| 1. |
- Hansen-Pupp, Ingrid, et al.
(författare)
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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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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 96:4, s. 1129-1135
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Tidskriftsartikel (refereegranskat)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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| 2. |
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| 3. |
- Pupp, Ingrid, et al.
(författare)
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Circulatory insulin-like growth factor-I and brain volumes in relation to neurodevelopmental outcome in very preterm infants
- 2013
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447 .- 0047-2506 .- 1478-6990. ; 74:5, s. 564-569
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To evaluate the relationships between postnatal change in circulatory insulin-like growth factor-I (IGF-I) concentrations, brain volumes, and developmental outcome at 2 y of age in very preterm infants. METHODS: IGF-I was measured weekly, and nutritional intake was calculated daily from birth until a postmenstrual age (PMA) of 35 wk. Individual beta coefficients for IGF-I, IGF-I(B), representing the rate of increase in IGF-I from birth until a PMA of 35 wk were calculated. Brain magnetic resonance imaging was performed at term age, with segmentation into total brain, cerebellar, gray matter, and unmyelinated white matter volume (UWMV). Developmental outcome was evaluated using Bayley Scales of Infant Development-II. RESULTS: Forty-nine infants, with mean gestational age (GA) of 26.0 wk, were evaluated at mean 24.6 mo corrected age. Higher IGF-I(B), UWMV, and cerebellar volume were associated with a decreased risk for a Mental Developmental Index (MDI) <85 (odds ratio (95% confidence interval): 0.6 (0.4-0.9), 0.96 (0.94-0.99), and 0.78 (0.6-0.96), respectively). In multivariate analysis, higher IGF-I(B) and higher UWMV combined with female gender constituted the two models with the highest predictive value for MDI > 85. CONCLUSION: A higher rate of increase in circulating IGF-I is associated with a decreased risk for subnormal MDI at 2 y of corrected age. This relationship is in part dependent on brain volume at term age.
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| 4. |
- Pupp, Ingrid, et al.
(författare)
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Fresh-frozen plasma as a source of exogenous insulin-like growth factor-I in the extremely preterm infant
- 2009
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Ingår i: J Clin Endocrinol Metab. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94:2, s. 477-482
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Preterm birth is followed by a decrease in circulatory levels of IGF-I and IGF binding protein (IGFBP)-3, proteins with important neurogenic and angiogenic properties. OBJECTIVE: Our objective was to evaluate the effects of iv administration of fresh-frozen plasma (FFP) from adult donors on circulatory levels of IGF-I and IGFBP-3 in extremely preterm infants. DESIGN, SETTING, AND PATIENTS: A prospective cohort study was performed in 20 extremely preterm infants [mean (SD) gestational age 25.3 (1.3) wk] with clinical requirement of FFP during the first postnatal week. Sampling was performed before initiation of transfusion, directly after, and at 6, 12, 24, and 48 h after completed FFP transfusion. MAIN OUTCOME MEASURES: Concentrations of IGF-I and IGFBP-3 before and after transfusion of FFP were determined. RESULTS: FFP with a mean (SD) volume of 11 ml/kg (3.1) was administered at a median postnatal age of 2 d (range 1-7). Mean (SD) IGF-I and IGFBP-3 concentrations in administered FFP were 130 (39) and 2840 microg/liter (615), respectively. Immediately after FFP transfusion, mean (SD) concentrations of IGF-I increased by 133% from 11 (6.4) to 25 microg/liter (9.3) (P < 0.001) and IGFBP-3 by 61% from 815 (451) to 1311 microg/liter (508) (P < 0.001). Concentrations of IGF-I and IGFBP-3 remained higher at 6 (P < 0.001, P = 0.009) and 12 h (P = 0.017, P = 0.018), respectively, as compared with concentrations before FFP transfusion. Typical half-life of administrated IGF-I was 3.4 h for a 1-kg infant. CONCLUSION: Transfusion of FFP to extremely preterm infants during the first postnatal week elevates levels of IGF-I and IGFBP-3.
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| 5. |
- Pupp, Ingrid, et al.
(författare)
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Inflammation at birth and the insulin-like growth factor system in very preterm infants.
- 2007
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Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 96:6, s. 830-836
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Tidskriftsartikel (refereegranskat)abstract
- Background: Foetal inflammation is associated with an increased risk of brain damage in preterm infants whereas IGF-I is essential for cerebral development and exhibits anti-apoptotic properties. Aim: To assess levels of IGF-I and IGF binding proteins at very preterm birth and to evaluate their relationship with foetal pro-inflammation and cerebral damage. Methods: Levels of IGF-I, IGF binding protein 3 (IGFBP-3), high- (hp) and low-phosphorylated (lp) IGFBP-1 in cord blood and neonatal blood at 72 h after delivery were analysed in relation to levels of cytokines and cerebral damage as detected by ultrasound in 74 inborn infants [mean gestational age (GA) 27.1 weeks]. Evaluation was performed separately according to birth weight for GA. Results: In cord blood of infants appropriate for gestational age (AGA) higher levels of IL-6 and IL-8 were associated with lower IGF-I (r = -0.38, p = 0.008 and r = -0.36, p = 0.014). Higher levels of IL-6, IL-8 and TNF-alpha were associated with both higher levels of lpIGFBP-1 (r = 0.54, p < 0.001, r = 0.50, p < 0.001 and r = 0.13, p = 0.012, respectively) and hpIGFBP-1 (r = 0.55, p < 0.001, r = 0.45, p = 0.002 and r = 0.32, p = 0.026, respectively). Infants with intraventricular haemorrhage grade III (n = 5) had higher levels of lp/hpIGFBP-1 in cord blood (p = 0.001 and 0.002, respectively). Conclusion: Pro-inflammation at birth is associated with changes in the IGF-system. This may be of importance for development of brain damage in preterm infants.
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| 6. |
- Pupp, Ingrid, et al.
(författare)
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Inflammation at Birth is associated with Subnormal Development in Very Preterm Infants.
- 2008
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Ingår i: Pediatric Research. - 1530-0447. ; 64, s. 183-188
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Tidskriftsartikel (refereegranskat)abstract
- Preterm birth carries a risk for impaired developmental outcome. We have previously described an association between increased levels of pro-inflammatory cytokines during the first 72 postnatal hours and cerebral damage as detected by ultrasound in a cohort of 74 very preterm infants. Sixty-seven of 71 surviving children with a mean (SD) GA of 27.1 (2.0) weeks were examined at 2 years corrected age with a standardized neurological examination and with Bayley Scales of Infant Development. We hypothesized that pro-inflammatory cytokine concentrations at or shortly after birth would be associated with an adverse developmental outcome. Increased concentrations of TNF-alpha in cord blood OR (95% CI) 3.3 (1.1-10.2), p=0.013 and at 6 h 7.8 (0.9-71.8), p=0.015 and of IL-6 in cord blood 1.7 (1.0-2.9), p=0.048 were associated with psychomotor developmental index <85. Increased concentrations of TNF-alpha in cord blood OR (95% CI) 3.6 (1.002-12.8), p=0.044 and of IL-8 in cord blood 3.5 (1.2-10.6), p=0.023 were associated with cerebral palsy. Associations of TNF-alpha and IL-8 in cord blood with the respective outcome measures remained significant after adjustment for other clinical variables. Pro-inflammation at birth is associated with impaired functional outcome at 2 years of corrected age in children with very preterm birth.
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| 7. |
- Pupp, Ingrid, et al.
(författare)
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Influence of insulin-like growth factor I and nutrition during phases of postnatal growth in very preterm infants
- 2011
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Ingår i: Pediatric Research. - 0031-3998. ; 69:5, s. 448-453
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Tidskriftsartikel (refereegranskat)abstract
- Pronounced growth restriction (GR) occurs after very preterm birth. The interaction between IGF-I, nutritional intake, and growth was evaluated prospectively in 64 infants with a mean (SD) GA of 25.7 (1.9) wk. Blood sampling of IGF-I and measurements of weight, length, and head circumference were performed weekly until discharge. Daily calculation of nutritional intake was performed. Standard deviation scores (SDSs) for growth parameters defined two growth phases: GR phase (birth until lowest SDS) and catch-up (CU) phase (lowest SDS until 35 gestational weeks). IGF-I concentrations during the first postnatal weeks were low and increased at 30 wk GA, irrespective of GA at birth, coinciding with initiation of CU growth. Concentrations of IGF-I were positively associated with change in weight SDS during the GR phase, p = 0.001 and CU phase, p = 0.004-0.027. Protein and energy intake were not associated with change in SDS weight during the GR phase as opposed to the CU phase (p < 0.001, respectively). Nutritional intake did not correlate to concentrations of IGF-I before 30 wk GA. IGF-I is associated with growth at an earlier postnatal age than nutrient intake and the effect of nutrition on levels of IGF-I may be restricted to the period of established CU growth. ABBREVIATIONS::
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| 8. |
- Sveinsdóttir, Kristbjörg, et al.
(författare)
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Relation of Retinopathy of Prematurity to Brain Volumes at Term Equivalent Age and Developmental Outcome at 2 Years of Corrected Age in Very Preterm Infants
- 2018
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 114:1, s. 46-52
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Tidskriftsartikel (refereegranskat)abstract
- Background: Retinopathy of prematurity (ROP) is a major complication of preterm birth and has been associated with later visual and nonvisual impairments. Objectives: To evaluate relationships between any stage of ROP, brain volumes, and developmental outcomes. Methods: This study included 52 very preterm infants (gestational age [mean +/- SD]: 26.4 +/- 1.9 weeks). Total brain, gray matter, unmyelinated white matter (UWMV), and cerebellar volumes were estimated in 51 out of 52 infants by magnetic resonance imaging at term-equivalent age. Bayley Scales of Infant Development were used to assess developmental outcomes in 49 out of 52 in-fants at a mean corrected age of 24.6 months. Results: Nineteen out of 52 infants developed any stage of ROP. Infants with ROP had a lower median (IQR) UWMV (173 [156-181] vs. 204 [186-216] mL, p < 0.001) and cerebellar volume (18.3 [16.5-20] vs. 22.3 [20.3-24.7] mL, p < 0.001) than infants without ROP. They also had a lower median (IQR) mental developmental index (72 [56-83] vs. 100 [88-104], p < 0.001) and a lower psychomotor developmental index (80 [60-85] vs. 92 [81-103], p = 0.002). Brain volumes and developmental outcomes did not differ among infants with different stages of ROP. Conclusion: Any stage of ROP in preterm infants was associated with a reduced brain volume and an impaired developmental outcome. These results suggest that common pathways may lead to impaired neural and neurovascular development in the brain and retina and that all stages of ROP may be considered in future studies on ROP and development. (c) 2018 S. Karger AG, Basel
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| 9. |
- Wikström, Sverre, 1978-, et al.
(författare)
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Carbon Dioxide and Glucose Affect Electrocortical Background in Extremely Preterm Infants
- 2011
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 127:4, s. 1028-1034
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate if PaCO2 and plasma glucose levels affect electrocortical activity. METHODS: Ours was an observational study of 32 infants with a gestational age of 22 to 27 weeks. We performed simultaneous single-channel electroencephalogram (EEG) and repeated blood gas/plasma glucose analyses during the first 3 days (n = 247 blood samples with corresponding EEG). Interburst intervals (IBIs) and EEG power were averaged at the time of each blood sample. RESULTS: There was a linear relationship between PaCO2 and IBI; increasing PaCO2 was associated with longer IBIs. One day after birth, a 1-kPa increase in PaCO2 was associated with a 16% increase in IBI in infants who survived the first week without severe brain injury. EEG power was highest at a PaCO2 value of 5.1 kPa and was attenuated both at higher and lower PaCO2 values. Corrected for carbon dioxide effects, plasma glucose was also associated with IBI. Lowest IBI appeared at a plasma glucose level of 4.0 mmol/L, and there was a U-shaped relationship between plasma glucose level and EEG with increasing discontinuity at glucose concentrations above and below 4.0 mmol/L. CONCLUSIONS: Both carbon dioxide and plasma glucose level influenced EEG activity in extremely preterm infants, and values considered to be within normal physiologic ranges were associated with the best EEG background. Increasing EEG discontinuity occurred at carbon dioxide levels frequently applied in lung-protection strategies; in addition, moderate hyperglycemia was associated with measurable EEG changes. The long-term effects of changes in carbon dioxide and glucose on brain function are not known. Pediatrics 2011; 127: e1028-e1034
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| 10. |
- Wikström, Sverre, 1978-, et al.
(författare)
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Early Electroencephalography Suppression and Postnatal Morbidities Correlate with Cerebral Volume at Term-Equivalent Age in Very Preterm Infants
- 2018
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Ingår i: Neonatology. - : S. Karger. - 1661-7800 .- 1661-7819. ; 113:1, s. 15-20
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Early brain activity is associated with long-term outcome. Establishing a relation also with postnatal brain growth may increase our understanding of early life influences on preterm brain development.OBJECTIVES: The aim of this study was to investigate whether early electroencephalography (EEG) activity in infants born very preterm is associated with brain volumes at term, and whether postnatal morbidity affects this association.METHODS: Very preterm infants (n = 38) with a median gestational age (GA) of 25.6 weeks had early recordings of single-channel EEG. The percentage of suppressed EEG, i.e., interburst intervals (IBI%) between 24 and 72 h of age, was analyzed in relation to brain volumes on magnetic resonance imaging performed at term-equivalent age, taking into account neonatal morbidities.RESULTS: Early electrocortical depression and a higher IBI% were associated with increased cerebrospinal fluid volume (CSFV) and lower total brain volume relative to intracranial volume, also after adjustment for GA, postnatal morbidities, morphine administration, and postnatal head growth. Overall, an increase in IBI% to 1 SD from the mean corresponded with an increase in CSFV to +0.7 SD and a decrease in brain volume to -0.7 SD. The presence of 2 or more postnatal morbidities were associated with around 10% lower brain volumes.CONCLUSIONS: More suppressed early EEG activity of very preterm infants is associated with lower brain volume and increased CSFV at term age, also when adjusting for postnatal morbidities. The findings indicate the importance of pre- and early postpartal determinants of postnatal brain growth, possibly also including activity-dependent mechanisms for brain growth.
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