Carolien Zwiers

Hemolytc disease of the fetus and the newborn

On 12 March 2019 Carolien Zwiers defended her PhD thesis 'Hemolytc disease of the fetus and the newborn' at Leiden University

Promotores: Prof D Oepkes MD PhD and Prof M de Haas MD PhD
Co-promotor: IL van Kamp MD PhD 

Venue: Academy building, Leiden


Hemolytic disease of the fetus and newborn is a serious condition that, if remained untreated, may result in fetal death. After birth, if too late detected, it may result in neurological damage. In the past decades, much has changed in the prevention, screening, monitoring and (intrauterine) treatment of HDFN.

The aim of this thesis was to review and critically analyze current management for this disease and to assess factors that contributed to reaching this point, in order to provide specific tools to further improve outcome.

It was observed that the routine RhIg (anti-D prophylaxis) also prevents the development of other type of RBC alloantibody specificities. This study was performed with the data of the nation wide cohort study OPZI at Sanquin. As part of the research, data was collected from RhD-negative women who developed anti-D antibodies (the OPZI2.0 study). With the data set it was assessed that based on the time in pregnancy of anti-D detection, the severity of disease in the first immunized pregnancy and the laboratory test result of the antibody-dependent cellular cytotoxicity test, the risk on increase of disease severity in subsequent pregnancies can be assessed.

An international study showed that early treatment with intravenous immunoglobulin (IVIg) treatment in pregnancy was associated with less severe fetal disease and a later moment of intra uterine transfusions. These three studies were performed in close collaboration between  the Department of Obstetrics, LUMC and the Center of Clinical Transfusion Research, Sanquin Research, Leiden.

Finally, with data sets collected at the LUMC, it was shown that outcome data of pregnancies complicated by even the severest forms of HDFN, at least in a setting of centralized screening and laboratory testing and specialized tertiary care centers, are considered excellent, and generally regarded to have reached an ‘as good as it gets’ level.