Abstract
Abstract
Introduction
Successful pregnancies with healthy newborns have been reported after all types of solid organ transplantation (SOT). Limited data in young children suggest similar development and health compared with the general population. However, fetal development may be influenced by factors such as immunosuppressive medication and the increased incidence of pregnancy complications, and forthcoming health problems may only become apparent later in the life of the offspring. To allow for better investigation of the long-term health of offspring born after SOT, we designed the Transplantlines Next Generation biobank and cohort study. This study will be the first with detailed data on overall health status at later age in offspring born to mothers after kidney, liver, pancreas (including pancreas islet), heart and lung transplantation (KTx, LiTx, PTx, HTx and LuTx, respectively).
Methods and analysis
Transplantlines Next Generation is a descriptive, prospective cohort study and biobank. It includes offspring aged≥16 years born after KTx or LiTx. Because of the scarcity of pregnancies after (solo) PTx, HTx and LuTx worldwide, and as a consequence the lack of information about these pregnancies, we want to include all offspring, at any age, born after (solo) PTx, HTx and/or LuTx in the Netherlands. Participants will attend a one-time visit for questionnaires, physical tests (for participants≥16 years including kidney ultrasound and 24-hour ambulatory blood pressure) and biological sample collection (urine, blood, faeces) for participants≥16 years of age for biobanking. Reference values and values from existing birth cohorts will serve as controls. Primary endpoints are cardiovascular and kidney health, assessed through growth charts, physical tests (eg, body composition, blood pressure, kidney ultrasound) and metabolic and kidney function biomarkers. Secondary aims include immunological status, microbiome analysis, quality of life and overall development.
Ethics and dissemination
Ethical approval has been obtained from the local medical ethical committee; the Institutional Review Board METc UMC Groningen (METc 2023/610). The study will be conducted according to the Declaration of Helsinki and in accordance with the Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts including the General Data Protection Regulation (GDPR). All participants will give written informed consent upon enrolment. TransplantLines Next Generation is designed to deliver pioneering insights into the health of offspring born after SOT. This knowledge will help optimise care and available information for families with a pregnancy wish after SOT and provide a rationale for future studies. The results of this study are planned to be submitted for publication in relevant peer-reviewed journals and will be presented at national and international conferences.
Trial registration number
Keywords: Transplant medicine, Pregnancy, Child, Follow-Up Studies
STRENGTHS AND LIMITATIONS OF THIS STUDY.
Extensive standardised data collection and biobank sampling on the health of adult offspring born after maternal solid organ transplantation.
Inclusion of offspring after all solid organ transplant types from all Dutch transplant centres.
One-time study visit.
Introduction
Studies have reported successful pregnancy outcomes with healthy newborns after all types of solid organ transplantation (SOT).1 Pregnancy after SOT is associated with an increased risk of fetal and maternal complications, such as gestational hypertension, pre-eclampsia, prematurity and low birth weight, whereby risks differ per kind of SOT, with highest risks after heart and lung transplantation (HTx and LuTx, respectively).1–3 Data on pregnancy after solo pancreas transplantation (PTx) (including pancreas islets) are limited to case reports.4 5 In a systematic review, focussing on the longer term outcomes (>1 year) of the children born after SOT, we found that data on SOT other than kidney transplantation (KTx) are rare and all data are largely limited to children at a young age.6 Data regarding longer term follow-up are scarce, with only five studies reporting global outcomes in offspring aged>18 years.7–11 The existing data in young children seem reassuring: development and overall health appear to be similar to the general population. However, because of the scarcity of especially follow-up into adulthood, these results need to be treated with caution.
In general, pregnancy complications such as pre-eclampsia and prematurity might influence the development of the offspring. Studies in the non-transplant population show that the risks of metabolic cardiovascular disorders, including reduced insulin sensitivity, obesity and hypertension at adult age are increased in children who were born after pregnancies complicated by hypertension, pre-eclampsia and/or prematurity.12 13 Moreover, low birth weight and preterm birth are associated with impaired kidney development.14 The combination of an increased incidence of pregnancy complications and the use of immunosuppressive medication by mothers during pregnancy may further amplify health risks for the offspring born after SOT.
It is possible that the (type of) immunosuppressive medication used by the mother during pregnancy affects the development of the fetus and that forthcoming health problems only become apparent later in life. Furthermore, next to the direct effect of the medication on the fetus, secondary effects of the medication, for example, on the maternal gut microbiome,15 could influence the gut microbiome and health and development of the infant.16 Data on the effects of medication during pregnancy are scarce but existing guidelines state that all immunosuppressive medication can be continued during pregnancy, with the exception of mycophenolate mofetil and mechanistic Target Of Rapamycin inhibitors. All kinds of immunosuppressive medication cross the placenta and tacrolimus has even been shown to accumulate in the placenta.17 In addition, tacrolimus, the immunosuppressive drug currently used in the majority of SOT patients, has vasoconstrictive properties which often lead to hypertension and nephrotoxicity in SOT patients.18 19 Studies in rabbits and rats showed that cyclosporine (a calcineurin inhibitor just like tacrolimus) use during pregnancy lead to glomerular and tubular damage and nephron loss in offspring at adult age.20 21 Studies on the kidney function of offspring born after SOT did not report on abnormalities for kidney function, but the studies were only conducted in young children.22–24 Willis et al did include older children (range 9 months to 18 years) and reported that 4/40 (10%) of the children had urinary tract abnormalities on ultrasound.25 To the best of our knowledge, there are no available data on cardiovascular and kidney function in adult offspring born after maternal SOT.
To gain more knowledge on overall health of the offspring born to mothers after KTx, HTx, LuTx, PTx and liver transplantation (LiTx) and to identify possible prenatal and perinatal risks for diseases later in life we want to perform a prospective cohort study: Transplantlines Next Generation (figure 1). Because of the scarcity of pregnancies after solo PTx, HTx and LuTx worldwide and as a consequence the lack of information about these children, we want to include all offspring, at any age, born after PTx (including pancreas islets), HTx or LuTx in the Netherlands. In this group the aim will be to assess the overall health of this group compared with a control group. All offspring born after KTx and LiTx and aged≥16 will be eligible for participation. To the best of our knowledge, this will be the first study worldwide that will collect and analyse detailed information about the overall health at a later age (≥16 years) in the offspring born after maternal SOT.
Figure 1. Overview of the design of Transplantlines Next Generation.
Methods and analysis
Study design
TransplantLines Next Generation is a descriptive, prospective cohort study and biobank (ClinicalTrials.gov Identifier: NCT07291258). Participants are invited for a one-time study visit. The primary aim is to assess the cardiovascular and kidney health of the offspring born after maternal SOT. Secondary aims are the immunological status, including microbiome and the overall development including quality of life of the offspring. For the children<16 years the primary aim will be to assess the general health compared with reference values and existing birth cohorts. Participants will be recruited from all SOT centres in the Netherlands. The study will be performed at the University Medical Center Groningen, the Netherlands. Patient inclusion started in October 2025 and is expected to be completed in July 2027.
Study population
The study population comprises offspring born to mothers with all types of SOT, including combined transplantations. All offspring born after maternal KTx and/or LiTx and aged≥16 years in the Netherlands 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, we want to include all offspring, at any age, born after PTx, HTx and/or LuTx in the Netherlands. Data will be compared with reference values and/or existing birth cohorts, and if applicable, part of the data will be compared with a control group of healthy adolescents and (young) adults from existing birth cohorts or the Lifelines cohort. Exclusion criteria for participation will be lack of sufficient mastery of the Dutch or English language. Since the aim of the study is descriptive, no power analyses were performed. An overall participation rate of 70% is expected across the different transplant populations and we aim for a total number of 150 participants.
Recruitment and consent
Eligible participants will be identified through recent previous national studies on pregnancy after KTx, LiTx, HTx and LuTx and if the participant (mother of the offspring) gave permission for contact for additional research, the mother will be contacted and asked for permission to send an information letter including informed consent to the offspring. National data to be collected on pregnancy after PTx will be identified and collected through our national network with treating physicians. Eligible participants who do not respond after 2 weeks will receive a reminder by post maximally two times. When the signed informed consent forms are received, an invitation for the study visit will be sent. For the participants<16 years, the code of conduct of the Paediatric Association of the Netherlands will be followed.
Study procedures and data collection
Participants will be invited for a one-time study visit of approximately 1.5–2 hours (figure 2). Participants will be asked to fill in a questionnaire beforehand and to bring a morning urine sample and a faeces sample. The study visit will consist of basic physical tests (including height and weight), an ultrasound of the kidneys and blood sample collection. After the study visit, a 24-hour ambulatory blood pressure measurement will be performed. For the participants aged<16 years, no sample collection and no ultrasound will be performed, and a Dinamap blood pressure measurement during the study visit will be performed instead of a 24-hour ambulatory blood pressure measurement. An overview of the parameters that will be collected is depicted in table 1.
Figure 2. Overview of the participation timeline of Transplantlines Next Generation. PWV, pulse wave velocity.
Table 1. Overview of the different tests and samples collected in Transplantlines Next Generation.
| Test | Details | |
|---|---|---|
| Physical tests | Weight | Two times, using a digital measuring scale |
| Height | Two times, using a measuring tape roll | |
| Waist–hip ratio | Two times, using a measuring tape roll | |
| Bioimpedance analysis including body fat and water composition | Using Quadscan 4000 | |
| Blood pressure and heart rate | Using an automatic or semiautomatic measuring device. 24-hour ambulatory blood pressure measurement for participants≥16 years. Participants<16 years or if not possible: a Dinamap measurement of 30 min | |
| Pulse wave velocity (vascular stiffness) | Only in participants≥16 years. Using Mobil-O-Graph. 24-hour measurement together with the blood pressure measurement | |
| Ultrasound of the kidneys | Only in participants≥16 years. Using a standardised protocol of the kidney and urinary tract. Performed by a trained echoscopist | |
| Biological samples | Blood
|
Only in participants≥16 years. Biobank sample will be stored at −80°C. Stored samples:
|
Urine
|
Only in participants ≥16 years. Participants will be asked to bring a first morning urine sample. Female participants will be asked to plan so that they do not have their period during urine collection. Biobank sample of 4 mL will be stored at −80°Cs | |
Faeces
|
Only in participants≥16 years. Biobank sample will be stored at −80°C | |
| Questionnaire data | Questions on medication use and chronic diseases | Chronic medication use (>3 months), antibiotic use and chronic diseases (present>6 months) |
| School level | Level of secondary (and tertiary) education including questions on repeating a grade | |
| Lifestyle | Questions on smoking, drugs, alcohol, sports | |
| Quality of life | Using the ‘Positieve Gezondheid’ Questionnaire30 | |
| Data from patient records | Growth charts | Collected via data from the children’s healthcare centre |
| Developmental information retrospectively collected from the children’s healthcare centre | Collected via data from the children’s healthcare centre | |
| Presence of chronic diseases | Collected via participants’ questionnaires and the records of the general practitioner | |
| Chronic medication use | Collected via participants’ questionnaires and the records of the general practitioner | |
| Data from patient record mother | Pregnancy characteristics and outcome | Including information about the immunosuppressive medication used during pregnancy and breastfeeding. The mother will be asked to sign IC for permission to link this data to the results of this study |
Huber et al.
CRP, C-reactive protein; CV, Cardiovascular; EDTA, Ethylenediaminetetraacetic acid; eGFR, Estimated glomerular filtration rate; HbA1c, Glycated hemoglobin; HDL, High-density lipoprotein; IC, Informed consent; LDL, Low-density lipoprotein; TG, Triglycerides.
The biological sample collection will include sample collection for a biobank. The collection will be in line with the Transplantlines Biobank and cohort study of the University Medical Center Groningen (UMCG).26 Furthermore, data on the pregnancy outcome after which the participant was born will be collected from the medical file of the mother. Separate informed consent to the mother will be asked for permission to link the data to this study. Information about the growth and development of the offspring and, if present, diseases and medication use will be collected from the medical files from the general practitioner and pharmacy and from data from the youth healthcare check-ups. Data will be compared with reference values and to a control group of healthy adolescents and (young) adults from existing birth cohorts or the Lifelines cohort.27
Data management and analysis
Study data will be collected and managed in electronic case report forms using REDCap electronic data capture tools hosted at UMCG.28 29 The study visits will be performed by the researchers.
The main aim of the study is to describe the health of the study population and compare this to a control group. Descriptive statistics will be used to characterise the study population. Normality of distribution will be tested with Shapiro-Wilk test. Normally distributed data will be described as mean (SD) and non-normally distributed data will be described using median (IQR).
The primary endpoints focus on the cardiovascular health and the presence of kidney disease which will be measured in multiple ways. The outcomes of the study group will be compared with reference values and to a control. We will make a comparison per variable with the general population via existing data (https://www.birthcohorts.net/). If it is not possible to make a comparison with the general population, we will use data from Lifelines and evaluate which variables we need to match (and what is possible with the data from Lifelines). Differences between the groups will be analysed using Student’s t-test for normally distributed variables and Mann-Whitney U test for non-normally distributed variables. Fisher’s exact test will be done for binary categorical variables. Multiple groups will be compared with help of the Kruskal-Wallis test. All analyses are exploratory in nature with emphasis on effect sizes, not statistical significance. Any significant findings will need to be interpreted taking into account multiple testing, depending on the number of tests performed to test a specific hypothesis (ie, with a variable adjustment of the p value). In the analyses, familial relationships will be taken into consideration and will be adjusted for.
Patient and public involvement
Patients were involved in an oral consultation to gauge interest in this study during a symposium on Pregnancy after Kidney Transplantation (Radboud UMC, 2022), specifically organised for patients and their families. During the symposium, both patients and their children expressed a strong desire to understand the potential consequences for the children. Subsequently, the project plan was submitted for advice to the patient advisory committee (PAC) of the Groningen Transplantation Center; one patient from the committee, the mother of a woman with a kidney transplant, reviewed the proposal and gave positive feedback on the research plan. The project plan was also submitted to the Dutch Kidney Patients Association, the ‘Nederlandse Vereniging voor Nierpatiënten’ (NVN) for advice. Two patients from the NVN’s patient advisory board provided input, and their suggestions were incorporated into the research plan. Once the study begins, we will ask the PAC and NVN patients to review the participant information and the information for the participants’ parents. Additionally, if possible, the results will be shared with and discussed by these groups.
Ethics and dissemination
Ethics
The study protocol has been approved by the Institutional Review Board METc UMC Groningen (METc 2023/610) and adheres to the UMCG Biobank Regulation. The study will be conducted according to the principles of the Declaration of Helsinki and in accordance with the Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts including the General Data Protection Regulation (GDPR). All participants will give written informed consent on enrolment. All transplantations in the study population were performed within established healthcare systems in Europe, where organ donation is regulated by national legislation and international ethical standards. The present study did not involve organ procurement, allocation or transplantation procedures, and no organs or tissues were sourced for the purpose of this research.
Data and samples will be pseudonymised by use of a separately stored code list during data collection. Pseudonymised data can only be accessed by the principal investigator and study delegates after authorisation by the principal investigator. Important protocol modifications will be communicated to relevant parties and published on https://clinicaltrials.gov/. Study investigators will have access to the final dataset. Access to the full protocol, participant-level dataset and statistical code will be granted on request.
Dissemination
The TransplantLines Next Generation study has been designed to deliver pioneering insights into the health of the offspring born after transplantation. Within the study, we are focusing on both quantitative analyses, for example, the presence of diseases and abnormal laboratory values, and qualitative outcomes regarding quality of life. This will provide knowledge used to optimise the care and information for families with a pregnancy wish after transplantation and will provide rationale for future studies. The results of this study are planned to be submitted for publication in relevant peer-reviewed journals and will be presented at national and international conferences. Moreover, the outcome will be incorporated into clinical guidelines.
Footnotes
Funding: This work is supported by Astellas (for the set up of the database, grant ID number: 90677357), the Dutch Kidney Foundation (grant ID number: 23OP+065), the Groningen Transplantation Fund and the Dutch Transplantation Fund.
Prepublication history for this paper is available online. To view these files, please visit the journal online (https://doi.org/10.1136/bmjopen-2025-115736).
Patient consent for publication: Not applicable.
Provenance and peer review: Not commissioned; peer reviewed for ethical and funding approval prior to submission.
Collaborators: COMPACT network: M Baas, M H L Christiaans, K Damman, E J P de Koning, C M den Hoed, J J Duvekot, M Groenewout, M E Hellemons, D A Hesselink, B M Kazemier, A T Lely, O Manintveld, M I F J Oerlemans, R C Painter, J R Prins, C Roozendaal, M F Schreuder, M E A Spaanderman, M Sueters, Y K O Teng, M E Tushuizen, O W H van der Heijden, F E van Reekum, F G I van Vilsteren, K T Verbruggen, E A M Verschuuren, L Vogt.
Patient and public involvement: Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
Contributor Information
on behalf of the COMPACT network group authorship:
Marije Baas, Maarten H L Christiaans, Kevin Damman, Eelco J P de Koning, Caroline M den Hoed, Hans J J Duvekot, Mariette Groenewout, Merel E Hellemons, Dennis A Hesselink, Brenda M Kazemier, Titia A T Lely, Olivier Manintveld, Marish I F J Oerlemans, Rebecca C Painter, Jelmer R Prins, Caroline Roozendaal, Michiel F Schreuder, Marc E A Spaanderman, Marieke Sueters, Onno Y K O Teng, Maarten E Tushuizen, Olivier W H van der Heijden, Franka E van Reekum, Frederike G I van Vilsteren, Rien K T Verbruggen, Erik A M Verschuuren, and Liffert Vogt
References
- 1.Philadelphia, PA: Gift of Life Institute; 2020. Transplant pregnancy registry international (TPRI) 2024 annual report. [Google Scholar]
- 2.Valentin N, Guerrido I, Rozenshteyn F, et al. Pregnancy Outcomes After Liver Transplantation: A Systematic Review and Meta-Analysis. Am J Gastroenterol. 2021;116:491–504. doi: 10.14309/ajg.0000000000001105. [DOI] [PubMed] [Google Scholar]
- 3.Shah S, Venkatesan RL, Gupta A, et al. Pregnancy outcomes in women with kidney transplant: Metaanalysis and systematic review. BMC Nephrol. 2019;20:24. doi: 10.1186/s12882-019-1213-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Rickels MR, Markmann E, Naji A. Successful pregnancies after islet transplantation for type 1 diabetes. Am J Transplant. 2019;19:298–9. doi: 10.1111/ajt.14972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Schive SW, Scholz H, Sahraoui A, et al. Graft function 1 year after pregnancy in an islet-transplanted patient. Transpl Int. 2015;28:1235–9. doi: 10.1111/tri.12596. [DOI] [PubMed] [Google Scholar]
- 6.Meinderts JR, Prins JR, Berger SP, et al. Follow-Up of Offspring Born to Parents With a Solid Organ Transplantation: A Systematic Review. Transpl Int. 2022;35:10565. doi: 10.3389/ti.2022.10565. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Devresse A, Jassogne C, Hubinont C, et al. Pregnancy Outcomes After Kidney Transplantation and Long-Term Evolution of Children: A Single Center Experience. Transplant Proc. 2022;54:652–7. doi: 10.1016/j.transproceed.2022.01.019. [DOI] [PubMed] [Google Scholar]
- 8.Egerup P, Carlson N, Bruun Oestergaard L, et al. Increased risk of neonatal complications and infections in children of kidney-transplanted women: A nationwide controlled cohort study. Am J Transplant. 2021;21:1171–8. doi: 10.1111/ajt.16259. [DOI] [PubMed] [Google Scholar]
- 9.Dębska-Ślizień A, Gałgowska J, Bułło-Piontecka B, et al. Pregnancy After Kidney Transplantation With Maternal and Pediatric Outcomes: A Single-Center Experience. Transplant Proc. 2020;52:2430–5. doi: 10.1016/j.transproceed.2020.01.122. [DOI] [PubMed] [Google Scholar]
- 10.Norrman E, Bergh C, Wennerholm U-B. Pregnancy outcome and long-term follow-up after in vitro fertilization in women with renal transplantation. Hum Reprod . 2015;30:205–13. doi: 10.1093/humrep/deu293. [DOI] [PubMed] [Google Scholar]
- 11.Scott JR, Ware Branch D, Holman J. Autoimmune and pregnancy complications in the daughter of a kidney transplant patient. Transplantation. 2002;73:815–6. doi: 10.1097/00007890-200203150-00028. [DOI] [PubMed] [Google Scholar]
- 12.Lindström L, Skjaerven R, Bergman E, et al. Chronic Hypertension in Women after Perinatal Exposure to Preeclampsia, Being Born Small for Gestational Age or Preterm. Paediatr Perinat Epidemiol. 2017;31:89–98. doi: 10.1111/ppe.12346. [DOI] [PubMed] [Google Scholar]
- 13.Lewandowski AJ, Leeson P. Preeclampsia, prematurity and cardiovascular health in adult life. Early Hum Dev. 2014;90:725–9. doi: 10.1016/j.earlhumdev.2014.08.012. [DOI] [PubMed] [Google Scholar]
- 14.Luyckx VA, Perico N, Somaschini M, et al. A developmental approach to the prevention of hypertension and kidney disease: a report from the Low Birth Weight and Nephron Number Working Group. Lancet. 2017;390:424–8. doi: 10.1016/S0140-6736(17)30576-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Swarte JC, Li Y, Hu S, et al. Gut microbiome dysbiosis is associated with increased mortality after solid organ transplantation. Sci Transl Med. 2022;14:eabn7566. doi: 10.1126/scitranslmed.abn7566. [DOI] [PubMed] [Google Scholar]
- 16.Sinha T, Brushett S, Prins J, et al. The maternal gut microbiome during pregnancy and its role in maternal and infant health. Curr Opin Microbiol. 2023;74:102309. doi: 10.1016/j.mib.2023.102309. [DOI] [PubMed] [Google Scholar]
- 17.Freriksen JJM, Feyaerts D, van den Broek PHH, et al. Placental disposition of the immunosuppressive drug tacrolimus in renal transplant recipients and in ex vivo perfused placental tissue. Eur J Pharm Sci. 2018;119:244–8. doi: 10.1016/j.ejps.2018.04.017. [DOI] [PubMed] [Google Scholar]
- 18.Rodrigues-Diez R, González-Guerrero C, Ocaña-Salceda C, et al. Calcineurin inhibitors cyclosporine A and tacrolimus induce vascular inflammation and endothelial activation through TLR4 signaling. Sci Rep. 2016;6:27915. doi: 10.1038/srep27915. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Malvezzi P, Rostaing L. The safety of calcineurin inhibitors for kidney-transplant patients. Expert Opin Drug Saf. 2015;14:1531–46. doi: 10.1517/14740338.2015.1083974. [DOI] [PubMed] [Google Scholar]
- 20.Tendron-Franzin A, Gouyon J-B, Guignard J-P, et al. Long-term effects of in utero exposure to cyclosporin A on renal function in the rabbit. J Am Soc Nephrol. 2004;15:2687–93. doi: 10.1097/01.ASN.0000139069.59466.D8. [DOI] [PubMed] [Google Scholar]
- 21.Slabiak-Blaz N, Adamczak M, Gut N, et al. 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;40:413–23. doi: 10.1159/000368515. [DOI] [PubMed] [Google Scholar]
- 22.Borek-Dziecioł B, Czaplinska N, Szpotanska-Sikorska M, et al. Selected Biochemical Parameters in Children of Mothers After Kidney Transplantation. Transplant Proc. 2020;52:2294–8. doi: 10.1016/j.transproceed.2020.02.100. [DOI] [PubMed] [Google Scholar]
- 23.Czaplińska N, Kociszewska-Najman B, Schreiber-Zamora J, et al. Analysis of the selected biochemical parameters of liver and kidney function in children of mothers after liver transplantation. Transplant Proc. 2014;46:2790–3. doi: 10.1016/j.transproceed.2014.09.059. [DOI] [PubMed] [Google Scholar]
- 24.Shaheen FA, al-Sulaiman MH, al-Khader AA. Long-term nephrotoxicity after exposure to cyclosporine in utero. Transplantation. 1993;56:224–5. doi: 10.1097/00007890-199307000-00044. [DOI] [PubMed] [Google Scholar]
- 25.Willis FR, Findlay CA, Gorrie MJ, et al. Children of renal transplant recipient mothers. J Paediatr Child Health. 2000;36:230–5. doi: 10.1046/j.1440-1754.2000.00500.x. [DOI] [PubMed] [Google Scholar]
- 26.Eisenga MF, Gomes-Neto AW, van Londen M, et al. Rationale and design of TransplantLines: a prospective cohort study and biobank of solid organ transplant recipients. BMJ Open. 2018;8:e024502. doi: 10.1136/bmjopen-2018-024502. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Scholtens S, Smidt N, Swertz MA, et al. Cohort Profile: LifeLines, a three-generation cohort study and biobank. Int J Epidemiol. 2015;44:1172–80. doi: 10.1093/ije/dyu229. [DOI] [PubMed] [Google Scholar]
- 28.Harris PA, Taylor R, Thielke R, et al. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42:377–81. doi: 10.1016/j.jbi.2008.08.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Harris PA, Taylor R, Minor BL, et al. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform. 2019;95:103208. doi: 10.1016/j.jbi.2019.103208. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Huber M, van Vliet M, Giezenberg M, et al. Towards a “patient-centred” operationalisation of the new dynamic concept of health: a mixed methods study. BMJ Open. 2016;6:e010091. doi: 10.1136/bmjopen-2015-010091. [DOI] [PMC free article] [PubMed] [Google Scholar]