| 1. |
- Ahearne, CE, et al.
(författare)
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Early Cord Metabolite Index and Outcome in Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy
- 2016
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 110:4, s. 296-302
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> A <sup>1</sup>H-NMR-derived metabolomic index based on early umbilical cord blood alterations of succinate, glycerol, 3-hydroxybutyrate and O-phosphocholine has shown potential for the prediction of hypoxic-ischaemic encephalopathy (HIE) severity. <b><i>Objective:</i></b> To evaluate whether this metabolite score can predict 3-year neurodevelopmental outcome in infants with perinatal asphyxia and HIE, compared with current standard biochemical and clinical markers. <b><i>Methods:</i></b> From September 2009 to June 2011, infants at risk of perinatal asphyxia were recruited from a single maternity hospital. Cord blood was drawn and biobanked at delivery. Neonates were monitored for development of encephalopathy both clinically and electrographically. Neurodevelopmental outcome was assessed at 36-42 months using the Bayley Scales of Infant and Toddler Development, ed. III (BSID-III). Death and cerebral palsy were also considered as abnormal end points. <b><i>Results:</i></b> Thirty-one infants had both metabolomic analysis and neurodevelopmental outcome at 36-42 months. No child had a severely abnormal BSID-III result. The metabolite index significantly correlated with outcome (ρ<sup>2</sup> = 0.30, p < 0.01), which is robust to predict both severe outcome (area under the receiver operating characteristic curve: 0.92, p <i>< </i>0.01) and intact survival (0.80, p = 0.01). There was no correlation between the index score and performance in the individual BSID-III subscales (cognitive, language, motor). <b><i>Conclusions:</i></b> The metabolite index outperformed other standard biochemical markers at birth for prediction of outcome at 3 years, but was not superior to EEG or the Sarnat score.
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| 2. |
- Almlen, A, et al.
(författare)
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Concentration dependence of a poly-leucine surfactant protein C analogue on in vitro and in vivo surfactant activity
- 2007
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 92:3, s. 194-200
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Modified natural surfactants currently used for treatment of respiratory distress syndrome contain about 0.5–1% (w/w phospholipids) of each of the surfactant proteins SP-B and SP-C. The supply of these preparations is limited and synthetic surfactant preparations containing lipids and peptides are under development. <i>Objectives:</i> To investigate the potential of different concentrations of the SP-C analogue SP-C33 in 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphoglycerol (68:31, w/w). <i>Methods:</i> Surface activity was evaluated in pulsating and captive bubble surfactometers and in immature newborn rabbits. <i>Results:</i> Preparations containing ≧1% SP-C33 achieve minimum surface tension <5 mN/m indicating good biophysical activity, and increase tidal volumes in premature rabbit fetuses to the same level as a modified natural surfactant preparation does. Alveolar patency at end expiration, as evaluated by measurement of lung gas volumes, histological assessment of alveolar expansion and determination of alveolar volume density, was lower in the animals treated with synthetic surfactant than in those receiving modified natural surfactant. <i>Conclusions:</i> These data suggest that SP-C33 is similarly efficient as the native peptide in improving surface properties of phospholipids mixtures and in increasing lung compliance in surfactant-deficient states, but that other components are needed to maintain alveolar stability at low airway pressures.
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| 3. |
- Almlen, A, et al.
(författare)
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Synthetic surfactant based on analogues of SP-B and SP-C is superior to single-peptide surfactants in ventilated premature rabbits
- 2010
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 98:1, s. 91-99
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Respiratory distress syndrome (RDS) is currently treated with surfactant preparations obtained from natural sources and attempts to develop equally active synthetic surfactants have been unsuccessful. One difference in composition is that naturally derived surfactants contain the two hydrophobic proteins SP-B and SP-C while synthetic preparations contain analogues of either SP-B or SP-C. It was recently shown that both SP-B and SP-C (or SP-C33, an SP-C analogue) are necessary to establish alveolar stability at end-expiration in a rabbit RDS model, as reflected by high lung gas volumes without application of positive end-expiratory pressure. <i>Objectives:</i> To study the efficacy of fully synthetic surfactants containing analogues of both SP-B and SP-C compared to surfactants with only one protein analogue. <i>Methods:</i> Premature newborn rabbits, treated with synthetic surfactants, were ventilated for 30 min without positive end-expiratory pressure. Tidal volumes as well as lung gas volumes at end-expiration were determined. <i>Results:</i> Treatment with 2% Mini-B (a short-cut version of SP-B) and 2% SP-C33, or its C-terminally truncated form SP-C30, in 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphoglycerol, 68:31 (w/w) resulted in median lung gas volumes of 8–9 ml/kg body weight, while animals treated with 2% Mini-B surfactant or 2% SP-C33/SP-C30 surfactant had lung gas volumes of 3–4 ml/kg, and those treated with Curosurf, a porcine surfactant, 15–17 ml/kg. In contrast, mixing SP-C33 with peptides with different distributions of positively charged and hydrophobic residues did not improve lung gas volumes. <i>Conclusions:</i> The data indicate that synthetic surfactants containing analogues of both SP-B and SP-C might be superior to single-peptide surfactants in the treatment of RDS.
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| 4. |
- Aman, J., et al.
(författare)
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Increased Fat Mass and Cardiac Septal Hypertrophy in Newborn Infants of Mothers with Well-Controlled Diabetes during Pregnancy
- 2011
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 100:2, s. 147-154
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Tidskriftsartikel (refereegranskat)abstract
- Background: Improved glycaemic control during pregnancy in mothers with type 1 diabetes (T1DM) and gestational diabetes (GDM) has resulted in a marked reduction of perinatal mortality and morbidity, but the prevalence of macrosomia is usually high. Objective: We used non-invasive anthropometric methods to estimate the body composition and the thickness of the interventricular heart septum in 18 infants of mothers with well-controlled T1DM, 10 infants of mothers with GDM and 28 infants of healthy control mothers matched for gestational age and mode of delivery. Methods: Skinfold measurements were obtained with a Harpenden calliper within 48 h after delivery. Echocardiography was also performed to measure the thickness of the interventricular septum. Cord blood was sampled for assays of C-peptide, leptin and IGF-I. Results: The rates of macrosomia (gestational age-adjusted birth weight >2 standard deviation score, SDS) were 56 and 30% in infants of mothers with T1DM and GDM, respectively, compared to 10% in control infants. The body fat content was 40% (0.2 kg) higher and the interventricular heart septum thickness was increased by 20% in both groups of infants of diabetic mothers. We found no associations between maternal levels of HbA1c during pregnancy and body composition or interventricular heart septum thickness. Cord levels of C-peptide and leptin were significantly higher in infants of T1DM mothers than in control infants. Cord leptin level was associated with birth weight SDS and percent body fat in infants of T1DM mothers. IGF-I was associated with percent body fat in infants of GDM mothers and control mothers. A multiple-regression analysis showed that 50% of the variation in body weight SDS could be determined, with IGF-I, leptin and C-peptide as independent variables. Conclusion: Both fat mass and cardiac septal thickness are increased in newborn infants of women with T1DM and GDM in spite of efforts to achieve good glycaemic control during pregnancy.
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| 5. |
- Artlich, A, et al.
(författare)
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Single breath analysis of endogenous nitric oxide in the newborn
- 2001
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Ingår i: Biology of the neonate. - : S. Karger AG. - 0006-3126. ; 79:1, s. 21-26
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Tidskriftsartikel (refereegranskat)abstract
- Nitric oxide (NO) is found in the exhaled gas of humans immediately after birth. However, variations of endogenous NO concentration during the breathing cycle have not been studied in newborns. We examined 24 newborns without acute respiratory compromise during spontaneous nasal breathing. Gas was sampled from the tip of a thin nasal catheter placed in the hypopharynx. Endogenous NO concentrations measured by chemiluminescence were assigned to the breathing cycle using synchronized CO<sub>2</sub> recording. Exhaled NO could reproducibly be measured at 1.9 ± 0.2 parts per billion (ppb, mean ± SEM). Autoinhaled nasal NO peaks during regular breathing were 12.0 ± 1.7 ppb and reached intermittent maxima of 52.2 ± 5.8 ppb. During regular breathing 6 infants exhibited sudden decreases of nasal NO peaks to periods with <50% amplitude suggesting transient shortage of autoinhaled nasal NO. We conclude that tidal NO analysis can be used to assess upper and lower airway NO production noninvasively during spontaneous breathing in the newborn.
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| 6. |
- Basabe-Burgos, O, et al.
(författare)
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Disulphide Bridges in Surfactant Protein B Analogues Affect Their Activity in Synthetic Surfactant Preparations
- 2019
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 115:2, s. 134-141
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Limited supply and complicated manufacturing procedure of animal-derived surfactants make the development of synthetic surfactants warranted. The synthesis of surfactant protein (SP)-B and SP-C is complicated and several analogues have been developed. Mini-BLeu is an analogue that corresponds to the first and last helix of SP-B joined by a loop and linked by 2 disulphide bridges. SP-C33Leu is an SP-C analogue that can be cost-efficiently produced, but no such analogue has yet been described for SP-B. <b><i>Objective:</i></b> To design short SP-B analogues which lack disulphide bridges, are easy to produce and are efficacious in a preterm rabbit fetus model of neonatal RDS. <b><i>Methods:</i></b> Synthetic surfactants were prepared by adding 2 or 8% (w/w) of synthetic variants of Mini-B27, similar to Mini-BLeu but with a short loop, or different peptides covering helix 1 of SP-B to 2% (w/w) of SP-C33Leu in 80 mg/mL of 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine/egg yolk phosphatidylcholine/1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphoglycerol, 50: 40: 10 (by weight). Premature newborn rabbit fetuses were treated with 200 mg/kg of the surfactant preparations and ventilated with defined pressures for 30 min without positive end-expiratory pressure. Tidal volumes were registered during the experiments and lung gas volumes were measured at the end of the ventilation period. <b><i>Results:</i></b> Synthetic surfactant containing the Mini-B27 analogue with 2 disulphides gives similar lung gas volumes as treatment with an animal-derived surfactant preparation, but all other SP-B analogues gave lower lung gas volumes. All synthetic surfactants studied gave no significant differences in compliances except the surfactant containing the Mini-B27 analogue without cysteines that performed somewhat better at 30 min. <b><i>Conclusion:</i></b> The helix-loop-helix SP-B analogues tested in this study require the presence of 2 disulphide bridges for optimal activity in a rabbit RDS model.
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| 7. |
- Beltempo, Marc, et al.
(författare)
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Respiratory Management of Extremely Preterm Infants : An International Survey
- 2018
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7800 .- 1661-7819. ; 114:1, s. 28-36
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There are significant international variations in chronic lung disease rates among very preterm infants yet there is little data on international variations in respiratory strategies.OBJECTIVE: To evaluate practice variations in the respiratory management of extremely preterm infants born at < 29 weeks' gestational age (GA) among 10 neonatal networks participating in the International Network for Evaluating Outcomes (iNeo) of Neonates collaboration.METHODS: A web-based survey was sent to the representatives of 390 neonatal intensive care units from Australia/New Zealand, Canada, Finland, Illinois (USA), Israel, Japan, Spain, Sweden, Switzerland, and Tuscany (Italy). Responses were based on practices in 2015.RESULTS: Overall, 321 of the 390 units responded (82%). The majority of units within networks (40-92%) mechanically ventilate infants born at 23-24 weeks' GA on continuous positive airway pressure (CPAP) with 30-39% oxygen in respiratory distress within 48 h after birth, but the proportion of units that offer mechanical ventilation for infants born at 25-26 weeks' GA at similar settings varied significantly (20-85% of units within networks). The most common respiratory strategy for infants born at 27-28 weeks' GA on CPAP with 30-39% oxygen with respiratory distress within 48 h after birth used by units also varied significantly among networks: mechanical ventilation (0-60%), CPAP (3-82%), intubation and surfactant administration with immediate extubation (0-75%), and less invasive surfactant administration (0-68%).CONCLUSIONS: There are marked variations but also similarities in respiratory management of extremely preterm infants between networks. Further collaboration and exploration is needed to better understand the association of these variations in practice with pulmonary outcomes.
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| 8. |
- Benterud, T, et al.
(författare)
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N-Acetylcysteine Amide Exerts Possible Neuroprotective Effects in Newborn Pigs after Perinatal Asphyxia
- 2017
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 111:1, s. 12-21
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Perinatal asphyxia and ensuing reoxygenation change the antioxidant capacity of cells and organs. <b><i>Objectives:</i></b> To analyze the neuroprotective effect of the antioxidant N-acetylcysteine amide (NACA) after perinatal hypoxia-reoxygenation with an emphasis on proinflammatory cytokines and the transcription factor NF-κB in the prefrontal cortex of neonatal pigs. <b><i>Methods:</i></b> Twenty-nine newborn pigs, aged 12-36 h, were subjected to global hypoxia and hypercapnia. One sham-operated group (n = 5) and 2 experimental groups (n = 12) were exposed to 8% oxygen, until the base excess was -20 mmol/l or the mean arterial blood pressure fell to <20 mm Hg (asphyxia with NACA or saline). The pigs were observed for 9.5 h after hypoxia. Samples of prefrontal cortex and plasma were analyzed. <b><i>Results:</i></b> Cortex: there was no significant difference in mRNA expression between the intervention groups regarding IL-1β, IL6, TNFα, MMP2, MMP9 or IL18. Pigs exposed to hypoxia-reoxygenation and treatment with NACA (NACA-pigs) had a significantly lower protein concentration of IL-1β than pigs treated with saline (placebo controls), i.e. 8.8 ± 3.9 versus 16.8 ± 10.5 pg/mg protein (p = 0.02). The activation of the transcription factor NF-κB (measured as the fold-change of phosphorylated p65<sup>Ser 536</sup>), was reduced in the NACA-pigs when compared to the placebo controls (5.2 ± 4.3 vs. 16.0 ± 13.5; p = 0.02). No difference between the intervention groups regarding brain histopathology or in the levels of 8-oxoguanine measured in the prefrontal cortex were observed. Plasma: the NACA-pigs had a stronger reduction of TNFα in the first 30 min following asphyxia compared with the placebo controls, i.e. 36 (30-44) versus 24 (14-32)% (p = 0.01). <b><i>Conclusion:</i></b> The reduced levels of the pivotal inflammatory markers IL-1β and TNFα and the transcription factor NF-κB may indicate that NACA has possible neuroprotective effects after perinatal asphyxia.
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| 9. |
- Berg, Johan Henrik Martin, et al.
(författare)
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Effect of Delayed Cord Clamping on Neurodevelopment at 3 Years : A Randomized Controlled Trial
- 2021
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Ingår i: Neonatology. - : S. Karger. - 1661-7800 .- 1661-7819. ; 118:3, s. 282-288
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Iron deficiency (ID) is associated with poor neurodevelopment. We have previously shown that delayed umbilical cord clamping (CC) improves iron stores at 8 months and neurodevelopment at 1 year in term, healthy infants in Nepal.Objective: The aim of this study was to assess the effects of delayed CC (≥180 s) compared to early CC (≤60 s) on neurodevelopment using the Ages and Stages Questionnaire (ASQ) at age 3 years.Methods: In 2014, 540 healthy Nepalese infants born at term were randomized in a 1:1 ratio to delayed or early CC. At 3 years of age, ASQ assessment was performed by phone interviews with parents. A score >1 standard deviation below the mean was defined as "at risk" for developmental impairment.Results: At 3 years of age, 350 children were followed up, 170 (63.0%) in the early CC group and 180 (66.7%) in the delayed CC group. No significant differences in ASQ scores in any domains between groups were found. However, more girls were "at risk" for affected gross motor development in the early CC group: 14 (18.9%) versus 6 (6.3%), p = 0.02.Conclusion: There were no significant differences in ASQ scores in any domains between groups. In the subgroup analysis, fewer girls who underwent delayed CC were "at risk" for delayed gross motor development. Due to the pronounced difference in iron stores at 8 months postpartum in this cohort, follow-up studies at an older age are motivated since neurodevelopmental impairment after early ID may be more detectable with increasing age.
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| 10. |
- Berg, Johan Henrik Martin, et al.
(författare)
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Effect of Delayed Cord Clamping on Neurodevelopment at 3 Years: A Randomized Controlled Trial.
- 2021
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 118:3, s. 282-288
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Tidskriftsartikel (refereegranskat)abstract
- Iron deficiency (ID) is associated with poor neurodevelopment. We have previously shown that delayed umbilical cord clamping (CC) improves iron stores at 8 months and neurodevelopment at 1 year in term, healthy infants in Nepal.The aim of this study was to assess the effects of delayed CC (≥180 s) compared to early CC (≤60 s) on neurodevelopment using the Ages and Stages Questionnaire (ASQ) at age 3 years.In 2014, 540 healthy Nepalese infants born at term were randomized in a 1:1 ratio to delayed or early CC. At 3 years of age, ASQ assessment was performed by phone interviews with parents. A score >1 standard deviation below the mean was defined as "at risk" for developmental impairment.At 3 years of age, 350 children were followed up, 170 (63.0%) in the early CC group and 180 (66.7%) in the delayed CC group. No significant differences in ASQ scores in any domains between groups were found. However, more girls were "at risk" for affected gross motor development in the early CC group: 14 (18.9%) versus 6 (6.3%), p = 0.02.There were no significant differences in ASQ scores in any domains between groups. In the subgroup analysis, fewer girls who underwent delayed CC were "at risk" for delayed gross motor development. Due to the pronounced difference in iron stores at 8 months postpartum in this cohort, follow-up studies at an older age are motivated since neurodevelopmental impairment after early ID may be more detectable with increasing age.
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