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1.
  • Albet-Torres, Nuria, et al. (författare)
  • Molecular motors on lipid bilayers and silicon dioxide: different driving forces for adsorption
  • 2010
  • Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-6848 .- 1744-683X. ; 6:14, s. 3211-3219
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding how different types of interactions govern adsorption of the myosin motor fragment heavy meromyosin (HMM) onto different substrates is important in functional studies of actomyosin and for the development of motor powered lab-on-a-chip applications. In this study, we have combined in vitro motility assays and quartz crystal microbalance with dissipation (QCM-D) monitoring to investigate the underlying adsorption mechanisms of HMM onto supported lipid bilayers in comparison with pure and silanized SiO2. The QCM-D results, combined with data showing actin transportation by HMM adsorbed onto positively charged supported lipid bilayers, suggest reversible HMM surface adsorption via the negatively charged coiled-coil tail region. In contrast, the QCM-D data for HMM adsorption onto negatively charged lipids support a model according to which HMM adsorbs onto negatively charged surfaces largely via the positively charged actin binding regions. Adsorption studies at low (30-65 mM) and high (185-245 mM) ionic strengths onto piranha cleaned SiO2 surfaces (contact angle
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2.
  • Cnattingius, Sven, et al. (författare)
  • Maternal Obesity and Risk of Preterm Delivery
  • 2013
  • Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 309:22, s. 2362-2370
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance Preterm birth is a leading cause of infant mortality, morbidity, and long-term disability, and these risks increase with decreasing gestational age. Obesity increases the risk of preterm delivery, but the associations between overweight and obesity and subtypes of preterm delivery are not clear. Objective To study the associations between early pregnancy body mass index (BMI) and risk of preterm delivery by gestational age and by precursors of preterm delivery. Design, Setting, and Participants Population-based cohort study of women with live singleton births in Sweden from 1992 through 2010. Maternal and pregnancy characteristics were obtained from the nationwide Swedish Medical Birth Register. Main Outcomes and Measures Risks of preterm deliveries (extremely, 22-27 weeks; very, 28-31 weeks; and moderately, 32-36 weeks). These outcomes were further characterized as spontaneous (related to preterm contractions or preterm premature rupture of membranes) and medically indicated preterm delivery (cesarean delivery before onset of labor or induced onset of labor). Risk estimates were adjusted for maternal age, parity, smoking, education, height, mother's country of birth, and year of delivery. Results Among 1 599 551 deliveries with information on early pregnancy BMI, 3082 were extremely preterm, 6893 were very preterm, and 67 059 were moderately preterm. Risks of extremely, very, and moderately preterm deliveries increased with BMI and the overweight and obesity-related risks were highest for extremely preterm delivery. Among normal-weight women (BMI 18.5-<25), the rate of extremely preterm delivery was 0.17%. As compared with normal-weight women, rates (%) and adjusted odds ratios (ORs [95% CIs]) of extremely preterm delivery were as follows: BMI 25 to less than 30 (0.21%; OR, 1.26; 95% CI, 1.15-1.37), BMI 30 to less than 35 (0.27%; OR, 1.58; 95% CI, 1.39-1.79), BMI 35 to less than 40 (0.35%; OR, 2.01; 95% CI, 1.66-2.45), and BMI of 40 or greater (0.52%; OR, 2.99; 95% CI, 2.28-3.92). Risk of spontaneous extremely preterm delivery increased with BMI among obese women (BMI >= 30). Risks of medically indicated preterm deliveries increased with BMI among overweight and obese women. Conclusions and Relevance In Sweden, maternal overweight and obesity during pregnancy were associated with increased risks of preterm delivery, especially extremely preterm delivery. These associations should be assessed in other populations.
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4.
  • Hedenius, Martina, et al. (författare)
  • Enhanced Recognition Memory after Incidental Encoding in Children with Developmental Dyslexia
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:5, s. e63998-
  • Tidskriftsartikel (refereegranskat)abstract
    • Developmental dyslexia (DD) has previously been associated with a number of cognitive deficits. Little attention has been directed to cognitive functions that remain intact in the disorder, though the investigation and identification of such strengths might be useful for developing new, and improving current, therapeutical interventions. In this study, an old/new recognition memory paradigm was used to examine previously untested aspects of declarative memory in children with DD and typically developing control children. The DD group was not only not impaired at the task, but actually showed superior recognition memory, as compared to the control children. These findings complement previous reports of enhanced cognition in other domains (e. g., visuo-spatial processing) in DD. Possible underlying mechanisms for the observed DD advantage in declarative memory, and the possibility of compensation by this system for reading deficits in dyslexia, are discussed.
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5.
  • Hedenius, Martina, et al. (författare)
  • Grammar predicts procedural learning and consolidation deficits in children with Specific Language Impairment
  • 2011
  • Ingår i: Research in Developmental Disabilities. - : Elsevier. - 0891-4222 .- 1873-3379. ; 32:6, s. 2362-2375
  • Tidskriftsartikel (refereegranskat)abstract
    • The Procedural Deficit Hypothesis (PDH) posits that Specific Language Impairment (SLI) can be largely explained by abnormalities of brain structures that subserve procedural memory. The PDH predicts impairments of procedural memory itself, and that such impairments underlie the grammatical deficits observed in the disorder. Previous studies have indeed reported procedural learning impairments in SLI, and have found that these are associated with grammatical difficulties. The present study extends this research by examining consolidation and longer-term procedural sequence learning in children with SLI. The Alternating Serial Reaction Time (ASRT) task was given to children with SLI and typically developing (TD) children in an initial learning session and an average of three days later to test for consolidation and longer-term learning. Although both groups showed evidence of initial sequence learning, only the TD children showed clear signs of consolidation, even though the two groups did not differ in longer-term learning. When the children were re-categorized on the basis of grammar deficits rather than broader language deficits, a clearer pattern emerged. Whereas both the grammar impaired and normal grammar groups showed evidence of initial sequence learning, only those with normal grammar showed consolidation and longer-term learning. Indeed, the grammar-impaired group appeared to lose any sequence knowledge gained during the initial testing session. These findings held even when controlling for vocabulary or a broad non-grammatical language measure, neither of which were associated with procedural memory. When grammar was examined as a continuous variable over all children, the same relationships between procedural memory and grammar, but not vocabulary or the broader language measure, were observed. Overall, the findings support and further specify the PDH. They suggest that consolidation and longer-term procedural learning are impaired in SLI, but that these impairments are specifically tied to the grammatical deficits in the disorder. The possibility that consolidation and longer-term learning are problematic in the disorder suggests a locus of potential study for therapeutic approaches. In sum, this study clarifies our understanding of the underlying deficits in SLI, and suggests avenues for further research.
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6.
  • Hedenius, Martina, 1970-, et al. (författare)
  • Impaired implicit sequence learning in children with developmental dyslexia
  • 2013
  • Ingår i: Research in Developmental Disabilities. - : Elsevier. - 0891-4222 .- 1873-3379. ; 34:11, s. 3924-3935
  • Tidskriftsartikel (refereegranskat)abstract
    • It has been proposed that an impairment of procedural memory underlies a range of linguistic, cognitive and motor impairments observed in developmental dyslexia (DD). However, studies designed to test this hypothesis using the implicit sequence learning paradigm have yielded inconsistent results. A fundamental aspect of procedural learning is that it takes place over an extended time-period that may be divided into distinct stages based on both behavioural characteristics and neural correlates of performance. Yet, no study of implicit sequence learning in children with DD has included learning stages beyond a single practice session. The present study was designed to fill this important gap by extending the investigation to include the effects of overnight consolidation as well as those of further practice on a subsequent day. The results suggest that the most pronounced procedural learning impairment in DD may emerge only after extended practice, in learning stages beyond a single practice session.
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7.
  • Hedenius, Martina (författare)
  • Procedural and Declarative Memory in Children with Developmental Disorders of Language and Literacy
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The procedural deficit hypothesis (PDH) posits that a range of language, cognitive and motor impairments associated with specific language impairment (SLI) and developmental dyslexia (DD) may be explained by an underlying domain-general dysfunction of the procedural memory system. In contrast, declarative memory is hypothesized to remain intact and to play a compensatory role in the two disorders. The studies in the present thesis were designed to test this hypothesis.Study I examined non-language procedural memory, specifically implicit sequence learning, in children with SLI. It was shown that children with poor performance on tests of grammar were impaired at consolidation of procedural memory compared to children with normal grammar. These findings support the PDH and are line with previous studies suggesting a link between grammar processing and procedural memory.In Study II, the same implicit sequence learning paradigm was used to test procedural memory in children with DD. The DD group showed a learning profile that was similar to that of children with SLI in Study I, with a significant impairment emerging late in learning, after extended practice and including an overnight interval. Further analyses suggested that the DD impairment may not be related to overnight consolidation but to the effects of further practice beyond the initial practice session. In contrast to the predictions of the PDH, the sequence learning deficit was unrelated to phonological processing skills as assessed with a nonword repetition task.Study III examined declarative memory in DD. The performance of the DD group was found to be not only intact, but even enhanced, compared to that of the control children. The results encourage further studies on the potential of declarative memory to compensate for the reading problems in DD.In sum, the results lend partial support for the PDH and suggest further refinements to the theory. Collectively, the studies emphasize the importance of going beyond a narrow focus on language learning and memory functions in the characterization of the two disorders. Such a broader cognitive, motor and language approach may inform the development of future clinical and pedagogical assessment and intervention practices for SLI and DD.
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8.
  • Johansson, Unn-Britt, et al. (författare)
  • Insulinpumpar vid diabetes
  • 2013
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • God kontroll av blodglukosnivån är viktig för att undvika följdsjukdomar av diabetes. Vid typ 1-diabetes och en del fall av typ 2-diabetes krävs så kallad intensiv insulinbehandling med flera injektioner per dag. Den vanligaste komplikationen vid denna behandling är lågt blodglukos (hypoglykemi) vilket kan få allvarliga följder [1,2]. Ett alternativ till intensiv insulinbehandling med injektioner är kontinuerlig insulintillförsel med pump, så kallad kontinuerlig subkutan insulininfusion (CSII).
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9.
  • Johansson, Unn-Britt, et al. (författare)
  • Kontinuerlig subkutan glukosmätning vid diabetes
  • 2013
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • God kontroll av blodglukosnivån är viktig för att undvika följdsjukdomar av diabetes. Blodglukos kan mätas av patienten själv med teststickor (self monitoring of blood glucose, SMBG) eller via en subkutan sensor (kontinuerlig subkutan glukosmätning, CGM). Vid typ 1-diabetes behövs rutinmässigt upprepade blodglukosmätningar varje dygn för att uppnå god glukoskontroll.SBU har utvärderat nytta och risk av behandling med kontinuerlig glukosmätning utan eller med insulinpump (SAP) vid diabetes hos barn, ungdomar och vuxna. I utvärderingen ingår också en hälsoekonomisk och etisk analys, samt en stor praxisundersökning som omfattade samtliga diabeteskliniker i Sverige
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10.
  • Kopparapu, Pradeep Kumar, et al. (författare)
  • Expression and localization of serotonin receptors in human breast cancer
  • 2013
  • Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 33:2, s. 363-370
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to examine the expression of serotonin receptors in patients with breast cancer and to explore their utility as diagnostic and prognostic markers. Immunohistochemical analysis was performed to examine the expression of serotonin (5-HT) receptor subtypes 1A, 1B, 2B and 4 in a tissue microarray containing tumor specimens from 102 patients. Statistical analysis was performed to correlate the expression of these proteins with regard to clinical parameters. We found that all four serotonin receptors (5-HTRs) exhibited different expression patterns in breast cancer specimens. In general strong staining for 5-HTR1A was observed on the membrane of cancer cells but it was detected only in the cytoplasm of non-malignant cells. 5-HTR1B and 5-HTR2B were predominantly expressed in the cytoplasm of breast cancer cells, while 5-HTR4 was exclusively found in the nucleus of malignant and non-malignant cells. Correlation analysis revealed a significant correlation of 5-HTR2B with estrogen receptor-α (ER-α) and 5-HTR4 with ER-α and progesterone (PR). In conclusion, the different expression patterns and subcellular localization of 5-HTRs in breast cancer may reflect their role in breast cancer progression.
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11.
  • Lundström, Jan O., et al. (författare)
  • High species richness of Chironomidae (Diptera) in temporary flooded wetlands associated with high species turn-over rates
  • 2010
  • Ingår i: Bulletin of entomological research. - 0007-4853 .- 1475-2670. ; 100:4, s. 433-444
  • Tidskriftsartikel (refereegranskat)abstract
    • Species richness and species turn-over of Chironomidae was studied in irregularly flooded wetlands of the River Dalalven flood-plains in central Sweden. The chironomid fauna, sampled with emergence traps in six wetlands over six summers, contained as much as 135 species, and the cumulative species curves indicated that the regional species pool contain several more species. Recurrent irregular floods may have induced this high chironomid species richness and the high species turn-over in the temporary wetlands, as the dominance between terrestrial and aquatic species shifted between years. Half of the wetlands were treated with Bacillus thuringiensis var. israelensis (Bti) against larvae of the floodwater mosquito Aedes sticticus. These treatments had no significant effect on chironomid species richness, but there was a higher species turn-over between years of primarily low abundance species in the treated wetlands. The cumulative number of species was also higher in the Bti-treated experimental wetlands than in the untreated reference wetlands. Thus, Bti treatment against mosquito larvae seemed to have only small effects on chironomid species richness but seemed to increase the colonisation-extinction dynamics.
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12.
  • Lundström, Jan O., et al. (författare)
  • Production of wetland Chironomidae (Diptera) and the effects of using Bacillus thuringiensis israelensis for mosquito control
  • 2010
  • Ingår i: Bulletin of entomological research. - Cambridge : Cambridge University Press. - 0007-4853 .- 1475-2670. ; 100:1, s. 117-125
  • Tidskriftsartikel (refereegranskat)abstract
    • Massive mosquito nuisance problems, caused by the flood-water mosquito Aedes sticticus, occur after floods in the flood plains of the River Dalalven, central Sweden. Since 2002, the biological mosquito larvicide Bacillus thuringiensis var. israelensis (Bti) has been used to control these mosquitoes. Here, we report results from the first six years of monitoring Chironomidae, the most Susceptible non-target organisms, in three wetlands with Bti-treatment against mosquitoes and in three wetlands without treatment. Emergence traps were used for continuous insect sampling from May to September each year, 2002-2007, and were emptied once a week. A total of 21,394 chironomids of 135 species were collected, and the Subfamily Orthocladiinae dominated the fauna followed by Chironominae and Tanypodinae. The annual chironomid production in the wetlands was low, with ail average of 1.91.7 individuals per m(2) and 42 g ash-free dry weight per m(2) We found no reduced production of chironomids at neither family, nor subfamily level, in Bti-treated as compared to untreated wetlands. This is the first long-term follow-up study of the possible effects of Bti-based mosquito larval control oil chironomid species production. In the short-term view, one species had higher production in treated areas. In the long-term view, four species had higher and one species had lower production in treated areas. We conclude that the B3ti-based control of floodwater mosquitoes does not cause and, major direct negative effects on chironomid production, and therefore does not seem to induce any risk for indirect negative effects on birds, bats or any other predators feeding on chironomids.
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14.
  • Lundström, Jan O, et al. (författare)
  • The geographic distribution of mosquito species in Sweden
  • 2013
  • Ingår i: Journal of the European Mosquito Control Association. - 2054-930X .- 1460-6127. ; 31, s. 21-35
  • Tidskriftsartikel (refereegranskat)abstract
    • Surveillance of the actual distribution of mosquito species in Northern Europe is fundamental for evaluating risk for emerging pathogens, and for research on potential vectors. The Swedish mosquito fauna composition and geographic distribution, originally described by Professor Christine Dahl in the 1970´s, included 43 species. We have compiled the information published from 1978 to 2012, and our own surveillance data from 2001 to 2013, and compared this with the species list and geographic distribution provided in "Taxonomy and geographic distribution of Swedish Culicidae" by Dahl (1977). New species detected during these 36 years were Culiseta (Culicella) ochroptera (Peus, 1935) published 1984, Aedes (Aedes) rossicus Dolbeskin, Goritzkaja & Mitrofanova, 1930 published 1986, Anopheles (Anopheles) beklemishevi published 1986, Aedes (Ochlerotatus) euedes (Howard, Dyar & Knab, 1912) published 2001, Aedes (Ochlerotatus) nigrinus (Eckstein, 1918) first recorded in 2012, and Anopheles (Anopheles) algeriensis Theobald, 1903, first recorded in 2013. We provide maps with the distribution by province for each species, including historic information up until 1977, and new records from 1978 to 2013, showing the similarities and differences between the old and the new records. Important findings in recent years include the wide distribution of the Sindbis virus enzootic vector Culex (Culex) torrentium Martinii, 1925, and the more limited distribution of the potential West Nile virus vector Culex (Culex) pipiens Linnaeus, 1758. The updated list of mosquito species in Sweden now includes 49 species.
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16.
  • Persson, Martina, et al. (författare)
  • Birth Size Distribution in 3,705 Infants Born to Mothers With Type 1 Diabetes A population-based study
  • 2011
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 34:5, s. 1145-1149
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE-To characterize birth size distribution in infants born to mothers with type 1 diabetes. In particular, the relationship between birth weight (BW) and length (BL) was studied because it may provide information on different causal pathways of fetal macrosomia commonly seen in diabetic pregnancies. RESEARCH DESIGN AND METHODS-This was a population-based cohort study of 3,705 infants of type 1 diabetic mothers (1,876 boys), with a gestational age of 28-43 weeks, born in Sweden between 1998 and 2007. BW and BL were retrieved from the Medical Birth Registry and expressed as SD scores (SDS). Ponderal index (PI) was calculated as BW in g/length in cm(3). A BW > 90th and a PI 90th percentile, the infant was categorized as disproportionately large. Values are mean (SD). RESULTS-The BW distribution for offspring of type 1 diabetic mothers was bell-shaped, significantly broader, and markedly shifted to the right (BWSDS: 1.27 [1.48]) of the reference. Of the infants born to diabetic mothers, 47% were LGA, and among them, 46% were disproportionately large compared with 35% in nondiabetic LGA infants (P < 0.001). Female offspring of type 1 diabetic mothers had significantly higher BWSDS than males (1.34 vs. 1.20, P < 0.01), and preterm infants had higher BWSDS than term infants (1.41 vs. 1.23, P < 0.01) CONCLUSIONS-Fetal macrosomia in type 1 diabetic pregnancies is due to a right-shift and broadening of the entire BW distribution. The large number of disproportionate LGA infants born to type 1 diabetic mothers suggests an underlying metabolic problem. Fetal macrosomia was more pronounced in preterm and female offspring of type 1 diabetic mothers.
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17.
  • Persson, Martina, et al. (författare)
  • Disproportionate Body Composition and Neonatal Outcome in Offspring of Mothers With and Without Gestational Diabetes Mellitus
  • 2013
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 36:11, s. 3543-3548
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: High birth weight is a risk factor for neonatal complications. It is not known if the risk differs with body proportionality. The primary aim of this study was to determine the risk of adverse pregnancy outcome in relation to body proportionality in large-for-gestational-age (LGA) infants stratified by maternal gestational diabetes mellitus (GDM).RESEARCH DESIGN AND METHODS: Population-based study of all LGA (birth weight [BW] >90th percentile) infants born to women with GDM (n = 1,547) in 1998-2007. The reference group comprised LGA infants (n = 83,493) born to mothers without diabetes. Data were obtained from the Swedish Birth Registry. Infants were categorized as proportionate (P-LGA) if ponderal index (PI) (BW in grams/length in cm(3)) was 90th percentile and as disproportionate (D-LGA) if PI >90th percentile. The primary outcome was a composite morbidity: Apgar score 0-3 at 5 min, birth trauma, respiratory disorders, hypoglycemia, or hyperbilirubinemia. Logistic regression analysis was used to obtain odds ratios (ORs) for adverse outcomes.RESULTS: The risk of composite neonatal morbidity was increased in GDM pregnancies versus control subjects but comparable between P- and D-LGA in both groups. D-LGA infants born to mothers without diabetes had significantly increased risk of birth trauma (OR 1.19 [95% CI 1.09-1.30]) and hypoglycemia (1.23 [1.11-1.37]). D-LGA infants in both groups had significantly increased odds of Cesarean section.CONCLUSIONS: The risk of composite neonatal morbidity is significantly increased in GDM offspring. In pregnancies both with and without GDM, the risk of composite neonatal morbidity is comparable between P- and D-LGA.
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18.
  • Persson, Malin, 1983-, et al. (författare)
  • Heavy Meromyosin Molecules Extending More Than 50 nm above Adsorbing Electronegative Surfaces
  • 2010
  • Ingår i: Langmuir. - : American Chemical Society (ACS). - 1520-5827 .- 0743-7463. ; 26:12, s. 9927-9936
  • Tidskriftsartikel (refereegranskat)abstract
    • In the in vitro motility assay, actin filaments are propelled by surface-adsorbed myosin motors, or rather, myosin motor fragments such as heavy meromyosin (HMM). Recently, efforts have been made to develop actomyosin powered nanodevices on the basis of this assay but such developments are hampered by limited understanding of the HMM adsorption geometry. Therefore, we here investigate the HMM adsorption geometries on trimethylchlorosilane-[TMCS-] derivatized hydrophobic surfaces and on hydrophilic negatively charged surfaces (SiO2). The TMCS surface is of great relevance in fundamental studies of actomyosin and both surface substrates are important for the development of motor powered nanodevices. Whereas both the TMCS and SiO2 surfaces were nearly saturated with HMM (incubation at 120 mu g mL(-1)) there was little actin binding on SiO2 in the absence of ATP and no filament sliding in the presence of ATP. This contrasts with excellent actin-binding and motility on TMCS. Quartz crystal microbalance with dissipation (QCM-D) studies demonstrate a HMM layer with substantial protein mass up to 40 nm above the TMCS surface, considerably more than observed for myosin subfragment 1 (SI; 6 nm). Together with the excellent actin transportation on TMCS, this strongly suggests that HMM adsorbs to TMCS mainly via its most C-terminal tail part. Consistent with this idea, fluorescence interference contrast (FLIC) microscopy showed that actin filaments are held by HMM 38 +/- 2 nm above the TMCS-surface with the catalytic site, on averge, 20-30 nm above the surface. Viewed in a context with FLIC, QCM-D and TIRF results, the lack of actin motility and the limited actin binding on SiO2 shows that HMM adsorbs largely via the actin-binding region on this surface with the C-terminal coiled-coil tails extending > 50 nm into solution. The results and new insights from this study are of value, not only for the development of motor powered nanodevices but also for the interpretation of fundamental biophysical studies of actomyosin function and for the understanding of surface protein interactions in general.
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19.
  • Persson, Martina, et al. (författare)
  • Pre-pregnancy body mass index and the risk of adverse outcome in type 1 diabetic pregnancies : a population-based cohort study
  • 2012
  • Ingår i: BMJ Open. - London, United Kingdom : BMJ Publishing Group Ltd. - 2044-6055. ; 2:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To assess the risk of perinatal complications in overweight and obese women with and without type 1 diabetes (T1DM).Design: Prospective population-based cohort study.Setting: This study was based on data from the Swedish Medical Birth Registry from 1998 to 2007.Participants: 3457 T1DM and 764 498 non-diabetic pregnancies were included. T1DM was identified based on ICD code O24.0. Mothers were categorised according to pre-pregnancy body mass index (BMI: weight in kilograms per height in square metres) as normal weight (BMI 18.5-24.9), overweight (BMI 25-29.9) or obese (BMI ≥30). Only women with singleton pregnancies and with data on BMI were included. PRIMARY/SECONDARY OUTCOMES: The primary outcome was large for gestational age (LGA: birth weight >90th percentile) infants. Secondary outcomes were major malformations, pre-eclampsia (PE), preterm delivery, perinatal mortality, delivery by Caesarean section and neonatal overweight. Logistic regression analysis was performed with normal weight non-diabetic women as the reference category and also within the diabetic cohort with normal weight type 1 diabetic women as the reference. The ORs were adjusted for ethnicity, maternal age, height, parity, smoking and chronic hypertension.Results: 35% of women with T1DM were overweight and 18% were obese, as compared with 26% and 11%, respectively, in non-diabetic pregnancies. The incidences of adverse outcome increased with greater BMI category. As compared with non-diabetic normal weight women, the adjusted OR for obese T1DM for LGA was 13.26 (95% CI 11.27 to 15.59), major malformations 4.11 (95% CI 2.99 to 5.65) and PE 14.19 (95% CI 11.50 to 17.50). T1DM was a significant effect modifier of the association between BMI and LGA, major malformations and PE (p<0.001).Conclusion: High pre-pregnancy BMI is an important risk factor for adverse outcome in type 1 diabetic pregnancies. The combined effect of both T1DM and overweight or obesity constitutes the greatest risk. It seems prudent to strive towards normal pre-pregnancy BMI in women with T1DM.
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20.
  • Persson, Marie, et al. (författare)
  • Reduced IFN-γ and IL-10 responses to paternal antigens during and after pregnancy in allergic women
  • 2012
  • Ingår i: Journal of Reproductive Immunology. - : Elsevier. - 0165-0378 .- 1872-7603. ; 95:1-2, s. 50-58
  • Tidskriftsartikel (refereegranskat)abstract
    • Normal pregnancy and allergy are both characterized by a T helper (Th) 2 deviation. In the current study, we hypothesized that paternal antigen-induced cytokine responses during pregnancy would be deviated toward Th2 and an anti-inflammatory profile, and that the Th2 deviation would be more pronounced in allergic pregnant women. Blood samples were collected longitudinally on three occasions during pregnancy and two occasions post partum (pp). Of the 86 women initially included, 54 women had a normal pregnancy and completed the sampling procedures. Twelve women fulfilled the criteria for allergy (allergic symptoms and circulating immunoglobulin [Ig] E antibodies to inhalant allergens) and 20 were non-allergic (nonsensitized without symptoms). The levels of Th1- and Th2-associated cytokines and chemokines, the Th17 cytokine IL-17 and the anti-inflammatory cytokine IL-10 of the groups were compared. Paternal antigen-induced IL-4 and IL-10 responses increased between the first and the third trimester. Allergy was associated with decreased paternal antigen-induced IFN-γ and CXCL10 secretion in the nonpregnant state (one year pp) and also decreased IFN-γ/IL-4 and IFN-γ/IL-13 ratios during pregnancy. We also observed a decreased paternal antigen-induced IL-10 response in allergic compared with non-allergic women during pregnancy, along with a decreased IL-10/IL-13 ratio. In conclusion, our findings support the hypothesis of lower Th1 responses toward paternal antigens in allergic than in non-allergic women, but also indicate that allergy is associated with a lower capacity to induce anti-inflammatory IL-10 responses after paternal antigen stimulation during pregnancy.
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21.
  • Persson, Martina (författare)
  • Type 1 diabetes in pregnancy : perinatal outcome with special reference to fetal macrosomia
  • 2012
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The aim of this epidemiological study was to elucidate whether in recent years, obstetric and perinatal outcomes in pregnancies complicated by type 1 diabetes (T1DM) have improved or not. The objective was also to identify possible risk factors for adverse outcome for the mother, fetus and the newborn. All studies (Ι-ΙV) included in this thesis were based on national data from the Swedish Medical Birth Registry, during the time period 1991-2007. In 5,089 type 1 diabetic pregnancies and 1.2 million controls we found significantly increased risks of all adverse outcomes in women with T1DM: adjusted odds ratios: severe preeclampsia: 4.47 (3.77-5.31), Caesarean delivery: 5.31 (4.97-5.69), stillbirth: 3.34 (2.46- 4.55), perinatal mortality: 3.29 (2.50-4.33), major malformations: 2.50 (2.13-2.94) and large for gestational age: LGA (birth weight ≥ +2 SD): 11.45 (10.61-12.36) (study Ι). The markedly elevated odds of an LGA outcome inspired us to characterize in more detail the distribution of birth size in a large national cohort of T1DM offspring (study ΙΙ n=3,705) and to investigate if disproportionate body composition was associated with increased risk of perinatal complications (study ΙΙΙ n=3,517). Percentiles for birth weight (BW), birth length (BL) and head circumference (HC) were formed based on data from non-diabetic pregnancies and standard deviation scores (SDS) were calculated for BW, BL and HC. The ponderal index (PI: BW in grams/(BL in cm) 3 was used as a proxy for body proportionality and fat mass and we defined disproportionate/overweight LGA as infants with a BW and PI ≥90th percentile for gestational age and gender. The distributions of BW, BL and HC were all unimodal but significantly shifted to the right of the normal reference. The distribution for BW was most markedly shifted to the right. 47% were LGA with a BW ≥90th adjusted percentile. The mean ponderal index (PI) was significantly increased and 46% of LGA infants were disproportionate with a PI ≥90th percentile and thus overweight at birth. A novel and unexpected finding was that fetal macrosomia was more pronounced in preterm and female infants (study ΙΙ). Surprisingly, neonatal outcome was independent of body proportionality in appropriate for gestational age (AGA) and LGA infants. The risk of adverse outcome was significantly increased in LGA compared with AGA infants born at term (study ΙΙΙ). There was a significant interaction between gestational age and body weight with prematurity overriding LGA as a risk factor for neonatal morbidity in moderately preterm infants. In study ΙV, we examined the risk of adverse outcome in relation to pre-pregnancy body mass index in a national cohort of 3,457 T1DM pregnancies compared to 764,498 non-diabetic pregnancies. Maternal overweight/obesity increases the risk of adverse outcome in both women with and without T1DM. Within the T1DM cohort, obesity was associated with increased odds of major malformations adjusted OR: 1.77 (1.18-2.65) and preeclampsia adjusted OR: 1.74 (1.35-2.25). T1DM was a significant effect modifier of the association between BMI and major malformations, preeclampsia, LGA and neonatal overweight. Conclusion: In spite of major improvements in the management of type 1 diabetic pregnancies over the years, the present findings clearly demonstrate that T1DM pregnancies still are associated with significantly increased risk of adverse outcomes. An important observation is the rising incidence of LGA infants, which partly can be attributed to a concomitant increase in maternal BMI. This development is worrying as LGA infants face an excess risk of both perinatal and future complications as compared to normal sized infants. The novel and unexpected finding of a gender difference in fetal macrosomia requires further investigations.
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