Since the first successful live birth to a woman with a kidney transplant in 1958,1 an increasing number of women are conceiving posttransplant. Kidney and liver are the most commonly transplanted organs in the United States. Patients with solid organ transplantation may voluntarily report their pregnancies on their own or in conjunction with their health care providers to the National Transplantation Pregnancy Registry (NTPR), which began collecting data from recipients in North America in 1991. A total of 1396 female transplant recipients (kidney, liver, liver–kidney, kidney–pancreas, heart, heart–lung, and lung) have reported 2463 pregnancies according to the 2014 annual report2 (Table 1). In 2005, the Women’s Health Committee of the American Society of Transplantation released a consensus document summarizing clinical practice recommendations for the management of pregnant transplant recipients; the consensus document has not been updated since 2005. This focused review will address concerns important to the obstetric anesthesia management of pregnant solid organ transplant recipients.
TIMING OF PREGNANCY AFTER TRANSPLANTATION
Data are lacking regarding the optimal transplant–conception interval. The 2005 American Society of Transplantation Consensus Conference suggested that pregnancy 1 year after transplant is safe as long as the patient has stable graft function (Table 2)3–14: no episodes of rejection in the past year, a low risk for opportunistic infections, stable renal function (including in those receiving organs other than a kidney), and a low stable dose of maintenance immunosuppression.15 Meta-analyses show improved maternal and neonatal outcomes and a decreased incidence of obstetric complications for renal recipients and liver recipients when conception is delayed for at least 1 year.16,17 For renal transplant patients, the initial recommendation was to wait 2 years before conceiving on the basis of the rejection risk. More recent and potent immunosuppressive strategies, however, have significantly decreased rejection rates in the first posttransplant year. Therefore, the advice to wait 2 years after a successful transplant is considered more restrictive than necessary.15 The consensus group emphasized that data regarding one transplant group cannot be extrapolated to those receiving another organ.15
Patients with end-organ failure experience hypothalamic–pituitary–gonadal dysfunction and thus impaired fertility.15 Gonadal dysfunction resolves in about 6 months after renal transplantation.15 Restoration of menstruation and fertility in renal and liver transplant recipients has been reported in meta-analyses.16–18 For the heart, lung, and heart–lung recipients, limited data regarding hypothalamic–pituitary–gonadal function after transplant are available; however, any pubertal delay caused by previous organ failure likely resolves with a well-functioning graft.18 Normal clinical and hormonal onset of puberty has been reported in adolescents after heart transplant.19
To avoid an unanticipated pregnancy within the first year after a transplant, it is suggested that posttransplant contraception be discussed with the patient. The optimal method of contraception has not been determined but should consider the type of transplanted organ, hormonal levels of the contraceptive, potential interactions of the contraceptive with immunosuppressive medications, the underlying medical conditions of the patient, and costs.15,20 Intrauterine devices may be the best option per expert opinion because they are long-acting, are reversible, are effective, have negligible drug interactions, and are low risk.20 Pregnancies in women with a history of a solid organ transplant are considered high risk and should be managed by a multidisciplinary team that includes a maternal-fetal medicine expert.20,21
Immunosuppressive medications are necessary to preserve graft function and prevent graft rejection during pregnancy.22 Physiologic changes during pregnancy may impact their pharmacodynamic properties, thus making it difficult to maintain appropriate blood levels during pregnancy.23 The maternal-fetal distribution of immunosuppressive medications is complex and can be affected by maternal weight gain, hemodynamic alterations, and drug metabolism by enzyme systems that are differentially expressed in placental and fetal tissues. The limited data available, along with the lack of controlled studies, suggest that monitoring drug levels during pregnancy and in the puerperium still provides the best guide for maintaining adequate immunosuppression, as doses may need to be increased or decreased.21
Mainstay immunosuppressive medications include corticosteroids, calcineurin inhibitors (cyclosporine, tacrolimus), and antiproliferative agents (azathioprine, sirolimus, mycophenolate mofetil). Maternal and fetal effects of these medications and monitoring variables are summarized in Table 3.14,21,24–43 All immunosuppressive medications have fetal and neonatal risks; however, current data suggest that administration of these medications during the first trimester is not strongly associated with an increased risk of congenital anomalies,44 with the exceptions of sirolimus and mycophenolate mofetil.31,35,37–39 During the second and third trimesters, effects on the fetal immune system may result in premature delivery and low-birth-weight neonates.44–46 However, underlying maternal disease and concurrent use of other medications may confound the association.
PERIOPERATIVE AND ANESTHETIC MANAGEMENT OF TRANSPLANT RECIPIENTS
Labor analgesia and anesthesia for cesarean delivery do not differ significantly for most transplant recipients with a functioning graft compared with nontransplanted patients. However, general considerations common to all solid organ transplant recipients who receive anesthetic care in the peripartum period are discussed in the sections to follow.
Increased Incidence of Obstetric Complications
The incidence of preeclampsia is reported as high as 30% in transplant recipients28; thus, patients are monitored routinely for hypertension, nephropathy, and preeclampsia.15 The risk of prematurity and low birth weight,14 as well as the rate of cesarean delivery (50% after liver transplant),32 are increased in transplant recipients.28,47 Preterm labor occurs in approximately 36% (liver) and 54% (renal) of transplant recipients. Data for heart and lung recipients are not known but are estimated to be similar.35
Hypertension, diabetes, and hyperlipidemia may exist before transplantation and can persist and worsen posttransplant because of immunosuppressive medications.24,35,48,49 The incidence of comorbidities varies by the type of immunosuppression.2 The NTPR reports that the incidence of diabetes during pregnancy ranges from 5% to 9% in kidney recipients, 1% to 13% in liver recipients, and 5% to 7% in heart recipients.2 Lung transplant recipients demonstrate the greatest incidence of diabetes (27%).2 The incidence of hypertension during pregnancy is reported as 25% to 60% in kidney recipients, 17% to 35% in liver recipients, 42% to 47% in heart recipients, and 57% in lung transplant recipients.2 Control of blood glucose may become difficult because of administration of corticosteroid immunosuppression administration.
Graft Function Assessment
Transplanted organs normally adapt well to the physiologic changes of pregnancy, and pregnancy itself does not increase the incidence of organ rejection.21 Therefore, for most recipients, the graft should be functioning well at the time of delivery. Progressive deterioration in organ function tests may indicate rejection. Graft function assessment is summarized in Table 2.3–14
Management of Immunosuppression
During pregnancy, clinical and laboratory monitoring of the organ’s functional status and immunosuppressive drug levels are performed every 4 weeks until 32 weeks, then every 2 weeks until 36 weeks, and then weekly until delivery as recommended by the NTPR.50,51 Immunosuppressive drug levels are monitored closely for a minimum of 1 month postpartum, especially if dosage is increased during pregnancy.50 Biopsy may be performed if rejection is suspected.50
Current medications, their side effects, and potential drug interactions with peripartum and anesthetic drugs should be considered (Table 3).14,21,24–43 During the peripartum period, patients should continue their immunosuppressive medications on their regular schedule. An augmented corticosteroid dose has been suggested because of the stress of labor and to prevent postpartum rejection33; however, there are no established dosing recommendations.
Presence of Infection
Transplant recipients are at an increased risk for viral, bacterial, fungal, and protozoan infections because of immunosuppression.14 They may not present with typical signs of infection (such as fever and leukocytosis); thus, a high index of suspicion is required for diagnosis. Prenatal surveillance for cytomegalovirus, toxoplasmosis, hepatitis B and C, human immunodeficiency virus, herpes simplex virus, syphilis, and rubella is indicated. Live vaccines are contraindicated in transplant recipients, and most patients will have been vaccinated for hepatitis B before transplantation.35,50
Prevention of Infection
Because transplant patients are immunosuppressed and prone to infection and subsequent graft loss, meticulous aseptic technique is essential for all procedures.9 Currently, there are no specific recommendations on prophylactic antibiotics before surgical procedures for immunosuppressed patients.14
Neuraxial Technique for Labor Analgesia and Cesarean Delivery
Platelet or coagulation factor defects may exist secondary to preeclampsia, liver dysfunction, kidney dysfunction, or effects of immunosuppressive agents (eg, azathioprine, biologic agents) and may preclude the use of neuraxial anesthetic techniques. There are no guidelines for assessing platelet levels and coagulation studies before neuraxial techniques for transplant recipients; however, patients who have been followed consistently during their pregnancies and have normal graft function most likely do not need additional laboratory assessment of their coagulation status before initiating neuraxial procedures.
Standard monitoring is adequate in most cases. Perioperative invasive monitoring, such as arterial or central venous pressure monitoring, should be considered after assessing the risk–benefit ratio in individual patients. The use of transthoracic echocardiography may provide the least invasive method to evaluate left ventricular filling volume for any patient, and transesophageal echocardiography is an option for patients receiving general anesthesia.
Blood Transfusion Concerns
Red blood cell antibodies arising from transplanted organs and directed against recipient red blood cells is a complication of solid organ transplantation.52 The blood bank should be contacted early to avoid delays in cross-matching blood. To avoid leukocyte-related reactions such as graft-versus-host disease, leukocyte-poor irradiated blood products should be used.53 Modern leukocyte depletion filters remove 99.9% of leukocytes.53
Thromboprophylaxis should be administered because of the high risk of thromboembolic complications in these patients, especially after cesarean delivery.14 The threshold for admission to an intensive care or high-dependency unit should be low.
Kidney Transplant Recipients
The kidney is the most frequently transplanted organ and has shown the best long-term survival rate of all transplanted organs.a It is important to select drugs that do not rely on renal excretion (eg, cisatracurium) and to avoid potentially nephrotoxic drugs (eg, nonsteroidal anti-inflammatory medications). Adequate intravascular fluid volume should be maintained to prevent renal hypoperfusion.
Liver Transplant Recipients
Recovery of drug metabolism capacity appears immediately after reperfusion of the liver graft14; however, renal dysfunction is common in liver transplant recipients and is an important pharmacologic consideration.14,54
Heart, Lung, and Heart–Lung Transplant Recipients
Since the first successful delivery of a parturient with a heart transplant in 1986,55 the NTPR reports a number of successful pregnancies in heart, lung, and combined heart-lung transplant patients (Table 1).2
The transplanted heart usually tolerates the hemodynamic changes during labor and delivery well.10 Concerns related to the anesthetic management of heart transplant recipients include physiologic and pharmacologic alterations secondary to cardiac denervation. All stress responses are delayed because of denervation but eventually occur. Under stress, endogenously released catecholamines directly stimulate the heart and slowly increase heart rate over 5 to 6 minutes, thus increasing the cardiac output.11 Signs of reinnervation of transplanted hearts after some years have been shown in canine models56; however, an electron microscopic study56 demonstrated that normal myocardial innervation is not likely to be restored. Therefore, for practical purposes, the heart can be regarded as denervated permanently.16 Anesthetic implications and considerations for the transplanted heart are summarized in Table 4.10,11,14,28,53,56–61
Neuraxial techniques may be performed for labor analgesia and cesarean delivery anesthesia. Epidural and spinal local anesthetics used for labor analgesia do not significantly affect hemodynamic and respiratory function. In the operating room, however, sudden development of a high neuraxial block with anesthetic dosing may be detrimental to organ function. Because of denervation, a decrease in cardiac output secondary to the decreased preload associated with a sympathectomy will not be compensated quickly by an increase in heart rate. Modified combined spinal-epidural dosing (ie, sequential combined spinal-epidural anesthesia), in which a low dose of spinal bupivacaine is followed by incremental epidural dosing through the catheter, or administration of incremental doses of local anesthetics through an epidural or continuous spinal catheter, may mitigate the risk of sudden hemodynamic changes. If vasopressors are required, the use of directly acting drugs such as norepinephrine are expected to produce dose-dependent positive inotropic and chronotropic effects in these patients, whereas indirectly acting drugs, such as ephedrine, cause a blunted response on heart rate and arterial blood pressure.14 Phenylephrine will increase systemic vascular resistance, and the reflex decrease in heart rate will not occur. Invasive monitoring is not routinely indicated unless more extensive surgery, such as cesarean hysterectomy, is planned, complications such as uterine atony or increased blood loss are anticipated, or there is poor graft function.
Heart transplant recipients have a frequent incidence of thromboembolic complications and left atrial thrombus; hence, thromboprophylaxis is recommended, especially after cesarean delivery.53 The timing of initiation of pharmacologic thromboprophylaxis should consider the timing of the neuraxial procedure to minimize the risk of neuraxial hematoma.
Lung and heart–lung transplant recipients appear to adapt well to the physiologic changes in pulmonary function during pregnancy in the absence of rejection.10,62 Ventilation and perfusion of the transplanted lung are considered equivalent to that of the normal lung, and gas exchange is normalized within 8 weeks of transplantation.63 The effects of the surgery itself, however, have implications for anesthetic management. Long-term complications of the bronchial anastomosis include stenosis, granulation, and mechanical distortion of the main bronchus.64 Patients with tracheal anastomosis lose the cough reflex because of denervation of afferent sensation below the level of the tracheal anastomosis.65–67 They may not be able to clear secretions and are prone to silent aspiration. Bronchoconstriction is common secondary to bronchial hyperresponsiveness.14 The lymphatic drainage in the transplanted lung is disrupted, thus excessive fluids may lead to pulmonary edema.64,65 After double lung transplantation with the en bloc technique,65 signs of cardiac denervation have been reported in >50% of double lung transplant recipients, most likely caused by surgical interruption of sympathetic and parasympathetic pathways during dissection of the recipient’s trachea.68
Neuraxial techniques may be performed for labor analgesia and cesarean delivery anesthesia. In the operating room, a neuraxial technique avoids instrumentation of the airway and the subsequent risk of bronchoconstriction and disruption of the tracheal or bronchial suture line. The use of a modified combined spinal–epidural technique, epidural catheter, or continuous spinal catheter in the operating room avoids sudden hemodynamic changes for patients with heart-lung transplants and also avoids further blunting of the cough reflex for recipients with tracheal anastomoses. Crystalloid volume should be given to maintain adequate preload in patients with concomitant heart transplant, but administered judiciously to avoid pulmonary edema in the transplanted lungs.64,65 Invasive hemodynamic monitoring and/or transthoracic echocardiography may be used to assist the careful titration of fluids and vasopressors.65
When general anesthesia is required in lung transplant patients, endotracheal intubation should be performed carefully to avoid traumatizing the tracheal suture line, especially after an en block heart–double–lung transplant, in which the suture line is proximal to the carina. The suture line for single-lung transplants generally is distal to the carina.64 Bronchodilators may be required after intubation because of bronchial hyperreactivity.63–65
After delivery, sudden severe bronchospasm has been reported after administration of the uterotonic agent carboprost (15-methyl prostaglandin F2α).69 Although there are no case reports of its use in lung transplant recipients, the risk of bronchospasm should be considered before the decision to administer carboprost is made.
Pregnant women with solid organ transplants experience physiologic changes of pregnancy, physiologic changes related to the transplanted graft, and side effects of immunosuppressive therapy. Fetal risks such as low birth weight, prematurity, and fetal malformations may influence timing and route of delivery. The decision on when and how to deliver the fetus should be made by a multidisciplinary team. Anesthesiologists must consider the optimal analgesic and anesthetic management for each individual patient with attention to preservation of transplanted solid organ function. Most women will not have contraindications to neuraxial techniques; strict aseptic technique is essential. Understanding the underlying transplanted organ physiology and side effects related to immunosuppressive medications is important to optimal care of these high-risk parturients.
Name: Daria M. Moaveni, MD.
Contribution: This author helped write portions of the manuscript.
Name: Jennifer H. Cohn, MD.
Contribution: This author helped write portions of the manuscript.
Name: Katherine G. Hoctor, MD.
Contribution: This author helped write portions of the manuscript.
Name: Ryan E. Longman, MD.
Contribution: This author helped write portions of the manuscript.
Name: J. Sudharma Ranasinghe, MD.
Contribution: This author helped write portions of the manuscript.
This manuscript was handled by: Cynthia A. Wong, MD.
The authors thank Maria Elkordy for her support during manuscript preparation.
a US Department of Health and Human Services Health Resources and Services Administration. United States Organ Transplantation OPTN & SRTR Annual Data Report 2012. United States Organ Transplantation. 2014. Available at: http://srtr.transplant.hrsa.gov/annual_reports/2012/pdf/2012_SRTR_ADR.pdf. Accessed April 27, 2015.
1. Murray JE, Reid DE, Harrison JH, Merrill JP. Successful pregnancies after human renal transplantation. N Engl J Med 1963;269:341–3.
3. Marcén R, Morales JM, Fernández-Rodriguez A, Capdevila L, Pallardó L, Plaza JJ, Cubero JJ, Puig JM, Sanchez-Fructuoso A, Arias M, Alperovich G, Serón D. Long-term graft function changes in kidney transplant recipients. NDT Plus 2010;3:ii2–8.
4. McKay DB, Josephson MA. Pregnancy after kidney transplantation. Clin J Am Soc Nephrol 2008;3(suppl 2):S117–25.
5. Airoldi J, Weinstein L. Clinical significance of proteinuria in pregnancy. Obstet Gynecol Surv 2007;62:117–24.
6. Singh S, Watt KD. Long-term medical management of the liver transplant recipient: what the primary care physician needs to know. Mayo Clin Proc 2012;87:779–90.
7. Bucklin BA, Fuller AJ. Suresh MS, Segal BS, Preston RL, Fernando R, Mason CL. Physiologic changes of pregnancy. Shnider and Levinson’s Anesthesia for Obstetrics. 2013:5th ed. Baltimore, MD: Lippincott Williams &Wilkins, 13.
8. Wakim-Fleming J, Zein NN. The liver in pregnancy: disease vs benign changes. Cleve Clin J Med 2005;72:713–21.
9. Cowan SW, Davison JM, Doria C, Moritz MJ, Armenti VT. Pregnancy after cardiac transplantation. Cardiol Clin 2012;30:441–52.
10. Wu DW, Wilt J, Restaino S. Pregnancy after thoracic organ transplantation. Semin Perinatol 2007;31:354–62.
11. Ashary N, Kaye AD, Hegazi AR, M Frost EA. Anesthetic considerations in the patient with a heart transplant. Heart Dis 2002;4:191–8.
12. Blasco MB, Pasameshwar J, Vuylsteke A. Anesthesia for noncardiac surgery in the heart transplant recipient Curr Opin Anaesthesiol 2009;22:109–13.
13. Novick RJ, Stitt LW, Al-Kattan K, Klepetko W, Schäfers HJ, Duchatelle JP, Khaghani A, Hardesty RL, Patterson GA, Yacoub MH. Pulmonary retransplantation: predictors of graft function and survival in 230 patients. Pulmonary Retransplant Registry. Ann Thorac Surg 1998;65:227–34.
14. Kostopanagiotou G, Smyrniotis V, Arkadopoulos N, Theodoraki K, Papadimitriou L, Papadimitriou J. Anesthetic and perioperative management of adult transplant recipients in nontransplant surgery. Anesth Analg 1999;89:613–22.
15. McKay DB, Josephson MA, Armenti VT, August P, Coscia LA, Davis CL, Davison JM, Easterling T, Friedman JE, Hou S, Karlix J, Lake KD, Lindheimer M, Matas AJ, Moritz MJ, Riely CA, Ross LF, Scott JR, Wagoner LE, Wrenshall L, Adams PL, Bumgardner GL, Fine RN, Goral S, Krams SM, Martinez OM, Tolkoff-Rubin N, Pavlakis M, Scantlebury V; Women’s Health Committee of the American Society of Transplantation. Reproduction and transplantation: report on the AST Consensus Conference on Reproductive Issues and Transplantation. Am J Transplant 2005;5:1592–9.
16. Deshpande NA, James NT, Kucirka LM, Boyarsky BJ, Garonzik-Wang JM, Montgomery RA, Segev DL. Pregnancy outcomes in kidney transplant recipients: a systematic review and meta-analysis. Am J Transplant 2011;11:2388–404.
17. Deshpande NA, James NT, Kucirka LM, Boyarsky BJ, Garonzik-Wang JM, Cameron AM, Singer AL, Dagher NN, Segev DL. Pregnancy outcomes of liver transplant recipients: a systematic review and meta-analysis. Liver Transpl 2012;18:621–9.
18. Douglas NC, Shah M, Shah M, Sauer MV. Fertility and reproductive disorders in female solid organ transplant recipients. Semin Perinatol 2007;31:332–8.
19. de Broux E, Huot CH, Chartrand S, Vobecky S, Chartrand C. Growth and pubertal development following pediatric heart transplantation: a 15-year experience at Ste-Justine Hospital. J Heart Lung Transplant 2000;19:825–33.
20. Deshpande NA, Coscia LA, Gomez-Lobo V, Moritz MJ, Armenti VT. Pregnancy after solid organ transplantation: a guide for obstetric management. Rev Obstet Gynecol 2013;6:116–25.
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. Hebert MF, Zheng S, Hays K, Shen DD, Davis CL, Umans JG, Miodovnik M, Thummel KE, Easterling TR. Interpreting tacrolimus concentrations during pregnancy and postpartum. Transplantation 2013;95:908–15.
23. Costantine MM. Physiologic and pharmacokinetic changes in pregnancy. Front Pharmacol 2014;5:65.
24. Bhat M, Al-Busafi S, Deschênes M, Ghali P. Care of the liver transplant patient. Can J Gastroenterol Hepatol 2014;28:213–9.
25. Blanford AT, Murphy BE. In vitro metabolism of prednisolone, dexamethasone, betamethasone, and cortisol by the human placenta. Am J Obstet Gynecol 1977;127:264–7.
26. Anderson GG, Rotchell Y, Kaiser DG. Placental transfer of methylprednisolone following maternal intravenous administration. Am J Obstet Gynecol 1981;140:699–701.
27. Khan BD. Cyclosporine. N Eng J Med 1989;321:1725–1738.
28. Riley ET. Obstetric management of patients with transplants. Int Anesthesiol Clin 1995;33:125–40.
29. Casele HL, Laifer SA. Association of pregnancy complications and choice of immunosuppressant in liver transplant patients. Transplantation 1998;65:581–3.
30. Saarikoski S, Seppälä M. Immunosuppression during pregnancy: transmission of azathioprine and its metabolites from the mother to the fetus. Am J Obstet Gynecol 1973;115:1100–6.
31. Nevers W, Pupco A, Koren G, Bozzo P. Safety of tacrolimus in pregnancy. Can Fam Physician 2014;60:905–6.
32. Casele HL, Laifer SA. Pregnancy after liver transplantation. Semin Perinatol 1998;22:149–55.
33. Lessan-Pezeshki M. Pregnancy after renal transplantation: points to consider. Nephrol Dial Transplant 2002;17:703–7.
34. Jankowska I, Oldakowska-Jedynak U, Jabiry-Zieniewicz Z, Cyganek A, Pawlowska J, Teisseyre M, Kalicinski P, Markiewicz M, Paczek L, Socha J. Absence of teratogenicity of sirolimus used during early pregnancy in a liver transplant recipient. Transplant Proc 2004;36:3232–3.
35. Vos R, Ruttens D, Verleden SE, Vandermeulen E, Bellon H, Vanaudenaerde BM, Verleden GM. Pregnancy after heart and lung transplantation. Best Pract Res Clin Obstet Gynaecol 2014;28:1146–62.
36. Fuchs KM, Coustan DR. Immunosuppressant therapy in pregnant organ transplant recipients. Semin Perinatol 2007;31:363–71.
37. Atcheson BA, Taylor PJ, Mudge DW, Johnson DW, Hawley CM, Campbell SB, Isbel NM, Pillans PI, Tett SE. Mycophenolic acid pharmacokinetics and related outcomes early after renal transplant. Br J Clin Pharmacol 2005;59:271–80.
38. Perez-Aytes A, Ledo A, Boso V, Sáenz P, Roma E, Poveda JL, Vento M. In utero exposure to mycophenolate mofetil: a characteristic phenotype? Am J Med Genet A 2008;146A:1–7.
39. Le Ray C, Coulomb A, Elefant E, Frydman R, Audibert F. Mycophenolate mofetil in pregnancy after renal transplantation: a case of major fetal malformations. Obstet Gynecol 2004;103:1091–4.
40. Moini M, Schilsky ML, Tichy EM. Review on immunosuppression in liver transplantation. World J Hepatol 2015;7:1355–68.
41. Emer JJ, Frankel A, Zeichner JA. A practical approach to monitoring patients on biological agents for the treatment of psoriasis. J Clin Aesthet Dermatol 2010;3:20–6.
42. Elsenberg JA, Armenti VT, Mc Grovy CH. National Transplantation Pregnancy Registry (NTPR): Use of muromonab-CD3 (OKT3) during pregnancy in female transplant recipients. Am Soc Transplant Phys 1997;20:108–12.
43. Horst S, Kane S. The use of biologic agents in pregnancy and breastfeeding. Gastroenterol Clin North Am 2014;43:495–508.
44. Kainz A, Harabacz I, Cowlrick IS, Gadgil SD, Hagiwara D. Review of the course and outcome of 100 pregnancies in 84 women treated with tacrolimus. Transplantation 2000;70:1718–21.
45. Tendron A, Gouyon JB, Decramer S. In utero exposure to immunosuppressive drugs: experimental and clinical studies. Pediatr Nephrol 2002;17:121–30.
46. Gerosa M, Meroni PL, Cimaz R. Safety considerations when prescribing immunosuppression medication to pregnant women. Expert Opin Drug Saf 2014;13:1591–9.
47. Coffin CS, Shaheen AA, Burak KW, Myers RP. Pregnancy outcomes among liver transplant recipients in the United States: a nationwide case-control analysis. Liver Transpl 2010;16:56–63.
48. Silkensen JR. Long-term complications in renal transplantation. J Am Soc Nephrol 2000;11:582–8.
49. Kasiske BL. Risk factors for accelerated atherosclerosis in renal transplant recipients. Am J Med 1988;84:985–92.
50. Armenti VT, Constantinescu S, Moritz MJ, Davison JM. Pregnancy after transplantation. Transplant Rev (Orlando) 2008;22:223–40.
51. Coscia LA, Constantinescu S, Moritz MJ, Frank AM, Ramirez CB, Maley WR, Doria C, McGrory CH, Armenti VT. Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation. Clin Transpl 2010:65–85.
52. Ramsey G. Red cell antibodies arising from solid organ transplants. Transfusion 1991;31:76–86.
53. Toivonen HJ. Anaesthesia for patients with a transplanted organ. Acta Anaesthesiol Scand 2000;44:812–33.
54. Csete M, Sipher MJ. Management of the transplant patient for nontransplant procedures. Adv Anesth 1994;11:407–31.
55. Löwenstein BR, Vain NW, Perrone SV, Wright DR, Boullón FJ, Favaloro RG. Successful pregnancy and vaginal delivery after heart transplantation. Am J Obstet Gynecol 1988;158:589–90.
56. Miyamoto Y, Curtiss EI, Kormos RL, Armitage JM, Hardesty RL, Griffith BP. Bradyarrhythmia after heart transplantation. Incidence, time course, and outcome. Circulation 1990;82:IV313–7.
57. Cheng DC, Ong DD. Anaesthesia for non-cardiac surgery in heart-transplanted patients. Can J Anaesth 1993;40:981–6.
58. Dash A. Anesthesia for patients with a previous heart transplant. Int Anesthesiol Clin 1995;33:1–9.
59. Sharpe MD, Gelb AW. Organ transplantation: anesthetic considerations for the previously transplanted patient. Anesthesiol Clin North Am 1994;12:827–43.
60. Camann WR, Goldman GA, Johnson MD, Moore J, Greene M. Cesarean delivery in a patient with a transplanted heart. Anesthesiology 1989;71:618–20.
61. Melton IC, Gilligan DM, Wood MA, Ellenbogen KA. Optimal cardiac pacing after heart transplantation. Pacing Clin Electrophysiol 1999;22:1510–27.
62. Baron O, Hubaut J, Galetta D, Treilhaud M, Horeau D, Despins P, Michaud J, Haloun A. Pregnancy and heart-lung transplantation. J Heart Lung Transplant 2002;21:914–7.
63. Studer SM, Levy RD, McNeil K, Orens JB. Lung transplant outcomes: a review of survival, graft function, physiology, health-related quality of life and cost-effectiveness. Eur Respir J 2004;24:674–85.
64. Feltracco P, Falasco G, Barbieri S, Milevoj M, Serra E, Ori C. Anesthetic considerations for nontransplant procedures in lung transplant patients. J Clin Anesth 2011;23:508–16.
65. Haddow GR. Anaesthesia for patients after lung transplantation. Can J Anaesth 1997;44:182–97.
66. Herve P, Silbert D, Cerrina J, Simonneau G, Dartevelle P. Impairment of bronchial mucociliary clearance in long-term survivors of heart/lung and double-lung transplantation. The Paris-Sud Lung Transplant Group. Chest 1993;103:59–63.
67. Higenbottam T, Jackson M, Woolman P, Lowry R, Wallwork J. The cough response to ultrasonically nebulized distilled water in heart-lung transplantation patients. Am Rev Respir Dis 1989;140:58–61.
68. Schaefers HJ, Waxman MB, Patterson GA, Frost AE, Maurer J, Cooper JD. Cardiac innervation after double lung transplantation. Toronto Lung Transplant Group. J Thorac Cardiovasc Surg 1990;99:22–9.
69. O’Leary AM. Severe bronchospasm and hypotension after 15-methyl prostaglandin F(2alpha) in atonic post partum haemorrhage. Int J Obstet Anesth 1994;3:42–4.