| 1. |
- Wennerholm, Ulla-Britt, 1948, et al.
(författare)
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Timing of umbilical cord clamping for neonatal and maternal outcomes
- 2012
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Ingår i: Health Technology Assessment, HTA center Region Västra Götaland. ; :48, s. 1-51
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Forskningsöversikt (refereegranskat)abstract
- Method and patient group Late versus early clamping of the umbilical cord- maternal and infant effects Question at issue Is early umbilical cord clamping not different from or better than late umbilical cord clamping regarding postpartum infant iron deficiency and iron deficiency anaemia variables, long-term cognitive function, loss of stem cells, maternal postpartum haemorrhage, manual removal of retained placenta and correct sampling for blood gas analysis? Studied risks and benefits for patients of the new health technology Level of evidence: The literature search identified four studies that fulfilled the selection criteria; a systematic review (SR) and three subsequently published randomised controlled trials (RCTs). The definition of early cord clamping varied from within 10 to < 60 sec between studies. The SR was methodologically of high quality but included mainly studies with high risk of bias. One of the RCTs was of high and the others of low quality. Infant outcomes O1 No studies evaluated cognitive function or loss of stem cells. Conclusions: There is some support for an increased risk of immediate anaemia (6.3% vs 1.2%) (GRADE ⊕⊕??) and support for lower immediate Hb (mean difference 18g/l) and haematocrit (GRADE ⊕⊕⊕?) with early as compared with late clamping. There is support for little or no difference regarding these outcomes at long-term (at 2 to 6 months of age) (GRADE ⊕⊕⊕?). There is some support for an increased risk of long-term iron deficiency (5.7% vs. 0.6%) (GRADE ⊕⊕??) and support for lower long-term ferritin levels (GRADE ⊕⊕⊕?). There is some support for little or no difference regarding jaundice requiring phototherapy and a low Apgar score (<7 at 5 min) (GRADE⊕⊕??) and insufficient support for an effect on the need for admittance to special baby care nursery or neonatal intensive care unit (GRADE ⊕???) ). Maternal outcomes O2 There is some support for little or no difference regarding severe postpartum bleeding (GRADE ⊕⊕??) and insufficient support for an effect on the need for manual removal of placenta (GRADE ⊕??? ).. Methodological outcome O3 There is insufficient scientific documentation to evaluate the rate of correct sampling for cord blood acid-base and gas analysis after early versus late clamping. Ethical questions Is early cord clamping of the healthy term neonate ethically acceptable in view of unknown long-term infant risks regarding cognitive function? Presently, late cord clamping does not allow cord blood collection. Future research may identify optimal timing of cord clamping, to resolve these ethical issues. Economical aspects There are no reasons to believe that initial costs are different.
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| 2. |
- Alm, Henrik, et al.
(författare)
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Exposure to brominated flame retardant PBDE-99 affects cytoskeletal protein expression in the neonatal mouse cerebral cortex
- 2008
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Ingår i: Neurotoxicology. - : Elsevier BV. - 0161-813X .- 1872-9711. ; 29:4, s. 628-637
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Tidskriftsartikel (refereegranskat)abstract
- Polybrominated diphenyl ethers (PBDEs) are environmental contaminants found in human and animal tissues worldwide. Neonatal exposure to the flame retardant 2,2', 4,4',5-pentabromodiphenyl ether (PBDE-99) disrupts normal brain development in mice, and results in disturbed spontaneous behavior in the adult. The mechanisms underlying the late effects of early exposure are not clear. To gain insight into the initial neurodevelopmental damage inflicted by PBDE-99, we investigated the short-term effects of PBDE-99 on protein expression in the developing cerebral cortex of neonatal mice, and the cytotoxic and apoptotic effects of PBDE-99 in primary cultures of fetal rat cortical cells. We used two-dimensional difference gel electrophoresis (2D-DIGE) to analyze protein samples isolated from the cortex of NMRI mice 24h after exposure to a single oral dose of 12 mg/kg PBDE-99 on post-natal day 10. Protein resolution was enhanced by sample pre-fractionation. In the cell model, we determined cell viability using the trypan blue exclusion assay, and apoptosis using immunocytochemical detection of cleaved caspase-3. We determined the identity of 111 differentially expressed proteins, 32 (29%) of which are known to be cytoskeleton-related. Similar to previous findings in the striatum, we found elevated levels of the neuron growth-associated protein Gap43 in the cortex. In cultured cortical cells, a high concentration of PBDE-99 (30 microM) induced cell death without any apparent increase in caspase-3 activity. These results indicate that the permanent neurological damage induced by PBDE-99 during the brain growth spurt involve detrimental effects on cytoskeletal regulation and neuronal maturation in the developing cerebral cortex.
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| 3. |
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| 4. |
- Alm, Henrik, et al.
(författare)
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In Vitro Neurotoxicity of PBDE-99 : Immediate and Concentration-Dependent Effects on Protein Expression in Cerebral Cortex Cells
- 2010
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 9:3, s. 1226-1235
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Tidskriftsartikel (refereegranskat)abstract
- Polybrominated diphenyl ethers (PBDEs) are commonly used flame retardants in various consumer products. Pre- and postnatal exposure to congeners of PBDEs disrupts normal brain development in rodents. Two-dimensional difference gel electrophoresis (2D-DIGE) was used to analyze concentration-dependent differences in protein expression in cultured cortical cells isolated from rat fetuses (GD 21) after 24 h exposure to PBDE-99 (3, 10, or 30 muM). Changes on a post-translational level were studied using a 1 h exposure to 30 muM PBDE-99. The effects of 24 h exposure to 3 and 30 muM PBDE-99 on mRNA levels were measured using oligonucleotide microarrays. A total of 62, 46, and 443 proteins were differentially expressed compared to controls after 24 h of exposure to 3, 10, and 30 muM PDBE-99, respectively. Of these, 48, 43, and 238 proteins were successfully identified, respectively. We propose that the biological effects of low-concentration PBDE-99 exposure are fundamentally different than effects of high-concentration exposure. Low-dose PBDE-99 exposure induced marked effects on cytoskeletal proteins, which was not correlated to cytotoxicity or major morphological effects, suggesting that other more regulatory aspects of cytoskeletal functions may be affected. Interestingly, 0.3 and 3 muM, but not 10 or 30 muM increased the expression of phosphorylated (active) Gap43, perhaps reflecting effects on neurite extension processes.
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| 5. |
- Alm, Henrik, et al.
(författare)
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Proteomic evaluation of neonatal exposure to 2,2,4,4,5-pentabromodiphenyl ether
- 2006
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 114:2, s. 254-259
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to the brominated flame retardant 2,2 ,4,4 ,5-pentabromodiphenyl ether (PBDE-99) during the brain growth spurt disrupts normal brain development in mice and results in disturbed spontaneous behavior in adulthood. The neurodevelopmental toxicity of PBDE-99 has been reported to affect the cholinergic and catecholaminergic systems. In this study we use a proteomics approach to study the early effect of PBDE-99 in two distinct regions of the neonatal mouse brain, the striatum and the hippocampus. A single oral dose of PBDE-99 (12 mg/kg body weight) or vehicle was administered to male NMRI mice on neonatal day 10, and the striatum and the hippocampus were isolated. Using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), we found 40 and 56 protein spots with significantly (p < 0.01) altered levels in the striatum and the hippocampus, respectively. We used matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF-MS) to determine the protein identity of 11 spots from the striatum and 10 from the hippocampus. We found that the levels of proteins involved in neurodegeneration and neuroplasticity (e.g., Gap-43/neuromodulin, stathmin) were typically altered in the striatum, and proteins involved in metabolism and energy production [e.g., alpha-enolase; gamma-enolase; ATP synthase, H+ transporting, mitochondrial F1 complex, beta subunit (Atp5b); and alpha-synuclein] were typically altered in the hippocampus. Interestingly, many of the identified proteins have been linked to protein kinase C signaling. In conclusion, we identify responses to early exposure to PBDE-99 that could contribute to persistent neurotoxic effects. This study also shows the usefulness of proteomics to identify potential biomarkers of developmental neurotoxicity of organohalogen compounds.
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| 6. |
- Austeng, Dordi, et al.
(författare)
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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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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 99:7, s. 978-992
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Brännström, Mats, 1958, et al.
(författare)
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Reproductive, obstetric, and long-term health outcome after uterus transplantation: results of the first clinical trial
- 2022
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 118:3, s. 576-585
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate reproductive, obstetric, and long-term health of the first completed study of uterus transplantation (UTx). Design: Prospective. Setting: University hospital. Patient(s): Nine live donor UTx procedures were conducted and seven were successful. Donors, recipients, and children born were observed. Intervention(s): In vitro fertilization was performed with embryo transfer (ET) of day 2 or day 5 embryos in natural cycles. Pregnancies and growth trajectory of the children born were observed. Health-related quality of life, psychosocial outcome, and medical health of donors and recipients were evaluated by questionnaires. Main Outcome Measure(s): The results of in vitro fertilization, pregnancies, growth of children, and long-term health of patients were reported. Result(s): Six women delivered nine infants, with three women giving birth twice (cumulative birth rates of 86% and 67% in surgically successful and performed transplants, respectively). The overall clinical pregnancy rate (CPR) and live birth rate (LBR) per ET were 32.6% and 19.6%, respectively. For day 2 embryos, the CPR and LBR per ET were 12.5% and 8.6%, respectively. For day 5 embryos, the CPR and LBR per ET were 81.8% and 45.4%, respectively. Fetal growth and blood flow were normal in all pregnancies. Time of delivery (median in full pregnancy weeks + days [ranges]) by cesarean section and weight deviations was 35 + 3 (31 + 6 to 38 + 0) and -1% (-13% to 23%), respectively. Three women developed preeclampsia and four neonates acquired respiratory distress syndrome. All children were healthy and followed a normal growth trajectory. Measures of long-term health in both donors and recipients were noted to be favorable. When UTx resulted in a birth, scores for anxiety, depression, and relationship satisfaction were reassuring for both the donors and recipients. Conclusion(s): The results of this first complete UTx trial show that this is an effective infertility treatment, resulting in births of healthy children and associated with only minor psychological and medical long-term effects for donors and recipients. Clinical Trial Registration Number: NCT02987023.
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| 8. |
- Fellman, Vineta, et al.
(författare)
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One-year survival of extremely preterm infants after active perinatal care in Sweden.
- 2009
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Ingår i: JAMA : the journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 301:21, s. 2225-33
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Tidskriftsartikel (refereegranskat)abstract
- Up-to-date information on infant survival after extremely preterm birth is needed for assessing perinatal care services, clinical guidelines, and parental counseling.
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| 9. |
- Hellström, William, et al.
(författare)
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C-Peptide Suppression during Insulin Infusion in the Extremely Preterm Infant Is Associated with Insulin Sensitivity
- 2019
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 104:9, s. 3902-3910
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Tidskriftsartikel (refereegranskat)abstract
- Context: Little is known about the individual response of glucose-regulating factors to administration of exogenous insulin infusion in extremely preterm infants. Objective: To evaluate longitudinal serum concentrations of insulin, C-peptide, and plasma glucose levels in a high-frequency sampling regimen in extremely preterm infants treated with insulin because of hyperglycemia. Design: Prospective longitudinal cohort study. Setting: Two university hospitals in Sweden between December 2015 and September 2016. Patients and Intervention: Serum samples were obtained from nine extremely preterm infants, gestational age between 22 (+3) and 26 (+5) weeks (+ days), with hyperglycemia (plasma-glucose >10 mmol/L) at the start of insulin infusion, at 12, 24, and every 24 hours thereafter during ongoing infusion, and 12, 24, and 72 hours after the end of insulin infusion. Main outcome measures: Longitudinal serum concentrations of insulin and C-peptide and plasma glucose levels. Results: During insulin infusion, the serum C-peptide concentrations decreased compared with at start of infusion (P = 0.036), and then increased after ending the infusion. Individual insulin sensitivity based on the nonfasting plasma glucose/insulin ratio at the start of insulin infusion correlated with the initial decrease in serum ΔC-peptide[after 12h] (P = 0.007) and the degree of lasting decrease in serum ΔC-peptide[after end of infusion] (P = 0.015). Conclusion: Exogenous insulin infusion suppressed the C-peptide concentration to individually different degrees. In addition, the effect of insulin infusion on β cells may be linked to individual insulin sensitivity, where a low insulin sensitivity resulted in a more pronounced decrease in C-peptide during insulin infusion.
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| 10. |
- Jergil, Måns, et al.
(författare)
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Exploring Transcriptional Response toValproic Acid and Valproic Acid Analogs in Human Embryonic Stem Cells
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Annan publikation (populärvet., debatt m.m.)abstract
- Developmental toxicity is a major concern for manufacturers of new pharmaceuticals,and current testing requires many laboratory animals. Human embryonic stem (hES)cells, potentially being close in function to cells in the developing embryo, mayprovide a technology for classification of candidate drugs in the early phase of toxicityevaluation. Altered gene expression in such system may be predictive of teratogenicproperties of a substance if important gene regulatory pathways are affected, and mayhence be used as appropriate endpoint. In the present study we used the pluripotenthES cell line SA002 (Cellartis AB), and microarrays to profile the response tovalproic acid (VPA), a known human teratogen causing increased risk of e.g. spinabifida and cognitive disorders in exposed embryos We also investigated three closelyrelated VPA analogs with differing in vivo teratogenicity in mice as well as histonedeacetylase (HDAC) inhibition, a proposed teratogenic mechanism of VPA. hEScells in an undifferentiated state were exposed for 24 h to either 1 mM VPA, 0.25mM or 0.5 mM (S)-2-pentyl-4-pentynoic acid a more potent teratogen and HDACinhibitor than VPA, 1 mM 3-propyl-heptanoic acid, a potent teratogen but not anHDAC inhibitor, 1 mM 2-ethyl-4-methyl-pentanoic acid, a non-teratogen and non-HDAC inhibitor, or 0.1% DMSO. Gene expression was subsequently profiled usingCodelink Human Whole Genome BioArrays. We found the HDAC inhibitors tostrongly deregulate largely the same genes. Further, a concordance of altered geneontology groups, predominantly neurogenic processes, was evident between all theteratogenic substances. Also, comparison with mouse ES cells showed an overlap ofderegulated genes as well as species specific gene to be deregulated.
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