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  • 1
    Online Resource
    Online Resource
    Fetal fraction of cell-free DNA in pregnancies after fresh or frozen embryo transfer following assisted reproductive technologies
    Oxford University Press (OUP) ; 2020
    In:  Human Reproduction Vol. 35, No. 6 ( 2020-06-01), p. 1267-1275
    Details
    In: Human Reproduction, Oxford University Press (OUP), Vol. 35, No. 6 ( 2020-06-01), p. 1267-1275
    Abstract: Is the fetal fraction (FF) of circulating cell-free DNA (cfDNA) affected in pregnancies following ART treatment with either fresh or frozen embryo transfer (ET) compared with natural conception? SUMMARY ANSWER This study shows a significant reduction in the FF in ART patients compared with naturally conceived pregnancies, which seems to be more pronounced after fresh ET compared with frozen ET. WHAT IS KNOWN ALREADY Non-invasive prenatal testing (NIPT) is based on cfDNA in maternal blood, of which about 10% is of placental origin and thus represents the fetal karyotype. Validation studies have demonstrated a high sensitivity, specificity and positive predictive value of NIPT for the detection of fetal trisomy 21, 18 and 13. Nevertheless, the FF of cfDNA is an important factor for NIPT test accuracy. Several studies have found a reduction in FF for pregnancies following ART in comparison with natural conception. However, knowledge on how the FF is affected in ART pregnancies after fresh ET compared with frozen ET is very limited. STUDY DESIGN, SIZE, DURATION The study was designed as a case–control study. A total of 54 women with an ongoing pregnancy following ART treatment were included. After exclusion for different reasons, statistical analyses were based on 23 NIPT samples from pregnant women treated with fresh ET and 26 NIPT samples from pregnant women treated with frozen-thawed ET in a modified natural cycle. Women were included between February 2018 and November 2018. The results were compared with a control group of 238 naturally conceived pregnancies with a high-risk result from the combined first trimester screening (cFTS). PARTICIPANTS/MATERIALS, SETTING, METHODS The study included women from the Fertility Clinics at Copenhagen University Hospital Hvidovre and Copenhagen University Hospital Rigshospitalet. Blood samples for NIPT analysis were drawn between 11 + 0 and 14 + 2 weeks of gestation and were all analyzed at the NIPT Center at Copenhagen University Hospital Hvidovre. The NIPT-test was performed by massive-parallel whole-genome sequencing. The FF was determined using the SeqFF algorithm. MAIN RESULTS AND THE ROLE OF CHANCE We found a reduction in FF in ART patients compared with naturally conceived pregnancies, and the reduction was more pronounced for ART pregnancies after fresh ET (mean FF = 0.049) compared with frozen ET (mean FF = 0.063) (multivariate analysis adjusted for maternal BMI, P = 0.02). Another multivariate analysis, adjusted for BMI and multiples of median (MoM) values for pregnancy-associated plasma protein-A (PAPP-A), demonstrated a significantly reduced FF for ART pregnancies (mean FF = 0.056) compared with naturally conceived pregnancies (mean FF = 0.072) (P & lt; 0.0001). We found that FF was significantly reduced with increasing maternal BMI (P & lt; 0.0001) and with decreasing MoM values of PAPP-A (P = 0.003). LIMITATIONS, REASONS FOR CAUTION A limitation of our study design was the relatively small sample size. Another limitation was that the control group was not matched with the ART-treated women. The majority of the women from the control group had a high risk from cFTS, thereby their biochemical markers were diverging. However, the biochemical markers for the ART-treated women with fresh or frozen ET were not divergent within the subgroups. WIDER IMPLICATIONS OF THE FINDINGS Concurrent with other studies demonstrating a reduced FF for singleton pregnancies after ART treatment compared with naturally conceived pregnancies, we found a reduction in FF between the two groups. This is one of the first studies to examine FF in ART pregnancies after fresh ET compared with frozen ET, hence the existing knowledge is limited. We find that FF is even more reduced in pregnancies following fresh ET compared with frozen ET, which might possibly reflect the predisposition of being small for gestational age after fresh ET compared with natural cycle frozen ET. STUDY FUNDING/COMPETING INTEREST(S) The study was supported by the A.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene Formaal (the A.P. Møller Foundation for General Purposes). All authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER NA.
    Type of Medium: Online Resource
    ISSN: 0268-1161 , 1460-2350
    URL: Article
    DOI: 10.1093/humrep/deaa110
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1484864-8
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  • 2
    Online Resource
    Online Resource
    A novel algorithm for classification of interatrial communications within the oval fossa in the newborn : Results from the Copenhagen Baby Heart Study
    Cambridge University Press (CUP) ; 2023
    In:  Cardiology in the Young Vol. 33, No. 10 ( 2023-10), p. 1942-1949
    Details
    In: Cardiology in the Young, Cambridge University Press (CUP), Vol. 33, No. 10 ( 2023-10), p. 1942-1949
    Abstract: An interatrial communication is present in most neonates. The majority are considered the “normal” patency of the oval foramen, while a minority are abnormal atrial septal defects. Differentiation between the two with transthoracic echocardiography may be challenging, and no generally accepted method of classification is presently available. We aimed to develop and determine the reliability of a new classification of interatrial communications in newborns. Methods and Results: An algorithm was developed based on echocardiographic criteria from 495 newborns (median age 11[8;13] days, 51.5% females). The algorithm defines three main categories: patency of the oval foramen, atrial septal defect, and no interatrial communication as well as several subtypes. We found an interatrial communication in 414 (83.6%) newborns. Of these, 386 (93.2%) were categorised as patency of the oval foramen and 28 (6.8%) as atrial septal defects. Echocardiograms from another 50 newborns (median age 11[8;13] days, 36.0% female), reviewed by eight experts in paediatric echocardiography, were used to assess the inter- and intraobserver variation of classification of interatrial communications into patency of the oval foramen and atrial septal defect, with and without the use of the algorithm. Review with the algorithm gave a substantial interobserver agreement (kappa = 0.66), and an almost perfect intraobserver agreement (kappa = 0.82). Without the use of the algorithm, the interobserver agreement between experienced paediatric cardiologists was low (kappa = 0.20). Conclusion: A new algorithm for echocardiographic classification of interatrial communications in newborns produced almost perfect intraobserver and substantial interobserver agreement. The algorithm may prove useful in both research and clinical practice.
    Type of Medium: Online Resource
    ISSN: 1047-9511 , 1467-1107
    URL: Article
    DOI: 10.1017/S1047951122003365
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2060876-7
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  • 3
    Online Resource
    Online Resource
    Targeted Rhesus immunoglobulin for RhD‐negative women undergoing an induced abortion: A clinical pilot study
    Wiley ; 2019
    In:  Acta Obstetricia et Gynecologica Scandinavica Vol. 98, No. 9 ( 2019-09), p. 1164-1171
    Details
    In: Acta Obstetricia et Gynecologica Scandinavica, Wiley, Vol. 98, No. 9 ( 2019-09), p. 1164-1171
    Abstract: The aim of this clinical pilot study was to examine the accuracy of noninvasive fetal RHD genotyping in early pregnancy (8 +0  to 11 +6  weeks) and to clarify whether targeted administration of Rhesus immunoglobulin (RhIg) is possible for women undergoing an induced abortion such that unnecessary injections can be avoided. The study examines the correlation between gestational age and the amount of cell‐free fetal DNA in maternal plasma, the fetal fraction of DNA and whether transportation time or body mass index affects these parameters. Material and methods Fifty‐two RhD‐negative women undergoing a surgically induced abortion were included. A maternal blood sample was collected prior to the abortion and a tissue sample was collected from the placental part of the abortion material after the intervention. Fetal RhD type was determined by PCR analysis of cell‐free fetal DNA extracted from maternal plasma and on DNA from the tissue sample, with the latter providing a reference standard. Copies of RHD /mL were determined on RHD ‐positive samples and the fetal fraction of DNA was calculated. Results We demonstrated complete concordance between results from plasma and tissue, with 31 RhD‐positive and 21 RhD‐negative samples, corresponding to 40% being RhD‐negative, specificity 100% [ 95% confidence interval (CI) 88.8‐100] and sensitivity 100% ( 95% CI 83.9‐100). We found no significant correlation between gestational age and the amount or the fraction of cell‐free fetal DNA in maternal plasma, nor did we find that transportation time or BMI significantly affected these factors in this setup. Conclusions Fetal RHD genotyping can be accurately performed from the 8th week of gestation and unnecessary injections of RhIg can be avoided for women undergoing an induced abortion. A larger study is needed to determine a more accurate sensitivity for the analysis early in pregnancy.
    Type of Medium: Online Resource
    ISSN: 0001-6349 , 1600-0412
    URL: Issue
    URL: Article
    DOI: 10.1111/aogs.v98.9
    DOI: 10.1111/aogs.13606
    RVK:
    YM 6500
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2024554-3
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  • 4
    Online Resource
    Online Resource
    Noninvasive prenatal testing and maternal obesity: A review
    Wiley ; 2020
    In:  Acta Obstetricia et Gynecologica Scandinavica Vol. 99, No. 6 ( 2020-06), p. 744-750
    Details
    In: Acta Obstetricia et Gynecologica Scandinavica, Wiley, Vol. 99, No. 6 ( 2020-06), p. 744-750
    Abstract: Noninvasive prenatal testing (NIPT) has become a popular screening test for the most common fetal aneuploidies. The performance of NIPT is affected by several factors including maternal obesity, which results in a greater rate of no‐calls for obese pregnant women. Guidelines regarding NIPT in prenatal screening have been published, but with few and divergent recommendations on the issue. We aimed to review the medical literature, guidelines from scientific societies and information material from commercial NIPT providers on no‐calls and maternal obesity. We systematically identified medical literature and guidelines from scientific societies using the database MEDLINE. Information material from commercial NIPT providers was found via a systematic search on Google.com. Nine medical studies investigating the association between maternal obesity and NIPT no‐calls were included. They all showed the same trend: increasing no‐call rate with increasing maternal obesity. The no‐call rate ranged from 0% to 4.2% for women with body mass index (BMI) 18.5‐24.9 and from 5.4% to 70.1% for women BMI ≥40. We identified 17 scientific societies with guidelines and 13 commercial NIPT providers. All were checked for information material on no‐calls and maternal obesity. To allow comparison, all guidelines were examined to answer the same three predefined questions. Of the 17 included scientific societies, 13 (76.5%) mentioned the association between maternal obesity and NIPT no‐calls, two (11.8%) specified weight limits and three (17.6%) advised against NIPT for severely obese pregnant women. None of the 13 commercial NIPT providers provided specific recommendations, but four (30.8%) cite maternal obesity as a potential cause for a no‐call. Because of the increasing number of patients in this group, we advocate updated recommendations to guide decision making in prenatal screening for obese pregnant women.
    Type of Medium: Online Resource
    ISSN: 0001-6349 , 1600-0412
    URL: Issue
    URL: Article
    DOI: 10.1111/aogs.v99.6
    DOI: 10.1111/aogs.13848
    RVK:
    YM 6500
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2024554-3
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  • 5
    Online Resource
    Online Resource
    National screening guidelines and developments in prenatal diagnoses and live births of Down syndrome in 1973–2016 in Denmark
    Wiley ; 2018
    In:  Acta Obstetricia et Gynecologica Scandinavica Vol. 97, No. 2 ( 2018-02), p. 195-203
    Details
    In: Acta Obstetricia et Gynecologica Scandinavica, Wiley, Vol. 97, No. 2 ( 2018-02), p. 195-203
    Abstract: Denmark was the first country in the world to implement a national, free‐for‐all offer of prenatal screening for Down syndrome to all pregnant women. It has a high uptake ( 〉 90%) compared to other countries. Thus, Denmark offers an interesting case for investigating the consequences of implementing comprehensive, national prenatal screening guidelines. The aim of this study was to describe the historical developments in invasive procedures, pre‐/postnatal diagnoses of Down syndrome and Down syndrome live births in the period 1973–2016 in Denmark. Material and methods Data on invasive procedures, pre‐ and postnatal Down syndrome diagnoses were retrieved from the Danish Cytogenetic Central Registry. Results From 1973 to 1993, screening based on maternal age and high‐risk indications resulted in a constant increase in invasive procedures. After the introduction of the triple test in 1994, invasive procedures decreased for the first time in 20 years. Following the introduction of an offer of combined screening to all pregnant women in 2004, the number of invasive procedures decreased markedly, while there was a concurrent increase in prenatal diagnoses of Down syndrome. Additionally, the number of Down syndrome live births decreased suddenly and significantly, but subsequently stabilized at 23–35 annual live births. Of these, the majority were diagnosed postnatally. Conclusion Though prenatal screening technologies constantly improve, it was the introduction of and adherence to national guidelines that resulted in marked shifts in screening procedures and outcome in Denmark.
    Type of Medium: Online Resource
    ISSN: 0001-6349 , 1600-0412
    URL: Issue
    URL: Article
    DOI: 10.1111/aogs.2018.97.issue-2
    DOI: 10.1111/aogs.13273
    RVK:
    YM 6500
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2024554-3
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  • 6
    Online Resource
    Online Resource
    Why we succeed and fail in detecting fetal growth restriction: A population‐based study
    Wiley ; 2021
    In:  Acta Obstetricia et Gynecologica Scandinavica Vol. 100, No. 5 ( 2021-05), p. 893-899
    Details
    In: Acta Obstetricia et Gynecologica Scandinavica, Wiley, Vol. 100, No. 5 ( 2021-05), p. 893-899
    Abstract: The objective of this study was to explore the association between detection of fetal growth restriction and maternal‐, healthcare provider‐ and organizational factors. Material and methods A historical, observational, multicentre study. All women who gave birth to a child with a birthweight 〈 2.3rd centile from 1 September 2012 to 31 August 2015 in Zealand, Denmark, were included. The population was identified through the Danish Fetal Medicine Database. Medical charts were reviewed to obtain data regarding maternal characteristics and information on the healthcare professionals. Date of authorization for the midwives and obstetricians involved was extracted from the Danish Health Authorization Registry. Multivariable Cox regression models were used to identify predictors of antenatal detection of fetal growth restriction, and analyses were adjusted for hospital, body mass index, parity, the presence of at least one risk factor and experience of the first midwife, number of midwife visits, number of visits to a doctor, the experience of the consultant midwife or the educational level of the doctor, the number of scans and gaps in continuity of midwife‐care. Antenatal detection was defined as an ultrasound estimated fetal weight 〈 2.3rd centile (corresponding to −2 standard deviations) prior to delivery. Results Among 78 544 pregnancies, 3069 (3.9%) had a fetal growth restriction. Detection occurred in 31% of fetal growth‐restricted pregnancies. Clinical experience (defined as years since graduation) of the first consultation midwife was positively associated with detection, with a hazard ratio [HR] of 1.15, 95% confidence interval [CI] 1.03‐1.28), for every 10 years of additional experience. The hazard of detection increased with the number of midwife consultations (HR 1.15, 95% CI 1.05‐1.26) and with multiparity (HR 1.28, 95% CI 1.03‐1.58). After adjusting for all covariates, an unexplained difference between hospitals ( P  = .01) remained. Conclusions The low‐risk nullipara may constitute an overlooked group of women at increased risk of antenatal non‐detection of fetal growth restriction. Being screened by experienced midwives during early pregnancy and having access to multiple midwife consultations may improve future diagnosis.
    Type of Medium: Online Resource
    ISSN: 0001-6349 , 1600-0412
    URL: Issue
    URL: Article
    DOI: 10.1111/aogs.v100.5
    DOI: 10.1111/aogs.14048
    RVK:
    YM 6500
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2024554-3
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  • 7
    Online Resource
    Online Resource
    Expression Pattern and Prognostic Impact of Vascular Endothelial Growth Factors VEGF and VEGF-C and Their Receptors Flt-1, KDR and Flt-4 in Peripheral T-Cell Lymphomas.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 689-689
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 689-689
    Abstract: The vascular endothelial growth factor family (VEGF, VEGF-B, -C and -D) is the main regulator of angiogenesis and lymphangiogenesis via their receptors, Flt-1, KDR and Flt-4. The aim of the present study was to estimate the microvascular density and investigate the expression of VEGF, VEGF-C and its receptors Flt-1, KDR and Flt-4 in peripheral T-cell lymphomas (PTCL). Material and methods: Microvessel density (MVD) was determined after CD34 immunohistochemical (IH) staining of endothelial cells in pre-therapeutic lymph-node biopsies from 107 cases of PTCL (64 unspecified, 1 angiocentric, 10 angioimmunoblastic and 32 anaplastic large cell T/0). 44 of these cases (28 unspecified, 1 angiocentric, 4 angioimmunoblatic and 11 anaplastic large cell T/0) were investigated for expression of angiogenic molecules, VEGF, VEGF-C and their receptors by IH at protein level. Furthermore, VEGF and VEGF-C mRNA expression was detected by non-isotopic ′in situ′ hybridization. The angiogenic scores were correlated to pre-therapeutic clinical parameters, treatment response and survival. Results: Tumoral expression of VEGF, VEGF-C and of their receptors was detected in the majority of the PTCL biopsies investigated (VEGF mRNA: 73%, VEGF protein: 95%; VEGF-C mRNA: 79%; VEGF-C protein: 79%; Flt-1 and KDR: 100%; Flt-4: 26%). All biopsies contained VEGF, Flt-1 and KDR positive vessels and VEGF-C was also widely expressed by the endothelial cells (3 negative cases), while endothelial Flt-4 expression was detected only in 43% of cases. High MVD scores correlated with an advanced clinical stadium (Ann Arbor) (p=0.047). A strong diffuse VEGF mRNA expression significantly correlated with a poorer overall survival (p=0.0015) as compared to focal or negative ISH signal. The predictive value of this parameter persisted at multivariate level independently of the International Prognostic Index (HR: 3.95, p=0.012, Cox regression). Conclusion: VEGF, VEGF-C and their receptors are expressed by both lymphoma and endothelial cells in the majority of PTCL cases. VEGF expression seems to have an adverse impact on survival. Larger studies of angiogenesis/lymphangiogenesis in PTCL are needed to clarify the biological role of these molecules and identify possible therapeutic targets.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.689.689
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    Online Resource
    Online Resource
    The Danish Fetal Medicine Database: establishment, organization and quality assessment of the first trimester screening program for trisomy 21 in Denmark 2008–2012
    Wiley ; 2015
    In:  Acta Obstetricia et Gynecologica Scandinavica Vol. 94, No. 6 ( 2015-06), p. 577-583
    Details
    In: Acta Obstetricia et Gynecologica Scandinavica, Wiley, Vol. 94, No. 6 ( 2015-06), p. 577-583
    Abstract: To describe the establishment and organization of the Danish Fetal Medicine Database and to report national results of first‐trimester combined screening for trisomy 21 in the 5‐year period 2008–2012. Design National register study using prospectively collected first‐trimester screening data from the Danish Fetal Medicine Database. Population Pregnant women in Denmark undergoing first‐trimester screening for trisomy 21. Methods Data on maternal characteristics, biochemical and ultrasonic markers are continuously sent electronically from local fetal medicine databases (Astraia Gmbh software) to a central national database. Data are linked to outcome data from the National Birth Register, the National Patient Register and the National Cytogenetic Register via the mother's unique personal registration number. First‐trimester screening data from 2008 to 2012 were retrieved. Main outcome measures Screening performance was assessed for the years 2008–2012 by calculating detection rates and screen‐positive rates. Results A total of 268 342 first‐trimester risk assessments for trisomy 21 were performed in singleton pregnancies. Participation rate in first‐trimester screening was 〉 90%. The national screen‐positive rate increased from 3.6% in 2008 to 4.7% in 2012. The national detection rate of trisomy 21 was reported to be between 82 and 90% in the 5‐year period. Conclusion A national fetal medicine database has been successfully established in Denmark. Results from the database have shown that at a national level first‐trimester screening performance for trisomy 21 is high with a low screen‐positive rate and a high detection rate.
    Type of Medium: Online Resource
    ISSN: 0001-6349 , 1600-0412
    URL: Issue
    URL: Article
    DOI: 10.1111/aogs.2015.94.issue-6
    DOI: 10.1111/aogs.12581
    RVK:
    YM 6500
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2024554-3
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  • 9
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    Online Resource
    Outcomes of monoamniotic twin pregnancies managed primarily in outpatient care—a Danish multicenter study
    Wiley ; 2019
    In:  Acta Obstetricia et Gynecologica Scandinavica Vol. 98, No. 4 ( 2019-04), p. 479-486
    Details
    In: Acta Obstetricia et Gynecologica Scandinavica, Wiley, Vol. 98, No. 4 ( 2019-04), p. 479-486
    Abstract: Monoamniotic twin pregnancies are high‐risk pregnancies, and management by inpatient or frequent outpatient care is recommended. We report the outcomes of a national cohort of monoamniotic twin pregnancies managed primarily as outpatients. Material and methods We prospectively analyzed the recorded data from the Danish Fetal Medicine Database, local databases, and medical records of all monoamniotic twin pregnancies diagnosed at the first trimester scan or later, and managed at the six major fetal medicine centers in Denmark over a 10‐year period. Results Sixty‐one monoamniotic twin pregnancies were included. Thirteen pregnancies were terminated early. Of the remaining 48 pregnancies with a normal first trimester scan, there were 36 fetal losses (25 spontaneous miscarriages 〈 22 +0  weeks, 3 late terminations and 8 intrauterine deaths 〉 22 weeks) and 60 liveborn children (62.5%), all of whom were delivered by cesarean delivery at a median gestational age of 33 +0  weeks. Three children had minor malformations and there was 1 pregnancy with twin‐to‐twin transfusion syndrome. After 26 +0  weeks, 78.8% were managed as outpatients. Intrauterine death occurred in 3.8% of outpatients and in 28.6% of inpatients (admitted due to complications). At weeks 32, 33 and 34, the prospective risk of intrauterine death was 6.9%, 4.2% and 5.9%, respectively. Conclusion In this nationwide, unselected population, only 62.5% of fetuses with a normal first trimester scan were born alive. In contrast, the mortality was 3.8% after 26 weeks among the 78.8% of the cohort that was managed as outpatients. More knowledge is still needed to predict which pregnancies are at the highest risk of intrauterine death.
    Type of Medium: Online Resource
    ISSN: 0001-6349 , 1600-0412
    URL: Issue
    URL: Article
    DOI: 10.1111/aogs.2019.98.issue-4
    DOI: 10.1111/aogs.13509
    RVK:
    YM 6500
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2024554-3
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  • 10
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    Online Resource
    The nucleotide sequence of the 3′ region of the murine leukemia virus SL16c4
    Oxford University Press (OUP) ; 1989
    In:  Nucleic Acids Research Vol. 17, No. 15 ( 1989), p. 6413-6413
    Details
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 17, No. 15 ( 1989), p. 6413-6413
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    URL: Article
    DOI: 10.1093/nar/17.15.6413
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 1989
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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