Long-term follow-up of the offspring born to mothers with a solid organ transplant.

Studies have reported successful pregnancy outcomes with healthy newborns after
all types of solid organ transplantations (SOT). A recent systematic review
performed by our center focused on the longer term outcomes (>1 year) of the
children born after SOT. We found that data regarding longer term follow-up is
scarce, limited to younger children and predominately focused on offspring born
after kidney transplantation (KTx) and liver transplantation (LiTx). Only five
studies reported outcomes on offspring aged >18 years. The limited existing
data in young children are reassuring, development and overall health appears
to be similar to the general population. However, it is possible that the
development of the fetus is affected by the transplantation and its
consequences such as the use of the immunosuppressive medication and the
increased incidence of the pregnancy complications, whereby important health
risks only become apparent later in life. To gain more insight into the overall
health of the offspring born solid organ transplantation and to identify
possible pre- and perinatal risks for diseases later in life we want to perform
a cross-sectional cohort study. To the best of our knowledge, this will be the
first study that will gather and analyze detailed information about the
cardiovascular, immunological and kidney health at a later age (>=16 years) in
the offspring born to mothers after KTx and LiTx, and the overall health of
offspring born to mothers with a heart and lung transplantation (HTx, LuTx
resp.)

The primary aim of the study is to assess the overall health of offspring born
to a mother with solid organ transplantation, and to identify possible pre- and
perinatal risks for diseases later in life. In addition, we would like to
collect and analyze detailed information on cardiovascular, immunological and
renal health later in life (>=16 years) in offspring of mothers after KTx and
LiTx, and would like to map the overall health of children of a mother with
heart and lung transplantation (HTx, LuTx respectively).

This will be a descriptive cross-sectional monocenter cohort study. All
offspring >=16 years of age born after KTx or LiTx and all offspring born at any
age after HTx and LuTx in the Netherlands will be eligible for inclusion.
Eligible participants will be identified via previous studies on pregnancy
after KTx, LiTx, HTx and LuTx. Participants will be invited for a one-time
study visit consisting of questionnaires, physical tests (including blood
pressure measurement and ultrasound of the kidneys) and biological sample
(urine, blood and feces) collection. Next to that a 24-hour ambulatory blood
pressure measurement will be performed in the participants >=16 years. The
biological sample collection will include sample collection for a biobank. The
collection will be in line with the Transplantlines Biobank and an amendment to
the Transplantlines Biobank will be submitted and specific informed consent for
linking the data of Transplantlines and the current study will be obtained from
all participants. For all participants it will be emphasized that the invasive
test (blood sample) is optional, participants can still participate in the
study if they don*t want a blood sample taken. For the participants aged <16
years of age no blood, urine and feces sample will be taken, and no ultrasound
of the kidney will be performed and a dinamap blood pressure measurement
instead of a 24-hour measurement will be performed. Furthermore, data on the
pregnancy will be used from three recent national studies, data from the
PARTOUT network (national working group on pregnancy after renal
transplantation), national data collected on pregnancy after LiTx (manuscript
in preparation) and national data on pregnancy after HTx and LuTx (manuscript
in preparation). Information about the growth and development of the offspring
and, if present, diseases and medication use will be collected from the medical
files of the general practitioner and pharmacy (LSP) and from data from the
youth healthcare check-ups. Permission to collect this data will be separately
mentioned on the IC. As a control group we will evaluate whether reference
values and / or data from existing birth cohorts are available. If not, pseudo
anonymized data from the Lifelines cohort will be used.

The burden for the participants consists of a one-time study visit to the
hospital which will take approximately 1,5/2 hours and a 24-hour ambulatory
blood pressure measurement after the study visit. The visit will consist of
questionnaires and basis physical tests (e.g. weight, height, blood pressure)
and an ultrasound of the kidneys. During this visit the following biological
samples will be collected: one blood sample consisting of 38 tubes (1275 ml
blood), a first morning urine sample and a feces sample. For the participants
<16 years of age no blood, urine and feces sample will be taken. We consider
this burden to be minimal. In the patient information we specifically mention
that participants can still participate if they don*t want to participate in
part of data collection (e.g. the blood sample or the ultrasound). If
indications for disease or abnormal results are found during the study, the
participant and the general practitioner of the participant will be contacted.