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1.	Bergman, Lina, 1982, et al. (författare) Blood-based cerebral biomarkers in preeclampsia: Plasma concentrations of NfL, tau, S100B and NSE during pregnancy in women who later develop preeclampsia - A nested case control study 2018 Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:5 Tidskriftsartikel (refereegranskat)abstract Objective To evaluate if concentrations of the neuronal proteins neurofilament light chain and tau are changed in women developing preeclampsia and to evaluate the ability of a combination of neurofilament light chain, tau, S100B and neuron specific enolase in identifying neurologic impairment before diagnosis of preeclampsia. A nested case-control study within a longitudinal study cohort was performed. 469 healthy pregnant women were enrolled between 2004-2007 and plasma samples were collected at gestational weeks 10, 25, 28, 33 and 37. Plasma concentrations of tau and neurofilament light chain were analyzed in 16 women who eventually developed preeclampsia and 36 controls throughout pregnancy with single molecule array (Simoa) method and compared within and between groups. S100B and NSE had been analyzed previously in the same study population. A statistical model with receiving characteristic operation curve was constructed with the four biomarkers combined. Plasma concentrations of neurofilament light chain were significantly increased in women who developed preeclampsia in gestational week 33 (11.85 ng/L, IQR 7.48-39.93 vs 6.80 ng/L, IQR 5.65-11.40) and 37 (22.15 ng/L, IQR 10.93-35.30 vs 8.40 ng/L, IQR 6.40-14.30) and for tau in gestational week 37 (4.33 ng/L, IQR 3.97-12.83 vs 3.77 ng/L, IQR 1.91-5.25) in contrast to healthy controls. A combined model for preeclampsia with tau, neurofilament light chain, S100B and neuron specific enolase in gestational week 25 displayed an area under the curve of 0.77, in week 28 it was 0.75, in week 33 it was 0.89 and in week 37 it was 0.83. Median week for diagnosis of preeclampsia was at 38 weeks of gestation. Concentrations of both tau and neurofilament light chain are increased in the end of pregnancy in women developing preeclampsia in contrast to healthy pregnancies. Cerebral biomarkers might reflect cerebral involvement before onset of disease.
2.	Bolin, Marie, et al. (författare) Histidine-Rich Glycoprotein as an Early Biomarker of Preeclampsia 2011 Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 24:4, s. 496-501 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Prediction of preeclampsia is of great interest and the coagulation system as well as the angiogenic pathway is known to be dysfunctional in preeclampsia. Histidine-rich glycoprotein (HRG) is a protein interacting with both these biological systems and the purpose of this prospective, longitudinal cohort study was to analyze whether there is a difference in circulating levels of HRG during pregnancy in women developing preeclampsia compared to normal healthy pregnancies. We furthermore wanted to evaluate whether HRG has the potential of being an early biomarker of preeclampsia. METHODS: A cohort of healthy pregnant women (n = 469) was enrolled at gestational weeks 8-12. Plasma samples were collected at gestational weeks 10, 25, 28, 33, and 37 and analyzed with an enzyme-linked immunosorbent assay. RESULTS: The levels of HRG decreased during pregnancy in all women, but the levels were significantly lower at gestational weeks 10, 25, and 28 in women who later developed preeclampsia than in normal pregnant women (P < 0.05, P < 0.05, and P < 0.05). CONCLUSION: Our data indicates that HRG levels in plasma might be a possible biomarker already in gestational week 10 for prediction of later onset of preeclampsia in a low risk population.
3.	Elbagir, Sahwa, et al. (författare) Elevated IgA antiphospholipid antibodies in healthy pregnant women in Sudan but not Sweden, without corresponding increase in IgA anti-β2 glycoprotein I domain 1 antibodies 2020 Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 29:5, s. 463-473 Tidskriftsartikel (refereegranskat)abstract Objective: The role of antiphospholipid antibodies (aPL) during apparently normal pregnancy is still unclear. IgA aPL are prevalent in populations of African origin. Our aim was to measure all isotypes of anticardiolipin (anti-CL) and anti–β2 glycoprotein I (anti-β2GPI) in healthy pregnant and non-pregnant women of different ethnicities.Methods: Healthy Sudanese pregnant women (n = 165; 53 sampled shortly after delivery), 96 age-matched Sudanese female controls and 42 healthy pregnant and 249 non-pregnant Swedish women were included. IgA/G/M anti-CL and anti-β2GPI were tested at one time point only with two independent assays in Sudanese and serially in pregnant Swedes. IgA anti-β2GPI domain 1 and as controls IgA/G/M rheumatoid factor (RF), IgG anti–cyclic citrullinated peptide 2 (anti-CCP2) and anti–thyroid peroxidase (anti-TPO) were investigated in Sudanese females.Results: Pregnant Sudanese women had significantly higher median levels of IgA anti-CL, IgA anti-β2GPI (p < 0.0001 for both antibodies using two assays) and IgM anti-β2GPI (both assays; p < 0.0001 and 0.008) compared with non-pregnant Sudanese. IgA anti-CL and anti-β2GPI occurrence was increased among Sudanese pregnant women compared with national controls. No corresponding increase during pregnancy was found for IgA anti-β2GPI domain 1 antibodies. Both IgG anti-CL and IgG control autoantibodies decreased during and directly after pregnancy among Sudanese. Serially followed Swedish women showed no changes in IgA aPL, whereas IgG/M anti-CL decreased.Conclusions: IgA aPL are increased in Sudanese but not in Swedish women, without corresponding increase in IgA domain 1. Whether due to ethnicity and/or environmental influences the occurrence of IgA aPL during Sudanese pregnancies, and its clinical significance, is yet to be determined.
4.	Elenis, Evangelia, et al. (författare) The histidine-rich glycoprotein A1042G polymorphism and recurrent miscarriage : a pilot study 2014 Ingår i: Reproductive Biology and Endocrinology. - : Springer Science and Business Media LLC. - 1477-7827. ; 12, s. 70- Tidskriftsartikel (refereegranskat)abstract Background: Histidine-rich Glycoprotein (HRG) has previously been shown to have an impact on implantation and fertility. The aim of this study was to investigate if there is an association between the HRG A1042G single nucleotide polymorphism (SNP) and recurrent miscarriage. Methods: The study was designed as a case-control study and the women were included at University Hospitals in Sweden. 186 cases with recurrent miscarriage were compared with 380 pregnant controls with no history of miscarriage. Each woman was genotyped for the HRG A1042G SNP. Results: The results indicated that the frequency of heterozygous HRG A1042G carriers was higher among controls compared to cases (34.7% vs 26.3%; p < 0.05). In a bivariate regression analysis, a negative association was found between recurrent miscarriage and heterozygous A/G carriers both in the entire study population (OR 0.67, 95% CI 0.45 - 0.99; p < 0.05) as well as in a subgroup of women with primary recurrent miscarriage (OR 0.37, 95% CI 0.16 - 0.84; p < 0.05). These results remained even after adjustment for known confounders such as age, BMI and thyroid disease (OR 0.36, 95% CI 0.15 - 0.84; p < 0.05). Conclusions: Women who are heterozygous carriers of the HRG A1042G SNP suffer from recurrent miscarriage more seldom than homozygous carriers. Thus, analysis of the HRG A1042G SNP might be of importance for individual counseling regarding miscarriage.
5.	Friis, Therese, et al. (författare) Cerebral Biomarkers and Blood-Brain Barrier Integrity in Preeclampsia 2022 Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 11:5 Tidskriftsartikel (refereegranskat)abstract Cerebral complications in preeclampsia contribute substantially to maternal mortality and morbidity. There is a lack of reliable and accessible predictors for preeclampsia-related cerebral complications. In this study, plasma from women with preeclampsia (n = 28), women with normal pregnancies (n = 28) and non-pregnant women (n = 16) was analyzed for concentrations of the cerebral biomarkers neurofilament light (NfL), tau, neuron-specific enolase (NSE) and S100B. Then, an in vitro blood-brain barrier (BBB) model, based on the human cerebral microvascular endothelial cell line (hCMEC/D3), was employed to assess the effect of plasma from the three study groups. Transendothelial electrical resistance (TEER) was used as an estimation of BBB integrity. NfL and tau are proteins expressed in axons, NSE in neurons and S100B in glial cells and are used as biomarkers for neurological injury in other diseases such as dementia, traumatic brain injury and hypoxic brain injury. Plasma concentrations of NfL, tau, NSE and S100B were all higher in women with preeclampsia compared with women with normal pregnancies (8.85 vs. 5.25 ng/L, p < 0.001; 2.90 vs. 2.40 ng/L, p < 0.05; 3.50 vs. 2.37 mu g/L, p < 0.001 and 0.08 vs. 0.05 mu g/L, p < 0.01, respectively). Plasma concentrations of NfL were also higher in women with preeclampsia compared with non-pregnant women (p < 0.001). Higher plasma concentrations of the cerebral biomarker NfL were associated with decreased TEER (p = 0.002) in an in vitro model of the BBB, a finding which indicates that NfL could be a promising biomarker for BBB alterations in preeclampsia.
6.	Granfors, Michaela, et al. (författare) Iodine deficiency in a study population of pregnant women in Sweden 2015 Ingår i: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 94:11, s. 1168-1174 Tidskriftsartikel (refereegranskat)abstract IntroductionIodine deficiency in utero may impair neurological development of the fetus. In Sweden, iodine nutrition is considered to be adequate in the general population. The aim of this study was to evaluate iodine nutrition during pregnancy in Sweden. Material and methodsIn this cross-sectional study, the total study population (n=459) consisted of two cohorts (Varmland County, n=273, and Uppsala County, n=186) of pregnant non-smoking women without pre-gestational diabetes mellitus or known thyroid disease before or during pregnancy. Spot urine samples were collected in the third trimester of pregnancy for median urinary iodine concentration (UIC) analysis. ResultsThe median UIC in the total study population was 98g/L (interquartile range 57-148g/L). ConclusionsAccording to WHO/UNICEF/IGN criteria, population-based median UIC during pregnancy should be 150-249g/L. Thus, our results indicate insufficient iodine status in the pregnant population of Sweden. There is an urgent need for further assessments in order to optimize iodine nutrition during pregnancy.
7.	Haroun, Sally, et al. (författare) Association between trefoil factor 3 gene variants and idiopathic recurrent spontaneous abortion 2014 Ingår i: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6483 .- 1472-6491. ; 29:6, s. 737-44 Tidskriftsartikel (refereegranskat)abstract Trefoil factor 3 (TFF3) gene is an inflammatory mediator expressed in human endometrium during the window of implantation. The aim of this study was to evaluate the possible genetic association of TFF3 variants in recurrent spontaneous abortion. Women with a history of recurrent spontaneous abortion (n = 164) and healthy pregnant women (n = 143) were genotyped for five TFF3 polymorphisms (rs225439 G/A, rs533093 C/T, rs225361 A/G, rs11701143 T/C and rs77436142 G/C). In addition, haplotypes formed within the gene were analysed. Within the recurrent spontaneous abortion group, women who at some point had given birth and childless women had 4.19 ± 1.75 and 5.34 ± 3.42 consecutive spontaneous abortions, respectively. Women who had experience recurrent spontaneous abortions had a lower allele frequency of the rs11701143 promoter region minor C allele compared with fertile women (0.02 versus 0.05, P = 0.015). Patients with rs225361 AG genotype had significantly more successful pregnancies before spontaneous abortion than those with homozygous AA and GG genotypes (P = 0.014). No significant differences in haplotype frequencies between patients and controls were detected. Possible genetic risk factors identified that might contribute to the pathogenesis of idiopathic recurrent spontaneous abortion were TFF3 gene variants.
8.	Kaihola, Helena, 1969-, et al. (författare) Effects of fluoxetine on human embryo development 2016 Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 10 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract The use of antidepressant treatment during pregnancy is increasing, and selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed antidepressants in pregnant women. Serotonin plays a role in embryogenesis, and serotonin transporters are expressed in two-cell mouse embryos. Thus, the aim of the present study was to evaluate whether fluoxetine, one of the most prescribed SSRI antidepressant world-wide, exposure influences the timing of different embryo developmental stages, and furthermore, to analyze what protein, and protein networks, are affected by fluoxetine in the early embryo development. Human embryos (17 = 48) were randomly assigned to treatment with 0.25 or 0.5 IiM fluoxetine in culture medium. Embryo development was evaluated by time-lapse monitoring. The fluoxetine-induced human embryo proteome was analyzed by shotgun mass spectrometry. Protein secretion from fluoxetine-exposed human embryos was analyzed by use of high-multiplex immunoassay. The lower dose of fluoxetine had no influence on embryo development. A trend toward reduced time between thawing and start of cavitation was noted in embryos treated with 0.5 it M fluoxetine (p = 0.065). Protein analysis by shotgun mass spectrometry detected 45 proteins that were uniquely expressed in fluoxetine-treated embryos. These proteins are involved in cell growth, survival, proliferation, and inflammatory response. Culturing with 0.5 p M, but not 0.25 p M fluoxetine, caused a significant increase in urokinase-type plasminogen activator (uPA) in the culture medium. In conclusion, fluoxetine has marginal effects on the timing of developmental stages in embryos, but induces expression and secretion of several proteins in a manner that depends on dose. For these reasons, and in line with current guidelines, the lowest possible dose of SSRI should be used in pregnant women who need to continue treatment.
9.	Kaihola, Helena, 1969-, et al. (författare) Levels of caspase-3 and histidine-rich glycoprotein in the embryo secretome as biomarkers of good-quality day-2 embryos and high-quality blastocysts 2019 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:12 Tidskriftsartikel (refereegranskat)abstract Morphological assessment at defined developmental stages is the most important method to select viable embryos for transfer and cryopreservation. Timing of different developmental stages in embryo development has been shown to correlate with its potential to develop into a blastocyst. However, improvements in pregnancy rates by using time-lapse techniques have been difficult to validate scientifically. Therefore, there is a need for new methods, preferably non-invasive methods based on metabolomics, genomics and proteomics, to improve the evaluation of embryo quality even further. The aim of this study was to investigate if different levels of caspase-3 and histidine-rich glycoprotein (HRG), secreted by the embryo into the culture media, can be used as biomarkers of embryo quality. In this study, a total of 334 samples of culture media were collected from in vitro fertilization (IVF) treatments at three different clinics. Protein analysis of the culture media was performed using multiplex proximity extension protein analysis to detect levels of caspase-3 and HRG in the embryo secretome. Protein levels were compared in secretome samples from high- and low-quality blastocysts and embryos that became arrested during development. Correlation between protein levels and time to morula formation was also analyzed. Furthermore, protein levels in secretomes from day-2 cultured embryos were compared on the basis of whether or not pregnancy was achieved. The results showed that caspase-3 levels were lower in secretomes from high-quality vs. low-quality blastocysts and those that became arrested (p ≤ 0.05 for both). In addition, higher HRG levels correlated with a shorter time to morula formation (p ≤ 0.001). Caspase-3 levels were also lower in secretomes from day-2 cultured embryos resulting in a pregnancy vs. those that did not (p ≤ 0.05). Furthermore, it was shown that caspase-3 might be used as a marker for predicting potential success rate after transfer of day-2 cultured embryos, where a caspase-3 cutoff level of 0.02 gave a prediction probability of 68% (p = 0.038). In conclusion, in future prediction models, levels of caspase-3 and HRG might be used as potential markers of embryo quality, and secreted caspase-3 levels could to some extent predict the outcome after transfer of day-2 cultured embryos.
10.	Kaihola, Helena, 1969-, et al. (författare) The effect of antenatal depression and selective serotonin reuptake inhibitor treatment on nerve growth factor signaling in human placenta 2015 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:1 Tidskriftsartikel (refereegranskat)abstract Depressive symptoms during pregnancy are common and may have impact on the developing child. Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed antidepressant treatment, but unfortunately, these treatments can also negatively affect the behavioral development and health of a child during pregnancy. In addition, serotonin (5-HT) exerts neurotrophic actions with thus far not fully known effects in the offspring. The neurotrophic growth factor (NGF) is involved in neuronal cell survival and differentiation, and altered placenta levels have been found to increase the risk for pregnancy complications, similar to those found in women treated with SSRIs. We therefore investigated whether the NGF signaling pathway was altered in the placenta from women treated with SSRIs (n = 12) and compared them with placenta from depressed (n = 12) and healthy mothers (n = 12). Results from immunohistochemical stainings revealed that placental NGF protein levels of SSRI-treated women were increased in both trophoblasts and endothelial cells compared with depressed and control women. In addition, downstream of the NGF receptor TrkA, increased levels of the signaling proteins ROCK2 and phosphorylated Raf-1 were found in stromal cells and a tendency towards increased levels of ROCK2 in trophoblasts and endothelial cells in SSRI-treated women when compared to healthy controls. SSRI-treated women also displayed increased levels of phosphorylated ROCK2 in all placental cell types studied in comparison with depressed and control women. Interestingly, in placental endothelial cells from depressed women, NGF levels were significantly lower compared to control women, but ROCK2 levels were increased compared with control and SSRI-treated women. Taken together, these results show that the NGF signaling and downstream pathways in the placenta are affected by SSRI treatment and/or antenatal depression. This might lead to an altered placental function, although the clinical relevance of our findings still needs to be investigated.
11.	Kaihola, Helena, 1969- (författare) The Effects of SSRI Treatment on Human Placenta and Embryo 2015 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract During pregnancy, 4 - 7% of women suffer from major depressive disorder. When antidepressive treatment is needed, selective serotonin reuptake inhibitors (SSRIs) are the most commonly used. Although severe complications from SSRI treatment are rare, association with a number of adverse pregnancy and fetal outcomes has been found. Also, antenatal depression per se has been shown to affect pregnancy outcomes. The overall aim of this thesis was to examine the effects of SSRIs on human placenta and embryo.In the first study, gene expression was investigated in placenta from depressed, SSRI-treated and healthy pregnant women, using microarray analysis. Antenatal depression and SSRI treatment induced alterations in gene expression, but only 20 genes in common were noted. Validation with qRT-PCR showed that six out of seven selected genes were altered in SSRI-treated women compared with controls, and two genes were altered between depressed women and controls.In study two, the protein levels in placenta from depressed, SSRI-treated and healthy pregnant women were investigated, focusing on the NGF signaling pathway. NGF, phosphorylated Raf-1, ROCK2 and phosphorylated ROCK2, were altered in both SSRI-treated and depressed women, although the proteins were regulated differently in the two groups.In the third study, human embryos were treated with fluoxetine. Embryo development and protein expression were studied. Fluoxetine had some effect on the timing of embryo developmental stages. Also, several proteins were uniquely found in fluoxetine-treated embryos compared with untreated embryos. Fluoxetine also altered the levels of proteins secreted from the embryo.In the fourth study, the human neuroblastoma cell line SH-SY5Y/TrkA was treated with TPA and NGF. The activation of Raf-1 was investigated and the involvement of Ras and PKC was studied. Both NGF and TPA activated Raf-1, but to a different extent and via different pathways. The NGF-induced activation of Raf-1 was mediated via Ras, while TPA induced signaling via PKC.In conclusion, SSRI treatment and antenatal depression influence placental gene and protein expression. These findings may affect placental development and function, which in turn could affect fetal development. Also, direct exposure of embryos to fluoxetine has some effects on embryo development and protein expression, which may affect the development of the fetus.
12.	Kaplan-Sturk, Rebecka, et al. (författare) Outcome of deliveries in healthy but obese women : obesity and delivery outcome 2013 Ingår i: BMC Research Notes. - : BioMed Central. - 1756-0500. ; 6:50 Tidskriftsartikel (refereegranskat)abstract BACKGROUND:Obesity among fertile women is a global problem. 25% of pregnant Swedish women are overweight at admission to the antenatal clinic and 12% of them are considered as obese. Previous studies have shown an increased risk of delivery complications with an elevated maternal BMI. The aim of this study was to evaluate delivery outcomes in relation to maternal BMI on admission to the antenatal clinic.A healthy group of 787 women with full-term pregnancies and spontaneous onset of labor were included in the study. Delivery outcome was assessed in relation to maternal BMI when attending the antenatal clinic.RESULTS:The results indicated that in deliveries where the maternal BMI was >30 a high frequency of abnormal CTG trace during the last 30 minutes of labor was shown. A blood sample for evaluation of risk of fetal hypoxia was performed in only eight percent of these deliveries. A spontaneous vaginal delivery without intervention was noted in 85.7%, and 12% of neonates were delivered with an adverse fetal outcome compared to 2.8% in the group with a maternal BMI<30 (p<0.001).CONCLUSION:These results indicate an increased risk at delivery for healthy, but obese women in labor. Furthermore, the delivery management may not always be optimal in these deliveries.
13.	Lindgren, Karin Elvine, 1984-, et al. (författare) Differences in secretome in culture media when comparing blastocysts and arrested embryos using multiplex proximity assay 2018 Ingår i: Upsala Journal of Medical Sciences. - : TAYLOR & FRANCIS LTD. - 0300-9734 .- 2000-1967. ; 123:3, s. 143-152 Tidskriftsartikel (refereegranskat)abstract Objectives: The aim of this study was to assess different patterns of the human embryo secretome analysed as protein levels in culture media. Furthermore, analyses to correlate protein levels with quality and timing to development of human embryos were performed.Material and methods: Human day-2 cryopreserved embryos were cultured for four days in an EmbryoScope((R)) with a time-lapse camera, and embryo quality was evaluated retrospectively. After culture, the media were collected and relative levels of secreted proteins were analysed using Proseek Multiplex Assays. Protein levels were evaluated in relation to timing to development and the ability to form a blastocyst.Results: Specific patterns of timing of development of blastocysts were found, where a difference in time to start of cavitation was found between high- and low-quality blastocysts. There appeared to be a correlation between specific protein patterns and successful formation of morulae and blastocysts. Embryos developing into blastocysts had higher levels of EMMPRIN than arrested embryos, and levels of caspase-3 were lower in high- versus low-quality blastocysts. Also, higher levels of VEGF-A, IL-6, and EMMPRIN correlated with shorter times to morula formation.Conclusions: The secretome and timing to development differ in embryos forming blastocysts and those that become arrested, and in high- versus low-quality blastocysts. The levels of certain proteins also correlate to specific times to development.
14.	Lindgren, Karin E., et al. (författare) Histidine-rich glycoprotein gene polymorphism in patients with recurrent miscarriage 2013 Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 92:8, s. 974-977 Tidskriftsartikel (refereegranskat)abstract Association between the histidine-rich glycoprotein (HRG) C633T single nucleotide polymorphism (SNP) and recurrent miscarriage was investigated in a case-control study. The cases constituted 187 women with recurrent miscarriage that were compared with 395 controls who had delivered a child and had no history of miscarriage. Blood samples were collected from each woman, genomic DNA was extracted and genotyped for the HRG C633T SNP. In the whole study population, the percentage of miscarriage was the same, regardless of genotype (C/C 31.2%, C/T 32.9% and T/T 32.5%). However, an association between homozygous T/T carriers and recurrent miscarriage was detected in a subgroup of women with primary recurrent miscarriage (odds ratio 2.44, 95% CI 1.01-5.92). Our results indicate an important role for the HRG C633T SNP in the occurrence of recurrent miscarriage.
15.	Olivier, Jocelien D A, 1978-, et al. (författare) The effects of antenatal depression and antidepressant treatment on placental gene expression 2015 Ingår i: Frontiers in cellular neuroscience. - : Frontiers Media SA. - 1662-5102. ; 8, s. 465- Tidskriftsartikel (refereegranskat)
16.	Olivier, Jocelien D A, et al. (författare) The effects of maternal depression and maternal selective serotonin reuptake inhibitor exposure on offspring 2013 Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 7, s. 73- Forskningsöversikt (refereegranskat)abstract It has been estimated that 20% of pregnant women suffer from depression and it is well-documented that maternal depression can have long-lasting effects on the child. Currently, common treatment for maternal depression has been the selective serotonin reuptake inhibitor medications (SSRIs) which are used by 2-3% of pregnant women in the Nordic countries and by up to 10% of pregnant women in the United States. Antidepressants cross the placenta and are transferred to the fetus, thus, the question arises as to whether children of women taking antidepressants are at risk for altered neurodevelopmental outcomes and, if so, whether the risks are due to SSRI medication exposure or to the underlying maternal depression. This review considers the effects of maternal depression and SSRI exposure on offspring development in both clinical and preclinical populations. As it is impossible in humans to study the effects of SSRIs without taking into account the possible underlying effects of maternal depression (healthy pregnant women do not take SSRIs), animal models are of great value. For example, rodents can be used to determine the effects of maternal depression and/or perinatal SSRI exposure on offspring outcomes. Unraveling the joint (or separate) effects of maternal depression and SSRI exposure will provide more insights into the risks or benefits of SSRI exposure during gestation and will help women make informed decisions about using SSRIs during pregnancy.
17.	Sterpu, Irene S., et al. (författare) Angiogenic factors as biomarkers for fetal wellbeing during delivery 2018 Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 218:1: Supplement, s. S186-S186 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
18.	Sterpu, Irene, et al. (författare) The association of second trimester biomarkers in amniotic fluid and fetal outcome 2019 Ingår i: The Journal of Maternal-Fetal & Neonatal Medicine. - : TAYLOR & FRANCIS LTD. - 1476-7058 .- 1476-4954. ; 32:21, s. 3627-3632 Tidskriftsartikel (refereegranskat)abstract Objective: To identify the level of amniotic fluid lactate (AFL), placental growth factor (PLGF), and vascular endothelial growth factor (VEGF) at second trimester amniocentesis, and to compare levels in normal pregnancies with pregnancies ending in a miscarriage, an intrauterine growth restricted fetus (IUGR) or decreased fetal movements.Study design: A prospective cohort study. Amniotic fluid was consecutively collected at amniocentesis in 106 pregnancies. Fetal wellbeing at delivery was evaluated from medical files and compared with the levels of AFL, VEGF, and PLGF at the time of amniocentesis.Results: The median level of AFL was 6.9 mmol/l, VEGF 0.088 pg/ml, and PLGF 0.208 pg/ml. The median levels of AFL in pregnancies ended in miscarriage were significantly higher (10.7 mmol/l) compared to those with a live new-born (6.9 mmol/L, p = .02). The levels of VEGF (p = .2) and PLGF (p = .7) were not affected. In pregnancies with an IUGR, the median level of AFL was higher compared to those with normal fetal growth (p = .003). No differences VEGF (p = .5), but significant lower PLGF were found in IUGR pregnancies (p = .03).Conclusions: Pregnancies ending in a miscarriage or with IUGR had significantly higher median values of AFL but lower values of PLGF in the amniotic fluid at the time of second trimester amniocentesis compared to normal pregnancies.
19.	Bergman, Lina, 1982- (författare) Cerebral biomarkers in women with preeclampsia 2017 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Preeclampsia and eclampsia are among the most common causes of maternal and fetal mortality and morbidity worldwide. There are no reliable means to predict eclampsia or cerebral edema in women with preeclampsia and knowledge of the brain involvement in preeclampsia is still limited. S100B and neuron specific enolase (NSE) are two cerebral biomarkers of glial- and neuronal origin respectively. They are used as predictors for neurological outcome after traumatic brain injuries and cardiac arrest but have not yet been investigated in preeclampsia.This thesis is based on one longitudinal cohort study of pregnant women (n=469, Paper I and III), one cross sectional study of women with preeclampsia and women with normal pregnancies (n=53 and 58 respectively, Paper II and IV) and one experimental animal study of eclampsia (Paper V).In Paper I and III, plasma concentrations of S100B and NSE were investigated throughout pregnancy in women developing preeclampsia (n=16) and in women with normal pregnancies (n=36) in a nested case control study. Plasma concentrations were increased in women developing preeclampsia in gestational week 33 and 37 for S100B and in gestational week 37 for NSE compared to women with normal pregnancies.In Paper II and IV, increased plasma concentrations of S100B and NSE were confirmed among women with preeclampsia compared to women with normal pregnancies. Furthermore, increased plasma concentrations of S100B correlated to visual disturbances among women with preeclampsia (Paper II) and plasma concentrations of S100B and NSE remained increased among women with preeclampsia one year after delivery (Paper IV).In Paper V, an experimental rat model of preeclampsia and eclampsia demonstrated increased serum concentrations of S100B after seizures in normal pregnancy (n=5) and a tendency towards increased plasma concentrations of S100B in preeclampsia (n=5) compared to normal pregnancy (n=5) without seizures. Furthermore, after seizures, animals with magnesium sulphate treatment demonstrated increased serum concentrations of S100B and NSE compared to no treatment.In conclusion; plasma concentrations of S100B and NSE are increased in preeclampsia during late pregnancy and postpartum and S100B correlates to visual disturbances in women with preeclampsia. The findings are partly confirmed in an animal model of eclampsia.
20.	Bergman, Lina, et al. (författare) Cerebral Biomarkers in Women With Preeclampsia Are Still Elevated 1 Year Postpartum 2016 Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 29:12, s. 1374-1379 Tidskriftsartikel (refereegranskat)abstract BACKGROUND There is evidence of cerebral involvement among women with preeclampsia. Levels of the cerebral biomarkers neuron-specific enolase (NSE) and S100B are elevated during pregnancy in women developing preeclampsia. It is although not known if these biomarkers return to normal range postpartum. The aim with this study was to compare levels of S100B and NSE during pregnancy and 1 year postpartum in women who have had preeclampsia to women with normal pregnancies. METHODS This study was a longitudinal study of cases (n = 53) with preeclampsia and controls (n = 58) consisted of normal pregnant women in matched gestational weeks. Plasma samples were collected at inclusion during pregnancy and 1 year postpartum. Plasma samples were analyzed for levels of S100B and NSE by enzyme-linked immunosorbent assays kits. RESULTS Levels of NSE and S100B in women with preeclampsia were higher during pregnancy than in women with normal pregnancies. One year postpartum, women who have had preeclampsia still had a higher median level of both NSE (5.07 vs. 4.28 mu g/l, P < 0.05) and S100B (0.07 vs. 0.06 mu g/l, P < 0.05) compared to women with previous normal pregnancies. High levels of NSE and S100B postpartum remained associated with previous preeclampsia after adjustment for confounding factors. Levels of NSE correlated to S100B during pregnancy and postpartum. CONCLUSIONS Levels of NSE and S100B are still elevated 1 year postpartum in women who have had preeclampsia in contrast to women with previous normal pregnancies. We hypothesize that there might be a persistent cerebral involvement among women with preeclampsia even 1 year postpartum.
21.	Bergman, Lina, et al. (författare) Effect of Experimental Preeclampsia, Seizure and MgSO4 Treatment in a Rat Model on Serum Levels of S100B and Neuron Specific Enolase Annan publikation (övrigt vetenskapligt/konstnärligt)
22.	Bergman, Lina, et al. (författare) Plasma Levels of S100B in Preeclampsia and Association With Possible Central Nervous System Effects 2014 Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 27:8, s. 1105-1111 Tidskriftsartikel (refereegranskat)abstract BACKGROUND:S100B is supposed to be a peripheral biomarker of central nervous system (CNS) injury. The purpose of this study was to compare levels of S100B in women with preeclampsia with levels in healthy pregnant control subjects and furthermore to analyze levels of S100B in relation to possible CNS effects.METHODS:A cross-sectional case-control study in antenatal care centers in Uppsala, Sweden, was performed. Fifty-three women with preeclampsia and 58 healthy pregnant women were recruited at similar gestational length; women with preeclampsia were recruited at time of diagnosis, and control subjects were recruited during their routine visit to an antenatal clinic. Plasma samples were collected, and levels of S100B were analyzed with an enzyme-linked immunosorbent assay. Information about demographic and clinical characteristics, including symptoms related to CNS affection, was collected from the medical records. The main outcome measures were plasma levels of S100B and possible CNS effects.RESULTS:Levels of S100B were significantly higher among women with preeclampsia than among control subjects (0.12 µg/L vs. 0.07 µg/L; P < 0.001). In preeclampsia, there was a significant association between high levels of S100B and visual disturbances (P < 0.05).CONCLUSIONS:S100B is increased among women with preeclampsia, and high levels of S100B associate with visual disturbances, which might reflect CNS affection in women with preeclampsia.
23.	Bergman, Lina, et al. (författare) Plasma Levels of the Cerebral Biomarker, Neuron-Specific Enolase, are Elevated During Pregnancy in Women Developing Preeclampsia 2016 Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 23:3, s. 395-400 Tidskriftsartikel (refereegranskat)abstract Objectives: Neuron-specific enolase (NSE) is considered to be a peripheral biomarker of central nervous system injury. The aim of this study was to compare levels of NSE throughout pregnancy, in healthy pregnant women and in women developing preeclampsia. Methods: A nested case-control study within a longitudinal study cohort was performed. Four hundred sixty nine healthy pregnant women were enrolled, and plasma samples were collected at gestational weeks 10, 25, 28, 33, and 37. Levels of NSE were analyzed in 16 women with preeclampsia and 36 controls throughout pregnancy with an enzyme-linked immunosorbent assay. Results: In gestational week 37, women who developed preeclampsia had significantly higher plasma levels of NSE than healthy pregnant controls (P < .001). The levels of NSE did not change between gestational weeks 10 and 37 in women who developed preeclampsia, but the levels decreased significantly in healthy pregnant controls (P < .001). Conclusion: In pregnant women developing preeclampsia, the levels of NSE remained high throughout pregnancy, whereas in healthy women, these tended to decline over time, especially at the 2 last time points. The result might be confounded in early pregnancy by extracerebral sources of NSE, such as the corpus luteum. Findings need to be confirmed in a larger prospective study.
24.	Bjersand, Kathrine, 1972-, et al. (författare) The clinical and prognostic correlation of HRNPM and SLC1A5 in pathogenesis and prognosis in epithelial ovarian cancer 2017 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:6 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: To evaluate the prognostic effect of the Heterogeneous nuclear ribonucleoprotein type M (HNRPM) and Solute carrier 1A5 (SLC1A5) in FIGO-stages I-II epithelial ovarian cancer.METHODS: A retrospective cohort study was designed to investigate the prognostic effect of HNRPM and SLC1A5, and the association with clinical-pathologic characteristics in 131 patients with FIGO-stages I-II epithelial ovarian cancer. Tissue microarrays were constructed and protein levels were assessed by immunohistochemistry (IHC).RESULTS: Positive HRNPM status was associated with positive staining for PUMA (P = 0.04), concomitant PUMA and p21 staining (P = 0.005), and VEGF-R2 (P = 0.003). Positive SLC1A5 staining was associated with positive staining of p27 (P = 0.030), PUMA (P = 0.039), concomitant PUMA and p27 staining, and VEGF-R2 (P = 0.039). In non-serous tumors (n = 72), the SLC1A5 positivity was associated with recurrent disease (P = 0.01). In a multivariable logistic regression analysis FIGO-stage (OR = 12.4), tumor grade (OR = 5.1) and SLC1A5 positivity (OR = 0.1) were independent predictive factors for recurrent disease. Disease-free survival (DFS) in women with SLC1A5-positive non-serous tumors was 92% compared with of 66% in patients with SLC1A5-negative non-serous tumors (Log-rank = 15.343; P = 0.008). In Cox analysis with DFS as endpoint, FIGO-stage (HR = 4.5) and SLC1A5 status (HR = 0.3) were prognostic factors.CONCLUSIONS: As the proteins HRNPM and SLC1A5 are associated with the cell cycle regulators p21 or p27, the apoptosis regulators PTEN and PUMA, and the VEGF-R2 it is concluded that both proteins have role in the pathogenesis of ovarian cancer. In patients with non-serous ovarian cancer SLC1A5 protects from recurrent disease, presumably by means of biological mechanisms that are unrelated to cytotoxic drug sensitivity.
25.	Bolin, Marie, et al. (författare) Hyperemesis gravidarum and risks of placental dysfunction disorders : a population-based cohort study 2013 Ingår i: British Journal of Obstetrics and Gynecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 120:5, s. 541-547 Tidskriftsartikel (refereegranskat)abstract Objective To study whether pregnancies complicated by hyperemesis gravidarum in the first (<12weeks) or second (1221weeks) trimester are associated with placental dysfunction disorders. Design Population-based cohort study. Setting Sweden. Population All pregnancies in the Swedish Medical Birth Register estimated to have started on 1 January 1997 or later and ended in a single birth on 31 December 2009 or earlier (n=1156050). Methods Odds ratios with 95% confidence intervals were estimated for placental dysfunction disorders in women with an inpatient diagnosis of hyperemesis gravidarum, using women without inpatient diagnosis of hyperemesis gravidarum as reference. Risks were adjusted for maternal age, parity, body mass index, height, smoking, cohabitation with the infant's father, infant's sex, mother's country of birth, education, presence of hyperthyreosis, pregestational diabetes mellitus, chronic hypertension and year of infant birth. Main outcome measures Placental dysfunction disorders, i.e. pre-eclampsia, placental abruption, stillbirth and small for gestational age (SGA). Results Women with hyperemesis gravidarum in the first trimester had only a slightly increased risk of pre-eclampsia. Women with hyperemesis gravidarum with first admission in the second trimester had a more than doubled risk of preterm (<37weeks) pre-eclampsia, a threefold increased risk of placental abruption and a 39% increased risk of an SGA birth (adjusted odds ratios [95% confidence intervals] were: 2.09 [1.383.16], 3.07 [1.885.00] and 1.39 [1.061.83], respectively). Conclusions There is an association between hyperemesis gravidarum and placental dysfunction disorders, which is especially strong for women with hyperemesis gravidarum in the second trimester.
26.	Bolin, Marie (författare) Pre-eclampsia – Possible to Predict? : A Biochemical and Epidemiological Study of Pre-eclampsia 2012 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Pre-eclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide. A predictor of pre-eclampsia would enable intervention, close surveillance and timely delivery, and thereby reduce the negative consequences of the disorder.The overall aim of this thesis was to study potential predictors of pre-eclampsia by biochemical and epidemiological methods.Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) are regulators of angiogenesis, which is important for placental development. In a prospective and longitudinal study of a low-risk population the Ang-1/Ang-2 ratio was evaluated. The Ang-1/Ang-2 ratio increased during pregnancy in all women but at gestational week 25 and 28 the ratios were significantly lower in women who later developed pre-eclampsia. The relevance of Histidine-rich glycoprotein (HRG), a protein with angiogenic properties, was furthermore evaluated. HRG levels decreased in all women, with significantly lower levels at gestational week 10, 25 and 28 in women who later developed pre-eclampsia. Thus both Ang-1/Ang-2 ratio and HRG may predict pre-eclampsia.To evaluate the predictive value of HRG in combination with uterine artery Doppler early in pregnancy a study was performed in a high-risk population. The results revealed that the combination was better able to predict preterm pre-eclampsia than each marker individually, with a sensitivity of 91% at a specificity of 62%. A possible association between hyperemesis gravidarum and pre-eclampsia, as well as other placental dysfunctional disorders, was investigated. Hyperemesis gravidarum may be caused by high levels of human chorionic gonadotrophin (hCG) and increased levels of hCG in the second trimester is associated with later development of pre-eclampsia. A cohort of all pregnancies in the Swedish medical birth register between 1997 and 2009 was studied. After adjustment for confounding factors an association between hyperemesis gravidarum in the second trimester and preterm pre-eclampsia, placental abruption and infants born small for gestational age was demonstrated.In conclusion, the ratio of Ang-1/Ang-2 as well as HRG in plasma may be potential predictors of pre-eclampsia. Combination with uterine artery Doppler further increases the predictive value of HRG for preterm pre-eclampsia. Hyperemesis gravidarum in the second trimester may be considered as a clinical risk predictor of pre-eclampsia and other placental dysfunctional disorders.
27.	Bolin, Marie, et al. (författare) Prediction of Preeclampsia by Combining Serum Histidine-Rich Glycoprotein and Uterine Artery Doppler 2012 Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 25:12, s. 1305-1310 Tidskriftsartikel (refereegranskat)abstract BackgroundPreeclampsia is associated with both maternal and perinatal morbidity and mortality. Histidine-rich glycoprotein (HRG) is a protein interacting with angiogenesis, coagulation, and inflammatory responses, processes known to be altered in preeclamptic pregnancies. Significantly lower levels of HRG have been demonstrated as early as in the first trimester in women later developing preeclampsia compared with normal pregnancies. The aim of this study was to investigate whether the combination of HRG and uterine artery Doppler ultrasonography can be used as a predictor of preeclampsia.MethodsA total of 175 women were randomly selected from a case-control study; 86 women had an uncomplicated pregnancy and 89 women later developed preeclampsia. Blood samples and pulsatility index (PI) were obtained from both cases and controls in gestational week 14.ResultsHRG levels were significantly lower in women who developed preterm preeclampsia compared with controls, but not for women developing preeclampsia in general. PI was significantly higher in the preeclampsia group compared with controls, especially in preterm preeclampsia. The combination of HRG and PI revealed a sensitivity of 91% and a specificity of 62% for preterm preeclampsia.ConclusionsThe combination of HRG and uterine artery Doppler may predict preterm preeclampsia in early pregnancy.
28.	Dabo, Fatimah, et al. (författare) Different SNP combinations in the GCH1 gene and use of labor analgesia 2010 Ingår i: Molecular Pain. - : SAGE Publications. - 1744-8069. ; 6, s. 41- Tidskriftsartikel (refereegranskat)abstract Background: The aim of this study was to investigate if there is an association between different SNP combinations in the guanosine triphosphate cyclohydrolase (GCH1) gene and a number of pain behavior related outcomes during labor. A population-based sample of pregnant women (n = 814) was recruited at gestational week 18. A plasma sample was collected from each subject. Genotyping was performed and three single nucleotide polymorphisms (SNP) previously defined as a pain-protective SNP combination of GCH1 were used. Results: Homozygous carriers of the pain-protective SNP combination of GCH1 arrived to the delivery ward with a more advanced stage of cervical dilation compared to heterozygous carriers and non-carriers. However, homozygous carriers more often used second line labor analgesia compared to the others. Conclusion: The pain-protective SNP combination of GCH1 may be of importance in the limited number of homozygous carriers during the initial dilation of cervix but upon arrival at the delivery unit these women are more inclined to use second line labor analgesia.
29.	Dabo, Fatimah, et al. (författare) Plasma Levels of beta-Endorphin During Pregnancy and Use of Labor Analgesia 2010 Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 17:8, s. 742-747 Tidskriftsartikel (refereegranskat)abstract beta-endorphins are endogenous opioid substances produced by the pituitary gland and placenta. The aims of this project were to longitudinally follow plasma levels of beta-endorphin during pregnancy in women with a healthy pregnancy and to investigate whether plasma levels of beta-endorphin in late pregnancy are associated with need for additional pain medication beyond nitrous oxide during labor. Plasma samples from 45 women were collected at gestational weeks 10, 25, 28, 33 and 37, and beta-endorphin was analyzed by radioimmunoassay (RIA). Plasma levels of beta-endorphin displayed a significant decrease in gestational weeks 28 and 33 compared to week 10, followed by a subsequent increase between gestational weeks 28 and 37. However, there was no change in levels of beta-endorphin between gestational weeks 10 and 37. Low levels of beta-endorphin at the end of pregnancy were associated with need for additional pain medication beyond nitrous oxide during labor, although the causal relationship is unclear.
30.	Dabo Pettersson, Fatimah, 1975-, et al. (författare) Anxiety, Depressed Mood and the Use of Labor Analgesia 2016 Ingår i: Archives of Women's Mental Health. - : Springer Science and Business Media LLC. - 1434-1816 .- 1435-1102. ; 19:1, s. 11-16 Tidskriftsartikel (refereegranskat)abstract Relatively little is known about mental health and labor pain. The aim of this study was to assess if self-rated antenatal depressed mood and anxiety are associated with pain-related behaviors and self-reported labor pain. We also wanted to replicate our previous finding of altered labor pain behavior in carriers of a specific guanosine triphosphate cyclohydrolase 1 gene (GCH1) haplotype. Ninety-nine women in gestational weeks 37 to 40 filled out questionnaires on depression and anxiety symptoms and later rated their labor pain by use of visual analog scales. Each subject was also genotyped for GCH1. Following adjustment for relevant confounders, women who arrived early to the delivery unit (cervical dilation < 5 cm) had a significantly higher antenatal Montgomery-sberg Depression Rating Scale (MADRS-S) score, p < 0.05, than late arrivers (cervical dilation > 5 cm). Women with increased Spielberger State-Trait Anxiety Inventory (STAI-T) scores reported higher self-rated pain prior to labor analgesia, p < 0.05, than women with low STAI-T scores. No association between the GCH1 pain-protective haplotype and cervical dilation was found, but a previously demonstrated association with increased use of second-line analgesia was confirmed. Depressed mood during pregnancy is associated with early arrival to the delivery department, whereas antenatal anxiety is associated with increased self-rated pain prior to labor analgesia.
31.	Dabo Pettersson, Fatimah, 1975- (författare) Genetics and Labor Pain Behavior 2011 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Labor may perhaps be the most painful a woman might experience, although characterized by large inter-individual variability. The perceived pain during labor is the result of diverse factors, i.e. her previous pain experiences, the analgesia she receives and maybe also her genes. The overall aim of this thesis was to investigate biological and psychological mechanisms underlying inter-individual differences in labor pain related behaviors. The mechanisms that characterize endogenous pain relief during labor are not fully understood, though it is known to be partly explained by the effects of β-endorphin (BE). BE plasma levels were followed longitudinally in a cohort of pregnant women and were found to remain unchanged between early and late pregnancy, although with a nadir in the beginning of the third trimester. Furthermore, women with low levels of BE in plasma at the end of the third trimester, required second line labor analgesia to a significantly higher extent than women with normal levels. In a population-based sample of 814 pregnant women we investigated if inter-individual differences in labor pain related behavior was influenced by the pain-protective single nucleotide polymorphism (SNP) combination of guanosine triphosphate cyclohydrolase (GCH1) and the opioid receptor µ-1 gene (OPRM1) A118G SNP. We identified a possible association between the pain-protective SNP combination of GCH1 and use of second line analgesia. No association was found between the OPRM1 and use of analgesia or labor pain related behavior. The association between self-rated antenatal depressed mood and anxiety in relation to pain behaviors and self-reported pain during labor was investigated. We found that depressed mood during pregnancy is associated with early arrival to the delivery department, whereas antenatal anxiety is associated with increased self-rated pain prior to labor analgesia. In conclusion, although an increasing number of studies strongly suggest that genetic predisposition plays an important role in pain and pain-related mechanisms, GCH1 and OPRM1 has little to offer in terms of individual counseling on labor analgesia. To enable the future use of genetic variability for pre-labor testing and counseling, a number of different genes reflecting pain mediation pathways, involving biological and psychological mechanisms, need to be analyzed in combination.
32.	Dabo Pettersson, Fatimah, 1975-, et al. (författare) The A118G Single Nucleotide Polymorphism of Human μ–Opioid Receptor Gene and Use of Labor Analgesia 2012 Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 19:9, s. 962-967 Tidskriftsartikel (refereegranskat)abstract The human µ-opioid receptor (MOR) is the major site of action of endogenous opioids and most of the clinically used opioid analgesics. The single-nucleotide polymorphism (SNP), A118G of the MOR 1 gene (OPRM1), has been associated with altered pain perception. The aim of this study was to investigate whether this polymorphism of OPRM1 is associated with a number of pain-related behaviors during labor. In this observational retrospective population-based study, pregnant women (n = 814) were recruited at gestational week 18. A plasma sample was collected from each participant and an SNP genotyping assay was performed. No differences in sociodemographic variables or labor pain-related outcomes, such as stage of cervical dilation on arrival at the delivery unit or use of any type of second-line analgesia during spontaneous labor, were found between noncarriers and G-allele carriers of OPRM1. We conclude that there is no association between the A118G polymorphism of OPRM1 regarding pain-related behavior during labor.
33.	Edvinsson, Åsa, 1982-, et al. (författare) Antenatal Depression and Placental Function : A Protein Validated Gene Expression Study 2018 Ingår i: Placenta. - : W B SAUNDERS CO LTD. - 0143-4004 .- 1532-3102. ; 69, s. E62-E62 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
34.	Edvinsson, Åsa, 1982- (författare) Biological Aspects of Peripartum Depression 2019 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Peripartum depression affects around 12% of women in pregnancy and postpartum, and about 2–3% of European pregnant women use antidepressants, mostly selective serotonin reuptake inhibitors (SSRIs). An increased risk of poor pregnancy outcomes has been described in women with antenatal depression and SSRI treatment during pregnancy. The biological mechanisms behind these complications are not fully understood and here we investigated several biological correlates of peripartum depression, and discriminated between the effects of antidepressant treatment and depression itself.In Paper I, attentional biases in pregnant and postpartum women were studied by using the Emotional Stroop Task, measuring reaction times to different stimuli. The major finding was shorter reaction times in postpartum depressed women, for emotionally valenced stimuli, which can be interpreted as emotional numbing.In Paper II, peripheral inflammatory markers were assessed by proximity extension assay technology in depressed, SSRI-treated and healthy pregnant women. Lower levels of 23 markers were found in women with antenatal depression, independent of treatment, compared with healthy controls. These findings suggest a dysregulated switch to the anti-inflammatory M2 milieu characterizing a normal third trimester.In Paper III, normal changes in inflammatory markers across pregnancy and postpartum were assessed in healthy pregnant and postpartum women. The majority (41) of the 50 markers that differed between groups were lower postpartum. These results clearly reflect the change in the immune system in pregnancy to postpartum transition.In Paper IV, placental gene and protein expression were investigated and nominally significant findings were noted for serotonin receptor 1A (HTR1A) and neuropeptide Y2 receptor (NPY2R), where women with untreated depression displayed higher gene expression than healthy controls. Protein expression analyses revealed higher levels of HTR1A in placentas from SSRI-treated women, compared with healthy controls and women with untreated depression. This suggests possible involvement of HTR1A in the effect of antenatal depression on the placenta.Overall, peripartum depression is associated with altered cognitive-emotional processing, lower levels of several mostly anti-inflammatory markers, and altered placental gene and protein expression. However, we found no major differences between untreated and treated depression.
35.	Edvinsson, Åsa, 1982- (författare) Is peripartum depression just another depression? 2016 Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract Depressive symptoms in pregnancy are common, reported by approximately 20% of pregnant women worldwide. Of these, around 4-7% fulfill the criteria for major depressive episode (MDE).The prevalence rates of MDE seem no different from those in non-pregnant women of childbearing ages, or may even be lower. Further, the clinical presentation of depressive symptoms in women of childbearing age does not differ depending on whether women are pregnant, postpartum or outside the peripartum period. For this reason, some researchers argue that peripartum depression is just another depression, merely occurring at a stressful point in life. Antenatal depression and antidepressant treatment have been associated with an increased risk of poor pregnancy outcomes, such as preterm birth, impaired placental function, decreased fetal body and head growth. Nevertheless, little is known about the biological mechanisms behind these complications and more research is needed to elucidate the underlying pathways.In this thesis we have studied 1) attentional bias in antenatal and postpartum depression, with or without antidepressant treatment and 2) peripheral inflammatory markers in pregnancy (depressed, SSRI-treated, healthy controls).The title for this thesis is: Is peripartum depression just another depression? Based on the findings we have obtained thus far, the answer would be no. One argument would be that, as presented in study I, women who suffer from antenatal and postpartum depression do not display the typical attentional bias to negative words that is characteristic of depressive states in the non-pregnant population. Whether this is due to protective mechanisms of pregnancy or due to features that distinguish antenatal and postpartum depression from non-peripartum depression remains to be demonstrated.Secondly, study II describes that women with antenatal depression had significantly lower levels of peripheral inflammatory markers than healthy pregnant controls. Hypothetically, this could be due to dysregulated switch to the antiinflammatory pro-M2 milieu that characterizes normal third trimester pregnancy. These findings are clearly at odds with the literature in non-pregnant samples, where depression has been associated with increased levels of proinflammatory cytokines, but should be interpreted in the context of pregnancy-induced changes in inflammatory response.Moreover, treatment for antenatal depression is not as straightforward as it is in non-pregnant patients. When considering treatment, the expecting mother has to be aware of the risk-benefit profile for herself and the child. While antidepressant therapy clearly improves the mood of treated women, our findings do not indicate that antidepressant treatment has any positive impact on their inflammatory profile.
36.	Edvinsson, Åsa, 1982-, et al. (författare) The effect of antenatal depression and antidepressant treatment on placental tissue : a protein-validated gene expression study. 2019 Ingår i: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393 .- 1471-2393. ; 19 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Antenatal depression affects 10-20% of pregnant women. Around 2-4% of European pregnant women use antidepressant treatment, most commonly selective serotonin reuptake inhibitors (SSRIs). Poor pregnancy outcomes, such as preterm birth and low birth weight, have been described in women with antenatal depression and in pregnant women on SSRI treatment. However, the effects of antenatal depression and antidepressant treatment on the placenta are largely unknown. The aim of this work was to compare placental gene and protein expression in healthy women, women with untreated antenatal depression and women on antidepressant treatment during pregnancy.METHODS: Placental samples from 47 controls, 25 depressed and 45 SSRI-treated women were analysed by means of qPCR using custom-designed TaqMan low-density arrays (TLDAs) for 44 genes previously known to be involved in the pathophysiology of depression, and expressed in the placenta. Moreover, placental protein expression was determined by means of immunohistochemistry in 37 healthy controls, 13 women with untreated depression and 21 women on antidepressant treatment. Statistical comparisons between groups were performed by one-way ANOVA or the Kruskal-Wallis test.RESULTS: Nominally significant findings were noted for HTR1A and NPY2R, where women with untreated depression displayed higher gene expression than healthy controls (p < 0.05), whereas women on antidepressant treatment had similar expression as healthy controls. The protein expression analyses revealed higher expression of HTR1A in placentas from women on antidepressant treatment, than in placentas from healthy controls (p < 0.05).CONCLUSION: The differentially expressed HTR1A, both at the gene and the protein level that was revealed in this study, suggests the involvement of HTR1A in the effect of antenatal depression on biological mechanisms in the placenta. More research is needed to elucidate the role of depression and antidepressant treatment on the placenta, and, further, the effect on the fetus.
37.	Edvinsson, Åsa, 1982-, et al. (författare) The effect of antenatal depression and antidepressant treatment on placental tissue: a protein-validated gene expression study Annan publikation (övrigt vetenskapligt/konstnärligt)
38.	Ehrsson, Ylva Tiblom, et al. (författare) Self-reported sexually transmitted infections among female university students. 2016 Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 121:1, s. 45-49 Tidskriftsartikel (refereegranskat)abstract AIM: To investigate the occurrence of self-reported sexually transmitted infections (STIs) and associated factors among female university students requesting contraceptive counselling.MATERIAL AND METHODS: Cross-sectional study. Female university students (n = 353) completed a waiting-room questionnaire in connection with contraceptive counselling at a Student Health Centre in Uppsala, Sweden.RESULTS: Ninety-three (26.3%) female students had experienced an STI. The three most frequently reported STIs were chlamydia trachomatis, condyloma, and genital herpes. The experience of an STI was significantly associated with the total number of sexual partners (OR 1.060, 95% CI 1.030-1.091, P < 0.001), being heterosexual (OR 4.640, 95% CI 1.321-16.290, P = 0.017), having experienced an abortion (OR 2.744, 95% CI 1.112-6.771, P = 0.028), not being HPV-vaccinated (OR 2.696, 95% CI 1.473-4.935, P = 0.001), and having had intercourse on first night without using a condom (OR 2.375, 95% CI 1.182-4.771, P = 0.015).CONCLUSIONS: Contraceptive counselling should also include information about primary and secondary prevention of STI, such as the importance of correct use of a condom and STI testing, to prevent a further spread of STIs.
39.	Elenis, Evangelia, et al. (författare) Adverse obstetric outcomes in pregnancies resulting from oocyte donation : a retrospective cohort case study in Sweden 2015 Ingår i: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393 .- 1471-2393. ; 15 Tidskriftsartikel (refereegranskat)abstract Background: Oocyte donation has been associated to gestational diabetes, hypertensive disorders, placental abnormalities, preterm delivery and increased rate of caesarean delivery while simultaneously being characterized by high rates of primiparity, advanced maternal age and multiple gestation constituting the individual risk of mode of conception difficult to assess. This study aims to explore obstetrical outcomes among relatively young women with optimal health status conceiving singletons with donated versus autologous oocytes (via IVF and spontaneously). Methods: National retrospective cohort case study involving 76 women conceiving with donated oocytes, 150 nulliparous women without infertility conceiving spontaneously and 63 women conceiving after non-donor IVF. Data on obstetric outcomes were retrieved from the National Birth Medical Register and the medical records of oocyte recipients from the treating University Hospitals of Sweden. Demographic and logistic regression analysis were performed to examine the association of mode of conception and obstetric outcomes. Results: Women conceiving with donated oocytes (OD) had a higher risk of hypertensive disorders [adjusted Odds Ratio (aOR) 2.84, 95 % CI (1.04-7.81)], oligohydramnios [aOR 12.74, 95 % CI (1.24-130.49)], postpartum hemorrhage [aOR 7.11, 95 % CI (2.02-24.97)] and retained placenta [aOR 6.71, 95 % CI (1.58-28.40)] when compared to women who conceived spontaneously, after adjusting for relevant covariates. Similar trends, though not statistically significant, were noted when comparing OD pregnant women to women who had undergone non-donor IVF. Caesarean delivery [aOR 2.95, 95 % CI (1.52-5.71); aOR 5.20, 95 % CI (2.21-12.22)] and induction of labor [aOR 3.00, 95 % CI (1.39-6.44); aOR 2.80, 95 % CI (1.10-7.08)] occurred more frequently in the OD group, compared to the group conceiving spontaneously and through IVF respectively. No differences in gestational length were noted between the groups. With regard to the indication of OD treatment, higher intervention was observed in women with diminished ovarian reserve but the risk for hypertensive disorders did not differ after adjustment. Conclusion: The selection process of recipients for medically indicated oocyte donation treatment in Sweden seems to be effective in excluding women with severe comorbidities. Nevertheless, oocyte recipients-despite being relatively young and of optimal health status-need careful counseling preconceptionally and closer monitoring prenatally for the development of hypertensive disorders.
40.	Elenis, Evangelia (författare) Genetic and epidemiological aspects of implantation defects : Studies on recurrent miscarriage, preeclampsia and oocyte donation 2016 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Implantation requires complex molecular and cellular events involving coagulation, angiogenesis and immunological processes that need to be well regulated for a pregnancy to establish and progress normally. The overall aim of this thesis was to study different models associated with atypical angiogenesis, impaired implantation and/or placentation, such as recurrent miscarriage (RM), oocyte donation (OD) and preeclampsia.Histidine-rich glycoprotein (HRG), a serum protein with angiogenic potential has been previously shown to have an impact on implantation and fertility. In two retrospective case-control studies, women suffering from RM (Study I) and gestational hypertensive disorders (GHD) (Study IV) have been compared to healthy control women, regarding carriership of HRG genotypes (HRG A1042G and C633T SNP, respectively). According to the findings of this thesis, heterozygous carriers of the HRG A1042G SNP suffer from RM more seldom than homozygous carriers (Study I). Additionally, the presence of the HRG 633T allele was associated with increased odds of GHD (GHD IV). Studies II and III comprised a national cohort of relatively young women with optimal health status conceiving singletons with donated oocytes versus autologous oocytes (spontaneously or via IVF). We explored differences in various obstetric (Study II) and neonatal (Study III) outcomes from the Swedish Medical Birth Register. Women conceiving with donated oocytes had a higher risk of GHD, induction of labor and cesarean section, as well as postpartum hemorrhage and retained placenta, when compared to autologously conceiving women. OD infants had higher odds of prematurity and lower birthweight and length when born preterm, compared to neonates from autologous oocytes. With regard to the indication of OD treatment, higher intervention but neverthelss favourable neonatal outcomes were observed in women with diminished ovarian reserve; the risk of GHD did not differ among OD recipients after adjustment.In conclusion, HRG genetic variation appears to contribute to placental dysfunction disorders. HRG is potential biomarker that may contribute in the prediction of the individual susceptibility for RM and GHD. Regarding OD in Sweden, the recipients-despite being of optimal age and health status- need careful preconceptional counselling and closer prenatal monitoring, mainly due to increased prevalence of hypertensive disorders and prematurity.
41.	Endler, Margit, et al. (författare) Oxidative stress and inflammation in retained placenta : a pilot study of protein and gene expression of GPX1 and NF kappa B 2016 Ingår i: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393 .- 1471-2393. ; 16 Tidskriftsartikel (refereegranskat)abstract Background: Retained placenta is associated with severe postpartum hemorrhage. Its etiology is unknown and its biochemistry has not been studied. We aimed to assess whether levels of the antioxidative enzyme Glutathione Peroxidase 1 (GPX1) and the transcription factor Nuclear Factor kappa beta (NF kappa beta), as markers of oxidative stress and inflammation, were affected in retained placentas compared to spontaneously released placentas from otherwise normal full term pregnancies. Methods: In a pilot study we assessed concentrations of GPX1 by ELISA and gene (mRNA) expression of GPX1, NF kappa beta and its inhibitor I kappa beta alpha, by quantitative real-time-PCR in periumbilical and peripheral samples from retained (n = 29) and non-retained (n = 31) placental tissue. Results: Median periumbilical GPX1 concentrations were 13.32 ng/ml in retained placentas and 17.96 ng/ml in nonretained placentas (p = 0.22), peripheral concentrations were 13.27 ng/ml and 19.09 ng/ml (p = 0.08). Retained placental tissue was more likely to have a low GPX1 protein concentration (OR 3.82, p = 0.02 for periumbilical and OR 3.95, p = 0. 02 for peripheral samples). Median periumbilical GPX1 gene expressions were 1.13 for retained placentas and 0.88 for non-retained placentas (p = 0.08), peripheral expression was 1.32 and 1.18 (p = 0.46). Gene expressions of NF kappa beta and I kappa beta alpha were not significantly different between retained and non-retained placental tissue. Conclusions: Women with retained placenta were more likely to have a low level of GPX1 protein concentration in placental tissue compared to women without retained placenta and retained placental tissue showed a tendency of lower median concentrations of GPX1 protein expression. This may indicate decreased antioxidative capacity as a component in this disorder but requires a larger sample to corroborate results.
42.	Granfors, Michaela, 1972- (författare) Hypothyroidism and Pregnancy 2015 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Hypothyroidism is a common endocrine disorder affecting women of reproductive age. On a global level, iodine deficiency is still the most common cause of hypothyroidism. Also genetic variations, in particular SNP rs4704397 in the PDE8B gene, are responsible for a significant proportion of TSH variations. Untreated hypothyroidism has significant adverse effects on pregnancy and fetal outcome. Most international guidelines suggest targeted thyroid testing in pregnant women with risk factors for thyroid disturbances.In a case-control study, an association between homozygous A/A as well as homozygous G/G carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage was found. The explanation for this association is unknown.In a nationwide survey, all guidelines for thyroid testing and management of hypothyroidism during pregnancy in Sweden were collected and compared with international guidelines. The local guidelines were variable and poorly compliant with the international guidelines.In a follow-up in one district, 5,254 pregnant women were included for subsequent review of their medical reports. We found a targeted thyroid testing rate of 20.1% in clinical practice, with an overall frequency of women with trimester-specific elevated TSH of 18.5%. More disturbingly, half of the women who were on levothyroxine treatment at the time of conception had an elevated TSH level at thyroid testing.In a subsequent cohort study of the 5,254 women, we found the prevalence of trimester-specific elevated TSH and overt hypothyroidism to be equal in targeted thyroid tested and untested women.In a cross-sectional study, a median urinary iodine concentration (UIC) of 98 μg/l was found in the study population. According to WHO/UNICEF/IGN criteria, the population-based median UIC during pregnancy should be 150-249 μg/l.In conclusion, genetic variations may contribute to adverse pregnancy outcomes. In clinical practice, thyroid testing and the management of hypothyroidism during pregnancy is unsatisfactory, regarding the whole chain from development of local guidelines to their implementation and to targeted thyroid testing. Moreover, our results indicate insufficient iodine status in the pregnant population of Sweden.
43.	Granfors, Michaela, et al. (författare) Targeted Thyroid Testing During Pregnancy in Clinical Practice 2014 Ingår i: Obstetrics and Gynecology. - 0029-7844 .- 1873-233X. ; 124:1, s. 10-15 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE:To evaluate the efficacy of a targeted thyroid testing approach during pregnancy in clinical practice.METHODS:This is a retrospective cohort study performed within Uppsala County, Sweden. Data were derived from the population-based Uppsala Biobank of Pregnant Women, in which blood samples are collected in conjunction with the routine ultrasound screening in gestational week 17-19. For this study, 5,254 pregnant women with an estimated date of delivery between January 1, 2009, and December 31, 2011, were included. On review of their medical records, women who were tested for thyroid dysfunction during pregnancy in clinical practice were identified (n=891). From the remaining untested women, 1,006 women were randomly selected for analyses of thyrotropin (TSH), free thyroxine levels, and thyroid peroxidase antibodies. Thyroid-stimulating hormone levels in both groups were analyzed with regard to trimester-specific upper reference levels as recommended by the International Endocrine Society Guidelines.RESULTS:The proportion of trimester-specific TSH elevation was 12.6% in the targeted thyroid testing group and 12.1% in the untested group (P=.8; odds ratio [OR] 1.04, 95% confidence interval [CI] 0.79-1.37). The proportion of overt hypothyroidism was 1.1% and 0.7% in the groups, respectively (P=.4; OR 1.57, 95% CI 0.55-4.45).CONCLUSIONS:The prevalence of trimester-specific elevated TSH and overt hypothyroidism was equal in targeted thyroid tested and untested women. When implemented in clinical practice, targeted thyroid testing is unsatisfactory. If ongoing studies provide support for treatment of pregnant women with elevated TSH, universal thyroid testing appears the most reasonable approach.
44.	Granfors, Michaela, 1972-, et al. (författare) Thyroid Testing and Management of Hypothyroidism During Pregnancy : A Population-based Study 2013 Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:7, s. 2687-2692 Tidskriftsartikel (refereegranskat)abstract Context: There are international guidelines on thyroid function testing and management of hypothyroidism during pregnancy. Few studies have evaluated how they are implemented into clinical practice. Objective: In this descriptive study, we assessed the implementation of international guidelines in this field into local guidelines and also into clinical practice. Design and Participants: In a nationwide survey, all guidelines in Sweden were collected (n = 29), and the adherence of the local guidelines to The Endocrine Society Guidelines 2007 was evaluated. In a follow-up in 1 district, 5254 pregnant women with an estimated date of delivery between January 1, 2009, and December 31, 2011, were included for subsequent review of their medical reports. Results: All but 1 district had guidelines on the subject. All local guidelines included fewer than the 10 listed reasons for thyroid testing recommended by The Endocrine Society Guidelines. Furthermore, most guidelines recommended additional types of thyroid function tests to TSH sampling and lower trimester-specific TSH upper reference limits for women on levothyroxine treatment (P < .001). In the follow-up, the thyroid testing rate was 20%, with an overall frequency of women with trimester-specific elevated TSH of 18.5%. More than half of the women (50.9%) who were on levothyroxine treatment at conception had an elevated TSH level at thyroid testing according to The Endocrine Society Guidelines. Conclusions: The local guidelines are variable and poorly compliant with international guidelines. Performance of thyroid testing is not optimal, and rates of elevated TSH at testing are extremely high in subgroups.
45.	Hellgren, Charlotte, 1985-, et al. (författare) Cortisol awakening response in late pregnancy in women with previous or ongoing depression 2013 Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 38:12, s. 3150-3154 Tidskriftsartikel (refereegranskat)abstract Pregnancy is associated with increased basal cortisol levels, and decreased hypothalamic-pituitary-adrenal (HPA) axis reactivity. The cortisol awakening response (CAR) is a measure of HPA-axis reactivity which has been reported to be increased in patients with ongoing depressive disorder and in individuals with remitted depression. In this study, we investigated HPA-axis reactivity in pregnant women with ongoing or previous depression. The CAR was assessed by measurement of salivary cortisol at awakening and 15, 30, and 45min post-awakening. Based on structured psychiatric interviews and repeated measurements of depressive symptoms during pregnancy, 134 women were included in one of the three groups: never depressed (n=57), depressed prior to the current pregnancy (n=39), and depressed during the current pregnancy (n=38). Given the prior findings of increased CAR in non-pregnant depressed subjects, we hypothesized that an ongoing or previous depression would result in a higher CAR. Contrary to our hypothesis, a mixed models analysis failed to yield significant group differences. Thus, our results suggest that never depressed pregnant women and women with depression during pregnancy have similar cortisol awakening responses. Furthermore, our findings suggest that the cortisol awakening response does not differ between currently healthy women with and without experience of a depressive episode during late pregnancy.
46.	Hellgren, Charlotte, 1985-, et al. (författare) Cortisol awakening response in late pregnancy in women with previous or ongoing depression 2013 Ingår i: Psychoneuroendocrinology. - 0306-4530 .- 1873-3360. ; 38:12, s. 3150-54 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Pregnancy involves an increase in basal cortisol, and a decrease in the hypothalamic-pituitary-adrenal (HPA) axis reactivity. The cortisol awakening response is a measure of HPA axis reactivity which has been reported to be altered in patients with an ongoing depressive episode, as well as in individuals with remitted depression.This study aimed to use the cortisol awakening response to study the HPA axis reactivity in relation to previous and ongoing depression in women during the third trimester of pregnancy. Based on structured interviews, and repeated questionnaires during pregnancy, 134 women were included in one of three groups: never depressed (n=57), depressed prior to the current pregnancy (n=39), and depressed during the current pregnancy (n=38). The hypothesis was that the women with ongoing, or previous, depression would have a higher cortisol awakening response than women who have never suffered from depression.Linear mixed models analysis revealed no group differences in the absolute cortisol levels or in the shape of the cortisol awakening response. We conclude that the difference in cortisol awakening response between women with and without experience of a depressive episode is not evident in late pregnancy.
47.	Hellgren, Charlotte, et al. (författare) Decreased startle modulation during anticipation in the postpartum period in comparison to late pregnancy 2012 Ingår i: Archives of Women's Mental Health. - : Springer Science and Business Media LLC. - 1434-1816 .- 1435-1102. ; 15:2, s. 87-94 Tidskriftsartikel (refereegranskat)abstract Knowledge about healthy women's psychophysiological adaptations during the large neuroendocrine changes of pregnancy and childbirth is essential in order to understand why these events have the potential to disrupt mental health in vulnerable individuals. This study aimed to compare startle response modulation, an objective psychophysiological measure demonstrated to be influenced by anxiety and depression, longitudinally across late pregnancy and the postpartum period. The acoustic startle response modulation was assessed during anticipation of affective images and during image viewing in 31 healthy women during gestational weeks 36-39 and again at 4 to 6 weeks postpartum. No startle modulation by affective images was observed at either time point. Significant modulation during anticipation stimuli was found at pregnancy assessment but was reduced in the postpartum period. The women rated the unpleasant images more negative and more arousing and the pleasant images more positive at the postpartum assessment. Self-reported anxiety and depressive symptoms did not change between assessments. The observed postpartum decrease in modulation of startle by anticipation suggests a relatively deactivated defense system in the postpartum period.
48.	Hellgren, Charlotte, et al. (författare) Low serum allopregnanolone is associated with elevated depressive symptoms in late pregnancy 2012 Ingår i: European Neuropsychopharmacology. - 0924-977X .- 1873-7862. ; 22, s. S228-S228 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
49.	Hellgren, Charlotte, et al. (författare) Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy 2014 Ingår i: Neuropsychobiology. - : S. Karger AG. - 0302-282X .- 1423-0224. ; 69:3, s. 147-153 Tidskriftsartikel (refereegranskat)abstract Allopregnanolone (3α-hydroxy-5α-pregnan-20-one) is a neurosteroid which has inhibitory function through interaction with the GABAA receptor. This progesterone metabolite has strong sedative and anxiolytic properties, and low endogenous levels have been associated with depressed mood. This study aimed to investigate whether the very high serum allopregnanolone levels in late pregnancy co-vary with concurrent self-rated symptoms of depression and anxiety. Ninety-six women in pregnancy weeks 37 - 40 rated symptoms of depression and anxiety with the Montgomery-Åsberg Depression Rating Scale (MADRS-S) and Spielberger State-Trait Anxiety Inventory (STAI-S and STAI–T). Their serum allopregnanolone was analyzed by celite chromatography and radioimmunoassay. Ten women had elevated depression scores (MADRS-S ≥ 13), and this group had significantly lower allopregnanolone levels compared to women with MADRS-S scores in the lower range (39.0 ± 17.9 nmol/l vs. 54.6 ± 18.7 nmol/l, p = 0.014). A significant negative correlation was found between self-rated depression scores and allopregnanolone concentrations (Pearson’s correlation coefficient = -0.220, p = 0.031). The linear association between self-rated depression scores and allopregnanolone serum concentrations remained significant when adjusted for gestational length, progesterone levels, and parity. Self-rated anxiety, however, was not associated with allopregnanolone serum concentrations during pregnancy. In conclusion, high allopregnanolone serum concentrations may protect against depressed mood during pregnancy.
50.	Hellgren, Charlotte, 1985- (författare) Physiological Stress Reactivity in Late Pregnancy 2013 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract During pregnancy, the basal activity is increased in both of our major stress response systems: the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. At the same time, the reactivity towards stressors is reduced. These alterations sustain maternal and fetal homeostasis, and are involved in the regulation of gestational length. Although the feto-placental hormone synthesis produces the main endocrinological changes, also the central nervous system undergoes adaptation. Together, these profound adjustments have been suggested to make women’s mental health more vulnerable during pregnancy and postpartum period. The aim of this thesis was to examine factors connected to physiological stress responses during the late pregnancy in relation to pain, labour onset, emotional reactivity, and mental health.The first study examined the pain and sympathetic response during cold stress, in relation to time to delivery. Women with fewer days to spontaneous delivery had lower sympathetic reactivity, while no pain measure was associated with time to delivery.In the second study, acoustic startle response modulation was employed to study emotional reactivity during late gestation, and at four to six weeks postpartum. The startle response was measured by eye-blink electromyography, while the participants watched pleasant and unpleasant pictures, and positive and negative anticipation stimuli. A significant reduction in startle modulation by anticipation was found during the postpartum assessment. However, no startle modulation by pleasant, or unpleasant, pictures was detected at either time-point.The serum level of allopregnanolone, a neurosteroid implied in pregnancy-induced hyporeactivity, was analysed in relation to self-reported symptoms of anxiety and depression. Although the participants reported low levels of depression, the women with the highest depression scores had significantly lower levels of serum allopregnanolone. There was no correlation between allopregnanolone and anxiety scores.In the fourth study, the cortisol awakening response was compared between women with depression during pregnancy, women with depression prior to pregnancy, and women who had never suffered from depression. No group differences in cortisol awakening response during late pregnancy were found.The results are in line with the previously described pregnancy-induced hyporesponsiveness, and add to the knowledge on maternal stress hyporeactivity, gestational length, and maternal mental health.

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