evaluated brain growth by measuring brain volumes using magnetic resonance imaging. Results: Mean IGF-I concentrations from birth to 35 GW correlated with total brain volume, unmyelinated white matter volume, gray matter volume, and cerebellar volume [r = 0.55 (P < 0.001); r = 0.55 (P < 0.001); r = 0.44 (P = 0.002); and r = 0.58 (P < 0.001), respectively]. Similar correlations were observed for IGFBP-3 concentrations. Correlations remained after adjustment for GA, mean protein and caloric intakes, gender, severe brain damage, and steroid treatment. Protein and caloric intakes were not related to brain volumes. Infants with BW small for GA had lower mean concentrations of IGF-I (P = 0.006) and smaller brain volumes (P = 0.001-0.013) than infants with BW appropriate for GA. Conclusion: Postnatal IGF-I and IGFBP-3 concentrations are positively associated with brain volumes at 40 GW in very preterm infants. Normalization of the IGF-I axis, directly or indirectly, may support normal brain development in very preterm infants.
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37. |
- Hikmat, O., et al.
(author)
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Expanding the phenotypic spectrum of BCS1L-related mitochondrial disease
- 2021
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In: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 8:11, s. 2155-2165
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Journal article (peer-reviewed)abstract
- Objective: To delineate the full phenotypic spectrum of BCS1L-related disease, provide better understanding of the genotype-phenotype correlations and identify reliable prognostic disease markers. Methods: We performed a retrospective multinational cohort study of previously unpublished patients followed in 15 centres from 10 countries. Patients with confirmed biallelic pathogenic BCS1L variants were considered eligible. Clinical, laboratory, neuroimaging and genetic data were analysed. Patients were stratified into different groups based on the age of disease onset, whether homozygous or compound heterozygous for the c.232A>G (p.Ser78Gly) variant, and those with other pathogenic BCS1L variants. Results: Thirty-three patients were included. We found that growth failure, lactic acidosis, tubulopathy, hepatopathy and early death were more frequent in those with disease onset within the first month of life. In those with onset after 1 month, neurological features including movement disorders and seizures were more frequent. Novel phenotypes, particularly involving movement disorder, were identified in this group. The presence of the c.232A>G (p.Ser78Gly) variant was associated with significantly worse survival and exclusively found in those with disease onset within the first month of life, whilst other pathogenic BCS1L variants were more frequent in those with later symptom onset. Interpretation: The phenotypic spectrum of BCS1L-related disease comprises a continuum of clinical features rather than a set of separate syndromic clinical identities. Age of onset defines BCS1L-related disease clinically and early presentation is associated with poor prognosis. Genotype correlates with phenotype in the presence of the c.232A>G (p.Ser78Gly) variant.
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38. |
- Huotilainen, Minna, et al.
(author)
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Auditory magnetic responses of healthy newborns
- 2003
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In: NeuroReport. - 1473-558X. ; 14:14, s. 1871-1875
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Journal article (peer-reviewed)abstract
- We recorded magnetic brain activity from healthy human newborns when they heard frequency changes in an otherwise repetitive sound stream. We were able to record the magnetic counterpart of the mismatch negativity (MMN) previously described only with electric recordings in infants. The results show that these recordings are possible, although still challenging due to the small head size and head movements. The modelling of the neural sources underlying the recorded responses suggests cortical sources in the temporal lobes.
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39. |
- Huotilainen, Minna, et al.
(author)
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Could audiovisual training be used to improve cognition in extremely low birth weight children?
- 2011
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In: Acta paediatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 100, s. 1489-1494
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Journal article (peer-reviewed)abstract
- Aim: To study whether a dyslexia remediation programme, Audilex, improves cognition in extremely low birth (ELBW) children. Methods: Six-year-old ELBW children were allocated to a 5-week training with Audilex or playing control computer games. Before and after intervention, auditory event-related brain potentials (ERP) to sound changes were recorded and reading related skills assessed. Primary outcome was the mismatch negativity (MMN) component of ERP. Secondary outcomes were Audilex Test (ability to perform the Audilex games), the reading skills after the intervention and 2 years later. Of eligible children, 39 (54%) consented and 22 (30%) completed the protocol. Results: The MMN responses to the frequency (p = 0.02) and duration deviants (p < 0.01) increased after Audilex training (n = 11), but not after control game playing (n = 11). Audilex Test performance was similar in both groups. The reading skills were similar after intervention and 2 years later; word reading score 59.7, 66.8 and 74.9 and comprehensive reading score 8.1, 8.8 and 9.4 in Audilex, Control and healthy class-mate children, respectively. Conclusions: Although all children did not complete the protocol, the results suggest that training with Audilex dyslexia programme might be beneficial for enhancing neural-level sound discrimation and possibly reading skills in ELBW children. A larger trial is warranted.
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40. |
- Högberg, Ulf, 1949-, et al.
(author)
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Difficult birth is the main contributor to birthrelated fracture and accidents to other neonatal fractures
- 2020
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In: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 109:10, s. 2040-2048
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Journal article (peer-reviewed)abstract
- AIM: Specific birthrelated fractures have been studied; underestimates might be a problem. We aimed to assess all fractures diagnosed as birthrelated as well as other neonatal fractures.METHODS: A population-based study on all infants born in Sweden 1997-2014; data was retrieved from the Swedish Health Registers (10th version of International Classification of Diseases. Outcome measures were birthrelated fractures (ICD-10 P-codes) and other neonatal fractures (ICD-10 S-codes).RESULTS: The overall fracture incidence was 2.9 per 1,000 live birth (N=5,336); 92.6% had P-codes and 7.4% (S-codes). Some birthrelated fractures were diagnosed beyond the neonatal period. Other neonatal fractures could have been birthrelated. Clavicle fracture, (88.8%) was associated with adverse maternal- and infant anthropometrics and birth complications. The few neonates with rib fractures all had concomitant clavicle fracture. For skull fractures, a minor part was birthrelated, most were associated with accidents. Half of the long bone fractures were associated with accidents. Birthrelated femur fractures were associated with bone fragility risk factors. Five infants with abuse diagnoses had fractures: skull (4), long bone (2), and rib (1).CONCLUSION: Birthrelated and other neonatal fractures are rarely diagnosed. Difficult birth is the main contributor to birthrelated fracture, and accidents to other neonatal fractures.
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41. |
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42. |
- Högberg, Ulf, 1949-, et al.
(author)
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Epidemiology of subdural haemorrhage during infancy : A population-based register study
- 2018
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:10
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Journal article (peer-reviewed)abstract
- Objectives To analyse subdural haemorrhage (SDH) during infancy in Sweden by incidence, SDH category, diagnostic distribution, age, co-morbidity, mortality, and maternal and perinatal risk factors; and its association with accidents and diagnosis of abuse. Methods A Swedish population-based register study comprising infants born between 1997 and 2014, 0-1 years of age, diagnosed with SDH-diagnoses according to the (International Classification of Diseases, 10th version (ICD10), retrieved from the National Patient Register and linked to the Medical Birth Register and the Death Cause Register. Outcome measures were: 1) Incidence and distribution, 2) co-morbidity, 3) fall accidents by SDH category, 4) risk factors for all SDHs in the two age groups, 0-6 and 7-365 days, and for ICD10 SDH subgroups: S06.5 (traumatic SDH), I62.0 (acute nontraumatic), SDH and abuse diagnosis. Results Incidence of SDH was 16.5 per 100 000 infants (n = 306). Median age was 2.5 months. For infants older than one week, the median age was 3.5 months. Case fatality was 6.5%. Male sex was overrepresented for all SDH subgroups. Accidental falls were reported in 1/3 of the cases. One-fourth occurred within 0-6 days, having a perinatal risk profile. For infants aged 7-365 days, acute nontraumatic SDH was associated with multiple birth, preterm birth, and small-for-gestational age. Fourteen percent also had an abuse diagnosis, having increased odds of being born preterm, and being small-for-gestational age. Conclusions The incidence was in the range previously reported. SDH among newborns was associated with difficult birth and neonatal morbidity. Acute nontraumatic SDH and SDH with abuse diagnosis had similar perinatal risk profiles. The increased odds for acute nontraumatic SDH in twins, preterm births, neonatal convulsions or small-for-gestational age indicate a perinatal vulnerability for SDH beyond 1st week of life. The association between prematurity/small-for-gestational age and abuse diagnosis is intriguing and not easily understood.
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43. |
- Högberg, Ulf, 1949-, et al.
(author)
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Population-based register study of children born in Sweden from 1997 to 2014 showed an increase in rickets during infancy
- 2019
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In: Acta Paediatrica. - : WILEY. - 0803-5253 .- 1651-2227. ; 108:11, s. 2034-2040
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Journal article (peer-reviewed)abstract
- Aim: This population-based study assessed the incidence of rickets in infants up to age of one born in Sweden from 1997 to 2014. We also examined maternal and perinatal factors and co-morbidity.Methods: We used Swedish National Board of Health and Welfare registers and data from Statistics Sweden. The outcome measure was an International Classification of Diseases, Tenth Revision, code for rickets.Results: There were 273 cases of rickets, with an incidence of 14.7 per 100 000 and a 10-fold incidence increase between 1997 and 2014. The majority (78.4%) were born preterm, half were small-for-gestational age (SGA) (birthweight <10th percentile), 4.8% were born to Asian-born mothers and 3.5% to African-born mothers. The adjusted odds ratios by birth week were 182 (95% CI: 121-272) before 32 weeks and 10.8 (95% CI: 6.72-17.4) by 32-36 weeks. Preterm infants with necrotising enterocolitis had very high odds for rickets and so did SGA term-born infants and those born to African-born mothers. The odds for rickets among preterm infants increased considerably during the later years.Conclusion: Rickets increased 10-fold in Sweden from 1997 to 2014 and was mainly associated with prematurity, SGA and foreign-born mothers. Possible reasons may include increased preterm survival rates and improved clinical detection and registration.
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44. |
- Högberg, Ulf, 1949-, et al.
(author)
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Preventable harm and child maltreatment diagnosis (eLetter)
- 2019
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In: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 366
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Journal article (peer-reviewed)abstract
- Objective: To systematically quantify the prevalence, severity, and nature of preventable patient harm across a range of medical settings globally.Design: Systematic review and meta-analysis.Data sources: Medline, PubMed, PsycINFO, Cinahl and Embase, WHOLIS, Google Scholar, and SIGLE from January 2000 to January 2019. The reference lists of eligible studies and other relevant systematic reviews were also searched.Review methods: Observational studies reporting preventable patient harm in medical care. The core outcomes were the prevalence, severity, and types of preventable patient harm reported as percentages and their 95% confidence intervals. Data extraction and critical appraisal were undertaken by two reviewers working independently. Random effects meta-analysis was employed followed by univariable and multivariable meta regression. Heterogeneity was quantified by using the I2 statistic, and publication bias was evaluated.Results: Of the 7313 records identified, 70 studies involving 337 025 patients were included in the meta-analysis. The pooled prevalence for preventable patient harm was 6% (95% confidence interval 5% to 7%). A pooled proportion of 12% (9% to 15%) of preventable patient harm was severe or led to death. Incidents related to drugs (25%, 95% confidence interval 16% to 34%) and other treatments (24%, 21% to 30%) accounted for the largest proportion of preventable patient harm. Compared with general hospitals (where most evidence originated), preventable patient harm was more prevalent in advanced specialties (intensive care or surgery; regression coefficient b=0.07, 95% confidence interval 0.04 to 0.10).Conclusions: Around one in 20 patients are exposed to preventable harm in medical care. Although a focus on preventable patient harm has been encouraged by the international patient safety policy agenda, there are limited quality improvement practices specifically targeting incidents of preventable patient harm rather than overall patient harm (preventable and non-preventable). Developing and implementing evidence-based mitigation strategies specifically targeting preventable patient harm could lead to major service quality improvements in medical care which could also be more cost effective.
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45. |
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46. |
- Hövel, Holger, et al.
(author)
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Auditory event-related potentials are related to cognition at preschool age after very preterm birth
- 2015
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In: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 77:4, s. 570-578
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Auditory event-related potentials (AERP) are neurophysiological correlates of sound perception and cognitive processes. Our aim was to study in very preterm born children at preschool age if AERP correlate with cognitive outcome. METHODS: Seventy children (mean +/- SD gestational age 27.4 +/- 1.9 wk, birth weight 996 +/- 288 g) were investigated at age 4.3-5.3 y with psychological testing (WPPSI-R, four subtests of NEPSY), Electroencephalogram was recorded while they listened to a repeated standard tone, randomly replaced by one of three deviants. Latencies and amplitudes for AERP components and mean amplitudes in successive 50-ms AERP time windows were measured. RESULTS: Better cognitive test results and higher gestational age correlated with shorter P1 latencies and more positive mean amplitudes 150-500 ms after stimulus change onset. Neonatal brain damage was associated with a negative displacement of AERP curves. Neonatal morbidity had an impact on earlier time windows while gestational age and brain damage on both early and later time windows. CONCLUSION: AERP measures were associated with cognitive outcome. Neonatal morbidity mainly affects early cortical auditory encoding, while immaturity and brain damage additionally influence higher cortical functions of auditory perception and distraction. Perinatal auditory environment might play a role in development of auditory processing.
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47. |
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48. |
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49. |
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