[Show abstract][Hide abstract] ABSTRACT: Epigenetic markers for cell free fetal DNA in the maternal blood circulation are highly interesting in the field of non-invasive prenatal testing since such markers will offer a possibility to quantify the amount of fetal DNA derived from different chromosomes in a maternal blood sample. The aim of the present study was to define new fetal specific epigenetic markers present in placental DNA that can be utilized in non-invasive prenatal diagnosis. We have conducted a high-resolution methylation specific beadchip microarray study assessing more than 450.000 CpG sites. We have analyzed the DNA methylation profiles of 10 maternal blood samples and compared them to 12 1st trimesters chorionic samples from normal placentas, identifying a number of CpG sites that are differentially methylated in maternal blood cells compared to chorionic tissue. To strengthen the utility of these differentially methylated CpG sites to be used with methyl-sensitive restriction enzymes (MSRE) in PCR-based NIPD, we furthermore refined the list of selected sites, containing a restriction sites for one of 16 different methylation-sensitive restriction enzymes. We present a list of markers on chromosomes 13, 18 and 21 with a potential for aneuploidy testing as well as a list of markers for regions harboring sub-microscopic deletion- or duplication syndromes.
[Show abstract][Hide abstract] ABSTRACT: To describe establishment and organisation of the Danish Fetal Medicine Database and to report national results of first trimester combined screening for trisomy 21 in the five year period 2008-2012.
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.
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 2008-2012 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 82-90% 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. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
No preview · Article · Jan 2015 · Acta Obstetricia Et Gynecologica Scandinavica
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: To assess the relationship between the finding of fetal femur
diaphysis length (FL) below the 5(th) percentile at the second-trimester scan and
pregnancy outcome, in a population in which more than 90% of women attend
first-trimester screening. METHODS: This was a retrospective study of all Danish
singleton pregnancies with a 17-22-week anomaly scan between 1 January 2008 and
30 June 2011. Information on FL and gestational age (GA) at anomaly scan, on
birth weight and GA at delivery and on chromosomal abnormalities was obtained
from the Danish Fetal Medicine Database. RESULTS: Short FL was identified in 2718
(1.8%) of 147,766 fetuses and was present in 11 (16.2%) of the 68 fetuses
affected by trisomy 21 (positive likelihood ratio (LR+) 8.8 (95% CI, 5.1-15.2)).
Trisomy 13/18 and unbalanced autosomal structural abnormalities were also
associated with a short FL in three (12.0%, LR+ 6.5 (95% CI, 2.3-18.9)) and eight
(32.0%, LR+ 17.4 (95% CI, 9.8-30.9)) of the cases, respectively. The risk of a
fetus having trisomy 21, trisomy 18, trisomy 13 or an unbalanced autosomal
structural abnormality was 1 : 123 (95% CI, 79-192), given a short FL.
Pregnancies with a fetus with short FL were more often affected by early preterm
delivery (before 34 weeks) (5.6%; odds ratio (OR) = 4.2 (95% CI, 3.5-4.9)) and
small-for-gestational-age (SGA) infants (13.9%; OR = 4.3 (95% CI, 3.8-4.8)).
CONCLUSION: Short FL at the second-trimester anomaly scan is associated with a
significantly higher relative risk of chromosomal abnormalities, and a
substantially higher absolute risk for SGA and early preterm delivery.
No preview · Article · Aug 2014 · Ultrasound in Obstetrics and Gynecology
[Show abstract][Hide abstract] ABSTRACT: Different fetal cell types have been found in the maternal blood during pregnancy in the past, but fetal cells are scarce, and the proportions of the different cell types are unclear. The objective of the present study was to identify specific fetal cell markers from fetal cells found in the maternal blood circulation at the end of the first trimester.
Twenty-three fetal cells were isolated from maternal blood by removing the red blood cells by lysis or combining this with removal of large proportions of maternal white blood cells by magnetic-activated cell sorting. Fetal cells identified by XY fluorescence in situ hybridization and confirmed by reverse-color fluorescence in situ hybridization were shot off microscope slides by laser capture microdissection. The expression pattern of a subset of expressed genes was compared between fetal cells and maternal blood cells using stem cell microarray analysis.
Twenty-eight genes were identified as fetal cell marker candidates.
Of the 28 fetal marker candidate genes, five coded for proteins, which are located on the outer surface of the cell membrane and not expressed in blood. The protein product of these five genes, MMP14, MCAM, KCNQ4, CLDN6, and F3, may be used as markers for fetal cell enrichment.
No preview · Article · Aug 2012 · Prenatal Diagnosis
[Show abstract][Hide abstract] ABSTRACT: Cervical collagen concentration decreases during pregnancy. The increased risk of preterm birth after a short interpregnancy interval may be explained by an incomplete remodeling of the cervix. The objective of this study was to describe the changes in cervical collagen concentration over 15 months after delivery.
The collagen concentrations were determined in cervical biopsy specimens that were obtained from 15 women at 3, 6, 9, 12, and 15 months after delivery.
The mean cervical collagen concentrations were 50%, 59%, 63%, 65%, and 65% of dry weight (SD, 4.2-6.5). This increase was statistically significant until month 9, but not between months 9 and 12.
Low collagen concentrations in the uterine cervix may contribute to the association between a short interpregnancy interval and preterm birth.
Preview · Article · Jul 2011 · American journal of obstetrics and gynecology
[Show abstract][Hide abstract] ABSTRACT: In 2004 The Danish National Board of Health introduced a new guideline regarding prenatal screening. All pregnant women are now offered a Down's syndrome risk assessment. The new guideline has had an impact on the number of invasive early prenatal procedures. The number of procedures fell by 50% from 2000 to 2006. 90% of the foetuses with Down's syndrome are detected prenatally. Denmark is one of the first countries in the world in which risk assessment for Down's syndrome has been successfully implemented at a national level.
No preview · Article · Jun 2010 · Ugeskrift for laeger