| 1. |
- Cobo, Teresa, et al.
(författare)
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A prediction model of histological chorioamnionitis and funisitis in preterm prelabor rupture of membranes: analyses of multiple proteins in the amniotic fluid.
- 2012
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Ingår i: The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. - : Informa UK Limited. - 1476-4954.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine the best prediction model of histological chorioamnionitis and funisitis in preterm prelabor rupture of membranes (PPROM) using selected candidate proteins in the amniotic fluid (AF). Material and methods: Prospective cohort study. Twenty-six AF proteins were assayed by a multiple immunoassay from 107 women with membranes rupture from 23+0 to 36+6 weeks. The Czech Republic policy is active management, and the majority of women were delivered within 72 h after the rupture of membranes, except for women with PPROM <28+0 weeks who were managed conservatively. The best predictive models to diagnose histological chorioamnionitis and funisitis were calculated by logistic regression depending on the gestational age (GA) at membrane rupture. Results: Both IL-6 and a combination of IL-10, and migration inhibiting factor (MIF) were the best predictive models of histological chorioamnionitis and funisitis, respectively, with sensitivity, specificity, positive and negative predictive values and positive likelihood ratio (LR+) of 62, 83, 37, 93 and 3.6 and of 63, 91, 53, 94 and 7.0, respectively. Depending on whether GA at membrane rupture was <32 or ≥ 32 weeks, IL-10, alone or in combination with MIF and triggering receptor expressed on myeloid cells-1, was the strongest inflammatory biomarker for funisitis (LR+10.6 and 36.6, respectively). Conclusion: Regardless of the GA at membrane rupture, IL-6 from the AF was the best predictor of histological chorioamnionitis. Amniotic fluid IL-10 was notably accurate in the prediction of funisitis.
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| 2. |
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| 3. |
- Cobo, Teresa, et al.
(författare)
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Intra-amniotic inflammation predicts microbial invasion of the amniotic cavity but not spontaneous preterm delivery in preterm prelabor membrane rupture.
- 2012
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Ingår i: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349.
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To predict microbial invasion of the amniotic cavity (MIAC) and spontaneous preterm delivery within seven days using a panel of selected proteins from amniotic fluid in a Swedish population of preterm prelabor membrane rupture (PPROM). Design. Prospective cohort study. Setting. Evaluation of intra-amniotic inflammation in preterm premature rupture of membranes. Population. Sixty-six pregnant women with preterm prelabor membrane rupture at 22(+0-) 33(+6) weeks' gestational age. Methods. Twenty-seven amniotic fluid proteins were assayed by a multiple immunoassay. Main outcome measures. The intra-amniotic inflammatory response was evaluated according to the presence of MIAC and the risk of spontaneous preterm delivery within seven days. A prediction model was constructed using logistic regression. Results. The overall rates of MIAC and spontaneous preterm delivery within seven days were 20% and 50%, respectively. There was a higher inflammatory response in women with MIAC than without. Earlier gestational age at delivery and lower birthweight were observed in the presence of microbial invasion of the amniotic cavity. Amniotic fluid Interleukin (IL)-6 and IL-10 were the best predictors of MIAC in terms of sensitivity (69%), specificity (81%), positive predictive value (47%), negative predictive value (91%) and positive likelihood ratio of 3.6. There were no differences in intra-amniotic inflammatory response according to the risk of spontaneous preterm delivery within seven days. Conclusion. Amniotic fluid IL-6 and IL-10 are the best inflammatory biomarkers to predict MIAC in women with PPROM. Intra-amniotic inflammation does not predict the occurrence of spontaneous preterm delivery within seven days of PPROM.
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| 4. |
- Deza-Lougovski, Yacila I., et al.
(författare)
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Circulating apoE4 protein levels from dried blood spots predict cognitive function in a large population-based survey setting
- 2024
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Ingår i: Alzheimer's & Dementia. - 1552-5260 .- 1552-5279.
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The apolipoprotein E (APOE) ε4 allele carries risk for cognitive impairment, but whether the level of circulating apoE4 protein in carriers affects cognition is unclear, as is how health and lifestyle impact circulating apoE4 levels.METHODS: We assayed apoE4 protein levels in dried blood spots of 12,532 adults aged 50+. Regression analyses tested the likelihood of cognitive impairment between groups and within those with detected apoE4 protein. Predictors of circulating apoE4 were assessed.RESULTS: We detected protein binding that indicates the presence of an APOE ε4 allele in 28.4% of this group. This group was more likely to have cognitive impairment, and this risk increases with age. However, higher apoE4 levels were associated with less likelihood of cognitive impairment within this group. Antihypertensive medication predicted apoE4 protein levels.DISCUSSION: The apoE4 isoform is associated with a deficient protein and worse cognition. This association is modulated by the level of circulating apoE4 protein in ε4 carriers.
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| 5. |
- Eising, Stefanie, et al.
(författare)
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Type 1 diabetes risk analysis on dried blood spot samples from population-based newborns: design and feasibility of an unselected case-control study
- 2007
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Ingår i: Paediatric and Perinatal Epidemiology. - : Wiley. - 0269-5022 .- 1365-3016. ; 21:6, s. 507-517
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Tidskriftsartikel (refereegranskat)abstract
- Development of type 1 diabetes mellitus (T1D) may be triggered pre- or perinatally by multiple factors. Identifying new predisposing T1D markers or combinations of markers in a large, well-characterised case-control collection may be important for future T1D prevention. The present work describes the design and feasibility of a large and unselected case-control study, which will define and evaluate prediction criteria for T1D at the time of birth. Danish registries (Biological Specimen Bank for Neonatal Screening, and the National Discharge Registry) made it possible to identify and collect dried blood spots (DBS) from newborns who later developed T1D (cases) born 1981-2002. DBS samples from 2086 cases and two matching control subjects per case were analysed for genetic and immune factors that are associated with T1D: (a) candidate genes (HLA, INS and CTLA4), (b) cytokines and inflammatory markers, (c) islet auto-antibodies (GAD65A, IA-2A). The objective of the study was to define reliable prediction tools for T1D using samples available at the time of birth. In a unique approach, the study linked a large unselected and population-based sample resource to well-ascertained clinical databases and advanced technology. It combined genetic, immunological and demographic data to develop prediction algorithms. It also provided a resource for future studies in which new genetic markers can be included as they are identified.
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| 6. |
- Hallingström, Maria, et al.
(författare)
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The association between selected mid-trimester amniotic fluid candidate proteins and spontaneous preterm delivery
- 2020
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Ingår i: Journal of Maternal-Fetal and Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 33:4, s. 583-592
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to explore inflammatory response and identify early potential biomarkers in mid-trimester amniotic fluid associated with subsequent spontaneous preterm delivery (PTD). Methods: A cohort study was performed at Sahlgrenska University Hospital/Östra, Gothenburg, Sweden, between 2008 and 2010. Amniotic fluid was collected from consecutive women undergoing mid-trimester transabdominal genetic amniocentesis at 14–19 gestational weeks. Clinical data and delivery outcome variables were obtained from medical records. The analysis included 19 women with spontaneous PTD and 118 women who delivered at term. A panel of 26 candidate proteins was analyzed using Luminex xMAP technology. Candidate protein concentrations were analyzed with ANCOVA and adjusted for plate effects. Results: The median gestational age at delivery was 35 + 3 weeks in women with spontaneous PTD and 40 + 0 weeks in women who delivered at term. Nominally significantly lower amniotic fluid levels of adiponectin (PTD: median 130,695 pg/mL (IQR 71,852–199,414) vs term: median 185,329 pg/mL (IQR (135,815–290,532)), granulocyte-macrophage colony stimulating factor (PTD: median 137 pg/mL (IQR 74–156) vs term: median 176 pg/mL (IQR 111–262)), and macrophage migration inhibitory factor (PTD: median 3025 pg/mL (IQR 1885–3891) vs term: median 3400 pg/mL (IQR 2181–5231)) were observed in the spontaneous PTD group, compared with the term delivery group, after adjusting for plate effects. No significant differences remained after Bonferroni correction for multiple comparisons. Conclusions: Our results are important in the process of determining the etiology behind spontaneous PTD but due to the non-significance after Bonferroni correction, the results should be interpreted with caution. Further analyses of larger sample size will be required to determine whether these results are cogent and to examine whether microbial invasion of the amniotic cavity or intra-amniotic inflammation occurs in asymptomatic women in the mid-trimester with subsequent spontaneous PTD.
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| 7. |
- Kacerovsky, Marian, et al.
(författare)
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Intraamniotic inflammatory response to bacteria: analysis of multiple amniotic fluid proteins in women with preterm prelabor rupture of membranes.
- 2012
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Ingår i: The Journal of Maternal-Fetal and Neonatal Medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. - : Informa UK Limited. - 1476-4954.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To analyse whether intraamniotic inflammation in response to bacteria is different below and above gestational age 32 weeks in pregnancies complicated by preterm prelabor rupture of membranes (PPROM). Methods: A prospective study was performed, and 115 women with singleton pregnancies complicated by PPROM at gestational ages between 24(0/7) and 36(6/7) weeks were included in the study. Transabdominal amniocenteses were performed. Amniotic fluid was analysed using polymerase chain reactions for genital mycoplasmas and cultured for aerobic and anaerobic bacteria. The concentrations of 26 proteins in the amniotic fluid were determined simultaneously using multiplex technology. Results: Bacteria were found in the amniotic fluid of 43% (49/115) of the women. The women were stratified into two subgroups according to gestational age 32 weeks. The amniotic fluid levels of four (interleukin-6, interleukin-10, CC chemokine ligands 2, and 3) and one specific (CC chemokine ligands 2) proteins were higher in women with the presence of bacteria in the amniotic fluid below and above 32 gestational weeks, respectively. Conclusions: An intraamniotic inflammatory response to bacteria in pregnancies complicated by PPROM seems to be different below and above 32 weeks of gestation.
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| 8. |
- Kacerovsky, Marian, et al.
(författare)
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Levels of multiple proteins in gingival crevicular fluid and intra-amniotic complications in women with preterm prelabor rupture of membranes.
- 2018
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Ingår i: The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. - : Informa UK Limited. - 1476-4954. ; 31:19, s. 2555-2563
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Tidskriftsartikel (refereegranskat)abstract
- The primary aim of this study was to identify the association between the local inflammatory response in gingival crevicular fluid measured by the levels of multiple proteins and maternal and intra-amniotic inflammatory responses measured by maternal serum C-reactive protein (CRP) and amniotic fluid interleukin (IL)-6 concentrations, respectively, in women with preterm prelabor rupture of membranes (PPROM).A prospective study was performed in which 78 women with singleton pregnancies complicated by PPROM between 24+0 and 36+6 weeks of gestation were included. Transabdominal amniocenteses were performed at the time of admission. A bedside assessment of amniotic fluid IL-6 was performed. Maternal serum CRP concentration was also measured at the time of admission. Gingival crevicular fluid was collected from the pocket of the selected tooth (the tooth with the deepest pocket) using standard sterile paper strips within 72h after admission. Twenty-six proteins in the gingival crevicular fluid were assessed by multiplex the Meso-Scale technology.No correlations between the levels of proteins in the gingival crevicular fluid and maternal serum CRP and amniotic fluid IL-6 concentrations were found, except for a weak positive correlation between granulocyte macrophage colony-stimulating factor and CRP.The local inflammatory response in the gingival crevicular fluid is not related to the maternal and intra-amniotic inflammatory responses in women with PPROM.
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| 9. |
- Liu, Xueping, et al.
(författare)
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Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P=3.96×10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.
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| 10. |
- Ottosson, Filip, et al.
(författare)
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Unraveling the metabolomic architecture of autism in a large Danish population-based cohort
- 2024
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Ingår i: BMC Medicine. - 1741-7015. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prevalence of autism in Denmark has been increasing, reaching 1.65% among 10-year-old children, and similar trends are seen elsewhere. Although there are several factors associated with autism, including genetic, environmental, and prenatal factors, the molecular etiology of autism is largely unknown. Here, we use untargeted metabolomics to characterize the neonatal metabolome from dried blood spots collected shortly after birth. Methods: We analyze the metabolomic profiles of a subset of a large Danish population-based cohort (iPSYCH2015) consisting of over 1400 newborns, who later are diagnosed with autism and matching controls and in two Swedish population-based cohorts comprising over 7000 adult participants. Mass spectrometry analysis was performed by a timsTOF Pro operated in QTOF mode, using data-dependent acquisition. By applying an untargeted metabolomics approach, we could reproducibly measure over 800 metabolite features. Results: We detected underlying molecular perturbations across several metabolite classes that precede autism. In particular, the cyclic dipeptide cyclo-leucine-proline (FDR-adjusted p = 0.003) and the carnitine-related 5-aminovaleric acid betaine (5-AVAB) (FDR-adjusted p = 0.03), were associated with an increased probability for autism, independently of known prenatal and genetic risk factors. Analysis of genetic and dietary data in adults revealed that 5-AVAB was associated with increased habitual dietary intake of dairy (FDR-adjusted p < 0.05) and with variants near SLC22A4 and SLC22A5 (p < 5.0e − 8), coding for a transmembrane carnitine transporter protein involved in controlling intracellular carnitine levels. Conclusions: Cyclo-leucine-proline and 5-AVAB are associated with future diagnosis of autism in Danish neonates, both representing novel early biomarkers for autism. 5-AVAB is potentially modifiable and may influence carnitine homeostasis.
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