| 1. |
- Bonamy, Anna-Karin Edstedt, et al.
(författare)
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Blood Pressure in 6-Year-Old Children Born Extremely Preterm
- 2017
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Ingår i: Journal of the American Heart Association. - : WILEY. - 2047-9980. ; 6:8
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Elens, Laure, et al.
(författare)
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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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Ingår i: Therapeutic Drug Monitoring. - 0163-4356 .- 1536-3694. ; 38:4, s. 525-533
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Högberg, Ulf, 1949-, et al.
(författare)
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Epidemiology of subdural haemorrhage during infancy : A population-based register study
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:10
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Mohlkert, Lilly -Ann, et al.
(författare)
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Preterm arteries in childhood : dimensions, intima-media thickness, and elasticity of the aorta, coronaries, and carotids in 6-y-old children born extremely preterm
- 2017
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Ingår i: Pediatric Research. - : NATURE PUBLISHING GROUP. - 0031-3998 .- 1530-0447. ; 81:2, s. 299-306
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Preterm birth increases risk for adult cardiovascular disease. We hypothesized that arteries in 6-y-old children born preterm are narrower, with thicker intima-media and stiffer than in peers born at term. METHODS: Children born extremely preterm (EXP, n = 176, birthweights: 348-1,161 g) and at term (CTRL, n = 174, birth weights: 2,430-4,315 g) were included. Using ultrasonography, we determined diameters of the coronaries (CA), common carotid arteries (CCA) and aorta, the carotid intima media thickness (CIMT), and the stiffness index of the CCA and aorta. RESULTS: Arteries were 5-10% narrower in EXP than in CTRL (P < 0.005) but after adjustment for body surface area, diameter differences diminished or disappeared. EXP-children born small for gestational age exhibited similar arterial dimensions as those born appropriate for date. The cIMT was 0.38 (SD = 0.04) mm and did not differ between groups. Carotid but not aortic stiffness was lower in EXP than in CTRL. CONCLUSION: In 6-y-old children born extremely preterm, conduit arteries are of similar or smaller size than in controls born at term, and they have no signs of accelerated intima media thickening or arterial stiffening. While these findings are reassuring for these children and their families, the causal pathways from preterm birth to adult cardiovascular disease remain unknown.
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| 5. |
- Mohlkert, Lilly-Ann, et al.
(författare)
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The Preterm Heart in Childhood : Left Ventricular Structure, Geometry, and Function Assessed by Echocardiography in 6-Year-Old Survivors of Periviable Births
- 2018
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Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Preterm birth has been associated with increased risk of cardiovascular morbidity in adult life. We evaluated whether preterm birth is associated with deviating cardiac structure and function before school start. Methods and Results: In total, 176 children aged 6 years and born extremely preterm (EXPT; gestational age of 22-26weeks) and 134 children born at term (control [CTRL]) were studied. We used echocardiography to assess left heart dimensions, geometry, and functions. Recording and off-line analyses of echocardiographic images were performed by operators blinded to group belonging. Body size, blood pressure, and heart rate were also measured. Rates of family history of cardiovascular disease and sex distribution were similar in the EXPT and CTRL groups. Heart rate and systolic blood pressure did not differ, whereas diastolic blood pressure was slightly higher in EXPT than CTRL participants. After adjusting for body surface area, left ventricular length, width, and aortic valve annulus diameter were 3% to 5% smaller in EXPT than CTRL participants. Left ventricular longitudinal shortening and systolic tissue velocity were 7% to 11% lower, and transversal shortening fraction was 6% higher in EXPT than CTRL participants. The EXPT group also exhibited lower atrial emptying velocities than the CTRL group. Sex, fetal growth restriction, or a patent ductus arteriosus in the neonatal period did not contribute to cardiac dimensions or performance. Conclusions: Six-year-old children born extremely preterm exhibit a unique cardiac phenotype characterized by smaller left ventricles with altered systolic and diastolic functions than same-aged children born at term.
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| 6. |
- Norman, Elisabeth, et al.
(författare)
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Individual variations in fentanyl pharmacokinetics and pharmacodynamics in preterm infants
- 2019
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 108:8, s. 1441-1446
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Tidskriftsartikel (refereegranskat)abstract
- Aim Fentanyl pharmacokinetics and pharmacodynamics are lacking in preterm infants. Our aim was to study these and their relation with a new formulation of fentanyl 5 mu g/mL for procedural pain. Methods Preterm infants were given 0.5 (n = 20, median gestational age 26.5; range 23.3-34.1 weeks) and 2 mu g/kg (n = 8, 27.4; 25.3-30.7 weeks) fentanyl, respectively, before skin-breaking procedures or tracheal intubation. Blood samples were collected after ten minutes, two, four, eight and 24 hours. Physiologic parameters were monitored and pain scores assessed. Results The median fentanyl concentrations were 0.18, 0.15, 0.15 and 0.57, 0.37, 0.35 ng/mL at 15-31 minutes, two and four hours and the half-lives were 1.6 to 20.5 or 4.1 to 32.6 hours for the low- and high-dose groups, respectively. A significant correlation was seen between weight at study inclusion and half-life (Spearman ' s r = -0.9, p < 0.001), volume of distribution (r = -0.8, p < 0.01) and clearance (r = -0.9, p < 0.01) in the low-dose group (n = 9). Pain assessment results were not correlated to pharmacokinetic variables. Fentanyl was well tolerated. Conclusion The inter-individual variation of fentanyl pharmacokinetics is large in preterm infants, and the dose of 0.5 mu g/kg seems not effective for skin-breaking procedures.
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| 7. |
- Purhonen, J, et al.
(författare)
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Ketogenic diet attenuates hepatopathy in mouse model of respiratory chain complex III deficiency caused by a Bcs1l mutation
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 957-
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial disorders are among the most prevalent inborn errors of metabolism but largely lack treatments and have poor outcomes. High-fat, low-carbohydrate ketogenic diets (KDs) have shown beneficial effects in mouse models of mitochondrial myopathies, with induction of mitochondrial biogenesis as the suggested main mechanism. We fed KD to mice with respiratory chain complex III (CIII) deficiency and progressive hepatopathy due to mutated BCS1L, a CIII assembly factor. The mutant mice became persistently ketotic and tolerated the KD for up to 11 weeks. Liver disease progression was attenuated by KD as shown by delayed fibrosis, reduced cell death, inhibition of hepatic progenitor cell response and stellate cell activation, and normalization of liver enzyme activities. Despite no clear signs of increased mitochondrial biogenesis in the liver, CIII assembly and activity were improved and mitochondrial morphology in hepatocytes normalized. Induction of hepatic glutathione transferase genes and elevated total glutathione level were normalized by KD. Histological findings and transcriptome changes indicated modulation of liver macrophage populations by the mutation and the diet. These results reveal a striking beneficial hepatic response to KD in mice with mitochondrial hepatopathy and warrant further investigations of dietary modification in the management of these conditions in patients.
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| 8. |
- Serenius, Fredrik, et al.
(författare)
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Neurodevelopmental Outcomes Among Extremely Preterm Infants 6.5 Years After Active Perinatal Care in Sweden
- 2016
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Ingår i: Jama Pediatrics. - Chicago : American Medical Association (AMA). - 2168-6203 .- 2168-6211. ; 170:10, s. 954-963
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Active perinatal care increases the rate of survival of extremely preterm infants, but there are concerns that improved survival might increase the rate of disabled survivors. OBJECTIVE To determine the neurodevelopmental outcomes of a national cohort of children 6.5 years of age who had been born extremely preterm (<27 weeks' gestational age) in Sweden. DESIGN, SETTING, AND PARTICIPANTS Population-based prospective cohort study of consecutively born extremely preterm infants. All of these infants were born in Sweden during the period from April 1, 2004, to March 31, 2007. Of 707 live-born extremely preterm infants, 486 (68.7%) survived to 6.5 years of age. These children were assessed and compared with matched controls who had been born at term. Comparison estimates were adjusted for demographic differences. Assessments ended in February 2014, and analysis started thereafter. MAIN OUTCOMES AND MEASURES Cognitive ability was measured with the fourth edition of the Wechsler Intelligence Scale for Children (WISC-IV), and the mean (SD) scores of the children who had been born extremely preterm were compared with those of the controls. Clinical examinations and parental questionnaires were used for diagnosis of cerebral palsy, hearing and vision impairments, and cognition for the children who were not assessed with the WISC-IV. RESULTS Of 486 eligible infants who were born extremely preterm, 441 (90.7%) were assessed at 6.5 years of age (59 by medical record review only) alongside 371 controls. The adjusted mean (SD) full-scale WISC-IV score was 14.2 (95% CI, 12.1-16.3) points lower for children who had been born extremely preterm than for controls. Cognitive disability was moderate for 18.8% of extremely preterm children and 2.2% of controls (P < .001), and it was severe for 11.1% of extremely preterm children and 0.3% of controls (P < .001). Cerebral palsy was observed in 9.5% of extremely preterm children and 0.0% of controls (P < .001), blindness was observed in 2.0% of extremely preterm children and 0.0% of controls (P < .001), and hearing impairment was observed in 2.1% of extremely preterm children and 0.5% of controls (P = .07). Overall, 36.1%(95% CI, 31.7%-40.6%) of extremely preterm children had no disability, 30.4%(95% CI 26.3%-34.8%) had mild disability, 20.2%(95% CI, 16.6%-24.2%) had moderate disability, and 13.4%(95% CI, 10.5%-16.9%) had severe disability. For extremely preterm children, moderate or severe overall disability decreased with gestational age at birth (adjusted odds ratio per week, 0.65 [95% CI, 0.54-0.79]; P < .001) and increased from 26.6% to 33.5%(P = .01) for children assessed both at 2.5 and 6.5 years. CONCLUSIONS AND RELEVANCE Of the 441 extremely preterm infants who had received active perinatal care, 293 (66.4%) had no or mild disability at 6.5 years; of the 371 controls, 11 (3.0%) had moderate or severe disability. Disability rates at 6.5 years increased relative to the rates at 2.5 years. Results are relevant for health care professionals and planners, and for clinicians counseling families facing extremely preterm births.
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| 9. |
- Tegelberg, Saara, et al.
(författare)
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Respiratory chain complex III deficiency due to mutated BCS1L : A novel phenotype with encephalomyopathy, partially phenocopied in a Bcs1l mutant mouse model
- 2017
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mitochondrial diseases due to defective respiratory chain complex III (CIII) are relatively uncommon. The assembly of the eleven-subunit CIII is completed by the insertion of the Rieske iron-sulfur protein, a process for which BCS1L protein is indispensable. Mutations in the BCS1L gene constitute the most common diagnosed cause of CIII deficiency, and the phenotypic spectrum arising from mutations in this gene is wide. Results: A case of CIII deficiency was investigated in depth to assess respiratory chain function and assembly, and brain, skeletal muscle and liver histology. Exome sequencing was performed to search for the causative mutation(s). The patient's platelets and muscle mitochondria showed respiration defects and defective assembly of CIII was detected in fibroblast mitochondria. The patient was compound heterozygous for two novel mutations in BCS1L, c.306A > T and c.399delA. In the cerebral cortex a specific pattern of astrogliosis and widespread loss of microglia was observed. Further analysis showed loss of Kupffer cells in the liver. These changes were not found in infants suffering from GRACILE syndrome, the most severe BCS1L-related disorder causing early postnatal mortality, but were partially corroborated in a knock-in mouse model of BCS1L deficiency. Conclusions: We describe two novel compound heterozygous mutations in BCS1L causing CIII deficiency. The pathogenicity of one of the mutations was unexpected and points to the importance of combining next generation sequencing with a biochemical approach when investigating these patients. We further show novel manifestations in brain, skeletal muscle and liver, including abnormality in specialized resident macrophages (microglia and Kupffer cells). These novel phenotypes forward our understanding of CIII deficiencies caused by BCS1L mutations.
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| 10. |
- Thunqvist, Per, et al.
(författare)
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Lung function after extremely preterm birth-A population-based cohort study (EXPRESS)
- 2018
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Ingår i: Pediatric Pulmonology. - : Wiley. - 8755-6863 .- 1099-0496. ; 53:1, s. 64-72
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Follow-up studies of children and young adults born very-to-moderately preterm show persistent and significant lung function deficits. The aim of the study was to determine lung function and airway mechanics in school-aged children born in 2004 to 2007 and extremely preterm (after 22-26 weeks of gestation).METHODS: In a population-based cohort of children born extremely preterm and controls born at term (n = 350), follow-up at 6½-years-of-age was performed using spirometry and impulse oscillometry. Associations to gestational age, smallness for gestational age (SGA), and bronchopulmonary dysplasia (BPD) were assessed.RESULTS: Children born extremely preterm had lower forced vital capacity (FVC, z-score: -0.7, 95%CI: -1.0;-0.4), forced expiratory volume (FEV1 , z-score: -1.1, 95%CI: -1.4; -0.8), higher frequency-dependence of resistance (R5-20 , 0.09, 95%CI: 0.05; 0.12 kPa · L-1 · s-1 ) and larger area under the reactance curve (AX, 0.78, 95%CI: 0.49; 1.07 kPa · L-1 ) than controls. In children born at 22-24 weeks of gestation, 24% had FVC and 44% had FEV1 below the lower limit of normal. SGA and severe BPD only marginally contributed to pulmonary outcomes. Asthma-like disease was reported in 40% of extremely preterm children and 15% of controls.CONCLUSION: Many children born extremely preterm have altered airway mechanics and significant obstructive reduction in lung function. This warrants consideration for treatment and continued follow-up.
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