Publications by authors named "Anne Cathrine Staff"

153 Publications

Audit of Early and Late Maternal Deaths in Georgia: Potential for Improving Substandard Obstetric Care.

Int J Womens Health 2021 17;13:205-219. Epub 2021 Feb 17.

Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

Introduction: Quality of care is an important factor in reducing preventable maternal deaths, yet it is a significant challenge in many countries. Substandard and poor quality of care is the leading factor in two-thirds of maternal deaths in European countries. Our study investigated the deaths of all women of reproductive age in 2012 in Georgia. The aim was to define the underlying causes of maternal deaths and to identify the factors in women's care which contributed to the fatal outcomes.

Methods: A national Reproductive Age Mortality Survey was conducted in Georgia in 2014-15. Data from multiple sources was triangulated to identify all deaths of women of reproductive age. This was followed by verbal autopsy diagnoses. Each case of early and late maternal death was investigated through interviews and medical record reviews at the last medical facility providing care for the deceased woman. A specialist panel reviewed and assigned underlying causes of death, assessed the management of each woman's condition, and identified elements of suboptimal care.

Results: We identified a total of 23 maternal deaths, including 15 (65%) early and eight (35%) late deaths. The maternal mortality ratio was 26.3 per 100 000 live births. The four leading causes of early maternal deaths were: sepsis, hemorrhage, embolism, and pregnancy-induced hypertension. Embolism and sepsis were the direct causes of the eight late maternal deaths. Cancer, tuberculosis, and postpartum suicide constituted the indirect causes of death. Improvements in care which would have made a difference to the outcomes were identified in 87% of early maternal deaths and 67% of late maternal deaths due to direct obstetric causes.

Discussion: Delayed recognition and inappropriate management of maternal complications were common across almost all cases studied. The findings from Georgia highlight the conclusion that most maternal deaths were preventable and that improvement in obstetric care is urgently required.
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http://dx.doi.org/10.2147/IJWH.S288763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899038PMC
February 2021

A possible role for HLA-G in development of uteroplacental acute atherosis in preeclampsia.

J Reprod Immunol 2021 04 2;144:103284. Epub 2021 Feb 2.

Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Norway; Division of Obstetrics and Gyneacology, Oslo University Hospital, Norway.

HLA-G, a non-classical HLA molecule expressed by extravillous trophoblasts, plays a role in the maternal immune tolerance towards fetal cells. HLA-G expression is regulated by genetic polymorphisms in the 3' untranslated region (3'UTR). Low levels of HLA-G in the maternal circulation and placental tissue are linked to preeclampsia. Our objective was to investigate whether variants of the 3'UTR of the HLA-G gene in mother and fetus are associated with acute atherosis, a pregnancy specific arterial lesion of the decidua basalis that is prevalent in preeclampsia. Paired maternal and fetal DNA samples from 83 normotensive and 83 preeclamptic pregnancies were analyzed. We sequenced the part of the HLA-G 3'UTR containing a 14-bp insertion/deletion region and seven single nucleotide polymorphisms (SNPs). Associations with acute atherosis were tested by logistic regression. The frequency of heterozygosity for the 14-bp polymorphism (Ins/Del) and the +3142 SNP (C/G) variant in the fetus are associated with acute atherosis in preeclampsia (66.7 % vs. 39.6 %, p = 0.039, and 69.0 % vs. 43.4 %, p = 0.024). Furthermore, the fetal UTR-3 haplotype, which encompasses the 14-bp deletion and the +3142G variant, is associated with acute atherosis in preeclampsia (15 % vs. 3.8 %, p = 0.016). In conclusion, HLA-G polymorphisms in the fetus are associated with acute atherosis. We hypothesize that these polymorphisms lead to altered HLA-G expression in the decidua basalis, affecting local feto-maternal immune tolerance and development of acute atherosis.
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http://dx.doi.org/10.1016/j.jri.2021.103284DOI Listing
April 2021

Syncytiotrophoblast stress in preeclampsia: the convergence point for multiple pathways.

Am J Obstet Gynecol 2020 Nov 8. Epub 2020 Nov 8.

Magee-Womens Research Institute, Magee-Womens Research Institute and Foundation, Pittsburgh, PA, Departments of Obstetrics, Gynecology, and Reproductive Sciences and Epidemiology, University of Pittsburgh, Pittsburgh, PA, and Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA.

Preeclampsia evolves in 2 stages: a placental problem that generates signals to the mother to cause a range of responses that comprise the second stage (preeclampsia syndrome). The first stage of early-onset preeclampsia is poor placentation, which we here call malplacentation. The spiral arteries are incompletely remodeled, leading to later placental malperfusion, relatively early in the second half of pregnancy. The long duration of the first stage (several months) is unsurprisingly associated with fetal growth restriction. The first stage of late-onset preeclampsia, approximately 80% of total cases, is shorter (several weeks) and part of a process that is common to all pregnancies. Placental function declines as it outgrows uterine capacity, with increasing chorionic villous packing, compression of the intervillous space, and fetal hypoxia, and causes late-onset clinical presentations such as "unexplained" stillbirths, late-onset fetal growth restriction, or preeclampsia. The second stages of early- and late-onset preeclampsia share syncytiotrophoblast stress as the most relevant feature that causes the maternal syndrome. Syncytiotrophoblast stress signals in the maternal circulation are probably the most specific biomarkers for preeclampsia. In addition, soluble fms-like tyrosine kinase-1 (mainly produced by syncytiotrophoblast) is the best-known biomarker and is routinely used in clinical practice in many locations. How the stress signals change over time in normal pregnancies indicates that syncytiotrophoblast stress begins on average at 30 to 32 weeks' gestation and progresses to term. At term, syncytiotrophoblast shows increasing markers of stress, including apoptosis, pyroptosis, autophagy, syncytial knots, and necrosis. We label this phenotype the "twilight placenta" and argue that it accounts for the clinical problems of postmature pregnancies. Senescence as a stress response differs in multinuclear syncytiotrophoblast from that of mononuclear cells. Syncytiotrophoblast irreversibly acquires part of the senescence phenotype (cell cycle arrest) when it is formed by cell fusion. The 2 pathways converge on the common pathologic endpoint, syncytiotrophoblast stress, and contribute to preeclampsia subtypes. We highlight that the well-known heterogeneity of the preeclampsia syndrome arises from different pathways to this common endpoint, influenced by maternal genetics, epigenetics, lifestyle, and environmental factors with different fetal and maternal responses to the ensuing insults. This complexity mandates a reassessment of our approach to predicting and preventing preeclampsia, and we summarize research priorities to maximize what we can learn about these important issues.
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http://dx.doi.org/10.1016/j.ajog.2020.09.047DOI Listing
November 2020

Fecal Microbiota Nutrient Utilization Potential Suggests Mucins as Drivers for Initial Gut Colonization of Mother-Child-Shared Bacteria.

Appl Environ Microbiol 2021 02 26;87(6). Epub 2021 Feb 26.

Faculty of Chemistry, Biotechnology, and Food Science, Norwegian University of Life Sciences, Ås, Norway

The nutritional drivers for mother-child sharing of bacteria and the corresponding longitudinal trajectory of the infant gut microbiota development are not yet completely settled. We therefore aimed to characterize the mother-child sharing and the inferred nutritional utilization potential for the gut microbiota from a large unselected cohort. We analyzed in depth gut microbiota in 100 mother-child pairs enrolled antenatally from the general population-based Preventing Atopic Dermatitis and Allergies in Children (PreventADALL) cohort. Fecal samples collected at gestational week 18 for mothers and at birth (meconium), 3, 6, and 12 months for infants were analyzed by reduced metagenome sequencing to determine metagenome size and taxonomic composition. The nutrient utilization potential was determined based on the Virtual Metabolic Human (VMH, www.vmh.life) database. The estimated median metagenome size was ∼150 million base pairs (bp) for mothers and ∼20 million bp at birth for the children. Longitudinal analyses revealed mother-child sharing ( < 0.05, chi-square test) from birth up to 6 months for 3 prevalent species (prevalence, >25% for all age groups). In a multivariate analysis of variance (ANOVA), the mother-child-shared were associated with vaginal delivery (1.7% explained variance,  = 0.0001). Both vaginal delivery and mother-child sharing were associated with host-derived mucins as nutrient sources. The age-related increase in metagenome size corresponded to an increased diversity in nutrient utilization, with dietary polysaccharides as the main age-related factor. Our results support host-derived mucins as potential selection means for mother-child sharing of initial colonizers, while the age-related increase in diversity was associated with dietary polysaccharides. The initial bacterial colonization of human infants is crucial for lifelong health. Understanding the factors driving this colonization will therefore be of great importance. Here, we used a novel high-taxonomic-resolution approach to deduce the nutrient utilization potential of the infant gut microbiota in a large longitudinal mother-child cohort. We found mucins as potential selection means for the initial colonization of mother-child-shared bacteria, while the transition to a more adult-like microbiota was associated with dietary polysaccharide utilization potential. This knowledge will be important for a future understanding of the importance of diet in shaping the gut microbiota composition and development during infancy.
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http://dx.doi.org/10.1128/AEM.02201-20DOI Listing
February 2021

Pregnancy and postpartum levels of circulating maternal sHLA-G in preeclampsia.

J Reprod Immunol 2021 02 17;143:103249. Epub 2020 Nov 17.

Division of Obstetrics and Gynaecology, Oslo University Hospital, Norway; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.

Preeclampsia is a leading cause of maternal and offspring mortality and morbidity, and predicts increased future cardiovascular disease risk. Placental dysfunction and immune system dysregulation are likely key pathophysiological factors. Soluble human leukocyte antigen G (sHLA-G) may dampen the specific immune response towards placental trophoblasts. Previous studies have shown low sHLA-G levels in preeclampsia, but postpartum, levels are unknown. Furthermore, the relationship between sHLA-G and sFlt-1 and PlGF, placental function markers, is unknown. We hypothesized that low maternal sHLA-G during pregnancy would be associated with placental dysfunction, including preeclampsia, gestational hypertension, and dysregulated sFlt-1 and PlGF, and that sHLA-G would remain decreased following preeclampsia. We included 316 pregnant women: 58 with early-onset preeclampsia (<34 weeks' gestation), 81 with late-onset preeclampsia (≥34 weeks' gestation), 25 with gestational hypertension, and 152 normotensive controls. Postpartum (1 or 3 years), we included 321 women: 29 with early-onset preeclampsia, 98 with late-onset preeclampsia, 57 with gestational hypertension, and 137 who were normotensive during their index pregnancies. In pregnancy, plasma sHLA-G was significantly lower both in the early- and late-onset preeclampsia groups compared to controls. In women with preeclampsia or gestational hypertension, sHLA-G was inversely correlated with serum sFlt-1. Postpartum, plasma sHLA-G levels were significantly higher in women who had had early-onset preeclampsia compared to controls. Our results support that sHLA-G may be important for placental function. Unexpectedly, sHLA-G was elevated up to 3 years after early-onset preeclampsia, suggesting an excessively activated immune system following this severe preeclampsia form, potentially contributing to future cardiovascular disease risk.
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http://dx.doi.org/10.1016/j.jri.2020.103249DOI Listing
February 2021

Will Postnatal Renin-Angiotensin System Blockade Improve Long-Term Maternal Cardiovascular Health After Preeclampsia?

Hypertension 2020 12 11;76(6):1704-1706. Epub 2020 Nov 11.

HELIOS Clinic, Berlin, Germany (R.D.).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16229DOI Listing
December 2020

De novo species identification using 16S rRNA gene nanopore sequencing.

PeerJ 2020 21;8:e10029. Epub 2020 Oct 21.

Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.

Nanopore sequencing is rapidly becoming more popular for use in various microbiota-based applications. Major limitations of current approaches are that they do not enable de novo species identification and that they cannot be used to verify species assignments. This severely limits applicability of the nanopore sequencing technology in taxonomic applications. Here, we demonstrate the possibility of de novo species identification and verification using hexamer frequencies in combination with k-means clustering for nanopore sequencing data. The approach was tested on the human infant gut microbiota of 3-month-old infants. Using the hexamer k-means approach we identified two new low abundant species associated with vaginal delivery. In addition, we confirmed both the vaginal delivery association for two previously identified species and the overall high levels of bifidobacteria. Taxonomic assignments were further verified by mock community analyses. Therefore, we believe our de novo species identification approach will have widespread application in analyzing microbial communities in the future.
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http://dx.doi.org/10.7717/peerj.10029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585375PMC
October 2020

Butyrate Levels in the Transition from an Infant- to an Adult-Like Gut Microbiota Correlate with Bacterial Networks Associated with and .

Genes (Basel) 2020 Oct 22;11(11). Epub 2020 Oct 22.

Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, 1430 Ås, Norway.

Relatively little is known about the ecological forces shaping the gut microbiota composition during infancy. Therefore, the objective of the present study was to identify the nutrient utilization- and short-chain fatty acid (SCFA) production potential of gut microbes in infants during the first year of life. Stool samples were obtained from mothers at 18 weeks of pregnancy and from infants at birth (first stool) at 3, 6, and 12-months of age from the general population-based PreventADALL cohort. We identified the taxonomic and SCFA composition in 100 mother-child pairs. The SCFA production and substrate utilization potential of gut microbes were observed by multiomics (shotgun sequencing and proteomics) on six infants. We found a four-fold increase in relative butyrate levels from 6 to 12 months of infant age. The increase was correlated to and its bacterial network, and relative abundance, while low butyrate at 12 months was correlated to and its associated network of bacteria. Both and expressed enzymes needed for butyrate production and enzymes related to dietary fiber degradation, while expressed mucus-, fucose, and human milk oligosaccharides (HMO)-related degradation enzymes. Therefore, we believe that the presence of its network, and are key bacteria in the transition from an infant- to an adult-like gut microbiota with respect to butyrate production. Our results indicate that the transition from an infant- to an adult-like gut microbiota with respect to butyrate producing bacteria, occurs between 6 and 12 months of infant age. The bacteria associated with the increased butyrate ratio/levels were and , which potentially utilize a variety of dietary fibers based on the glycoside hydrolases (GHs) expressed. with a negative association to butyrate potentially utilizes mucin, fucose, and HMO components. This knowledge could have future importance in understanding how microbial metabolites can impact infant health and development.
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http://dx.doi.org/10.3390/genes11111245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690385PMC
October 2020

Fetal microchimerism and implications for maternal health.

Obstet Med 2020 Sep 6;13(3):112-119. Epub 2019 Dec 6.

Division of Obstetrics and Gyneacology, Oslo University Hospital, Oslo, Norway.

This review paper outlines the definition, pathophysiology, and potential maternal health consequences of cellular fetal microchimerism, the maternal acquisition of intact cells of fetal origin during pregnancy. Increased rates and amounts of cellular fetal microchimerism are associated with several placental syndromes, including preeclampsia and fetal growth restriction. The discovery of cellular fetal microchimerism and methods of detection are briefly outlined, and we present the mechanisms hypothesized to govern pregnancy-related and long-term maternal health effects of cellular fetal microchimerism. Specifically, we discuss the potential implications of cellular fetal microchimerism in wound healing, autoimmunity, cancer, and possibly cardiovascular disease. Cellular fetal microchimerism represents a novel area of research on maternal and transgenerational health and disease, providing exciting opportunities for developing new disease biomarkers and precision medicine with targeted prophylaxis against long-term maternal disease.
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http://dx.doi.org/10.1177/1753495X19884484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543167PMC
September 2020

Allergic disease and risk of stress in pregnant women: a PreventADALL study.

ERJ Open Res 2020 Oct 13;6(4). Epub 2020 Oct 13.

Dept of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.

Background: Maternal stress during pregnancy may negatively affect the health of mother and child. We therefore aimed to identify the proportion of women reporting high maternal stress in mid and late pregnancy and explore whether symptoms of maternal allergic disease are associated with perceived maternal stress in late pregnancy.

Method: The population-based Preventing Atopic Dermatitis and Allergy in Children (PreventADALL) study enrolled 2697 pregnant women at their 18-week routine ultrasound examination in Norway and Sweden. Information about sociodemographic factors, symptoms and doctor-diagnosed asthma, allergic rhinitis, atopic dermatitis, food allergy, and anaphylaxis and stress using the 14-item perceived stress scale (PSS) was collected at 18 weeks (mid) and 34 weeks (late) pregnancy. High stress was defined as a PSS score ≥29. Scores were analysed using multivariate logistic and linear regression.

Results: Among the 2164 women with complete PSS data, 17% reported asthma, 20% atopic dermatitis, 23% allergic rhinitis, 12% food allergy and 2% anaphylaxis. The proportion of women reporting high stress decreased from 15% at mid to 13% at late pregnancy (p<0.01). The adjusted odds ratio for high stress in late pregnancy was 2.25 (95% CI 1.41-3.58) for self-reported symptoms of asthma, 1.46 (95% CI 1.02-2.10) for allergic rhinitis and 2.25 (95% CI 1.32-3.82) for food allergy. A multivariate linear regression model confirmed that symptoms of asthma (β coefficient 2.11; 0.71-3.51), atopic dermatitis (β coefficient 1.76; 0.62-2.89) and food allergy (β coefficient 2.24; 0.63-3.84) were independently associated with increased PSS score.

Conclusion: Allergic disease symptoms in pregnancy were associated with increased stress, highlighting the importance of optimal disease control in pregnancy.
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http://dx.doi.org/10.1183/23120541.00175-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553112PMC
October 2020

Maternal placental growth factor and soluble fms-like tyrosine kinase-1 reference ranges in post-term pregnancies: A prospective observational study.

PLoS One 2020 20;15(10):e0240473. Epub 2020 Oct 20.

Division of Obstetrics and Gynaecology, Oslo University Hospital Ullevål, Oslo, Norway.

Background: Post-term pregnancies have increased risks for adverse fetal and maternal outcomes. Maternal concentrations of the placenta-associated proteins placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) have been identified as predictors for preeclampsia and fetal growth restriction, both syndromes of placental dysfunction. We have proposed that low maternal circulating PlGF and increased sFlt-1 are general markers for syncytiotrophoblast stress, which increases at and beyond term, even in apparently uncomplicated pregnancies. Our aim was to establish circulating PlGF, sFlt-1, and sFlt-1/PlGF reference ranges in healthy post-term pregnancies (gestational week ≥40+2), comparing with healthy term pregnancies and evaluating associations between time to delivery and biomarker percentiles.

Methods: Of 501 healthy, singleton post-term pregnancies prospectively recruited between September 2016 and December 2017 at our tertiary obstetric department, 426 with an uncomplicated delivery outcome contributed PlGF and sFlt-1 serum concentrations for reference range construction. A retrospective, cross-sectional, term group with an uncomplicated delivery outcome (n = 146) served as comparison. Differences in percentile values between groups and confidence intervals were calculated by quantile regression.

Results: In post-term pregnancies the 5th, 50th, and 95th percentiles for PlGF were: 70, 172, and 496 pg/mL; for sFlt-1: 2074, 4268, and 9141 pg/mL; and for sFlt-1/PlGF 5.3, 25.5, and 85.2. Quantile regression analyses comparing the post-term to the term group showed for PlGF a trend towards higher 10th through 30th percentiles, for sFlt-1 significantly higher 10th through 80th percentiles, and for sFlt-1/PlGF ratio significantly higher 30th percentile and significantly lower 95th percentile. PlGF below the 5th percentile and sFlt-1/PlGF ratio above the 95th percentile was associated with shorter time to delivery (p = 0.031 and p = 0.025, respectively).

Conclusions: Our findings support the concept of increasing syncytiotrophoblast stress post-term in clinically healthy pregnancies. Whether post-term dysregulated angiogenic markers reflect a biological placental clock merits further investigation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240473PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575115PMC
December 2020

Failure of physiological transformation and spiral artery atherosis: their roles in preeclampsia.

Am J Obstet Gynecol 2020 Sep 21. Epub 2020 Sep 21.

Division of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.

Physiological transformation with remodeling of the uteroplacental spiral arteries is key to a successful placentation and normal placental function. It is an intricate process that involves, but is not restricted to, complex interactions between maternal decidual immune cells and invasive trophoblasts in the uterine wall. In normal pregnancy, the smooth muscle cells of the arterial tunica media of uteroplacental spiral arteries are replaced by invading trophoblasts and fibrinoid, and the arterial diameter increases 5- to 10-fold. Poor remodeling of the uteroplacental spiral arteries is linked to early-onset preeclampsia and several other major obstetrical syndromes, including fetal growth restriction, placental abruption, and spontaneous preterm premature rupture of membranes. Extravillous endoglandular and endovenous trophoblast invasions have recently been put forth as potential contributors to these syndromes as well. The well-acknowledged disturbed extravillous invasion of maternal spiral arteries in preeclampsia is summarized, as are briefly novel concepts of disturbed extravillous endoglandular and endovenous trophoblast invasions. Acute atherosis is a foam cell lesion of the uteroplacental spiral arteries associated with poor remodeling. It shares some morphologic features with early stages of atherosclerosis, but several molecular differences between these lesions have also recently been revealed. Acute atherosis is most prevalent at the maternal-fetal interface, at the tip of the spiral arteries. The localization of acute atherosis downstream of poorly remodeled arteries suggests that alterations in blood flow may trigger inflammation and foam cell development. Acute atherosis within the decidua basalis is not, however, confined to unremodeled areas of spiral arteries or to hypertensive disorders of pregnancy and may even be present in some clinically uneventful pregnancies. Given that foam cells of atherosclerotic lesions are known to arise from smooth muscle cells or macrophages activated by multiple types of inflammatory stimulation, we have proposed that multiple forms of decidual vascular inflammation may cause acute atherosis, with or without poor remodeling and/or preeclampsia. Furthermore, we propose that acute atherosis may develop at different gestational ages, depending on the type and degree of the inflammatory insult. This review summarizes the current knowledge of spiral artery remodeling defects and acute atherosis in preeclampsia. Some controversies will be presented, including endovascular and interstitial trophoblast invasion depths, the concept of 2-stage trophoblast invasion, and whether the replacement of maternal spiral artery endothelium by fetal endovascular trophoblasts is permanent. We will discuss the role of acute atherosis in the pathophysiology of preeclampsia and short- and long-term health correlates. Finally, we suggest future opportunities for research on this intriguing uteroplacental interface between the mother and fetus.
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http://dx.doi.org/10.1016/j.ajog.2020.09.026DOI Listing
September 2020

Stromal Cell-Derived Factor (SDF) 2 and the Endoplasmic Reticulum Stress Response of Trophoblast Cells in Gestational Diabetes Mellitus and Hyperglycaemic Condition.

Curr Vasc Pharmacol 2021 ;19(2):201-209

Institute of Biomedical Sciences, Department of Cell and Developmental Biology, University of São Paulo, 05508-000 São Paulo, SP, Brazil.

Background And Aim: The endoplasmic reticulum (ER) stress response and the unfolded protein response (UPR) are essential cellular mechanisms to ensure the proper functioning of ER in adverse conditions. However, activation of these pathways has also been associated with insulin resistance and cell death in pathological conditions such as diabetes mellitus. In the present study, we investigated whether stromal cell-derived factor 2 (SDF2)-an ER stress-responsive factor-is related to ER response in placental cells exposed to maternal gestational diabetes mellitus (GDM) or to a hyperglycaemic in vitro condition.

Objective: The study aimed to investigate the role of SDF2 in BeWo cells , a trophoblast cell line originating from choriocarcinoma , and in placental tissue under hyperglycaemic conditions.

Methods: Protein levels of SDF2 and UPR factors, glucose-related protein 78 (GRP78) and eukaryotic initiation factor 2 alpha (elF2 alpha) were evaluated in the placentae of pregnant women diagnosed with GDM and treated by diet-control (insulin was added when necessary). The mRNA expression of SDF2 and UPR factors CHOP and sXBP1 were assessed in cultured BeWo cells challenged with glucose and treated with or without insulin.

Results: SDF2 expression was increased in the placentae of GDM women treated with diet. However, its values were similar to those of normoglycemic controls when the GDM women were treated with insulin and diet. BeWo cells cultured with high glucose and insulin showed decreased SDF2 expression, while high glucose increased CHOP and sXBP1 expression, which was then significantly reverted with insulin treatment.

Conclusion: Our findings extend the understanding of ER stress and SDF2 expression in placentae exposed to hyperglycaemia, highlighting the relevance of insulin in reducing the levels of ER stress factors in placental cells. Understanding the effect of ER stress partners such as SDF2 on signalling pathways involved in gestation, complicated by hyperglycaemia, is pivotal for basic biomedical research and may lead to new therapeutic possibilities.
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http://dx.doi.org/10.2174/1570161118666200606222123DOI Listing
January 2021

The provision of epidural analgesia during labor according to maternal birthplace: a Norwegian register study.

BMC Pregnancy Childbirth 2020 May 26;20(1):321. Epub 2020 May 26.

Division of Obstetrics and Gynaecology, Oslo University Hospital, Sognsvannsveien 20, 0372, Oslo, Norway.

Background: The provision of epidural analgesia during labor is ideally a shared decision between the woman and her health care provider. However, immigrant characteristics such as maternal birthplace could affect decision-making and thus access to pain relief. We aimed to assess disparities in the provision of epidural analgesia in planned vaginal birth according to maternal region of birth.

Methods: We performed a nation-wide register study of 842,496 live-born singleton deliveries in Norway between 2000 and 2015. Maternal birthplace was categorized according to the Global Burden of Disease framework. The provision of epidural analgesia was compared in regression models stratified by parity and mode of delivery.

Results: Compared to native-born women, primiparous women from Latin America/Caribbean countries with an instrumental vaginal delivery were most likely to be provided epidural analgesia (OR 2.12, 95%CI 1.69-2.66), whilst multiparous women from Sub-Saharan Africa with a spontaneous vaginal delivery were least likely to be provided epidural analgesia (OR 0.42, 95% C 0.39-0.44). Longer residence time was associated with a higher likelihood of being provided analgesia, whereas effects of maternal education varied by Global Burden of Disease group.

Conclusions: Disparities in the likelihood of being provided epidural analgesia were observed by maternal birthplace. Further studies are needed to consider whether the identified disparities represent women's own preferences or if they are the result of heterogeneous access to analgesia during labor.
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http://dx.doi.org/10.1186/s12884-020-03021-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249666PMC
May 2020

Functional and structural vascular biomarkers in women 1 year after a hypertensive disorder of pregnancy.

Pregnancy Hypertens 2020 Jul 24;21:23-29. Epub 2020 Apr 24.

Faculty of Medicine, University of Oslo, Oslo, Norway; Division of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway.

Objectives: Women with a previous hypertensive disorder of pregnancy (HDP: gestational hypertension and preeclampsia) have increased long-term cardiovascular disease risk. Recent meta-analyses show adverse levels of non-invasive functional and structural cardiovascular risk markers such as pulse wave velocity (PWV), heart-rate adjusted augmentation index (AIx75), carotid intima-media thickness (CIMT), and reactive hyperemia index (RHI) after HDPs, and suggest using these for cardiovascular risk stratification. However, it is not known if a previous HDP predict levels of these markers beyond classical cardiovascular risk factors. Study design and main outcome measures. We assessed PWV, AIx75, CIMT, RHI, classical cardiovascular risk factors, and pregnancy characteristics in 221 women 1 year postpartum (controls: 95, previous HDP: 126). Uni- and multi- variate regression analysis were conducted to assess associations between previous HDP and PWV, AIx75, CIMT or RHI. We adjusted for classical cardiovascular risk factors and pregnancy characteristics. A p-level < 0.05 was considered statistically significant.

Results: PWV was associated with previous HDP on univariate analysis. This effect was confounded by blood pressure and not significant after adjustment. We found no significant associations between AIx75, RHI, CIMT, and a previous HDP, neither before nor after adjustments.

Conclusions: Associations between a previous HDP and PWV, AIx75, CIMT, or RHI 1 year postpartum can largely be explained by adverse levels of classical cardiovascular risk markers in women with a previous HDP. Women with previous HDP should receive primary prevention of cardiovascular disease, but PWV, AIx75, CIMT or RHI are unlikely to aid in cardiovascular risk stratification 1 year postpartum.
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http://dx.doi.org/10.1016/j.preghy.2020.04.008DOI Listing
July 2020

Multiplex Analysis of Circulating Maternal Cardiovascular Biomarkers Comparing Preeclampsia Subtypes.

Hypertension 2020 06 27;75(6):1513-1522. Epub 2020 Apr 27.

From the Department of Obstetrics and Gynecology, Oslo University Hospital, Ullevål, Norway (T.L., M.S., K.M., A.C.S.).

Preeclampsia, a hypertensive pregnancy disorder, links to increased long-term maternal cardiovascular disease (CVD). The risk is further increased with early-onset preeclampsia (EPE) and delivery of a growth-restricted child. We hypothesized that circulating biomarkers associated with CVD risk differed between preeclampsia subtypes and controls. We compared EPE; n=37, delivery
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14580DOI Listing
June 2020

Maternal Mortality in Georgia: Incidence, Causes and Level of Underreporting: A National Reproductive Age Mortality Study 2014.

Int J Womens Health 2020 9;12:277-286. Epub 2020 Apr 9.

Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

Introduction: Accurate data on maternal mortality are essential for assessing progress towards Sustainable Development Goals (SDG).The aim of the study was to determine the incidence and causes of maternal deaths in Georgia, then explore the potential for improvement of quality of maternal health care. The study's secondary aims were to identify the level of underreporting of maternal deaths in Georgian vital statistics over 1 year (2012) and to compare these results with previous data from 2006. The study findings allow to support the country in developing evidence-based policies and tracking progress towards meeting SDG targets.

Methods: A national Reproductive Age Mortality Survey (RAMOS) was conducted in Georgia in 2014-15. Multiple data sources were used to identify deaths of women aged 15-49 years between January and December 2012. All deaths in women of reproductive age were investigated through verbal autopsy (VA) diagnoses. Deaths in women during pregnancy or one-year postpartum were further investigated by conducting interviews and medical record reviews at the last medical facility which provided health care for the woman during her fatal condition. A specialist panel reviewed these cases and assigned underlining causes of deaths.

Results: We found that 98% of deaths among women of reproductive age were registered by Georgia's civil registration and vital statistics system (CRVS). A total of 918 deaths met the study inclusion criteria. Thirty-six (4.1%) women died during pregnancy or within one-year postpartum. Among these 36 deaths, 23 (63.8%) were maternal deaths, 15 early (either during pregnancy or 42 days postpartum) and eight late (43-365 days postpartum) deaths (65.2% vs 34.8%). The remaining 13 of 36 deaths were coincidental deaths. Fourteen maternal deaths were reported by official statistics and nine deaths were not included in these statistics. Thus, the underreporting rate was 39%. Direct obstetric causes accounted for 73.9% (n=17) of maternal deaths, whereas 26.1% (n=6) were indirect. The leading causes of direct maternal deaths were infection (21.7%), hemorrhage (17.4%), pulmonary embolism (13.0%), and pregnancy-induced hypertension (8.7%). The RAMOS study calculated a maternal mortality ratio (early maternal deaths) of 26.3 per 100,000 live births compared with the official figure of 22.8 per 100,000 live births.

Discussions: Registration of early maternal deaths significantly improved since last survey in 2008, while indirect and late maternal deaths continue to be unrecognized, as reflected in official Georgian statistics. The difference between RAMOS study findings and officially reported maternal mortality rates is minimal, showing improvements in detection of maternal deaths by the national maternal mortality surveillance system. The greatest number of direct obstetric deaths occur in the first week postpartum, which likely reflects deficiencies in quality of care.
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http://dx.doi.org/10.2147/IJWH.S227349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154943PMC
April 2020

HLA-G whole gene amplification reveals linkage disequilibrium between the HLA-G 3'UTR and coding sequence.

HLA 2020 08 17;96(2):179-185. Epub 2020 May 17.

Department of Immunohematology, Leiden University Medical Center, Leiden, The Netherlands.

Polymorphic sites in the HLA-G gene may influence expression and function of the protein. Knowledge of the association between high-resolution HLA-G alleles and 3-prime untranslated (3'UTR) haplotypes is useful for studies on the role of HLA-G in transplantation, pregnancy, and cancer. We developed a next generation sequencing (NGS)-based typing assay enabling full phasing over the whole HLA-G gene sequence with inclusion of the 3'UTR region. DNA from 171 mother-child pairs (342 samples) was studied for: (a) HLA-G allele information by the NGSgo-AmpX HLA-G assay, (b) 3'UTR haplotype information by an in-house developed sequence-based typing method of a 699/713 base pair region in the 3'UTR, and (c) the full phase HLA-G gene sequence, by combining primers from both assays. The mother to child inheritance allowed internal verification of newly identified alleles and of association between coding and UTR regions. The NGSgo workflow compatible with Illumina platforms was employed. Data was interpreted using NGSengine software. In 99.4% of all alleles analyzed, the extended typing was consistent with the separate allele and 3'UTR typing methods. After repeated analysis of four samples that showed discrepancy, consistency reached 100%. A high-linkage disequilibrium between IPD-IMGT/HLA Database-defined HLA-G alleles and the extended 3'UTR region was identified (D' = 0.994, P < .0001). Strong associations were found particularly between HLA-G*01:04 and UTR-3, between HLA-G*01:01:03 and UTR-7, and between HLA-G*01:03:01 and UTR-5 (for all: r = 1). Six novel HLA-G alleles and three novel 3'UTR haplotype variants were identified, of which three and one, respectively, were verified in the offspring.
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http://dx.doi.org/10.1111/tan.13909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384165PMC
August 2020

Maternal use of nicotine products and breastfeeding 3 months postpartum.

Acta Paediatr 2020 12 29;109(12):2594-2603. Epub 2020 Apr 29.

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Aim: We aimed to determine the prevalence of and factors associated with maternal use of nicotine products in relation to breastfeeding.

Methods: Nicotine use 3 months postpartum was determined in the Scandinavian PreventADALL mother-child birth cohort study recruiting 1837 women from 2014 to 2016. Electronic questionnaires at 18 weeks pregnancy and 3 months postpartum provided information on snus use, smoking or other nicotine use, infant feeding and socio-economic factors. The risk of nicotine use in relation to breastfeeding was analysed with logistic regression.

Results: Overall, 5.6% of women used snus (2.9%), smoked (2.7%) or both (n = 2) 3 months postpartum, while one used other nicotine products. Among the 1717 breastfeeding women, 95.1% reported no nicotine use, while 2.4% used snus, 2.5% smoked and one dual user. Compared to 3.7% nicotine use in exclusively breastfeeding women (n = 1242), the risk of nicotine use increased by partly (OR 2.26, 95% CI 1.45-3.52) and no breastfeeding (OR 4.58, 95% CI 2.57-8.21). Nicotine use before (14.5% snus, 16.4% smoking) or in pregnancy (0.2% snus, 0.4% smoking) significantly increased the risk of using nicotine during breastfeeding.

Conclusion: Few breastfeeding women used snus or smoked 3 months postpartum, with increased risk by nicotine use before or during pregnancy.
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http://dx.doi.org/10.1111/apa.15299DOI Listing
December 2020

Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial.

Lancet 2020 03 19;395(10228):951-961. Epub 2020 Feb 19.

Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.

Background: Skin emollients applied during early infancy could prevent atopic dermatitis, and early complementary food introduction might reduce food allergy in high-risk infants. The study aimed to determine if either regular skin emollients applied from 2 weeks of age, or early complementary feeding introduced between 12 and 16 weeks of age, reduced development of atopic dermatitis by age 12 months in the general infant population.

Methods: This population-based 2×2 factorial, randomised clinical trial was done at Oslo University Hospital and Østfold Hospital Trust, Oslo, Norway; and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine ultrasound pregnancy screening at 18 weeks were cluster-randomised at birth from 2015 to 2017 to the following groups: (1) controls with no specific advice on skin care while advised to follow national guidelines on infant nutrition (no intervention group); (2) skin emollients (bath additives and facial cream; skin intervention group); (3) early complementary feeding of peanut, cow's milk, wheat, and egg (food intervention group); or (4) combined skin and food interventions (combined intervention group). Participants were randomly assigned (1:1:1:1) using computer- generated cluster randomisation based on 92 geographical living area blocks as well as eight 3-month time blocks. Carers were instructed to apply the interventions on at least 4 days per week. Atopic dermatitis by age 12 months was the primary outcome, based on clinical investigations at 3, 6 and 12 months by investigators masked to group allocation. Atopic dermatitis was assessed after completing the 12-month investigations and diagnosed if either of the UK Working Party and Hanifin and Rajka (12 months only) diagnostic criteria were fulfilled. The primary efficacy analyses was done by intention-to-treat analysis on all randomly assigned participants. Food allergy results will be reported once all investigations at age 3 years are completed in 2020. This was a study performed within ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood; the Lung and Environment). The study is registered at clinicaltrials.gov, NCT02449850.

Findings: 2697 women were recruited between Dec 9, 2014, and Oct 31, 2016, from whom 2397 newborn infants were enrolled from April 14, 2015, to April 11, 2017. Atopic dermatitis was observed in 48 (8%) of 596 infants in the no intervention group, 64 (11%) of 575 in the skin intervention group, 58 (9%) of 642 in the food intervention group, and 31 (5%) of 583 in the combined intervention group. Neither skin emollients nor early complementary feeding reduced development of atopic dermatitis, with a risk difference of 3·1% (95% CI -0·3 to 6·5) for skin intervention and 1·0% (-2·1 to 4·1) for food intervention, in favour of control. No safety concerns with the interventions were identified. Reported skin symptoms and signs (including itching, oedema, exanthema, dry skin, and urticaria) were no more frequent in the skin, food, and combined intervention groups than in the no intervention group.

Interpretation: Neither early skin emollients nor early complementary feeding reduced development of atopic dermatitis by age 12 months. Our study does not support the use of these interventions to prevent atopic dermatitis by 12 months of age in infants.

Funding: The study was funded by several public and private funding bodies: The Regional Health Board South East, The Norwegian Research Council, Health and Rehabilitation Norway, The Foundation for Healthcare and Allergy Research in Sweden-Vårdalstiftelsen, Swedish Asthma and Allergy Association's Research Foundation, Swedish Research Council-the Initiative for Clinical Therapy Research, The Swedish Heart-Lung Foundation, SFO-V at the Karolinska Institute, Freemason Child House Foundation in Stockholm, Swedish Research Council for Health, Working Life and Welfare-FORTE, Oslo University Hospital, the University of Oslo, and Østfold Hospital Trust.
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http://dx.doi.org/10.1016/S0140-6736(19)32983-6DOI Listing
March 2020

Food and nutrient intake and adherence to dietary recommendations during pregnancy: a Nordic mother-child population-based cohort.

Food Nutr Res 2019 20;63. Epub 2019 Dec 20.

Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

Background: A woman's food intake during pregnancy has important implications not only for herself but also for the future health and well-being of her child. Suboptimal dietary quality has been consistently reported in many high-income countries, reflecting poor adherence to dietary guidelines.

Objective: This study aimed to explore the intake of food and nutrients in a cohort of pregnant women in Norway and their adherence to Nordic Nutrition Recommendations (NNR) and Norwegian food-based guidelines (NFG).

Design: We investigated the dietary intake in 1,674 pregnant women from the mother-child birth cohort, PreventADALL, recruited at approximately 18-week gestational age. Dietary intake was assessed by an electronic validated food frequency questionnaire (PrevFFQ) in the first half of pregnancy.

Results: Total fat intake was within the recommended intake (RI) range in most women; however, the contribution of saturated fatty acids to the total energy intake was above RI in the majority (85.2%) of women. Carbohydrate intake was below RI in 43.9% of the women, and 69.5% exceeded the RI of salt. Intakes of fiber, vegetables, and fish were high in a large part of the population. Many women had a high probability of inadequate intakes of the following key micronutrients during pregnancy: folate (54.4%), iron (49.6%), calcium (36.2%), vitamin D (28.7%), iodine (24.4%), and selenium (41.3%). A total of 22.8% women reported an alcohol intake of >1 g/day, and 4.4% reported an alcohol intake of >10 g/day. Women with higher educational levels showed a tendency towards healthier eating habits, except for higher intakes of alcohol and coffee, compared to women with lower educational level.

Discussion: Excessive saturated fat intake and limited intake of many important micronutrients during pregnancy were common, potentially increasing the risk for adverse pregnancy and birth outcomes.

Conclusions: This study highlights the need for improved nutritional guidance to pregnant women across all educational levels.
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http://dx.doi.org/10.29219/fnr.v63.3676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939665PMC
December 2019

Uteroplacental acute atherosis in preeclamptic pregnancies: Rates and clinical outcomes differ by tissue collection methods.

Pregnancy Hypertens 2020 Jan 21;19:11-17. Epub 2020 Feb 21.

Division of Obstetrics and Gynaecology, Oslo University Hospital, Ullevål and Faculty of Medicine, University of Oslo, Norway.

Objectives: Acute atherosis (AA) is a uteroplacental spiral artery lesion, identified by intramural lipid-laden foam cells, with highest rates in preeclampsia (PE). We compared AA detection rates in preeclampsia (PE) across three different decidual spiral artery collection methods in same patients. We tested whether the rate and topographical distribution of AA associates with clinical parameters.

Study Design: Three decidual tissue types were harvested from each of 107 preeclamptic women delivered by cesarean section. Routine sampled basal surface placenta (decidua basalis, DB) and fetal membrane roll (decidua parietalis, DP) biopsies were compared with decidual vacuum suction biopsies (DB), regarding spiral artery rate and AA presence. Spiral arteries and AA were identified using predefined, immunohistochemically based criteria on serial sections.

Main Outcome Measures And Results: Detection of spiral arteries (87%) and AA (35%) was highest in DB samples collected by vacuum suction compared to the two other methods. Pregnancies with AA detected in vacuum suctioned DB had lower gestational age at delivery, lower birth weight percentile and more often fetal growth restriction. Basal plate DB samples demonstrating AA associated with pregnancies affected by pathological fetal Dopplers, whereas AA detected in DP membrane rolls, did not.

Conclusions: Placental bed vacuum suction provides more spiral arteries and higher AA rate, suggesting underestimation of AA in conventional pathology samples of basal plate DB biopsies and DP. The association of AA with PE-related clinical parameters varies according to tissue collection method. Longitudinal studies could elucidate whether AA also identifies women with future premature cardiovascular risk.
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http://dx.doi.org/10.1016/j.preghy.2019.11.007DOI Listing
January 2020

Risk prediction of maternal cardiovascular disease one year after hypertensive pregnancy complications or gestational diabetes mellitus.

Eur J Prev Cardiol 2020 08 10;27(12):1273-1283. Epub 2019 Oct 10.

Faculty of Medicine, University of Oslo, Norway.

Background: Previous preeclampsia, gestational hypertension and gestational diabetes mellitus show a firm epidemiological association to maternal cardiovascular disease risk. Cardiovascular disease risk assessment is recommended in women after these pregnancy complications, but not offered in most countries. We therefore wanted to evaluate the applicability of currently recommended cardiovascular disease risk scores for women one-year postpartum of such pregnancy complications.

Design And Methods: We tested applicability of three scoring systems, the Atherosclerotic Cardiovascular Disease (ASCVD) score, the Joint British Societies for the Prevention of Cardiovascular Disease (JBS3) score and Framingham 30 year Risk Score-Cardiovascular Disease (FRS-CVD) in 235 women one-year postpartum (controls: 94, gestational hypertension: 35, preeclampsia: 81, gestational diabetes mellitus: 25). Statistical analysis was performed with Mann-Whitney test for continuous and Fisher's mid-corrected and Pearson's for dichotomous variables. A value of  < 0.050 was considered significant.

Results: Most women (87.7%) were below 40 years of age, rendering 10-year risk estimations recommended by American and European societies inapplicable. FRS-CVD could be assessed in all women. Significantly fewer could be assessed by the ASCVD (81.5%) and JBS3 (91.6%). All scoring systems showed small, but significant increases in risk scores for one or more of the pregnancy complication groups, but none at the risk magnitude for cardiovascular disease shown in epidemiological studies.

Conclusion: We demonstrate that ASCVD, JBS3 and FRS-CVD are inadequate in assessing cardiovascular disease risk one-year postpartum. We suggest that pregnancy complications need to be considered separately when evaluating maternal cardiovascular disease risk and need for postpartum follow-up.
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http://dx.doi.org/10.1177/2047487319879791DOI Listing
August 2020

Predicting Skin Barrier Dysfunction and Atopic Dermatitis in Early Infancy.

J Allergy Clin Immunol Pract 2020 02 27;8(2):664-673.e5. Epub 2019 Sep 27.

Department of Toxicology and Risk Assessment, Norwegian Institute of Public Health, Oslo, Norway.

Background: Dry skin is associated with increased transepidermal water loss (TEWL), which has been found to precede atopic dermatitis (AD) in childhood.

Objective: We aimed to identify parental, prenatal, and perinatal predictive factors of dry skin, high TEWL, and AD at 3 months of age, and to determine if dry skin or high TEWL at 3 months can predict AD at 6 months.

Methods: From the Preventing Atopic Dermatitis and Allergies in children prospective birth cohort study, we included 1150 mother-child pairs. Dry skin, TEWL, and eczema were assessed at 3- and 6-month investigations. Eczema, used as a proxy for AD, was defined as the presence of eczematous lesions, excluding differential diagnoses to AD. High TEWL was defined as TEWL >90th percentile, equaling 11.3 g/m/h. Potential predictive factors were recorded from electronic questionnaires at 18- and 34-week pregnancy and obstetric charts.

Results: Significant predictive factors (P < .05) for dry skin at 3 months were delivery >38 gestational weeks and paternal age >37 years; for high TEWL, male sex, birth during winter season, and maternal allergic disease; and for eczema, elective caesarean section, multiparity, and maternal allergic diseases. Dry skin without eczema at 3 months was predictive for eczema at 6 months (adjusted odds ratio: 1.92, 95% confidence interval: 1.21-3.05; P = .005), whereas high TEWL at 3 months was not.

Conclusion: In early infancy, distinct parental- and pregnancy-related factors were predictive for dry skin, high TEWL, and AD. Dry skin at 3 months of age was predictive for AD 3 months later.
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http://dx.doi.org/10.1016/j.jaip.2019.09.014DOI Listing
February 2020

Why Do Circulating Biomarkers Predict Early-Onset Preeclampsia, and Can They Also Predict Future Maternal Cardiovascular Health?

Hypertension 2019 11 16;74(5):1084-1086. Epub 2019 Sep 16.

From the Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Norway; and Division of Obstetrics and Gynaecology, Oslo University Hospital, Norway.

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13722DOI Listing
November 2019

Long-term cardiovascular health after stopping pre-eclampsia.

Lancet 2019 09 28;394(10204):1120-1121. Epub 2019 Aug 28.

Faculty of Medicine, University of Oslo, Blindern 0381, Oslo, Norway; Division of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(19)31993-2DOI Listing
September 2019

Maternal and paternal atopic dermatitis and risk of atopic dermatitis during early infancy in girls and boys.

J Allergy Clin Immunol Pract 2020 01 15;8(1):416-418.e2. Epub 2019 Jul 15.

Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Dermatology, Oslo University Hospital, Oslo, Norway.

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http://dx.doi.org/10.1016/j.jaip.2019.06.039DOI Listing
January 2020

The two-stage placental model of preeclampsia: An update.

J Reprod Immunol 2019 09 8;134-135:1-10. Epub 2019 Jul 8.

Division of Obstetrics and Gynaecology, Oslo University Hospital, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address:

Early-onset preeclampsia has been linked to poor placentation and fetal growth restriction, whereas late-onset preeclampsia was suggested to result from maternal factors. We have proposed an alternative model, suggesting that both early- and late-onset preeclampsia result from placental syncytiotrophoblast stress. This stress represents a common endpoint of several Stage 1 processes, promoting the clinical stage 2 of preeclampsia (new-onset hypertension and proteinuria or other signs of end-organ dysfunction), but the causes and timing of placental malperfusion differ. We have suggested that late-onset preeclampsia, without evidence of poor spiral artery remodelling, may be secondary to intraplacental (intervillous) malperfusion due to mechanical restrictions. As the growing placenta reaches its size limit, malperfusion and hypoxia occurs. This latter pathway reflects what is observed in postmature or multiple pregnancies. Our revised two-stage model accommodates most risk factors for preeclampsia including primiparity, chronic pre-pregnancy disease (e.g. obesity, diabetic-, chronic hypertensive-, and some autoimmune diseases), and pregnancy risk factors (e.g. multiple or molar pregnancies, gestational diabetes or hypertension, and low circulating Placental Growth Factor). These factors may increase the risk of progressing to the second stage of preeclampsia (both early- and late-onset) by affecting one of or both pathways leading to Stage 1, as well as potentially accelerating the steps towards Stage 2, including priming the maternal cardiovascular susceptibility to inflammatory factors shed by the placenta. This paper reviews previous preeclampsia findings and concepts, which fit with the revised two-stage model, and argues that "maternal" preeclampsia does not exist, as all preeclampsia requires a placenta.
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http://dx.doi.org/10.1016/j.jri.2019.07.004DOI Listing
September 2019