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

NCT07291258 | Recruiting

• 3 other identifiers: METc 2023/61010768NL85646.042.23
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Background Pregnancy after all types of solid organ transplantation (SOT) is possible, although these have higher risk of pregnancy complications for mother and child, such as preeclampsia and preterm birth. Thus, the development of the unborn child seems to be affected by the transplant and its consequences such as the immunosuppressive medication use. Worldwide data regarding follow-up after birth is scarce. The very limited existing data existing only in young children are reassuring. However, the investigators hypothesize that there are health risks for the children. Given the side effects of the immunosuppressive medication on patients and limited knowledge from animal studies, the investigators particularly expect cardiovascular effects such as hypertension and kidney damage. These develop over a long time-period and lead late to symptoms. Aims Aim of this study is to gain more insight into the overall health of offspring born after SOT. Primary aim is to assess the cardiovascular health and the presence of kidney disease, and compare these with reference values from the general population or birth cohorts. Secondary aims are the immunological status including the microbiome of the child given the maternal immunosuppressive medication use, and the overall development of the offspring, including qualitative research regarding the quality of life. Third aim is to assess if there are differences in health between offspring born to mothers with a kidney, liver, pancreas (including pancreas islet), heart and lung transplantation (KTx, LiTx, PTx, HTx, LuTx resp.). The investigators also want to establish a biobank for later follow-up research. Study design This will be a 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. The investigators estimate that there will be about 150(-220) participants. Before the study visit, participants will be asked to complete a questionnaire. Participants will be invited for a one-time study visit consisting of physical tests (including ultrasound of the kidneys and a 24-hour ambulatory blood pressure measurement) and biological sample (urine, blood and feces) collection, including sample collection for biobanking. 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. As a control group pseudoanonymized data from the Lifelines cohort will be used. Deliverables To the best of our knowledge, this will be the first study worldwide that will gather and analyze detailed information about the cardiovascular, kidney and immunological health at a later age (≥16 years) in the offspring born to mothers after KTx, LiTx, PTx, HTx and LuTx. This information will be important for the preconceptional counseling of families with a pregnancy wish after transplantation and thereby contribute to the health of women with a SOT. Next to that, find adverse effects of the pregnancy after transplantation on the offspring are found, the investigators expect there will be modifiable factors and/or early screening/interventions that can reduce these risks and thereby contribute to the health of the offspring.

Conditions

Solid Organ Transplantation; Pregnancy; Long-term Follow-up; Kidney Transplant; Liver Transplant; Pancreas Transplant; Lung Transplantation; Offspring, Adult; Children; Cardiovascular Abnormalities; Kidney Disease; Quality of Life; Heart Transplantation

Keywords

Solid organ transplantation; Pregnancy; Offspring; Long-term follow-up; kidney transplantation; liver transplantation; pancreas transplantation; pancreas islet transplantation; Heart transplantation; lung transplantation

Outcome Measures

Primary Outcomes (15)

• Growth charts

  The primary aim is to assess the cardiovascular and renal health of the offspring born after maternal SOT. One of the outcome measures are growth charts during childhood years.

  Retrospective data on the childhood growth from birth up till 6 years of age and lenght and weight at baseline.

• BMI

  The primary aim is to assess the cardiovascular and renal health of the offspring born after maternal SOT. One of the outcome measures is the BMI based on height (m) and weight (kg).

  Baseline

• Body fat and water percentage as measured with a bio-impednace meter (BIA).

  The primary aim is to assess the cardiovascular and renal health of the offspring born after maternal SOT. One of the outcome measures are the body fat and water percentage as measured with a bio-impednace meter (BIA).

  Baseline

• waist-hip ratio

  The primary aim is to assess the cardiovascular and renal health of the offspring born after maternal SOT. One of the outcome measures are waist-hip-ratio.

  Baseline

• Blood pressure

  The primary aim is to assess the cardiovascular and renal health of the offspring born after maternal SOT. One of the outcome measures is blood pressure, measured with a 240hour ambulatory measurement.

  Baseline

• Ultrasound of the kidneys

  The primary aim is to assess the cardiovascular and renal health of the offspring born after maternal SOT. One of the outcome measures is an ultrasound of the kidneys.

  Baseline

• Glucose

  The primary aim is to assess the cardiovascular and renal health of the offspring born after maternal SOT. One of the outcome measures is the glucose levels.

  Baseline

• HbA1c

  The primary aim is to assess the cardiovascular and renal health of the offspring born after maternal SOT. One of the outcome measures is the HbA1c.

  Baseline

• Cholesterol

  The primary aim is to assess the cardiovascular and renal health of the offspring born after maternal SOT. One of the outcome measures is cholesterol (HDL, LDL, triglycerides)

  Baseline

• Albuminuria

  The primary aim is to assess the cardiovascular and renal health of the offspring born after maternal SOT. One of the outcome measures is albuminuria.

  Baseline

• eGFR

  The primary aim is to assess the cardiovascular and renal health of the offspring born after maternal SOT. One of the outcome measures is estimated GFR.

  Baseline

• Pulse wave velocity (PWV)

  The primary aim is to assess the cardiovascular and renal health of the offspring born after maternal SOT. One of the outcome measures is a 24 hour pulse wave velocity (PWV) measurement.

  Baseline

• Troponine

  The primary aim is to assess the cardiovascular and renal health of the offspring born after maternal SOT. One of the outcome measures is troponine.

  Baseline

• creatine kinase

  The primary aim is to assess the cardiovascular and renal health of the offspring born after maternal SOT. One of the outcome measures is creatine kinase.

  Baseline

• High sensitive CRP

  The primary aim is to assess the cardiovascular and renal health of the offspring born after maternal SOT. One of the outcome measures is high sensitive CRP

  Baseline

Secondary Outcomes (10)

• Antibiotic use

  Retrospective, antibiotic use from birth untill study visit (baseline). Subdivided in antibiotic use during childhood (birth untill 18 years of age) and antibiotic use during adult life (18 years of age untill study visit/baseline)

• Hospital admissions due to infectious disease

  Retrospective, hospital admissions from birth until study visit (baseline). Subdivided in admissions during childhood (birth until 18 years of age) and admissions during adult life (18 years of age until study visit/baseline)

• IgA

  Baseline

• IgM

  Baseline

• IgG

  Baseline

Other Outcomes (1)

• Differences between the offspring born to mothers with a KTx, LiTx, PTx, HTx and LuTx

  Analysis of abnormal findings at study visit subdivided into abnormal findings during childhood (until 18 years of age) and abnormal findings at study visit/baseline (one-time visit).

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All offspring born after maternal KTx or LiTx and aged ≥16 years in the Netherlands will be eligible for inclusion. All offspring, at any age born after PTx (including pancreas islet transplantation), HTx or LuTx in the Netherlands will be eligible for inclusion. 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 (or if they don't want to participate in another specific part of the study.) Data will be compared to reference values and/or existing birth cohorts, and if applicable, part of the data will be compared to a control group of healthy adolescents and (young) adults from existing birth cohorts or the Lifelines cohort.

You may qualify if:

• Mother with a KTx, LiTx, PTx (including pancreas islet transplantation), HTx or LuTx before pregnancy (including mothers with multiple transplantation types)
• Age ≥16 years for offspring born to mother with a KTx or LiTx

You may not qualify if:

• No informed consent
• Non Dutch or English speaking

Sponsors & Collaborators

• Groningen Transplantation Fund (GTC): collaborator
• Dutch Transplantation Fund: collaborator
• Dutch Kidney Foundation: collaborator
• Astellas Pharma Europe B.V.: collaborator
• Stichting Eerstelijns Diagnostiek Nederland (SEDN): collaborator
• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, Provincie Groningen, 9713GZ, Netherlands

RECRUITING

Related Publications (9)

• Transplant Pregnancy Registry International (TPRI), 2022 annual report, Gift of Life Institute, Philadelphia, PA.

  RESULT

• Eisenga MF, Gomes-Neto AW, van Londen M, Ziengs AL, Douwes RM, Stam SP, Oste MCJ, Knobbe TJ, Hessels NR, Buunk AM, Annema C, Siebelink MJ, Racz E, Spikman JM, Bodewes FAJA, Pol RA, Berger SP, Drost G, Porte RJ, Leuvenink HGD, Damman K, Verschuuren EAM, de Meijer VE, Blokzijl H, Bakker SJL. Rationale and design of TransplantLines: a prospective cohort study and biobank of solid organ transplant recipients. BMJ Open. 2018 Dec 31;8(12):e024502. doi: 10.1136/bmjopen-2018-024502.

  PMID: 30598488 RESULT

• Slabiak-Blaz N, Adamczak M, Gut N, Grajoszek A, Nyengaard JR, Ritz E, Wiecek A. Administration of Cyclosporine A in Pregnant Rats - the Effect on Blood Pressure and on the Glomerular Number in Their Offspring. Kidney Blood Press Res. 2015;40(4):413-23. doi: 10.1159/000368515. Epub 2015 Jul 27.

  PMID: 26227088 RESULT

• Tendron-Franzin A, Gouyon JB, Guignard JP, Decramer S, Justrabo E, Gilbert T, Semama DS. Long-term effects of in utero exposure to cyclosporin A on renal function in the rabbit. J Am Soc Nephrol. 2004 Oct;15(10):2687-93. doi: 10.1097/01.ASN.0000139069.59466.D8.

  PMID: 15466273 RESULT

• Lewandowski AJ, Leeson P. Preeclampsia, prematurity and cardiovascular health in adult life. Early Hum Dev. 2014 Nov;90(11):725-9. doi: 10.1016/j.earlhumdev.2014.08.012. Epub 2014 Sep 7.

  PMID: 25209092 RESULT

• Lindstrom L, Skjaerven R, Bergman E, Lundgren M, Klungsoyr K, Cnattingius S, Wikstrom AK. Chronic Hypertension in Women after Perinatal Exposure to Preeclampsia, Being Born Small for Gestational Age or Preterm. Paediatr Perinat Epidemiol. 2017 Mar;31(2):89-98. doi: 10.1111/ppe.12346. Epub 2017 Feb 20.

  PMID: 28218407 RESULT

• Shah S, Venkatesan RL, Gupta A, Sanghavi MK, Welge J, Johansen R, Kean EB, Kaur T, Gupta A, Grant TJ, Verma P. Pregnancy outcomes in women with kidney transplant: Metaanalysis and systematic review. BMC Nephrol. 2019 Jan 23;20(1):24. doi: 10.1186/s12882-019-1213-5.

  PMID: 30674290 RESULT

• Valentin N, Guerrido I, Rozenshteyn F, Pinotti R, Wu YC, Collins K, Shah M, Hershman M, Weisberg I. Pregnancy Outcomes After Liver Transplantation: A Systematic Review and Meta-Analysis. Am J Gastroenterol. 2021 Mar 1;116(3):491-504. doi: 10.14309/ajg.0000000000001105.

  PMID: 33657039 RESULT

• Meinderts JR, Prins JR, Berger SP, De Jong MFC. Follow-Up of Offspring Born to Parents With a Solid Organ Transplantation: A Systematic Review. Transpl Int. 2022 Aug 5;35:10565. doi: 10.3389/ti.2022.10565. eCollection 2022.

  PMID: 35992748 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood sample, first morning urine sample, feces sample

MeSH Terms

Conditions

Cardiovascular Abnormalities; Kidney Diseases

Condition Hierarchy (Ancestors)

Cardiovascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Margriet F.C. de Jong, MD, PhD, MBA

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Margriet F.C. de Jong, MD, PhD, MBA

CONTACT

+31655256391; m.f.c.de.jong@umcg.nl

Jildau R. Meinderts, MD

CONTACT

j.r.meinderts@umcg.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2025
• First Posted: December 18, 2025
• Study Start: October 15, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: December 18, 2025

Record last verified: 2025-11

Locations

NL (1)