Estimating placental oxygen transport capacity is highly desirable, as impaired placental functio... more Estimating placental oxygen transport capacity is highly desirable, as impaired placental function is associated with fetal growth restriction (FGR) and poor neonatal outcome. In clinical obstetrics, a noninvasive method to estimate the placental oxygen transport is not available, and the current methods focus on fetal well-being rather than on direct assessment of placental function. In this article, we aim to estimate the placental oxygen transport using the hyperoxic placental blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) response. In 21 normal pregnancies and in four cases of severe early onset FGR, placental BOLD MRI was performed in a 1.5 Tesla MRI system (TR:8000 msec, TE:50 msec, Flip angle:90). Placental histological examination was performed in the FGR cases. In normal pregnancies, the average hyperoxic placental BOLD response was 12.6 ± 5.4% (mean ± SD). In the FGR cases, the hyperoxic BOLD response was abnormal only in cases with histological signs of maternal hypoperfusion of the placenta. The hyperoxic placental BOLD response is mainly derived from an increase in the saturation of maternal venous blood. In the normal placenta, the pO2 of the umbilical vein is closely related to the pO2 of the uterine vein. Therefore, the hyperoxic placental BOLD response may reflect the placental oxygen supply to the fetus. In early onset FGR, the placental oxygen transport is reduced mainly because of the maternal hypoperfusion, and in these cases the placental BOLD response might be altered. Thus, the placental BOLD MRI might provide direct noninvasive assessment of placental oxygen transport.
Annexin A5 is an essential component of placental integrity that may potentially mediate suscepti... more Annexin A5 is an essential component of placental integrity that may potentially mediate susceptibility to phenotypes of compromised pregnancy. A promoter haplotype termed M2 of the coding gene ANXA5 has been implicated in various pregnancy complications such as preeclampsia and recurrent pregnancy loss (RPL), however with inconclusive results. A retrospective case-control study combining resequencing and restriction fragment length polymorphism (RFLP) analysis was undertaken in 313 women with unexplained RPL and 214 fertile women from Estonia and Denmark to estimate the RPL disease risk of the M2 haplotype in Northern Europe. Comparative prevalence of the studied ANXA5 genetic variants in human populations was estimated based on the 1000 Genomes Project (n = 675, whole-genome sequencing data) and the KORA S3 500K dataset of South German samples (n = 1644, genome-wide genotyping data). Minor allele frequency of common polymorphisms in ANXA5 promoter was up to two-fold lower among Es...
The Magnetic Resonance Imaging (MRI) variable T2* depends on multiple factors. One important fact... more The Magnetic Resonance Imaging (MRI) variable T2* depends on multiple factors. One important factor is the presence of deoxyhemoglobin. We aimed to describe placental T2* in normal pregnancies and in pregnancies with fetal growth restriction (FGR). We included 24 normal pregnancies (gestational week 24-40) and four FGR cases with estimated fetal weight below the 1(st) centile. Prior to the MRI, an ultrasound examination including Doppler flow measurements was performed. Placental histological examination was made in the FGR cases. The T2* value was calculated using a gradient echo sequence with readout at 16 echo times. In the normal pregnancies, repeat T2* measurements and inter-observer reproducibility were assessed in order to estimate the reproducibility of the method. The method was robust regarding the technical - and the inter-observer reproducibility. However, some slice to slice variation existed due to the heterogeneous nature of the normal placenta. We therefore based the T2*-estimations on the average of two slices from each placenta. In the normal pregnancies, the placental T2* value decreased significantly with gestational age being 120 ± 17 ms (mean, SD) in week 24, 84 ± 16 ms in week 32, and 47 ± 17 ms in week 40. Three FGR cases had abnormal Doppler flows, histological signs of maternal hypoperfusion and a reduced T2* value (Z-scores < -3.5). In the fourth FGR case, Doppler flows, placental histology and T2* value (Z-score -0.34) were normal. The established reference values for placental T2* may be clinically useful as the T2* values were significantly reduced in FGR-cases with histological signs of maternal hypoperfusion.
South Greenland is a recognized gold province that hosts Greenland's first gold mine, Nalunaq... more South Greenland is a recognized gold province that hosts Greenland's first gold mine, Nalunaq. Because Nalunaq consists of an auriferous quartz-vein hosted in altered metavolanic rocks these rocks were traditionally regarded as being most favourable for gold exploration and only limited gold exploration was carried out in other settings. Here we present recent results from exploration work that targeted granitic rocks at Amphibolite Ridge (AR) about 25 km north of Nalunaq. Diamond drilling has intersected large portions of gold mineralized granitic rocks together with auriferous quartz-veins associated with shear zones. The hydrothermal alteration fluids have added gold to the granitoids, and the presence of bismuth-rich tellurides implies that the fluids responsible for the introduction of gold were also enriched in Bi and Te. The granitic rocks were subjected to Kfs (K-feldspar), sericite and carbonate hydrothermal alteration together with silicification. Surface mapping of th...
To assess outcome in terms of live-birth rate after fresh or frozen IVF/intracytoplasmic sperm in... more To assess outcome in terms of live-birth rate after fresh or frozen IVF/intracytoplasmic sperm injection assisted reproductive technology (ART) cycles where immunomodulation was given to patients with recurrent pregnancy loss after prior ART treatments. Retrospective cohort study. Tertiary care university hospital. Fifty-two patients with a history of at least three consecutive pregnancy losses after ART who underwent at least one further ART cycle with concurrent immunomodulation in 2003-2012. Immunomodulation with IV immunoglobulin and prednisone starting from before ET and continuing in the first trimester if pregnancy was established. Live-birth rate per ET and cumulative live-birth rate after up to five ETs. Nineteen patients (36.5%) achieved a live birth after the first ET with immunomodulation, and a total of 32 patients achieved a live birth in the study period, resulting in a cumulative live-birth rate of 61.5%. There was no significant difference in baseline and immunologi...
Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expres... more Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on the extra-villous trophoblast and seems to have immunomodulatory functions during pregnancy. Studies have linked HLA-G polymorphisms to pregnancy complications such as preeclampsia and recurrent miscarriage. Levels of soluble HLA-G (sHLA-G) in blood plasma from non-pregnant donors seem to be associated with these polymorphisms. In the current study, we have genotyped 246 mothers and their offspring for HLA-G polymorphisms in the 3'-untranslated region (3'UTR) and measured sHLA-G in maternal blood plasma samples from gestational week 20 and at term, as well as in fetal umbilical cord blood samples. This is the first large study simultaneously performing HLA-G genotyping of mother and offspring and measuring sHLA-G in both maternal and umbilical cord blood. The results showed that increasing numbers of 14bp ins (rs66554220) alleles in the mother-child genotype combinations were associated with higher maternal sHLA-G levels at term when restricting the analysis to 14bp ins/del heterozygous mothers (p=0.015). Furthermore, increasing numbers of 14InsG haplotypes (14bp ins/del and +3142C/G (rs1063320) polymorphism) in mother-child genotype combinations were associated with higher levels of sHLA-G at term in heterozygous 14DelC/14InsG mothers (p=0.005). In conclusion, the results indicate that there is an association between combined feto-maternal HLA-G genotypes and sHLA-G levels in maternal blood plasma.
Platelet concentrates, irradiated with 15 Gy and stored for 5 days at room temperature under stan... more Platelet concentrates, irradiated with 15 Gy and stored for 5 days at room temperature under standardized conditions, were evaluated by in vitro tests and electron microscopy, in a paired study with nonirradiated platelets from the same concentrates, to investigate their usefulness for transfusion. The results showed no significant differences between the two groups in pH, pO2, pCO2, in vitro platelet aggregation, LDH, beta-thromboglobulin and thromboxane-B2. Examination by electron microscopy showed a higher degree of degranulation in the 5-day-old platelets but no certain difference between irradiated versus nonirradiated platelets. On the basis of satisfactory in vitro storage properties, platelet concentrates can be stored for 5 days in PL-1240 bags after irradiation. However, we recommend irradiation just before transfusion whenever possible.
HLA typing was performed in 49 families, each containing at least one woman with a history of une... more HLA typing was performed in 49 families, each containing at least one woman with a history of unexplained recurrent spontaneous abortion (RSA), and reproductive histories were recorded for the siblings. Abortion rate in sisters sharing two HLA haplotypes with the proband was significantly (p less than 0.01) increased, whereas abortion rates of brothers' wives seemed independent of the brothers' degree of HLA sharing with the proband. Birthweights of offspring of both the sisters and the brothers decreased with increasing HLA haplotype identity between the sibling and the proband (p = 0.05). The mean birthweight of infants of siblings sharing both parental haplotypes with the proband was 3158 g which was significantly (p less than 0.02) less than the average birthweight in Denmark (3417 g). Significantly (p less than 0.05) decreased mean birthweight in infants of brothers who were HLA-identical with the proband suggested that the disposition to growth retardation could be inherited with HLA also through the male gametes. It has been shown that, in their few successful pregnancies, women with RSA bear infants with a birthweight which is approximately 300 g less than normal. The present study demonstrated that the two obstetrical conditions, RSA and retarded fetal growth, share common genetic markers: HLA. It is suggested that HLA or HLA-linked genes causing growth retardation in fetuses are part of the putative complex of genes involved in the pathogenesis of recurrent abortion.
Estimating placental oxygen transport capacity is highly desirable, as impaired placental functio... more Estimating placental oxygen transport capacity is highly desirable, as impaired placental function is associated with fetal growth restriction (FGR) and poor neonatal outcome. In clinical obstetrics, a noninvasive method to estimate the placental oxygen transport is not available, and the current methods focus on fetal well-being rather than on direct assessment of placental function. In this article, we aim to estimate the placental oxygen transport using the hyperoxic placental blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) response. In 21 normal pregnancies and in four cases of severe early onset FGR, placental BOLD MRI was performed in a 1.5 Tesla MRI system (TR:8000 msec, TE:50 msec, Flip angle:90). Placental histological examination was performed in the FGR cases. In normal pregnancies, the average hyperoxic placental BOLD response was 12.6 ± 5.4% (mean ± SD). In the FGR cases, the hyperoxic BOLD response was abnormal only in cases with histological signs of maternal hypoperfusion of the placenta. The hyperoxic placental BOLD response is mainly derived from an increase in the saturation of maternal venous blood. In the normal placenta, the pO2 of the umbilical vein is closely related to the pO2 of the uterine vein. Therefore, the hyperoxic placental BOLD response may reflect the placental oxygen supply to the fetus. In early onset FGR, the placental oxygen transport is reduced mainly because of the maternal hypoperfusion, and in these cases the placental BOLD response might be altered. Thus, the placental BOLD MRI might provide direct noninvasive assessment of placental oxygen transport.
Annexin A5 is an essential component of placental integrity that may potentially mediate suscepti... more Annexin A5 is an essential component of placental integrity that may potentially mediate susceptibility to phenotypes of compromised pregnancy. A promoter haplotype termed M2 of the coding gene ANXA5 has been implicated in various pregnancy complications such as preeclampsia and recurrent pregnancy loss (RPL), however with inconclusive results. A retrospective case-control study combining resequencing and restriction fragment length polymorphism (RFLP) analysis was undertaken in 313 women with unexplained RPL and 214 fertile women from Estonia and Denmark to estimate the RPL disease risk of the M2 haplotype in Northern Europe. Comparative prevalence of the studied ANXA5 genetic variants in human populations was estimated based on the 1000 Genomes Project (n = 675, whole-genome sequencing data) and the KORA S3 500K dataset of South German samples (n = 1644, genome-wide genotyping data). Minor allele frequency of common polymorphisms in ANXA5 promoter was up to two-fold lower among Es...
The Magnetic Resonance Imaging (MRI) variable T2* depends on multiple factors. One important fact... more The Magnetic Resonance Imaging (MRI) variable T2* depends on multiple factors. One important factor is the presence of deoxyhemoglobin. We aimed to describe placental T2* in normal pregnancies and in pregnancies with fetal growth restriction (FGR). We included 24 normal pregnancies (gestational week 24-40) and four FGR cases with estimated fetal weight below the 1(st) centile. Prior to the MRI, an ultrasound examination including Doppler flow measurements was performed. Placental histological examination was made in the FGR cases. The T2* value was calculated using a gradient echo sequence with readout at 16 echo times. In the normal pregnancies, repeat T2* measurements and inter-observer reproducibility were assessed in order to estimate the reproducibility of the method. The method was robust regarding the technical - and the inter-observer reproducibility. However, some slice to slice variation existed due to the heterogeneous nature of the normal placenta. We therefore based the T2*-estimations on the average of two slices from each placenta. In the normal pregnancies, the placental T2* value decreased significantly with gestational age being 120 ± 17 ms (mean, SD) in week 24, 84 ± 16 ms in week 32, and 47 ± 17 ms in week 40. Three FGR cases had abnormal Doppler flows, histological signs of maternal hypoperfusion and a reduced T2* value (Z-scores < -3.5). In the fourth FGR case, Doppler flows, placental histology and T2* value (Z-score -0.34) were normal. The established reference values for placental T2* may be clinically useful as the T2* values were significantly reduced in FGR-cases with histological signs of maternal hypoperfusion.
South Greenland is a recognized gold province that hosts Greenland's first gold mine, Nalunaq... more South Greenland is a recognized gold province that hosts Greenland's first gold mine, Nalunaq. Because Nalunaq consists of an auriferous quartz-vein hosted in altered metavolanic rocks these rocks were traditionally regarded as being most favourable for gold exploration and only limited gold exploration was carried out in other settings. Here we present recent results from exploration work that targeted granitic rocks at Amphibolite Ridge (AR) about 25 km north of Nalunaq. Diamond drilling has intersected large portions of gold mineralized granitic rocks together with auriferous quartz-veins associated with shear zones. The hydrothermal alteration fluids have added gold to the granitoids, and the presence of bismuth-rich tellurides implies that the fluids responsible for the introduction of gold were also enriched in Bi and Te. The granitic rocks were subjected to Kfs (K-feldspar), sericite and carbonate hydrothermal alteration together with silicification. Surface mapping of th...
To assess outcome in terms of live-birth rate after fresh or frozen IVF/intracytoplasmic sperm in... more To assess outcome in terms of live-birth rate after fresh or frozen IVF/intracytoplasmic sperm injection assisted reproductive technology (ART) cycles where immunomodulation was given to patients with recurrent pregnancy loss after prior ART treatments. Retrospective cohort study. Tertiary care university hospital. Fifty-two patients with a history of at least three consecutive pregnancy losses after ART who underwent at least one further ART cycle with concurrent immunomodulation in 2003-2012. Immunomodulation with IV immunoglobulin and prednisone starting from before ET and continuing in the first trimester if pregnancy was established. Live-birth rate per ET and cumulative live-birth rate after up to five ETs. Nineteen patients (36.5%) achieved a live birth after the first ET with immunomodulation, and a total of 32 patients achieved a live birth in the study period, resulting in a cumulative live-birth rate of 61.5%. There was no significant difference in baseline and immunologi...
Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expres... more Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on the extra-villous trophoblast and seems to have immunomodulatory functions during pregnancy. Studies have linked HLA-G polymorphisms to pregnancy complications such as preeclampsia and recurrent miscarriage. Levels of soluble HLA-G (sHLA-G) in blood plasma from non-pregnant donors seem to be associated with these polymorphisms. In the current study, we have genotyped 246 mothers and their offspring for HLA-G polymorphisms in the 3'-untranslated region (3'UTR) and measured sHLA-G in maternal blood plasma samples from gestational week 20 and at term, as well as in fetal umbilical cord blood samples. This is the first large study simultaneously performing HLA-G genotyping of mother and offspring and measuring sHLA-G in both maternal and umbilical cord blood. The results showed that increasing numbers of 14bp ins (rs66554220) alleles in the mother-child genotype combinations were associated with higher maternal sHLA-G levels at term when restricting the analysis to 14bp ins/del heterozygous mothers (p=0.015). Furthermore, increasing numbers of 14InsG haplotypes (14bp ins/del and +3142C/G (rs1063320) polymorphism) in mother-child genotype combinations were associated with higher levels of sHLA-G at term in heterozygous 14DelC/14InsG mothers (p=0.005). In conclusion, the results indicate that there is an association between combined feto-maternal HLA-G genotypes and sHLA-G levels in maternal blood plasma.
Platelet concentrates, irradiated with 15 Gy and stored for 5 days at room temperature under stan... more Platelet concentrates, irradiated with 15 Gy and stored for 5 days at room temperature under standardized conditions, were evaluated by in vitro tests and electron microscopy, in a paired study with nonirradiated platelets from the same concentrates, to investigate their usefulness for transfusion. The results showed no significant differences between the two groups in pH, pO2, pCO2, in vitro platelet aggregation, LDH, beta-thromboglobulin and thromboxane-B2. Examination by electron microscopy showed a higher degree of degranulation in the 5-day-old platelets but no certain difference between irradiated versus nonirradiated platelets. On the basis of satisfactory in vitro storage properties, platelet concentrates can be stored for 5 days in PL-1240 bags after irradiation. However, we recommend irradiation just before transfusion whenever possible.
HLA typing was performed in 49 families, each containing at least one woman with a history of une... more HLA typing was performed in 49 families, each containing at least one woman with a history of unexplained recurrent spontaneous abortion (RSA), and reproductive histories were recorded for the siblings. Abortion rate in sisters sharing two HLA haplotypes with the proband was significantly (p less than 0.01) increased, whereas abortion rates of brothers' wives seemed independent of the brothers' degree of HLA sharing with the proband. Birthweights of offspring of both the sisters and the brothers decreased with increasing HLA haplotype identity between the sibling and the proband (p = 0.05). The mean birthweight of infants of siblings sharing both parental haplotypes with the proband was 3158 g which was significantly (p less than 0.02) less than the average birthweight in Denmark (3417 g). Significantly (p less than 0.05) decreased mean birthweight in infants of brothers who were HLA-identical with the proband suggested that the disposition to growth retardation could be inherited with HLA also through the male gametes. It has been shown that, in their few successful pregnancies, women with RSA bear infants with a birthweight which is approximately 300 g less than normal. The present study demonstrated that the two obstetrical conditions, RSA and retarded fetal growth, share common genetic markers: HLA. It is suggested that HLA or HLA-linked genes causing growth retardation in fetuses are part of the putative complex of genes involved in the pathogenesis of recurrent abortion.
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