Thesis Florentine Thurik
On 8 December 2016 Florentine Thurik defended her thesis ‘Cell-free placental DNA beyond Down syndrome - Lessons learned from fetal RHD genotyping’ at the University of Amsterdam.
Promotors: prof CE van der Schoot MD PhD and prof A Franx MD PhD
Co-promotor: GCML Page-Christiaens PhD
The research for this thesis was conducted at the Dept of Experimental Immunohematology of Sanquin Research.
Summary
The presence of cell-free fetal DNA in maternal blood was first described in 1997 by Lo et al. These DNA fragments derive from the placenta and are therefore named cell-free placental DNA (cfpDNA) throughout the thesis.
The first section of the thesis (chapter 2-6) discusses health care around hemolytic disease and the newborn (HDFN) and fetal and neonatal alloimmune thrombocytopenia (FNAIT), and the use of cfpDNA for fetal RHD screening for HDFN prevention are analyzed. We conclude that fetal RHD screening is a reliable method to target anti-D immunoglobulin prophylaxis to solely women who are at risk for maternal anti-D alloimmunisation. Additionally, we show that vanishings twins and a history of bone marrow transplantation could be potential causes for false-positive fetal RHD screening results.
The second section of the thesis (chapters 7-9) focuses on the variation in cfpDNA levels and on associations between cfpDNA levels and placenta related adverse pregnancy outcomes (APOs). Associations with APOs such as preeclampsia and preterm birth are present when cfpDNA levels are measured in the third trimester, but absent when measured in the first trimester. No associations were found between first and third trimester cfpDNA levels. The results of section two combined suggest that the factors that influence cfpDNA levels in the first trimester differ from those in the third trimester.
Chapters
Chapter 1
General Introduction and scope of the thesis
SECTION I
Chapter 2
Haemolytic disease of the fetus and newborn.
Vox Sang 2015; 109(2):99-113.
Chapter 3
Noninvasive prenatal blood group and HPA-1a genotyping: the current European experience.
Transfusion 2013; 53(11 Suppl 2):2834-6.
Chapter 4
Sensitivity of foetal RHD screening for safe guidance of targeted anti-D immunoglobulin prophylaxis: a prospective cohort study of a nation-wide programme in the Netherlands.
Chapter 5
Analysis of false-positive results of fetal RHD typing in a national screening program reveals vanishing twins as potential cause for discrepancy.
Prenat Diagn 2015; 35(8):754-60.
Chapter 6
Fetal RHD genotyping after bone marrow transplantation.
Transfusion. 2016; 56(8):2122-6.
SECTION II
Chapter 7
Third trimester cell-free placental DNA levels, placental health and pregnancy outcome: a prospective observational cohort study.
Chapter 8
Absolute first trimester cell-free DNA levels and their associations with adverse pregnancy outcomes.
Chapter 9
No association between first and third trimester cell-free placental DNA levels in maternal blood.
Chapter 10
General Discussion
Chapter 11
Summary
Download
Download PhD thesis (university repository)