Epidemic of parvovirus B19 and disease severity in pregnant people, Denmark, January to March 2024.

We report an epidemic of parvovirus B19 infections in Denmark during the first quarter of 2024, with a peak incidence 3.5 times higher than during the most recent epidemic in 2017. In total, 20.1% (130/648) of laboratory-confirmed cases were pregnant. Severe adverse outcomes were observed among 12.3% (16/130) of pregnant people and included foetal anaemia, foetal hydrops and miscarriage. Parvovirus B19 infection is not systematically monitored, but a national laboratory-based surveillance system is currently being established in Denmark.

Prenatal detection of major congenital malformations in a cohort of 19 367 Danish fetuses with a complete follow-up six months after birth.

INTRODUCTION: To investigate the performance of the second-trimester ultrasound scan regarding ultrasound-detectable congenital malformations in a Danish region. The study sample was population-based, with 6 months of postnatal follow-up. Hospital records and autopsy reports were reviewed in each case to validate the prenatal ultrasound diagnosis. MATERIAL AND METHODS: This population-based cohort study included all fetuses (n = 19.367) alive at the second-trimester scan in four hospitals in a Danish region. The final diagnosis of the malformations was based on hospital records during the 6-month postnatal follow-up. In case of termination or stillbirth, the result from the autopsy report was used to validate the prenatal ultrasound diagnosis. RESULTS: The detection rate of congenital malformations in the prenatal screening program was 69%, where 18% was detected on the first-trimester scan and 51% on the second-trimester scan. Another 8% was detected in the third trimester. Specificity was 99.9%. The positive predictive value of the screening program was 94.5%, and the negative predictive value was 99.5%. The overall prevalence of malformations was 16.8 per 1000 fetuses, most frequently in the heart and the urinary tract. CONCLUSIONS: This study shows that the national screening program for congenital malformations can detect many severe malformations and is an effective screening test for malformations.

Triple trouble: uncovering the risks and benefits of early fetal reduction in trichorionic triplets in a large national Danish cohort study.

BACKGROUND: Triplet pregnancies are high risk for both the mother and the infants. The risks for infants include premature birth, low birthweight, and neonatal complications. Therefore, the management of triplet pregnancies involves close monitoring and may include interventions, such as fetal reduction, to prolong the pregnancy and improve outcomes. However, the evidence of benefits and risks associated with fetal reduction is inconsistent. OBJECTIVE: This study aimed to compare the outcomes of trichorionic triplet pregnancies with and without fetal reduction and with nonreduced dichorionic twin pregnancies and primary singleton pregnancies. STUDY DESIGN: All trichorionic triplet pregnancies in Denmark, including those with fetal reduction, were identified between 2008 and 2018. In Denmark, all couples expecting triplets are informed about and offered fetal reduction. Pregnancies with viable fetuses at the first-trimester ultrasound scan and pregnancies not terminated were included. Adverse pregnancy outcome was defined as a composite of miscarriage before 24 weeks of gestation, stillbirth at 24 weeks of gestation, or intrauterine fetal death of 1 or 2 fetuses. RESULTS: The study cohort was composed of 317 trichorionic triplet pregnancies, of which 70.0% of pregnancies underwent fetal reduction to a twin pregnancy, 2.2% of pregnancies were reduced to singleton pregnancies, and 27.8% of pregnancies were not reduced. Nonreduced triplet pregnancies had high risks of adverse pregnancy outcomes (28.4%), which was significantly lower in triplets reduced to twins (9.0%; difference, 19.4%, 95% confidence interval, 8.5%-30.3%). Severe preterm deliveries were significantly higher in nonreduced triplet pregnancies (27.9%) than triplet pregnancies reduced to twin pregnancies (13.1%; difference, 14.9%, 95% confidence interval, 7.9%-21.9%). However, triplet pregnancies reduced to twin pregnancies had an insignificantly higher risk of miscarriage (6.8%) than nonreduced twin pregnancies (1.1%; difference, 5.6%; 95% confidence interval, 0.9%-10.4%). CONCLUSION: Triplet pregnancies reduced to twin pregnancies had significantly lower risks of adverse pregnancy outcomes, severe preterm deliveries, and low birthweight than nonreduced triplet pregnancies. However, triplet pregnancies reduced to twin pregnancies were potentially associated with a 5.6% increased risk of miscarriage.

Comprehensive prenatal diagnostics: Exome versus genome sequencing.

OBJECTIVE: This study aimed to assess the diagnostic yield of prenatal genetic testing using trio whole exome sequencing (WES) and trio whole genome sequencing (WGS) in pregnancies with fetal anomalies by comparing the results with conventional chromosomal microarray (CMA) analysis. METHODS: A total of 40 pregnancies with fetal anomalies or increased nuchal translucency (NT ≥ 5 mm) were included between the 12th and 21st week of gestation. Trio WES/WGS and CMA were performed in all cases. RESULTS: The trio WES/WGS analysis increased the diagnostic yield by 25% in cases with negative CMA results. Furthermore, all six chromosomal aberrations identified by CMA were independently detected by WES/WGS analysis. In total, 16 out of 40 cases obtained a genetic sequence variant, copy number variant, or aneuploidy explaining the phenotype, resulting in an overall WES/WGS diagnostic yield of 40%. WES analysis provided a more reliable identification of mosaic sequence variants than WGS because of its higher sequencing depth. CONCLUSIONS: Prenatal WES/WGS proved to be powerful diagnostic tools for fetal anomalies, surpassing the diagnostic yield of CMA. They have the potential to serve as standalone methods for prenatal diagnosis. The study highlighted the limitations of WGS in accurately detecting mosaic variants, which is particularly relevant when analyzing chorionic villus samples.

First trimester serum apolipoproteins in the prediction of late-onset preeclampsia.

Late-onset preeclampsia occurring after 34 weeks of gestation is the most common form of preeclampsia, but little is known about either etiology or prevention. Current detection methods for preeclampsia in early pregnancy have not shown promising results in detecting late-onset preeclampsia. The aim of this study was to assess whether apolipoproteins in combination with maternal medical history and biophysical factors can be used as an early detection method for late-onset preeclampsia. This nested case-cohort study was based at Odense University Hospital, Denmark. Women attending their first trimester scan were invited to participate if they understood Danish or English, were above the age of 18, and had singleton pregnancies. Blood pressure, maternal medical history, uterine artery pulsatility indices, and blood samples were collected at inclusion. Outcome data were collected from participants' medical files postpartum, and cases were selected when preeclampsia diagnostics were present. Serum samples were analyzed by targeted mass spectrometry using a biomarker panel consisting of 12 apolipoproteins. Logistic regression analyses were performed and finally receiver operating curves were completed. The cohort consisted of 27 cases and 194 normotensive controls, randomized from 340 eligible participants. Significant differences were found between the two groups' baseline characteristics but none of the apolipoproteins showed significant difference (p < 0.05). The ROC-curve combining maternal characteristics, mean arterial pressure and two apolipoproteins showed the best sensitivity of 55.5% at a 10% false-positive rate and an area under the curve of 0.873. In conclusion, apolipoproteins did not improve the detection of late-onset preeclampsia in a combined screening model.

Risks and pregnancy outcome after fetal reduction in dichorionic twin pregnancies: a Danish national retrospective cohort study.

BACKGROUND: Twin pregnancies carry a higher risk of congenital and structural malformations, and pregnancy complications including miscarriage, stillbirth, and intrauterine fetal death, compared with singleton pregnancies. Carrying a fetus with severe malformations or abnormal karyotype places the remaining healthy fetus at an even higher risk of adverse outcome and pregnancy complications. Maternal medical conditions or complicated obstetrical history could, in combination with twin pregnancy, cause increased risks for both the woman and the fetuses. To our knowledge, no previous studies have evaluated and compared the outcomes of all dichorionic twin pregnancies and compared the results of reduced twins with those of nonreduced and primary singletons in a national cohort. These data are important for clinicians when counseling couples about fetal reduction and its implications. OBJECTIVE: This study aimed to describe and compare the risks of adverse pregnancy outcomes, including the risk of pregnancy loss, in a national cohort of all dichorionic twins-reduced, nonreduced, and primary singletons. In addition, we examined the implications of gestational age at fetal reduction on gestational age at delivery. STUDY DESIGN: This was a retrospective cohort study of all Danish dichorionic twin pregnancies, including pregnancies undergoing fetal reduction and a large proportion of randomly selected primary singleton pregnancies with due dates between January 2008 and December 2018. The primary outcome measures were adverse pregnancy outcomes (defined as miscarriage before 24 weeks, stillbirth from 24 weeks, or single intrauterine fetal death in nonreduced twin pregnancies), preterm delivery, and obstetrical pregnancy complications. Outcomes after fetal reduction were compared with those of nonreduced dichorionic twins and primary singletons. RESULTS: In total, 9735 dichorionic twin pregnancies were included, of which 172 (1.8%) were reduced. In addition, 16,465 primary singletons were included. Fetal reductions were performed between 11 and 23 weeks by transabdominal needle-guided injection of potassium chloride, and outcome data were complete for all cases. Adverse pregnancy outcome was observed in 4.1% (95% confidence interval, 1.7%-8.2%) of reduced twin pregnancies, and 2.4% (95% confidence interval, 0.7%-6.1%) were delivered before 28 weeks, and 4.2% (95% confidence interval, 1.7%-8.5%) before 32 weeks. However, when fetal reduction was performed before 14 weeks, adverse pregnancy outcomes occurred in only 1.4% (95% confidence interval, 0.0%-7.4%), and delivery before 28 and 32 weeks diminished to 0% (95% confidence interval, 0.0%-5.0%) and 2.8% (95% confidence interval, 0.3%-9.7%), respectively. In contrast, 3.0% (95% confidence interval, 2.7%-3.4%) of nonreduced dichorionic twins had an adverse pregnancy outcome, and 1.9% (95% confidence interval, 1.7%-2.1%) were delivered before 28 weeks, and 7.3% (95% confidence interval, 6.9%-7.7%) before 32 weeks. Adverse pregnancy outcomes occurred in 0.9% (95% confidence interval, 0.7%-1.0%) of primary singletons, and 0.2% (95% confidence interval, 0.1%-0.3%) were delivered before 28 weeks, and 0.7% (95% confidence interval, 0.6%-0.9%) before 32 weeks. For reduced twins, after taking account of maternal factors and medical history, it was demonstrated that the later the fetal reduction was performed, the earlier the delivery occurred (P<.01). The overall risk of pregnancy complications was significantly lower among reduced twin pregnancies than among nonreduced dichorionic twin pregnancies (P=.02). CONCLUSION: In a national 11-year cohort including all dichorionic twin pregnancies, transabdominal fetal reduction by needle guide for fetal or maternal indication was shown to be safe, with good outcomes for the remaining co-twin. Results were best when the procedure was performed before 14 weeks.

Parental information about the option to apply for pregnancy termination after the detection of a congenital abnormality and factors influencing parental decision-making: a cohort study.

BACKGROUND: The detection of an abnormality during prenatal screening implies that the parents are informed about possible treatment and management of the pregnancy, birth, and postnatal course. This information should enable the parents to make decisions regarding the pregnancy, especially in cases where termination of pregnancy may be an option. The objectives of this study were to investigate how often doctors informed parents about pregnancy termination when the fetus had an anomaly and which demographic factors were related to parental decision-making. METHODS: This was a retrospective cohort study with prospectively collected data of fetuses diagnosed with an abnormality during prenatal screening between 2014 and 2016 in Denmark. We categorized the abnormalities into five long-term prognosis groups and analyzed their association with the doctor provided information about termination. We tested the association between demographic variables and parental decisions using univariate and multivariate statistical analyses. RESULTS: Three hundred and twenty fetuses were diagnosed with an abnormality. In 67% of these cases, the parents were informed about termination. All parents whose fetus had a lethal prognosis were informed about termination. By comparison, the parents of 98% of fetuses with genetic disorders, 96% of fetuses with poor prognosis, 69% of fetuses with uncertain prognosis, and 12% of fetuses with good prognosis were informed about termination. Of these parents, 92% chose to terminate. A lethal long-term prognosis was the only factor related to parental decision to terminate a pregnancy. CONCLUSIONS: Doctors mainly informed parents about the option of pregnancy termination for conditions with a poor or lethal long-term prognosis or for genetic disorders. Only conditions with a lethal prognosis were significantly related to the parental decision to terminate the pregnancy.

First trimester serum matrix metalloproteinase-7 is a poor predictor of late-onset preeclampsia.

OBJECTIVES: This study aims to evaluate matrix metalloproteinase-7 as a first trimester biomarker for late-onset preeclampsia, both alone and in combination with mean arterial pressure, uterine artery pulsatility index, and maternal characteristics. STUDY DESIGN: We conducted a nested case-control study from a prospective cohort consisting of 416 pregnant women who attended a routine first trimester scan. Baseline variables were obtained at inclusion and analysed subsequently to formation of case and control groups. The study was designed to detect a mean difference of > 15% in matrix metalloproteinase-7 concentrations between groups with a statistical power of 80%. MAIN OUTCOME MEASURES: The primary outcome was preeclampsia with delivery after 34 weeks of pregnancy. RESULTS: The median matrix metalloproteinase-7 concentration in cases of late-onset preeclampsia (n = 27) was marginally lower compared to normotensive controls but this difference was not statistically significant. Matrix metalloproteinase-7 predicted 14.8% of cases at a 10% false-positive rate. Addition of matrix metalloproteinase-7 to any combination of variables did not significantly improve their performance. CONCLUSIONS: Matrix metalloproteinase-7 is not a useful biomarker for late-onset preeclampsia, neither alone nor in combination with mean arterial pressure, uterine artery pulsatility index, or maternal characteristics.

Neonatal complications and neurophysiological development in twins - a long-term follow-up study.

OBJECTIVES: To investigate the association between neonatal complications and neurophysiological development in twins at 18 and 48-60 months of age. METHODS: This was a secondary analysis of 841 Danish mono- and dichorionic diamniotic twins from a randomized controlled trial (PREDICT study), which included an assessment of the twin's neurophysiological development using the Ages and Stages Questionnaire (ASQ) that had been filled out by the parents at 18 and 48 or 60 months. The correlation within twin pairs was accounted for by the method of generalized estimating equation. Models were adjusted for maternal educational score and gestational age at delivery. RESULTS: ASQ data were available for 823 children at 18 months and 425 children at 48 or 60 months. Low maternal educational score and preterm delivery <34 weeks were associated with a lower ASQ score at 48-60 months (-15.4 points (95%CI -26.4; -4.5) and -13.2 points (95%CI -23.8; -2.5), respectively). Neonatal sepsis and a compound of intraventricular hemorrhage, retinopathy of prematurity and necrotizing enterocolitis (IVH/ROP/NEC) were associated with lower ASQ score at 18 months (-15.3 points (95%CI -28.1; -2.5) and -30.8 points (95%CI -59.5; -2.1), respectively). Children with IVH/ROP/NEC had a lower ASQ score at 48-60 months (-34.2 points (95%CI -67.9; -0.6)). The associations were not specific to only one ASQ domain. CONCLUSION: Several neonatal complications are associated with poorer neurophysiological development in twins during childhood, even after adjustment for gestational age at delivery.

Decision Threshold for Kryptor sFlt-1/PlGF Ratio in Women With Suspected Preeclampsia: Retrospective Study in a Routine Clinical Setting.

Background The objective was to evaluate predictive performance and optimal decision threshold of the Kryptor soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio when implemented for routine management of women presenting with symptoms of preeclampsia. Methods and Results Observational retrospective study of a cohort of 501 women with suspected preeclampsia after 20 weeks of gestation. Women referred to maternity ward for observation of preeclampsia had an sFlt-1/PlGF ratio test included in routine diagnostic workup. Maternal and offspring characteristic data included maternal risk factors, outcomes, delivery mode, and indication for suspected preeclampsia. Biochemical measurements to determine sFlt-1/PlGF ratio were performed using the BRAHMS/Kryptor sFlt-1/PlGF ratio immunoassays. Results were analyzed by area under receiver-operating characteristic curve. Preeclampsia occurred in 150 of 501 (30%) of symptomatic women with an sFlt-1/PlGF ratio determined before the time of diagnosis. Area under receiver-operating characteristic curve for diagnosis of early-onset preeclampsia within 1 and 4 weeks was 0.98 (95% CI, 0.96-1.00) and 0.95 (95% CI, 0.92-0.98), respectively. For late-onset preeclampsia, predictive performance within 1 and 4 weeks was lower: 0.90 (95% CI, 0.85-0.94) and 0.85 (95% CI, 0.80-0.90), respectively. The optimal single sFlt-1/PlGF ratio threshold for all preeclampsia and late-onset preeclampsia within 1 and 4 weeks was 66. The negative and positive predictive values for ruling out and ruling in developing preeclampsia within 1 week were 96% and 70%, respectively. Conclusions The Kryptor sFlt-1/PlGF ratio is a useful clinical tool ruling out and in preeclampsia within 1 week. Prediction within 4 weeks is superior for early-onset preeclampsia. A single decision threshold of 66 is indicated for use in clinical routine.

Epileptic encephalopathy caused by ARV1 deficiency: Refinement of the genotype-phenotype spectrum and functional impact on GPI-anchored proteins.

Early infantile epileptic encephalopathy 38 (EIEE38, MIM #617020) is caused by biallelic variants in ARV1, encoding a transmembrane protein of the endoplasmic reticulum with a pivotal role in glycosylphosphatidylinositol (GPI) biosynthesis. We ascertained seven new patients from six unrelated families harboring biallelic variants in ARV1, including five novel variants. Affected individuals showed psychomotor delay, hypotonia, early onset refractory seizures followed by regression and specific neuroimaging features. Flow cytometric analysis on patient fibroblasts showed a decrease in GPI-anchored proteins on the cell surface, supporting a lower residual activity of the mutant ARV1 as compared to the wildtype. A rescue assay through the transduction of lentivirus expressing wild type ARV1 cDNA effectively rescued these alterations. This study expands the clinical and molecular spectrum of the ARV1-related encephalopathy, confirming the essential role of ARV1 in GPI biosynthesis and brain function.

Reasons for non-participation in malformation scans in Denmark: a cohort study.

BACKGROUND: The aim of the study was to estimate the proportion of women giving birth in two hospitals in the Region of Southern Denmark who did not attend the malformation scan and to elucidate the reasons for not participating. METHODS: In this register-based descriptive study, we used patient administration systems to identify women who had given birth at two Danish hospitals between March 2013 and January 2015. We then linked this information with the hospital database for fetal medicine (Astraia) to identify women who did not attend the malformation scan at week 18-20. We reviewed the medical records of these women to validate the data and to identify the reason for non-participation. RESULTS: Of 7690 births, 153 (2%) women did not attend the malformation scan. The main reason for non-participation was a passive deselection (81%). Most of these women were not present in Denmark at the time of the malformation scan (61%) and few women declined (8%). CONCLUSIONS: Less than 2% of a birth cohort in two major hospitals in Denmark did not attend the free offer of a malformation scan. Most of these women (81%) did not actively decide against the malformation scan. Very few (0.2%) declined the malformation scan. Non-attendance is not always due to an active decision made by the pregnant woman.

Short- and long-term perinatal outcome in twin pregnancies affected by weight discordance.

INTRODUCTION: The objective was to investigate the association between chorionicity-specific intertwin birthweight discordance and adverse outcomes including long-term follow up at 6, 18, and 48-60 months after term via Ages and Stages Questionnaire. MATERIAL AND METHODS: In this secondary analysis of a cohort study (Oldenburg et al., n = 1688) and a randomized controlled trial (PREDICT study, n = 1045) twin pairs were divided into three groups according to chorionicity-specific birthweight discordance: <75th percentile, 75th-90th percentile and >90th percentile. Information on infant mortality, admittance to neonatal intensive care units, and gestational age at delivery was available for all pairs. Detailed neonatal outcomes were available for 656 pairs from PREDICT, of which 567 pairs had at least one Ages and Stages Questionnair follow-up. Logistic regression models were used for dichotomous outcomes. Ages and Stages Questionnair scores were compared using the method of generalized estimating equation to account for the correlation within twins. RESULTS: The 75th and 90th percentiles for birthweight discordance were 14.8 and 21.4% for monochorionic and 16.0 and 23.8% for dichorionic twins. After adjustment for small for gestational age and gender, birthweight discordance >75th and >90th percentile was associated with induced delivery <34 weeks [odds ratio 1.71 (95% confidence interval 1.11-2.65) and odds ratio 2.83 (95% confidence interval 1.73-4.64), respectively]. Discordance >75th-percentile was associated with an increased risk of infant mortality after 28 days [odds ratio 4.69 (95% confidence interval 1.07-20.45)] but not with major neonatal complications or with low mean Ages and Stages Questionnair scores at 6, 18, and 48-60 months after term. CONCLUSION: Chorionicity-specific intertwin birthweight discordance is a risk factor for induced preterm delivery and infant mortality, but not for lower scores for neurophysiological development at 6, 18, and 48-60 months.

Prospective population-based cohort study of maternal obesity as a source of error in gestational age estimation at 11-14 weeks.

INTRODUCTION: An impact of maternal obesity on ultrasound dating of pregnancy at 11-14 gestational weeks is possible and was investigated. MATERIAL AND METHODS: A prospective cohort study based on the Danish national population during a 4-year period in which we entered all mothers with singleton pregnancies who had a known last menstrual period (LMP), a recorded booking of body mass index (BMI), and a late first trimester ultrasound dating scan using crown-rump-length measurement (gestational age 11+0 -13+6  weeks). Almost all scans were performed transabdominally. Transvaginal ultrasound was only performed in the case of limited visibility by transabdominal scanning. Differences between LMP and ultrasound estimated date of delivery (EDD) were stratified by BMI classes. Odds ratios (ORs) were calculated and adjusted for maternal age, parity and smoking. RESULTS: In total, 187 486 women were analyzed: 21.8% were overweight and 12.3% obese. Ultrasound EDD was ≥7 days later than by LMP in 5.8% of normal-weight women, 7.3% of obese women, and 10.0% of women with morbid obesity. Compared with normal BMI (18.5-24.9), the OR for postponing EDD increased with increasing BMI; BMI 25-29.9 [OR 0.97, 95% confidence interval (CI) 0.93-1.02], BMI 30-34.9 (OR 1.14, 95% CI 1.07-1.23), BMI 35-39.9 (OR 1.28, 95% CI 1.15-1.42), and BMI 40+ (OR 1.73, 95% CI 1.50-1.98). Lean pregnant women (BMI <18.5) also had a higher chance of having EDD postponed 7 days or more (OR 1.11, 95% CI 1.01-1.22). CONCLUSION: Rising maternal BMI appears to be associated with postponement of ultrasound EDD.

Kidney anomalies diagnosed by prenatal ultrasound screening and associated non-urinary malformations: a nationwide prevalence study.

OBJECTIVES: To estimate the prevalence of kidney anomalies at second trimester ultrasound screening, and furthermore, to investigate pregnancy outcomes and the pattern of additional malformations. METHODS: We previously identified all women attending second-trimester ultrasound scans in Denmark between 1 January 2007 and 31 December 2012. Using the Astraia databases and the Danish National Patient Registry, we identified all fetuses with kidney anomalies diagnosed prenatally in these women. In addition to the prevalence of fetuses with kidney anomalies, we estimated the live birth prevalence ratio of non-urinary malformations, comparing the prevalences in infants with and without prenatally diagnosed kidney anomalies. RESULTS: The prevalence of fetuses with kidney anomalies at second trimester scans was 11.4 per 10 000 fetuses. Among the 412 fetuses identified, 127 pregnancies were terminated. For live born children the prevalence of additional non-urinary malformations was four times higher (95% CI: 3-5) compared with the prevalence among children without prenatal kidney anomalies. Digestive system anomalies were particularly prevalent. CONCLUSION: These population-based data provide additional insight into the course of pregnancy and birth outcomes following prenatal diagnoses of kidney anomalies. © 2016 John Wiley & Sons, Ltd.

The Danish Fetal Medicine Database: establishment, organization and quality assessment of the first trimester screening program for trisomy 21 in Denmark 2008-2012.

OBJECTIVE: 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.

[Array-comparative genomic hybridization is a new and promising method for prenatal chromosomal diagnosis]. / Array-komparativ genomisk hybridisering er en ny og lovende metode til prænatal kromosomundersøgelse .

Array-comparative genomic hybridization (array-CGH) is a very sensitive method for identifying chromosomal imbalances and is now used on a clinical basis for prenatal diagnosis. This article reviews the advantages and disadvantages of the method, the ethical considerations and the current recommendations for prenatal use in Denmark according to a new national guideline from The Danish Society of Foetal Medicine and the Danish Society of Medical Genetics.

MRI, PET/CT and ultrasound in the preoperative staging of endometrial cancer - a multicenter prospective comparative study.

OBJECTIVES: The aim of this prospective multicenter study was to evaluate and compare the diagnostic performance of PET/CT, MRI and transvaginal two-dimensional ultrasound (2DUS) in the preoperative assessment of endometrial cancer (EC). METHODS: 318 consecutive women with EC were included when referred to three Danish tertiary gynecological centers for surgical treatment. Preoperatively they were PET/CT-, MRI-, and 2DUS scanned. The imaging results were compared to the final pathological findings. This study was approved by the National Committee on Health Research Ethics. RESULTS: For predicting myometrial invasion, we found sensitivity, specificity, PPV, NPV, and accuracy for PET/CT to be 93%, 49%, 41%, 95% and 61%, for MRI to be 87%, 57%, 44%, 92%, and 66% and for 2DUS to be 71%, 72%, 51%, 86% and 72%. For predicting cervical invasion, the values were 43%, 94%, 69%, 85% and 83%, respectively, for PET/CT, 33%, 95%, 60%, 85%, and 82%, respectively, for MRI, and 29%, 92%, 48%, 82% and 78% for 2DUS. Finally, for lymph node metastases, the values were 74%, 93%, 59%, 96%, and 91% for PET/CT and 59%, 93%, 40%, 97% and 90% for MRI. When comparing the diagnostic performance we found PET/CT, MRI and 2DUS to be comparable in predicting myometrial invasion. For cervical invasion and lymph node metastases, however, PET/CT was the best. CONCLUSIONS: None of the modalities can yet replace surgical staging. However, they all contributed to important knowledge and were, furthermore, able to upstage low-risk patients who would not have been recommended lymph node resection based on histology and grade alone.

Cytokines and the risk of preterm delivery in twin pregnancies.

OBJECTIVE: To estimate the association between cytokine levels in twin pregnancies and risk of spontaneous preterm delivery, including the effect of progesterone treatment. METHODS: This secondary analysis of a randomized placebo-controlled trial investigating the effect of progesterone treatment on preterm delivery in twin pregnancies included 523 women with available dried blood spot samples collected before treatment with progesterone (n=258) or placebo (n=265) and after 4-8 weeks of treatment. Samples were analyzed for cytokines using a sandwich immunoassay. Cytokine levels in spontaneous preterm delivery at 34-37 weeks of gestation and spontaneous preterm delivery before 34 weeks of gestation were compared with delivery at 37 weeks of gestation or more for placebo-treated women. The association between interleukin (IL)-8 and risk of spontaneous preterm delivery before 34 weeks of gestation was estimated further, including comparison according to treatment. Statistical analyses included Kruskal-Wallis test, Mann-Whitney U test, linear regression, and Cox regression analysis. RESULTS: We found a statistically significant association between IL-8 and spontaneous preterm delivery. At 23-33 weeks of gestation, the median IL-8 level was 52 pg/mL (interquartile range 39-71, range 19-1,061) for term deliveries compared with 65 pg/mL (interquartile range 43-88, range 14-584) for spontaneous preterm delivery at 34-37 weeks of gestation and 75 pg/mL (interquartile range 57-102, range 22-1,715) for spontaneous preterm delivery before 34 weeks of gestation (P<.001). Risk of spontaneous preterm delivery was associated with a large weekly increase in IL-8 (hazard ratio 2.0, 95% confidence interval [CI] 1.2-3.3). There was no effect of progesterone treatment on IL-8 levels. Levels of IL-8 at 18-24 weeks of gestation were associated with a cervix less than 30 mm (odds ratio 1.8, 95% CI 1.2-2.7). CONCLUSION: Risk of spontaneous preterm delivery before 34 weeks of gestation is increased in women with high IL-8 levels. Progesterone treatment does not affect IL-8 levels.