Long term follow-up after intrauterine transfusion

Intrauterine transfusions (IUT) are nowadays the mainstay for severe fetal
anemia. The main cause of fetal anemia is maternal red blood cell (RBC)
alloimmunization. Other frequent causes include Parvo B19 infection and
feto-maternal hemorrhage (FMH).
Pregnant women with Rh-D hemolytic disease of the fetus, receive a median of 3
(range 1-8) intrauterine transfusions. We found that 25% of these women develop
additional erythrocyte antibodies after IUT and that >70% of these females
possess multiple antibodies at delivery, which complicate transfusion treatment
and future pregnancies. Such high incidence of red cell immunization exceeds
the immunization rate of any poly-transfused patient group. The mechanism of
this high immunization rate is unknown. Several factors may contribute, such as
an altered immune state of pregnancy, the way and small volume of the
transfusion, the dual exposure to MHC-haplotype-shared fetal cells in
combination with random donors, prolonged donor cell survival and genetic
factors of recipient, child and donors. In particular, MHC-restriction more or
less efficiently presentation of RBC antigens may play a role. This study will
address several of the putative mechanisms associated with RBC (and HLA/HPA)
antibody formation with the aim to identify factors to predict the risk for
alloimmunization against particular RBC antigens. This can lead to a change in
transfusion policy, in particular future avoidance of certain mismatches for
transfusion thereby increasing transfusion safety. Moreover the study creates
the opportunity to determine factors leading to the persistence of antibodies
against fetal or transfusion antigens.
Although several studies have reported on the much improved short-term outcome
after IUTs, only few studies have focused on the long-term neurodevelopmental
outcome. Most follow-up studies show that despite the severity of fetal
hemolytic disease, developmental outcome for children treated with intrauterine
transfusions can be expected to be normal. The main limitation of these studies
is the small number of patients included. Moreover cognitive development and
quality of life assessment was not always included in the follow-up studies.
The second aim of this study is to determine the long-term neuromotor
development, cognitive development and psychosocial well-being in a large group
of children treated with IUT for fetal anemia.
In addition, the contact after 20 or more years offer the opportunity to
evaluate long-term health sequelae as chimeras has been associated with
autoimmune diseases in females.

Identify, in the heavily RBC alloimmunized population of females after HDN
treatment whether particular MHC class II alleles are associated with presence
or absence of particular RBC immunization.
The second aim of this study is to determine the long-term neuromotor
development, cognitive development and psychosocial well-being in a large group
of children treated with IUT for fetal anemia.

Observational cohort study
All women and their live-borne children, who have been treated with
intra-uterine transfusions for severe fetal anemia in the past 20 years will be
asked to participate in the study. After informed consent, a blood sample is
withdrawn. From young children, in-stead of a blood sample, a mouth-swap or a
saliva sample will be taken.
The follow-up visit includes a physical and standardized neurological
examination in children.
The mothers will be asked to fill in a protocolled questionnaire.

Study persons will be invited to come to the LUMC, where blood or saliva
sampling or mouth swab and filling in questionnaires will take place. The
follow-up visit also includes a physical and standardized neurological
examination.
The risks are those associated with routine venepuncture. Participation does
not result in any direct benefit.