| 1. |
- Cizmeci, Mehmet N, et al.
(författare)
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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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Ingår i: Journal of Pediatrics. - : Elsevier BV. - 1097-6833 .- 0022-3476. ; 208, s. 2-197
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Cizmeci, Mehmet N, et al.
(författare)
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Randomized Controlled Early versus Late Ventricular Intervention Study in Posthemorrhagic Ventricular Dilatation : Outcome at 2 Years
- 2020
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Ingår i: Journal of Pediatrics. - : Elsevier BV. - 1097-6833 .- 0022-3476. ; 226, s. 3-35
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Tidskriftsartikel (refereegranskat)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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| 3. |
- 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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| 4. |
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| 5. |
- Noponen, Tommi, et al.
(författare)
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Circulatory Effects of Inhaled Iloprost in the Newborn Preterm Lamb.
- 2009
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Ingår i: Pediatric Research. - 1530-0447. ; 66, s. 416-422
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Tidskriftsartikel (refereegranskat)abstract
- Inhaled nitric oxide (iNO) has an established role in the treatment of pulmonary hypertension in the newborn. However, costs and potential toxicity associated with iNO have generated interest in alternative inhaled selective pulmonary vasodilators such as iloprost. In a preterm lamb model of respiratory distress syndrome, we studied effects of increasing doses of iloprost followed by iNO on right ventricular pressure (RVP) and circulation including cerebral oxygenation. Fetal sheep were randomized to three doses (0.2 - 4 mg/kg) of iloprost (n=9) or saline (n=10), administered as 15 min inhalations with 15 min intervals after a 60-min postnatal stabilisation. No differences were found in RVP, arterial pO2, or cardiac index according to treatment. The cerebral oxygenation, measured with near-infrared spectroscopy, deteriorated in control lambs, but not in iloprost lambs. Iloprost treatment followed by iNO resulted in a larger decrease (p=0.007) in RVP than saline treatment followed by iNO. In conclusion, iloprost stabilised cerebral oxygenation and when followed by iNO had a larger effect on RVP than iNO alone. Although species differences may be relevant, these results suggest that iloprost should be studied in newborn infants for the treatment of pulmonary hypertension.
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| 6. |
- Perez de Sá, Valéria, et al.
(författare)
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High brain tissue oxygen tension during ventilation with 100% oxygen after fetal asphyxia in newborn sheep
- 2009
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Ingår i: Pediatric Research. - 0031-3998 .- 1530-0447. ; 65:1, s. 57-61
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Tidskriftsartikel (refereegranskat)abstract
- The optimal inhaled oxygen fraction for newborn resuscitation is still not settled. We hypothesized that short-lasting oxygen ventilation after intrauterine asphyxia would not cause arterial or cerebral hyperoxia, and therefore be innocuous. The umbilical cord of fetal sheep was clamped and 10 min later, after delivery, ventilation with air (n = 7) or with 100% oxygen for 3 (n = 6) or 30 min (n = 5), followed by air, was started. Among the 11 lambs given 100% oxygen, oxygen tension (PO2) was 10.7 (1.8-56) kPa [median (range)] in arterial samples taken after 2.5 min of ventilation. In those ventilated with 100% oxygen for 30 min, brain tissue PO2 (PbtO2) increased from less than 0.1 kPa in each lamb to individual maxima of 56 (30-61) kPa, whereas in those given oxygen for just 3 min, PbtO2 peaked at 4.2 (2.9-46) kPa. The maximal PbtO2 in air-ventilated lambs was 2.9 (0.8-5.4) kPa. Heart rate and blood pressure increased equally fast in the three groups. Thus, prolonged ventilation with 100% oxygen caused an increase in PbtO2 of a magnitude previously only reported under hyperbaric conditions. Reducing the time of 100% oxygen ventilation to 3 min did not consistently avert systemic hyperoxia.
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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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