| 1. |
- 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 Among these, life support was withdrawn in 55 infants because of anticipation of poor long-term outcome.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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| 2. |
- 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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| 3. |
- Ley, David, et al.
(author)
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Longitudinal infusion of a complex of insulin-like growth factor-I and IGF-binding protein-3 in five preterm infants : pharmacokinetics and short-term safety.
- 2013
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In: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 73:1, s. 68-74
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Journal article (peer-reviewed)abstract
- Background:In preterm infants, low levels of insulin-like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3) are associated with impaired brain growth and retinopathy of prematurity (ROP). Treatment with IGF-I/IGFBP-3 may be beneficial for brain development and may decrease the prevalence of ROP.Methods:In a phase II pharmacokinetics and safety study, five infants (three girls) with a median (range) gestational age (GA) of 26 wk + 6 d (26 wk + 0 d to 27 wk + 2 d) and birth weight of 990 (900-1,212) g received continuous intravenous infusion of recombinant human (rh)IGF-I/rhIGFBP-3. Treatment was initiated during the first postnatal day and continued for a median (range) duration of 168 (47-168) h in dosages between 21 and 111 µg/kg/24 h.Results:Treatment with rhIGF-I/rhIGFBP-3 was associated with higher serum IGF-I and IGFBP-3 concentrations (P < 0.001) than model-predicted endogenous levels. Of 74 IGF-I samples measured during study drug infusion, 37 (50%) were within the target range, 4 (5%) were above, and 33 (45%) were below. The predicted dose of rhIGF-I/rhIGFBP-3 required to establish circulating levels of IGF-I within the intrauterine range in a 1,000 g infant was 75-100 µg/kg/24 h. No hypoglycemia or other adverse effects were recorded.Conclusion:In this study, continuous intravenous infusion of rhIGF-I/rhIGFBP-3 was effective in increasing serum concentrations of IGF-I and IGFBP-3, and was found to be safe.
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| 4. |
- Ley, David, et al.
(author)
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Longitudinal infusion of insulin-like growth factor-I and IGF-binding protein-3 complex to five preterm infants: pharmacokinetics and short term safety.
- 2013
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In: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 63:1, s. 68-74
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Journal article (peer-reviewed)abstract
- Background:In preterm infants, low levels of insulin like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3) are associated with impaired brain growth and retinopathy of prematurity (ROP).Treatment with IGF-I/IGFBP-3 may be beneficial for brain development and decrease prevalence of ROP.Methods:In a phase II pharmacokinetic and safety study, five infants (3 girls) with a median (range) gestational age (GA) of 26+6 (26+0 - 27+2) weeks and birth weight (BW) of 990 (900-1212) g received continuous intravenous infusion of rhIGF-I/rhIGFBP-3. Treatment was initiated during the first postnatal day and continued for median (range) 168h (47-168) in doses between 21 - 111 µg/kg/24h.Results:Treatment with rhIGF-I/rhIGFBP-3 was associated with higher serum IGF-I and IGFBP-3 concentrations (p<0.001) than model-predicted endogenous levels. Out of 74 IGF-I samples measured during study drug infusion, 37 (50%) were within target range, 4 (5%) above and 33 (45%) were below. Predicted dose of rhIGF-I/rhIGFBP-3 to establish circulating levels of IGF-I within the intrauterine range in a 1000g infant was 75-100 µg/kg/24h. No hypoglycemia or other adverse effects were recorded.Conclusion:Continuous intravenous infusion of rhIGF-I/rhIGFBP-3 was effective in increasing serum concentrations of IGF-I and IGFBP-3. Administration during study was safe.Pediatric Research (2012); doi:10.1038/pr.2012.146.
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| 5. |
- Pupp, Ingrid, et al.
(author)
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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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In: 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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Journal article (peer-reviewed)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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| 6. |
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| 7. |
- Andersson, Ola, et al.
(author)
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Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months : a randomised controlled trial
- 2011
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In: BMJ. British Medical Journal. - : BMJ, british Medical Association. - 0959-8146 .- 0959-535X. ; 343, s. d7157-
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate the effects of delayed umbilical cord clamping, compared with early clamping, on infant iron status at 4 months of age in a European setting. DESIGN: Randomised controlled trial. SETTING: Swedish county hospital. PARTICIPANTS: 400 full term infants born after a low risk pregnancy. INTERVENTION: Infants were randomised to delayed umbilical cord clamping (≥180 seconds after delivery) or early clamping (≤10 seconds after delivery). MAIN OUTCOME MEASURES: Haemoglobin and iron status at 4 months of age with the power estimate based on serum ferritin levels. Secondary outcomes included neonatal anaemia, early respiratory symptoms, polycythaemia, and need for phototherapy. RESULTS: At 4 months of age, infants showed no significant differences in haemoglobin concentration between the groups, but infants subjected to delayed cord clamping had 45% (95% confidence interval 23% to 71%) higher mean ferritin concentration (117 μg/L v 81 μg/L, P<0.001) and a lower prevalence of iron deficiency (1 (0.6%) v 10 (5.7%), P=0.01, relative risk reduction 0.90; number needed to treat=20 (17 to 67)). As for secondary outcomes, the delayed cord clamping group had lower prevalence of neonatal anaemia at 2 days of age (2 (1.2%) v 10 (6.3%), P=0.02, relative risk reduction 0.80, number needed to treat 20 (15 to 111)). There were no significant differences between groups in postnatal respiratory symptoms, polycythaemia, or hyperbilirubinaemia requiring phototherapy. CONCLUSIONS: Delayed cord clamping, compared with early clamping, resulted in improved iron status and reduced prevalence of iron deficiency at 4 months of age, and reduced prevalence of neonatal anaemia, without demonstrable adverse effects. As iron deficiency in infants even without anaemia has been associated with impaired development, delayed cord clamping seems to benefit full term infants even in regions with a relatively low prevalence of iron deficiency anaemia. Trial registration Clinical Trials NCT01245296.
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| 8. |
- Andersson, Ola, et al.
(author)
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Effect of Delayed vs Early Umbilical Cord Clamping on Iron Status and Neurodevelopment at Age 12 Months A Randomized Clinical Trial
- 2014
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In: JAMA PEDIATR. - : American Medical Association (AMA). - 2168-6203. ; 168:6, s. 547-554
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Journal article (peer-reviewed)abstract
- IMPORTANCE Prevention of iron deficiency in infancy may promote neurodevelopment. Delayed cord clamping (DCC) can prevent iron deficiency during the first 6 months of life. However, no data are available on long-term effects on infant outcomes in relation to time for umbilical cord clamping. OBJECTIVE To investigate effects of DCC, as compared with early cord clamping (ECC), on infant iron status and neurodevelopment at age 12 months in a European setting. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 382 full-term infants born after a low-risk pregnancy at a Swedish county hospital. Follow-up at 12 months included evaluation of iron status (ferritin level, transferrin saturation, transferrin receptor level, reticulocyte hemoglobin level, and mean cell volume) and parental assessment of neurodevelopment by the Ages and Stages Questionnaire, second edition (ASQ). INTERVENTIONS Infants were randomized to DCC (>= 180 seconds after delivery) or ECC (<= 10 seconds after delivery). MAIN OUTCOMES AND MEASURES The main outcome was iron status at age 12 months; the secondary outcome was ASQ score. RESULTS In total, 347 of 382 infants (90.8%) were assessed. The DCC and ECC groups did not differ in iron status (mean ferritin level, 35.4 vs 33.6 ng/mL, respectively; P =.40) or neurodevelopment (mean ASQ total score, 229.6 vs 233.1, respectively; P =.42) at age 12 months. Predictors of ferritin levels were infant sex and ferritin in umbilical cord blood. Predictors of ASQ score were infant sex and breastfeeding within 1 hour after birth. For both outcomes, being a boy was associated with lower results. Interaction analysis showed that DCC was associated with an ASQ score 5 points higher among boys (mean [SD] score, 229 [43] for DCC vs 224 [39] for ECC) but 12 points lower among girls (mean [SD] score, 230 [39] for DCC vs 242 [36] for ECC), out of a maximum of 300 points (P =.04 for the interaction term). CONCLUSIONS AND RELEVANCE Delayed cord clamping did not affect iron status or neurodevelopment at age 12 months in a selected population of healthy term-born infants. However, it may not be possible to demonstrate minor effects on neurodevelopment with the size of the study population and the chosen method for assessment. The current data indicate that sex may influence the effects on infant development after DCC in different directions. The magnitude and biological reason for this finding remain to be investigated.
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| 9. |
- Andersson, Ola, et al.
(author)
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Effects of delayed compared with early umbilical cord clamping on maternal postpartum hemorrhage and cord blood gas sampling : a randomized trial
- 2013
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 92:5, s. 567-574
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Journal article (peer-reviewed)abstract
- Objective. To investigate the effect of delayed cord clamping (DCC) compared with early cord clamping (ECC) on maternal postpartum hemorrhage (PPH) and umbilical cord blood gas sampling. Design. Secondary analysis of a parallel-group, single-center, randomized controlled trial. Setting. Swedish county hospital. Population. 382 term deliveries after a low-risk pregnancy. Methods. Deliveries were randomized to DCC (>= 180 seconds, n = 193) or ECC (<= 10 seconds, n = 189). Maternal blood loss was estimated by the midwife. Samples for blood gas analysis were taken from one umbilical artery and the umbilical vein, from the pulsating unclamped cord in the DCC group and from the double-clamped cord in the ECC group. Samples were classified as valid when the arterial-venous difference was -0.02 or less for pH and 0.5 kPa or more for pCO(2). Main outcome measures. PPH and proportion of valid blood gas samples. Results. The differences between the DCC and ECC groups with regard to PPH(1.2%, p = 0.8) and severe PPH(-2.7%, p = 0.3) were small and non-significant. The proportion of valid blood gas samples was similar between theDCC (67%, n = 130) and ECC (74%, n = 139) groups, with 6% (95% confidence interval: -4%-16%, p = 0.2) fewer valid samples after DCC. Conclusions. Delayed cord clamping, compared with early, did not have a significant effect on maternal postpartum hemorrhage or on the proportion of valid blood gas samples. We conclude that delayed cord clamping is a feasible method from an obstetric perspective.
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| 10. |
- Andersson, Ola, et al.
(author)
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Effects of delayed cord clamping on neurodevelopment and infection at four months of age : a randomised trial
- 2013
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In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 102:5, s. 525-531
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Journal article (peer-reviewed)abstract
- Aim To investigate the effect that delayed and early umbilical cord clamping have on neurodevelopment, immunoglobulin G (IgG) and symptoms of infection during the first 4months of life.Methods Full-term infants (n=382) were randomised to delayed (180sec) or early cord clamping (10sec). The Ages and Stages Questionnaire (ASQ) was used to assess neurodevelopment at 4months. Immunoglobulin G was measured at birth, 23days and 4months. Parents recorded any symptoms indicating infection during the first 4months of life.Results The total scores from the ASQ did not differ between groups. However, the delayed cord clamping (DCC) group had a higher mean (SD) score in the problem-solving domain [55.3 (7.2) vs. 53.5 (8.2), p=0.03] at 4months and a lower mean (SD) score in the personal-social domain [49.5 (9.3) vs. 51.8 (8.1), p=0.01]. The IgG level was higher in the DCC group at 23days (11.7 vs. 11.0g/L, p=0.004), but did not differ between the groups at 4months. Symptoms of infection were comparable between the groups.Conclusion Delayed cord clamping did not affect overall neurodevelopment or symptoms of infection up to 4months of age, but may have an impact on specific neurodevelopmental domains.
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