Data collection and outcome definitions
Relevant clinical data from all previous non-immunized and immunized pregnancies were collected in the OPZI 2.0 database. Furthermore, we obtained treatment details to assess the severity of HDFN of all pregnancies with RhD antibodies and RhD-positive foetuses . From Sanquin Diagnostic Services, laboratory data were retrieved (including antibody titers, ADCC results and the presence of additional antibodies).
In the current study, ‘first immunized pregnancy ’ is defined as the first pregnancy with RhD antibodies and a RhD-positive child. ‘Subsequent pregnancy’ is defined as the second pregnancy with RhD antibodies and a RhD-positive child.
Our main outcome was disease severity, which was categorized as follows:
  1. No HDFN: no antenatal or postnatal treatment
  2. Mild HDFN: non-intensive phototherapy (≤2 lamps), or only one day intensive phototherapy (>2 lamps), with or without a red blood cell transfusion during the first month after birth
  3. Moderate HDFN: intensive phototherapy (>2 lamps) for more than one day or neonatal exchange transfusion (in the Netherlands neonatal exchange transfusion has been gradually replaced by intensive phototherapy)
  4. Severe HDFN: intrauterine transfusion or HDFN-related death.
In case of missing data on disease severity, patients were assigned to a disease category based on the other, non-missing disease parameters (laboratory results, phototherapy duration and intensity, etc.). In twin pregnancy, disease severity was categorized according to the most severely affected child.