C. K. Ekelund

Impact of a new national screening policy for Down's syndrome in Denmark: population based cohort study

Objectives To evaluate the impact of a screening strategy in the first trimester, introduced in Denmark during 2004-6, on the number of infants born with Down’s syndrome and the number of chorionic villus samplings and amniocenteses, and to determine detection and false positive rates in the screened population in 2005 and 2006. Design Population based cohort study. Setting 19 Danish departments of gynaecology and obstetrics and a central cytogenetic registry 2000-7. Participants 65 000 pregnancies per year. Main outcome measures The primary outcomes measured were number of fetuses and newborn infants with Down’s syndrome diagnosed prenatally and postnatally and number of chorionic villus samplings and amniocenteses carried out. Secondary outcomes measured were number of women screened in 2005 and 2006, screen positive rate, and information on screening in 2005 and 2006 for infants with a postnatal diagnosis of Down’s syndrome. Results The number of infants born with Down’s syndrome decreased from 55-65 per year during 2000-4 to 31 in 2005 and 32 in 2006. The total number of chorionic villus samplings and amniocenteses carried out decreased from 7524 in 2000 to 3510 in 2006. The detection rate in the screened population in 2005 was 86% (95% confidence interval 79% to 92%) and in 2006 was 93% (87% to 97%). The corresponding false positive rates were 3.9% (3.7% to 4.1%) and 3.3% (3.1% to 3.4%). Conclusion The introduction of a combined risk assessment during the first trimester at a national level in Denmark halved the number of infants born with Down’s syndrome. The strategy also resulted in a sharp decline in the number of chorionic villus samplings and amniocenteses carried out, even before full implementation of the policy.

Effects of blood sample handling procedures on measurable inflammatory markers in plasma, serum and dried blood spot samples

The interests in monitoring inflammation by immunoassay determination of blood inflammatory markers call for information on the stability of these markers in relation to the handling of blood samples. The increasing use of stored biobank samples for such ventures that may have been collected and stored for other purposes, justifies the study hereof. Blood samples were stored for 0, 4, 24, and 48 h at 4 degrees C, room temperature (RT), and at 35 degrees C, respectively, before they were separated into serum or plasma and frozen. Dried blood spot samples (DBSS) were stored for 0, 1, 2, 3, 7, and 30 days at the same temperatures. 27 inflammatory markers in serum and plasma and 25 markers in DBSS were measured by a previously validated multiplex sandwich immunoassay using Luminex xMAP technology. The measurable concentrations of several cytokines in serum and plasma were significantly increased when blood samples were stored for a period of time before the centrifugation, for certain cytokines more than 1000 fold compared to serum and plasma isolated and frozen immediately after venepuncture. The concentrations in serum generally increased more than in plasma. The measurable concentrations of inflammatory markers also changed in DBSS stored under various conditions compared to controls frozen immediately after preparation, but to a much lesser degree than in plasma or serum. The study demonstrates that trustworthy measurement of several inflammatory markers relies on handling of whole blood samples at low temperatures and rapid isolation of plasma and serum. Effects of different handling procedures for all markers studied are given. DBSS proved to be a robust and convenient way to handle samples for immunoassay analysis of inflammatory markers in whole blood.

Potential diagnostic consequences of applying non-invasive prenatal testing: population-based study from a country with existing first-trimester screening

Targeted non‐invasive prenatal testing (NIPT) tests for trisomies 21, 18 and 13 and sex chromosome aneuploidies and could be an alternative to traditional karyotyping. The aim of this study was to determine the risk of missing other abnormal karyotypes of probable phenotypic significance by NIPT.

Risk of fetal loss associated with invasive testing following combined first‐trimester screening for Down syndrome: a national cohort of 147 987 singleton pregnancies

To assess prospectively the risk of fetal loss associated with chorionic villus sampling (CVS) and amniocentesis (AC) following combined first‐trimester screening (cFTS) for Down syndrome.

First-trimester screening for trisomy 21 in Denmark: implications for detection and birth rates of trisomy 18 and trisomy 13.

In Denmark a new national guideline for prenatal screening and diagnosis was issued in 2004 according to which all pregnant women should be offered a first‐trimester combined risk assessment for trisomy 21 (T21). The aim of this study was to investigate whether the new screening strategy for T21 has changed the gestational age at which trisomy 18 (T18) and trisomy 13 (T13) are diagnosed prenatally, and the number of infants born with T18 or T13.

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

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.

Prenatal detection of congenital heart disease in a low risk population undergoing first and second trimester screening

The prenatal detection rate of congenital heart disease (CHD) is low compared with other fetal malformations. Our aim was to evaluate the prenatal detection of CHD in Eastern Denmark.

Increased nuchal translucency, normal karyotype and infant development

To investigate whether chromosomally normal fetuses with a nuchal translucency (NT) ≥ 99th percentile (3.5 mm) in the first trimester have an increased risk of delayed development at 2 years of age.

Detection of triploidy at 11–14 weeks' gestation: a cohort study of 198 000 pregnant women

To assess the detection rate of triploidy at first‐trimester screening for trisomy 21 and evaluate outcome in triploid pregnancies.

Impact of type 1 diabetes and glycemic control on fetal aneuploidy biochemical markers

Objective. To determine the influence of type 1 diabetes mellitus (T1DM) on the first trimester serum markers of fetal aneuploidy; pregnancy‐associated plasma protein‐A (PAPP‐A) and free beta subunit of human chorionic gonadotropin (free β‐hCG) and to evaluate the influence of glycemic control on these parameters in the pregnant diabetic women. Design. Retrospective study. Setting. Data were extracted from electronic obstetric and laboratory databases at two Danish University Hospitals. Population. Based on 36 415 pregnancies without T1DM (non‐T1DM) and 331 pregnancies with T1DM; β‐hCG and PAPP‐A were obtained at 8+0 to 14+2 gestational weeks. Methods. Medians for PAPP‐A and free β‐hCG were generated and multiple of the normal gestation‐specific median (MoM) values were calculated for each separate pregnancy. After adjustment for maternal weight, ethnicity and smoking status, MoM values were compared across the T1DM and non‐T1DM groups, respectively. Additionally, the relationship between PAPP‐A MoM and HgbA1C was examined in 348 T1DM pregnancies by Spearmans rank correlation. Main outcome measures. Difference in biochemical marker levels between T1DM and non‐T1DM. Results. PAPP‐A was 0.86 MoM in T1DM pregnancies and 1.01 MoM in non‐T1DM pregnancies, p < 0.0001. Conversely, free β‐hCG was not altered in T1DM pregnancies (T1DM 0.99 MoM, non‐T1DM 0.98 MoM; p=0.14). There was a significant inverse correlation between HgbA1C and PAPP‐A (rho=−0.12, p=0.02). Conclusions. In T1DM pregnancies, PAPP‐A MoM values were lower than in non‐T1DM pregnancies. This suggests that correction should be considered in first trimester biochemical screening for fetal aneuploidy in T1DM women.