http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, 2014; 27(17): 1816–1819 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2013.879699
REVIEW ARTICLE
Twin pregnancy after kidney transplantation: what’s on? A case report and review of literature
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Selcuk Universitesi on 01/08/15 For personal use only.
Salvatore Gizzo1, Marco Noventa1, Carlo Saccardi1, Gianluca Paccagnella1, Tito Silvio Patrelli2, Erich Cosmi1, and Donato D’Antona1 1
Department of Woman and Child Health, University of Padua, Padua, Italy and 2Department of Obstetrics, Gynaecological and Neonatology Sciences, University of Parma, Parma, Italy Abstract
Keywords
Objective: To describe the maternal and neonatal outcome of a twin pregnancy in a renal transplant recipient patient and reviewe the current literature on this theme. Methods: A case of 27 years old woman with a twin pregnancy arisen spontaneously in a renal transplant recipient from living donor characterized by an episode of slight anemia, mild hypertension, and a subsequent optimal maternal/neonatal outcome. During admission, the patient was treated with iron therapy, nifedipine, and methyldopa due to anemia and hypertension episodes. Strict monitoring of patient’s blood and urinary parameters, ultrasound fetues evaluation, and fetal lung maturity induction was performed. Results: Both anemia and hypertension were controlled through pharmacological intervention. During the second admission, the serum creatinine was 185 mmol/L and urine examination showed a proteinuria of 0.3 g/L. Ultrasound evaluation showed fetal wellness for both twin. Patient underwent caesarean section and gave birth to two healthy babies. Conclusions: It is necessary to define more strict criteria for the management of women with twin pregnancy and a history of renal transplantation to ensure the better maternal and neonatal outcome.
High-risk pregnancy, kidney transplantation, maternal-fetal wellness, obstetrical management, twin pregnancy
Background Women with an end-stage renal disease have a fertility rate 10 times lower than the healthy women of childbearing age [1]. Lower fertility rate seems to be related to an altered hypothalamic function. These patients, indeed, show high serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) [2]. Previous studies suggest that a successful renal transplant could restore a normal hormonal status and consequent fertility [1,3–5]. Murray et al. [6] published the first case of pregnancy after renal transplant and, more recently, Malatesta and Woo, based on European guidelines, proposed specific guidelines for planned pregnancy in such illness [7–9]. The most important recommendation is related to pregnancy interval time after the transplantation. One year is required for the recipient from a living-related donor’s (LRD) kidney, and 2 years in case of a living non-related donor (LNRD). Other recommendations are neither recent episode of acute rejection nor evidence of ongoing rejection, serum creatinine less than 177 mmol/l (better less than 133 mmol/l), normal blood pressure or single drug hypertensive treatment, absence Address for correspondence: Salvatore Gizzo, MD, Dipartimento della Salute della Donna e del Bambino, U.O.C. di Ginecologia e Ostetricia, Via Giustiniani 3, 35128 Padova, Italy. Tel: +39 333 5727248, +39 049 8213400. Fax: +39 049 8211785. E-mail: [email protected]
History Received 16 November 2012 Revised 4 December 2013 Accepted 29 December 2013 Published online 3 February 2014
or minimal proteinuria, no pyelocaliceal dilatation at renal ultrasound, low dose of immunosuppressive drugs (prednisone 515 mg/d, azathioprine 52 mg/kg/d, cyclosporine 54 mg/ kg/d, tacrolimus at a therapeutic dose), withdrawal of mycophenolate mofetil, and sirolimus before conception. During pregnancy, close obstetric controls and close monitoring of serum immunosuppressive drugs’ concentration are strictly recommended [1,3,9]. Through a close observance of all these recommendations, renal transplant’s (RT) recipient might be more susceptible to pregnancy complications than their healthy counterparts [1]. Major pregnancy complications described were hypertension, gestational diabetes, preeclampsia, premature delivery, preterm labor, intrauterine growth restriction, acute rejection, and graft loss; finally the majority of reported cases were delivered by a caesarean section [1,10,11]. Despite a lot of recommendations are proposed about the management of single pregnancy, nowadays, no guidelines concerning the management of twin pregnancy in RT recipient patients are reported. The main limitations in defining the best obstetrical and systemic follow-up are related to the poor data available in the literature and very low incidence of twin pregnancy in this little cohort of patients [12]. In our report, we describe a case of twin pregnancy arisen spontaneously in a RT recipient from living donor with good pregnancy course and subsequent optimal maternal/neonatal outcome.
DOI: 10.3109/14767058.2013.879699
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Selcuk Universitesi on 01/08/15 For personal use only.
Case presentation We report a case of a 27-year-old woman referred to our medical service due to severe anemia (Hb 71 g/L) in primipara at 26 weeks of gestation in a bicorial, biamniotic spontaneous twin pregnancy. Her past medical history revealed the onset of membrano-proliferative glomerulonephritis at 15 years old, evolved after 9 years in chronic renal failure. At 24 years of age, she underwent kidney transplantation from living donor (mother) and placement of the transplant in the right iliac fossa. The patient was treated with immunosuppressive drugs consisting a combination of daily Tacrolimus (FK), prednisolone, and micofenolato mofetile (the last immediately stopped at the beginning of the pregnancy). The patient referred a first trimester Estein–Barr virus (EBV) infection with detectable serum EBV-DNA successfully treated with Aciclovir 800 mg twice a day until negativization of viral load. At admission, patients showed reassuring vital signs (blood pressure: 125/85 mmHg, heart rate: 82 bpm, preserved diuresis). According to nephrologists’ advices, patients were treated with 2 weeks endovenous marital therapy with a rapid increase of serum Hb levels. During hospitalization, maternal check-up showed normal values of blood pressure without the necessity of antihypertensive therapy, a serum creatinine of 114 mmol/L, and a daily proteinuria of 0.24 g/L. At admission, corticosteroids’ fetal lung maturity induction was performed and fetal wellbeing was strictly monitored. At ultrasound, both fetuses showed regular growth pattern, amniotic fluid, and Doppler flowmetry, After 2 weeks, the patient was discharged with a normal renal function. At 31 weeks of gestation, she was again hospitalized for sickness and blood pressure raised up to 150/95 mm/Hg. The serum creatinine was 185 mmol/L, uric acid 0.49 mmol/L, and urea 9.8 mmol/L. Urine examination showed a proteinuria of 0.3 g/L. Blood pressure was normalized by daily nifedipine 10 mg and methyldopa 500 mg. Despite the vaginal swab resulting negative for no resident bacteria and protozoa, 3 d later, a premature preterm rupture of membranes occurred. After a second cycle of Bethametasone, she underwent caesarean section with the birth of two healthy babies both in cephalic presentation. The first twin was a male with a weight of 1690 g and a length of 49 cm, Apgar 9 and 10, at 1st and 5th min; the second one was a female with a weight of 1920 g and a length of 48 cm, Apgar 9 and 10 at 1st and 5th min. The puerperal course was complicated by the necessity of antihypertensive therapy implementation with nifedipine 40 mg/d and methyldopa 1500 g/d. Four days later, at discharge, serum creatinine level and blood pressure returned within the normal range. Today, 1 year later, mother and both children are in good physical condition.
Discussion Kidney transplantation is accepted worldwide as the only useful approach to increase the chances of conception in women with chronic renal failure [1]. Despite kidney transplantation could be a chance to improve fertility rate, pregnancies in receiving patients are often associated with severe maternal, fetal, and perinatal complications [1,3,10].
Twin pregnancy & kidney transplantation
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Maternal’s most frequent complications have been described by Deshpades et al. [1] and Va´zquez-Rodrı´guez et al. [3] and include gestational hypertension (more than 50% of deliveries), pre-eclampsia (27%), gestational diabetes (8%), and a relative increased risk of acute kidney rejection during pregnancy (8%). In addition, Perales-Puchalt et al. [13] and Armenti et al. [14] reported maternal anemia in more than 50% of these patients. Fetal’s most frequent complications described were: prematurity, respiratory failure, low birth weight, intrauterine growth restriction (IUGR), and intrauterine fetal death [1,3,15]. Concerning the way of delivery, almost all the cases described reported that the cesarean section as the most common choice, based on maternal or fetal indication [1]. Three pre-pregnancy factors were associated with adverse pregnancy outcomes [1]: bad blood pressure control, often associated with IUGR, preterm delivery, miscarriages, and low birth weight [16,17]; elevated serum creatinine level and proteninuria, both generally correlated with graft loss and preeclampsia onset [18,19]. Furthermore, pregnancy outcome seems to be related even to maternal age, since younger women demonstrated a lower incidence of miscarriage and a better pregnancy outcome [1,8,20,21]. Likewise, a longer interval time between RT and pregnancy (more than 2 years) seems to be an important factor for a positive pregnancy outcome [1,8,20,21]. Considering a twin pregnancy, we may think that the complications and risk factors described above can be even worse [22,23]. Sciarra et al. in 1975 reported the first case of twin pregnancy in RT women with a favorable outcome for one set of twins in a series of 16 single pregnancies after kidney transplantation [24]. In 1980, the European Dialysis and Transplant Association described four sets of twin, and one set of triplets among 120 pregnancies after RT [25]. Prieto et al. [26] in 1989 and Jimenez et al. [27] in 1995 described a successful twin and triplet pregnancy with an excellent outcome without complication for mother and child either. Burrows et al. in 1988 reported a successful twin pregnancy after RT maintained on cyclosporine A immunosuppression. In this case, dizygotic twins were delivered at 35 weeks of gestation, weighing 2452 and 2386 g without maternal or fetal complications reported [28]. Vyas et al. [29] in 1999 described the outcome of a twin pregnancy in a woman, with previous RT under Tacrolimus treatment. At 32 weeks of gestation, a cesarean section was performed, and both babies developed a severe respiratory distress syndrome and congestive heart failure. One baby died of the complications, the other one recovered after a more aggressive treatment with antihypertensive drugs. The authors concluded that the outcome in this set of twin may have been due to the result of cardiomyopathy secondary to Tacrolimus therapy. Boris Furman et al. [22] in 1998 described two cases of multiple pregnancies (triplets and twins) in renal allograft recipients. The authors reported that the first patient (pregnancy after induction of ovulation) underwent a fetal reduction from triplet to twin. After the procedure, no important changes of plasma creatinine or blood pressure were described. At 36 weeks of gestation, a cesarean section was performed and the woman delivered two healthy babies (a female of 1460 g and a male of 1910 g). Post-operative
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course was uneventful, and 6 months later, no signs of maternal renal function impairment were reported. The second patient (pregnancy after in vitro fertilization and embryo transfer) did not meet the optimal criteria for a ‘‘safe’’ pregnancy in RT recipients (serum creatinine level: 1.3 mg/dl, proteinuria: 6 g/24 h, and gestational hypertension: 180/110 mmHg). She delivered, by cesarean section, two healthy boys (33 weeks of gestation) without the onset of neonatal respiratory distress syndrome. The postoperative course was uneventful for both mother and children. Skhiri et al. [30] in 2005 reported an uneventful twin pregnancy after renal transplantation treated with double immunosuppressive therapy (Prednisolone–Azathioprine) that ended successfully and delivered by caesarian section. On the basis of European Guidelines [9], our patient could be considered eligible for pregnancy program with an estimating low risk (transplantation for more than 2 years, good trend of blood pressure, serum creatinine less than 1.5 mg/dl, and absence of proteinuria), she was hospitalized two times during pregnancy: first for anemia and second for gestational hypertension. In the literature, the adequate counseling and eligibility criteria for previous transplanted patients are well defined for the single pregnancy, but they remain unclear for twin or multiple pregnancies obtained spontaneously or after in vitro fertilization. Considering the majority of manuscript analyzed, we generally described a good maternal and neonatal outcome in this cohort of patients. However, considering the very small sample size of all these studies, we cannot establish with incontrovertible safety that the criteria reported by EBPG for single pregnancy in RT recipient could be extend to multiple pregnancies [9]. Based on these uncertainties, the management of these women is often left to single centers and individual physicians’ experience. Considering that twin or multiple pregnancies in healthy women implies different strategies and adjunctive device, it is our opinion that in RT patients, it should be necessary to define more strictly criteria for maternal–fetal wellbeing monitoring, risk assessment, and treatment option. On this basis, we suggest a close monitoring of maternal weigh, blood pressure, renal function, proteinuria, infections screening, and tacrolimus/cyclosporine blood level at least every 2 weeks both before and after delivery. It is necessary to perform a strict fetal surveillance with monthly ultrasound evaluation up to two times a week in the third trimester. Moreover, we suggest a close multidisciplinary management between nephrologists, who followed the patient after RT, and obstetricians, who followed the pregnancy, in order to estimate the single-patient risk and to define the optimal timing of delivery to ensure the best maternal and fetal outcome.
Acknowledgements Authors acknowledge all equip of nephrologists.
Declaration of interest All authors declare that they have no conflict of interest.
J Matern Fetal Neonatal Med, 2014; 27(17): 1816–1819
Contribution to authorship S. Gizzo and M. Noventa: project development, data collection, and manuscript writing. D. D’Antona and C. Saccardi: obstetrical management. G. Paccagnella and T. S. Patrelli: manuscript writing and English revision. D. D’Antona and E. Cosmi: area expertise and final approver. Patient consent: Authors confirm that they have obtained the written permission of those patients whose ‘‘case’’ is being presented.
References 1. 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. 2. Anantharaman P, Schmidt RJ. Sexual function in chronic kidney disease. Adv Chronic Kidney Dis 2007;14:119–25. 3. Va´zquez-Rodrı´guez JG, Rı´os-Chavarrı´a AL. Perinatal complications in women with kidney transplant. Nefrologia 2012; 32:639–46. 4. Watnick S. Pregnancy and contraceptive counseling of women with chronic kidney disease and kidney transplants. Adv Chronic Kidney Dis 2007;14:126–31. 5. 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. 6. Murray JE, Reid DE, Harrison JH, Merrill JP. Successful pregnancies after human renal transplantation. N Engl J Med 1963;269:341–3. 7. Framarino dei Malatesta M, Corona LE, De Luca L, et al. Successful pregnancy in a living-related kidney transplant recipient who received sirolimus throughout the whole gestation. Transplantation 2011;91:e69–71. 8. Kim HW, Seok HJ, Kim TH, et al. The experience of pregnancy after renal transplantation: pregnancies even within postoperative 1 year may be tolerable. Transplantation 2008;85: 1412–9. 9. EBPG Expert Group on Renal Transplantation. European best practice guidelines for renal transplantation. Section IV: long-term management of the transplant recipient. IV.10. Pregnancy in renal transplant recipients. Nephrol Dial Transplant 2002;17:50–5. 10. Fontana I, Santori G, Fazio F, Valente U. The pregnancy rate and live birth rate after kidney transplantation: a single-center experience. Transplant Proc 2012;44:1910–11. 11. Celik G, To¨z H, Ertilav M, et al. Biochemical parameters, renal function, and outcome of pregnancy in kidney transplant recipient. Transplant Proc 2011;43:2579–83. 12. Vayssie`re C, Benoist G, Blondel B, et al. French College of Gynaecologists and Obstetricians. Twin pregnancies: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF). Eur J Obstet Gynecol Reprod Biol 2011; 156:12–7. 13. Perales-Puchalt A, Vila Vives JM, Lo´pez Montes J, et al. Pregnancy outcomes after kidney transplantation–immunosuppressive therapy comparison. J Matern Fetal Neonatal Med 2012;25: 1363–6. 14. Armenti VT. Pregnancy after transplantation: milestones and assessments of risk. Am J Transplant 2011;11:2275–6. 15. Lo´pez V, Martı´nez D, Vin˜olo C, et al. Pregnancy in kidney transplant recipients: effects on mother and newborn. Transplant Proc 2011;43:2177–8. 16. Areia A, Galvao A, Pais MS, et al. Outcome of pregnancy in renal allograft recipients. Arch Gynecol Obstet 2009;279:273–7. 17. Coscia LA, Constantinescu S, Moritz MJ, et al. Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation. Clin Transpl 2009; 103–22. 18. Alfi AY, Al-essawy MA, Al-lakany M, et al. Successful pregnancies post renal transplantation. Saudi J Kidney Dis Transpl 2008;19: 746–50.
DOI: 10.3109/14767058.2013.879699
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Selcuk Universitesi on 01/08/15 For personal use only.
19. Kashanizadeh N, Nemati E, Sharifi-Bonab M, et al. Impact of pregnancy on the outcome of kidney transplantation. Transplant Proc 2007;39:1136–8. 20. Rahamimov R, Ben-Haroush A, Wittenberg C, et al. Pregnancy in renal transplant recipients: long-term effect on patient and graft survival. A single-center experience. Transplantation 2006;81: 660–4. 21. McKay DB, Josephson MA. Pregnancy in recipients of solid organs: effects on mother and child. N Engl J Med 2006;354:1281–93. 22. Furman B, Wiznitzer A, Hackmon R, et al. Multiple pregnancies in women after renal transplantation. Case report that rises a management dilemma. Eur J Obstet Gynecol Reprod Biol 1999; 84:107–10. 23. Kennedy C, Hussein W, Spencer S, et al. Reproductive health in Irish female renal transplant recipients. Ir J Med Sci 2012;181:59–63. 24. Sciarra JJ, Toledo-Pereyra LH, Bendel RP, Simmons RL. Pregnancy following renal transplantation. Am J Obstet Gynecol 1975;123:411–25.
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25. European Dialysis and Transplant Association. Successful pregnancies in women treated by dialysis and kidney transplantation. Br J Obstet Gynaecol 1980;87:839–45. 26. Prieto C, Errasti P, Olaizola JI, et al. Successful twin pregnancies in renal transplant recipients taking cyclosporine. Transplantation 1989;48:1065–7. 27. Jimenez E, Gonzalez-Caraballo Z, Morales-Otero L, SantiagoDelpin EA. Triplets born to a kidney transplant recipient. Transplantation 1995;59:435–6. 28. Burrows DA, O’Neil TJ, Sorrells TL. Successful twin pregnancy after renal transplant maintained on cyclosporine A immunosuppression. Obstet Gynecol 1988;72:459–61. 29. Vyas S, Kumar A, Piecuch S, et al. Outcome of twin pregnancy in a renal transplant recipient treated with tacrolimus. Transplantation 1999;67:490–2. 30. Skhiri H, Guedri Y, Achour A, et al. Twin pregnancy after renal transplantation: first case reported in Tunisia. Tunis Med 2005;83: 240–2.
REVIEW ARTICLE
Twin pregnancy after kidney transplantation: what’s on? A case report and review of literature
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Selcuk Universitesi on 01/08/15 For personal use only.
Salvatore Gizzo1, Marco Noventa1, Carlo Saccardi1, Gianluca Paccagnella1, Tito Silvio Patrelli2, Erich Cosmi1, and Donato D’Antona1 1
Department of Woman and Child Health, University of Padua, Padua, Italy and 2Department of Obstetrics, Gynaecological and Neonatology Sciences, University of Parma, Parma, Italy Abstract
Keywords
Objective: To describe the maternal and neonatal outcome of a twin pregnancy in a renal transplant recipient patient and reviewe the current literature on this theme. Methods: A case of 27 years old woman with a twin pregnancy arisen spontaneously in a renal transplant recipient from living donor characterized by an episode of slight anemia, mild hypertension, and a subsequent optimal maternal/neonatal outcome. During admission, the patient was treated with iron therapy, nifedipine, and methyldopa due to anemia and hypertension episodes. Strict monitoring of patient’s blood and urinary parameters, ultrasound fetues evaluation, and fetal lung maturity induction was performed. Results: Both anemia and hypertension were controlled through pharmacological intervention. During the second admission, the serum creatinine was 185 mmol/L and urine examination showed a proteinuria of 0.3 g/L. Ultrasound evaluation showed fetal wellness for both twin. Patient underwent caesarean section and gave birth to two healthy babies. Conclusions: It is necessary to define more strict criteria for the management of women with twin pregnancy and a history of renal transplantation to ensure the better maternal and neonatal outcome.
High-risk pregnancy, kidney transplantation, maternal-fetal wellness, obstetrical management, twin pregnancy
Background Women with an end-stage renal disease have a fertility rate 10 times lower than the healthy women of childbearing age [1]. Lower fertility rate seems to be related to an altered hypothalamic function. These patients, indeed, show high serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) [2]. Previous studies suggest that a successful renal transplant could restore a normal hormonal status and consequent fertility [1,3–5]. Murray et al. [6] published the first case of pregnancy after renal transplant and, more recently, Malatesta and Woo, based on European guidelines, proposed specific guidelines for planned pregnancy in such illness [7–9]. The most important recommendation is related to pregnancy interval time after the transplantation. One year is required for the recipient from a living-related donor’s (LRD) kidney, and 2 years in case of a living non-related donor (LNRD). Other recommendations are neither recent episode of acute rejection nor evidence of ongoing rejection, serum creatinine less than 177 mmol/l (better less than 133 mmol/l), normal blood pressure or single drug hypertensive treatment, absence Address for correspondence: Salvatore Gizzo, MD, Dipartimento della Salute della Donna e del Bambino, U.O.C. di Ginecologia e Ostetricia, Via Giustiniani 3, 35128 Padova, Italy. Tel: +39 333 5727248, +39 049 8213400. Fax: +39 049 8211785. E-mail: [email protected]
History Received 16 November 2012 Revised 4 December 2013 Accepted 29 December 2013 Published online 3 February 2014
or minimal proteinuria, no pyelocaliceal dilatation at renal ultrasound, low dose of immunosuppressive drugs (prednisone 515 mg/d, azathioprine 52 mg/kg/d, cyclosporine 54 mg/ kg/d, tacrolimus at a therapeutic dose), withdrawal of mycophenolate mofetil, and sirolimus before conception. During pregnancy, close obstetric controls and close monitoring of serum immunosuppressive drugs’ concentration are strictly recommended [1,3,9]. Through a close observance of all these recommendations, renal transplant’s (RT) recipient might be more susceptible to pregnancy complications than their healthy counterparts [1]. Major pregnancy complications described were hypertension, gestational diabetes, preeclampsia, premature delivery, preterm labor, intrauterine growth restriction, acute rejection, and graft loss; finally the majority of reported cases were delivered by a caesarean section [1,10,11]. Despite a lot of recommendations are proposed about the management of single pregnancy, nowadays, no guidelines concerning the management of twin pregnancy in RT recipient patients are reported. The main limitations in defining the best obstetrical and systemic follow-up are related to the poor data available in the literature and very low incidence of twin pregnancy in this little cohort of patients [12]. In our report, we describe a case of twin pregnancy arisen spontaneously in a RT recipient from living donor with good pregnancy course and subsequent optimal maternal/neonatal outcome.
DOI: 10.3109/14767058.2013.879699
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Selcuk Universitesi on 01/08/15 For personal use only.
Case presentation We report a case of a 27-year-old woman referred to our medical service due to severe anemia (Hb 71 g/L) in primipara at 26 weeks of gestation in a bicorial, biamniotic spontaneous twin pregnancy. Her past medical history revealed the onset of membrano-proliferative glomerulonephritis at 15 years old, evolved after 9 years in chronic renal failure. At 24 years of age, she underwent kidney transplantation from living donor (mother) and placement of the transplant in the right iliac fossa. The patient was treated with immunosuppressive drugs consisting a combination of daily Tacrolimus (FK), prednisolone, and micofenolato mofetile (the last immediately stopped at the beginning of the pregnancy). The patient referred a first trimester Estein–Barr virus (EBV) infection with detectable serum EBV-DNA successfully treated with Aciclovir 800 mg twice a day until negativization of viral load. At admission, patients showed reassuring vital signs (blood pressure: 125/85 mmHg, heart rate: 82 bpm, preserved diuresis). According to nephrologists’ advices, patients were treated with 2 weeks endovenous marital therapy with a rapid increase of serum Hb levels. During hospitalization, maternal check-up showed normal values of blood pressure without the necessity of antihypertensive therapy, a serum creatinine of 114 mmol/L, and a daily proteinuria of 0.24 g/L. At admission, corticosteroids’ fetal lung maturity induction was performed and fetal wellbeing was strictly monitored. At ultrasound, both fetuses showed regular growth pattern, amniotic fluid, and Doppler flowmetry, After 2 weeks, the patient was discharged with a normal renal function. At 31 weeks of gestation, she was again hospitalized for sickness and blood pressure raised up to 150/95 mm/Hg. The serum creatinine was 185 mmol/L, uric acid 0.49 mmol/L, and urea 9.8 mmol/L. Urine examination showed a proteinuria of 0.3 g/L. Blood pressure was normalized by daily nifedipine 10 mg and methyldopa 500 mg. Despite the vaginal swab resulting negative for no resident bacteria and protozoa, 3 d later, a premature preterm rupture of membranes occurred. After a second cycle of Bethametasone, she underwent caesarean section with the birth of two healthy babies both in cephalic presentation. The first twin was a male with a weight of 1690 g and a length of 49 cm, Apgar 9 and 10, at 1st and 5th min; the second one was a female with a weight of 1920 g and a length of 48 cm, Apgar 9 and 10 at 1st and 5th min. The puerperal course was complicated by the necessity of antihypertensive therapy implementation with nifedipine 40 mg/d and methyldopa 1500 g/d. Four days later, at discharge, serum creatinine level and blood pressure returned within the normal range. Today, 1 year later, mother and both children are in good physical condition.
Discussion Kidney transplantation is accepted worldwide as the only useful approach to increase the chances of conception in women with chronic renal failure [1]. Despite kidney transplantation could be a chance to improve fertility rate, pregnancies in receiving patients are often associated with severe maternal, fetal, and perinatal complications [1,3,10].
Twin pregnancy & kidney transplantation
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Maternal’s most frequent complications have been described by Deshpades et al. [1] and Va´zquez-Rodrı´guez et al. [3] and include gestational hypertension (more than 50% of deliveries), pre-eclampsia (27%), gestational diabetes (8%), and a relative increased risk of acute kidney rejection during pregnancy (8%). In addition, Perales-Puchalt et al. [13] and Armenti et al. [14] reported maternal anemia in more than 50% of these patients. Fetal’s most frequent complications described were: prematurity, respiratory failure, low birth weight, intrauterine growth restriction (IUGR), and intrauterine fetal death [1,3,15]. Concerning the way of delivery, almost all the cases described reported that the cesarean section as the most common choice, based on maternal or fetal indication [1]. Three pre-pregnancy factors were associated with adverse pregnancy outcomes [1]: bad blood pressure control, often associated with IUGR, preterm delivery, miscarriages, and low birth weight [16,17]; elevated serum creatinine level and proteninuria, both generally correlated with graft loss and preeclampsia onset [18,19]. Furthermore, pregnancy outcome seems to be related even to maternal age, since younger women demonstrated a lower incidence of miscarriage and a better pregnancy outcome [1,8,20,21]. Likewise, a longer interval time between RT and pregnancy (more than 2 years) seems to be an important factor for a positive pregnancy outcome [1,8,20,21]. Considering a twin pregnancy, we may think that the complications and risk factors described above can be even worse [22,23]. Sciarra et al. in 1975 reported the first case of twin pregnancy in RT women with a favorable outcome for one set of twins in a series of 16 single pregnancies after kidney transplantation [24]. In 1980, the European Dialysis and Transplant Association described four sets of twin, and one set of triplets among 120 pregnancies after RT [25]. Prieto et al. [26] in 1989 and Jimenez et al. [27] in 1995 described a successful twin and triplet pregnancy with an excellent outcome without complication for mother and child either. Burrows et al. in 1988 reported a successful twin pregnancy after RT maintained on cyclosporine A immunosuppression. In this case, dizygotic twins were delivered at 35 weeks of gestation, weighing 2452 and 2386 g without maternal or fetal complications reported [28]. Vyas et al. [29] in 1999 described the outcome of a twin pregnancy in a woman, with previous RT under Tacrolimus treatment. At 32 weeks of gestation, a cesarean section was performed, and both babies developed a severe respiratory distress syndrome and congestive heart failure. One baby died of the complications, the other one recovered after a more aggressive treatment with antihypertensive drugs. The authors concluded that the outcome in this set of twin may have been due to the result of cardiomyopathy secondary to Tacrolimus therapy. Boris Furman et al. [22] in 1998 described two cases of multiple pregnancies (triplets and twins) in renal allograft recipients. The authors reported that the first patient (pregnancy after induction of ovulation) underwent a fetal reduction from triplet to twin. After the procedure, no important changes of plasma creatinine or blood pressure were described. At 36 weeks of gestation, a cesarean section was performed and the woman delivered two healthy babies (a female of 1460 g and a male of 1910 g). Post-operative
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Selcuk Universitesi on 01/08/15 For personal use only.
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course was uneventful, and 6 months later, no signs of maternal renal function impairment were reported. The second patient (pregnancy after in vitro fertilization and embryo transfer) did not meet the optimal criteria for a ‘‘safe’’ pregnancy in RT recipients (serum creatinine level: 1.3 mg/dl, proteinuria: 6 g/24 h, and gestational hypertension: 180/110 mmHg). She delivered, by cesarean section, two healthy boys (33 weeks of gestation) without the onset of neonatal respiratory distress syndrome. The postoperative course was uneventful for both mother and children. Skhiri et al. [30] in 2005 reported an uneventful twin pregnancy after renal transplantation treated with double immunosuppressive therapy (Prednisolone–Azathioprine) that ended successfully and delivered by caesarian section. On the basis of European Guidelines [9], our patient could be considered eligible for pregnancy program with an estimating low risk (transplantation for more than 2 years, good trend of blood pressure, serum creatinine less than 1.5 mg/dl, and absence of proteinuria), she was hospitalized two times during pregnancy: first for anemia and second for gestational hypertension. In the literature, the adequate counseling and eligibility criteria for previous transplanted patients are well defined for the single pregnancy, but they remain unclear for twin or multiple pregnancies obtained spontaneously or after in vitro fertilization. Considering the majority of manuscript analyzed, we generally described a good maternal and neonatal outcome in this cohort of patients. However, considering the very small sample size of all these studies, we cannot establish with incontrovertible safety that the criteria reported by EBPG for single pregnancy in RT recipient could be extend to multiple pregnancies [9]. Based on these uncertainties, the management of these women is often left to single centers and individual physicians’ experience. Considering that twin or multiple pregnancies in healthy women implies different strategies and adjunctive device, it is our opinion that in RT patients, it should be necessary to define more strictly criteria for maternal–fetal wellbeing monitoring, risk assessment, and treatment option. On this basis, we suggest a close monitoring of maternal weigh, blood pressure, renal function, proteinuria, infections screening, and tacrolimus/cyclosporine blood level at least every 2 weeks both before and after delivery. It is necessary to perform a strict fetal surveillance with monthly ultrasound evaluation up to two times a week in the third trimester. Moreover, we suggest a close multidisciplinary management between nephrologists, who followed the patient after RT, and obstetricians, who followed the pregnancy, in order to estimate the single-patient risk and to define the optimal timing of delivery to ensure the best maternal and fetal outcome.
Acknowledgements Authors acknowledge all equip of nephrologists.
Declaration of interest All authors declare that they have no conflict of interest.
J Matern Fetal Neonatal Med, 2014; 27(17): 1816–1819
Contribution to authorship S. Gizzo and M. Noventa: project development, data collection, and manuscript writing. D. D’Antona and C. Saccardi: obstetrical management. G. Paccagnella and T. S. Patrelli: manuscript writing and English revision. D. D’Antona and E. Cosmi: area expertise and final approver. Patient consent: Authors confirm that they have obtained the written permission of those patients whose ‘‘case’’ is being presented.
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DOI: 10.3109/14767058.2013.879699
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