Guttorm Nils Haugen

• Bonnichsen, Maja Lecic; Qvigstad, Elisabeth; Nyfløt, Lill Trine; Haugen, Guttorm Nils; Denault, William Robert Paul & Roland, Marie Cecilie (2026). Effects of gestational weight gain and HbA1C on fetal growth and birthweight in women with obesity. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. doi: 10.1111/aogs.70298. Fulltekst i vitenarkiv
• 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
• 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.

• Michelsen, Trond Melbye; Sajjad, Muhammad Umar; Haugen, Guttorm Nils; Moore, Lorna; Julian, Colleen G. & Sørbye, Ingvil Krarup [Vis alle 7 forfattere av denne artikkelen] (2025). Maternal body mass index is related to fetal uptake of glucose and oxygen via fetal insulin resistance rather than fetal glucose levels. Philosophical Transactions of the Royal Society of London. Biological Sciences. ISSN 0962-8436. 380(1933). doi: 10.1098/rstb.2024.0178. 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
• Sajjad, Muhammad Umar; Henriksen, Tore; Haugen, Guttorm Nils & Michelsen, Trond Melbye (2025). Placental hexokinase activity is related to fetal blood flow distribution in a cross-sectional study of healthy human pregnancies at term. Placenta. ISSN 0143-4004. 168, s. 1–8. doi: 10.1016/j.placenta.2025.05.015. Fulltekst i vitenarkiv
• Nordklev, Cecilie Bryn; Haugen, Guttorm Nils; Sande, Ragnar; Ebbing, Cathrine; Skrede, Solveig & Glad, Ragnhild [Vis alle 7 forfattere av denne artikkelen] (2025). Holdninger til NIPT-test blant gravide under 35 år. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 145(15). doi: 10.4045/tidsskr.25.0374. Fulltekst i vitenarkiv Vis sammendrag

  Bakgrunn: Med non-invasiv prenatal test (NIPT), en genetisk analyse basert på en blodprøve fra den gravide, kan man vurdere sannsynligheten for at fosteret har trisomi 13, 18 eller 21. Siden 2022 har man i norsk svangerskapsomsorg tilbudt tidlig ultralyd til alle gravide, mens NIPT-test tilbys gravide som ved fødselstermin er 35 år eller eldre. Formålet med studien var å kartlegge holdninger til NIPT-test blant gravide under 35 år. Materiale og metode: Desember 2024–januar 2025 distribuerte vi et spørreskjema ved fem av landets universitetssykehus til alle gravide under 35 år som møtte til tidlig ultralyd. Resultater: Blant 1 265 inviterte besvarte 1 260 (99,6 %) undersøkelsen. Blant 1 200 gravide som svarte på spørsmål om NIPT-test burde tilbys alle gravide gjennom det offentlige helsevesenet, svarte 915 (76,2 %) ja. Av 1 188 som svarte at de hadde hørt om NIPT-test, hadde 211 (17,9 %) betalt for og fått utført testen. Fortolkning: Tre av fire gravide under 35 år i Norge er positive til at NIPT-test tilbys alle gravide som en del av tidlig prenatal diagnostikk i det offentlige helsevesenet.

• Oftedal, Aurora; Kaasen, Anne; Karlsen, Taran; Haugen, Guttorm Nils & Bekkhus, Mona (2025). Maternal Distress in Pregnancies After Previous Fetal Anomaly: A Longitudinal Cohort Study. BJOG: An International Journal of Obstetrics and Gynaecology. ISSN 1470-0328. doi: 10.1111/1471-0528.18343. Fulltekst i vitenarkiv Vis sammendrag

  Objective To assess mental health throughout pregnancy among women with a history of diagnosis of fetal anomaly. Design Prospective observational study. Setting Tertiary referral centre for fetal medicine. Population Pregnant women with a history of fetal anomaly (study group; n  = 75) and women without such a history (comparison group; n  = 111). A subgroup of women in the study group ( n  = 28) participated in two different pregnancies, where the first had a diagnosis of fetal anomaly and the second did not. Methods Women completed the Edinburgh Postnatal Depression Scale (EPDS) and Impact of Events Scale (IES) at four timepoints between gestational age 18 weeks and 36 weeks. Main Outcomes Trajectories of EPDS and IES across time in the study group and comparison group, as well as differences in EPDS and IES in the healthy pregnancy and the pregnancy with a diagnosis of fetal anomaly in the subgroup. Results Having a history of previous diagnosis of fetal anomaly was associated with elevated levels of depression and traumatic stress throughout pregnancy, even in healthy pregnancies (e.g., EPDS mean difference = 2.65, 95% CI [1.91, 3.21]). The difference between groups was largest early in pregnancy and decreased with increasing gestational age. Furthermore, women in the subgroup experienced much higher levels of distress in the pregnancy with a diagnosis of fetal anomaly than in their healthy pregnancy (e.g., EPDS mean difference = 8.7, 95% CI [6.40, 11.15]). Conclusion The results highlight the importance of considering women's history of fetal anomaly and prenatal loss even in healthy pregnancies.

• BJARKØ, LISA; Fugelseth, Drude Merete; Haugen, Guttorm Nils & Nestaas, Eirik (2024). Early postnatal transitional circulation in fetal growth restricted neonates. Early Human Development. ISSN 0378-3782. 201. doi: 10.1016/j.earlhumdev.2024.106170. Fulltekst i vitenarkiv
• 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.

• Henriksen, Tore; Sajjad, Muhammad Umar; Haugen, Guttorm Nils & Michelsen, Trond Melbye (2024). Placental energy metabolism: Evidence for a placental-maternal lactate-ketone trade in the human. Placenta. ISSN 0143-4004. 148, s. 31–37. doi: 10.1016/j.placenta.2024.01.020. Fulltekst i vitenarkiv Vis sammendrag

  Introduction Glucose from placenta is the predominant energy source for the fetus. Individual placentas exhibit a range of glucose handling from apparent net production to high consumption, presumably reflecting an ability of placenta to secure both own and fetal energy needs. A dependency of placenta on glucose as the main energy source could impede fetal supply. Placenta seems to release lactate to maternal side implying loss of energy. Whether placenta takes up ketones is unclear. Our main hypothesis was that the human placenta can release lactate to the maternal side but take up maternal ketones. Methods An in vivo study of term uncomplicated pregnancies including 56 women delivered by cesarean section. We measured uterine and umbilical blood flow by Doppler ultrasonography, combined with blood sampling from maternal radial artery, uterine vein, umbilical artery and vein. Lactate and ketones were determined by quantitative nuclear magnetic resonance. Results Placenta released lactate to the maternal side (median −36.65 μmol/min. Q1, Q3: 78.53, 13.29), p < 0.001), but not to the fetal side. A net uptake of maternal ketones was found (median (Q1, Q3): 59.12 (30.64, 131.46) μmol acetate equivalents/min, p < 0.001) which largely was metabolized by the uteroplacenta. The uptake of ketones was comparable in energy to the loss of lactate. Discussion Placenta may release lactate to the maternal side. The energy lost by lactate may be compensated by uptake of maternal ketones. This lactate-ketone trade could benefit both placenta and the fetus by providing lactate for maternal gluconeogenesis and ketones for uteroplacental oxidative energy production.

• Bekkhus, Mona; Oftedal, Aurora; Haugen, Guttorm Nils; Mortensen, Berit & Kaasen, Anne (2024). Acute symptoms of depression and traumatic stress in men and women who terminate pregnancy after detection of fetal anomaly: A prospective observational study. BJOG: An International Journal of Obstetrics and Gynaecology. ISSN 1470-0328. doi: 10.1111/1471-0528.17884. Fulltekst i vitenarkiv Vis sammendrag

  Objective: To assess acute and long-term stress in men and women after the detection of fetal anomalies leading to pregnancy termination. Design: Prospective observational study. Setting: Tertiary referral centre for fetal medicine. Population: From the initial sample of 180 pregnant women with a fetal anomaly detected by ultrasound examination, a total of 87 women terminated their pregnancy, with 72 partners included in the sample. At the time of detection, the group of women (n = 93) and their partners (n = 81) who did not terminate the pregnancy following a diagnosis were included as a comparison group. Methods: These women and their partners were asked to complete the Edinburgh Postnatal Depression Scale (EPDS) and the Impact of Events Scale (IES) questionnaires, both at the time of initial detection and at 6 weeks after the termination of the pregnancy. Main outcome measures: Responses to the EPDS and the IES at the time of initial detection and at 6 weeks after pregnancy termination. Results: Women who underwent pregnancy termination reported higher symptom levels of depression, but not traumatic stress, prior to the termination than women who chose not to terminate their pregnancy. Among men, there was a difference across depression and all subscales of traumatic stress (e.g. IES intrusion: mean difference 5.31; 95% CI 2.32–8.31). Women experienced more depressive symptoms over time than men (β = 4.33, P < 0.001) and higher symptom levels on all subscales of traumatic stress (e.g. IES intrusion: β = 5.27; P < 0.001). Conclusions: Overall, our study underscores the heightened levels of depression and traumatic stress experienced by prospective parents, particularly prior to the decision to terminate a pregnancy following the detection of a fetal anomaly. Although women generally report more pronounced symptoms, it is noteworthy that men also experience considerable traumatic stress during this challenging time.

• 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.

• Bonnichsen, Maja Lecic; Gunnes, Nina; Nyfløt, Lill Trine; Haugen, Guttorm Nils & Roland, Marie Cecilie (2024). Prepregnancy body mass index and visceral fat exhibit divergent associations with metabolic factors in pregnant women with obesity: A Norwegian cohort study. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 103(12), s. 2511–2521. doi: 10.1111/aogs.14968. Fulltekst i vitenarkiv Vis sammendrag

  Introduction Pregnancy involves changes in maternal metabolism that differ between normal-weight women and women with overweight or obesity, including changes in glucose, insulin, lipids, and adipokines. These changes contribute to altered risk profiles for adverse outcomes for both mother and child during pregnancy, childbirth, and postpartum. We explored associations between visceral fat and prepregnancy body mass index (pBMI), respectively, with glucose and lipid metabolism, as well as with adipokines and C-reactive protein (CRP), measured fasting in early and late pregnancy. We hypothesized that among women with pBMI ≥35 kg/m2, visceral fat measured around gestational week 18 (visceral fat18) would show associations with greater number of metabolic variables during pregnancy, than pBMI. Material and Methods This prospective longitudinal cohort study was conducted at the Department of Gynecology and Obstetrics at Drammen Hospital from 2016 to 2019. We included 166 nulliparous (47.6%) and parous pregnant women with pBMI ≥35 kg/m2 and singleton pregnancy. Women with type 1 diabetes were excluded. We evaluated associations of pBMI and visceral fat estimated with bioimpedance weight around gestational week 18 (visceral fat18) with fasting metabolic measures around gestational weeks 18 and 36 using median regression models. We used the paired t-test or the Wilcoxon signed-rank test, as appropriate, to analyze changes in metabolic measures from early to late pregnancy, and median regression to estimate crude and adjusted differences in medians of 21 maternal metabolic measures associated with one-unit changes in pBMI and visceral fat18, respectively. Results pBMI and visceral fat18 were highly correlated and showed associations with similar metabolic measures in pregnancy in crude analysis. After mutual adjustment for each other in addition to age and parity, pBMI was associated with glucose metabolism, in particular fasting insulin, whereas visceral fat18 was primarily associated with leptin. Conclusions Among pregnant women with BMI ≥35 kg/m2, easily obtainable pBMI and the more resource-demanding estimate of visceral fat18 exhibit divergent associations with metabolic measures; pBMI was positively associated with insulin, glucose, and HbA1c, while visceral fat18 was positively associated with leptin. We did not find visceral fat18 to be associated with greater number of metabolic factors than pBMI.

• Langen, Ingrid; Langesæter, Eldrid; Gunnes, Nina; Almaas, Vibeke Marie; Haugen, Guttorm Nils & Estensen, Mette-Elise [Vis alle 7 forfattere av denne artikkelen] (2024). Hypertensive disorders of pregnancy among women with cardiovascular disease in Norway: A historical cohort study. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 103(7), s. 1457–1465. doi: 10.1111/aogs.14841. Fulltekst i vitenarkiv Vis sammendrag

  Introduction Women with cardiovascular disease may be at increased risk of hypertensive disorders of pregnancy (HDP). We aimed to: (1) Investigate the occurrence of HDP in a cohort of pregnant women with cardiovascular disease and compare it with the occurrence in the general population. (2) Assess the association between maternal cardiovascular risk and risk of HDP. Material and methods We reviewed clinical data on a cohort of 901 pregnancies among 708 women with cardiovascular disease who were followed at the National Unit for Pregnancy and Heart Disease and gave birth at Oslo University Hospital between 2003 and 2018. The exposure under study was maternal cardiovascular risk, classified as low, moderate, or high based on a modified classification by the World Health Organization. The main outcome of interest was HDP, which included pre-eclampsia and gestational hypertension. The proportion of HDP cases in the general population in the same period was extracted from the Medical Birth Registry of Norway. We used logistic regression to estimate crude and adjusted odds ratios (OR) of HDP, with associated 95% confidence intervals (CIs), for women with moderate- and high cardiovascular risk compared to women with low risk. Results The occurrence of HDP in the study cohort was 12.1% (95% CI: 10.0%–14.4%) and varied between 8.7% (95% CI: 6.5%–11.3%) in the low-risk group, 15.7% (95% CI: 11.1%–21.4%) in the moderate-risk group, and 22.2% (95% CI: 15.1%–30.8%) in the high-risk group. By contrast, the nationwide occurrence of HDP was 5.1% (95% CI: 5.1%–5.2%). In the study cohort, the proportions of pregnancies with gestational hypertension and pre-eclampsia were similar (6.3% and 5.8%, respectively). Compared to pregnancies with low cardiovascular risk, the adjusted OR of HDP was 2.04 (95% CI: 1.21–3.44) in the moderate-risk group and 2.99 (95% CI: 1.73–5.18) in the high-risk group. Conclusions The occurrence of hypertensive disease of pregnancy in the study cohort was more than doubled compared to the general population in Norway. The risk of HDP increased with maternal cardiovascular risk group. We recommend taking into account maternal cardiovascular risk group when assessing risk and prophylaxis of HDP.

• 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

• 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.

• 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.

• 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.

• 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, 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.

• Nestaas, Eirik; BJARKØ, LISA; Kiserud, Torvid; Haugen, Guttorm Nils & Fugelseth, Drude (2023). Heart function by M-mode and tissue Doppler in the early neonatal period in neonates with fetal growth restriction. Early Human Development. ISSN 0378-3782. 183. doi: 10.1016/j.earlhumdev.2023.105809. Fulltekst i vitenarkiv Vis sammendrag

  Background: Fetal growth restricted (FGR) neonates have increased risk of circulatory compromise due to failure of normal transition of circulation after birth. Aim: Echocardiographic assessment of heart function in FGR neonates first three days after birth. Study design: Prospective observational study. Subjects: FGR- and non-FGR neonates. Outcome measures: M-mode excursions and pulsed-wave tissue Doppler velocities normalised for heart size and E/e′ of the atrioventricular plane day one, two and three after birth. Results: Compared with controls (non-FGR of comparable gestational age, n = 41), late-FGR (gestational age ≥ 32 weeks, n = 21) exhibited higher septal excursion (15.9 (0.6) vs. 14.0 (0.4) %, p = 0.021) (mean (SEM)) and left E/e′ (17.3 (1.9) vs.11.5 (1.3), p = 0.019). Relative to day three, indexes on day one were higher for left excursion (21 (6) % higher on day one, p = 0.002), right excursion (12 (5) %, p = 0.025), left e′ (15 (7) %, p = 0.049), right a′ (18 (6) %, p = 0.001), left E/e′ (25 (10) %, p = 0.015) and right E/e′ (17 (7) %, p = 0.013), whereas no index changed from day two to day three. Late-FGR had no impact on changes from day one and two to day three. No measurements differed between early-FGR (n = 7) and late-FGR. Conclusions: FGR impacted neonatal heart function the early transitional days after birth. Late-FGR hearts had increased septal contraction and reduced left diastolic function compared with controls. The dynamic changes in heart function between first three days were most evident in lateral walls, with similar pattern in late-FGR and non-FGR. Early-FGR and late-FGR exhibited similar heart function.

• 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.

• Arntzen, Trine; Mikkelsen, Audun; Emblem, Ragnhild; Lai, Xiaoran & Haugen, Guttorm Nils (2023). Prenatal Diagnosis of Esophageal Atresia – Performance and Consequences. Journal of Pediatric Surgery. ISSN 0022-3468. 58(11), s. 2075–2080. doi: 10.1016/j.jpedsurg.2023.05.015. Fulltekst i vitenarkiv Vis sammendrag

  Background Prenatal diagnosis of congenital malformations is considered favorable. Esophageal atresia (EA) is prenatally detected in 10–40% of patients. The aims of our study were to assess factors influencing the prenatal detection rate and to study the outcome in EA patients with and without prenatal diagnosis. Method We included 136 patients in two time periods, group 1 (1996–2002, n = 68) and group 2 (2014–2020, n = 68). We registered clinical variables; prenatal signs, perinatal and postnatal outcome from the electronic patient record. Results Twenty-five patients (18%) had a prenatal diagnosis of EA, significantly more during 2014–2020 (28%), than during 1996–2002 (9%). Patients with EA type A or B and with associated anomalies had increased likelihood of prenatal diagnosis, odds ratio (OR) 9.00 (1.99–40.69) and 3.53 (1.24–10.06), respectively. Among the 25 patients with prenatal diagnosis all had polyhydramnios and 16 had small/absent stomach. Prenatally diagnosed patients arrived significantly earlier at the surgical unit (median 2 h (2 h-1 days) vs 21 h (2 h-1275 days)), had more delayed primary anastomosis (OR 8.80 (2.68–28.92)) and anastomotic stricture (OR 3.11 (1.20–8.04)), longer length of stay (median 62 days (11–212 days) vs 20 days (2–270 days)) and longer time on ventilator (median 5 days (1–25 days) vs 1.5 days (0.5–33 days)) compared to patients without prenatal diagnosis. In multivariate analysis prenatal diagnosis predicts length of stay. Conclusion Prenatally diagnosed EA patients have more; type A and B malformations, associated anomalies and neonatal morbidity. Consequences of the assumed benefits of prenatal diagnosis; opportunity of early arrival to surgical care and prenatal counselling, must be further studied.

• 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.

• Sajjad, Muhammad Umar; Henriksen, Tore; Roland, Marie Cecilie; Haugen, Guttorm Nils & Michelsen, Trond Melbye (2023). Maternal body mass index, birthweight, and placental glucose metabolism: evidence for a role of placental hexokinase. American Journal of Obstetrics and Gynecology. ISSN 0002-9378. s. 1–10. doi: 10.1016/j.ajog.2023.10.043. Fulltekst i vitenarkiv Vis sammendrag

  Background The principal fetal energy source is glucose provided by the placental transfer of maternal glucose. However, the placenta’s glucose consumption exhibits considerable variation. Hexokinase is the first and one of the rate-limiting enzymes of glycolysis that phosphorylates glucose to glucose-6-phosphate. The role of placental hexokinase activity in human placental glucose metabolism is unknown. Objective This study aimed to test the hypothesis that placental hexokinase activity is related to maternal body mass index, placental glucose uptake and consumption, and birthweight. Study Design Overall, 67 healthy pregnant participants at term were included in this study at Oslo University Hospital, Oslo, Norway. Placental hexokinase activity was measured by using a colorimetric assay. The mass of glucose taken up by the uteroplacental unit and the fetus was obtained by measuring arteriovenous glucose differences combined with Doppler assessment of uterine and umbilical blood flow. Blood samples were obtained from the maternal radial artery, uterine vein, and umbilical artery and vein. The uteroplacental glucose consumption constituted the difference between uteroplacental and fetal glucose uptakes. The Spearman rank correlation was performed for statistical analyses to study the correlation of placental hexokinase activity (milliunit per milligram of protein) with prepregnancy body mass index, maternal glucose and insulin, birthweight, uteroplacental glucose uptake and consumption, and fetal glucose uptake (micromole per minute). Partial rank correlation analysis was performed when controlling for hours of fasting or placental weight. Results Hexokinase activity was detectable in all placental tissue samples. The mean activity was 19.6 (standard deviation, 4.64) mU/mg protein. Placental hexokinase activity correlated positively with prepregnancy body mass index (Spearman rho=0.33; P=.006). On controlling for hours of fasting, hexokinase activity showed positive correlations with both maternal glucose (r=0.30; P=.01) and insulin (r=0.28; P=.02). Hexokinase activity was positively correlated with uteroplacental glucose uptake (Spearman rho=0.31; P=.01) and consumption (Spearman rho=0.28; P=.02). Hexokinase activity did not correlate with fetal glucose uptake. On controlling for placental weight, hexokinase activity showed a positive correlation with birthweight (r=0.31; P=.01). Conclusion Our findings suggest that placental hexokinase, being crucial for uteroplacental retention of glucose for disposition, is related to both maternal body mass index and birthweight independent of placental weight. Placental hexokinase may play a central role in the relationship between maternal glucose dysregulation and fetal growth. Thus, the current study supports the need to develop clinically useful tools to assess the metabolic properties of the placenta.

• 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/).

• Oftedal, Aurora; Bekkhus, Mona; Haugen, Guttorm Nils; Czajkowski, Nikolai Olavi & Kaasen, Anne (2022). The impact of diagnosed fetal anomaly, diagnostic severity and prognostic ambiguity on parental depression and traumatic stress: a prospective longitudinal cohort study. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 101(11), s. 1291–1299. doi: 10.1111/aogs.14453. Fulltekst i vitenarkiv Vis sammendrag

  Introduction - The detection of a fetal anomaly during routine obstetric ultrasound is a potentially traumatic experience. The aim of this study is to examine longitudinally the impact of diagnosis of fetal anomaly on symptoms of depression and traumatic stress among mothers and fathers, and to examine how variations in psychological adjustment relate to diagnostic severity and prognostic ambiguity.<p> <p>Material and methods - In this prospective observational study conducted at a tertiary perinatal referral center, 81 mothers and 69 fathers with ultrasound findings of fetal anomaly completed the Edinburgh Postnatal Depression Scale (EPDS) and Impact of Events Scale (IES) at four time points in pregnancy (T1–T4) and 6 weeks after birth (T5). We compared this with depression and traumatic stress in a sample of non-affected parents (n = 110 mothers, 98 fathers).<p> <p>Results - Linear mixed effects models indicated that parents who received a diagnosis of fetal anomaly experienced higher levels of depression and traumatic stress over time, compared with non-affected parents. Depression: mean difference mothers = 4.46 ± 0.47, fathers = 2.80 ± 0.42. Traumatic stress: mean difference mothers = 20.04 ± 2.13, fathers = 12.66 ± 1.74. Parents with a more severe diagnosis experienced elevated symptoms compared with parents with a less severe diagnosis. Among mothers, prognostic ambiguity and changes in the anticipated diagnosis after birth were also associated with increased distress, regardless of whether the change was for the better or worse.<p> <p>Conclusions - Diagnosis of fetal anomaly increases risk of depression and traumatic stress in expectant mothers and fathers, both acutely and over time.

• Bjarkø, Lisa; Fugelseth, Drude; Harsem, Nina Kittelsen; Kiserud, Torvid; Haugen, Guttorm Nils & Nestaas, Eirik (2022). Cardiac morphology in neonates with fetal growth restriction. Journal of Perinatology. ISSN 0743-8346. 43. doi: 10.1038/s41372-022-01538-8. Fulltekst i vitenarkiv Vis sammendrag

  Objective: Assess effects of fetal growth restriction (FGR) on cardiac modelling in premature and term neonates. Study design: Prospective echocardiographic study of a cohort of FGR neonates (n = 21) and controls (n = 41) with normal prenatal growth and circulation. Results: Unadjusted for gestational age, birth weight, sex, and twin/singleton, Late-FGR neonates had smaller hearts than controls, with globular left ventricles and symmetrical right ventricles. Adjusted estimates showed smaller left ventricles and similarly sized right ventricles, with symmetrical left and right ventricles. Early-FGR (compared with Late-FGR) had smaller hearts and globular left ventricles in unadjusted estimates, but after adjustment, sizes and shapes were similar. Conclusion: FGR had significant impact on cardiac modelling, seen in both statistical models unadjusted and adjusted for gestational age, birth weight, sex, and twin/singleton. The adjustments, however, refined the results and revealed more specific effects of FGR, thus underscoring the importance of statistical adjustments in such studies.

• Henriksen, Tore; Roland, Marie Cecilie; Sajjad, Muhammad Umar; Haugen, Guttorm Nils & Michelsen, Trond Melbye (2022). Uteroplacental versus fetal use of glucose in healthy pregnancies at term. A human in vivo study. Placenta. ISSN 0143-4004. 128, s. 116–122. doi: 10.1016/j.placenta.2022.09.001. Fulltekst i vitenarkiv
• 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.

• Oftedal, Aurora; Bekkhus, Mona; Haugen, Guttorm Nils; Hjemdal, Odin; Czajkowski, Nikolai Olavi & Kaasen, Anne (2022). Long-Term Impact of Diagnosed Fetal Anomaly on Parental Traumatic Stress, Resilience, and Relationship Satisfaction. Journal of Pediatric Psychology. ISSN 0146-8693. 48(2), s. 181–192. doi: 10.1093/jpepsy/jsac085. Fulltekst i vitenarkiv Vis sammendrag

  Knowledge regarding the long-term psychological adjustment of parents to children with prenatal diagnosis of congenital malformation is scarce. The aim of this study is to examine traumatic stress trajectories, resilience, and relationship satisfaction among parents to children with prenatal diagnosis of a congenital malformation, and to compare this to a sample of non-affected parents. Methods A prospective longitudinal cohort study was conducted at a tertiary perinatal referral center. Ninety-three mothers and 80 fathers who received a diagnosis of fetal anomaly during obstetric ultrasound examination (study group), and 110 mothers and 98 fathers with normal ultrasound findings (comparison group), reported their traumatic stress at four timepoints during pregnancy (T1-T4), 6 weeks after birth (T5), and 10-12 years after birth (T6). Resilience and relationship satisfaction was reported at 10-12 years after birth. Results Parents to children with a congenital malformation experienced significantly elevated traumatic stress levels over time, compared with parents of children without congenital malformation. The difference between groups was largest acutely after diagnosis and remained significant 10-12 years after the birth of the child. Resilience and relationship satisfaction levels were similar in both groups. Conclusions Despite experiencing high levels of traumatic stress over time, parents to children with a congenital malformation reported resilience and relationship satisfaction at similar levels to non-affected parents. This suggests that despite ongoing long-term distress, parents are still able to maintain positive psychological coping resources.

• 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.

• Zahid, Saba Muneer; Opheim, Gun Lisbeth; Henriksen, Tore; Michelsen, Trond Melbye & Haugen, Guttorm Nils (2022). Effect of a standardized maternal meal on fetal middle cerebral artery Doppler indices: A single-blinded crossover study. PLOS ONE. 17(8), s. 1–12. doi: 10.1371/journal.pone.0272062. Fulltekst i vitenarkiv Vis sammendrag

  Objective Measures of Doppler blood flow velocity profiles are an integral part of monitoring fetal well-being during pregnancy. These examinations are performed at different times of the day and at different maternal meal states. In uncomplicated pregnancies, we assessed the effect of a standardized maternal meal on middle cerebral artery (MCA) and umbilical artery (UA) Doppler blood flow velocity pulsatility indices (PIs) and MCA peak systolic velocity (PSV). Methods In this prospective single-blinded crossover study 25 healthy women were examined at 36 weeks of pregnancy. The first examination was performed in the morning following overnight fast, and repeated after extended fast (state A), and after a standard breakfast meal (state B). Results Irrespective of maternal prandial status, the MCA-PI values were lower in the 2nd compared to the 1st examination (-0.187; p = 0.071, and -0.113; p = 0.099, state A and B, respectively). Compared to the values in the 1st examination, the UA-PI values, were higher after extended fast (0.014; p = 0.436), and lower post-prandially (-0.036; p = 0.070). The difference (state B minus state A) between the meal states were not significant (0.074; p = 0.487 and -0.050; p = 0.058, for MCA-PI and UA-PI, respectively). Adjusting for the possible influence of fetal heart rate on MCA-PI and UA-PI, the differences between meal states remained non-significant (p = 0.179, p = 0.064, respectively). The MCA-PSV values increased after the meal (6.812; p = 0.035), whereas no increase was observed following extended fast (0.140; p = 0.951). The difference in MCA-PSV values between the two meal states was not significant (6.672; p = 0.055). Conclusion Our results demonstrate possible diurnal variations in MCA-PI and UA-PI, with and without adjustment for fetal heart rate, that seem to be unaffected by maternal meal intake in healthy pregnancies.

• Skjerven, Håvard Ove; Lie, Anine; Vettukattil, Muhammad Riyas; Rehbinder, Eva Maria; Leblanc, Marissa Erin & Asarnoj, Anna [Vis alle 29 forfattere av denne artikkelen] (2022). Early food intervention and skin emollients to prevent food allergy in young children (PreventADALL): a factorial, multicentre, cluster-randomised trial. The Lancet. ISSN 0140-6736. 399(10344), s. 2398–2411. doi: 10.1016/S0140-6736(22)00687-0. Fulltekst i vitenarkiv Vis sammendrag

  Background: Primary prevention of food allergy by early introduction of allergenic foods seems promising. We aimed to determine whether early food introduction or the application of regular skin emollients in infants from a general population reduced the risk of food allergy. Methods: This 2 × 2 factorial, cluster-randomised trial was done at Oslo University Hospital and Østfold Hospital Trust, Oslo, Norway, and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine 18-week ultrasound examination were cluster-randomised at birth to the following groups: (1) no intervention group; (2) the skin intervention group (skin emollients; bath additives and facial cream; from age 2 weeks to

• Gudmundsdottir, Hrefna Katrin; Carlsen, Oda Cecilie; Bains, Karen Eline Stensby; Färdig, Martin; Haugen, Guttorm Nils & Jonassen, Christine M [Vis alle 13 forfattere av denne artikkelen] (2022). Infant lung function and maternal physical activity in the first half of pregnancy. European Respiratory Journal Open Research (ERJ Open Research). 8(4). doi: 10.1183/23120541.00172-2022. Fulltekst i vitenarkiv Vis sammendrag

  Background and aim Physical activity (PA) in pregnancy is important for maternal and possibly offspring health. To study the early origins of lung function we aimed to determine whether PA in the first half of pregnancy is associated with lung function in healthy 3-month-old infants. Methods From the general population-based Preventing Atopic Dermatitis and Allergies in Children birth cohort recruiting infants antenatally in Norway and Sweden, all 812 infants (48.8% girls) with available tidal flow–volume measures in the awake state at 3 months of age and mid-pregnancy data on PA were included. PA was self-reported by the mothers and, based on intensity, we categorised them as active or inactive during pregnancy. Furthermore, we defined active mothers as fairly or highly active. The main outcome was a ratio of time to peak tidal expiratory flow to expiratory time ( t PTEF / t E ) &lt;0.25. Associations were analysed by logistic regression, adjusting for maternal age, education, parity, pre-pregnancy body mass index, in utero nicotine exposure and parental atopy. Results The mean± sd t PTEF / t E was 0.391±0.08 and did not differ significantly according to maternal PA level in pregnancy. The 290 infants of inactive mothers had higher odds of having t PTEF / t E &lt;0.25 compared to infants of all active mothers (OR 2.07, 95% CI 1.13–3.82; p=0.019) and compared to infants (n=224) of fairly active (OR 2.83, 95% CI 1.26–7.24; p=0.018) but not highly active mothers (n=298). Conclusion Based on self-reported maternal PA in the first half of pregnancy, 3-month-old infants of inactive compared to active mothers had higher odds of a low t PTEF / t E .

• Endre, Kim Magnus Advocaat; Landrø, Linn Aina Ysland; LeBlanc, Marissa Erin; Gjersvik, Petter; Carlsen, Karin C. Lødrup & Haugen, Guttorm [Vis alle 15 forfattere av denne artikkelen] (2021). Diagnosing atopic dermatitis in infancy using established diagnostic criteria: a cohort study. British Journal of Dermatology. ISSN 0007-0963. 186(6), s. 50–58. doi: 10.1111/bjd.19831. Fulltekst i vitenarkiv Vis sammendrag

  Background Diagnosing atopic dermatitis (AD) in infants is challenging. Objectives To determine the incidence and persistence of eczema and AD in infants using the UK Working Party (UKWP) and Hanifin and Rajka (H&R) criteria. Methods A cohort of 1834 infants was examined clinically at 3, 6 and 12 months of age. AD was diagnosed by UKWP (3, 6 and 12 months) and H&R (12 months) criteria. Logistic regression models were used to assess the relationship between AD and eczema. Results Eczema was observed in 628 (34·2%) infants (n = 240, n = 359 and n = 329 at 3, 6 and 12 months, respectively), with AD diagnosed in 212 (33·7%) infants with any eczema and in 64/78 (82%) infants with eczema at all three visits. The odds of AD were lower with first presentation of eczema at 6 [odds ratio (OR) 0·33, 95% confidence interval (CI) 0·22–0·48] or 12 months (OR 0·49, 95% CI 0·32–0·74) than at 3 months, and higher in infants with eczema at three (OR 23·1, 95% CI 12·3–43·6) or two (OR 6·5, 95% CI 4·3–9·9) visits vs. one visit only. At 12 months, 156/329 (47·4%) fulfilled the UKWP and/or H&R criteria; 27 (8%) fulfilled the UKWP criteria only and 65 (20%) only the H&R criteria. Of the 129 infants who fulfilled the H&R criteria, 44 (34·1%) did not meet the itch criterion. Conclusions Used in combination and at multiple timepoints, the UKWP and H&R criteria for AD may be useful in clinical research but may have limited value in most other clinical settings.

• Tedner, Sandra G.; Söderhäll, Cilla; Konradsen, Jon R.; Bains, Karen Eline Stensby; Borres, Magnus P. & Carlsen, Kai-Håkon [Vis alle 24 forfattere av denne artikkelen] (2021). Extract and molecular-based early infant sensitization and associated factors—A PreventADALL study. Allergy. European Journal of Allergy and Clinical Immunology. ISSN 0105-4538. doi: 10.1111/all.14805. Fulltekst i vitenarkiv Vis sammendrag

  Background: More knowledge about sensitization patterns in early infancy, including impact of molecular allergology, is needed to help predict future allergy development more accurately. Objective: We aimed to determine the prevalence and patterns of allergic sensitization at 3 months of age, and explore possible associated factors. Methods: From the Scandinavian antenatally recruited PreventADALL mother–child cohort, we included 1110 3-month infants with available serum. Sensitization was defined as s-IgE of ≥0.1 kUA/L by Phadiatop Infant® (ThermoFisher Scientific) including birch, cat, grass, dog, milk, egg, peanut and wheat. Further ImmunoCAP analyses to ovomucoid, casein, Ara h 1-3, omega-5-gliadin were performed in food extract s-IgE-positive children. Maternal sensitization was defined as s-IgE ≥ 0.35 kUA/L to Phadiatop® (inhalant allergen mix) and/or Fx5 (food allergen mix) at 18-week pregnancy. Results: Overall 79 (7.3%) infants had specific sensitization, many with low s-IgE-levels (IQR 0.16–0.81 kUA/L), with 78 being sensitized to food extract allergens; 41 to egg, 27 to milk, 10 to peanut, and 25 to wheat. A total of 62/78 were further analysed, 18 (29%) had s-IgE to ovomucoid, casein, Ara h 1-3 and/or omega-5-gliadin. Eight infants (0.7%) were sensitized to inhalant allergens. Maternal sensitization to food allergens was associated with infant sensitization, odds ratio 3.64 (95% CI 1.53–8.68). Conclusion: Already at 3 months of age, 7% were sensitized to food, mostly without detectable s-IgE to food allergen molecules, and <1% to inhalant allergens. Maternal food sensitization was associated with infants’ sensitization.

• Carlsen, Oda Cecilie; Gudmundsdóttir, Hrefna Katrín; Bains, Karen Eline Stensby; Bertelsen, Randi Jacobsen; Carlsen, Karin C. Lødrup & Carlsen, Kai-Håkon [Vis alle 27 forfattere av denne artikkelen] (2021). Physical activity in pregnancy: a Norwegian-Swedish mother-child birth cohort study. AJOG Global Reports. 1(1). doi: 10.1016/j.xagr.2020.100002. Fulltekst i vitenarkiv Vis sammendrag

  BACKGROUND Physical activity during pregnancy is important for maternal and offspring health. Optimal conditions during pregnancy may help reduce the burden of noncommunicable diseases. National and international guidelines recommend at least 150 minutes of physical activity of at least moderate intensity per week. To optimize physical activity in pregnant women, it is important to identify factors associated with higher levels of physical activity. OBJECTIVE This study aimed to explore types and levels of physical activity in midpregnancy in Norway and Sweden and to identify factors associated with higher levels of physical activity. MATERIALS AND METHODS From the population-based mother-child cohort Preventing Atopic Dermatitis and Allergies in Children study recruiting 2697 women in Norway and Sweden from 2014 to 2016, we included 2349 women who answered an electronic questionnaire at enrollment in midpregnancy. Women were asked about regular physical activity in the last 2 weeks of pregnancy and afterward for types and levels of physical activity in pregnancy and before pregnancy and socioeconomic status, lifestyle, and maternal health. Logistic regression analyses were used to identify factors associated with higher levels of physical activity in pregnancy, defined as >30 minutes per session of ≥2 times per week of moderate- or high-intensity brisk walking, strength training, jogging, and bicycling. RESULTS No regular physical activity during the last 2 weeks before answering the questionnaire at midpregnancy was reported by 689 women (29%). In this study, 1787 women (76%) reported weekly strolling during pregnancy. Regular physical activity at least twice weekly in the first half of pregnancy was reported as brisk walking by 839 women (36%), bicycling by 361 women (15%), strength training by 322 women (14%), and other activities by <10% of women. Among the 1430 women with regular moderate- or high-intensity physical activity, the estimated median duration per week was 120 minutes. Higher physical activity levels were achieved in 553 women (23.5%) by brisk walking, 287 women (12.2%) by strength training, 263 women (11.2%) by bicycling, and 114 women (4.9%) by jogging. Higher physical activity levels were positively associated with regular physical activity before pregnancy, dog ownership, and atopic dermatitis and negatively associated with higher body mass index, study location in Østfold, previous pregnancy or pregnancies, non-Nordic origin, suburban living, and sick leave. CONCLUSION At midpregnancy, 29% of women were inactive, and less than 50% of women had at least 2 hours of moderate-intensity physical activity weekly. Awareness of physical activity in pregnancy should be discussed at pregnancy follow-up visits, particularly among women with higher body mass index, sick leave, previous pregnancy or pregnancies, and non-Nordic origin.

• Kristiansen, Oddrun; Zucknick, Manuela; Reine, Trine M.; Kolset, Svein Olav; Jansson, Thomas & Powell, Theresa L. [Vis alle 9 forfattere av denne artikkelen] (2021). Mediators linking maternal weight to birthweight and neonatal fat mass in healthy pregnancies. Journal of Clinical Endocrinology and Metabolism (JCEM). ISSN 0021-972X. 106(7), s. 1977–1993. doi: 10.1210/clinem/dgab166. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Context Lifestyle interventions have not efficaciously reduced complications caused by maternal weight on fetal growth, requiring insight into explanatory mediators. Objective We hypothesized that maternal mediators, including adiponectin, leptin, insulin, and glucose, mediate effects of pregestational BMI (pBMI) and gestational weight gain (GWG) on birthweight and neonatal fat mass percentage (FM%) through placental weight and fetal mediators, including insulin levels (Ifv) and venous-arterial glucose difference (ΔGfva). Hypothesized confounders were maternal age, gestational age, and parity. Methods A cross-sectional study of healthy mother-offspring-pairs (n = 165) applying the 4-vessel in vivo sampling method at Oslo University Hospital, Norway. We obtained pBMI, GWG, birthweight, and placental weight. FM% was available and calculated for a subcohort (n = 84). We measured circulating levels of adiponectin, leptin, glucose, and insulin and performed path analysis and traditional mediation analyses based on linear regression models. Results The total effect of pBMI and GWG on newborn size was estimated to be 30 g (range, 16-45 g) birthweight and 0.17 FM% (range, 0.04-0.29 FM%) per kg∙m–2 pBMI and 31 g (range, 18-44 g) and 0.24 FM% (range, 0.10-0.37 FM%) per kg GWG. The placental weight was the main mediator, mediating 25-g birthweight and 0.11 FM% per kg∙m–2 pBMI and 25-g birthweight and 0.13 FM% per kg GWG. The maternal mediators mediated a smaller part of the effect of pBMI (3.8-g birthweight and 0.023 FM% per kg∙m–2 pBMI) but not GWG. Conclusion Placental weight was the main mediator linking pBMI and GWG to birthweight and FM%. The effect of pBMI, but not GWG, on birthweight and FM%, was also mediated via the maternal and fetal mediators.

• Oftedal, Aurora; Bekkhus, Mona; Haugen, Guttorm Nils; Braithwaite, Elizabeth; Bollerslev, Jens & Godang, Kristin [Vis alle 8 forfattere av denne artikkelen] (2021). Changes in maternal cortisol, cortisol binding globulin and cortisone levels following diagnosis of fetal anomaly. Psychoneuroendocrinology. ISSN 0306-4530. 135. doi: 10.1016/j.psyneuen.2021.105574. Fulltekst i vitenarkiv Vis sammendrag

  The diagnosis of fetal anomaly can be a major stressor to the expectant mother. Current understanding of the relationship between psychological stress and cortisol in pregnancy is limited. This study examined: (1) differences in the ratio of serum cortisol to cortisol binding globulin (SC/CBG) and cortisone levels among women with and without a diagnosis of fetal anomaly, (2) the association between self-reported stress and cortisol from mid to late pregnancy, and (3) the agreement between two different techniques for analyzing cortisol: liquid chromatography-tandem mass spectrometry (LC-MS/MS) and radioimmunoassay (RIA). Thirty-six pregnant women with a diagnosis of fetal anomaly (study group) and 101 women with healthy pregnancies (comparison group) provided blood samples and completed self-report questionnaires at gestational weeks 18–24 (T1) and 30 (T2). In the comparison group, mean SC/CBG increased from 0.341 nmol/L at T1 to 0.415 at T2 (p < .001), whereas in the study group there was no change (0.342 nmol/L at T1, 0.343 at T2). There was no difference in cortisone levels between the groups at either timepoints. There was a negative association between both depression and traumatic stress at T1, and SC/CBG at T2 (p < .05). There was no association between general distress and SC/CBG. The two methods for analyzing cortisol gave similar results, but with LC-MS/MS showing a lower detection limit than RIA. Increased cortisol with advancing gestational age is expected, thus these findings indicate that under certain conditions of severe stress there may be a suppression of maternal cortisol increase from mid to late gestation. The discrepancy does not seem to be due to differences in the metabolization of cortisol, as indicated by the similar levels of cortisone. Further research is needed in order to understand the potential underlying mechanisms limiting the expression of cortisol in response to certain types of stress in pregnancy.

• Endre, Kim Magnus Advocaat; Landrø, Linn Aina Ysland; LeBlanc, Marissa Erin; Gjersvik, Petter; Carlsen, Karin Cecilie Lødrup & Haugen, Guttorm Nils [Vis alle 15 forfattere av denne artikkelen] (2021). Eczema distribution in girls and boys during infancy: A cohort study on atopic dermatitis. Journal of Allergy and Clinical Immunology: In Practice. ISSN 2213-2198. 9(9), s. 3513–3516. doi: 10.1016/j.jaip.2021.04.053. Fulltekst i vitenarkiv
• Værnesbranden, Caren Magdalena Rydland; Wiik, Johanna; Sjøborg, Katrine Dønvold; Staff, Anne Cathrine; Carlsen, Karin Cecilie Lødrup & Haugen, Guttorm Nils [Vis alle 20 forfattere av denne artikkelen] (2021). Maternal human papillomavirus infections at mid-pregnancy and delivery in a Scandinavian mother–child cohort study. International Journal of Infectious Diseases. ISSN 1201-9712. 108, s. 574–581. doi: 10.1016/j.ijid.2021.05.064. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Human papillomavirus (HPV) infections are common, especially during women’s reproductive years, with unclear obstetrical impact. This study aimed to identify HPV prevalence at mid-gestation and delivery, type-specific persistence from mid-gestation to delivery, and risk factors for HPV infection and persistence. Methods In 757 women from a Scandinavian prospective mother–child cohort, HPV was analyzed in first-void urine samples at mid-gestation and delivery. We used Seegene Anyplex II HPV28 PCR assay for genotyping and semi-quantifying 28 genital HPV genotypes, including 12 high-risk HPVs (HR-HPV). Socio-demographic and health data were collected through e-questionnaires. Results Any-HPV genotype (any of 28 assessed) was detected in 38% of the study cohort at mid-gestation and 28% at delivery, and HR-HPVs in 24% and 16%, respectively. The most prevalent genotype was HPV16: 6% at mid-gestation and 4% at delivery. Persistence of Any-HPV genotype was 52%, as was HR-HPV genotype-specific persistence. A short pre-conception relationship with the child’s father and alcohol intake during pregnancy increased HPV infection risk at both time points. Low viral load at mid-gestation was associated with clearance of HPV infections at delivery. Conclusion HPV prevalence was higher at mid-gestation compared with delivery, and low viral load was associated with clearance of HPV at delivery.

• Hoyer, A.; Rehbinder, Eva Maria; Färdig, Martin; Asad, Samina; Carlsen, Karin Cecilie Lødrup & Endre, Kim Magnus Advocaat [Vis alle 22 forfattere av denne artikkelen] (2021). Filaggrin mutations in relation to skin barrier and atopic dermatitis in early infancy. British Journal of Dermatology. ISSN 0007-0963. s. 1–9. doi: 10.1111/bjd.20831. Fulltekst i vitenarkiv Vis sammendrag

  Background Loss-of-function mutations in the skin barrier gene filaggrin (FLG) increase the risk of atopic dermatitis (AD), but their role in skin barrier function, dry skin and eczema in infancy is unclear. Objectives To determine the role of FLG mutations in impaired skin barrier function, dry skin, eczema and AD at 3 months of age and throughout infancy. Methods FLG mutations were analysed in 1836 infants in the Scandinavian population-based PreventADALL study. Transepidermal water loss (TEWL), dry skin, eczema and AD were assessed at 3, 6 and 12 months of age. Results FLG mutations were observed in 166 (9%) infants. At 3 months, carrying FLG mutations was not associated with impaired skin barrier function (TEWL > 11·3 g m−2 h−1) or dry skin, but was associated with eczema [odds ratio (OR) 2·89, 95% confidence interval (CI) 1·95–4·28; P < 0·001]. At 6 months, mutation carriers had significantly higher TEWL than nonmutation carriers [mean 9·68 (95% CI 8·69–10·68) vs. 8·24 (95% CI 7·97–8·15), P < 0·01], and at 3 and 6 months mutation carriers had an increased risk of dry skin on the trunk (OR 1·87, 95% CI 1·25–2·80; P = 0·002 and OR 2·44, 95% CI 1·51–3·95; P < 0·001) or extensor limb surfaces (OR 1·52, 95% CI 1·04–2·22; P = 0·028 and OR 1·74, 95% CI 1·17–2·57; P = 0·005). FLG mutations were associated with eczema and AD in infancy. Conclusions FLG mutations were not associated with impaired skin barrier function or dry skin in general at 3 months of age, but increased the risk for eczema, and for dry skin on the trunk and extensor limb surfaces at 3 and 6 months.

• Hilde, Katarina; Carlsen, Karin Cecilie Lødrup; Bains, Karen Eline Stensby; Gudmundsdóttir, Hrefna Katrín; Jonassen, Christine M & Kreyberg, Ina [Vis alle 18 forfattere av denne artikkelen] (2021). Fetal Thoracic Circumference and Lung Volume and Their Relation to Fetal Size and Pulmonary Artery Blood Flow. Journal of ultrasound in medicine. ISSN 0278-4297. s. 1–9. doi: 10.1002/jum.15785. Fulltekst i vitenarkiv Vis sammendrag

  Objective: Research on early origins of lung disease suggests the need for studying the relationships of thoracic and lung size with fetal size and pulmonary circulation. The primary aim of this study is therefore to explore the associations between fetal thoracic circumference, lung volume, and fetal size. We also aim to assess if lung volume and thoracic circumference are associated with fetal pulmonary artery blood flow velocity measures. Methods: Cross-sectional assessment of singleton pregnancies from the general population (n = 447) at 30 gestational weeks (GW) was performed using ultrasound measurement of fetal thoracic circumference, lung volume, head and abdominal circumference, and femur length. We obtained Doppler blood flow velocity measures from the proximal branches of the fetal pulmonary artery. Associations between variables were studied using Pearson's correlation and multiple linear regression analyses. Results: Both thoracic circumference and lung volume correlated with fetal size measures, ranging from r = 0.64 between thoracic circumference and abdominal circumference, to r = 0.28 between lung volume and femur length. Adjustment for gestational age, maternal nicotine use, pre-pregnancy body mass index, and fetal sex marginally influenced the associations with abdominal circumference. The correlations of thoracic circumference and lung volume with pulmonary artery blood flow velocity measures were weak (r ≤ 0.17). Conclusion: We found moderate to low correlation between thoracic circumference, lung volume, and fetal size at 30 GW. The closest relationship was with the abdominal circumference. We found low correlations of thoracic circumference and lung volume with pulmonary artery blood flow velocity measures.

• Nilsen, Morten; Lokmic, Asima; Angell, Inga Leena; Carlsen, Karin C. Lødrup; Carlsen, Kai-Håkon & Haugen, Guttorm [Vis alle 18 forfattere av denne artikkelen] (2021). Fecal Microbiota Nutrient Utilization Potential Suggests Mucins as Drivers for Initial Gut Colonization of Mother-Child-Shared Bacteria. Applied and Environmental Microbiology. ISSN 0099-2240. 87(6). doi: 10.1128/AEM.02201-20. Fulltekst i vitenarkiv
• Magi, Caroline-Aleksi Olsson; Backlund, Anders Bjerg; Carlsen, Karin C. Lødrup; Almqvist, Catarina; Carlsen, Kai-Håkon & Granum, Berit [Vis alle 17 forfattere av denne artikkelen] (2020). Allergic disease and risk of stress in pregnant women: a PreventADALL study. European Respiratory Journal Open Research (ERJ Open Research). 6(4), s. 1–9. doi: 10.1183/23120541.00175-2020. Fulltekst i vitenarkiv Vis sammendrag

  Background Maternal stress during pregnancy may negatively affect the health of mother and child. We therefore aimed to identify the proportion of women reporting high maternal stress in mid and late pregnancy and explore whether symptoms of maternal allergic disease are associated with perceived maternal stress in late pregnancy. Method The population-based Preventing Atopic Dermatitis and Allergy in Children (PreventADALL) study enrolled 2697 pregnant women at their 18-week routine ultrasound examination in Norway and Sweden. Information about sociodemographic factors, symptoms and doctor-diagnosed asthma, allergic rhinitis, atopic dermatitis, food allergy, and anaphylaxis and stress using the 14-item perceived stress scale (PSS) was collected at 18 weeks (mid) and 34 weeks (late) pregnancy. High stress was defined as a PSS score ≥29. Scores were analysed using multivariate logistic and linear regression. Results Among the 2164 women with complete PSS data, 17% reported asthma, 20% atopic dermatitis, 23% allergic rhinitis, 12% food allergy and 2% anaphylaxis. The proportion of women reporting high stress decreased from 15% at mid to 13% at late pregnancy (p&lt;0.01). The adjusted odds ratio for high stress in late pregnancy was 2.25 (95% CI 1.41–3.58) for self-reported symptoms of asthma, 1.46 (95% CI 1.02–2.10) for allergic rhinitis and 2.25 (95% CI 1.32–3.82) for food allergy. A multivariate linear regression model confirmed that symptoms of asthma (β coefficient 2.11; 0.71–3.51), atopic dermatitis (β coefficient 1.76; 0.62–2.89) and food allergy (β coefficient 2.24; 0.63–3.84) were independently associated with increased PSS score. Conclusion Allergic disease symptoms in pregnancy were associated with increased stress, highlighting the importance of optimal disease control in pregnancy.

• Hilde, Katarina; Carlsen, Karin C. Lødrup & Haugen, Guttorm (2020). Doppler measures of blood flow in right and left branches of the fetal pulmonary artery. Journal of Maternal-Fetal & Neonatal Medicine. ISSN 1476-7058. s. 1–5. doi: 10.1080/14767058.2020.1807509. Fulltekst i vitenarkiv Vis sammendrag

  Objective To compare Doppler blood flow velocity measures in the right and left proximal branch of the fetal pulmonary artery at 30 gestational weeks. Methods Doppler blood flow velocity waveforms were recorded in both fetal proximal pulmonary artery branches in 62 healthy fetuses at 30 gestational weeks. Pulsatility index, peak systolic velocity, time averaged maximum velocity, time velocity integral, fetal heart rate, acceleration- and ejection time with their ratio, time of one heart cycle and time velocity integral were recorded. Paired-samples t-test was used to compare measures from the right and left pulmonary branch. Results We observed significantly higher peak systolic velocity, time averaged maximum velocity, time velocity integral, acceleration time and acceleration time/ejection time ratio in the right compared to the left pulmonary artery (p < .001). Sampling angle, pulsatility index, fetal heart rate, ejection time and time of one heart cycle were similar in both pulmonary branches. Conclusion Our study conducted at 30 weeks gestational age found significantly different blood flow velocity waveform measures in the right and left pulmonary artery branches in contrast to previous reports of similar velocities.

• Bekkhus, Mona; Oftedal, Aurora; Braithwaite, Elizabeth; Haugen, Guttorm & Kaasen, Anne (2020). Paternal psychological stress after detection of fetal anomaly during pregnancy. A prospective longitudinal observational study. Frontiers in Psychology. 11:1848, s. 1–13. doi: 10.3389/fpsyg.2020.01848. Fulltekst i vitenarkiv Vis sammendrag

  Background and Aims: Knowledge of carrying a fetus with a prenatal diagnosed anomaly may cause acute psychological stress to the parents. Most studies focus on maternal stress, yet fathers are often present at the ultrasound examinations and birth, and therefore may be affected, similarly, to the expectant mother. However, to date no existing studies have examined how detection of a fetal anomaly emotionally affects the expectant fathers throughout the pregnancy. Our aim was to longitudinally examine general health perceptions, social dysfunction and psychological distress in a subgroup of men where fetal anomaly was detected during pregnancy. Methods and Results: This study is part of the SOFUS study, a prospective, longitudinal, observational study. Participants were recruited when referred for an ultrasound examination conducted by a specialist in fetal medicine at Oslo University Hospital on suspicion of fetal malformation (study group). We examined differences between the men in the study group (N = 32) and a comparison group (N = 83) on the General Health Questionnaire (GHQ), Impact of Event Scale (IES) and Edinburgh Postnatal Depression Scale (EDPS) across four time points in pregnancy. Results from repeated measured ANOVA suggests that depression decreased over time among men in both groups (η2 = 0.15, p < 0.001). This effect was stronger in the study group, and differed from the comparison group (η2 = 0.08, p < 0.001). There was also a main effect of time on IES scores, which decreased over time for both men in the study group and in the comparison group (η2 = 0.32, p < 0.001). That is, men in the study group were higher on IES initially, but this effect decreased more in the study group than in the comparison group. Men in the study group and comparison group did not differ on perceived general health (GHQ: p = 0.864). Conclusion: Results suggests that detection of a fetal anomaly has implications for paternal mental health during pregnancy. Expectant fathers scored higher on EPDS and IES than the comparison group in the acute phase after detection of fetal anomaly, thus there is impetus to provide psychological support for fathers, as well as mothers, at this difficult time.

• Opheim, Gun Lisbeth; Holme, Ane Moe; Holm, Maia Blomhoff; Michelsen, Trond Melbye; Zahid, Saba Muneer & Roland, Marie Cecilie [Vis alle 8 forfattere av denne artikkelen] (2020). The impact of umbilical vein blood flow and glucose concentration on blood flow distribution to the fetal liver and systemic organs in healthy pregnancies. The FASEB Journal. ISSN 0892-6638. 34(9), s. 12481–12491. doi: 10.1096/fj.202000766R. Fulltekst i vitenarkiv Vis sammendrag

  Glucose is a major energy substrate for the fetus, including liver, heart, and brain metabolism. The umbilical vein (UV) blood flow supplies the fetal liver directly from the placenta, whereas a fraction is shunted via ductus venosus (DV) to the fetal systemic circulation bypassing the fetal liver. We hypothesized UV glucose concentration to be a major regulator of the distribution of glucose supply between the fetal liver and DV, and explored the influence of maternal metabolic status on this distribution. We included 124 healthy women with normal singleton pregnancies, scheduled for elective cesarean section. UV and DV blood flow measurements were performed by Doppler ultrasound immediately before, and blood samples were obtained during surgery. UV blood flow was significantly correlated with DV blood flow, liver blood flow, and the DV shunting fraction, while UV glucose concentration was not. For normal‐weight mothers, the maternal‐fetal glucose gradient was positively correlated with DV shunting fraction, and negatively with liver blood flow. For the fetuses of the overweight mothers no such correlation was found. This indicates that within the normal physiological range the human fetus makes adaptations of blood flow to ensure individual needs related to the offered maternal energy supply.

• Nilsen, Morten; Schinagl, Carina Madelen; Angell, Inga Leena; Arntzen, Magnus Øverlie; Carlsen, Karin C. Lødrup & Carlsen, Kai-Håkon [Vis alle 18 forfattere av denne artikkelen] (2020). Butyrate Levels in the Transition from an Infant-to an Adult-Like Gut Microbiota Correlate with Bacterial Networks Associated with Eubacterium Rectale and Ruminococcus Gnavus. Genes. 11(11). doi: 10.3390/genes11111245. Fulltekst i vitenarkiv Vis sammendrag

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

• Skjerven, Håvard Ove; Rehbinder, Eva Maria; Vettukattil, Muhammad Riyas; LeBlanc, Marissa Erin; Granum, Berit & Haugen, Guttorm [Vis alle 35 forfattere av denne artikkelen] (2020). Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial. The Lancet. ISSN 0140-6736. 395(10228), s. 951–961. doi: 10.1016/S0140-6736(19)32983-6. Fulltekst i vitenarkiv
• Gustavsen, Alice; Njerve, Ida Unhammer; Sitras, Vasilis; Haugen, Guttorm; Tølløfsrud, Per Arne & Akkøk, Cigdem Ahaein (2020). En ung kvinne med transfusjonsutlost svangerskapskomplikasjon. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 140(1), s. 1–6. doi: 10.4045/tidsskr.19.0117. Fulltekst i vitenarkiv
• Nordhagen, Live Solveig; Kreyberg, Ina; Bains, Karen Eline Stensby; Carlsen, Kai-Håkon; Glavin, Kari & Skjerven, Håvard Ove [Vis alle 19 forfattere av denne artikkelen] (2020). Maternal use of nicotine products and breastfeeding 3 months postpartum. Acta Paediatrica. ISSN 0803-5253. 109(12), s. 2594–2603. doi: 10.1111/apa.15299. Fulltekst i vitenarkiv Vis sammendrag

  Aim: We aimed to determine the prevalence of and factors associated with maternal use of nicotine products in relation to breastfeeding. Methods: Nicotine use 3 months postpartum was determined in the Scandinavian PreventADALL mother-child birth cohort study recruiting 1837 women from 2014 to 2016. Electronic questionnaires at 18 weeks pregnancy and 3 months postpartum provided information on snus use, smoking or other nicotine use, infant feeding and socio-economic factors. The risk of nicotine use in relation to breastfeeding was analysed with logistic regression. Results: Overall, 5.6% of women used snus (2.9%), smoked (2.7%) or both (n = 2) 3 months postpartum, while one used other nicotine products. Among the 1717 breastfeeding women, 95.1% reported no nicotine use, while 2.4% used snus, 2.5% smoked and one dual user. Compared to 3.7% nicotine use in exclusively breastfeeding women (n = 1242), the risk of nicotine use increased by partly (OR 2.26, 95% CI 1.45- 3.52) and no breastfeeding (OR 4.58, 95% CI 2.57-8.21). Nicotine use before (14.5% snus, 16.4% smoking) or in pregnancy (0.2% snus, 0.4% smoking) significantly increased the risk of using nicotine during breastfeeding. Conclusion: Few breastfeeding women used snus or smoked 3 months postpartum, with increased risk by nicotine use before or during pregnancy.

• Opheim, Gun Lisbeth; Henriksen, Tore & Haugen, Guttorm (2019). The effect of a maternal meal on fetal liver blood flow. PLOS ONE. 14(6), s. 1–13. doi: 10.1371/journal.pone.0216176. Fulltekst i vitenarkiv Vis sammendrag

  Introduction During the third trimester of development, the human fetus accumulates fat, an important energy reservoir during the early postnatal period. The fetal liver, perfused by the nutrient-rich and well-oxygenated blood coming directly from the placenta, is assumed to play a central role in these processes. Earlier studies have linked fetal liver blood flow with maternal nutritional status and response to the maternal oral glucose tolerance test. Our aim was to explore the effect of a regular maternal meal on fetal liver blood flow at two timepoints during the third trimester, representing the start and towards the end of the fetal fat accretion period. We also sought to explore the influence of prepregancy body mass index on how the maternal meal affects fetal liver blood flow. Methods Using ultrasound Doppler, we examined 108 healthy women with singleton pregnancies in gestational weeks 30 and 36. At each visit, the first examination was performed with the participant in a fasting state at 08.30 a.m., followed by a standard breakfast meal of approximately 400 kcal. The examination was repeated after 105 minutes. Umbilical vein and ductus venosus blood flow was estimated from diameter and blood flow velocity measurements. Fetal liver flow was calculated as umbilical vein flow minus ductus venosus flow, and change in liver blood flow as flow after minus before the meal. The total group was divided into a normal-weight group (prepregancy body mass index 18.5–25.0 kg/m2; n = 83) and an overweight group (prepregancy body mass index >25.0 kg/m2; n = 21). Four women with prepregancy body mass index <18.5 kg/m2 were excluded from these analyses. Non-parametric statistical hypothesis tests were used for group comparisons. Results For the total group, we observed a significant increase in median (10th - 90th percentile) liver flow 28.9 (‒67.9–111.6) ml/min (p = 0.002) following the meal in week 36, but not in week 30, ‒2.63 (‒53.2–65.0) ml/min (p = 0.91). This result in turn yielded a statistically significant increase in delta liver flow from weeks 30 to 36 of 26.0 (‒107.1–146.6) ml/min (p = 0.008). The increase in postprandial liver flow was observed only in the normal-weight group in week 36. Accordingly, the delta liver flow values between the two weight groups were significantly different in week 36 (p = 0.006) but not in week 30 (p = 0.155). Among the normal-weight women, the increase in delta liver blood flow from weeks 30 to 36 was 39.3 (‒83.0–156.1) ml/min (p<0.001); in contrast, we observed no statistically significant change in the overweight group (‒44.5 (‒229.0–123.2) ml/min; p = 0.073). As a substitute for liver size, we divided the delta liver flow values by abdominal circumference and found no changes in the statistical significance results within or between the two weight groups. Conclusion In our healthy study population, we observed a statistically significant difference in liver blood flow after maternal intake of a regular meal. This effect depended on gestational age and maternal prepregancy body mass index, but apparently was independent of liver size, based on abdominal circumference as a proxy measure.

• Rehbinder, Eva Maria; Endre, Kim Magnus Advocaat; Carlsen, Karin C. Lødrup; Asarnoj, Anna; Bains, Karen Eline Stensby & Berents, Teresa Løvold [Vis alle 21 forfattere av denne artikkelen] (2019). Predicting skin barrier dysfunction and atopic dermatitis in early infancy. Journal of Allergy and Clinical Immunology: In Practice. ISSN 2213-2198. s. 1–15. doi: 10.1016/j.jaip.2019.09.014. Fulltekst i vitenarkiv Vis sammendrag

  Dry skin is associated with increased transepidermal water loss (TEWL), which has been found to precede atopic dermatitis (AD) in childhood. Objective We aimed to identify parental, prenatal, and perinatal predictive factors of dry skin, high TEWL, and AD at 3 months of age, and to determine if dry skin or high TEWL at 3 months can predict AD at 6 months. Methods From the Preventing Atopic Dermatitis and Allergies in children prospective birth cohort study, we included 1150 mother-child pairs. Dry skin, TEWL, and eczema were assessed at 3- and 6-month investigations. Eczema, used as a proxy for AD, was defined as the presence of eczematous lesions, excluding differential diagnoses to AD. High TEWL was defined as TEWL >90th percentile, equaling 11.3 g/m2/h. Potential predictive factors were recorded from electronic questionnaires at 18- and 34-week pregnancy and obstetric charts. Results Significant predictive factors (P < .05) for dry skin at 3 months were delivery >38 gestational weeks and paternal age >37 years; for high TEWL, male sex, birth during winter season, and maternal allergic disease; and for eczema, elective caesarean section, multiparity, and maternal allergic diseases. Dry skin without eczema at 3 months was predictive for eczema at 6 months (adjusted odds ratio: 1.92, 95% confidence interval: 1.21-3.05; P = .005), whereas high TEWL at 3 months was not. Conclusion In early infancy, distinct parental- and pregnancy-related factors were predictive for dry skin, high TEWL, and AD. Dry skin at 3 months of age was predictive for AD 3 months later.

• Michelsen, Trond Melbye; Holme, Ane Moe; Holm, Maia Blomhoff; Roland, Marie Cecilie; Haugen, Guttorm & Powell, Theresa L. [Vis alle 8 forfattere av denne artikkelen] (2019). Uteroplacental glucose uptake and fetal glucose consumption: A quantitative study in human pregnancies. Journal of Clinical Endocrinology and Metabolism (JCEM). ISSN 0021-972X. 104(3), s. 873–882. doi: 10.1210/jc.2018-01154. Fulltekst i vitenarkiv Vis sammendrag

  Context Maternal glucose levels and body mass index (BMI) are determinants of fetal overgrowth, but their relation to fetal glucose consumption is not well characterized in human pregnancy. Objectives To quantify uteroplacental glucose uptake and the allocation of glucose between the placenta and fetus and to identify factors that affect fetal glucose consumption. Design Human in vivo study in term pregnancies. Setting Oslo University Hospital, Norway. Participants One hundred seventy-nine healthy women with elective cesarean section. Interventions Uterine and umbilical blood flow was determined using Doppler ultrasonography. Glucose and insulin were measured in the maternal radial artery and uterine vein and the umbilical artery and vein. In a subcohort (n = 33), GLUT1 expression was determined in isolated syncytiotrophoblast basal and microvillous plasma membranes. Main Outcome Measures Uteroplacental glucose uptake and placental and fetal glucose consumption quantified by the Fick principle. Results Median (Q1, Q3) uteroplacental glucose uptake was 117.1 (59.1, 224.9) μmol⋅min−1, and fetal and placental glucose consumptions were 28.9 (15.4, 41.8) µmol⋅min−1⋅kg fetus−1 and 51.4 (−65.8, 185.4) µmol⋅min−1⋅kg placenta−1, respectively. Fetal glucose consumption correlated with birth weight (ρ: 0.34; P < 0.001) and maternal–fetal glucose gradient (ρ: 0.60; P < 0.001), but not with maternal BMI or uteroplacental glucose uptake. Uteroplacental glucose uptake was correlated to placental glucose consumption (ρ: 0.77; P < 0.001). Fetal and placental glucose consumptions were inversely correlated (ρ: −0.47; P < 0.001), but neither was correlated with placental GLUT1 expression. Conclusion These findings suggest that fetal glucose consumption is balanced against the placental needs for glucose and that placental glucose consumption is a key modulator of maternal–fetal glucose transfer in women.

• Horne, Hildegunn; Holme, Ane Moe; Roland, Marie Cecilie; Holm, Maia Blomhoff; Haugen, Guttorm & Henriksen, Tore [Vis alle 7 forfattere av denne artikkelen] (2019). Maternal-fetal cholesterol transfer in human term pregnancies. Placenta. ISSN 0143-4004. 87, s. 23–29. doi: 10.1016/j.placenta.2019.09.001. Fulltekst i vitenarkiv
• Schinagl, Carina Madelen; Rehbinder, Eva Maria; Carlsen, Karin C. Lødrup; Gudbrandsgard, Malén; Carlsen, Kai-Håkon & Haugen, Guttorm [Vis alle 17 forfattere av denne artikkelen] (2019). Food and nutrient intake and adherence to dietary recommendations during pregnancy: A nordic mother?child population-based cohort. Food & Nutrition Research (FNR). ISSN 1654-6628. 63:3676, s. 1–11. doi: 10.29219/fnr.v63.3676. Fulltekst i vitenarkiv Vis sammendrag

  Background: A woman’s food intake during pregnancy has important implications not only for herself but also for the future health and well-being of her child. Suboptimal dietary quality has been consistently reported in many high-income countries, reflecting poor adherence to dietary guidelines. Objective: This study aimed to explore the intake of food and nutrients in a cohort of pregnant women in Norway and their adherence to Nordic Nutrition Recommendations (NNR) and Norwegian food-based guidelines (NFG). Design: We investigated the dietary intake in 1,674 pregnant women from the mother–child birth cohort, PreventADALL, recruited at approximately 18-week gestational age. Dietary intake was assessed by an electronic validated food frequency questionnaire (PrevFFQ) in the first half of pregnancy. Results: Total fat intake was within the recommended intake (RI) range in most women; however, the contribution of saturated fatty acids to the total energy intake was above RI in the majority (85.2%) of women. Carbohydrate intake was below RI in 43.9% of the women, and 69.5% exceeded the RI of salt. Intakes of fiber, vegetables, and fish were high in a large part of the population. Many women had a high probability of inadequate intakes of the following key micronutrients during pregnancy: folate (54.4%), iron (49.6%), calcium (36.2%), vitamin D (28.7%), iodine (24.4%), and selenium (41.3%). A total of 22.8% women reported an alcohol intake of >1 g/day, and 4.4% reported an alcohol intake of >10 g/day. Women with higher educational levels showed a tendency towards healthier eating habits, except for higher intakes of alcohol and coffee, compared to women with lower educational level. Discussion: Excessive saturated fat intake and limited intake of many important micronutrients during pregnancy were common, potentially increasing the risk for adverse pregnancy and birth outcomes. Conclusions: This study highlights the need for improved nutritional guidance to pregnant women across all educational levels.

• Kreyberg, Ina; Bains, Karen Eline Stensby; Carlsen, Kai-Håkon; Granum, Berit; Gudmundsdóttir, Hrefna Katrín & Haugen, Guttorm [Vis alle 17 forfattere av denne artikkelen] (2019). Stopping when knowing: use of snus and nicotine during pregnancy in Scandinavia. European Respiratory Journal Open Research (ERJ Open Research). 5(2). doi: 10.1183/23120541.00197-2018. Fulltekst i vitenarkiv Vis sammendrag

  In young women, the use of snus increases in parallel with decreasing smoking rates but the use in pregnancy is unclear. Our aims were to determine the prevalence of snus use, smoking and other nicotine-containing product use during pregnancy, and to identify predictors for snus use in pregnancy. Prevalence was determined for 2528 women in Norway and Sweden based on the Preventing Atopic Dermatitis and ALLergies (PreventADALL) study, a population-based, mother–child birth cohort. Electronic questionnaires were completed in pregnancy week 18 and/or week 34, and potential predictors of snus use were analysed using logistic regression models. Ever use of any snus, tobacco or nicotine-containing products was reported by 35.7% of women, with similar rates of snus use (22.5%) and smoking (22.6%). Overall, 11.3% of women reported any use of nicotine-containing products in pregnancy up to 34 weeks, most often snus alone (6.5%). Most women (87.2%) stopped using snus by week 6 of pregnancy. Snus use in pregnancy was inversely associated with age and positively associated with urban living and personal or maternal history of smoking. While 11.3% of women used snus or other nicotine-containing products at some time, most stopped when recognising their pregnancy. Younger, urban living, previously smoking women were more likely to use snus in pregnancy.

• Kreyberg, Ina; Bains, Karen Eline Stensby; Carlsen, Kai-Håkon; Granum, Berit; Hilde, Katarina & Gudmundsdóttir, Hrefna Katrín [Vis alle 19 forfattere av denne artikkelen] (2019). Snus in pregnancy and infant birth size: A mother–child birth cohort study. European Respiratory Journal Open Research (ERJ Open Research). 5(4), s. 1–10. doi: 10.1183/23120541.00255-2019. Fulltekst i vitenarkiv Vis sammendrag

  Rationale: While recent studies show that maternal use of snus during pregnancy is increasing, the potential effects on infant birth size is less investigated, with conflicting results. Objectives: We aimed to determine if maternal use of snus during pregnancy influences the infant anthropometric and proportional size measures at birth. Methods: In 2313 mother–child pairs from the population-based, mother–child birth cohort PreventADALL (Preventing Atopic Dermatitis and ALLergies) in Norway and Sweden, we assessed nicotine exposure by electronic questionnaire(s) at 18 and 34 weeks of pregnancy, and anthropometric measurements at birth. Associations between snus exposure and birth size outcomes were analysed by general linear regression. Results: Birthweight was not significantly different in infants exposed to snus in general, and up to 18 weeks of pregnancy in particular, when adjusting for relevant confounders including maternal age, gestational age at birth, pre-pregnancy body mass index, parity, fetal sex and maternal gestational weight gain up to 18 weeks. We found no significant effect of snus use on the other anthropometric or proportional size measures in multivariable linear regression models. Most women stopped snus use in early pregnancy. Conclusion: Exposure to snus use in early pregnancy, with most women stopping when knowing about their pregnancy, was not associated with birth size. We were unable to conclude on effects of continued snus use during pregnancy because of lack of exposure in our cohort.

• Opheim, Gun Lisbeth; Zucknick, Manuela; Henriksen, Tore & Haugen, Guttorm (2018). A maternal meal affects clinical Doppler parameters in the fetal middle cerebral artery. PLOS ONE. 13(12). doi: 10.1371/journal.pone.0209990. Fulltekst i vitenarkiv Vis sammendrag

  Introduction Middle cerebral artery (MCA) and umbilical artery (UA) Doppler blood flow pulsatility indices (PIs) and MCA peak systolic velocity (PSV) are essential variables for clinically evaluating fetal well-being. Here we examined how a maternal meal influenced these Doppler blood flow velocity variables. Methods This prospective cohort study included 89 healthy Caucasian women with normal singleton pregnancies (median age, 32 years). Measurements were performed at gestational weeks 30 and 36, representing the start and near the end of the energy-depositing period. Measured variables included the MCA-PI, UA-PI, fetal heart rate (FHR) and MCA-PSV. The cerebroplacental ratio (CPR) was calculated as the ratio of MCA-PI to UA-PI. The first examination was performed in the fasting state at 08:30 a.m. Then participants ate a standard breakfast (approximate caloric intake, 400kcal), and the examination was repeated ~105 min after the meal. Results Without adjustment for FHR, fetal MCA-PI decreased after the meal at week 30 (‒0.115; p = 0.012) and week 36 (‒0.255; p < 0.001). All PI values were negatively correlated with FHR. After adjustment for FHR, MCA-PI still decreased after the meal at week 30 (‒0.087; p = 0.044) and week 36 (‒0.194; p < 0.001). The difference between the two gestational weeks was non-significant (p = 0.075). UA-PI values did not significantly change at week 30 (p = 0.253) or week 36 (p = 0.920). CPR revealed significant postprandial decreases of −0.17 at week 30 (p = 0.006) and −0.22 at week 36 (p = 0.001). Compared to fasting values, MCA-PSV was significantly higher after food intake: +3.9 cm/s at week 30 (p < 0.001) and +5.9 cm/s at week 36 (p < 0.001). Conclusion In gestational weeks 30 and 36, we observed a postprandial influence that was apparently specific to fetal cerebral blood flow.

• Holm, Maia Blomhoff; Kristiansen, Oddrun; Holme, Ane Moe; Bastani, Nasser Ezzatkhah; Horne, Hildegunn & Blomhoff, Rune [Vis alle 9 forfattere av denne artikkelen] (2018). Placental release of taurine to both the maternal and fetal circulations in human term pregnancies. Amino Acids. ISSN 0939-4451. 50(9), s. 1205–1214. doi: 10.1007/s00726-018-2576-9. Fulltekst i vitenarkiv Vis sammendrag

  Taurine is regarded as an essential amino acid in utero, and fetal taurine supply is believed to rely solely on placental transfer from maternal plasma. Despite its potential role in intrauterine growth restriction and other developmental disturbances, human in vivo studies of taurine transfer between the maternal, placental, and fetal compartments are scarce. We studied placental transfer of taurine in uncomplicated human term pregnancies in vivo in a cross-sectional study of 179 mother-fetus pairs. During cesarean section, we obtained placental tissue and plasma from incoming and outgoing vessels on the maternal and fetal sides of the placenta. Taurine was measured by liquid chromatography–tandem mass spectrometry. We calculated paired arteriovenous differences, and measured placental expression of the taurine biosynthetic enzyme cysteine sulfinic acid decarboxylase (CSAD) with quantitative real-time polymerase chain reaction and western blot. We observed a fetal uptake (p < 0.001), an uteroplacental release (p < 0.001), and a negative placental consumption of taurine (p = 0.001), demonstrating a bilateral placental release to the maternal and fetal compartments. Increasing umbilical vein concentrations and fetal uptake was associated with the uteroplacental release to the maternal circulation (rs = − 0.19, p = 0.01/rs = − 0.24, p = 0.003), but not with taurine concentrations in placental tissue. CSAD-mRNA was expressed in placental tissue, suggesting a potential for placental taurine synthesis. Our observations show that the placenta has the capacity to a bilateral taurine release, indicating a fundamental role of taurine in the human placental homeostasis beyond the supply to the fetus.

• Magelssen, Morten; Solberg, Berge; Supphellen, Magne & Haugen, Guttorm (2018). Attitudes to prenatal screening among Norwegian citizens: liberality, ambivalence and sensitivity. BMC Medical Ethics. 19(80), s. 1–8. doi: 10.1186/s12910-018-0319-9. Fulltekst i vitenarkiv Vis sammendrag

  Background Norway’s liberal abortion law allows for abortion on social indications, yet access to screening for fetal abnormalities is restricted. Norwegian regulation of, and public discourse about prenatal screening and diagnosis has been exceptional. In this study, we wanted to investigate whether the exceptional regulation is mirrored in public attitudes. Method An electronic questionnaire with 11 propositions about prenatal screening and diagnosis was completed by 1617 Norwegian adults (response rate 8.5%). Results A majority of respondents supports increased access to prenatal screening with ultrasound (60%) and/or full genome sequencing of fetal DNA (55%) available for all pregnant women. Significant minorities indicate, however, that a public offer of prenatal screening for all pregnant women would signal that people with Down syndrome are unwanted (46%) or could be criticized for contributing to a ‘sorting society’ (48%). Conclusions Results indicate deeper ambivalences and a cultural sensitivity to the ethical challenges of prenatal screening and subsequent abortions. The specific diagnosis of Down syndrome and the fear of becoming a ‘sorting society’ which sorts human life due to diagnoses, appear to play prominent roles in citizen deliberations. The low response rate means that a non-response bias cannot be excluded, yet reasons why results are still likely to be of value are discussed.

• Findal, Gry; Helbig, Anne; Haugen, Guttorm; Jenum, Pål & Stray-Pedersen, Babill (2017). Management of suspected primary Toxoplasma gondii infection in pregnant women in Norway: Twenty years of experience of amniocentesis in a low-prevalence population. BMC Pregnancy and Childbirth. 17:127(1), s. 1–9. doi: 10.1186/s12884-017-1300-1. Fulltekst i vitenarkiv Vis sammendrag

  Background Primary infection with Toxoplasma gondii during pregnancy may pose a threat to the fetus. Women infected prior to conception are unlikely to transmit the parasite to the fetus. If maternal serology indicates a possible primary infection, amniocentesis for toxoplasma PCR analysis is performed and antiparasitic treatment given. However, discriminating between primary and latent infection is challenging and unnecessary amniocenteses may occur. Procedure-related fetal loss after amniocentesis is of concern. The aim of the present study was to determine whether amniocentesis is performed on the correct patients and whether the procedure is safe for this indication. Methods Retrospective study analysing data from all singleton pregnancies (n = 346) at Oslo University Hospital undergoing amniocentesis due to suspected maternal primary toxoplasma infection during 1993–2013. Maternal, neonatal and infant data were obtained from clinical hospital records, laboratory records and pregnancy charts. All serum samples were analysed at the Norwegian Institute of Public Health or at the Toxoplasma Reference Laboratory at Oslo University Hospital. The amniocenteses were performed at Oslo University Hospital by experienced personnel. Time of maternal infection was evaluated retrospectively based on serology results. Results 50% (173) of the women were infected before pregnancy, 23% (80) possibly in pregnancy and 27% (93) were certainly infected during pregnancy. Forty-nine (14%) women seroconverted, 42 (12%) had IgG antibody increase and 255 (74%) women had IgM positivity and low IgG avidity/high dye test titre. Fifteen offspring were infected with toxoplasma, one of them with negative PCR in the amniotic fluid. Median gestational age at amniocentesis was 16.7 gestational weeks (GWs) (Q1 = 15, Q3 = 22), with median sample volume 4 ml (Q1 = 3, Q3 = 7). Two miscarriages occurred 4 weeks after the procedure, both performed in GW 13. One of these had severe fetal toxoplasma infection. Conclusions Half of our study population were infected before pregnancy. In order to reduce the unnecessary amniocenteses we advise confirmatory serology 3 weeks after a suspect result and suggest that the serology is interpreted by dedicated multidisciplinary staff. Amniocentesis is safe and useful as a diagnostic procedure in diagnosing congenital toxoplasma infection when performed after 15 GW.

• Kaasen, Anne; Helbig, Anne; Malt, Ulrik Fredrik; Næs, Tormod; Skari, Hans & Haugen, Guttorm (2017). Maternal psychological responses during pregnancy after ultrasonographic detection of structural fetal anomalies: A prospective longitudinal observational study. PLOS ONE. 12(3). doi: 10.1371/journal.pone.0174412. Fulltekst i vitenarkiv Vis sammendrag

  In this longitudinal prospective observational study performed at a tertiary perinatal referral centre, we aimed to assess maternal distress in pregnancy in women with ultrasound findings of fetal anomaly and compare this with distress in pregnant women with normal ultrasound findings. Pregnant women with a structural fetal anomaly (n = 48) and normal ultrasound (n = 105) were included. We administered self-report questionnaires (General Health Questionnaire-28, Impact of Event Scale-22 [IES], and Edinburgh Postnatal Depression Scale) a few days following ultrasound detection of a fetal anomaly or a normal ultrasound (T1), 3 weeks post-ultrasound (T2), and at 30 (T3) and 36 weeks gestation (T4). Social dysfunction, health perception, and psychological distress (intrusion, avoidance, arousal, anxiety, and depression) were the main outcome measures. The median gestational age at T1 was 20 and 19 weeks in the group with and without fetal anomaly, respectively. In the fetal anomaly group, all psychological distress scores were highest at T1. In the group with a normal scan, distress scores were stable throughout pregnancy. At all assessments, the fetal anomaly group scored significantly higher (especially on depression-related questions) compared to the normal scan group, except on the IES Intrusion and Arousal subscales at T4, although with large individual differences. In conclusion, women with a known fetal anomaly initially had high stress scores, which gradually decreased, resembling those in women with a normal pregnancy. Psychological stress levels were stable and low during the latter half of gestation in women with a normal pregnancy.

• Holme, Ane Moe; Holm, Maia Blomhoff; Roland, Marie Cecilie; Horne, Hildegunn; Michelsen, Trond Melbye & Haugen, Guttorm [Vis alle 7 forfattere av denne artikkelen] (2017). The 4-vessel sampling approach to integrative studies of human placental physiology in vivo. Journal of Visualized Experiments. 2017(126). doi: 10.3791/55847. Fulltekst i vitenarkiv Vis sammendrag

  The human placenta is highly inaccessible for research while still in utero. The current understanding of human placental physiology in vivo is therefore largely based on animal studies, despite the high diversity among species in placental anatomy, hemodynamics and duration of the pregnancy. The vast majority of human placenta studies are ex vivo perfusion studies or in vitro trophoblast studies. Although in vitro studies and animal models are essential, extrapolation of the results from such studies to the human placenta in vivo is uncertain. We aimed to study human placenta physiology in vivo at term, and present a detailed protocol of the method. Exploiting the intraabdominal access to the uterine vein just before the uterine incision during planned cesarean section, we collect blood samples from the incoming and outgoing vessels on the maternal and fetal sides of the placenta. When combining concentration measurements from blood samples with volume blood flow measurements, we are able to quantify placental and fetal uptake and release of any compound. Furthermore, placental tissue samples from the same mother-fetus pairs can provide measurements of transporter density and activity and other aspects of placental functions in vivo. Through this integrative use of the 4-vessel sampling method we are able to test some of the current concepts of placental nutrient transfer and metabolism in vivo, both in normal and pathological pregnancies. Furthermore, this method enables the identification of substances secreted by the placenta to the maternal circulation, which could be an important contribution to the search for biomarkers of placenta dysfunction.

• Haugen, Guttorm; Bollerslev, Jens & Henriksen, Tore (2016). Human umbilical and fetal cerebral blood flow velocity waveforms following maternal glucose loading: A cross-sectional observational study. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 95(6), s. 683–689. doi: 10.1111/aogs.12913. Fulltekst i vitenarkiv
• Fredheim, Olav Magnus; Hansen, Thor Willy Ruud; Haugen, Guttorm & Magelssen, Morten (2016). Bør man kunne tilby keisersnitt ved trisomi 13 og 18? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 136(7), s. 630–632. doi: 10.4045/tidsskr.15.0037. Fulltekst i vitenarkiv
• Haugen, Guttorm; Novakovic, Zarko; Kirste, Unni M; Husby, Henrik & Dorenberg, Eric Jürgen (2015). Uterine artery Doppler flow velocity waveform analysis following uterine fibroid embolisation. Journal of Obstetrics and Gynaecology. ISSN 0144-3615. 35(3), s. 316–317. doi: 10.3109/01443615.2014.940298. Fulltekst i vitenarkiv
• Helbig, Anne; Kaasen, Anne; Malt, Ulrik Fredrik & Haugen, Guttorm (2014). Maternal psychological distress and placental circulation in pregnancies after a previous offspring with congenital malformation. PLOS ONE. 9(1). doi: 10.1371/journal.pone.0086597. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Antenatal maternal psychological distress may be associated with reduced placental circulation, which could lead to lower birthweight. Studies investigating this in humans show mixed results, which may be partially due to type, strength and timing of distress. In addition, the arterial vascular resistance measures often used as outcome measures do not detect smaller changes in placental volume blood flow. We aimed to investigate the effect of a specific stressor, with increased levels of stress early in pregnancy, on the fetoplacental volume blood flow in third trimester. Methods: This was a prospective observational study of 74 pregnant women with a congenital malformation in a previous fetus or child. Psychological distress was assessed twice, around 16 and 30 weeks’ gestation. Psychometric measures were the General Health Questionnaire-28 (subscales anxiety and depression), Edinburgh Postnatal Depression Scale, and Impact of Event Scale-22 (subscales intrusion, avoidance, and arousal). Placental circulation was examined at 30 weeks, using Doppler ultrasonography, primarily as fetoplacental volume blood flow in the umbilical vein, normalized for abdominal circumference; secondarily as vascular resistance measures, obtained from the umbilical and the uterine arteries. Results: Maternal distress in second but not third trimester was associated with increased normalized fetoplacental blood flow (P-values 0.006 and 0.013 for score . mean for depression and intrusion, respectively). Post-hoc explorations suggested that a reduced birthweight/placental weight ratio may mediate this association. Psychological distress did not affect vascular resistance measures in the umbilical and uterine arteries, regardless of adjustment for confounders. Conclusions: In pregnant women with a previous fetus or child with a congenital malformation, higher distress levels in second trimester were associated with third trimester fetoplacental blood flow that was higher than expected for the size of the fetus. The results do not support placental blood flow reduction as a pathway between maternal distress and reduced birthweight.

• Paasche, Marie Cecilie; Friis, Camilla Margrethe; Godang, Kristin; Bollerslev, Jens; Haugen, Guttorm & Henriksen, Tore (2014). Maternal factors associated with fetal growth and birthweight are independent determinants of placental weight and exhibit differential effects by fetal sex. PLOS ONE. 9(2). doi: 10.1371/journal.pone.0087303. Fulltekst i vitenarkiv
• Haugen, Guttorm; Bollerslev, Jens & Henriksen, Tore (2014). Human fetoplacental and fetal liver blood flow after maternal glucose loading: A cross-sectional observational study. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 93(8), s. 778–785. doi: 10.1111/aogs.12419. Fulltekst i vitenarkiv
• Helbig, Anne; Kaasen, Anne; Malt, Ulrik Fredrik & Haugen, Guttorm (2013). Does Antenatal Maternal Psychological Distress Affect Placental Circulation in the Third Trimester? PLOS ONE. 8(2). doi: 10.1371/journal.pone.0057071. Fulltekst i vitenarkiv

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• Nestaas, Eirik; BJARKØ, LISA; Kiserud, Torvid; Haugen, Guttorm Nils & Fugelseth, Drude (2024). Corrigendum to “Heart function by M-mode and tissue Doppler in the early neonatal period in neonates with fetal growth restriction”, [Early Hum. Dev. 183 (2023) 105809] (Early Human Development (2023) 183, (S0378378223001056), (10.1016/j.earlhumdev.2023.105809)). Early Human Development. ISSN 0378-3782. doi: 10.1016/j.earlhumdev.2024.106032. Fulltekst i vitenarkiv
• BJARKØ, LISA; Fugelseth, Drude; Harsem, Nina Kittelsen; Kiserud, Torvid; Haugen, Guttorm Nils & Nestaas, Eirik (2024). Correction to: Cardiac morphology in neonates with fetal growth restriction (Journal of Perinatology, (2023), 43, 2, (187-195), 10.1038/s41372-022-01538-8). Journal of Perinatology. ISSN 0743-8346. doi: 10.1038/s41372-024-02104-0. Fulltekst i vitenarkiv
• Bonnichsen, Maja Lecic; Nyfløt, Lill Trine; Haugen, Guttorm Nils & Roland, Marie Cecilie (2023). SEVERE MATERNAL OBESITY AND ACTIVE LABOUR. Fulltekst i vitenarkiv Vis sammendrag

  Introduction/Purpose Maternal obesity is associated with prolonged duration of labour and arrested labour along with extended list of adverse outcomes for mother and child. To study expulsion time (ET) in induced and non-induced, nulliparous and parous parturients with severe pre-pregnant obesity (pBMI≥35). Methods "Healthy mother-lifelong health for mother and child" was a prospective, longitudinal, observational study, conducted at Drammen Hospital between 2016 and 2019, including 166 pregnant women with pBMI≥35. We collected detailed data on labour induction, duration of active labour (AL, from 4 cm dilatation and contractions) including ET, and mode of delivery. We compared groups by median regression, adjusting for parity. Results Among the 125 women (75%) with vaginal birth, 90 women (72%) were induced and 8 women (6%) were delivered by vacuum. 54% of induced women and 63% of non-induced were parous. Median duration of AL was 3 hrs. (P0; 4 hrs. vs. P≥1; 2 hrs. p=0.091) in non-induced labours and 3.5 hrs. (P0; 5 hrs. vs. P≥1; 2 hrs. p=0.008) in induced labours, while ET was 19.5 min (P0; 29min vs. P≥1; 11min, p=0.006) and 17 min (P0; 25.5min vs. P≥1; 8, p=0.001) respectively. Neither duration of active labour (p=0.540) or expulsion time (p=0.583) was significantly different in the two labour groups. Conclusions Despite the majority of labours being induced, we found that 75% delivered vaginally with short median duration of active labour and expulsion time. We found no significant differences in active labour or expulsion time when comparing non-induced and induced labours.

• Oftedal, Aurora; Bekkhus, Mona; Haugen, Guttorm Nils & Kaasen, Anne (2022). The development of parental traumatic stress following the detection of fetal anomaly. Fulltekst i vitenarkiv
• Oftedal, Aurora; Bekkhus, Mona; Haugen, Guttorm Nils & Kaasen, Anne (2022). The impact of diagnosed fetal anomaly, diagnostic severity, and prognostic ambiguity on parental depression and traumatic stress. Fulltekst i vitenarkiv
• Oftedal, Aurora; Bekkhus, Mona; Haugen, Guttorm Nils & Kaasen, Anne (2021). The relation of traumatic stress to cortisol following the detection of fetal anomaly. Fulltekst i vitenarkiv
• Oftedal, Aurora; Bekkhus, Mona; Haugen, Guttorm Nils & Kaasen, Anne (2021). Utvikling av symptomer på depresjon og posttraumatisk stress etter påvist fosteravvik ved ultralyd. Fulltekst i vitenarkiv
• Blomhoff, Anne; Ebbing, Cathrine; Eggebø, Torbjørn Moe; Glad, Ragnhild; Haug, Marte Gjøl & Haugen, Guttorm [Vis alle 15 forfattere av denne artikkelen] (2020). De foreslåtte endringene i bioteknologiloven er et fremskritt for kvinnehelsen. 15 representanter fra det fostermedisinske fagmiljø. [Journal]. Aftenposten. Fulltekst i vitenarkiv
• Laine, Katariina; Haugen, Guttorm; Johnsen, Synnøve Lian & Salvesen, Kjell Å (2019). Det er på tide å innføre ultralyd i uke 12. Fire spesialister i fødselshjelp og kvinnesykdommer. Fulltekst i vitenarkiv
• Kaasen, Anne & Haugen, Guttorm (2018). Ultrasonographic detection of fetal malformation and parental longitudinal psychological stress responses. Fulltekst i vitenarkiv
• Carlsen, Karin C. Lødrup; Rehbinder, Eva Maria; Skjerven, Håvard Ove; Carlsen, Monica Hauger; Fatnes, Thea Aspelund & Fugeli, Pål [Vis alle 20 forfattere av denne artikkelen] (2018). Preventing Atopic Dermatitis and ALLergies in Children-the PreventADALL study. Allergy. European Journal of Allergy and Clinical Immunology. ISSN 0105-4538. 73(10), s. 2063–2070. doi: 10.1111/all.13468. Fulltekst i vitenarkiv
• Kaasen, Anne; Helbig, Anne; Malt, Ulrik Fredrik; Skari, Hans; Næs, Tormod & Haugen, Guttorm (2017). Parental psychological stress responses in pregnancy after ultrasonographic detection of fetal malformation. Fulltekst i vitenarkiv
• Kreyberg, Ina; Nordhagen, Live Solveig; Bains, Karen Eline Stensby; Hilde, Katarina; Skjerven, Håvard Ove & Nordlund, Bjørn [Vis alle 12 forfattere av denne artikkelen] (2017). Is tobacco products by 18 weeks pregnancy outdated in Scandinavia? Fulltekst i vitenarkiv
• Helbig, Anne; Kaasen, Anne; Malt, Ulrik Fredrik & Haugen, Guttorm (2016). Does maternal psychological distress in third trimester affect fetal cerebro-placental circulation measures? Fulltekst i vitenarkiv
• Helbig, Anne; Kaasen, Anne; Malt, Ulrik Fredrik & Haugen, Guttorm (2016). Does early antenatal maternal psychological distress affect fetal cerebro-placental circulation in third trimester? Fulltekst i vitenarkiv
• Fredheim, Olav Magnus; Hansen, Thor Willy Ruud; Haugen, Guttorm & Magelssen, Morten (2016). O. Fredheim og medarbeidere svarer :. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 136(11), s. 980–981. doi: 10.4045/tidsskr.16.0488. Fulltekst i vitenarkiv
• Fredheim, Olav Magnus; Hansen, Thor Willy Ruud; Haugen, Guttorm & Magelssen, Morten (2016). Re: Keisersnitt ved trisomi 13 og 18 - en verdibasert vurdering :. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 136(14/15), s. 1187–1187. doi: 10.4045/tidsskr.16.0660. Fulltekst i vitenarkiv
• Fredheim, Olav Magnus; Hansen, Thor Willy Ruud; Haugen, Guttorm & Magelssen, Morten (2016). O. Fredheim og medarbeidere svarer. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 136(10), s. 893–893. doi: 10.4045/tidsskr.16.0440. Fulltekst i vitenarkiv
• Kiserud, Torvid & Haugen, Guttorm (2016). Umbilical circulation, Fetal and neonatal physiology, 5th ed. Elsevier. ISSN 9780323352147. s. 599–610. Fulltekst i vitenarkiv
• Opheim, Gun Lisbet; Henriksen, Tore & Haugen, Guttorm (2016). The influence of a standard breakfast meal on the fetal middle cerebral and umbilical artery pulsatility indices. Fulltekst i vitenarkiv
• Haugen, Guttorm; Bollerslev, Jens & Henriksen, Tore (2016). Human uterine blood flow velocity waveforms following maternal glucose loading related to fetal size: a cross-sectional observational study. Fulltekst i vitenarkiv
• Eggebø, Torbjørn Moe & Haugen, Guttorm (2016). Fosterreduksjon ved ukompliserte tvillingsvangerskap. Dagens medisin. ISSN 1501-4290. Fulltekst i vitenarkiv
• Haugen, Guttorm (2015). Is acetylcholine constriction of umbilical vessels clinically relevant? BJOG: An International Journal of Obstetrics and Gynaecology. ISSN 1470-0328. 122, s. 1640–1640. Fulltekst i vitenarkiv
• Kaasen, Anne; Helbig, Anne; Malt, Ulrik Fredrik; Næs, Tormod; Skari, Hans & Haugen, Guttorm (2014). Maternal Psychological responses after detection of a fetal malformation - a longtudinal study in pregnancy. Fulltekst i vitenarkiv

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