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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2016  |  Volume : 27  |  Issue : 2  |  Page : 227-232
Pregnancy after renal transplantation: Effects on mother, child, and renal graft function


Department of Nephrology, Dialysis and Kidney Transplantation, CHU Ibn Sina, Rabat, Morroco

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Date of Web Publication11-Mar-2016
 

   Abstract 

The aim of this study was to report our experience of pregnancy in renal transplant (RT) patients and its medium and long-term effects on the renal graft as well as the maternal fetal complications. We studied 21 pregnancies in 12 RT patients with mean age of 29.9 ± 5.3 years. The mean duration of RT to 1 st pregnancy was 42 (21-68.5) months and the median follow-up period was 112.5 (138-165) months. The pregnancy was planned in 28.6% of the cases. At the time of the diagnosis of the pregnancy, all the patients were maintained on corticosteroids and cyclosporine, 14.3% of the patients were on mycophenolate mofetil, and 71.4% of the patients were on azathioprine. The high blood pressure was present before the pregnancy in 33.3% of the patients. During pregnancy, proteinuria appeared in 20% of the cases, urinary tract infection in 33.3%, and preeclampsia in 5%. Anemia was present in all the patients during pregnancy. The doses of cyclosporine were increased during pregnancy. The mean term of delivery was 37 ± 2 weeks. Premature delivery was observed in 19% of the cases, fetal death in utero in 10%, and abortion in 15%. The number of living children was 16, with a mean birth weight of 3014 ± 515 g; the weight was lower than 2500 g in three (15%) cases. In the long-term follow-up, we noticed two cases of acute rejection related to patients' noncompliance, and four cases of chronic allograft nephropathy, without a switch to dialysis. We conclude that pregnancy in RT patients requires multidisciplinary care because of the increased risks of maternal and fetal complications. Each pregnancy needs to be planned; all parameters have to be studied and evaluated in order to allow for optimization of outcome and minimization of complications.

How to cite this article:
El Houssni S, Sabri S, Benamar L, Ouzeddoun N, Bayahia R, Rhou H. Pregnancy after renal transplantation: Effects on mother, child, and renal graft function. Saudi J Kidney Dis Transpl 2016;27:227-32

How to cite this URL:
El Houssni S, Sabri S, Benamar L, Ouzeddoun N, Bayahia R, Rhou H. Pregnancy after renal transplantation: Effects on mother, child, and renal graft function. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2019 Sep 21];27:227-32. Available from: http://www.sjkdt.org/text.asp?2016/27/2/227/178204

   Introduction Top


Kidney transplantation is the treatment of choice for end-stage renal disease. It provides a quick recovery of gonad function, [1] rendering it comparable to the general population rate of infertility in women with a renal transplant (RT) (≈10%). [2] However, pregnancy in RT is still highly risky for mother, fetus, and renal graft. [3] Complications during pregnancy and factors associated with these complications are not well quantified, as well as the effect of pregnancy on graft survival and the optimal interval that should exist between transplantation and pregnancy. [4]

The aim of our study was to report our experience with the occurrence of pregnancy in RT patients, determine its progress and its impact on renal function and long-term graft survival besides the maternofetal complications.


   Patients and Methods Top


We retrospectively studied pregnancies occurring in RT women followed up in our center between 1998 and 2012. Clinical and laboratory parameters were identified from medical records.

During pregnancy, the nephrologist follow-up occurred monthly and consisted of clinical evaluation (blood pressure and peripheral edema and other signs of preeclampsia) and laboratory investigations (serum creatinine, uric acid, serum aminotransferase, hemoglobin, 24 h proteinuria, urine culture and residual blood level of cyclosporine). The obstetrical care was provided by an obstetrician every month with a clinical examination and Doppler ultrasound. After 34 weeks of gestation (WG), the patients were evaluated each week until delivery. All the women were initiated on aspirin (100 mg/ day) from 21 st to 34 th WG. The mode of delivery was based on the obstetric indications.

Pregnancies were allowed after two years of RT in case of normal renal function in the absence of hypertension and proteinuria. Hypertension was defined as a blood pressure over or equal to 140/90 mm Hg. Preeclampsia was defined as pregnancy-induced hypertension with positive proteinuria (>300 mg/day) beyond 20 WG. Anemia was defined as hemoglobin levels below 11 g/dL. Preterm birth was defined as birth before 37 WG, and low birth weight as weight <2500 g.

In case of scheduled pregnancy, mycophenolate mofetil (MMF) was switched to azathioprine (AZA). After delivery, the AZA was switched back to MMF at the end of the 1 st week. Breastfeeding was not allowed, and all the patients underwent lactation slowdown.


   Statistical Analysis Top


Analysis of the collected data was performed using SPSS version 10.0 software. Quantitative parameters were expressed according to their divisions as mean ± standard deviation or median (quartile). Quality parameters were expressed as actual (percent). P <0.05 was considered as statistical significance.


   Results Top


There were 21 pregnancies in 12 RT women; nine of them were primiparous, and seven out of 12 (58%) patients had two pregnancies after RT.

The average age of the patients at the time of pregnancy was 29.9 ± 5.3 years. Ten women were transplanted from related living donors. The initial nephropathy was unknown in eight patients. The median interval between RT and pregnancy was 42 (21-68.5) months, seven pregnancies occurred before the end of the 2 nd year of RT. All the pregnancies were spontaneous except six of them (28.6%) were planned. Hypertension before pregnancy was observed in seven (31.0%) pregnancies; none showed proteinuria. All the patients had serum creatinine <13 mg/L (114.4 μmol/L) before pregnancy.

Maintenance immunosuppression consisted primarily of corticosteroids, azathioprine, and cyclosporine. Three patients with unplanned pregnancies were on MMF, which was switched to AZA as soon as the diagnosis of pregnancy was confirmed [Table 1].
Table 1: Clinical manifestations and laboratory investigation at time pregnancy diagnosis in renal transplant patients.

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Hypertension was observed during nine (42.8%) pregnancies; two patients developed hypertension during pregnancy. In patients with previous hypertension, there was no increase of blood pressure.

Proteinuria turned positive in one patient during the second quarter of gestation and in another in the third quarter, and in two patients in the postpartum period.

The mean of creatinine was 0.97 mg/dL and 0.85 mg/dL in prepregnancy and the second quarter of gestation, respectively, and increased to 1.0 mg/dL in the third quarter and three months postpartum, (P <0.001). The mean hemoglobin level was 12.2 g/dL and 9.5 g/dL in the prepregnancy and the second quarter respectively, and increased to 11 g/dL in the postpartum period, (P <0.001). Oral iron supplements were initiated in 20 cases and iron injection (100 mg/week for 7 weeks) in one patient. Erythropoietin was used in three cases.

The average dose of cyclosporine was 2.96 ± 0.81 mg/kg/day during the first quarter of gestation, and it was increased in the second and third quarter to 3.46 ± 0.89 mg/kg/day and 3.62 ± 1.03 mg/kg/day, respectively, (P <0.001). Changes in doses of corticosteroids and AZA were not significant. The evolution of pregnancy was marked by the occurrence of one case of preeclampsia, seven (33.3%) cases of urinary infection including two cases of acute pyelonephritis, and one case of hepatic cytolysis six weeks after the introduction of alpha-methyldopa. No cases of eclampsia, gestational diabetes, or acute renal failure were noted.

There were three abortions (14.3%); one of them was a spontaneous at five WG in a patient whose pregnancy was neither scheduled nor authorized and receiving MMF. Four (19%) deliveries were preterm and 14 (66.7%) at term; the average term was 37 ± 2 WG. The mode of delivery was cesarean section in 11 (52.4%) cases.

In the postpartum period, there were two cases of mother infections (urinary and episiotomy abscess) and one case of bleeding after delivery. All the patients underwent a slowdown in lactation. Oral contraception was initiated within 21 days postpartum. Three patients underwent permanent contraception by a tubal ligation. Fetal development was marked by the occurrence of two (9.5%) fetal deaths. In the 16 living children, the mean birth weight was 3014 ± 515 g. Three cases of low birth weight were reported. No cases of neonatal malformations were observed. Finally, one newborn baby presented with generalized convulsions related hypocalcemia at 65 mg/L [Table 2].
Table 2: Characteristics and outcomes in pregnancies of renal transplant patients.

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No acute rejection episodes were observed during pregnancy. After a median follow-up of 112.5 (138-165) months, there were two cases of acute rejection at 12 months postpartum in relation with poor adherence to treatment, and four cases of chronic rejection that were detected nine months after childbirth. No patient returned to dialysis.


   Discussion Top


In our study, pregnancy occurred in 30.8%of RT women at childbearing age. It far exceeds the data in the literature (2-5%). [5],[6] However, there are associated adverse effects of pregnancy on the RT patients including high blood pressure, elevated creatinine, and development of proteinuria. [4] KDIGO guidelines 2009 allowed pregnancy after one year of RT in case of stable renal function (creatinine clearance >40 ml/min), proteinuria below 1 g/day, and cessation of teratogenic drugs. [7] In our patients, taking into account these recommendations, all criteria of good prognosis were present, except for three pregnancies occurring before the end of the 1 st year of transplantation and three pregnancies that began while the patients were maintained on MMF. Nearly 50% of the pregnancies were unplanned RT. [8] In our study, they represented 71.4%, and this is related to poor adherence of patients to oral contraception. Spontaneous abortion was observed in 14-20% of cases. [4],[9] Among our pregnancies, only one (4.7%) resulted from a spontaneous abortion at five WG. In RT women, the glomerular filtration rate increases during pregnancy as in the general population, but its amplitude depends on the level of baseline renal function. [10],[11] The English registry has studied the evolution of renal function during pregnancy and the postpartum in 193 cases. Serum creatinine decreased from 125 μmol/L in prepregnancy to 110 mmol/L in the second quarter to go up to 112 mmol/L in the third quarter, then to 130 mmol/L in three to six months postpartum. These differences are significant. [12] In our study, serum creatinine decreased significantly during the second quarter of gestation.

Maternal complications include mainly hypertension (60-80%) with the risk of preeclampsia (20-30%). [10],[11],[13],[14],[15] In our study, only one case of preeclampsia was noted, and this can be explained by our small size sample. Immunosuppressive therapy renders RT pregnant women more susceptible to infection with urinary tract infection, [8] and may be observed seen in 40% of the cases. [11]

Neonatal complications manifest mainly as low birth weight (20-30%) and prematurity (45-60%). [10],[11],[13] Cesarean delivery was indicated in our patients in 52.4% of cases, and this was comparable to the published data (over 50%). [4],[13] The incidence of malformations (3-5%) was comparable to the general population. [15],[16]

The use of MMF is associated with structural abnormalities, so it is advisable to stop at least six weeks prior to conception. [2],[4],[7] In our study, we did not notice any defects in two living children starting pregnancies while they were on MMF.

Breastfeeding is not indicated in RT women after delivery because immunosuppressive agents are found in variable levels in breast milk, and their consequences on the newborn are not well known. [17]

The incidence of acute rejection does not seem to increase during pregnancy, which causes a moderate decrease in immunity. [13],[14] The risk factors include the presence of a history of acute rejection before pregnancy and inadequacy of adjustment of immunosuppressive doses. [11] In studies comparing pregnant and nonpregnant RT women, pregnancy was not a factor for long-term chronic graft rejection. [14],[18],[19],[20]

In conclusion, fertility is quickly restored in the RT, explaining the need for early contraception. Successful pregnancy in RT women is possible if it is planned and authorized. The multidisciplinary approach including nephrologist, gynecologist, and pediatrician helps prevent maternofetal and renal complications.

Conflict of interest: None declared.

 
   References Top

1.
Gill JS, Zalunardo N, Rose C, Tonelli M. The pregnancy rate and live birth rate in kidney transplant recipients. Am J Transplant 2009;9:1541-9.  Back to cited text no. 1
    
2.
Richman K, Gohh R. Pregnancy after renal transplantation: A review of registry and single-center practices and outcomes. Nephrol Dial Transplant 2012;27:3428-34.  Back to cited text no. 2
[PUBMED]    
3.
Bouattar T, Hakim H, Rhou H, Benamar L, Bayahia R, Ouzeddoun N. Pregnancy in renal transplant recipients. Transplant Proc 2009;41:1586-8.  Back to cited text no. 3
    
4.
Deshpande NA, James NT, Kucirka LM, et al. Pregnancy outcomes in kidney transplant recipients: A systematic review and metaanalysis. Am J Transplant 2011;11:2388-404.  Back to cited text no. 4
    
5.
Tan PK, Tan A, Koon TH, Vathsala A. Effect of pregnancy on renal graft function and maternal survival in renal transplant recipients. Transplant Proc 2002;34:1161-3.  Back to cited text no. 5
    
6.
Ghafari A, Sanadgol H. Pregnancy after renal transplantation: Ten-year single-center experience. Transplant Proc 2008;40:251-2.  Back to cited text no. 6
    
7.
Kasiske BL, Zeier MG, Craig JC, et al. Kdigo clinical practice guideline for the care of kidney transplant recipients. Sexual and fertility: Female fertility. Am J Transplant 2009;9 Suppl 3:S106-9.  Back to cited text no. 7
    
8.
Ducarme G, Ceccaldi PF, Toupance O, Graesslin O, Rieu P, Gabriel R. Pregnancy after renal transplantation. Obstetrical follow-up and impact on renal graft function. Gynecol Obstet Fertil 2006;34:209-13.  Back to cited text no. 8
    
9.
Cruz Lemini MC, Ibargüengoitia Ochoa F, Villanueva González MA. Perinatal outcome following renal transplantation. Int J Gynaecol Obstet 2007;96:76-9.  Back to cited text no. 9
    
10.
Davison JM, Bailey DJ. Pregnancy following renal transplantation. J Obstet Gynaecol Res 2003;29:227-33.  Back to cited text no. 10
    
11.
Fuchs KM, Wu D, Ebcioglu Z. Pregnancy in renal transplant recipients. Semin Perinatol 2007;31:339-47.  Back to cited text no. 11
    
12.
Sibanda N, Briggs JD, Davison JM, Johnson RJ, Rudge CJ. Pregnancy after organ transplantation: A report from the UK Transplant pregnancy registry. Transplantation 2007;83: 1301-7.  Back to cited text no. 12
    
13.
Tissier I, Dreyfus M, Woehl-Jaegle ML, el Khadime A, Ndocko MA, Ritter J. Pregnancy after renal transplantation. Obstetrical follow up and long term outcome of the renal graft. J Gynecol Obstet Biol Reprod (Paris) 1999;28: 550-5.  Back to cited text no. 13
    
14.
Pezeshki M, Taherian AA, Gharavy M, Ledger WL. Menstrual characteristics and pregnancy in women after renal transplantation. Int J Gynaecol Obstet 2004;85:119-25.  Back to cited text no. 14
    
15.
Wyld ML, Clayton PA, Jesudason S, Chadban SJ, Alexander SI. Pregnancy outcomes for kidney transplant recipients. Am J Transplant 2013;13:3173-82.  Back to cited text no. 15
    
16.
Yildirim Y, Uslu A. Pregnancy in patients with previous successful renal transplantation. Int J Gynaecol Obstet 2005;90:198-202.  Back to cited text no. 16
    
17.
McKay DB, Josephson MA. Pregnancy in recipients of solid organs - Effects on mother and child. N Engl J Med 2006;354:1281-93.  Back to cited text no. 17
    
18.
Levidiotis V, Chang S, McDonald S. Pregnancy and maternal outcomes among kidney transplant recipients. J Am Soc Nephrol 2009; 20:2433-40.  Back to cited text no. 18
    
19.
Basaran O, Emiroglu R, Seçme S, Moray G, Haberal M. Pregnancy and renal transplantation. Transplant Proc 2004;36:122-4.  Back to cited text no. 19
    
20.
Miranda CT, Melaragno C, Camara NO, Pacheco-Silva A, Medina-Pestana PJ. Adverse effects of pregnancy on renal allograft function. Transplant Proc 2002;34:506-7.  Back to cited text no. 20
    

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Correspondence Address:
Siham El Houssni
Department of Nephrology, Dialysis and Kidney Transplantation, CHU Ibn Sina, Rabat
Morroco
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DOI: 10.4103/1319-2442.178204

PMID: 26997374

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