Anne Cathrine (Annetine) Staff

• Hagen, Kristine Krüger; Eyjolfsdottir, Brynhildur; Dahl, Gunn Fallås; Wang, Yun; Lund, Kjersti Vassmo & Nordskar, Nina Jebens [Vis alle 13 forfattere av denne artikkelen] (2026). Early post-operative complications after fertility-sparing surgery for cervical carcinoma: a retrospective study of a centralized national cohort of 127 consecutive women. International Journal of Gynecological Cancer. ISSN 1048-891X. doi: 10.1016/j.ijgc.2026.104986. Fulltekst i vitenarkiv
• Miltenburg, Andrea Solnes; Kiritta, Richard; Kidenya, Benson R.; Amoakoh, Hannah Brown; Schielen, Peter C.J.I. & Manyogote, Felix [Vis alle 15 forfattere av denne artikkelen] (2026). PRESHA — Preventing severe hypertensive adverse events in pregnancy and childbirth: a study protocol for establishing a prospective cohort study and biobank in urban Tanzania. Frontiers in Global Women's Health. 7. doi: 10.3389/fgwh.2026.1812275. Fulltekst i vitenarkiv
• Sundet, Birgitte Kordt; Fiskå, Bendik Seth; Staff, Anne Cathrine; Jacobsen, Daniel Pitz; Bratseth, Vibeke & Palmero, Sheryl [Vis alle 13 forfattere av denne artikkelen] (2026). Circulating neutrophil extracellular traps and deoxyribonuclease in gestational diabetes mellitus. Journal of Reproductive Immunology. ISSN 0165-0378. 176. doi: 10.1016/j.jri.2026.104928.
• Klepp, Kristina; Moe, Kjartan; Jacobsen, Daniel Pitz; Sugulle, Meryam; Angel, Kristin & Lueder, Thomas Gero von [Vis alle 8 forfattere av denne artikkelen] (2026). Circulating Cardiovascular Biomarkers 1–3 Years Following Hypertensive Pregnancy Disorders: Associations With Postpartum Cardiovascular Structure and Function. Reproductive Sciences. ISSN 1933-7191. doi: 10.1007/s43032-026-02171-y. Fulltekst i vitenarkiv Vis sammendrag

  Hypertensive disorders of pregnancy (HDP) confer increased cardiovascular disease (CVD) risk postpartum. Screening methods targeting women with increased risk are lacking, limiting personalized follow-up. Circulating biomarkers may assist CVD risk stratification. We aimed to assess whether circulating biomarkers were associated with measures of cardiovascular structure and function following HDP and normotensive pregnancies (controls). We examined 275 women 1–3 years postpartum (176 following HDP and 99 parous controls). Circulating biomarkers (hs-CRP, non-HDL cholesterol, glucose, eGFR, cTnT, NT-proBNP, GDF-15, sHLA-G, SAA1) and cardiovascular function and structure measures were examined [pulse wave velocity (PWV), carotid intima-media thickness (CIMT) and echocardiography]. Group differences were tested by Mann-Whitney U test and chi-square. Associations were assessed by univariate regression analyses. A p-value < 0.05 was considered statistically significant. Women following HDP displayed significantly higher rates of hypertension (5% vs. 0%) and metabolic syndrome (7% vs. 1%) than controls. Circulating biomarker levels were similar between study groups. In univariate regression analyses for the prior HDP group, non-HDL cholesterol was significantly associated with PWV and CIMT. Additionally, glucose and hs-CRP were significantly associated with PWV. These associations were not reproduced for controls, except for non-HDL cholesterol which was significantly associated with CIMT. In conclusion, women following HDP and normotensive pregnancies had similar postpartum levels of circulating biomarkers, but circulating biomarkers were significantly associated with measures of arterial stiffness (PWV and CIMT) in women with prior HDP. Our findings support current guidelines recommending CVD follow-up after HDP. Non-HDL cholesterol, glucose and hs-CRP may possibly help refining personalized cardiovascular follow-up postpartum.

• Vallevik, Elin Ørbeck; Holten-Andersen, Mads Nikolaj; Carlsen, Karin Cecilie Lødrup; Skjerven, Håvard Ove; Vettukattil, Riyas & Rueegg, Corina Silvia [Vis alle 14 forfattere av denne artikkelen] (2026). Oscillometric blood pressure values in infants at 3, 6 and 12 months of age: a cohort study. BMJ Paediatrics Open. 10(1). doi: 10.1136/bmjpo-2026-004761. Fulltekst i vitenarkiv
• Staff, Anne Cathrine; Sjaavik, Anja Dusik; Noll, Josef; Sugulle, Meryam; Fiskå, Bendik Seth & Klovning, Atle [Vis alle 11 forfattere av denne artikkelen] (2026). Co-creation of a mobile health program (MumCare) for preventing maternal cardiovascular disease after pregnancy complications. Frontiers in Global Women's Health. 7. doi: 10.3389/fgwh.2026.1717203. Fulltekst i vitenarkiv
• Fiskå, Bendik Seth; Turowski, Gitta Erika; Rocha, Maria Linda; Lekva, Tove; Ueland, Thor & Staff, Anne Cathrine [Vis alle 7 forfattere av denne artikkelen] (2026). Placenta tissue-based and circulating markers of cellular senescence in gestational diabetes mellitus. Placenta. ISSN 0143-4004. 177, s. 8–16. doi: 10.1016/j.placenta.2026.02.015. Fulltekst i vitenarkiv
• Bentsen, Ingerid; Waldum, Åsa; Sugulle, Meryam & Staff, Anne Cathrine (2026). Self-reported primary preventive follow-up of women’s cardiovascular health after hypertensive pregnancy complications and gestational diabetes. Pregnancy Hypertension. ISSN 2210-7789. 44. doi: 10.1016/j.preghy.2026.101474. Fulltekst i vitenarkiv
• Berents, Frida Victoria; Skram, Marius Kurås; Carlsen, Karin Cecilie Lødrup; Granum, Berit Brunstad; Haugen, Guttorm Nils & Hedlin, Gunilla [Vis alle 15 forfattere av denne artikkelen] (2026). Maternal BMI, early-life growth, and atopic dermatitis by age 3 years. Journal of Allergy and Clinical Immunology: Global (JACI: Global). 5(3). doi: 10.1016/j.jacig.2026.100693. Fulltekst i vitenarkiv Vis sammendrag

  Background: Childhood atopic dermatitis is associated with maternal gestational weight gain, whereas an association with prepregnancy body mass index (ppBMI) or fetal and newborn anthropometric measurements is unclear. Objective: Our aim was to determine whether, primarily, maternal ppBMI and, secondarily, offspring newborn anthropometric measurements or fetal growth are associated with atopic dermatitis by age 3 years. Methods: In 2107 mother-child pairs (54% boys) from the general population–based Scandinavian PreventADALL (Preventing Atopic Dermatitis and Allergies) cohort, maternal ppBMI was reported at time of enrollment (at midpregnancy). Thoracic and abdominal circumferences were measured by ultrasound at midpregnancy and again at birth, as were weight and length. Fetal growth, including thoracic and abdominal growth and fetal weight gain, was estimated from midpregnancy to birth. Atopic dermatitis was diagnosed using standard criteria at 3, 6, 12, 24, and age 36 months. Results: Atopic dermatitis was diagnosed in 525 of the 2107 children (25%) by age 3 years, with a positive association with increasing maternal BMI (adjusted odds ratio [aOR] per BMI unit = 1.03 [95% CI = 1.00-1.06]). Furthermore, increasing birth length (mean = 50.5 ± 2.0 cm) was positively associated with atopic dermatitis (aOR = 1.06 [95% CI = 1.01-1.12]), whereas short birth length (<48 cm) was inversely associated with atopic dermatitis (aOR = 0.71 [95% CI = 0.51-1.0]). Neither birth weight nor thoracic, abdominal, or upper arm circumference at birth nor fetal growth was associated with atopic dermatitis. Conclusion: Increasing maternal ppBMI and increasing birth length were positively associated with offspring atopic dermatitis by age 3 years, whereas short birth length was associated with a lower risk of atopic dermatitis.

• Ziesler, Charlotte Philippa Øxnevad; Staff, Anne Cathrine; Klepp, Kristina; Sugulle, Meryam & Moe, Kjartan (2026). Physical activity and cardiovascular risk factors after hypertensive pregnancy complications. Pregnancy Hypertension. ISSN 2210-7789. 44. doi: 10.1016/j.preghy.2026.101466. Fulltekst i vitenarkiv
• Anwar, Rabia; Pande, Amit; Singh, Manvendra; Huang, Zhi; Hallett, Eve & Xie, Yiran [Vis alle 19 forfattere av denne artikkelen] (2025). ERV3-MLT1 provides cis-regulatory elements for human placental functioning and are commonly dysregulated in human-specific preeclampsia. Genome Biology. ISSN 1465-6906. 26(1). doi: 10.1186/s13059-025-03821-1. Fulltekst i vitenarkiv Vis sammendrag

  Background Owing to their transcription factor binding sites, endogenous retroviruses (ERVs) can act as cis-regulatory-elements (CREs). By invading genomes in waves, ERVs offer a substrate for lineage-specific adaptations but also, when dysregulated, for lineage-specific disorders. Their role as CREs in rapid placental evolution, and in the human-specific placental disorder preeclampsia, may thus provide a paradigmatic exemplar. Here then we systematically identify ERV-derived CREs controlling human placental gene expression with dysregulation in preeclampsia. Results We identify 87 ERV-derived CREs located upstream of genes expressed in the placenta. A subset of nine, all belonging to the ERV3-MLT1/2 families and dating to the mouse–human common ancestor, are consistently dysregulated in trophoblasts from preeclampsia samples. Of the nine ERV3-MLT1-linked genes dysregulated in preeclampsia, five are novel candidates, while four were previously associated with preeclampsia, though their ERV-based regulation was not recognized. Focusing on EPS8L1, we predict enhancer activity of upstream MLT1(G1) and validate using reporter assay and genome editing. This vertebrate-specific gene is expressed in progenitor cytotrophoblasts and syncytiotrophoblasts and is overexpressed in preeclampsia, correlating with preeclampsia biomarkers and is not elevated in related pregnancy disorders. A soluble form of EPS8L1 is detectable in maternal plasma as early as between 24 weeks of gestation. EPS8L1 knockout in trophoblast in vitro is lethal, and its overexpression alters trophoblast behaviors characteristic of preeclampsia. Conclusions We conclude that ERV3-MLT1functions as a trophoblast-specific CRE for several human genes and may be dysregulated in preeclampsia. As EPS8L1 has a form in maternal circulation, it may have utility in diagnostics.

• Chua, Kristine J.; Quilang, Rachel C.; Sallinger, Katja; Aktipis, Christina Athena; Arck, Petra & Bianchi, Diana W. [Vis alle 32 forfattere av denne artikkelen] (2025). Identifying Key Questions and Challenges in Microchimerism Biology. Advanced Science. 12(48). doi: 10.1002/advs.202514969. Fulltekst i vitenarkiv
• Ng, Shu Wing; Ng, Allen C.; Ng, Michelle C.; Ng, Shu Kay; Arcuri, Felice & Genega, Elizabeth M. [Vis alle 13 forfattere av denne artikkelen] (2025). Preeclampsia is Associated with Altered Expression of Ferroptosis Biomarkers in Placental but not Maternal Vasculature. Reproductive Sciences. ISSN 1933-7191. doi: 10.1007/s43032-025-01935-2. Fulltekst i vitenarkiv
• Klepp, Kristina; Moe, Kjartan; Angel, Kristin; Lueder, Thomas Gero von; Sugulle, Meryam & Ziesler, Charlotte Philippa Øxnevad [Vis alle 8 forfattere av denne artikkelen] (2025). Cardiovascular phenotype in women 1–3 years after hypertensive pregnancy disorders: Impact of sex-independent and pregnancy-specific risk factors. Pregnancy Hypertension. ISSN 2210-7789. 43. doi: 10.1016/j.preghy.2025.101404. Fulltekst i vitenarkiv
• Jacobsen, Daniel Pitz; Fjeldstad, Heidi; Olsen, Maria Belland; Sugulle, Meryam; Schjørlien, Therese & Skjelland, Mona Elisabeth [Vis alle 8 forfattere av denne artikkelen] (2025). Postpartum levels of circulating fetal microchimeric cells are lower after early-onset preeclampsia. Journal of Reproductive Immunology. ISSN 0165-0378. 172. doi: 10.1016/j.jri.2025.104646. Fulltekst i vitenarkiv Vis sammendrag

  Fetal cells may persist in the mother following pregnancy, termed fetal microchimerism. These cells have been attributed positive and negative effects. The number of fetal cells transferred during pregnancy appears to be higher in preeclampsia. Here, we investigate whether fetal cell presence and quantity in the maternal circulation 1–8 years postpartum is influenced by a previous preeclamptic pregnancy. We also relate fetal cells detected postpartum to fetal cells detected during pregnancy, time since index pregnancy, parity, fetal sex and maternal characteristics. A cohort of 139 women was included in the present study: 21 with previous early-onset preeclampsia, 31 with previous late-onset preeclampsia and 87 with a clinically uncomplicated index pregnancy. Circulating fetal microchimerism was detected in maternal buffy coat using qPCR, targeting alleles unique to the fetus. Pregnancy buffy coat samples were available for 129 of the 139 included women. Early-onset, but not late-onset, preeclampsia was associated with reduced quantity of fetal microchimeric cells in maternal circulation postpartum. Fetal cells detected during pregnancy, time since index pregnancy, parity, fetal sex and maternal characteristics were not predictive of microchimerism postpartum in our cohort. Our findings suggest that early-onset, but not late-onset preeclampsia, affects circulating microchimerism postpartum. Our observation that fetal microchimerism postpartum did not correlate with number of fetal cells detected during pregnancy nor time since index pregnancy supports the notion that fetal microchimerism is a dynamic phenomenon, with fetal cells moving in and out of maternal circulation and surrounding tissues, possibly affected by the current physiologic state of the mother.

• Hagen, Kristine Krüger; Lie, Agnes Kathrine; Dahl, Gunn Fallås; Eyjólfsdóttir, Brynhildur; Wang, Yun & Ranum, Petter Skauen [Vis alle 12 forfattere av denne artikkelen] (2025). The Silva pattern-based classification and oncological outcomes in women undergoing fertility-sparing surgery for early-stage cervical cancer. International Journal of Gynecological Cancer. ISSN 1048-891X. 35(9). doi: 10.1016/j.ijgc.2025.102012. Fulltekst i vitenarkiv
• Sundet, Birgitte Kordt; Carlsen, Karin Cecilie Lødrup; Haugen, Guttorm Nils; Hedlin, Gunilla; Hilde, Katarina & Jonassen, Christine M [Vis alle 17 forfattere av denne artikkelen] (2025). Midpregnancy maternal circulating angiogenic biomarkers: Associations with placental dysfunction-related pregnancy complications and fetal sex. Placenta. ISSN 0143-4004. 171, s. 52–61. doi: 10.1016/j.placenta.2025.09.006. Fulltekst i vitenarkiv
• Engal, Eden; Gershon, Adi; Melamed, Shiri; Sharma, Aveksha; Ner-Gaon, Hadas & Herman, Shiri Jaffe [Vis alle 17 forfattere av denne artikkelen] (2025). Gestational diabetes mellitus alters placental precursor mRNA splicing. Diabetes. ISSN 0012-1797. 75(1), s. 193–204. doi: 10.2337/db25-0333. Fulltekst i vitenarkiv
• Slaats, Emiel; Schuch, Katharina; Sallinger, Katja; Schönberger, Julia; Bramreiter, Bernadette Luise & Anholts, Jaqueline [Vis alle 11 forfattere av denne artikkelen] (2025). Single Nucleotide Polymorphism Typing Going Spatial: In Situ Padlock Probes Targeting mRNA Variants to Identify Haploidentical Cells within the Tissue Environment. Clinical Chemistry. ISSN 0009-9147. 72(1), s. 163–172. doi: 10.1093/clinchem/hvaf119. Fulltekst i vitenarkiv
• Jacobsen, Daniel Pitz; Olsen, Maria Belland; Fjeldstad, Heidi; Sugulle, Meryam & Staff, Anne Cathrine (2025). Human leukocyte antigens and fetal microchimerism: Relating fetal-origin cells in maternal circulation to maternal and fetal HLA genetics. Journal of Reproductive Immunology. ISSN 0165-0378. 173. doi: 10.1016/j.jri.2025.104826. Fulltekst i vitenarkiv Vis sammendrag

  Fetal microchimerism denotes the presence of small amounts of fetal cells within the mother, which may persist for decades after pregnancy. The mechanisms by which these semiallogeneic cells avoid alloreactivity and manage to persist for years within the host are unknown. Previous reports have linked microchimerism to human leukocyte antigen (HLA) variants, such as HLA-C groups based on killer cell Immunoglobulin-like receptor (KIR) reactivity, HLA-DQA1*05:01, and soluble HLA-G (sHLA-G). In the present study, we attempt to verify these associations during pregnancy and postpartum. We included 255 pregnant women and 188 women between one and eight years postpartum. Data on HLA-C and HLADQA genotypes, as well as maternal circulating sHLA-G were available for a varying number of women, with cohorts ranging from 167 to 252 during pregnancy and 79–118 postpartum. Maternal and fetal HLA-C groups did not correlate with microchimerism during pregnancy or postpartum. HLA-C group mismatch from the perspective of the mother, on the other hand, negatively correlated with presence and quantity of fetal microchimerism in maternal circulation in the postpartum cohort, but not during pregnancy. Neither HLA-DQA1*05:01 nor circulating levels of sHLA-G were associated with microchimerism measurements. We confirm a negative correlation between circulating fetal microchimerism postpartum and fetal-maternal HLA-C mismatch based on KIR reactivity. Considering that such an association was not found at an HLA-C allele level in a previous publication, our present observation indicates that the interaction between microchimeric cell HLA-C variants and host killer-cell immunoglobulin-like receptors may be relevant for the longevity of microchimerism.

• Trent, Pernille Kristina Bjerre; Leitzinger, Nils; Wang, Yun; Dahl, Gunn Fallås; Eyjólfsdóttir, Brynhildur & Dahl, Jørgen Fallås [Vis alle 10 forfattere av denne artikkelen] (2025). The detection rate of metastatic lymph nodes comparing sentinel lymph node biopsy and lymphadenectomy for staging of intermediate- and high-risk endometrial carcinoma. International Journal of Gynecological Cancer. ISSN 1048-891X. 35(5). doi: 10.1016/j.ijgc.2025.101810. Fulltekst i vitenarkiv Vis sammendrag

  Objective The primary aim of this study was to compare the detection rates of nodal metastases between lymphadenectomy (LND) and sentinel lymph node (SLN) in intermediate- and high-risk patients with assumed uterine-confined disease. Methods This was a single-center observational study of patients from a tertiary referral center (2006-2023). Intermediate risk was defined as endometrioid adenocarcinoma grade 1/2 with ≥50% myoinvasion or grade 3 with <50% myoinvasion. High risk was defined as endometrioid adenocarcinoma grade 3 with ≥50% myoinvasion, non-endometrioid histologies regardless of myoinvasion or cervical involvement of any histology, and myoinvasion. All SLNs underwent pathologic ultra-staging. Nodal metastases were defined as the presence of macro- or micro-metastases. The comparison of metastatic lymph node rates by nodal assessment method was performed using the χ2 test and multivariable logistic regression analysis. Results A total of 996 patients were included (333 in the intermediate-risk group and 663 in the high-risk group). In the intermediate-risk group 192/333 (58%) patients underwent LND and 141/333 (42%) underwent SLN. Nodal metastases were detected in 11% and 9% of the LND and SLN cohorts (p = .46). Increasing proportions of staged patients were observed after SLN implementation (57% vs 78%) (p < .001). In the high-risk group, 412/663 (62%) patients underwent LND, and 251/663 (38%) underwent SLN. Nodal metastases were detected in 19% and 14% of the LND and SLN cohorts, respectively (p = .11). The majority of isolated tumor cells were observed in endometrioid histologies compared to non-endometrioid histologies (71% vs 29%, p = .01). Increasing proportions of staged patients were observed after SLN implementation (82% vs 88%) (p = .02). In the multivariable analysis, no association was observed between the nodal assessment method and the detection rates of nodal metastases in either risk group. Conclusions In this predominantly high-risk population, the implementation of an SLN algorithm did not compromise the detection of nodal metastases. As more patients are comprehensively staged after SLN implementation, we expect more accurate surgical staging and adjuvant therapy allocation in this specific patient group in the future.

• Sundet, Birgitte Kordt; Sugulle, Meryam; Jacobsen, Daniel Pitz; Bratseth, Vibeke; Palmero, Sheryl & Kindberg, Kristine Lovise Mørk [Vis alle 13 forfattere av denne artikkelen] (2025). Predelivery maternal circulating neutrophil extracellular traps and deoxyribonuclease in placental dysfunction and preeclampsia. American Journal of Obstetrics and Gynecology. ISSN 0002-9378. 234(2), s. 550–569. doi: 10.1016/j.ajog.2025.10.003. Fulltekst i vitenarkiv Vis sammendrag

  Background Neutrophil extracellular traps consist of DNA and protein and are secreted by neutrophils upon activation. They are stable structures but may be degraded by deoxyribonucleases. Neutrophil extracellular traps can induce endothelial dysfunction, an important feature of the preeclampsia pathophysiology. However, the levels of neutrophil extracellular traps biomarkers and deoxyribonuclease in the maternal circulation during preeclampsia, gestational hypertension, and fetal growth restriction, as well as potential associations to placental dysfunction, remain to be elucidated. Objective We aimed to investigate levels of circulating neutrophil extracellular traps biomarkers and deoxyribonuclease in women with early-onset and late-onset preeclampsia, gestational hypertension, and isolated fetal growth restriction compared to clinically healthy pregnancies. Additionally, we aimed to compare these biomarkers with circulating placental dysfunction biomarkers and maternal as well as fetal clinical proxies of placental dysfunction in women with preeclampsia. Study design Plasma and serum samples from women categorized as having early-onset preeclampsia (n=49), late-onset preeclampsia (n=202), gestational hypertension (n=105), isolated fetal growth restriction (n=50), and normotensive, euglycemic controls (n=1126) were analyzed by immunoassays for the circulating neutrophil extracellular traps biomarkers citrullinated histone H3 and myeloperoxidase-DNA and deoxyribonuclease and for the placental dysfunction biomarkers soluble fms-like tyrosine kinase-1 and placental growth factor. The Kruskal-Wallis H test was used to compare biomarker levels across groups. Post hoc pairwise comparisons were conducted using Dunn's test, with Bonferroni correction applied to adjust for multiple comparisons. In women with early-onset and late-onset preeclampsia, the residuals were not normally distributed. Therefore, univariable and multivariable quantile (median) regression for estimating models for the conditional median function were used to study associations between our biomarkers of interest and proxies for placental dysfunction. A 2-sided P value of <.05 was considered statistically significant. Results Women with early-onset and late-onset preeclampsia, but not gestational hypertension or isolated fetal growth restriction, had lower median levels of circulating citrullinated histone H3 (both adjusted P<.001) and deoxyribonuclease (both adjusted P<.001) compared to controls. Women with late-onset preeclampsia had lower myeloperoxidase-DNA (adjusted P<.001) compared to controls. Univariable regression analyses within the preeclampsia group revealed positive associations between citrullinated histone H3 and placental growth factor (P=.004) and negative associations between citrullinated histone H3 and soluble fms-like tyrosine kinase-1 (P=.034) and between deoxyribonuclease and soluble fms-like tyrosine kinase-1 (P=.038). In multivariable regression analyses, citrullinated histone H3 and placental growth factor (P=.009) and deoxyribonuclease and gestational age at blood sampling (P=.001) were positively associated, whereas citrullinated histone H3 (P=.027) and deoxyribonuclease (P=.034) were negatively associated with systolic blood pressure. Finally, citrullinated histone H3 was associated with newborn weight ≤10th percentile, representing a fetal proxy for placental dysfunction (P=.036). Conclusion The lower levels of circulating neutrophil extracellular traps and deoxyribonuclease in women with preeclampsia, but not in gestational hypertension or isolated fetal growth restriction, as well as associations between citrullinated histone H3 and biomarkers of placental dysfunction may indicate that neutrophil extracellular traps play a role in the placental dysfunction that exclusively characterizes preeclampsia. Additionally, the association between low citrullinated histone H3, low deoxyribonuclease, and high maternal blood pressure may suggest that insufficient presence of circulating deoxyribonucleases contributes to the excessive vascular inflammation in women with preeclampsia.

• Berge, Magnus Bollum; Jacobsen, Anne Flem; Yli, Branka Markovic; Staff, Annetine; Gunnes, Nina & Falk, Ragnhild Sørum [Vis alle 8 forfattere av denne artikkelen] (2025). A direct comparison of the diagnostic accuracy of ST segment analysis (STAN) and fetal scalp blood sample lactate: A population-based observational study. European Journal of Obstetrics, Gynecology, and Reproductive Biology. ISSN 0301-2115. 308, s. 147–152. doi: 10.1016/j.ejogrb.2025.03.002. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Fetal scalp blood sample (FBS) lactate and ST analysis (STAN) are adjuncts to cardiotocography (CTG) in high-risk deliveries, aiming to increase the specificity of the fetal monitoring. These methods have never been compared directly, through simultaneous evaluation in the same deliveries. Material and methods: We conducted a prospective, population-based study on deliveries with singleton, cephalic fetuses in gestational week ≥ 36 + 0 monitored with internal CTG. Cases were defined as deliveries with umbilical cord artery pH ≤ 7.10. For each case, the following three deliveries with umbilical cord artery pH > 7.10 were included as controls. The sensitivity and specificity of FBS lactate and STAN for the predefined adverse neonatal outcomes were compared using McNemar’s test. Results: Of 10,000 women included by passive consent, 178 deliveries were included as cases, and 516 as controls. STAN had a significantly higher sensitivity for the main outcome (pH ≤ 7.10) compared to FBS lactate (49 % vs. 40 %, p = 0.03). Although STAN showed a tendency toward a higher sensitivity for the secondary outcomes, differences were not statistically significant (p = 0.14–0.50). FBS lactate had significantly higher specificity for all outcomes (main outcome 88 % vs. 69 %, p < 0.01). Conclusions: STAN demonstrated a higher sensitivity for moderate acidemia compared to FBS lactate, but with lower specificity for all outcomes. These results do not not provide evidence to support the choice of one fetal surveillance system over the other. Further research should focus on how potential advantages of either method could be combined.

• Bowe, Sophie; Mitlid-Mork, Birgitte; Staff, Annetine & Sugulle, Meryam (2025). PlGF and sFlt-1, reduced fetal movements and adverse delivery outcome of a likely placental cause: A real world prospective observational study. European Journal of Obstetrics, Gynecology, and Reproductive Biology. ISSN 0301-2115. 307, s. 34–42. doi: 10.1016/j.ejogrb.2025.01.029. Fulltekst i vitenarkiv
• Klepp, Kristina; Staff, Annetine; Sugulle, Meryam & Moe, Kjartan (2025). Body mass index is similar to alternative anthropometric indices in evaluating plasma lipids as proxy for cardiovascular disease in women with previous hypertensive disorders of pregnancy: A cross-sectional study. Women's Health. ISSN 1745-5057. 21. doi: 10.1177/17455057241310316. Fulltekst i vitenarkiv Vis sammendrag

  Background: Women with previous hypertensive disorders of pregnancy (HDP) have increased risk of cardiovascular disease (CVD). Overweight is a modifiable risk factor for both conditions. Anthropometric indices such as waist circumference, hip circumference, waist-to-hip ratio, estimated total body fat, a body shape index, waist-to-hip-to-height ratio, and index of central obesity improve estimation of cardiovascular death risk in the general population as compared to body mass index (BMI). Objectives: We aimed to assess whether alternative body mass composition indices associate more strongly with postpartum blood lipid levels, as a proxy for CVD risk, than BMI. We also aimed to investigate whether associations differ between women with previous normotensive or hypertensive index pregnancies. Design: In this cross-sectional study, we examined 296 women 1 or 3 years after an index pregnancy that was normotensive (n = 116) or complicated by a hypertensive pregnancy disorder, including preeclampsia (n = 133) or gestational hypertension (n = 47). Methods: Uni- and multivariable regression analyses, adjusted for age and smoking, were conducted to evaluate associations between postpartum body mass composition indices and blood lipids. p < 0.05 was considered statistically significant. Results: Median BMI and overweight rates were higher in women with previous HDP than in controls (23.9 kg/m2 versus 22.8 kg/m2 and 44.4% versus 30.2%, both p ⩽ 0.03). No body mass composition indices in any pregnancy complication group showed stronger associations with adverse lipid levels than BMI. However, women with previous HDP more often displayed significant associations between adverse body mass composition indices and adverse lipid levels, compared with controls. Conclusion: Alternative anthropometric measurements are not better suited to evaluate circulating lipids as proxy for CVD risk after HDP, compared to BMI. We hence recommend using BMI in CVD risk assessment after HDP due to its current widespread use and feasibility.

• Oversand, Sissel Hegdahl; Staff, Annetine; Volløyhaug, Ingrid & Svenningsen, Rune (2025). Impact of levator ani muscle avulsions on Manchester procedure outcomes: A 5-year follow-up study. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. doi: 10.1111/aogs.15102. Fulltekst i vitenarkiv
• Jacobsen, Daniel Pitz; Fjeldstad, Heidi Elisabeth Storebø; Olsen, Maria Belland; Sugulle, Meryam & Staff, Annetine (2025). Microchimerism and pregnancy complications with placental dysfunction. Seminars in Immunopathology. ISSN 1863-2297. 47(1). doi: 10.1007/s00281-025-01045-w. Fulltekst i vitenarkiv
• Gerdin, Sabina Wärnberg; Skjerven, Håvard Ove; Konradsen, Jon R.; Borres, Magnus P.; Granum, Berit & Jonassen, Christine M [Vis alle 16 forfattere av denne artikkelen] (2025). The Effect of Early Food Introduction and Skin Emollients on Pollen Sensitization: A Randomized Trial (PreventADALL) Sub-Study. Journal of Allergy and Clinical Immunology: In Practice. ISSN 2213-2198. 13(6), s. 1325–1334. doi: 10.1016/j.jaip.2025.03.046. Fulltekst i vitenarkiv Vis sammendrag

  Background Pollen sensitization may be directed toward proteins also found in plant foods. Objective We explored whether early food introduction and skin emollients prevented birch and grass sensitization at age 3 years and whether the effect was mediated by skin barrier function or modified by season of birth. Methods In the population-based, randomized, controlled Preventing Atopic Dermatitis and Allergy in Children trial, information on allergic sensitization by age 3 years was available in 2,066 children. Newborns were randomized (1:1:1:1) to no (controls); to food (tastes of peanut, cow’s milk, wheat, and egg from 3 months) or skin (oil baths and facial cream from 2 weeks); or to both interventions. Sensitization was defined as specific IgE 0.1 kUA/L or greater and/or skin prick test wheal 3 mm or greater. A mediator analysis assessed the skin intervention’s effect through transepidermal water loss at 3 months. An interaction analysis estimated effect modification by month of birth. Results At age 3 years, 117 of 1,492 children (7.8%) were sensitized to birch and 40 of 1,482 children (2.7%) to timothy. Compared with controls, crude odds ratio (95% CI) in the food, skin, and combined intervention groups, respectively, was 1.10 (0.63-1.93), 2.38 (1.43-3.95), and 0.70 (0.37-1.34) for birch, and 0.58 (0.21-1.60), 1.73 (0.77-3.91), and 1.00 (0.40-2.49) for grass sensitization. A significant indirect effect of the skin intervention through transepidermal water loss was observed, but there was no significant modification by month of birth for either intervention. Conclusions Early food introduction did not affect the risk of pollen sensitization. Infants with skin intervention had increased risk only of birch sensitization, mediated by reduced skin barrier function in early infancy.

• Berge, Magnus; Kessler, Jørg; Staff, Annetine & Jacobsen, Anne Flem (2025). The diagnostic accuracy of different fetal blood sample lactate cutoffs in labor, utilizing the StatStrip Xpress® lactate-meter: A population-based observational study. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 104(8), s. 1496–1504. doi: 10.1111/aogs.15140. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: A recent study recommended 5.2 mmol/L as a cutoff for fetal blood sample (FBS) lactate in labor for the StatStrip Lactate®/Lactate Xpress® lactate meter. In the present study, we validated FBS lactate cutoffs in a larger population-based setting, with different CTG guidelines, testing external validity. Material and Methods: We conducted a prospective population-based study at Oslo University Hospital, Ullevål, Norway, a tertiary referral obstetric department with 7000 annual deliveries. Women with a singleton fetus in cephalic presentation in gestational week ≥36 + 0 were included in the analyses. We used ROC curves to calculate the area under the curve (AUC) and estimate the optimal cutoff for the following adverse neonatal outcomes: Umbilical cord pH ≤7.10, umbilical cord pH ≤7.05, metabolic acidosis (pH <7.0 and Base deficitextracellular fluid > 12 mmol/L), 1-minute Apgar score <4, 5-min Apgar score <7, hypoxic ischemic encephalopathy, and transfer to the neonatal intensive care unit. Analyses were restricted to women with a FBS lactate within 25 min prior to delivery. The study is registered in clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT04779294). Results: Of 7816 included women, 1466 (19%) had a FBS lactate measurement within 25 min prior to delivery. The calculated optimal cutoff for FBS lactate varied by outcomes: 5-min Apgar score <7: AUC 0.69 (0.57–0.80), cutoff 4.0 mmol/L; metabolic acidosis: AUC 0.92 (0.78–1.00), cutoff 7.0 mmol/L; hypoxic ischemic encephalopathy: AUC 0.95 (0.86–1.00), cutoff 4.7 mmol/L. Sensitivity increased for some of the outcomes with a decreasing cutoff. Specificity increased for all outcomes with an increasing cutoff. Conclusions: We consider an FBS lactate cutoff of ≥5.2 mmol/L a good balance between high sensitivity for adverse neonatal outcomes and an acceptable number of needed interventions.

• Bains, Karen Eline Stensby; Kreyberg, Ina; Färdig, Martin; Granum, Berit; Gudmundsdottir, Hrefna Katrin & Haugen, Guttorm Nils [Vis alle 17 forfattere av denne artikkelen] (2024). Maternal use of snus as smokeless tobacco in pregnancy and infant lung function. European Respiratory Journal Open Research (ERJ Open Research). 10(4). doi: 10.1183/23120541.00958-2023. Fulltekst i vitenarkiv Vis sammendrag

  Background Smoking in pregnancy has detrimental effects on infant respiratory health, while the effects of other nicotine-containing products on infant lung function are unclear. We aimed to explore if smokeless tobacco such as snus used in pregnancy increased the risk of lower lung function in infancy and if the associations differed by sex. Methods From the Scandinavian population-based Preventing Atopic Dermatitis and ALLergies in Children birth cohort, we included 1163 infants with available tidal flow-volume measurements at 3 months of age and maternal self-reported use of nicotine-containing products in pregnancy. The risk of a ratio of time to peak tidal expiratory flow to total expiratory time <25th percentile by any nicotine exposure, snus exclusively and cigarette smoking with or without other nicotine-containing products was explored by regression analyses adjusting for maternal age, education and asthma. Results Overall 120 out of 1163 (10.3%) infants were exposed to any nicotine in utero, 71 out of 120 by snus exclusively and 49 out of 120 by smoking, with six also exposed to snus. By pregnancy week 6, 85.8% of mothers reported stopping nicotine use. The risk of lower lung function was higher in children exposed in utero to nicotine-containing products with an odds ratio (OR) of 1.63 (95% confidence interval (CI) 1.02–2.59) with a similar tendency for snus exclusively (OR 1.55, 95% CI 0.88–2.71) and smoking (OR 1.79, 0.84–3.84). Effect estimates were similar after adjusting for covariates. No differences of the effect by sex were observed. Conclusion Our study suggests that in utero exposure to not only cigarettes, but also snus, may negatively affect infant lung function.

• Staff, Anne Cathrine; Costa, Maria Laura; Dechend, Ralf; Jacobsen, Daniel Pitz & Sugulle, Meryam (2024). Hypertensive disorders of pregnancy and long-term maternal cardiovascular risk: Bridging epidemiological knowledge into personalized postpartum care and follow-up. Pregnancy Hypertension. ISSN 2210-7789. 36. doi: 10.1016/j.preghy.2024.101127. Fulltekst i vitenarkiv Vis sammendrag

  Cardiovascular disease (CVD) is globally the leading cause of death and disability. Sex-specific causes of female CVD are under-investigated. Pregnancy remains an underinvestigated sex-specific stress test for future CVD and a hitherto missed opportunity to initiate prevention of CVD at a young age. Population-based studies show a strong association between female CVD and hypertensive disorders of pregnancy. This association is also present after other pregnancy complications that are associated with placental dysfunction, including fetal growth restriction, preterm delivery and gestational diabetes mellitus. Few women are, however, offered systematic cardio-preventive follow-up after such pregnancy complications. These women typically seek help from the health system at first clinical symptom of CVD, which may be decades later. By this time, morbidity is established and years of preventive opportunities have been missed out. Early identification of modifiable risk factors starting postpartum followed by systematic preventive measures could improve maternal cardiovascular health trajectories, promoting healthier societies. In this non-systematic review we briefly summarize the epidemiological associations and pathophysiological hypotheses for the associations. We summarize current clinical follow-up strategies, including some proposed by international and national guidelines as well as user support groups. We address modifiable factors that may be underexploited in the postpartum period, including breastfeeding and blood pressure management. We suggest a way forward and discuss the remaining knowledge gaps and barriers for securing the best evidence-based follow-up, relative to available resources after a hypertensive pregnancy complication in order to prevent or delay onset of premature CVD.

• Staff, Anne Cathrine; Fjeldstad, Heidi; Olsen, Maria Belland; Øgaard, Jonas Daniel Sjøberg; Viken, Marte Kathrine & Kramer, Cynthia S. M. [Vis alle 12 forfattere av denne artikkelen] (2024). Foetal Microchimerism Correlates With Foetal-Maternal Histocompatibility Both During Pregnancy and Postpartum. HLA. ISSN 2059-2302. 104:e15717(4), s. 1–11. doi: 10.1111/tan.15717. Fulltekst i vitenarkiv Vis sammendrag

  Foetal cells are detectable in women decades postpartum, a state termed foetal microchimerism. The interplay between these semi-allogeneic foetal cells and the mother could be affected by genetic mismatches in the HLA loci. Here, we relate HLA allele and molecular mismatch values to the presence and quantity of foetal microchimerism in the maternal circulation during pregnancy and postpartum. A total of 76 pregnant women were included, of which 59 were followed up 1–8 years postpartum. Maternal and foetal DNA was genotyped for HLA class I and II loci. Foetal cells in maternal buffy coat were detected by qPCR, targeting inherited paternal alleles. Antibody-verified eplet mismatch and Predicted Indirectly Recognisable HLA Epitopes (PIRCHE) scores were calculated to quantify foetal-maternal histocompatibility from the mother's perspective. Circulating foetal cells were detected in 50.0% (38/76) of women during pregnancy, and 25.4% (15/59) postpartum. During pregnancy, HLA class II antibody-verified eplet mismatch load and PIRCHE scores correlated negatively with the presence and quantity of foetal cells in the maternal circulation. Postpartum, HLA class I allele mismatches correlated negatively with foetal microchimerism presence, while HLA class II allele mismatches, HLA class I and II antibody-verified eplet mismatch load, and PIRCHE-I and PIRCHE-II scores correlated negatively with both microchimerism presence and quantity. The correlation between mismatch parameters aimed at evaluating the risk of humoral and T cell-mediated allorecognition and foetal microchimerism was more evident postpartum than during pregnancy. The observed predictive effect of foetal-maternal histocompatibility on foetal microchimerism suggests that circulating foetal cells are subject to clearance by the maternal immune system. We propose that allorecognition of foetal cells in the maternal circulation and tissues influences any long-term effect that foetal microchimerism may have on maternal health.

• Rehbinder, Eva Maria; Gerdin, Sabina Wärnberg; Hoyer, Angela; Bradley, Maria; Carlsen, Karin C. Lødrup & Granum, Berit [Vis alle 15 forfattere av denne artikkelen] (2024). Frequent oil baths and skin barrier during infancy in the PreventADALL study. British Journal of Dermatology. ISSN 0007-0963. 191(1), s. 49–57. doi: 10.1093/bjd/ljae091. Fulltekst i vitenarkiv Vis sammendrag

  Background In the general population randomized controlled trial PreventADALL, frequent emollient bath additives from 2 weeks of age did not prevent atopic dermatitis, while the effect on skin barrier function throughout infancy is not established. Objectives The primary aim of this exploratory substudy was to assess the effect of mineral-based oil baths on transepidermal water loss (TEWL) and dry skin through infancy, and secondarily to explore if filaggrin (FLG) mutations modified the effect. Methods Overall, 2153 infants were included and randomized to either the ‘Skin intervention’ (SI) group (n = 995) (oil bath 4 times weekly from 2 weeks through 8 months) or ‘No skin intervention’ (NSI) group (n = 1158), with TEWL measurements at 3, 6 and/or 12 months of age. Information on FLG mutation status was available for 1683 of these infants. Effects of the skin intervention on TEWL and dry skin through infancy were assessed by mixed-effects regression modelling. Background characteristics and protocol adherence were collected from electronic questionnaires, birth records and weekly diaries. Results The TEWL (95% confidence interval) was on average 0.42 g m–2 h–1 (0.13–0.70, P = 0.004) higher in the SI group compared with the NSI group through the first year of life, with significantly higher levels at 3 months [8.6 (8.3–9.0) vs. 7.6 (7.3–7.9)], but similar at 6 and 12 months. Dry skin was observed significantly more often in the NSI group compared with the SI group at 3 months (59% vs. 51%) and at 6 months of age (63% vs. 53%), while at 12 months of age, the difference was no longer significant. At 3 months, the TEWL of FLG mutation carriers was similar to the TEWL in the SI group. No interaction between SI and FLG mutation was found in the first year of life. Conclusions Infants given frequent oil baths from 2 weeks of age had reduced skin barrier function through infancy compared with controls, largely attributed to higher TEWL at 3 months of age, while the skin at 3 and 6 months appeared less dry in infants subjected to the skin intervention.

• Sugulle, Meryam; Fiskå, Bendik Seth; Jacobsen, Daniel Pitz; Fjeldstad, Heidi Elisabeth Storebø & Staff, Anne Cathrine (2024). Placental Senescence and the Two-Stage Model of Preeclampsia. American journal of reproductive immunology. ISSN 1046-7408. 92(1). doi: 10.1111/aji.13904. Fulltekst i vitenarkiv
• Sukmanee, Jarawee; Rothmanee, Penkae; Sriwimol, Wilaiwan; Staff, Anne Cathrine & Liabsuetrakul, Tippawan (2024). Cardiovascular Biomarkers and Blood Pressure at 6 Weeks and 6-12 Months Postpartum in Women With or Without Hypertensive Disorders During Pregnancy: A Prospective Study. Journal of Health Science and Medical Research (JHSMR). 42(3). doi: 10.31584/jhsmr.20231019. Fulltekst i vitenarkiv Vis sammendrag

  Objective: To measure and compare cardiovascular biomarkers and blood pressure in women with hypertensive disorders of pregnancy (HDP) to those with normotensive pregnancies evaluated at 6 weeks and 6-12 months after delivery. Material and Methods: A prospective cohort study of postpartum women following HDP and normotensive pregnancies at 6 weeks and 6-12 months postpartum was conducted. Postpartum blood pressure and cardiovascular biomarkers including body mass index (BMI), levels of serum high-sensitivity C-reactive protein (hs-CRP), creatinine, glucose, glycated hemoglobin, low-density lipoprotein cholesterol, and levels of urine microalbumin/creatinine ratio (UACR), sodium, and potassium were quantified. Results: A total of 118 women involving 40 with previous preeclampsia (PE), 27 with gestational hypertension (GHT), 10 with chronic hypertension (CHT) during recent pregnancy, and 41 normotensive pregnancies were enrolled at 6 weeks postpartum, of whom 73 (61.9%) completed the study at 6-12 months postpartum. Women in the PE and GHT groups had significantly elevated blood pressure, serum hs-CRP and hypertension at 6 weeks and 6-12 months postpartum. Both the PE and CHT groups had an increase in UACR at 6-12 months postpartum. Multivariate linear regression showed that a history of PE and GHT was independently and persistently associated with increased postpartum blood pressure. Conclusion: Women with HDP had increased blood pressure, risk of hypertension, and increased levels of biomarkers associated with cardiovascular risk at both 6 weeks and 6-12 months postpartum, including serum hs-CRP and UACR. Women with HDP should be counselled about cardiovascular risks as early as 6 weeks postpartum.

• Værnesbranden, Caren Magdalena Rydland; Staff, Anne Cathrine; Wiik, Johanna; Sjøborg, Katrine Dønvold; Rüegg, Corina Silvia & Sugulle, Meryam [Vis alle 21 forfattere av denne artikkelen] (2024). Placental human papillomavirus infections and adverse pregnancy outcomes. Placenta. ISSN 0143-4004. 152, s. 23–30. doi: 10.1016/j.placenta.2024.05.126. Fulltekst i vitenarkiv Vis sammendrag

  Introduction Knowledge on prevalence and association of human papillomavirus (HPV) in third trimester placentae and adverse pregnancy outcomes is limited. We investigated the prevalence of placental HPV at delivery, explored urine HPV characteristics associated with placental HPV and whether placental HPV increased the risk adverse pregnancy outcomes. Methods Pregnant women were enrolled in the Scandinavian PreventADALL mother-child cohort study at midgestation. Human papillomavirus genotyping was performed on placental biopsies collected at delivery (n = 587) and first-void urine at midgestation and delivery (n = 556). Maternal characteristics were collected by questionnaires at gestational week 18 and 34. Adverse pregnancy outcomes were registered from chart data including hypertensive disorders of pregnancy, gestational diabetes mellitus and newborns small for gestational age. Uni- and multivariable regression models were used to investigate associations. Results Placental HPV was detected in 18/587 (3 %). Twenty-eight genotypes were identified among the 214/556 (38 %) with midgestational urine HPV. Seventeen of the 18 women with placental HPV were midgestational HPV positive with 89 % genotype concordance. Midgestational high-risk-(HR)-HPV and high viral loads of Any- or HR-HPV were associated with placental HPV. Persisting HPV infection from midgestation to delivery was not associated with placental HPV. Adverse pregnancy outcomes were seen in 2/556 (0.4 %) of women with placental HPV. Discussion In this general cohort of pregnant women, the prevalence of placental HPV was 3 %, and midgestational urinary HPV 38 %. High HPV viral load increased the risk for placental HPV infections. We observed no increased risk for adverse pregnancy outcomes in women with placental HPV.

• Aanstad, Kristin Jerve; Pripp, Are Hugo; Dalbye, Rebecka; Pay, Aase Serine Devold; Staff, Anne Cathrine & Kaasen, Anne [Vis alle 7 forfattere av denne artikkelen] (2024). Intrapartum fetal monitoring practices in Norway: A population-based study. Sexual & Reproductive HealthCare. ISSN 1877-5756. 41. doi: 10.1016/j.srhc.2024.101006. Fulltekst i vitenarkiv Vis sammendrag

  Objective: To describe intrapartum fetal monitoring methods used in all births in Norway in 2019–2020, assess adherence to national guidelines, investigate variation by women’s risk status, and explore associations influencing monitoring practices. Methods: A nationwide population-based study. We collected data about all pregnancies with a gestational age ≥ 22 weeks during 2019–2020 from the Medical Birth Registry of Norway. We used descriptive analyses, stratified for risk status, to examine fetal monitoring methods used in all deliveries. Univariable and multivariable logistic regression models were used to determine factors associated with monitoring with cardiotocography (CTG) in low-risk, straightforward births. Results: In total, 14 285 (14%) deliveries were monitored with only intermittent auscultation (IA), 46 214 (46%) with only CTG, and 33 417 (34%) with IA and CTG combined. Four percent (2 067/50 533) of women with risk factors were monitored with IA only. Half (10 589/21 282) of the low-risk women with straightforward births were monitored with CTG. Maternal and fetal characteristics, size of the birth unit and regional practices influenced use of CTG monitoring in this group. Conclusions: Most births are monitored with CTG only, or combined with IA. Half the women with low-risk pregnancies and straightforward births were monitored with CTG although national guidelines recommending IA.

• Fjeldstad, Heidi; Jacobsen, Daniel Pitz; Johnsen, Guro Mørk; Sugulle, Meryam; Chae, Angel & Kanaan, Sami B. [Vis alle 8 forfattere av denne artikkelen] (2024). Fetal-origin cells in maternal circulation correlate with placental dysfunction, fetal sex, and severe hypertension during pregnancy. Journal of Reproductive Immunology. ISSN 0165-0378. 162. doi: 10.1016/j.jri.2024.104206. Fulltekst i vitenarkiv Vis sammendrag

  Fetal microchimerism (FMc) arises when fetal cells enter maternal circulation, potentially persisting for decades. Increased FMc is associated with fetal growth restriction, preeclampsia, and anti-angiogenic shift in placenta-associated proteins in diabetic and normotensive term pregnancies. The two-stage model of preeclampsia postulates that placental dysfunction causes such shift in placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLt-1), triggering maternal vascular inflammation and endothelial dysfunction. We investigated whether anti-angiogenic shift, fetal sex, fetal growth restriction, and severe maternal hypertension correlate with FMc in hypertensive disorders of pregnancy with new-onset features (n = 125). Maternal blood was drawn pre-delivery at > 25 weeks' gestation. FMc was detected by quantitative polymerase chain reaction targeting paternally inherited unique fetal alleles. PlGF and sFlt-1 were measured by immunoassay. We estimated odds ratios (ORs) by logistic regression and detection rate ratios (DRRs) by negative binomial regression. PlGF correlated negatively with FMc quantity (DRR = 0.2, p = 0.005) and female fetal sex correlated positively with FMc prevalence (OR = 5.0, p < 0.001) and quantity (DRR = 4.5, p < 0.001). Fetal growth restriction no longer correlated with increased FMc quantity after adjustment for correlates of placental dysfunction (DRR = 1.5, p = 0.272), whereas severe hypertension remained correlated with both FMc measures (OR = 5.5, p = 0.006; DRR = 6.3, p = 0.001). Our findings suggest that increased FMc is independently associated with both stages of the two-stage preeclampsia model. The association with female fetal sex has implications for microchimerism detection methodology. Future studies should target both male and female-origin FMc and focus on clarifying which placental mechanisms impact fetal cell transfer and how FMc impacts the maternal vasculature.

• Hoel, Sissel; Moe, Kjartan; Sugulle, Meryam; Petrovski, Goran; Veiby, Nina & Staff, Anne Cathrine (2024). Retinal oximetry and microvascular assessment after hypertensive pregnancy complications. Acta Ophthalmologica. ISSN 1755-375X. 102(6), s. 653–661. doi: 10.1111/aos.16651. Fulltekst i vitenarkiv Vis sammendrag

  Purpose Women with hypertensive disorders of pregnancy (HDP) are at increased risk of developing premature cardiovascular disease (CVD). The mechanisms behind this are not fully understood, but microvascular alterations have been documented in retinal arterioles and venules. The aim of this study was to use non-invasive retinal imaging to investigate the structural and functional properties of arterioles, venules and capillaries in this patient group. Methods We examined 27 women with previous HDP and 23 controls at 3 years postpartum. The retinal microvasculature was assessed by vessel calibre measurements, retinal oximetry and optical coherence tomography angiography. Differences were analysed using non-parametric tests and multiple regression analyses, adjusted for age and body mass index. Results Median arteriolar oxygen saturation (SaO2; 94.2% vs. 93.0%), venular oxygen saturation (SvO2; 60.1% vs. 62.4%) and arteriovenous saturation difference (AV-difference; 32.8% vs. 32.3%) were similar across groups. Capillary vessel density (VD; 46.2% vs. 46.3%), skeletonised VD (VSD; 21.3 vs. 21.1 mm/mm2) and vessel diameter index (21.65 vs. 21.86) were also comparable. In the HDP group, mean arterial pressure (MAP) was positively correlated with AV-difference (R2 = 0.209) and negatively correlated with arteriolar diameter (CRAE; r2 = 0.382). Conclusions Structural microvascular alterations appear not to be key biomarkers for CVD risk after HDP as early as 3 years postpartum in otherwise healthy women. Further studies are needed to evaluate whether such changes occur later in life. MAP was associated with AV-difference only in the HDP group, suggesting specific mechanisms affecting functional microvascular properties in these women.

• Nonn, Olivia; Debnath, Olivia; Valdes, Daniela S.; Sallinger, Katja; Secener, Ali Kerim & Fischer, Cornelius [Vis alle 42 forfattere av denne artikkelen] (2024). Senescent Syncytiotrophoblast Secretion During Early Onset Preeclampsia. Hypertension. ISSN 0194-911X. doi: 10.1161/HYPERTENSIONAHA.124.23362. Fulltekst i vitenarkiv Vis sammendrag

  BACKGROUND: Preeclampsia is a severe hypertensive disorder in pregnancy that causes preterm delivery, maternal and fetal morbidity, mortality, and life-long sequelae. Understanding the pathogenesis of preeclampsia is a critical first step toward protecting mother and child from this syndrome and increased risk of cardiovascular disease later in life. However, effective early predictive tests and therapies for preeclampsia are scarce. METHODS: To identify novel markers and signaling pathways for early onset preeclampsia, we profiled human maternal-fetal interface units (fetal villi and maternal decidua) from early onset preeclampsia and healthy controls using single-nucleus RNA sequencing combined with spatial transcriptomics. The placental syncytiotrophoblast is in direct contact with maternal blood and forms the barrier between fetal and maternal circulation. RESULTS: We identified different transcriptomic states of the endocrine syncytiotrophoblast nuclei with patterns of dysregulation associated with a senescence-associated secretory phenotype and a spatial dysregulation of senescence in the placental trophoblast layer. Elevated senescence markers were validated in placental tissues of clinical multicenter cohorts. Importantly, several secreted senescence-associated secretory phenotype factors were elevated in maternal blood already in the first trimester. We verified the secreted senescence markers, PAI-1 (plasminogen activator inhibitor 1) and activin A, as identified in our single-nucleus RNA sequencing model as predictive markers before clinical preeclampsia diagnosis. CONCLUSIONS: This indicates that increased syncytiotrophoblast senescence appears weeks before clinical manifestation of early onset preeclampsia, suggesting that the dysregulated preeclamptic placenta starts with higher cell maturation resulting in premature and increased senescence-associated secretory phenotype release. These senescence-associated secretory phenotype markers may serve as an additional early diagnostic tool for this syndrome.

• Værnesbranden, Caren Magdalena Rydland; Staff, Anne Cathrine; Wiik, Johanna; Sjøborg, Katrine Dønvold; Rueegg, Corina Silvia & Sugulle, Meryam [Vis alle 19 forfattere av denne artikkelen] (2024). Human papillomavirus infections during pregnancy and adverse pregnancy outcomes: a Scandinavian prospective mother-child cohort study. BMC Pregnancy and Childbirth. 24(1). doi: 10.1186/s12884-024-06958-2. Fulltekst i vitenarkiv Vis sammendrag

  Background Human papillomaviruses are common in the urogenital tract amongst women of childbearing age. A few studies indicate a possible association between human papillomavirus infections in pregnancy and adverse pregnancy outcomes whilst other studies find no such association. We aimed to investigate the association between human papillomavirus infections during pregnancy and adverse pregnancy outcomes linked to placental dysfunction, including hypertensive disorders of pregnancy, gestational diabetes mellitus and newborns small for gestational age. Materials and methods Pregnant women from the general population in Norway and Sweden were enrolled at the time of routine mid-gestational ultrasound examination. Urine samples collected at mid-gestation in 950 and at delivery in 753 participants, were analyzed for 28 human papillomavirus genotypes, including 12 high-risk genotypes. Participants completed electronic questionnaires at enrollment and medical records were reviewed for background characteristics and for the following adverse pregnancy outcomes: hypertensive disorders of pregnancy including gestational hypertension, preeclampsia, superimposed preeclampsia, eclampsia and Hemolysis Elevated Liver enzymes and Low Platelets (HELLP) syndrome, gestational diabetes mellitus, and newborns small for gestational age. Associations between adverse pregnancy outcomes and (a) any human papillomavirus, high-risk human papillomavirus and human papillomavirus genotype 16 infection at mid-gestation, (b) multiple genotype infections at mid-gestation, and (c) persisting infections during pregnancy were assessed with univariable and multivariable logistic regression models. Missing covariates were imputed using multiple imputation. Results At mid-gestation, 40% (377/950) of women were positive for any of the 28 genotypes, 24% (231/950) for high-risk genotypes and human papillomavirus 16 was found in 6% (59/950) of the women. Hypertensive disorders of pregnancy was observed in 9% (83/950), gestational diabetes mellitus in 4% (40/950) and newborns small for gestational age in 7% (67/950). Human papillomavirus infection with any genotype, high-risk or human papillomavirus genotype 16 at mid-gestation was not associated with adverse pregnancy outcomes. No associations were found for multiple genotype infections at mid-gestation or persisting infections. Conclusion In a general population of pregnant women, we found no evidence of human papillomavirus infections during pregnancy being associated with hypertensive disorders of pregnancy, gestational diabetes mellitus, or newborns small for gestational age. Trial registration Trial registration The study is registered at ClincialTrials.gov; NCT02449850 on May 19th, 2015. Graphical Abstract

• Søfteland, Solrun; Sebitloane, Motshedisi; Galappaththi-Arachchige, Hashini Nilushika; Kleppa, Elisabeth; Holmen, Sigve & Pillay, Pavitra [Vis alle 14 forfattere av denne artikkelen] (2024). Diagnosis of female genital schistosomiasis and other genital infections in young South African women: challenges in the syndromic approach. Frontiers in Tropical Diseases. 5. doi: 10.3389/fitd.2024.1379526. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Female genital schistosomiasis is a common but neglected disease, which results in symptoms similar to sexually transmitted infections in Schistosoma haematobium-endemic areas of Africa and Middle East. In primary healthcare of low-income countries, healthcare professionals use syndromic management protocols for guidance when treating symptoms of genital infection, due to lack of laboratory resources. These protocols do not include treatment for female genital schistosomiasis, despite the overlap of symptoms. Women are at risk of not receiving the appropriate treatment. The aim of this study was to investigate challenges and missed opportunities when using syndromic management protocols for sexually transmitted infections in female genital schistosomiasis-endemic areas. Methods: This is a secondary analysis of data from a large cross-sectional prevalence study conducted in 2011 in KwaZulu-Natal, South Africa. Young women in schistosomiasis-endemic areas were asked about genital symptoms and und

• Färdig, Martin; Hoyer, Angela; Almqvist, Catarina; Bains, Karen Eline S.; Carlsen, Karin C. Lødrup & Gudmundsdottir, Hrefna Katrin [Vis alle 18 forfattere av denne artikkelen] (2024). Infant lung function and early skin barrier impairment in the development of asthma at age 3 years. Allergy. European Journal of Allergy and Clinical Immunology. ISSN 0105-4538. 79(3), s. 667–678. doi: 10.1111/all.16024. Fulltekst i vitenarkiv Vis sammendrag

  Background Largely unexplored, we investigated if lower lung function, impaired skin barrier function by transepidermal water loss (TEWL), eczema, and filaggrin (FLG) mutations in infancy were associated with asthma in early childhood. Methods From the factorially designed randomized controlled intervention study PreventADALL, we evaluated 1337/2394 children from all randomization groups with information on asthma at age 3 years, and at age 3 months either lung function, TEWL, eczema, and/or FLG mutations. Lower lung function was defined as the time to peak tidal expiratory flow to expiratory time (tPTEF/tE) <0.25, and skin barrier impairment as a high TEWL >9.50 g/m2/h. Eczema was clinically observed, and DNA genotyped for FLG mutations. Asthma was defined as asthma-like symptoms (≥3 episodes of bronchial obstruction) between age 2–3 years as well as a history of doctor-diagnosed asthma and/or asthma medication use. Associations were analyzed in logistic regression models, presented with adjusted ORs (aOR) and 95% confidence intervals (CI). Results Lower lung function and skin barrier impairment were associated with asthma in general; aOR (95% CI) 5.4 (2.1, 13.7) and 1.6 (1.1, 2.5), while eczema and FLG mutations were associated with asthma in children with atopic dermatitis or allergic sensitization only. Stratifying for sex, the risk of asthma was only increased in boys with lower lung function; aOR (95% CI) 7.7 (2.5, 23.6), and in girls with FLG mutations; aOR (95% CI) 3.5 (1.5, 8.2). Conclusion Lower lung function and impaired skin barrier function in infancy may increase the risk of asthma at age 3 years.

• Trent, Pernille Kristina Bjerre; Eriksson, Ane Gerda Zahl; Staff, Anne Cathrine; Juul-Hansen, Knut Erling; Burger, Emily Annika & Wangen, Knut Reidar (2024). A cost-effectiveness analysis of sentinel lymph node biopsy compared with lymphadenectomy in intermediate- and high-risk endometrial carcinoma. International Journal of Gynecological Cancer. ISSN 1048-891X. 35(1). doi: 10.1136/ijgc-2024-005906. Fulltekst i vitenarkiv Vis sammendrag

  Background Sentinel lymph node biopsy (SLN) is increasingly used for surgical staging of endometrial carcinoma. Objective To estimate the effect and cost-effectiveness of the implementation of an SLN algorithm for surgical staging in patients with intermediate- and high-risk endometrial carcinoma compared with lymphadenectomy. Methods We performed a model-based, cost-effectiveness analysis using primary data from a tertiary referral hospital that included 829 patients with endometrial carcinoma undergoing surgical staging. We quantified the health and economic outcomes from two time periods, before and after implementation of the SLN algorithm by robotic surgery. Costs were measured directly from the hospital’s financial department, while long-term health outcomes were estimated using self-reported lymphedema and health-related quality-of-life among survivors. Sensitivity analyses were conducted to evaluate uncertainty. Results We projected that the SLN implementation period, predominately reflecting use of robotic SLN, simultaneously improved health outcomes (0.08 incremental quality-adjusted life-years) and lowered costs (US$1051) compared with the prior period involving robotic or open lymphadenectomy. SLN remained more beneficial and less costly across key sensitivity analyses—namely, varying the cost of the robotic platform, surgical equipment, number of yearly robotic procedures, percentage of robotic procedures versus percentage of laparotomies, length of stay, and lymphedema development. After 1000 simulations of the model, SLN implementation provided greater health benefits for lower costs (ie, cost saving) in 89% of simulations. Conclusion Implementation of an SLN algorithm in the staging of intermediate- and high-risk endometrial carcinoma improved health outcomes for lower costs compared with lymphadenectomy. Cost-effectiveness could further improve by continuing to increase the proportion of robotic procedures.

• Nedberg, Nora Hersoug; Nystad, Mona; Ahlen, Maria Therese; Bertelsen, eirin listau; Guz, Katarzyna & Uhrynowska, Małgorzata [Vis alle 13 forfattere av denne artikkelen] (2024). Placenta-associated biomarkers and pregnancy outcome in HPA-1a alloimmunization: A prospective cohort study. Placenta. ISSN 0143-4004. 158, s. 185–191. doi: 10.1016/j.placenta.2024.10.014. Fulltekst i vitenarkiv Vis sammendrag

  Introduction - Fetal and neonatal alloimmune thrombocytopenia (FNAIT) results from parental incompatibility in human platelet antigens (HPA) and subsequent maternal sensitization. The HPA-1a epitope is also expressed on placental tissue. Chronic placental inflammation and lower birth weight is observed more often in HPA-1a alloimmunized pregnancies, suggesting a placental component in the pathophysiology of FNAIT. Today, prediction of FNAIT severity is limited. The aim of the study was to investigate whether dysregulated maternal angiogenic proteins are associated with neonatal outcome in HPA-1a alloimmunized pregnancies.<p> <p>Material and methods - Eighty-seven HPA-1a negative pregnant women were identified from a large prospective screening study in Poland (PREVFNAIT) including 43 HPA-1a immunized and 44 non-immunized controls. Placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) were measured in maternal plasma from 2nd and 3rd trimester by enzyme-linked immunosorbent assay and levels/ratios were compared between study groups, using uni- and multivariable analyses. Main outcome measures were either classic FNAIT-related (severe thrombocytopenia, petechia, intracranial hemorrhage), placenta-related (small for gestational age) or a composite variable combining them all.<p> <p>Results - There were no significant differences in plasma concentrations of sFlt-1, PlGF, sEng nor sFlt-1/PlGF ratio when comparing immunized and non-immunized pregnancies. Among HPA-1a alloimmunized pregnancies, increasing levels of the sFlt-1 protein in 3rd trimester were significantly associated with lower neonatal platelet count (multivariable linear regression, p = 0.024). Increased sFlt-1 and sFlt-1/PlGF ratio in 3rd trimester were significantly associated with higher odds of a composite adverse neonatal outcome in alloimmunized pregnancies (multivariable logistic regression, p = 0.029 and p = 0.019, respectively).<p> <p>Conclusion - An anti-angiogenic profile in HPA-1a alloimmunized mothers is associated with a composite adverse neonatal outcome. This suggests that sFlt-1 and the sFlt-1/PlGF ratio may assist in predelivery risk stratification and clinical management decisions for FNAIT.

• Jacobsen, Daniel Pitz; Fjeldstad, Heidi Elisabeth Storebø; Sugulle, Meryam; Johnsen, Guro Mørk; Olsen, Maria Belland & Kanaan, Sami [Vis alle 7 forfattere av denne artikkelen] (2023). Fetal microchimerism and the two-stage model of preeclampsia. Journal of Reproductive Immunology. ISSN 0165-0378. 159. doi: 10.1016/j.jri.2023.104124. Fulltekst i vitenarkiv Vis sammendrag

  Fetal cells cross the placenta during pregnancy and some have the ability to persist in maternal organs and circulation long-term, a phenomenon termed fetal microchimerism. These cells often belong to stem cell or immune cell lineages. The long-term effects of fetal microchimerism are likely mixed, potentially depending on the amount of fetal cells transferred, fetal-maternal histocompatibility and fetal cell-specific properties. Both human and animal data indicate that fetal-origin cells partake in tissue repair and may benefit maternal health overall. On the other hand, these cells have been implicated in inflammatory diseases by studies showing increased fetal microchimerism in women with autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. During pregnancy, preeclampsia is associated with increased cell-transfer between the mother and fetus, and an increase in immune cell subsets. In the current review, we discuss potential mechanisms of transplacental transfer, including passive leakage across the compromised diffusion barrier and active recruitment of cells residing in the placenta or fetal circulation. Within the conceptual framework of the two-stage model of preeclampsia, where syncytiotrophoblast stress is a common pathophysiological pathway to maternal and fetal clinical features of preeclampsia, we argue that microchimerism may represent a mechanistic link between stage 1 placental dysfunction and stage 2 maternal cardiovascular inflammation and endothelial dysfunction. Finally, we postulate that fetal microchimerism may contribute to the known association between placental syndromes and increased long-term maternal cardiovascular disease risk. Fetal microchimerism research represents an exciting opportunity for developing new disease biomarkers and targeted prophylaxis against maternal diseases.

• Fjeldstad, Heidi Elisabeth Storebø; Jacobsen, Daniel Pitz; Johnsen, Guro Mørk; Sugulle, Meryam; Chae, Angel & Kanaan, Sami B. [Vis alle 8 forfattere av denne artikkelen] (2023). Poor glucose control and markers of placental dysfunction correlate with increased circulating fetal microchimerism in diabetic pregnancies. Journal of Reproductive Immunology. ISSN 0165-0378. 159, s. 1–9. doi: 10.1016/j.jri.2023.104114. Fulltekst i vitenarkiv Vis sammendrag

  Fetal microchimerism (FMc) arises during pregnancy as fetal cells enter maternal circulation and remain decades postpartum. Circulating FMc is increased in preeclampsia, fetal growth restriction, and as we recently showed, is associated with biomarkers of placental dysfunction in normotensive term pregnancies. Diabetes mellitus (DM) also correlates with placental dysfunction. We hypothesize that poor glucose control and markers of placental dysfunction are associated with increased circulating FMc in diabetic pregnancies. We included 122 pregnancies preceding active labor (pregestational DM, n = 77, gestational DM (GDM), n = 45) between 2001 and 2017. Maternal and fetal samples were genotyped for various human leukocyte antigen (HLA) loci, and other polymorphisms to identify fetus-specific alleles. We used validated polymerase chain reaction (PCR) assays to quantify FMc in maternal peripheral blood buffy coat. Negative binomial regression with adjustment for confounders was used to assess FMc quantity. In pregestational DM, increased circulating FMc correlated with elevation of HbA1c (≥ 6.0 %) (detection rate ratio (DRR) = 4.9, p = 0.010) and a 1000 pg/mL rise in the anti-angiogenic biomarker soluble fms-like tyrosine kinase-1 (sFlt-1) (DRR = 1.1, p = 0.011). In GDM, increased FMc correlated with elevated 2-hour oral glucose tolerance test results (DRR = 2.3, p = 0.046) and birthweight < 10th or > 90th percentile (DRR = 4.2, p = 0.049). These findings support our novel hypothesis that FMc correlates with poor glucose control and various aspects of placental dysfunction in DM. Whether increased FMc in pregnancies with poor glucose control and placental dysfunction contributes to the risk of preeclampsia in diabetic pregnancies and to the increased risk of chronic cardiovascular disease later in life remains to be investigated.

• Trent, Pernille Kristina Bjerre; Nordskar, Nina Jebens; Wangen, Knut Reidar; Engeskaug, Ida; Opheim, Linn Øvstebø & Aune, Guro [Vis alle 10 forfattere av denne artikkelen] (2023). Self-reported lower extremity lymphedema and quality of life after surgical staging of endometrial carcinoma: A population based cross-sectional study. Gynecologic Oncology. ISSN 0090-8258. 175, s. 72–80. doi: 10.1016/j.ygyno.2023.05.070. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Sentinel lymph node biopsy (SLN) has replaced lymphadenectomy in staging of endometrial carcinoma. The aims of the study were to explore the prevalence of self-reported lymphedema (LEL), identify factors associated with LEL, compare quality of life (QoL) scores using thresholds of clinical importance, and assess correlation between different questionnaires. Methods Women who underwent staging for endometrial carcinoma from 2006 to 2021 were invited to complete the Lower Extremity Lymphedema Screening Questionnaire (LELSQ), EORTC QLQ-C30, QLQ-EN24 and EQ-5D-5L. Results Of 2156 invited survivors, 61% participated in the study, whereof 1127 were evaluable by LELSQ. The LEL prevalence was 51%, 36% and 40% after lymphadenectomy, SLN and hysterectomy, respectively (p < 0.001). Higher BMI, undergoing lymphadenectomy and receiving adjuvant chemotherapy were associated with LEL; odds ratios 1.07 (95% CI 1.05–1.09), 1.42 (95% CI 1.03–1.97) and 1.43 (95% CI 1.08–1.89) respectively. QoL was lower for women with LEL compared to those without. In women with musculoskeletal complaints the prevalence of LEL was 59%, 50% and 53% after lymphadenectomy, SLN and hysterectomy (p = 0.115), respectively, compared to 39%, 17% and 18% (p < 0.001) in women without musculoskeletal complaints. Spearman's correlation was moderate to strong between the questionnaires. Conclusion SLN implementation is not associated with increased LEL prevalence compared to hysterectomy alone, but is associated with a significantly lower prevalence compared to lymphadenectomy. LEL is associated with lower QoL. Our study demonstrates moderate to strong correlation between self-reported LEL and QoL scores. Available questionnaires may not distinguish between symptoms caused by LEL and musculoskeletal disease.

• Färdig, Martin; Gudmundsdottir, Hrefna Katrin; Hoyer, Angela; Bains, Karen Eline Stensby; Almqvist, Catarina & Jonassen, Christine Genevieve Monceyron [Vis alle 13 forfattere av denne artikkelen] (2023). Skin Barrier Function and Infant Tidal Flow-Volume Loops—A Population-Based Observational Study. Children. 10(1). doi: 10.3390/children10010088. Fulltekst i vitenarkiv Vis sammendrag

  Background: The relationship between the skin barrier- and lung function in infancy is largely unexplored. We aimed to explore if reduced skin barrier function by high transepidermal water loss (TEWL), or manifestations of eczema or Filaggrin (FLG) mutations, were associated with lower lung function in three-month-old infants. Methods: From the population-based PreventADALL cohort, 899 infants with lung function measurements and information on either TEWL, eczema at three months of age and/or FLG mutations were included. Lower lung function by tidal flow-volume loops was defined as a ratio of time to peak tidal expiratory flow to expiratory time (tPTEF/tE) &lt;0.25 and a tPTEF &lt;0.17 s (&lt;25th percentile). A high TEWL &gt;8.83 g/m2/h (&gt;75th percentile) denoted reduced skin barrier function, and DNA was genotyped for FLG mutations (R501X, 2282del4 and R2447X). Results: Neither a high TEWL, nor eczema or FLG mutations, were associated with a lower tPTEF/tE. While a high TEWL was associated with a lower tPTEF; adjusted OR (95% CI) 1.61 (1.08, 2.42), the presence of eczema or FLG mutations were not. Conclusions: Overall, a high TEWL, eczema or FLG mutations were not associated with lower lung function in healthy three-month-old infants. However, an inverse association between high TEWL and tPTEF was observed, indicating a possible link between the skin barrier- and lung function in early infancy.

• Fiskå, Bendik Seth; Pay, Aase Serine Devold; Staff, Anne Cathrine & Sugulle, Meryam (2023). Gestational diabetes mellitus, follow-up of future maternal risk of cardiovascular disease and the use of eHealth technologies—a scoping review. Systematic Reviews. 12(1). doi: 10.1186/s13643-023-02343-w. Fulltekst i vitenarkiv Vis sammendrag

  Background Globally, gestational diabetes mellitus complicates 1 in 6 pregnancies and increases future risk of type 2 diabetes and cardiovascular disease in the affected women. There is a lack of consensus on the optimal follow-up of these women. eHealth is emerging as a health care tool, but its practical utility and advantages over standard care in the follow-up after pregnancy complications remains to be determined. Our aim was to systematically review the existing literature on cardiovascular follow-up after gestational diabetes, the utility of eHealth technology for this purpose, and to identify research gaps. Methods WeperformedasystematicscopingreviewfollowingapublishedprotocolandtheJoannaBriggsmethodol- ogy for studies up until May 2022. Four databases were searched: Ovid MEDLINE, Embase, Maternity and Infant Care, and Cochrane Database of Systematic Reviews. Primary research articles and systematic reviews were included in the final analyses. Two reviewers independently screened abstracts and performed full text assessment. Data was extracted using a data charting form. In all stages of the process, if consensus was not reached, a third reviewer was consulted. The findings from the data charting process provided the basis for summarizing the findings from the included studies. Results The search of the databases generated 2772 hits. After removing duplicates and manually adding a total of 19 studies, reviews, and guidelines, a total of 2769 titles and abstracts were screened, and 97 papers underwent full-text review. In the final analyses, 15 articles and 12 systematic reviews were included, whereas guidelines are presented as supplementary material. No studies were identified that examined follow-up regarding long-term overall cardiovascular risk after gestational diabetes. Various lifestyle interventions were tested for individual cardiovascular risk factors, with diverging effects. eHealth technologies were found acceptable by participants but had no consistent, statistically significant effect on relevant health outcomes. Conclusions This scoping review of the existing literature revealed neither an established systematic cardiovascular follow-up strategy for women after gestational diabetes nor evidence that eHealth technologies are superior to con- ventional follow-up. Further research into the utility of eHealth in cardiovascular follow-up after complicated pregnan- cies should include longer-term follow-up and core cardiovascular outcomes.

• Hilde, Katarina; Gudmundsdottir, Hrefna Katrin; Bains, Karen Eline Stensby; Carlsen, Karin Cecilie Lødrup; Färdig, Martin & Jonassen, Christine M [Vis alle 15 forfattere av denne artikkelen] (2023). Third trimester fetal lung volume, thoracic circumference, and early infant lung function. Pediatric Pulmonology. ISSN 8755-6863. 58(7), s. 2050–2058. doi: 10.1002/ppul.26431. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background We aimed to investigate the relationship between fetal third trimester lung volume (LV), thoracic circumference (TC), fetal weight, as well as fetal thoracic and weight growth, and early infant lung function. Methods Fetal LV, TC and estimated weight were measured with ultrasound at 30 gestational weeks in 257 fetuses from the general population‐based prospective cohort study Preventing Atopic Dermatitis and ALLergies in Children (PreventADALL). Fetal thoracic growth rate and weight increase were calculated using TC and estimated fetal weight measured by ultrasound during pregnancy, and TC and birthweight of the newborn. Lung function was assessed by tidal flow‐volume measurement in awake infants at 3 months of age. The associations between fetal size (LV, TC, and estimated weight) and growth (thoracic growth rate and fetal weight increase) measures and the time to peak tidal expiratory flow to expiratory time ratio ( t PTEF / t E ) as well as tidal volume standardized for body weight ( V T /kg) were analyzed using linear and logistic regression models. Results We observed no associations between fetal LV, TC or estimated fetal weight and t PTEF / t E as a continuous variable, t PTEF / t E  &lt; 25th percentile, or V T /kg. Similarly, fetal thoracic growth and weight increase were not associated with infant lung function. Analyses stratified for sex showed a significant inverse association between fetal weight increase and V T /kg ( p  = 0.02) in girls. Conclusion Overall, fetal third trimester LV, TC, estimated fetal weight, thoracic growth rate and weight increase were not associated with infant lung function at 3 months of age.

• Rapin, Alexis; Rehbinder, Eva Maria; Macowan, Matthew; Pattaroni, Céline; Carlsen, Karin Cecilie Lødrup & Harris, Nicola L. [Vis alle 17 forfattere av denne artikkelen] (2023). The skin microbiome in the first year of life and its association with atopic dermatitis. Allergy. European Journal of Allergy and Clinical Immunology. ISSN 0105-4538. 78(7), s. 1949–1063. doi: 10.1111/all.15671. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background Early‐life microbial colonization of the skin may modulate the immune system and impact the development of atopic dermatitis (AD) and allergic diseases later in life. To address this question, we assessed the association between the skin microbiome and AD, skin barrier integrity and allergic diseases in the first year of life. We further explored the evolution of the skin microbiome with age and its possible determinants, including delivery mode. Methods Skin microbiome was sampled from the lateral upper arm on the first day of life, and at 3, 6, and 12 months of age. Bacterial communities were assessed by 16S rRNA gene amplicon sequencing in 346 infants from the PreventADALL population‐based birth cohort study, representing 970 samples. Clinical investigations included skin examination and skin barrier function measured as trans‐epidermal water loss (TEWL) at the site and time of microbiome sampling at 3, 6, and 12 months. Parental background information was recorded in electronic questionnaires, and delivery mode (including vaginal delivery (VD), VD in water, elective caesarean section (CS) and emergency CS) was obtained from maternal hospital charts. Results Strong temporal variations in skin bacterial community composition were found in the first year of life, with distinct patterns associated with different ages. Confirming our hypothesis, skin bacterial community composition in the first year of life was associated with skin barrier integrity and later onsets of AD. Delivery mode had a strong impact on the microbiome composition at birth, with each mode leading to distinct patterns of colonization. Other possible determinants of the skin microbiome were identified, including environmental and parental factors as well as breastfeeding. Conclusion Skin microbiome composition during infancy is defined by age, transiently influenced by delivery mode as well as environmental, parental factors and breastfeeding. The microbiome is also associated with skin barrier integrity and the onset of AD.

• Wiik, Johanna; Værnesbranden, Caren Magdalena Rydland; Jonassen, Christine M; Staff, Anne Cathrine; Carlsen, Karin Cecilie Lødrup & Granum, Berit [Vis alle 20 forfattere av denne artikkelen] (2023). Maternal human papillomavirus infection during pregnancy and preterm delivery: A mother–child cohort study in Norway and Sweden. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 102(3), s. 344–354. doi: 10.1111/aogs.14509. Fulltekst i vitenarkiv Vis sammendrag

  Introduction Human papillomavirus (HPV) infection is common in women of reproductive age. Infection and inflammation are leading causes for preterm delivery (PTD), but the role of HPV infection in PTD and prelabor rupture of membranes (PROM) is unclear. We aimed to explore whether HPV infection during pregnancy in general, and high-risk-HPV (HR-HPV) infection specifically, increased the risk of PTD, preterm prelabor rupture of membranes (PPROM), PROM at term, and/or chorioamnionitis. Material and Methods In pregnant women, who were participating in a prospective multicenter cohort study from a general population in Norway and Sweden (PreventADALL, ClinicalTrials.gov NCT02449850), HPV DNA was analyzed in available urine samples at mid-gestation (16–22 weeks) and at delivery, and in the placenta after delivery with Seegene Anyplex II HPV28 PCR assay. The risk of PTD, PPROM, PROM, and chorioamnionitis was analyzed using unadjusted and adjusted logistic regression analyses for any 28 HPV genotypes, including 12 HR-HPV genotypes, compared with HPV-negative women. Further, subgroups of HPV (low-risk/possibly HR-HPV, HR-HPV-non-16 and HR-HPV-16), persistence of HR-HPV from mid-gestation to delivery, HR-HPV-viral load, and presence of multiple HPV infections were analyzed for the obstetric outcomes. Samples for HPV analyses were available from 950 women with singleton pregnancies (mean age 32 years) at mid-gestation and in 753 also at delivery. Results At mid-gestation, 40% of women were positive for any HPV and 24% for HR-HPV. Of the 950 included women, 23 had PTD (2.4%), nine had PPROM (0.9%), and six had chorioamnionitis (0.6%). Of the term pregnancies, 25% involved PROM. The frequency of PTD was higher in HR-HPV-positive women (8/231, 3.5%) than in HPV-negative women (13/573, 2.3%) at mid-gestation, but the association was not statistically significant (odds ratio 1.55; 95% confidence interval 0.63–3.78). Neither any HPV nor subgroups of HPV at mid-gestation or delivery, nor persistence of HR-HPV was significantly associated with increased risk for PTD, PPROM, PROM, or chorioamnionitis. No HPV DNA was detected in placentas of women with PTD, PPROM or chorioamnionitis. Conclusions HPV infection during pregnancy was not significantly associated with increased risk for PTD, PPROM, PROM, or chorioamnionitis among women from a general population with a low incidence of adverse obstetric outcomes.

• Aasbø, Gunvor; Staff, Anne Cathrine; Blix, Ellen; Pay, Aase Serine Devold; Waldum, Åsa & Rivedal, Sunniva [Vis alle 7 forfattere av denne artikkelen] (2023). Expectations related to home-based telemonitoring of high-risk pregnancies: A qualitative study addressing healthcare providers' and users' views in Norway. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. s. 1–10. doi: 10.1111/aogs.14726. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: A pregnancy can be evaluated as high-risk for the woman and/or the fetus based on medical history and on previous or ongoing pregnancy characteristics. Monitoring high-risk pregnancies is crucial for early detection of alarming features, enabling timely intervention to ensure optimal maternal and fetal health outcomes. Home-based telemonitoring (HBTM) is a marginally exploited opportunity in antenatal care. The aim of this study was to illuminate healthcare providers' and users' expectations and views about HBTM of maternal and fetal health in high-risk pregnancies before implementation. Material and methods: To address diverse perspectives regarding HBTM of high-risk pregnancies, four different groups of experienced healthcare providers or users were interviewed (n = 21). Focus group interviews were conducted separately with midwives, obstetricians, and women who had previously experienced stillbirth. Six individual interviews were conducted with hospitalized women with ongoing high-risk pregnancies, representing potential candidates for HBTM. None of the participants had any previous experience with HBTM of pregnancies. The study is embedded in a social constructivist research paradigm. Interviews were analyzed using a thematic approach. Results: The participants acknowledged the benefits and potentials of more active roles for both care recipients and providers in HBTM. Concerns were clearly addressed and articulated in the following themes: eligibility and ability of women, availability of midwives and obstetricians, empowerment and patient safety, and shared responsibility. All groups problematized issues crucial to maintaining a sense of safety for care recipients, and healthcare providers also addressed issues related to maintaining a sense of safety also for the care providers. Conditions for HBTM were understood in terms of optimal personalized training, individual assessment of eligibility, and empowerment of an active patient role. These conditions were linked to the importance of competent and experienced midwives and obstetricians operating the monitoring, as well as the availability and continuity of care provision. Maintenance of safety in HBTM in high-risk pregnancies was crucial, particularly so in situations involving emerging acute health issues. Conclusions: HBTM requires new, proactive roles among midwives, obstetricians, and monitored women, introducing a fine-tuned balance between personalized and standardized care to provide safe, optimal monitoring of high-risk pregnancies.

• Opheim, Linn Øvstebø; Engeskaug, Ida; Trent, Pernille Kristina Bjerre; Thorsen, Lene; Staff, Anne Cathrine & Nordskar, Nina Jebens [Vis alle 9 forfattere av denne artikkelen] (2023). Associations between modifiable lifestyle factors and health-related quality of life among endometrial carcinoma survivors - A cross-sectional study. Gynecologic Oncology. ISSN 0090-8258. 179, s. 52–62. doi: 10.1016/j.ygyno.2023.10.012. Fulltekst i vitenarkiv Vis sammendrag

  Objective To explore possible associations between modifiable lifestyle factors and health-related quality of life (HRQoL) in endometrial carcinoma survivors by assessing differences in HRQoL between survivors meeting and not meeting the World Health Organization's (WHO) recommendations regarding physical activity, BMI, and smoking. Methods This was a cross-sectional population-based study in women having undergone surgery for assumed early-stage endometrial carcinoma. Thresholds for clinical importance based on the EORTC QoL working group were used to interpret scores. Effect size (ES) was interpreted as small (d = 0.2–0.49), medium (d = 0.5–0.8), and large (d > 0.8). Results In total, 1200 evaluable women were included. Meeting physical activity recommendations and BMI <25 kg/m2 was associated with significantly better global health status, (ES) = 0.18 and ES = −0.11, respectively. On multivariate analysis, women meeting physical activity recommendations had significantly higher scores on physical- (ES = 0.31), role- (ES = 0.15), and social functioning (ES = 0.15), and lower levels of fatigue (ES = −0.16), pain (ES = −0.10), and appetite loss (ES = −0.15) (all p < 0.05) compared to non-meeting survivors. Participants with BMI ≥25 kg/m2 had lower scores for social functioning (ES = −0.10), and higher levels of pain (ES = 0.13) and dyspnea (ES = 0.12) (all p < 0.05) compared to those with BMI <25 kg/m2. Smokers had lower scores for emotional functioning (ES = −0.09) and higher levels of diarrhea (ES = 0.10) (all p < 0.05) compared to non-smokers. Conclusion Meeting WHO recommendations for modifiable life-style factors is associated with better HRQoL among endometrial carcinoma survivors: Being sufficiently physical active and having a BMI <25 kg/m2 are significantly associated with better self-reported global health status. All modifiable factors are associated with better functioning, and reduced symptom-burden.

• Santos, Margarida Varela dos; Holth, Arild; Lindemann, Kristina Yvonne Kathe; Staff, Anne Cathrine & Davidson, Ben (2023). Clinical significance of L1CAM expression in metastatic tubo-ovarian high-grade serous carcinoma. Gynecologic Oncology. ISSN 0090-8258. 176, s. 76–81. doi: 10.1016/j.ygyno.2023.07.004. Fulltekst i vitenarkiv Vis sammendrag

  Objective To analyze the expression and prognostic role of L1CAM in tubo-ovarian high-grade serous carcinoma (HGSC). Methods L1CAM protein expression by immunohistochemistry was analyzed in 644 HGSC (413 effusions, 231 surgical specimens). Expression was analyzed for association with clinicopathologic parameters and survival. Results L1CAM protein expression was found in 401/413 (97%) effusions and 209/231 (90%) surgical specimens, with significantly higher staining extent in effusions (p < 0.001). L1CAM protein expression in effusions was unrelated to clinicopathologic parameters (p > 0.05). In surgical specimens, higher L1CAM expression was significantly related to primary (intrinsic) chemoresistance (p = 0.017). High (>25%) L1CAM expression in HGSC effusions (p = 0.02), older patient age (p = 0.013), FIGO stage IV disease (p < 0.001) and larger residual disease volume (p = 0.001) were significantly associated with shorter overall survival (OS) in univariate analysis. In Cox multivariate analysis, only FIGO stage (p = 0.001) and residual disease volume (p = 0.003) were independent prognosticators of OS. L1CAM expression in effusions was unrelated to progression-free survival (PFS). There was no association between L1CAM expression in surgical specimens and survival. Conclusion L1CAM is overexpressed in HGSC effusions compared to surgical specimens. Its overexpression in effusions is significantly associated with shorter OS, but not independently of established prognostic factors such as FIGO stage and residual disease volume.

• Trent, Pernille Kristina Bjerre; Falk, Ragnhild Sørum; Staff, Anne Cathrine; Jorde, Doris & Eriksson, Ane Gerda Zahl (2023). Translation and cross-cultural adaptation of the Gynecologic Cancer Lymphedema Questionnaire and the Lower Extremity Lymphedema Screening Questionnaire. International Journal of Gynecological Cancer. ISSN 1048-891X. 33(2), s. 231–235. doi: 10.1136/ijgc-2022-003979. Fulltekst i vitenarkiv Vis sammendrag

  Objective There is a paucity of international data regarding self-reported lower extremity lymphedema and quality of life after surgery for gynecological cancer. Validated questionnaires are emerging, but translated versions are lacking. Cross-cultural adaptation is important to reduce the risk of introducing bias into a study. Objective To translate and culturally adapt the Gynecologic Cancer Lymphedema Questionnaire and the Lower Extremity Lymphedema Screening Questionnaire for a Norwegian population. Methods Permission to use the original English versions of the Gynecologic Cancer Lymphedema Questionnaire and the Lower Extremity Lymphedema Screening Questionnaire for translation was obtained. The questionnaires were translated using a procedure based on standard guidelines, including forward translation by native speakers of the target language, synthesis, back translation, and review. Seventeen patients from the Norwegian Radium Hospital gynecological cancer outpatient clinic, all expected to have stable disease, were invited for questionnaire test–retest by completing the same questionnaires twice at 3–4-week intervals. Internal consistency was assessed by calculating Cronbach’s alpha. Test–retest reliability was assessed using an intra-class correlation coefficient. Results Twelve patients completed the questionnaires twice. Cronbach’s alpha was 0.75 for the Gynecologic Cancer Lymphedema Questionnaire and 0.89 for the Lower Extremity Lymphedema Screening Questionnaire. The intra-class correlation coefficient was 0.86 for the Gynecologic Cancer Lymphedema Questionnaire and 0.91 for the Lower Extremity Lymphedema Screening Questionnaire. Conclusions Translation and cross-cultural adaptation of these internationally validated patient-reported outcomes questionnaires for survivors of lower extremity lymphedema in gynecological cancer was feasible. The Norwegian translation of the Gynecologic Cancer Lymphedema Questionnaire and the Lower Extremity Lymphedema Screening Questionnaire showed acceptable internal consistency and the test–retest reliability was excellent.

• Fjeldstad, Heidi Elisabeth Storebø; Jacobsen, Daniel Pitz; Johnsen, Guro Mørk; Sugulle, Meryam; Chae, Angel & Kanaan, Sami B. [Vis alle 8 forfattere av denne artikkelen] (2023). Markers of placental function correlate with prevalence and quantity of nucleated fetal cells in maternal circulation in normotensive term pregnancies. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 102(6), s. 690–698. doi: 10.1111/aogs.14547. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Introduction Transplacental fetal cell transfer results in the engraftment of fetal‐origin cells in the pregnant woman's body, a phenomenon termed fetal microchimerism. Increased fetal microchimerism measured decades postpartum is implicated in maternal inflammatory disease. Understanding which factors cause increased fetal microchimerism is therefore important. During pregnancy, circulating fetal microchimerism and placental dysfunction increase with increasing gestational age, particularly towards term. Placental dysfunction is reflected by changes in circulating placenta‐associated markers, specifically placental growth factor (PlGF), decreased by several 100 pg/mL, soluble fms‐like tyrosine kinase‐1 (sFlt‐1), increased by several 1000 pg/mL, and the sFlt‐1/PlGF ratio, increased by several 10 (pg/mL)/(pg/mL). We investigated whether such alterations in placenta‐associated markers correlate with an increase in circulating fetal‐origin cells. Material and methods We included 118 normotensive, clinically uncomplicated pregnancies (gestational age 37+1 up to 42+2 weeks‘ gestation) pre‐delivery. PlGF and sFlt‐1 (pg/mL) were measured by Elecsys® Immunoassays. We extracted DNA from maternal and fetal samples and genotyped four human leukocyte antigen loci and 17 other autosomal loci. Paternally inherited, unique fetal alleles served as polymerase chain reaction (PCR) targets for detecting fetal‐origin cells in maternal buffy coat. Fetal‐origin cell prevalence was assessed by logistic regression, and quantity by negative binomial regression. Statistical exposures included gestational age (weeks), PlGF (100 pg/mL), sFlt‐1 (1000 pg/mL) and the sFlt‐1/PlGF ratio (10 (pg/mL)/(pg/mL)). Regression models were adjusted for clinical confounders and PCR‐related competing exposures. Results Gestational age was positively correlated with fetal‐origin cell quantity (DRR = 2.2, P = 0.003) and PlGF was negatively correlated with fetal‐origin cell prevalence (odds ratio [OR] 100 = 0.6, P = 0.003) and quantity (DRR 100 = 0.7, P = 0.001). The sFlt‐1 and the sFlt‐1/PlGF ratios were positively correlated with fetal‐origin cell prevalence (OR 1000 = 1.3, P = 0.014 and OR 10 = 1.2, P = 0.038, respectively), but not quantity (DRR 1000 = 1.1, P = 0.600; DRR 10 = 1.1, P = 0.112, respectively). Conclusions Our results suggest that placental dysfunction as evidenced by placenta‐associated marker changes, may increase fetal cell transfer. The magnitudes of change tested were based on ranges in PlGF, sFlt‐1 and the sFlt‐1/PlGF ratio previously demonstrated in pregnancies near and post‐term, lending clinical significance to our findings. Our results were statistically significant after adjusting for confounders including gestational age, supporting our novel hypothesis that underlying placental dysfunction potentially is a driver of increased fetal microchimerism.

• Hilde, Katarina; Gudmundsdottir, Hrefna Katrin; Bains, Karen Eline Stensby; Färdig, Martin; Carlsen, Karin Cecilie Lødrup & Jonassen, Christine M [Vis alle 14 forfattere av denne artikkelen] (2023). Fetal pulmonary artery Doppler blood flow velocity measures and early infant lung function. A prospective cohort study. Journal of Maternal-Fetal & Neonatal Medicine. ISSN 1476-7058. 36(1). doi: 10.1080/14767058.2023.2213796. Fulltekst i vitenarkiv Vis sammendrag

  Background Reduced lung function at birth has evident antenatal origins and is associated with an increased risk of wheezing and asthma later in life. Little is known about whether blood flow in the fetal pulmonary artery, may impact postnatal lung function. Objective Our primary aim was to investigate the potential associations between fetal Doppler blood flow velocity measures in the fetal branch pulmonary artery, and infant lung function by tidal flow-volume (TFV) loops at three months of age in a low-risk population. Our secondary aim was to explore the association between Doppler blood flow velocity measures in the umbilical and middle cerebral arteries, and the same lung function measures. Methods In 256 non-selected pregnancies from the birth cohort study Preventing Atopic Dermatitis and ALLergies in Children (PreventADALL) we performed fetal ultrasound examination with Doppler blood flow velocity measurements at 30 gestational weeks (GW). We recorded the pulsatility index, peak systolic velocity, time-averaged maximum velocity, acceleration time/ejection time ratio, and time velocity integral primarily in the proximal pulmonary artery close to the pulmonary bifurcation. The pulsatility index was measured in the umbilical and middle cerebral arteries and the peak systolic velocity in the middle cerebral artery. The cerebro-placental ratio (ratio between pulsatility index in the middle cerebral and umbilical arteries) was calculated. Infant lung function was assessed using TFV loops in awake, calmly breathing three months old infants. The outcome was the time to peak tidal expiratory flow to expiratory time ratio (tPTEF/tE), tPTEF/tE <25th percentile, and tidal volume per kg body weight (VT/kg). Potential associations between fetal Doppler blood flow velocity measures and infant lung function were assessed using linear and logistic regressions. Results The infants were born at median (min - max) 40.3 (35.6 − 42.4) GW, with a mean (SD) birth weight of 3.52 (0.46) kg, and 49.4% were females. The mean (SD) tPTEF/tE was 0.39 (0.1) and the 25th percentile was 0.33. Neither univariable nor multivariable regression models revealed any associations between fetal pulmonary blood flow velocity measures and tPTEF/tE, tPTEF/tE <25th percentile, or VT/kg at three months of age. Similarly, we did not observe associations between Doppler blood flow velocity measures in the umbilical and middle cerebral arteries and infant lung function measures. Conclusion In a cohort of 256 infants from the general population, fetal third-trimester Doppler blood flow velocity measures in the branch pulmonary, umbilical, and middle cerebral arteries were not associated with infant lung function measures at three months of age.

• Nilsen, Katinka; Staff, Anne Cathrine & Krogsrud, Stine Kleppe (2023). Paracetamol use in pregnancy: Not as safe as we may think? Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 102(4), s. 652–656. doi: 10.1111/aogs.14557. Fulltekst i vitenarkiv
• Nilsen, Morten; Nygaard, Unni Cecilie; Brodin, Petter; Carlsen, Karin Cecilie Lødrup; Fredheim, Cecilie & Haugen, Guttorm Nils [Vis alle 19 forfattere av denne artikkelen] (2023). Gut bacteria at 6 months of age are associated with immune cell status in 1-year-old children. Scandinavian Journal of Immunology. ISSN 0300-9475. doi: 10.1111/sji.13346. Fulltekst i vitenarkiv Vis sammendrag

  Age-related gut bacterial changes during infancy have been widely studied, but it remains still unknown how these changes are associated with immune cell composition. This study's aim was to explore if the temporal development of gut bacteria during infancy prospectively affects immune cell composition. Faecal bacteria and short-chain fatty acids were analysed from 67 PreventADALL study participants at four timepoints (birth to 12 months) using reduced metagenome sequencing and gas chromatography. Immune cell frequencies were assessed using mass cytometry in whole blood samples at 12 months. The infants clustered into four groups based on immune cell composition: clusters 1 and 2 showed a high relative abundance of naïve cells, cluster 3 exhibited increased abundance of classical- and non-classical monocytes and clusters 3 and 4 had elevated neutrophil levels. At all age groups, we did observe significant associations between the gut microbiota and immune cell clusters; however, these were generally from low abundant species. Only at 6 months of age we observed significant associations between abundant (>8%) species and immune cell clusters. Bifidobacterium adolescentis and Porphyromonadaceae are associated with cluster 1, while Bacteroides fragilis and Bifidobacterium longum are associated with clusters 3 and 4 respectively. These species have been linked to T-cell polarization and maturation. No significant correlations were found between short-chain fatty acids and immune cell composition. Our findings suggest that abundant gut bacteria at 6 months may influence immune cell frequencies at 12 months, highlighting the potential role of gut microbiota in shaping later immune cell composition.

• Jacobsen, Daniel Pitz; Fjeldstad, Heidi Elisabeth Storebø; Sugulle, Meryam; Johnsen, Guro Mørk; Olsen, Maria Belland & Kanaan, Sami B. [Vis alle 7 forfattere av denne artikkelen] (2023). Fetal microchimerism and the two-stage model of preeclampsia. Journal of Reproductive Immunology. ISSN 0165-0378. 159. doi: 10.1016/j.jri.2023.104124. Fulltekst i vitenarkiv Vis sammendrag

  Fetal cells cross the placenta during pregnancy and some have the ability to persist in maternal organs and circulation long-term, a phenomenon termed fetal microchimerism. These cells often belong to stem cell or immune cell lineages. The long-term effects of fetal microchimerism are likely mixed, potentially depending on the amount of fetal cells transferred, fetal-maternal histocompatibility and fetal cell-specific properties. Both human and animal data indicate that fetal-origin cells partake in tissue repair and may benefit maternal health overall. On the other hand, these cells have been implicated in inflammatory diseases by studies showing increased fetal microchimerism in women with autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. During pregnancy, preeclampsia is associated with increased cell-transfer between the mother and fetus, and an increase in immune cell subsets. In the current review, we discuss potential mechanisms of transplacental transfer, including passive leakage across the compromised diffusion barrier and active recruitment of cells residing in the placenta or fetal circulation. Within the conceptual framework of the two-stage model of preeclampsia, where syncytiotrophoblast stress is a common pathophysiological pathway to maternal and fetal clinical features of preeclampsia, we argue that microchimerism may represent a mechanistic link between stage 1 placental dysfunction and stage 2 maternal cardiovascular inflammation and endothelial dysfunction. Finally, we postulate that fetal microchimerism may contribute to the known association between placental syndromes and increased long-term maternal cardiovascular disease risk. Fetal microchimerism research represents an exciting opportunity for developing new disease biomarkers and targeted prophylaxis against maternal diseases.

• Färdig, Martin; Lie, Anine; Borres, Magnus P.; Ekenkrantz, Tina; Granum, Berit & Haugen, Guttorm Nils [Vis alle 15 forfattere av denne artikkelen] (2023). Eosinophil-derived neurotoxin levels in early childhood and association with preschool asthma – A prospective observational study. Clinical and Experimental Allergy. ISSN 0954-7894. 53(11), s. 1198–1211. doi: 10.1111/cea.14409. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Introduction Eosinophil‐derived neurotoxin (EDN) is related to childhood asthma, while normal values are lacking. We aimed to document serum EDN levels at 1 and 3 years in general and in non‐atopic children, and explore if EDN levels differed by sex or were associated with preschool asthma at 3 years. Methods From the PreventADALL birth cohort, we included 1233 children with EDN analysed using ImmunoCAP at 1 and/or 3 years. Non‐atopic children had no history of wheeze, asthma, allergic sensitization or atopic dermatitis. Preschool asthma was defined as having ≥3 episodes of bronchial obstruction between 2 and 3 years, plus doctor diagnosed asthma and/or asthma medication use by 3 years. The upper limit of normal (ULN) of EDN was defined as the 95th percentile. With Youden Index we calculated EDN cut‐off levels for risk of preschool asthma. Results The overall median (ULN) EDN levels were 27.4 (121) μg/L at 1 year ( n  = 787), and 20.1 (87.8) μg/L at 3 years ( n  = 857). Non‐atopic children had EDN levels of 24.0 (107) μg/L at 1 year ( n  = 147), and 17.3 (84.6) μg/L at 3 years ( n  = 173). EDN levels were higher in boys compared to girls; 32.0 (133) versus 24.5 (97.0) μg/L at 1 year, and 20.9 (96.3) versus 19.0 (72.4) μg/L at 3 years. Preschool asthma was observed in 109/892 (12.2%) children. Higher EDN levels at 1 (&gt;26.7 μg/L) and 3 (≥20.5 μg/L) years were associated with preschool asthma; adjusted OR (95% CI) 2.20 (1.09, 4.41) and 4.68 (2.29, 9.55), respectively. Conclusion and Clinical Relevance We report EDN values in early childhood, demonstrating higher levels at 1 compared to 3 years and in boys compared to girls at both ages. Higher EDN levels at both ages were associated with preschool asthma. However, EDN cut‐off levels for preschool asthma were overall lower than the ULN of non‐atopic children, limiting translation into clinical practice.

• Nilsen, Morten; Rehbinder, Eva Maria; Carlsen, Karin Cecilie Lødrup; Haugen, Guttorm Nils; Hedlin, Gunilla & Jonassen, Christine M [Vis alle 17 forfattere av denne artikkelen] (2023). A Globally Distributed Bacteroides caccae Strain Is the Most Prevalent Mother-Child Shared Bacteroidaceae Strain in a Large Scandinavian Cohort. Applied and Environmental Microbiology. ISSN 0099-2240. 89(7), s. 1–15. doi: 10.1128/aem.00789-23. Fulltekst i vitenarkiv Vis sammendrag

  Bacteroides and Phocaeicola, members of the family Bacteroidaceae, are among the first microbes to colonize the human infant gut. While it is known that these microbes can be transmitted from mother to child, our understanding of the specific strains that are shared and potentially transmitted is limited. In this study, we aimed to investigate the shared strains of Bacteroides and Phocaeicola in mothers and their infants. We analyzed fecal samples from pregnant woman recruited at 18 weeks of gestation from the PreventADALL study, as well as offspring samples from early infancy, including skin swab samples taken within 10 min after birth, the first available fecal sample (meconium), and fecal samples at 3 months of age. We screened 464 meconium samples for Bacteroidaceae, with subsequent selection of 144 mother-child pairs for longitudinal analysis, based on the presence of Bacteroidaceae, longitudinal sample availability, and delivery mode. Our results showed that Bacteroidaceae members were mainly detected in samples from vaginally delivered infants. We identified high prevalences of Phocaeicola vulgatus, Phocaeicola dorei, Bacteroides caccae, and Bacteroides thetaiotaomicron in mothers and vaginally born infants. However, at the strain level, we observed high prevalences of only two strains: a B. caccae strain and a P. vulgatus strain. Notably, the B. caccae strain was identified as a novel component of mother-child shared strains, and its high prevalence was also observed in publicly available metagenomes worldwide. Our findings suggest that mode of delivery may play a role in shaping the early colonization of the infant gut microbiota, in particular the colonization of Bacteroidaceae members.

• Berge, Magnus Bollum; Kessler, Jørg; Yli, Branislava Markovic; Staff, Anne Cathrine; Gunnes, Nina & Jacobsen, Anne Flem (2023). Neonatal outcomes associated with time from a high fetal blood lactate concentration to operative delivery. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 102(8), s. 1106–1114. doi: 10.1111/aogs.14597. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Adjunctive technologies to cardiotocography intend to increase the specificity of the diagnosis of fetal hypoxia. If correctly diagnosed, time to delivery could affect neonatal outcome. In the present study, we aimed to investigate the effect of time from when fetal distress is indicated by a high fetal blood sample (FBS) lactate concentration to operative delivery on the risk of adverse neonatal outcomes. Material and methods: We conducted a prospective observational study. Deliveries with a singleton fetus in cephalic presentation at 36+0weeks of gestation or later were included. Adverse neonatal outcomes, related to decision-to-delivery interval (DDI), were investigated in operative deliveries indicated by an FBS lactate concentration of at least 4.8 mmol/L. We applied logistic regression to estimate crude and adjusted odds ratios (aOR) of various adverse neonatal outcomes, with associated 95% confidence intervals (CI), for a DDI exceeding 20 minutes, compared with a DDI of 20 minutes or less. ClinicalTrials.gov Identifier: NCT04779294. Results: The main analysis included 228 women with an operative delivery indicated by an FBS lactate concentration of 4.8 mmol/L or greater. The risk of all adverse neonatal outcomes was significantly increased for both DDI groups compared with the reference group (deliveries with an FBS lactate below 4.2 mmol/L within 60 minutes before delivery). In operative deliveries indicated by an FBS lactate concentration of 4.8 mmol/L or more, there was a significantly increased risk of a 5-minute Apgar score less than 7 if the DDI exceeded 20 minutes, compared with a DDI of 20 minutes or less (aOR 8.1, 95% CI 1.1–60.9). We found no statistically significant effect on other short-term outcomes for deliveries with DDI longer than 20 minutes, compared with those with DDI of 20 minutes or less (pH ≤7.10: aOR 2.0, 95% CI 0.5–8.4; transfer to the neonatal intensive care unit: aOR 1.1, 95% CI 0.4–3.5). Conclusions: After a high FBS lactate measurement, the increased risk of adverse neonatal outcome is further augmented if the DDI exceeds 20 minutes. These findings give support to current Norwegian guidelines for intervention in cases of fetal distress.

• Hoel, Sveinung Torsteinsen; Wiik, Johanna; Carlsen, Karin Cecilie Lødrup; Endre, Kim Magnus Advocaat; Gudmundsdottir, Hrefna Katrin & Haugen, Guttorm Nils [Vis alle 18 forfattere av denne artikkelen] (2023). Birth mode is associated with development of atopic dermatitis in infancy and early childhood. Journal of Allergy and Clinical Immunology: Global (JACI: Global). 2(3). doi: 10.1016/j.jacig.2023.100104. Fulltekst i vitenarkiv
• Mägi, Caroline-Aleksi Olsson; Despriee, Åshild W.; Småstuen, Milada Cvancarova; Almqvist, Catarina; Bahram, Fuad & Bakkeheim, Egil [Vis alle 20 forfattere av denne artikkelen] (2022). Maternal Stress, Early Life Factors and Infant Salivary Cortisol Levels. Children. 9(5). doi: 10.3390/children9050623. Fulltekst i vitenarkiv Vis sammendrag

  Background: Salivary cortisol (SC), a commonly used biomarker for stress, may be disrupted by negative events in pregnancy, at birth and in infancy. We aimed to explore if maternal perceived stress (PSS) in or after pregnancy and SC levels in pregnancy were associated with SC in early infancy, and, secondly, to identify early life factors associated with infants' SC levels (iSC). Methods: At 3 months of age, SC was analyzed in 1057 infants participating in a Nordic prospective mother-child birth cohort study. Maternal PSS was available from questionnaires at 18- and 34-week gestational age (GA) and 3-month post-partum, and SC was analyzed at 18-week GA. Early life factors included sociodemographic and infant feeding from questionnaires, and birth data from medical charts. Associations to iSC were analyzed by Spearman correlation and multinomial logistic regression analyses. Results: In this exploratory study neither PSS at any time point nor maternal SC (mSC) were associated with iSC. Higher birth weight was associated with higher levels of iSC, while inverse associations were observed in infants to a mother not living with a partner and mixed bottle/breastfeeding. Conclusions: Maternal stress was not associated with iSC levels, while birth weight, single motherhood and infant feeding may influence iSC levels. Keywords: PreventADALL; infant; perceived stress; salivary cortisol. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license https://creativecommons.org/licenses/by/4.0/).

• Fosheim, Ingrid Knutsdotter; Jacobsen, Daniel Pitz; Sugulle, Meryam; Alnæs-Katjavivi, Patji; Fjeldstad, Heidi & Ueland, Thor [Vis alle 8 forfattere av denne artikkelen] (2022). Serum amyloid A1 and pregnancy zone protein in pregnancy complications and correlation with markers of placental dysfunction. American Journal of Obstetrics & Gynecology MFM (AJOG MFM). 5(1). doi: 10.1016/j.ajogmf.2022.100794. Fulltekst i vitenarkiv Vis sammendrag

  BACKGROUND: Hypertensive disorders of pregnancy (preeclampsia, gestational hypertension, and chronic hypertension), diabetes mellitus, and placental dysfunction confer an increased risk of long-term maternal cardiovascular disease. Preeclampsia is also associated with acute atherosis that involves lesions of uteroplacental spiral arteries, resembling early stages of atherosclerosis. Serum amyloid A1 is involved in hypercoagulability and atherosclerosis and may aggregate into amyloid—aggregations of misfolded proteins. Pregnancy zone protein may inhibit amyloid aggregation. Amyloid is involved in Alzheimer's disease and cardiovascular disease; it has been identified in preeclampsia, but its role in preeclampsia pathophysiology is unclear.<p> <p>OBJECTIVE: We hypothesized that serum amyloid A1 would be increased and pregnancy zone protein decreased in hypertensive disorders of pregnancy and diabetic pregnancies and that serum amyloid A1 and pregnancy zone protein would correlate with placental dysfunction markers (fetal growth restriction and dysregulated angiogenic biomarkers) and acute atherosis. <p>STUDY DESIGN: Serum amyloid A1 is measurable in both the serum and plasma. In our study, plasma from 549 pregnancies (normotensive, euglycemic controls: 258; early-onset preeclampsia: 71; late-onset preeclampsia: 98; gestational hypertension: 30; chronic hypertension: 9; diabetes mellitus: 83) was assayed for serum amyloid A1 and pregnancy zone protein. The serum levels of angiogenic biomarkers soluble fms-like tyrosine kinase-1 and placental growth factor were available for 547 pregnancies, and the results of acute atherosis evaluation were available for 313 pregnancies. The clinical characteristics and circulating biomarkers were compared between the pregnancy groups using the MannWhitney U, chi-squared, or Fisher exact test as appropriate. Spearman’s rho was calculated for assessing correlations. <p>RESULTS: In early-onset preeclampsia, serum amyloid A1 was increased compared with controls (17.1 vs 5.1 mg/mL, P<.001), whereas pregnancy zone protein was decreased (590 vs 892 mg/mL, P=.002). Pregnancy zone protein was also decreased in diabetes compared with controls (683 vs 892 mg/mL, P=.01). Serum amyloid A1 was associated with placental dysfunction (fetal growth restriction, elevated soluble fmslike tyrosine kinase-1 to placental growth factor ratio). Pregnancy zone protein correlated negatively with soluble fms-like tyrosine kinase-1 to placental growth factor ratio in all study groups. Acute atherosis was not associated with serum amyloid A1 or pregnancy zone protein. <p>CONCLUSION: Proteins involved in atherosclerosis, hypercoagulability, and protein misfolding are dysregulated in early-onset preeclampsia and placental dysfunction, which links them and potentially contributes to future maternal cardiovascular disease.

• Mitlid-Mork, Birgitte; Bowe, Sophie; Staff, Anne Cathrine & Sugulle, Meryam (2022). Alterations in maternal sFlt-1 and PlGF: Time to labor onset in term-/late-term pregnancies with and without placental dysfunction. Pregnancy Hypertension. ISSN 2210-7789. 30, s. 148–153. doi: 10.1016/j.preghy.2022.10.004. Fulltekst i vitenarkiv Vis sammendrag

  Objectives To investigate the placenta-associated biomarkers placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) longitudinally in late third trimester extending to late-term pregnancies, and their correlation with time to labor onset in pregnancies with and without placental syndromes (ie preeclampsia and/or fetal growth restriction). Also, to compare whether time to labor onset after induction differ between these groups. Study design Pregnant women (n = 338, of which 75 had a placental syndrome) with serial blood samples from gestational week ≥37 until labor onset were included. Maternal serum PlGF and sFlt-1 concentrations were analyzed by immunoassay postpartum. Main outcome measures Rate of alteration in sFlt-1, PlGF and the sFlt-1/PlGF ratio prior to labor onset. Secondary outcome was rates of delivery within 48 h of labor induction. Results In placental syndrome pregnancies, sFlt-1 and sFlt-1/PlGF ratio increased more rapidly between the two last samples prior to labor onset compared to uncomplicated pregnancies (both p < 0.01), but there was no difference in the PlGF decrease (p = 0.513). Time to labor onset was significantly shorter in pregnancies with placental syndromes compared to those without (p = 0.001). In the induced deliveries, there was no difference in delivery within 48 h between the two groups. Conclusions An increase in sFlt-1 and sFlt-1/PlGF ratio at term prior to labor onset is more rapid in pregnancies with placental syndromes. This more rapid antiangiogenic shift might indicate a pregnancy more prone to acute placental failure and more inflammatory prepared for labor onset. Effect of labor induction was not impacted by placental dysfunction.

• Jacobsen, Daniel Pitz; Røysland, Ragnhild; Strand, Heidi; Moe, Kjartan; Sugulle, Meryam & Omland, Torbjørn [Vis alle 7 forfattere av denne artikkelen] (2022). Cardiovascular biomarkers in pregnancy with diabetes and associations to glucose control. Acta Diabetologica. ISSN 0940-5429. 59(9), s. 1229–1236. doi: 10.1007/s00592-022-01916-w. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Aim Cardiovascular disease (CVD) is a leading cause of death in both men and women. Type 1 and 2 diabetes mellitus (DM1 and DM2) are well-known risk factors for CVD. In addition, gestational diabetes mellitus (GDM) is a female sex-specific risk factor for CVD. Here, we measure circulating concentrations of cardiac troponin T (cTNT), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) during pregnancy—a window of time often referred to as a cardiovascular stress test for women. Methods This study utilized data from 384 pregnant women: 64 with DM1, 16 with DM2, 35 with GDM and 269 euglycemic controls. Blood was predominantly sampled within a week before delivery. Cardiovascular biomarker concentrations were measured in serum using electrochemiluminescence immunoassay. Result Circulating cTnT levels were higher in women with DM1, DM2 and GDM as compared to controls, whereas NT-proBNP and GDF-15 levels were only increased in women with DM1. Glucose dysregulation, assessed by third trimester HbA1c levels, positively correlated with all three CVD biomarker levels, whereas pregestational body mass index correlated negatively with GDF-15. Conclusions Our results support the presence of myocardial affection in women with diabetic disorders during pregnancy. Although pregestational DM1 in this study was associated with the most adverse CVD biomarker profile, women with GDM displayed an adverse cTnT profile similar to what we found in women with pregestational DM2. This supports that women with GDM should be offered long-term intensified cardiovascular follow-up and lifestyle advice following delivery, similarly to the well-established CV follow-up of women with pregestational DM.

• Linge, Lydia Lande; Sugulle, Meryam; Wallukat, Gerd; Dechend, Ralf & Staff, Anne Cathrine (2022). Circulating angiotensin II type I receptor – autoantibodies in diabetic pregnancies. Journal of Reproductive Immunology. ISSN 0165-0378. 155. doi: 10.1016/j.jri.2022.103777. Fulltekst i vitenarkiv Vis sammendrag

  Pregnant women with either pre-existing or gestational diabetes mellitus are at increased risk of preeclampsia as well as future cardiovascular disease. The renin-angiotensin system is dysregulated in both diabetes mellitus and preeclampsia. In preeclampsia, maternal levels of circulating agonistic autoantibodies against the angiotensin II Type I receptor (AT1-AAs) are increased. Circulating AT1-AAs are thought to contribute to both the pathophysiology of preeclampsia and the increased risk of future cardiovascular disease. Studies exploring AT1-AA in diabetes outside pregnancy suggest their potential for both metabolic and cardiovascular pathogenicity. No studies have investigated AT1-AAs in diabetic pregnancies. We hypothesized elevated maternal circulating AT1-AA levels in pregnancies complicated by any type of diabetes mellitus. Third-trimester maternal serum from 39 women (controls: n = 10; type 1 diabetes: n = 9; type 2 diabetes: n = 10; gestational diabetes=10) were analyzed for AT1-AA using an established bioassay method. Circulating AT1-AAs were present in 70% (7/10) of the controls and 83% (24/29) of the diabetes group (P = 0.399). Presence of AT1-AA was correlated to hsCRP levels (P = 0.036), but neither with maternal circulating angiogenic factors (soluble fms-like tyrosine kinase-1 and placental growth factor), nor with maternal or fetal characteristics indicative of metabolic disease or placental dysfunction. Our study is the first to demonstrate presence of circulating AT1-AAs in pregnant women with any type of diabetes. Our findings suggest AT1-AAs presence in pregnancy independently of placental dysfunction, nuancing the current view on their pathogenicity. Whether AT1-AAs per se contribute to increased risk of adverse pregnancy outcomes and future cardiovascular disease remains currently unanswered.

• Sheikh, Jameela; Allotey, John; Kew, Tania; Fernández-Félix, Borja M.; Zamora, Javier & Khalil, Asma [Vis alle 50 forfattere av denne artikkelen] (2022). Effects of race and ethnicity on perinatal outcomes in high-income and upper-middle-income countries: an individual participant data meta-analysis of 2 198 655 pregnancies. The Lancet. ISSN 0140-6736. 10(400), s. 2049–2062. doi: 10.1016/S0140-6736(22)01191-6. Fulltekst i vitenarkiv Vis sammendrag

  Background Existing evidence on the effects of race and ethnicity on pregnancy outcomes is restricted to individual studies done within specific countries and health systems. We aimed to assess the impact of race and ethnicity on perinatal outcomes in high-income and upper-middle-income countries, and to ascertain whether the magnitude of disparities, if any, varied across geographical regions. Methods For this individual participant data (IPD) meta-analysis we used data from the International Prediction of Pregnancy Complications (IPPIC) Network of studies on pregnancy complications; the full dataset comprised 94 studies, 53 countries, and 4 539 640 pregnancies. We included studies that reported perinatal outcomes (neonatal death, stillbirth, preterm birth, and small-for-gestational-age babies) in at least two racial or ethnic groups (White, Black, south Asian, Hispanic, or other). For our two-step random-effects IPD meta-analysis, we did multiple imputations for confounder variables (maternal age, BMI, parity, and level of maternal education) selected with a directed acyclic graph. The primary outcomes were neonatal mortality and stillbirth. Secondary outcomes were preterm birth and a small-for-gestational-age baby. We estimated the association of race and ethnicity with perinatal outcomes using a multivariate logistic regression model and reported this association with odds ratios (ORs) and 95% CIs. We also did a subgroup analysis of studies by geographical region. Findings 51 studies from 20 high-income and upper-middle-income countries, comprising 2 198 655 pregnancies, were eligible for inclusion in this IPD meta-analysis. Neonatal death was twice as likely in babies born to Black women than in babies born to White women (OR 2·00, 95% CI 1·44–2·78), as was stillbirth (2·16, 1·46–3·19), and babies born to Black women were at increased risk of preterm birth (1·65, 1·46–1·88) and being small for gestational age (1·39, 1·13–1·72). Babies of women categorised as Hispanic had a three-times increased risk of neonatal death (OR 3·34, 95% CI 2·77–4·02) than did those born to White women, and those born to south Asian women were at increased risk of preterm birth (OR 1·26, 95% CI 1·07–1·48) and being small for gestational age (1·61, 1·32–1·95). The effects of race and ethnicity on preterm birth and small-for-gestational-age babies did not vary across regions. Interpretation Globally, among underserved groups, babies born to Black women had consistently poorer perinatal outcomes than White women after adjusting for maternal characteristics, although the risks varied for other groups. The effects of race and ethnicity on adverse perinatal outcomes did not vary by region.

• Waldum, Åsa; Lukasse, Mirjam; Staff, Anne Cathrine; Falk, Ragnhild Sørum; Sørbye, Ingvil & Jacobsen, Anne Flem (2022). Intrapartum pudendal nerve block analgesia and childbirth experience in primiparous women with vaginal birth: A cohort study. Birth. ISSN 0730-7659. 50(1), s. 1–10. doi: 10.1111/birt.12697. Fulltekst i vitenarkiv Vis sammendrag

  Background A negative childbirth experience has short- and long-term consequences for both mother and child. This study aimed to investigate the association between intrapartum pudendal nerve block (PNB) analgesia and childbirth experience. Methods Primiparous women with a singleton cephalic vaginal live births at term at Oslo University Hospital from January 1, 2017, to June 1, 2019, were eligible for inclusion. The main outcome was total score on a childbirth experience questionnaire (range 1.0–4.0, higher score indicates better childbirth experience). An absolute risk difference of 0.10 was considered clinically relevant. Propensity score matching was used to adjust for differences in baseline characteristics between women with and without PNB. The analyses were stratified by spontaneous vs instrumental birth. Subanalyses of the questionnaire's domains (own capacity, professional support, perceived safety, and participation) were performed. Results Of 979 participating women, mean age was 32 years. Childbirth experience did not differ between women with and without PNB, either in spontaneous (absolute risk difference of the mean: −0.05, P value 0.36) or in instrumental birth (absolute risk difference of the mean: 0.03, P value 0.61). There were no statistically significant differences between PNB group scores for the separate domains. Conclusions Women's childbirth experiences did not differ between birthing people with or without PNB, either in spontaneous or in instrumental births. The clinical implications of our study should be interpreted in light of the pain-relieving effects of PNB.PNB should be provided on clinical indication, including for individuals with severe labor pain.

• Nordhagen, Live Solveig; Løfsgaard, Vibeke; Småstuen, Milada Cvancarova; Glavin, Kari; Carlsen, Kai-Håkon & Carlsen, Monica Hauger [Vis alle 21 forfattere av denne artikkelen] (2022). Maternal food-avoidance diets and dietary supplements during breastfeeding. Nursing Open. 10(1), s. 230–240. doi: 10.1002/nop2.1298. Fulltekst i vitenarkiv Vis sammendrag

  Aims To identify maternal food-avoidance diets and dietary supplement use during breastfeeding, and to explore factors associated with food avoidance diets. Design A prospective mother–child birth cohort study. Methods Electronic questionnaires were answered by 1,462 breastfeeding mothers 6 months postpartum in the Preventing Atopic Dermatitis and Allergies in Children (PreventADALL) study from 2014–2016. Demographic and antenatal factors were analysed for associations with food avoidance diets in 1,368 women by multiple logistic regression. Results Overall, 289 breastfeeding women (19.8%) avoided at least one food item in their diet, most commonly cow's milk in 99 women (6.8%). Foods were most often avoided due to conditions in the child, maternal factors or lifestyle choice. The odds for food avoidance diets were 2.1 (95% CI: 1.3, 3.4) for food allergy (presumed or diagnosed) and 19.4 (5.4, 70.1) for celiac disease in the mother. Dietary supplements were reported by nearly 80%, most commonly cod liver oil.

• Gudmundsdottir, Hrefna Katrin; Hilde, Katarina; Bains, Karen Eline Stensby; Färdig, Martin; Haugen, Guttorm Nils & Leblanc, Marissa Erin [Vis alle 13 forfattere av denne artikkelen] (2022). Fetal thoracic circumference in mid-pregnancy and infant lung function. Pediatric Pulmonology. ISSN 8755-6863. 58(1), s. 35–45. doi: 10.1002/ppul.26153. Fulltekst i vitenarkiv Vis sammendrag

  Background and Aim: Impaired lung function in early infancy is associated with later wheeze and asthma, while fetal thoracic circumference (TC) predicts severity of neonatal lung hypoplasia. Exploring fetal origins of lung function in infancy, we aimed to determine if fetal TC in mid‐pregnancy was associated with infant lung function. Methods: From the prospective Scandinavian general population‐based PreventADALL mother–child birth cohort, all 851 3‐month‐old infants with tidal flow‐volume measurements in the awake state and ultrasound fetal size measures at 18 (min–max 16–22) weeks gestational age were included. Associations between fetal TC and time to peak tidal expiratory flow to expiratory time (tPTEF/tE) were analyzed in linear regression models. To account for gestational age variation, we adjusted TC for simultaneously measured general fetal size, by head circumference (TC/HC), abdominal circumference (TC/AC), and femur length (TC/FL). Multivariable models were adjusted for maternal age, maternal asthma, pre‐pregnancy body mass index, parity, nicotine exposure in utero, and infant sex. Results: The infants (47.8% girls) were born at mean (SD) gestational age of 40.2 (1.30) weeks. The mean (SD) tPTEF/tE was 0.39 (0.08). The mean (SD) TC/HC was 0.75 (0.04), TC/AC 0.87 (0.04), and TC/FL 4.17 (0.26), respectively. Neither TC/HC nor TC/AC were associated with infant tPTEF/tE while a week inverse association was observed between TC/FL and tPTEF/tE (β ^ = −0.03, 95% confidence interval [−0.05, −0.007], p = 0.01). Conclusion: Mid‐pregnancy fetal TC adjusted for fetal head or abdominal size was not associated with tPTEF/tE in healthy, awake 3‐month‐old infants, while a weak association was observed adjusting for fetal femur length.

• Kedziora, Sarah M.; Obermayer, Benedikt; Sugulle, Meryam; Herse, Florian; Kräker, Kristin & Haase, Nadine [Vis alle 11 forfattere av denne artikkelen] (2022). Placental transcriptome profiling in subtypes of diabetic pregnancies Is strongly confounded by fetal sex. International Journal of Molecular Sciences. ISSN 1661-6596. 23:15388(23), s. 1–16. doi: 10.3390/ijms232315388. Fulltekst i vitenarkiv Vis sammendrag

  The placenta is a temporary organ with a unique structure and function to ensure healthy fetal development. Placental dysfunction is involved in pre-eclampsia (PE), fetal growth restriction, preterm birth, and gestational diabetes mellitus (GDM). A diabetic state affects maternal and fetal health and may lead to functional alterations of placental metabolism, inflammation, hypoxia, and weight, amplifying the fetal stress. The placental molecular adaptations to the diabetic environment and the adaptive spatio–temporal consequences to elevated glucose or insulin are largely unknown (2). We aimed to identify gene expression signatures related to the diabetic placental pathology of placentas from women with diabetes mellitus. Human placenta samples (n = 77) consisting of healthy controls, women with either gestational diabetes mellitus (GDM), type 1 or type 2 diabetes, and women with GDM, type 1 or type 2 diabetes and superimposed PE were collected. Interestingly, gene expression differences quantified by total RNA sequencing were mainly driven by fetal sex rather than clinical diagnosis. Association of the principal components with a full set of clinical patient data identified fetal sex as the single main explanatory variable. Accordingly, placentas complicated by type 1 and type 2 diabetes showed only few differentially expressed genes, while possible effects of GDM and diabetic pregnancy complicated by PE were not identifiable in this cohort. We conclude that fetal sex has a prominent effect on the placental transcriptome, dominating and confounding gene expression signatures resulting from diabetes mellitus in settings of well-controlled diabetic disease. Our results support the notion of placenta as a sexual dimorphic organ. Keywords: diabetes mellitus; human; placenta; pregnancy; RNA sequencing

• Sundet, Birgitte Kordt; Kreyberg, Ina; Staff, Anne Cathrine; Carlsen, Karin Cecilie Lødrup; Bains, Karen Eline Stensby & Berg, Jens Petter [Vis alle 20 forfattere av denne artikkelen] (2022). The effect of nicotine-containing products and fetal sex on placenta-associated circulating midpregnancy biomarkers. Biology of Sex Differences. 13(1). doi: 10.1186/s13293-022-00443-1. Fulltekst i vitenarkiv Vis sammendrag

  In utero exposure to nicotine, largely assessed by smoking, is a risk factor for impaired offspring health, while potential effects of non-combustible nicotine use such as snus (oral moist tobacco), are less well-known. Maternal serum concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) may be viewed as “placenta health markers”, known to differ by fetal sex. Maternal smoking during pregnancy has been associated with lower levels of circulating sFlt-1, while the effect of snus on placenta-associated angiogenic factors is unknown. Our aim was to explore if snus and/or smoking exposure was associated with midpregnancy maternal levels of sFlt-1, PlGF and sFlt-1/PlGF ratio if these associations were modified by fetal sex. Methods Midpregnancy (16–22 gestational weeks) serum from 2603 Scandinavian women enrolled in the population-based multi-center PreventADALL (Preventing Atopic Dermatitis and ALLergies in children) study was analysed for sFlt-1 and PlGF concentrations by electrochemiluminescence, deriving the sFlt-1/PGF ratio. Nicotine use was assessed by electronic questionnaires at enrollment in 2278 of the women. Univariable and multivariable linear regression models on log transformed outcomes were used to assess the association between nicotine use and biomarker levels. Interaction terms were included to identify whether the associations were modified by fetal sex. Results Median sFlt-1, PlGF and sFlt-1/PlGF ratios among women with nicotine exposure information were similar to those of all included women and differed by fetal sex. Current snus use was significantly associated with reduced maternal circulating PlGF levels in adjusted analyses [β − 0.12, (95% CI − 0.20; 0.00) compared to never use, p = 0.020]. A significant interaction between fetal sex and snus exposure was observed for PIGF (p = 0.031). Prior or periconceptional snus use was significantly associated with PIGF in male fetus pregnancies [β − 0.05 (95% CI − 0.09 to (− 0.02)) and β − 0.07 (95% CI − 0.12 to (− 0.02)) compared to never use, p = 0.002]. Smoking was not significantly associated with any circulating biomarkers levels. Conclusions Midpregnancy maternal angiogenic profile differed by periconceptional snus use and fetal sex. Snus exposure, perceived as “safe” by users, before or during pregnancy seems to affect midpregnancy placental health in a sex dimorphic manner.

• Lie, Anine; Gerdin, Sabina Wärnberg; Skrindo, Ingebjørg; Rehbinder, Eva Maria; Jonassen, Christine M & LeBlanc, Marissa Erin [Vis alle 14 forfattere av denne artikkelen] (2022). Evaluation of Skin Prick Test Reading Time at 10 versus 15 min in Young Infants. International Archives of Allergy and Immunology. ISSN 1018-2438. 183(8), s. 824–834. doi: 10.1159/000522526. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: The optimal time point for reading the mean wheal diameter (MWD) of a skin prick test (SPT) in infants is not established. We aimed to assess if either of two reading time points of the SPT, 10 or 15 min, was superior to detect allergic sensitization (AS) in 6-month-old infants. Methods: In 1,431 6-month-old infants from the population-based Preventing Atopic Dermatitis and ALLergies in children (PreventADALL) mother-child cohort, the SPT was performed with standard solutions for egg, cow’s milk, peanut, wheat, soy, birch, timothy, dog, and cat. The MWD was measured after 10 and 15 min. AS was defined as a positive SPT with MWD ≥2 mm larger than the negative control. Results: Overall, 149 (10.4%) infants were sensitized to at least one allergen at 10 and/or 15 min, while 138 (9.6%) had a positive SPT at 10 min and 141 (9.9%) at 15 min. A total of 12,873 allergen pricks were performed with 212 (1.6%) being positive at any time point, 194 (1.5%) positive at 10 min, and 196 (1.5%) positive at 15 min. The mean (95% CI) histamine MWD of 3.8 (3.8, 3.9) mm at 10 min was significantly larger than the 3.6 (3.6, 3.7) mm at 15 min. Discussion/Conclusions: Reading the SPT after both 10 and 15 min increased the number of 6-month-old infants with documented AS compared to reading after one time point only. As neither 10 nor 15 min reading time was superior to the other in detecting AS, our results indicate that readings at both time points should be considered. However, the histamine MWD was significantly larger at 10 min compared to 15 min. Reappraisal of SPT reading in infancy may be warranted.

• Jacobsen, Daniel Pitz; Røysland, Ragnhild; Strand, Heidi; Moe, Kjartan; Sugulle, Meryam & Omland, Torbjørn [Vis alle 7 forfattere av denne artikkelen] (2022). Circulating cardiovascular biomarkers during and after preeclampsia: Crosstalk with placental function? Pregnancy Hypertension. ISSN 2210-7789. 30, s. 103–109. doi: 10.1016/j.preghy.2022.09.003. Fulltekst i vitenarkiv Vis sammendrag

  Cardiovascular disease (CVD) is the leading cause of death in women, yet sex-specific risk factors remain understudied. Preeclampsia and other adverse pregnancy outcomes imply an increased maternal cardiovascular risk. We hypothesized that cardiac troponin T (cTnT), N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) are increased in such pregnancies and correlate with markers of placental dysfunction. We also investigated these cardiovascular biomarkers 1 or 3 years postpartum. Prior to delivery, we included serum from 417 pregnant women: 55 early-onset preeclampsia (EO-PE), 63 late-onset preeclampsia (LO-PE), 30 gestational hypertension (GH) and 269 healthy controls. Postpartum, we included 341 women 1 or 3 years after delivery: 26 EO-PE, 107 LO-PE, 61 GH, and 147 healthy pregnancies. Prior to delivery, median cTnT and NT-proBNP concentrations were higher in women with EO-PE, LO-PE, or GH than in controls. Median GDF-15 was higher in EO-PE and LO-PE compared to controls. Postpartum, GDF-15 was elevated in women with previous EO-PE. Markers of placental dysfunction correlated with CVD biomarkers in pregnancy, but not postpartum. Our findings underscore the cardiovascular burden of hypertensive disorders of pregnancy and the crosstalk with placental function. The upregulation of circulating GDF-15 following early-onset preeclampsia is in line with the epidemiological excessive risk of premature CVD in this group of women. GDF-15 may be explored for targeting postpartum women with most to gain from intensified preventive follow-up for CVD.

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• Waldum, Åsa; Pay, Aase Serine Devold; Aasbø, Gunvor; Mishra, Vinod Kumar; Sugulle, Meryam & Staff, Anne Cathrine (2025). The HOME (home monitoring of high-risk pregnancies) study: a study protocol for an observational study of a telemedicine-assisted follow-up at home vs. hospitalization. doi: 10.3389/fgwh.2025.1599153. Fulltekst i vitenarkiv
• Stivang, Maria Cecilie; Buerengen, Therese; Bernitz, Stine; Øian, Pål; Staff, Annetine & Olsen, Inge Christoffer [Vis alle 10 forfattere av denne artikkelen] (2025). The Norwegian WHO Labour Care Guide Trial; A stepped wedge cluster randomised trial. Fulltekst i vitenarkiv
• Staff, Annetine; Thomasy, Hannah; Arck, Petra; Boddy, Amy & Kroneis, Thomas (2024). A Stranger to Oneself: The Mystery of Fetal Microchimerism. [Journal]. The Scientist. Fulltekst i vitenarkiv Vis sammendrag

  https://www.the-scientist.com/a-stranger-to-oneself-the-mystery-of-fetal-microchimerism-72022

• Staff, Annetine; Fjeldstad, Heidi Elisabeth Storebø; Jacobsen, Daniel Pitz & Sugulle, Meryam (2024). Placental dysfunction, fetal microchimerism, and long-term maternal cardiovascular risk. Fulltekst i vitenarkiv
• Trent, Pernille Kristina Bjerre; Nordskar, Nina Jebens; Wangen, Knut Reidar; Engeskaug, Ida; Opheim, Linn Øvstebø & Aune, Guro [Vis alle 10 forfattere av denne artikkelen] (2024). Corrigendum to “Self-reported lower extremity lymphedema and quality of life after surgical staging of endometrial carcinoma: A population based cross-sectional study” [Gynecologic Oncology 175 (2023) 72–80, (S0090825823003232), (10.1016/j.ygyno.2023.05.070)]. Gynecologic Oncology. ISSN 0090-8258. 183, s. 7–8. doi: 10.1016/j.ygyno.2024.02.026. Fulltekst i vitenarkiv
• Aanstad, Kristin Jerve; Pripp, Are Hugo; Dalbye, Rebecka; Pay, Aase Serine Devold; Staff, Anne Cathrine & Kaasen, Anne [Vis alle 7 forfattere av denne artikkelen] (2024). Overuse of intrapartum CTG monitoring in low-risk women in Norway. Sexual & Reproductive HealthCare. ISSN 1877-5756. 42. doi: 10.1016/j.srhc.2024.101032. Fulltekst i vitenarkiv
• Staff, Anne Cathrine; Hansson, Stefan & Smárason, Alexander K. (2024). Christopher Redman. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 103(10), s. 2112–2113. doi: 10.1111/aogs.14963. Fulltekst i vitenarkiv
• Aanstad, Kristin Jerve; Pripp, Are Hugo; Dalbye, Rebecka; Pay, Aase Serine Devold; Staff, Anne Cathrine & Kaasen, Anne [Vis alle 7 forfattere av denne artikkelen] (2024). A low cesarean section rate is not a reason for overusing CTG. Sexual & Reproductive HealthCare. ISSN 1877-5756. 41. doi: 10.1016/j.srhc.2024.101017. Fulltekst i vitenarkiv
• Staff, Annetine (2024). Covid-19 i graviditet - risiko for mor og barn. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 144(1), s. 1–3. doi: 10.4045/tidsskr.23.0847. Fulltekst i vitenarkiv
• Jacobsen, Daniel Pitz; Fjeldstad, Heidi Elisabeth Storebø; Olsen, Maria Belland & Staff, Annetine (2023). Det finnes celler i kroppen din som stammer fra noen andre. Kan de være skadelige? Fulltekst i vitenarkiv Vis sammendrag

  https://www.forskersonen.no/biologi-kvinnehelse-medisin-og-helse/det-finnes-celler-i-kroppen-din-som-stammer-fra-noen-andre-kan-de-vaere-skadelige/2228845

• Staff, Annetine (2023). Placental dysfunction and increased fetal cell transfer: providing long-lasting cardiovascular messages to the mother. Fulltekst i vitenarkiv
• Fiskå, Bendik Seth; Pay, Aase Serine Devold; Staff, Anne Cathrine & Sugulle, Meryam (2023). Correction: Gestational diabetes mellitus, follow-up of future maternal risk of cardiovascular disease and the use of eHealth technologies – a scoping review (Systematic Reviews, (2023), 12, 1, (178), 10.1186/s13643-023-02343-w). Systematic Reviews. 12(1). doi: 10.1186/s13643-023-02383-2. Fulltekst i vitenarkiv
• Salvesen, Kjell Åsmund Blix; Staff, Annetine & Lian, Ingrid Alsos (2023). Veien videre - screening av hvem? - konsekvenser. Fulltekst i vitenarkiv
• Tiller, Heidi; Nedberg, Nora Hersoug; Nystad, Mona; Ahlen, Maria Therese; Bertelsen, eirin listau & Husebekk, Anne [Vis alle 8 forfattere av denne artikkelen] (2023). New insights on maternal platelet alloimmunization and placenta function. Fulltekst i vitenarkiv
• Ziesler, Charlotte P.Ø.; Staff, Anne Cathrine; Sugulle, Meryam & Moe, Kjartan (2023). Corrigendum to “Low physical activity levels 1 year after pregnancy complications” [Pregnancy Hyperten. 25 (2021) 136–142, (S221077892100060X), (10.1016/j.preghy.2021.05.022)]. Pregnancy Hypertension. ISSN 2210-7789. 33, s. 30–31. doi: 10.1016/j.preghy.2023.06.003. Fulltekst i vitenarkiv
• Salvesen, Kjell Åsmund Blix & Staff, Anne Cathrine (2023). Ny og nyttig screening for preeklampsirisiko. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(4). doi: 10.4045/tidsskr.22.0784. Fulltekst i vitenarkiv
• Staff, Annetine; Olsen, Maria Belland & Kong, Xiang Yi (2022). Kvinnehelse og forskning på Kvinnehelse. Fulltekst i vitenarkiv
• Fjeldstad, Heidi Elisabeth Storebø; Johnsen, Guro Mørk; Sugulle, Meryam & Staff, Annetine (2022). Føtale celler i mors sirkulasjon ved normotensive svangerskap til termin: korrelasjon med biomarkører for placentadysfunksjon. Fulltekst i vitenarkiv
• Fjeldstad, Heidi Elisabeth Storebø; Jacobsen, Daniel Pitz; Johnsen, Guro Mørk; Sugulle, Meryam & Staff, Annetine (2022). Fetal microchimerism and dysregulation of PlGF in pregnancy. Fulltekst i vitenarkiv
• Staff, Anne Cathrine (2022). Svangerskap hos kvinner født i utlandet. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 142(17). doi: 10.4045/tidsskr.22.0673. Fulltekst i vitenarkiv
• Klepp, Kristina; Staff, Annetine; Moe, Kjartan & Sugulle, Meryam (2026). Cardiometabolic indices following pregnancy complications: Impact of sex-independent and pregnancy-specific risk factors. Universitetet i Oslo. ISSN 9788234808722. Fulltekst i vitenarkiv Vis sammendrag

  Hypertensive disorders of pregnancy are associated with adverse cardiovascular changes and increased risk of future maternal cardiovascular disease. Pregnancy may be considered a cardiovascular stress test, as it puts extra strain on the heart and blood vessels. A cardiovascular follow-up is therefore recommended after such hypertensive pregnancy complications. However, optimal screening strategies for personalized cardiovascular disease risk evaluation and prevention remain unclear. This thesis aimed to explore both pregnancy-specific and sex-independent cardiovascular risk factors and their associations with a broad range of clinical, biochemical and imaging cardiovascular biomarkers. To this end, 319 women from the clinical Health after Pregnancy Complications (HAPPY) study were examined 1-3 years after a normotensive or a hypertensive pregnancy. We found that women with a recent history of a hypertensive pregnancy disorder had more unfavorable cardiometabolic profiles than women with prior normotensive pregnancy. Our findings support previous reports of adverse cardiovascular risk profiles after such hypertensive pregnancy complications, also after adjustment for other known sex-independent risk factors. This thesis supports the need for intensified and personalized cardiovascular follow-up already from the first years after hypertensive disorders of pregnancy. Cardiovascular follow-up should include assessments of classical, modifiable risk factors (e.g., hypertension, overweight, hyperglycemia and dyslipidemia) to enable early personalized prevention of cardiovascular disease in women.

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