| 1. |
- Bodin, Charlotte Rosenkrantz, et al.
(author)
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Ultrasound in Prenatal Diagnostics and Its Impact on the Epidemiology of Spina Bifida in a National Cohort from Denmark with a Comparison to Sweden
- 2018
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In: BioMed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141. ; 2018
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Journal article (peer-reviewed)abstract
- Objectives. The aim of this study was to assess the incidence, the prenatal detection rate by ultrasound, and the pregnancy outcome of spina bifida (SB) in Denmark (DK) in 2008-2015 and to compare results to national data from Sweden. Methods. Data were retrieved from the Danish Fetal Medicine Database, which includes International Classification of Diseases-(ICD-) 10 codes for pre-or postnatally diagnoses and pregnancy outcome. Missing data were obtained from the National Patient Register. Livebirth data with myelomeningocele (MMC) in Sweden were obtained from different databases. Results. There were 234 cases with SB in DK in 2008-2015. The incidence of SB was 4.9: 10,000; 89% were detected with ultrasound prior to week 22; 90% of these pregnancies were terminated (ToP); 91% were isolated malformations of which 11% showed abnormal karyotype. The incidence of newborns with MMC was 1.3: 10,000 in Sweden. Conclusions. Ultrasound screening has a major impact on the epidemiology of SB. The prenatal detection rate of SB was high, and most SB cases were isolated and had a normal karyotype. Among women with a prenatal fetal diagnosis of SB, 90% chose to have ToP. The incidence of newborns with SB was higher in Sweden than in DK.
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| 2. |
- Kaipe, Helen, et al.
(author)
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MAIT Cells at the Fetal-Maternal Interface During Pregnancy
- 2020
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In: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 11
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Research review (peer-reviewed)abstract
- One of the main functions of the human placenta is to provide a barrier between the fetal and maternal blood circulations, where gas exchange and transfer of nutrients to the developing fetus take place. Despite being a barrier, there is a multitude of crosstalk between maternal immune cells and fetally derived semi-allogeneic trophoblast cells. Therefore, the maternal immune system has a difficult task to both tolerate the fetus but at the same time also defend the mother and the fetus from infections. Mucosal-associated invariant T (MAIT) cells are an increasingly recognized subset of T cells with anti-microbial functions that get activated in the context of non-polymorphic MR1 molecules, but also in response to inflammation. MAIT cells accumulate at term pregnancy in the maternal blood that flows into the intervillous space inside the placenta. Chemotactic factors produced by the placenta may be involved in recruiting and retaining particular immune cell subsets, including MAIT cells. In this Mini-Review, we describe what is known about MAIT cells during pregnancy and discuss the potential biological functions of MAIT cells at the fetal-maternal interface. Since MAIT cells have anti-microbial and tissue-repairing functions, but lack alloantigen reactivity, they could play an important role in protecting the fetus from bacterial infections and maintaining tissue homeostasis without risks of mediating harmful responses toward semi-allogenic fetal tissues.
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| 3. |
- Solders, Martin, et al.
(author)
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Maternal Adaptive Immune Cells in Decidua Parietalis Display a More Activated and Coinhibitory Phenotype Compared to Decidua Basalis
- 2017
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In: Stem Cells International. - : Hindawi Limited. - 1687-9678 .- 1687-966X. ; 2017
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Journal article (peer-reviewed)abstract
- © 2017 Martin Solders et al. The maternal part of the placenta, the decidua, consists of maternal immune cells, decidual stromal cells, and extravillous fetal trophoblasts. In a successful pregnancy, these cell compartments interact to provide an intricate balance between fetal tolerance and antimicrobial defense. These processes are still poorly characterized in the two anatomically different decidual tissues, basalis and parietalis. We examined immune cells from decidua basalis and parietalis from term placentas (n=15) with flow cytometry. By using multivariate discriminant analysis, we found a clear separation between the two decidual compartments based on the 81 investigated parameters. Decidua parietalis lymphocytes displayed a more activated phenotype with a higher expression of coinhibitory markers than those isolated from basalis and contained higher frequencies of T regulatory cells. Decidua basalis contained higher proportions of monocytes, B cells, and mucosal-associated invariant T (MAIT) cells. The basalis B cells were more immature, and parietalis MAIT cells showed a more activated phenotype. Conventional T cells, NK cells, and MAIT cells from both compartments potently responded with the production of interferon-γ and/or cytotoxic molecules in response to stimulation. To conclude, leukocytes in decidua basalis and parietalis displayed remarkable phenotypic disparities, indicating that the corresponding stromal microenvironments provide different immunoregulatory signals.
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| 4. |
- Tiblad, Eleonor
(author)
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New strategies to prevent fetal and neonatal complications in Rhesus D immunization
- 2012
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Doctoral thesis (other academic/artistic)abstract
- The general purpose of this thesis was to investigate if fetal and neonatal complications due to RhD immunization in the mother could be prevented by 1) reducing procedure-related complications in intrauterine blood transfusions and by 2) reducing the incidence of RhD immunization by providing routine antenatal anti-D prophylaxis during pregnancy selectively to non-immunized RhD negative women with RhD positive fetuses. Paper I was a retrospective study including 284 intrauterine transfusions in 84 women 1990-2010. Perinatal survival was 91.8 %. Complications occurred in 4.9 % of procedures of which 1.4 % were fatal. Procedure-related complications were significantly more common when transfusions were performed in a free loop of the umbilical cord compared to the intrahepatic part of the umbilical vein (OR 5.4, 95% CI: 1.2 to 23.7, P=0.025). There was no significant difference between the intrahepatic route and the placental cord insertion (P=0.83). Paper II was a pharmacokinetic study on 16 women measuring plasma concentrations of anti-D IgG at predefined time points after administration in gestational weeks 28-30. The half-life was in median 23 days (12.5 - 30.3). At ten weeks after injection, plasma concentrations ranging from 1-4 ng/mL were found in all samples available for analysis. We estimated that 75 % of women would have had detectable anti-D IgG concentrations ≥1 ng/mL at the time of delivery. In paper III we performed a large prospective cohort study on the diagnostic accuracy of a single-exon noninvasive method to determine fetal RHD genotype in the first trimester of pregnancy. Plasma samples from 4118 pregnancies were included in the analysis. Median gestational age for blood sampling was 10 weeks. From eight gestational weeks, sensitivity was 98.9 % (95% CI 98.3 - 99.3) and specificity 98.9 % (95% CI 98.1 - 99.4). From 10 weeks of gestation sensitivity was 99.3 % and from 22 weeks 100 %. Paper IV was a retrospective study on all (290) RhD immunized pregnant women in Stockholm 1990-2008. Fifty-one % (147/290) of the women were sensitized with their first-born child and 33 % (96/290) with their second born child. At least half of the women were immunized in the third trimester, which could possibly have been prevented with antenatal prophylaxis. Fifty-six % (144/259) of the neonates in subsequent pregnancies required treatment for hemolytic disease, independently of in which order or pregnancy the women were immunized. In paper V we performed a prospective cohort study offering anti-D prophylaxis in gestational week 28-30 selectively to all RhD negative pregnant women in Stockholm with an RHD positive fetus. Selective prophylaxis was provided in 4590 pregnancies resulting in an incidence of RhD immunization in the study cohort of 0.21 percent (95% CI 0.12 - 0.31) (20/9380). The reference cohort consisted of all RhD pregnant women giving birth in the same region 2004-2008 and the incidence in this group was 0.46 percent (95% CI 0.37 - 0.56) (86/18.546). The risk ratio (RR) for sensitization was 0.46 (95% CI 0.28 - 0.75) with the new program. This thesis shows that without routine antenatal anti-D prophylaxis, the majority of women become RhD immunized during pregnancy with their first or second child. The risk of hemolytic disease of the fetus and newborn is the same regardless of in which order of pregnancy a woman become immunized and occurs in more than half of subsequent pregnancies. Non-invasive fetal RHD genotyping in the first trimester of pregnancy can be performed with high accuracy and enables administration of routine antenatal anti-D prophylaxis (RAADP) selectively to RhD negative women with RHD positive fetuses. This reduces the risk of RhD immunization to 0.21 percent. RAADP usually lasts for ten weeks after injection but thereafter concentrations are variable and not all women will have detectable anti-D levels at term and post-term, which might be a cause of residual immunizations. Perinatal survival in pregnancies requiring intrauterine blood transfusion is high, but the risk of procedure-related complications can be further reduced by applying a safer technique and with timely referrals to a specialized center before severe anemia develops.
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| 5. |
- Vikberg, Sara, et al.
(author)
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Labour promotes systemic mobilisation of monocytes, T cell activation and local secretion of chemotactic factors in the intervillous space of the placenta
- 2023
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In: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 14
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Journal article (peer-reviewed)abstract
- During pregnancy, maternal blood circulates through the intervillous space of the placenta and the reciprocal interactions between foetal tissues and maternal immune cells makes the intervillous space a unique immunological niche. Labour is characterised by a proinflammatory response in the myometrium, but the relationship between local and systemic changes during the onset of labour remains elusive. We here aimed to investigate how the systemic and intervillous circulatory systems are affected during labour from an immunological point of view. We report that the proportion of monocytes is dramatically higher in peripheral (PB), intervillous blood (IVB) and decidua in labouring (n = 14) compared to non-labouring women (n = 15), suggesting that labour leads to both a systemic and local mobilisation of monocytes. Labour was associated with a relative increase of effector memory T cells in the intervillous space compared to the periphery, and MAIT cells and T cells showed an elevated expression of activation markers both in PB and IVB. Intervillous monocytes consisted to a higher degree of CD14(+)CD16(+) intermediate monocytes compared to peripheral monocytes, independently of mode of delivery, and displayed an altered phenotypic expression pattern. A proximity extension assay analysis of 168 proteins revealed that several proteins associated to myeloid cell migration and function, including CCL2 and M-CSF, were upregulated in IVB plasma in labouring women. Thus, the intervillous space could be a bridging site for the communication between the placenta and the periphery, which contribute to monocyte mobilisation and generation of inflammatory reactions during spontaneous labour.
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| 6. |
- Wikman, Agneta Taune, et al.
(author)
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Noninvasive Single-Exon Fetal RHD Determination in a Routine Screening Program in Early Pregnancy.
- 2012
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In: Obstetrics and Gynecology. - 1873-233X. ; 120:2, s. 227-234
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To develop a simple and robust assay suitable for fetal RHD screening in first-trimester pregnancy and to estimate the sensitivity and specificity of the test after its implementation in an unselected pregnant population. METHODS: Pregnant women attending their first antenatal visit were included, and fetal RHD determination was performed for all women who typed RhD-negative by routine serology. DNA was extracted by an automated system and quantitative polymerase chain reaction was done by an assay based on exon 4. Reporting criteria were simple and strict. RESULTS: Four thousand one hundred eighteen pregnancies, with a median gestational age of 10 weeks, were included. After 211 (5.1%) reanalyses, fetal RHD was reported positive in 2,401 (58.3%), negative in 1,552 (37.7%), and inconclusive in 165 (4.0%) based on the first sample. After a second sample in 147 of 165, only 14 remained inconclusive, all resulting from a weak or silent maternal RHD gene. Using blood group serology of the newborns as the gold standard, the false-negative rate was 55 of 2,297 (2.4%) and the false-positive rate was 15 of 1,355 (1.1%). After exclusion of samples obtained before gestational week 8, the false-negative rate was 23 of 2,073 (1.1%) and the false-positive rate was 14 of 1,218 (1.1%). Both sensitivity and specificity were close to 99% provided samples were not collected before gestational week 8. From gestational week 22, sensitivity was 100%. CONCLUSION: : Fetal RHD detection in early pregnancy using a single-exon assay in a routine clinical setting is feasible and accurate. LEVEL OF EVIDENCE: : I.
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