Eva Pajkrt

Screening for fetal trisomies by maternal age and fetal nuchal translucency thickness at 10 to 14 weeks of gestation

Objective To evaluate screening for chromosomal defects by a combination of fetal nuchal translucency thickness and maternal age.

Accuracy of circulating placental growth factor, vascular endothelial growth factor, soluble fms‐like tyrosine kinase 1 and soluble endoglin in the prediction of pre‐eclampsia: a systematic review and meta‐analysis

Please cite this paper as: Kleinrouweler C, Wiegerinck M, Ris‐Stalpers C, Bossuyt P, van der Post J, von Dadelszen P, Mol B, Pajkrt E, for the EBM CONNECT Collaboration. Accuracy of circulating placental growth factor, vascular endothelial growth factor, soluble fms‐like tyrosine kinase 1 and soluble endoglin in the prediction of pre‐eclampsia: a systematic review and meta‐analysis. BJOG 2012;119:778–787.

Co-variables in first trimester maternal serum screening

The objective of this study was to determined the influence of maternal weight, maternal smoking habits, gravidity, parity and fetal gender on the level of maternal serum marker used in first trimester screening for Down syndrome. A total of 2449 singleton unaffected pregnancies from two centres were studied. Maternal serum free β‐human chorionic gonadotrophin (hCG) and α‐fetoprotein (AFP) concentrations had been measured in all pregnancies, and pregnancy associated plasma protein (PAPP)‐A levels had been measured in 924. All results were expressed as multiples of the gestation specific median (MoM) values after regression, using each centres own medians. Information on maternal weight was available in 2259 pregnancies, on self‐reported current cigarette smoking in 1364 (of whom 117 (8.6%) were smokers), on gravidity in 1371, parity in 1303 and fetal gender in 253. All three markers showed a statistically significant negative association with maternal weight (p<0.0005) and in the subsequent analyses MoM values were weight adjusted using standard methods. The median PAPP‐A level in smokers was 0.81 MoM, a significant reduction (p<0.005); free β‐hCG was also reduced (median 0.89 MoM) but not significantly (p=0.17), and AFP was unaltered. The median AFP level in primagravidas was highly significantly greater than that in gravid women (p<0.0005). In PAPP‐A the reverse effect was seen but it did not reach statistical significance (p=0.15) and there was no effect for free β‐hCG. Results of a similar magnitude and direction were found for parity. The median level of free β‐hCG was higher (p=0.0005), and the median AFP lower in female pregnancies. Maternal weight and, for PAPP‐A, maternal smoking are important first trimester screening co‐variables. Gravidity, parity and fetal gender also seem to influence one or more first trimester markers. Copyright

Early pregnancy screening for fetal aneuploidy with serum markers and nuchal translucency.

We determined the aneuploidy detection rate achievable by early pregnancy screening with pregnancy associated plasma protein (PAPP)‐A, free β human chorionic gonadotrophin (hCG) and ultrasound nuchal translucency (NT) measurement. Women having prenatal diagnosis were scanned, and a blood sample was taken and stored. Stored samples were tested and a total of 37 were found to have Down syndrome, 8 to have Edwards syndrome and 255 were controls. Results were expressed in multiples of the gestation‐specific median (MOM) value in the controls after regression and, for the serum markers, maternal weight adjustment. In Down syndrome the medians were for PAPP‐A 0.63 MOM (95 per cent confidence interval (CI) 0.45–0.87); free β‐hCG 1.88 MOM (1.33–2.66); and NT 2.34 MOM (1.70–3.22). Using these parameters the expected detection rate for a 5 per cent false‐positive rate for different marker combinations were: 55.3 per cent for PAPP‐A and free β‐hCG; 68.4 per cent for NT alone; and 84.6 per cent for PAPP‐A, free β‐hCG and NT. The median values for Edwards syndrome were: 0.17 MOM for PAPP‐A; 0.18 MOM for free β‐hCG; and 2.64 MOM for NT. Early pregnancy screening with the combined measurement of maternal serum PAPP‐A and free β‐hCG and fetal nuchal translucency could achieve a high Down syndrome detection rate. Copyright

New aids for the non‐invasive prenatal diagnosis of achondroplasia: dysmorphic features, charts of fetal size and molecular confirmation using cell‐free fetal DNA in maternal plasma

To improve the prenatal diagnosis of achondroplasia by constructing charts of fetal size, defining frequency of sonographic features and exploring the role of non‐invasive molecular diagnosis based on cell‐free fetal deoxyribonucleic acid (DNA) in maternal plasma.

Prenatal detection of congenital heart disease—results of a national screening programme

Congenital heart disease (CHD) is the most common congenital malformation and causes major morbidity and mortality. Prenatal detection improves the neonatal condition before surgery, resulting in less morbidity and mortality. In the Netherlands a national prenatal screening programme was introduced in 2007. This study evaluates the effects of this screening programme.

Attitudes of pregnant women and male partners towards non-invasive prenatal testing and widening the scope of prenatal screening

Non-invasive prenatal testing (NIPT) and its potential to test for multiple disorders has received much attention. This study explores attitudes of women and men towards NIPT, and their views on widening the scope of prenatal testing in a country with a low uptake of prenatal screening (The Netherlands). Five focus groups with low-risk pregnant women (n=28), three focus groups with men (n=19) and 13 interviews with high- and low-risk pregnant women were conducted. Participants felt that current prenatal screening has great disadvantages such as uncertain results and risk of miscarriage from follow-up diagnostics. Characteristics of NIPT (accurate, safe and early testing) could therefore diminish these disadvantages of prenatal screening and help lower the barrier for participation. This suggests that NIPT might allow couples to decide about prenatal testing based mostly on their will to test or not, rather than largely based on fear of miscarriage risk or the uncertainty of results. The lower barrier for participation was also seen as a downside that could lead to uncritical use or pressure to test. Widening the scope of prenatal testing was seen as beneficial for severe disorders, although it was perceived difficult to determine where to draw the line. Participants argued that there should be a limit to the scope of NIPT, avoiding testing for minor abnormalities. The findings suggest that NIPT could enable more meaningful decision-making for prenatal screening. However, to ensure voluntary participation, especially when testing for multiple disorders, safeguards on the basis of informed decision-making will be of utmost importance.

Effect of study design on the association between nuchal translucency measurement and Down syndrome

OBJECTIVE To evaluate the effect of verification bias on the accuracy of first-trimester nuchal translucency measurement for Down syndrome detection. METHODS We used MEDLINE and EMBASE to identify all papers relating the results of nuchal translucency measurement to fetal karyotype. The detected studies were scored for verification bias. Fifteen studies without and ten with verification bias were included. RESULTS Sensitivity and specificity were calculated for each study. For studies with verification bias, adjusted estimates of the sensitivity were calculated assuming a fetal loss rate for Down syndrome pregnancies of 48%. The sample size weighted sensitivity was 55% in studies without and 77% in those with verification bias, for specificities of 96% and 97%, respectively. After adjustment for verification bias, the sample size weighted sensitivity changed from 77% to 63%. CONCLUSION Studies with verification bias reported higher sensitivities, but also slightly higher specificities of nuchal translucency measurement than studies without verification bias. The difference in sensitivity is greater than could be explained by verification bias. We postulate that the experience of the sonographist might be an explanation for the differences.

Low uptake of the combined test in the Netherlands : which factors contribute?

The aim of this study was to evaluate which of the following factors affect the uptake of the combined test (CT) in the Netherlands: womens socio‐demographic background, attitude towards Down syndrome, attitude towards termination of pregnancy, counseling process, reimbursement policy, and knowledge on the aim of the CT.

Trial by Dutch Laboratories for Evaluation of Non-Invasive Prenatal Testing. Part I - Clinical Impact

To evaluate the clinical impact of nationwide implementation of genome‐wide non‐invasive prenatal testing (NIPT) in pregnancies at increased risk for fetal trisomies 21, 18 and 13 (TRIDENT study).