Pregnancy following renal transplantation in Sri Lanka

Objective To assess the outcome and complications of pregnancy following renal transplantation in Sri Lanka. Methods Ten pregnancies following transplantation man­ aged between January 1993 and July 1999 by the Univer­ sity Obstetrics and Gynaecology Unit, De Soysa Hospital for Women, Colombo were reviewed. Results Five women had planned pregnancy with an aver­ age duration from transplantation to conception of 2.3 (± 0.2) years; five had an unplanned pregnancy within 12 months of transplantation. All were treated with immuno­ suppressives, with none developing rejection. In the planned pregnancy group, 3 developed pregnancy induced hyper­ tension and 3 impaired glucose tolerance. All delivered mature healthy babies with an average birth weight of 2.6 (±0.3) kg. In the unplanned group, 1 developed cholestatic jaundice and delivered a growth retarded baby at 36 weeks. Another developed severe pulmonary oedema at 34 weeks (due to a past myocardial infarction) resulting in a fresh stillbirth. Two others has mid-trimester foetal deaths complicating severe diabetes mellitus. The conception at 3 months after transplantation developed diabetes mellitus and pregnancy induced hypertension, and delivered a live growth retarded baby. None had deterioration of renal function. Conclusion Although a successful outcome is possible with stringent pre-pregnancy selection, maternal morbid­ ity and foetal wastage can be high in those without.


Introduction
Kidney transplantation is the most suitable mode of renal replacement for end-stage renal failure.It is more ef fective than long term dialysis in restoring fertility and permitting successful pregnancy.Renal, endocrine and sexual function are reported to become normal soon after successful transplantation (1,2).Reports of high rates of successful pregnancies fol lowing transplantation are from centres with well estab lished programs which are located predominantly in the west.Since 198S, 42 women in the childbearing age have undergone live related donor renal transplantation in Sri Lanka (3).This is the first report on pregnancy outcome following transplantation in Sri Lanka.
l Senior Lecturer, and ^Professor and Head, Department of Obstetrics and Gynaecology, 2 Professor and Head, Depart ments of Clinical Medicine and *Surgery, Faculty of Medicine, University of Colombo (Revised version accepted 25 October 2000).

Methods
An analysis of the outcome of pregnancy of women after renal transplantation managed by the University Obstetrics and Gynaecology Unit, De Soysa Hospital for Women, Colombo from January 1993 to December 1998 is presented.They were referred for antenatal care by the Transplant Team of the University of Colombo.
The pregnancies were managed using a standard pro tocol at a combined antenatal clinic.All patients were clini cally evaluated regarding general medical health at ante natal booking.Special consideration was given to blood pressure and cardiac function.The following variables were recorded serially at antenatal follow up: maternal blood pressure, weight gain and well being, maternal infection screen, abdominal ultrasound examination, serum urea, creatinine and electrolyte levels, 24-hour creatinine clear ance, urine microscopy and culture, full blood count and a six-point blood glucose series.Obstetric and medical com plications detected during pregnancy were managed ap propriately.During the antenatal period the patient and her husband were counselled regarding appropriate post partum family planning methods.
Medical and obstetric indicators determined the mode of delivery.All patients deemed suitable for vaginal deliv ery were allowed a trial of labour.Steroid cover, antibiotic prophylaxis and epidural analgesia were used for the de livery of all patients.When patients were identified as chronic carriers of hepatitis B, the cord blood was tested for hepatitis B surface antigen, hepatitis B specific immu noglobulin was injected to the baby within 6 hours of birth and active immunisation against hepatitis B was commenced by injecting to the opposite limb.

Results
The 10 women in their first pregnancy following live related donor renal transplantation were all in the first tri mester at antenatal booking.The average maternal age was 31 years (range 21 to 38).Five were planned pregnan cies in women who had undergone transplantation 24 to 30 months before conception.The transplantation to con ception intervals in the remaining 5 women who had un planned pregnancies were between 3 and 12 months.

Pregnancy outcomes
The immunosuppressive therapy in the planned preg nancy group consisted of prednisolone 10 mg daily and azathioprine lmg/kg body weight once daily.Three women were positive for hepatitis B surface antigen, with no evi dence of liver dysfunction.Three women developed mod erate pregnancy induced hypertension (PIH) in the third trimester, one of whom developed intrauterine foetal growth retardation and reduction in liquor volume confirmed by ultrasound examination.Three developed impaired glu cose tolerance (IGT) of pregnancy.All were delivered by elective caesarean section for obstetric reasons.All preg nancies had a successful foetal outcome with live healthy babies weighing 2.2 to 2.9 kg.None of the babies, tested positive for hepatitis B when the umbilical cord blood was evaluated.The baby of the mother with lupus had an uneventful neonatal period.All women opted for sterilisation by tubal ligation following delivery (Table ).
In the group with unplanned conceptions, one woman was a primigravida.She developed cholestatic jaundice at 29 weeks of gestation, which persisted up to term.Her serology for viral hepatitis and cytomegalovirus was nega tive.She required an elective caesarean section at 36 weeks for foetal growth retardation.A live baby weighing 2.1 kg was delivered.Two others had severe diabetes mellitus.One had type 1 diabetes of 15 years' duration, was in her fifth pregnancy with no living children, and had conceived 11 months after transplantation.She had chronic hyper tension, peripheral vascular disease, diabetic neuropathy and retinopathy, and was positive for hepatitis B surface antigen with normal liver function.She developed preg nancy induced hypertension, gross oedema and chronic ulceration of a foot and had a death in utero at 29 weeks' of gestation.The other had steroid induced diabetes, and was the mother of an 8-year old child born before the onset of renal disease.She had undergone transplanta tion 6 months before conception and was taking predniso lone 20 mg daily.She developed obstructive jaundice, tested positive for hepatitis B surface antigen with no features of hepatic failure.She had an intrauterine death at 29 weeks.The jaundice resolved post-delivery and she underwent sterilisation.Another woman who conceived 6 months fol lowing renal transplantation developed heart failure at 36 weeks due to left ventricular dysfunction caused by a pre vious anterior myocardial infarction.She also tested posi tive for hepatitis B surface antigen, and developed moder ate hypertension.She had spontaneous onset of labour and developed foetal distress.'An emergency caesarean section was performed and a fresh stillborn baby weighing 2.2 kg was delivered She underwent surgical sterilisation.The woman who conceived 3 months after renal transplan tation was in her third pregnancy with no living children.She developed moderate pregnancy induced hypertension and severe diabetes requiring insulin therapy.She under went an elective caesarean section at 36 weeks and a live growth retarded baby weighing 1.9 kg was delivered.The immunosuppressive therapy in this group of women con sisted of prednisolone 20 mg daily, azathioprine 2 mg/kg and cyclosporine 10 mg/kg daily.

Discussion
More than 2000 pregnancies following renal trans plantation have been reported, predominantly from the western world (4-8).There are no reports from South Asia.It is estimated that 1 in 50 women of child-bearing age with a functioning renal transplant becomes pregnant.Nearly 30% of conceptions following transplantation abort spon taneously in the first trimester, but more than 90% of those that survived the first trimester have had a successful out come (9).A much higher rate of fertility was observed in this series, with 10 out of 42 women in the child-bearing age group becoming pregnant.Moreover, this figure may be an underestimate in view of probable unreported early miscarriages.The high fertility reflects the desire of Sri Lankan women following renal transplantation to bear chil dren or unmet family planning needs.Survival figures indicate that 80% of recipients of kid neys from live related donors are alive at 5 years, with more than 50% expected to survive for at least 10 years (10).If graft function is maintained at 2 years the chances of al lograft survival at 3 and 10 years is high (11).When a woman with a transplanted kidney becomes pregnant, a major concern is that the mother may not survive or remain well enough to rear the child.Indeed, about 10% of these women may be dead within 7 years of pregnancy.

Papers
Although in this series a successful outcome was achieved in 70%, there was a high maternal morbidity and foetal wastage.It is recommended to wait for 18 to 24 months after renal transplant to allow time for recovery from sur gery, for graft function to stabilise and for the immunosup pression to reach maintenance levels.Other recommenda tions for starting a pregnancy are that the woman is normotensive with minimal or no proteinuria, has no evidence of graft rejection or pelvicalyceal distension, and has a stable creatinine less than 130 umol/1 (12).Only 30% of women in this series met all these requirements.Although the num ber is small in this series, its results show that if these criteria are fulfilled much less complications would occur during pregnancy.
The common complications that occur among poorly selected patients include pre-eclampsia, gestational dia betes, foetal growth retardation and maternal cardiac and hepatic dysfunction.The high prevalence of hepatitis B carrier status is another factor that needs to be considered in the evaluation for fitness, although it is not a barrier for a planned conception.The high rate of caesarean section in this series differs from that previous reports.The indica tions for caesarean section in this series were chiefly poor previous obstetric outcome, advanced maternal age and foetal growth retardation.Our policy has been to comply with the patient's request for sterilisation at the time of a successful caesarean delivery.The management of women of child-bearing age who undergo successful renal transplantation should include a keen awareness of their improved fertility and associated complications, and the careful selection, timing and appropriate management of pregnancy.