SEARCH

SEARCH BY CITATION

On Monday 10 March 1958 a healthy baby boy was delivered by caesarean section to a woman who, prior to pregnancy, had received a kidney transplant from her identical twin sister. That delivery and the events preceding it, although not reported until much later1, heralded the start of interdisciplinary co-operation that has now coped worldwide with over 7000 pregnancies.

Not all pregnancies have been successful and/or reported, but certainly in recent years improvements in our understanding of pregnancy physiology and the advances in nephrological and transplantation as well as obstetric and neonatal paediatric practice have improved outcomes for mother and baby2. Nowadays, medical concern no longer just focuses on coping with established pregnancies but also concentrates on pre-pregnancy counselling, the specific gestational and renal problems in these women and the remote effects of pregnancy on both renal prognosis and the offspring.

The publication of case reports, single centre experiences, reviews and registry data has detailed various problems to date2. The ongoing message is that couples who want a child must still be encouraged to discuss all the facts and implications, including the harsh realities of a nonsuccessful pregnancy and long term implications, including maternal survival prospects2–5

The key facts are as follows2,6–10. Therapeutic abortion is undertaken in just under 20% of conceptions and the spontaneous miscarriage rate is around 14%, the same as for the normal population. Of the conceptions that continue beyond the first trimester, 94% end successfully. In most women, renal function is augmented during pregnancy, but permanent impairment occurs in 15% of pregnancies. In others there may be transient deterioration in late pregnancy (with or without proteinuria) and while it is likely that pregnancy does not compromise long term renal prognosis more information is needed. There is a 30% chance of developing hypertension, pre-eclampsia or both. Preterm delivery occurs in 45% to 60%, and intrauterine growth retardation in at least 20% of pregnancies. Despite its pelvic location, the transplanted kidney rarely produces dysto-cia and is not injured during vaginal delivery. Caesarean section is generally reserved for obstetric reasons only. Neonatal complications include respiratory distress syndrome, leucopenia, thrombocytopenia, adreno-cortical insufficiency and infection. No predominant or frequent developmental abnormalities have been described and data on infancy and childhood are encouraging.

Until now, UK pregnancy data traditionally have been supplied to the Registry of the European Dialysis and Transplant Association (EDTA)11–14. But data provision from individual centres has been variable, and there has been no way of assessing this within the UK. Nor has there been any systematic attempt to collect data about the small number of pregnancies in patients after liver, pancreas-kidney or cardiothoracic transplant.

On the other hand, for all other aspects of transplantation collection of UK data is the responsibility of the UK Transplant Support Service Authority (UKTSSA) which has a highly developed data collection and analysis operation, the National Transplant Database, located in Bristol. These data management services have recently been further refined through the establishment of the UK National Transplant Network (UKNTN), with computer terminals placed within all the Transplant Units throughout the UK. Through this network, Transplant Units already supply annual follow up information on all transplanted patients; the follow up form used for this purpose has been modified to include an Annex for the collection of pregnancy data. However, this will only work if clinicians are willing to take part and, with their support staff, co-operate by providing this information.

Given this co-operation, the additional load on transplant and obstetric units should be small and it will provide the simplest and most effective way in which we can complete the important step of collecting post-transplant pregnancy data from all obstetric units. Our physician colleagues are keen to help and bearing in mind the small amount of obstetric input needed nationwide, this initiative should be supported enthusiastically by British obstetricians.

By way of comparison, in the United States, a National Transplantation Pregnancy Register (NTPR) was established in 1991 and since then, data have accrued from almost 800 pregnancies15–21. The NTPR relies on additional questionnaires distributed to all American centres with transplant co-ordinators. Physicians are requested to identify relevant patients who themselves complete questionnaires and are later contacted for additional information, such as co-morbid conditions. This system is providing relevant new information, and although the supervisors are aware that other significant American publications will continue9,22–25and that compliance is extremely variable across such a large number of centres, there is now an ongoing database, however incomplete. In the UK we have the opportunity to develop a Registry quickly and simply that would be complete, consistent and accurate and would soon be able to complement other efforts worldwide.

The science and practice of transplantation medicine is constantly evolving. Many changes lie ahead, including new immunosuppressive drugs and rationalisation of their dosage, steroid withdrawal, induction regimens to develop tolerance and other donor options including xenografts. All of these will ultimately impinge on obstetric practice and the obstetrician will need to maintain close ties with transplant centres and personnel in order to be aware of patient management issues. Not only will more and more successful pregnancies ensue but better predictors of satisfactory maternal and newborn survival, together with that of the graft itself, will be possible.

Because of the relatively small numbers involved, a National Registry will provide the only viable means of studying outcomes of post-transplant pregnancy, so providing clinicians with timely and relevant information and the guidelines that they need. Furthermore, given that events in utero may have a very delayed effect on health in adult life26,27 long term value for the offspring will only accrue if record keeping is systematic and conducted nationally. From all points of view, the more comprehensive the data, the better the quality of information will be. With the agreement of Transplant Units, the necessary changes and extensions to the follow up form have been made, with data collection now underway. Obstetric units and Transplant Unit personnel are already collaborating.

It will probably be two years or more before sufficient data have been gathered to enable meaningful analysis and the publication of any findings. But in the longer term, with the accumulation of greater numbers of all types of long surviving recipients, a comprehensive UKTSSA Registry already in place will provide a valuable aid to evidence based medicine in this area.

References

  1. Top of page
  2. References
  • 1
    Murray JE, Reid DE, Harrison JH, Merrill JP. Successful pregnancies after human renal transplantation. N Engl J Med 1963; 269: 341343.
  • 2
    Davison JM. Pregnancy in renal allograft recipients: problems, prognosis and practicalities. Baillieres Clin Obstet Gynaecol 1994; 8: 501525.
  • 3
    Davison JM. Towards long-term graft survival in renal transplantation: pregnancy. Nephrol Dial Transplant 1995; 10 (Suppl 1): 8589.
  • 4
    London N, Farmery SM, Will EJ, Davison AM, Lodge JPA. Risk of neoplasia in renal transplant patients. Lancet 1995; 346: 403406.
  • 5
    Opelz G. Are post-transplant lymphomas inevitable Nephrol Dial Transplant 1996; 11: 19521955.
  • 6
    Cararach V, Carmona F, Monleon FJ, Andreu J. Pregnancy after renal transplantation: 25years experience in Spain. Br J Obstet Gynaecol 1993; 100: 122125.
  • 7
    Davison JM, Dellagrammatikas, Parkin JM. Maternal azatioprine therapy and depressed haemoporesis in babies of renal allograft patients. Br J Obstet Gynaecol 1985; 92: 233239.
  • 8
    Salmela KT, Kyllonen LEJ, Holmberg C, Gronhagen-Riska C. Impaired renal function after pregnancy in renal transplant recipients. Transplant 1993; 56: 13721375.
  • 9
    First MR, Combs CA, Weiskittel P, Miodovinik M. Lack of effect of pregnancy on renal allograft survival or function. Transplant 1995; 59: 47277.
  • 10
    Sturgiss SN, Davison JM. Effect of pregnancy on long-term function of renal allografts. Am J Kid Dis 1995; 26: 5456.
  • 11
    The Registration Committee of the European Dialysis and Transplant Association. Successful pregnancies in women treated by dialysis and kidney transplantation. Br J Ohstet Gynaecol 1980; 87: 839845.
  • 12
    Rizzoni G, Ehrich JHH, Brunner FP et al. Combined report on regular dialysis and transplantation of children in Europe. Nephrol Dial Transplant 1989; 4: 3140.
  • 13
    Raine AEG, Margreiter R, Brunner FP et al. Report on management of renal failure in Europe XXII. Nephrol Dial Transplant 1991; 7 Suppl 2: 735.
  • 14
    Rizzoni G, Ehrich JHH, Broyer M et al. Successful pregnancies in women on renal replacement therapy: report from the EDTA Registry. Nephrol Dial Transplant 1992; 7: 19.
  • 15
    Ahlswede KM, Armenti VT, Mokritz MJ. Premature births in female transplant recipients: degree and effect of immunosuppressive regimen. Surg For 1992; 443: 524525.
  • 16
    Armenti VT, Ahlswede BA, Moritz MJ, Jarrell BE. National Transplantation Registry: analysis of pregnancy outcomes of female kidney recipients with relation to time interval from transplantation to conception. Transplant Proc 1993; 25: 10361037.
  • 17
    Armenti VT, Ahlswede KM, Ahlswede BA, Jarrell BE, Moritz MJ, Burke JF. National Transplant Registry: outcomes of 154 pregnancies in cyclosporine-treated female kidney transplant recipients. Transplant 1994; 57: 502506.
  • 18
    Armenti VT, Stefanosky EV, Cater JR, McGory CH, Radomski J S, Moritz MJ. Pregnancy in transplant recipients. J Transp Coord 1995; 5: 130136.
  • 19
    Radomski JS, Moritz MJ, Munoz SJ, Cater JR, Jarrell BE, Annenti VT. National Transplantation Pregnancy Registry: analysis of pregnancy outcomes in female liver transplant recipients. Liver Transplant Surg 1995; 1: 281284.
  • 20
    Branch KR, Wagoner LE, Mannion JD et al. Comparison of first and subsequent pregnancies in female cardiac transplant recipients. J Heart Lung Transplant 1996; 15: 556.
  • 21
    Gaughan WJ, Moritz MJ, Radomski JS, Burke JF, Armenti VT. National Transplantation Pregnancy Registry: report on outcomes in cyclosporine-treated female kidney transplant recipients with an interval from transplant to pregnancy of greater than 5 years. Am J Kid Dis 1996; 28: 266269.
  • 22
    Baxi LV, Rho RB. Pregnancy after cardiac transplantation. Am J Obstet Gynecol 1993; 169: 3334.
  • 23
    Ville Y, Fernandez H, Samuel D, Bismuth H, Frydman R. Pregnancy in liver transplant recipients: course and outcome in 19 cases. Am J Obstet Gynecol 1993; 168: 896902.
  • 24
    Wagoner LE, Taylor DO, Olseen SL. Immunosuppressive therapy, management and outcome of heart transplant recipients during pregnancy. J Heart Lung Transplant 1993; 13: 9931000.
  • 25
    Eskander M, Gader S, Ong BY. Two successful deliveries in a heart transplant recipient. Obstet Gynecol 1996; 87: 880.
  • 26
    Reimers TJ, Sluss PM. 6-mercaptopurine treatment of pregnant mice: effects on second and third generations. Science 1978; 201: 6567.
  • 27
    Barker DJP, Gluckman PD, Godfrey KM, Harding JE, Owens JA, Robinson JS. Fetal nutrition and cardiovascular disease in adult life. Lancet 1993; 341: 938941.