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1.
  • Carlsen, O. C. L., et al. (author)
  • Physical activity in pregnancy: a Norwegian-Swedish mother-child birth cohort study
  • 2021
  • In: AJOG Global Reports. - : Elsevier BV. - 2666-5778. ; 1:1
  • Journal article (peer-reviewed)abstract
    • 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.
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3.
  • Hilde, K., et al. (author)
  • Fetal Thoracic Circumference and Lung Volume and Their Relation to Fetal Size and Pulmonary Artery Blood Flow
  • 2022
  • In: Journal of Ultrasound in Medicine. - : Wiley. - 0278-4297 .- 1550-9613. ; 41:4, s. 985-993
  • Journal article (peer-reviewed)abstract
    • 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.
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4.
  • Hoel, Sveinung T., et al. (author)
  • Birth mode is associated with development of atopic dermatitis in infancy and early childhood
  • 2023
  • In: Journal of Allergy and Clinical Immunology: Global. - : Elsevier BV. - 2772-8293. ; 2:3
  • Journal article (peer-reviewed)abstract
    • Background: Birth by caesarean section (CS) is associated with development of allergic diseases, but its role in the development of atopic dermatitis (AD) is less convincing. Objective: Our primary aim was to determine if birth mode was associated with AD in 3-year-olds and secondarily to determine if birth mode was associated with early onset and/or persistent AD in the first 3 years of life. Methods: We included 2129 mother–child pairs from the Scandinavian population-based prospective PreventADALL cohort with information on birth mode including vaginal birth, either traditional (81.3%) or in water (4.0%), and CS before (6.3%) and after (8.5%) onset of labor. We defined early onset AD as eczema at 3 months and AD diagnosis by 3 years of age. Persistent AD was defined as eczema both in the first year and at 3 years of age, together with an AD diagnosis by 3 years of age. Results: AD was diagnosed at 3, 6, 12, 24, and/or 36 months in 531 children (25%). Compared to vaginal delivery, CS was overall associated with increased odds of AD by 3 years of age, with adjusted odds ratio (95% confidence interval) of 1.33 (1.02-1.74), and higher odds of early onset AD (1.63, 1.06-2.48). The highest odds for early onset AD were observed in infants born by CS after onset of labor (1.83, 1.09-3.07). Birth mode was not associated with persistent AD. Conclusion: CS was associated with increased odds of AD by 3 years of age, particularly in infants presenting with eczema at 3 months of age.
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  • Jar-Allah, Tagrid, et al. (author)
  • Abnormal cervical cytology is associated with preterm delivery: A population based study
  • 2019
  • In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 98:6, s. 777-786
  • Journal article (peer-reviewed)abstract
    • Introduction: Increasing evidence suggests that cervical intraepithelial neoplasia, with or without subsequent treatment, is associated with preterm delivery. We aimed to explore the association between abnormal cervical cytology of different severity and the subsequent obstetric outcomes such as preterm delivery. Material and methods: The historical register-based cohort study comprised 19822 women in the Western Region of Sweden who had at least one abnormal cervical cytology from 1978 to 2012 before the age of 45 and a subsequent singleton delivery. The reference group comprised 39644 women with normal cervical cytology and a subsequent singleton delivery, matched by age and parity. Data were retrieved from the Swedish National Cervical Screening Registry, linked to the Swedish Medical Birth Register and Statistic Sweden. The study outcomes were spontaneous preterm delivery before 37 and 34weeks, low birthweight (≤2500g), small-for-gestational-age, preterm premature rupture of membranes and neonatal mortality. Multivariable log binominal regression analyses were applied. Results: Preterm delivery before 37weeks was more common among women with abnormal cervical cytology compared with reference group: 6% vs 4.5%; adjusted relative risk 1.30 (95% confidence interval 1.21-1.39). High vs low-grade abnormal cervical cytology implied a higher risk: 7% vs 5.8% (P<0.001). Early preterm delivery before 34weeks, preterm premature rupture of membranes and low birthweight, but not small-for-gestational-age and neonatal mortality, were significantly more common in women with abnormal cervical cytology compared with the reference group. Conclusions: Abnormal cervical cytology may imply an increased risk of preterm delivery. Further studies are needed to investigate whether that risk is related to treatment.
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  • Kacerovsky, Marian, et al. (author)
  • Cervical excisional treatment increases the risk of intra-amniotic infection in subsequent pregnancy complicated by preterm prelabor rupture of membranes.
  • 2023
  • In: American journal of obstetrics and gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 229:1
  • Journal article (peer-reviewed)abstract
    • Excisional treatment of cervical intraepithelial neoplasia or very early stages of cervical cancer increases the risk of preterm prelabor rupture of membranes (PPROM) in subsequent pregnancies. The risk increases with the length of the excised cone. The subset of PPROM with a history of cervical excisional treatment could also be jeopardized by a higher risk intra-amniotic infection/inflammation . However, there is a paucity of relevant information on this field.To assess the differences in the rates of intra-amniotic infection/inflammation and early-onset neonatal sepsis between singleton PPROM pregnancies without and with a history of cervical excisional treatment and to identify an association between these complications of PPROM and the excised cone length.This retrospective cohort study included 770 PPROM pregnancies in whom transabdominal amniocentesis was performed as part of standard clinical management to determine intra-amniotic environment. The maternal and perinatal medical records of all included women were reviewed to obtain information on the absence or presence of a history of cervical excisional treatment and neonatal outcomes. Women whose records contained any information on a history of cervical excisional treatment were contacted by phone and in writing to inform them of the study and request permission to collect relevant information from their medical records. Women were divided into four subgroups according to the presence of microorganisms and/or their nucleic acids (through culturing and molecular biology method) in amniotic fluid and/or intra-amniotic inflammation (through amniotic fluid interleukin-6 concentration evaluation): intra-amniotic infection (presence of both), sterile intra-amniotic inflammation (intra-amniotic inflammation alone), microbial invasion of the amniotic cavity without inflammation (the presence of microorganisms and/or their nucleic acids in amniotic fluid alone), and negative amniotic fluid for infection/inflammation (absence of both).A history of cervical excisional treatment was found in 10% (76/765) of the women. Of these, 82% (62/76) had a history of only one treatment, and information on the cone length was available for 97% (60/62) of them. Women with a history of cervical excisional treatment had higher rates of intra-amniotic infection [with: 25% (19/76) vs. without: 12% (85/689), adj. OR: 2.5, adj. p = 0.004], microbial invasion of the amniotic cavity without inflammation [with: 25% (19/76) vs. without: 11% (74/689), adj. OR: 3.1, adj. p < 0.0001], and early-onset neonatal sepsis [with: 8% (11/76) vs. without: 3% (23/689), adj. OR: 2.9, adj. p = 0.02] than those without cervical excisional treatment. Quartiles of the cone length (range: 3-32 mm) were used to categorize the women into four quartile subgroups (1st quartile: 3-8 mm; 2nd quartile: 9-12 mm; 3rd quartile: 13-17 mm, and 4th quartile: 18-32 mm). Cone length of ≥ 18 mm was associated with higher rates of intra-amniotic infection [with: 29% (5/15) vs. without: 12% (85/689), adj. OR: 3.0, adjusted p = 0.05], microbial invasion of the amniotic cavity without inflammation [with: 40% (6/15) vs. without: 11% (74/689), adj. OR: 6.1, adj. p = 0.003), and early-onset neonatal sepsis [with: 20% (3/15) vs. without: 3% (23/689), adj. OR: 5.7, adj. p = 0.02].History of cervical excisional treatment increases risks of intra-amniotic infection, microbial invasion of the amniotic cavity without inflammation, and development of early-onset neonatal sepsis in a subsequent pregnancy complicated by preterm prelabor rupture of membranes.
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  • Pay, Aase Serine D, et al. (author)
  • Symphysis-fundus height measurement to predict small-for-gestational-age status at birth: a systematic review.
  • 2015
  • In: BMC pregnancy and childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 15
  • Journal article (peer-reviewed)abstract
    • Fetal growth restriction is among the most common and complex problems in modern obstetrics. Symphysis-fundus (SF) height measurement is a non-invasive test that may help determine which women are at risk. This study is a systematic review of the literature on the accuracy of SF height measurement for the prediction of small-for-gestational-age (SGA) status at birth in unselected and low-risk pregnancies.
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  • Skjerven, H. O., et al. (author)
  • Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial
  • 2020
  • In: The Lancet. - 0140-6736. ; 395:10228, s. 951-961
  • Journal article (peer-reviewed)abstract
    • Background: Skin emollients applied during early infancy could prevent atopic dermatitis, and early complementary food introduction might reduce food allergy in high-risk infants. The study aimed to determine if either regular skin emollients applied from 2 weeks of age, or early complementary feeding introduced between 12 and 16 weeks of age, reduced development of atopic dermatitis by age 12 months in the general infant population. Methods: This population-based 2×2 factorial, randomised clinical trial was done at Oslo University Hospital and Østfold Hospital Trust, Oslo, Norway; and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine ultrasound pregnancy screening at 18 weeks were cluster-randomised at birth from 2015 to 2017 to the following groups: (1) controls with no specific advice on skin care while advised to follow national guidelines on infant nutrition (no intervention group); (2) skin emollients (bath additives and facial cream; skin intervention group); (3) early complementary feeding of peanut, cow's milk, wheat, and egg (food intervention group); or (4) combined skin and food interventions (combined intervention group). Participants were randomly assigned (1:1:1:1) using computer- generated cluster randomisation based on 92 geographical living area blocks as well as eight 3-month time blocks. Carers were instructed to apply the interventions on at least 4 days per week. Atopic dermatitis by age 12 months was the primary outcome, based on clinical investigations at 3, 6 and 12 months by investigators masked to group allocation. Atopic dermatitis was assessed after completing the 12-month investigations and diagnosed if either of the UK Working Party and Hanifin and Rajka (12 months only) diagnostic criteria were fulfilled. The primary efficacy analyses was done by intention-to-treat analysis on all randomly assigned participants. Food allergy results will be reported once all investigations at age 3 years are completed in 2020. This was a study performed within ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood; the Lung and Environment). The study is registered at clinicaltrials.gov, NCT02449850. Findings: 2697 women were recruited between Dec 9, 2014, and Oct 31, 2016, from whom 2397 newborn infants were enrolled from April 14, 2015, to April 11, 2017. Atopic dermatitis was observed in 48 (8%) of 596 infants in the no intervention group, 64 (11%) of 575 in the skin intervention group, 58 (9%) of 642 in the food intervention group, and 31 (5%) of 583 in the combined intervention group. Neither skin emollients nor early complementary feeding reduced development of atopic dermatitis, with a risk difference of 3·1% (95% CI –0·3 to 6·5) for skin intervention and 1·0% (–2·1 to 4·1) for food intervention, in favour of control. No safety concerns with the interventions were identified. Reported skin symptoms and signs (including itching, oedema, exanthema, dry skin, and urticaria) were no more frequent in the skin, food, and combined intervention groups than in the no intervention group. Interpretation: Neither early skin emollients nor early complementary feeding reduced development of atopic dermatitis by age 12 months. Our study does not support the use of these interventions to prevent atopic dermatitis by 12 months of age in infants. Funding: The study was funded by several public and private funding bodies: The Regional Health Board South East, The Norwegian Research Council, Health and Rehabilitation Norway, The Foundation for Healthcare and Allergy Research in Sweden-Vårdalstiftelsen, Swedish Asthma and Allergy Association's Research Foundation, Swedish Research Council—the Initiative for Clinical Therapy Research, The Swedish Heart-Lung Foundation, SFO-V at the Karolinska Institute, Freemason Child House Foundation in Stockholm, Swedish Research Council for Health, Working Life and Welfare—FORTE, Oslo University Hospital, the University of Oslo, and Østfold Hospital Trust. © 2020 Elsevier Ltd
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10.
  • Vaernesbranden, M. R., et al. (author)
  • Maternal human papillomavirus infections at mid-pregnancy and delivery in a Scandinavian mother-child cohort study
  • 2021
  • In: International Journal of Infectious Diseases. - : Elsevier BV. - 1201-9712. ; 108, s. 574-581
  • Journal article (peer-reviewed)abstract
    • 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. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/).
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  • Vaernesbranden, Magdalena R., et al. (author)
  • Placental human papillomavirus infections and adverse pregnancy outcomes
  • 2024
  • In: PLACENTA. - 0143-4004 .- 1532-3102. ; 152, s. 23-30
  • Journal article (peer-reviewed)abstract
    • 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 Anyor 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.
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  • Wiik, Johanna, et al. (author)
  • Associations between cervical intraepithelial neoplasia during pregnancy, previous excisional treatment, cone-length and preterm delivery: a register-based study from western Sweden
  • 2022
  • In: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 20:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Excisional treatment of cervical intraepithelial neoplasia (CIN) has been associated with increased risk of preterm delivery (PTD), although the underlying mechanism is as yet unclear. Studies on formalin-fixed excised tissue indicate that the risk increases with cone-length, but the magnitude of increase is uncertain, especially in case of minor excisions (≤10 mm), as well compared to women with untreated CIN during pregnancy. This study assesses the impact of cone-length at previous treatment for CIN as well as diagnosis of CIN during pregnancy on the risk of PTD. METHODS: A register-based cohort study in western Sweden linking cervical cytology, histology, and treatment data from the Swedish National Cervical Screening Registry to data on obstetric outcomes in singleton pregnancies 2008-2016 from the Swedish Medical Birth Registry. These groups were compared for PTD and other obstetric outcomes: (1) women with one excisional treatment (n=3250, including a subgroup (n=2408) with cone-length measured before fixation; (2) women with untreated CIN diagnosed during pregnancy (n=1380); and (3) women with normal cytology (n=42,398). Logistic regression analyses were adjusted for socioeconomic and health-related confounders. RESULTS: Treated women had increased risk of PTD (adjusted odds ratio (aOR) 1.60, 95% confidence interval (CI) 1.21-2.12), spontaneous PTD (aOR 1.95, 95% CI 1.40-2.72) and preterm prelabor rupture of membranes (pPROM) (aOR 2.74, 95% CI 1.66-4.51) compared to the CIN during pregnancy group. ORs were similar when compared to the normal cytology group. Risks of these outcomes increased with cone-length. Mean cone-length was 9.1 mm. Cone-length ≤10 mm was associated with increased risk of PTD (aOR 1.41, 95% CI 1.02-1.94), spontaneous PTD (aOR 1.73, 95% CI 1.18-2.54), and pPROM (aOR 2.44, 95% CI 1.40-4.28), compared to the CIN during pregnancy group. The PTD risk was similar for cone-lengths 3-10 mm, thereafter increasing by 15% with each additional millimeter. CONCLUSIONS: This study suggests that all excisional treatment, including small cones, are associated with increased risk of PTD and pPROM. Risks increase further with cone-length. In women of reproductive age, clinicians should aim to remove all CIN but minimal healthy cervical tissue. Cone-length should be recorded at treatment, for future prenatal risk estimation.
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  • Wiik, Johanna, et al. (author)
  • Associations of treated and untreated human papillomavirus infection with preterm delivery and neonatal mortality: A Swedish population-based study
  • 2021
  • In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 18:5
  • Journal article (peer-reviewed)abstract
    • Background Treatment of cervical intraepithelial neoplasia (CIN) is associated with an increased risk of preterm delivery (PTD) although the exact pathomechanism is not yet understood. Women with untreated CIN also seem to have an increased risk of PTD. It is unclear whether this is attributable to human papillomavirus (HPV) infection or other factors. We aimed to investigate whether HPV infection shortly before or during pregnancyAU , as:well Hereandelsewhere as previous treat- ; IchangedHPVin ment for CIN, is associated with an increased risk of PTD and other adverse obstetric and neonatal outcomes. Methods and findings This was a retrospective population-based register study of women with singleton deliveries registered in the Swedish Medical Birth Register 1999–2016 (n = 1,044,023). The study population had a mean age of 30.2 years (SD 5.2) and a mean body mass index of 25.4 kg/m (SD 3.0), and 44% of the women were nulliparous before delivery. Study groups were defined based on cervical HPV tests, cytology, and histology, as registered in the Swedish National Cervical Screening Registry. Women with a history of exclusively normal cytology (n = 338,109) were compared to women with positive HPV tests (n = 2,550) or abnormal cytology (n = 11,727) within 6 months prior to conception or during the pregnancy, women treated for CIN3 before delivery (n = 23,185), and women with CIN2+ diagnosed after delivery (n = 33,760). Study groups were compared concerning obstetric and neonatal outcomes by logistic regression, and comparisons were adjusted for socioeconomic and health-related confounders. HPV infection was associated with PTD (adjusted odds ratio [aOR] 1.19, 95% CI 1.01–1.42, p = 0.042), preterm prelabor rupture of membranes (pPROM) (aOR 1.52, 95% CI 1.18–1.96, p < 0.001), prelabor rupture of membranes (PROM) (aOR 1.24, 95% CI 1.08–1.42, p = 0.002), and neonatal mortality (aOR 2.69, 95% CI 1.25–5.78, p = 0.011). Treatment for CIN was associated with PTD (aOR 1.85, 95% CI 1.76–1.95, p < 0.001), spontaneous PTD (aOR 2.06, 95% CI 1.95–2.17, p < 0.001), pPROM (aOR 2.36, 95% CI 2.19–2.54, p < 0.001), PROM (aOR 1.11, 95% CI 1.05–1.17, p < 0.001), intrauterine fetal death (aOR 1.35, 95% CI 1.05–1.72, p = 0.019), chorioamnionitis (aOR 2.75, 95% CI 2.33–3.23, p < 0.001), intrapartum fever (aOR 1.24, 95% CI 1.07–1.44, p = 0.003), neonatal sepsis (aOR 1.55, 95% CI 1.37–1.75, p < 0.001), and neonatal mortality (aOR 1.79, 95% CI 1.30–2.45, p < 0.001). Women with CIN2+ diagnosed within 3 years after delivery had increased PTD risk (aOR 1.18, 95% CI 1.10–1.27, p < 0.001). Limitations of the study include the retrospective design and the fact that because HPV test results only became available in 2007, abnormal cytology was used as a proxy for HPV infection. Conclusions In this study, we found that HPV infection shortly before or during pregnancy was associated with PTD, pPROM, PROM, and neonatal mortality. Previous treatment for CIN was associated with even greater risks for PTD and pPROM and was also associated with PROM, neonatal mortality, and maternal and neonatal infectious complications.
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14.
  • Wiik, Johanna, et al. (author)
  • Cervical microbiota in women with cervical intra-epithelial neoplasia, prior to and after local excisional treatment, a Norwegian cohort study
  • 2019
  • In: Bmc Womens Health. - : Springer Science and Business Media LLC. - 1472-6874. ; 19
  • Journal article (peer-reviewed)abstract
    • BackgroundLocal treatment for cervical intraepithelial neoplasia (CIN) by Loop Electrosurgical Excision Procedure (LEEP) has been correlated with reproductive morbidity, while the cervicovaginal microbiota is also known to affect the risk of preterm delivery. CIN and treatment by LEEP might change the cervical microbiota. The main aim of this study was to describe the cervical microbiota before and after LEEP and assess its associaton with cone depth and HPV persistence. Further, we aimed to compare the microbiota to references with normal cervical cytology.MethodsBetween 2005 and 2007, we prospectively identified 89 women planned for LEEP in a Norwegian hospital and recruited 100 references with a normal cervical cytology. Endocervical swabs were collected prior to treatment and at six (n=77) and 12months (n=72) post LEEP for bacterial culture and PCR, and post LEEP for DNA testing for human papillomavirus (HPV). We compared the cervical microbiota composition before and after treatment and between women planned for LEEP vs references.ResultsThere was a reduction in the number of non-Lactobacillus bacterial species six and 12months after LEEP compared to before treatment and a tendency towards a concomitant increase in Lactobacillus. No association between the detection of cervical bacteria, HPV persistence or cone depth was found.Women planned for LEEP carried significantly more Bacteroides spp., Gardnerella vaginalis, Mycoplasma hominis and Ureaplasma parvum as well as a greater number of bacterial species than the references.ConclusionsLocal excisional treatment appears to alter the cervical microbiota towards a less diverse microbiota. Women with CIN have a more diverse cervical microbiota compared to women with normal cervical cytology.
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15.
  • Wiik, Johanna (author)
  • Human papillomavirus infection and preterm delivery
  • 2022
  • Doctoral thesis (other academic/artistic)abstract
    • Background: Persistent human papillomavirus (HPV) infection causes cervical intraepithelial neoplasia (CIN). Excisional treatment of CIN has been linked to increased risk of preterm delivery (PTD). The specific mechanism behind is however unclear. Also untreated CIN has been associated with an increased risk of PTD. It is unknown whether this is attributable to the HPV infection itself or other causes. Aims: To examine whether HPV infection, untreated CIN and/or previous treatment for CIN is associated with PTD and other adverse obstetric outcomes. To study possible causal pathways for an association, including cone length of treatment, changes in cervical microbiota and infectious complications. Material and methods: Paper I; a Swedish register-based study (1999-2016), studying obstetric outcomes in women with normal cervical cytology (NCC) (n=338,109), abnormal cytology (n=11,727) or positive HPV test (n=2,550) - in conjunction with pregnancy, previously treated women (n=23,185), and women with CIN2+ diagnosed after pregnancy (n=33,760). Paper II; a register-based study from western Sweden (2008-2016), comparing obstetric outcomes in women with NCC (n=42,398), women with CIN during pregnancy (n=1,380) and previously treated women (n=3,250) including a subgroup with cone length measured at treatment (n=2,408). Paper III; a prospective observational study in Sweden/Norway (n=950) comparing obstetric outcomes in women with or without HPV infection detected in urine at mid-pregnancy and at delivery. Paper IV; a prospective observational study in Norway with culture and PCR of cervical microbiota in women with CIN (n=89) before and six and 12 months after LEEP and also compared to women with NCC (n=100). Results: Paper I; HPV infection (HPVtest) compared to NCC was associated with PTD (aOR 1.2, 95% CI 1.0-1.4), and preterm prelabor rupture of membranes (pPROM) (aOR 1.5, 1.2-2.0), but treated women had higher risk compared to women with HPV infection; PTD (aOR 1.7, 1.4-2.0), pPROM (aOR 1.6, 1.2-2.0). Treatment but also HPV infection were associated with increased risk of neonatal mortality and PROM at term and treatment also with chorioamnionitis and neonatal sepsis. Paper II; Treatment was associated with an increased risk of PTD (aOR 1.6, 1.2-2.1), pPROM (aOR 2.7, 1.7-4.5), and PROM at term compared to women with CIN, and risks increased with cone length. Small treatments (≤10 mm) were also associated with increased risk for PTD and pPROM. Paper III; Women positive for high-risk-HPV genotypes at mid-pregnancy had a higher frequency of PTD compared to those negative for high-risk-HPV, but comparisons were non-significant. Paper IV; Treatment resulted in a reduction of non-Lactobacillus bacterial species. More types of bacterial species were detected in women planned for LEEP than in women with NCC. Conclusion: Women with HPV infection have increased risk of PTD, pPROM and neonatal mortality. Excisional treatment for CIN, also minor excisions, increases the risks for PTD and pPROM further compared to having untreated CIN/HPV infection. The risks increase with cone length. Previous treatment is also associated with increased risk of PROM at term and maternal and neonatal infectious complications. Treatment appears not to result in a more diverse or dysbiotic cervical microbiota while CIN is associated with increased bacterial diversity.
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16.
  • Wiik, Johanna, et al. (author)
  • Maternal human papillomavirus infection during pregnancy and preterm delivery, a mother–child cohort study in Norway and Sweden
  • 2023
  • In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 102:3, s. 344-354
  • Journal article (peer-reviewed)abstract
    • 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.
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