Author information
Shah S*, Warke H**, Mayadeo N***.
(*Third year resident, **Associate Professor, ***Professor, Department of Obstetrics and Gynecology, KEM hospital, Mumbai, India).
Abstract
Authors here present a case of successful pregnancy in a patient with renal transplant.
Introduction
The chances of a successful pregnancy are lower in patients with end stage renal disease which affects the hypothalamic pituitary axis, resulting in anovulatory menstrual cycles and decreased libido. After renal transplantation pregnancy rates significantly increase. Close monitoring of the patient and fetus results in overall good maternal as well as fetal outcome in a post renal transplant patient.
Case Report
A 35 years old woman married since 14 years, gravida 4 with 1 living issue and 2 spontaneous abortions, presented with 34 weeks of gestation with complaint of decreased fetal movements since 2 days. Patient was a known case of chronic kidney disease with renal transplant done 9 years ago at our tertiary care centre. She was diagnosed as a case of chronic kidney disease in 2007 when she had an episode of febrile illness for which medical opinion was taken in our institution. On evaluation patient had bilaterally contracted kidneys with abnormal renal function tests and hypertension. She was started on medications for the same. Later in the same year she was admitted for 4 months in the intensive care unit with complaints of fever, anasarca, breathlessness, palpitations, and anuria and had to undergo dialysis thrice a week. In 2008 patient underwent a successful renal transplant and was started on cyclosporine, prednisolone, mycophenolate mofetil, carvedilol and amlodipine. She had regular follow up with nephrologist. She conceived twice two and three years after the renal transplant and both pregnancies resulted in spontaneous abortions. In the third pregnancy nine years after the transplant she registered for antenatal care at our institute at 11 weeks of gestation. She was admitted for further evaluation and management. Patient and her husband were explained all the maternal and fetal risks regarding continuation of pregnancy, as well as effects of drugs on the fetus. They opted to continue the pregnancy. She had regular antenatal checkups and nephrology follow up. Apart from calcium and hematinics patient was on tab cyclosporine 50 mg and 20 mg in the morning and night respectively, tab prednisolone 5mg per day, tab azathioprine 50mg per day, tab alpha methyl dopa 500 mg thrice daily and tab labetalol 100 mg twice daily.
On admission at 35 weeks with decreased fetal movements her general condition was fair, with a pulse rate of 86/ min regular in rate, rhythm and volume, blood pressure recorded was 160/ 90 mm Hg in right upper arm. Respiratory and cardiovascular auscultatory findings were normal. On per abdomen examination fundal height was corresponding to 28 weeks of gestation, presentation was cephalic, fetal heart sounds were 146 bpm regular and there was no uterine activity or scar tenderness. On per vaginum examination cervical os was closed and uneffaced. There were no premonitory symptoms, bilateral knee jerks were normal and urine albumin was absent. Routine investigations normal; serum creatinine was1.5 mg%. Anomaly scan done at 22 weeks of gestation was normal. USG obstetric doppler scan was showed intrauterine gestation of 30 weeks 3 days with and estimated fetal weight of 1630 grams and absent end diastolic flow in umbilical artery with diastolic notch in uterine artery suggestive of intrauterine growth restriction with fetoplacental and uteroplacental insufficiency and brain sparing effect. Ultrasound of transplanted kidney was normal. Patient and relatives were explained about the maternal and fetal high risks and they wanted operative intervention for fetal indication. Decision for emergency lower segment cesarean section was taken in view of previous lower segment cesarean section with absent diastolic flow in umbilical artery with intrauterine growth restriction. She delivered a female child of 1.238 kg with Apgar of 9/10.
Patient was discharged on day 10 postoperatively. Baby was admitted in neonatal intensive care unit for 11 days in view of preterm with very low birth weight and small for gestational age. Baby had neonatal hyperbilirubinemia on day 3 of life for which she was given single surface phototherapy. Initially was started on intravenous fluids which were then gradually shifted to full maternal breast milk feeds. Baby was discharged on day 11 with adequate weight gain and after establishing breast feeding.
Discussion
Renal impairment results in reduced prolactin clearance and increased levels of prolactin, luteinizing hormone and follicle stimulating hormone resulting in reduced levels of estrogen and progesterone. High levels of gonadotropins disrupt the negative feedback mechanism and hence there is no LH surge, thus no ovulation. 73 % of patients on dialysis have irregular menstrual cycles and 50% of them have amenorrhea.[1] Studies have shown that after undergoing a successful renal transplant the infertility reverses. 5- 12 % of women have conceived after undergoing a renal transplant in their child bearing age with 60 - 80% success rate.[2, 3]
First successful post renal transplant pregnancy has been reported in 1958, in which a 23 year old patient had received a donor kidney from her own twin sister in 1956 and later she delivered a 3.3 kg baby by cesarean section 2 years after transplant.[4] Pregnancy following renal transplantation is of concern in two main aspects, that is the maternal as well as the fetal aspects.
There is no increased risk of rejection of the transplanted allograft following pregnancy and the allograft can withstand the hemodynamic changes during pregnancy provided pre-pregnancy serum creatinine level is less than 1.4 mg/dl and proteinuria is less than 500 mg %. If there is nephrotic range proteinuria the risk of spontaneous abortion, intrauterine growth retardation, and prematurity is increased.[5] Most important maternal complication which is of concern is hypertension and preeclampsia. The incidence rate is found to be six times greater than a normal population. Incidence of hypertension is about 52 to 69% and that of preeclampsia 24 and 38%. More importantly it is difficult to diagnose superimposed preeclampsia because of preexisting proteinuria as well as hyperuricemia which may be due to calcineurin inhibitors used. Another complication is risk of recurrent infections especially urinary tract infection. Asymptomatic bacteriuria should be treated and prophylactic therapy should be given during the entire course of pregnancy. Perinatal morbidity per se is not increased if there are no maternal complications like hypertension or deteriorating renal function. If such complications are present, the rate of spontaneous or missed abortions is 11- 26 % and the rate of preterm deliveries is increased by 13 times, with 12 times rise in low birth weight babies and 5 times rise in small for gestational age.[6]
Immunosuppresants are to be continued even during the pregnancy. Most of the drugs used are category C drugs whose benefit outweighs the risks. Calcineurin inhibitors used are tacrolimus and cyclosporine. Studies have shown that very low levels are transferred through placenta into fetal circulation and only about half the amount of that of mother is found in the fetal blood.[7] Azathioprine is a category D drug which is used because it gets converted to 6 – mercaptopurine which crosses placenta but is not converted to its toxic metabolite in fetus due to lack of production of inosinate pyrophosphorylase enzyme by fetal liver. Hence the adverse teratogenic effects of azathioprine are avoided and fetus is not harmed. Almost 90 % of corticosteroids used are metabolized in placenta before reaching the fetus. Mycophenolate and sirolimus have adverse effects and need to be stopped at least six weeks prior to conception. Mycophenolate mofitil is found to increase the risks of spontaneous abortions and fetal congenital anomalies such as cleft lip and palate, congenital heart defects, microtia, hypoplastic nails, congenital diaphragmatic hernia. Breast feeding can be continued with the use of immunosuppressant drugs, no adverse side effects have been reported.
Hence patients with renal transplant can conceive and have successful pregnancies with team effort of an obstetrician, nephrologist and neonatologist.
References
- Matuszkiewicz-Rowińska J, Skórzewska K, Radowicki S. Endometrial morphology and pituitary-gonadal axis dysfunction in women of reproductive age undergoing chronic haemodialysis—a multicentre study, Nephrology Dialysis Transplantation, 2004; 19(8): 2074–2077.
- Sturgiss SN, Davison JM. Effect of pregnancy on long-term function of renal allografts. Am J Kidney Dis. 1992;19(2):167-72.
- Armenti VT, Daller JA, Constantinescu S, Silva P, Radomski JS, Moritz MJ, et al. Report from the National Transplantation Pregnancy Registry: outcomes of pregnancy after transplantation. Clin Transpl. 2006: 57-70.
- Murray JE, Reid DE, Harrison JH, Merrill JP. Successful pregnancies after human renal transplantation, N Engl J Med. 1963; 269:341–343.
- European best practice guidelines for renal transplantation. Section IV: long-term management of the transplant recipient. IV.10. Pregnancy in renal transplant recipients, EBPG Expert Group on Renal Transplantation. Nephrol Dial Transplant. 2002;17 Suppl 4:50-5.
- Coscia LA, Constantinescu S, Moritz MJ, Frank AM, Ramirez CB, Doria C et al. Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation. Clinical Transpl. 2008: 89-105.
- Venkataramanan R, Koneru B, Wang C. Cyclosporine and its metabolites in mother and baby. Transplantation. 1988; 46(3):468–469.
Shah S, Warke H, Mayadeo N. Pregnancy In A Post Renal Transplant Patient. JPGO 2017. Volume 4 No.10. Available from: http://www.jpgo.org/2017/10/pregnancy-in-post-renal-transplant_1.html