Long-term Follow-up of the Offspring Born to Mothers With a Solid Organ Transplant, Transplantlines Next Generation

Rationale: 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 the investigators 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, LiTx, pancreas (including pancreas islet transplantation), heart and lung transplantation (PTx, HTx, LuTx resp.) Objective: The primary aim of this study is to assess the cardiovascular and kidney health of the offspring born after SOT in the mother. Secondary aims are the immunological status including the microbiome of the child and the overall development of the offspring. Third, the investigators want to assess if there are differences in health between offspring born to mothers with a KTx, LiTx, PTx, HTx and LuTx. For the offspring aged \<16 years of age the aim is to compare their overall health to the general population. Study design: 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 PTx, 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 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 (METc 2014/077) and an amendment to the Transplantlines Biobank is made 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, 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). National data to be collected on pregnancy after PTx will be identified and collected through our national network with treating physicians. 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 the investigators 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. Study population: The investigators want to include all offspring aged ≥16 years of age born after KTx or LTx in the mother in the Netherlands. Around 165 children after KTx and around 30 children born after LTx will be eligible for inclusion. Because of the scarcity of pregnancies after PTx, HTx and LuTx worldwide, and as a consequence the lack of information about these pregnancies, the investigators want to include all offspring, at any age, born after PTx, HTx or LuTx heart in the Netherlands. Around 5 children born after HTx and around 12 children born after LuTx will be eligible for inclusion, for children born after PTx this number is still unknown, but will be few. In these young participants the focus will be on the overall health of this group in comparison to a control group. Overall data will be compared to reference values and to a control group of healthy adolescents and (young) adults from existing birth cohorts or the Lifelines cohort. Main study parameters/endpoints: The primary endpoints of the study focus on the cardiovascular and kidney health which will be assessed by growth charts and developmental information retrospectively collected from the children's health care center, physical tests (weight and height, body fat and water percentage (BIA), waist-hip-ratio, blood pressure, heart rate and ultrasound of the kidneys) and with biological samples (metabolic parameters: glucose, HbA1c, cholesterol, HDL, LDL, triglycerides, as well as kidney functional parameters: albuminuria, estimated GFR, tubular function).

Time frame: Baseline