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Transplantation is recognized as life saving for individuals suffer- Resumption of normal menstrual function and fertility may occur
ing from end-stage organ failure. For many young women, within weeks to months after transplantation with subsequent
improved transplant success rates and newer ˜˜obstetric- conception dependent on the recipient™s pattern of episodes of
friendly™™ immunosuppressant drugs have allowed them the rejection and infection and evidence of stable graft function. In
opportunity of achieving normal reproductive function, with addition, use of minimum immunosuppressive therapy with
the subsequent choice of childbearing. The most extensive drugs developed after the introduction of cyclosporine A (CyA),
may reduce the risk for delivery of low birthweight infants.7 The
experience with pregnancy in the posttransplant parturient has
been in renal recipients with the first successful posttransplant incidence of prepregnancy hypertension, diabetes mellitus (DM),
pregnancy occurring in 1958.1 Since then, thousands of success- and renal insufficiency may also impact maternal and pregnancy
outcome.8 An understanding of the optimum criteria for consid-
ful deliveries have been reported in women after liver, heart,
simultaneous kidney“pancreas and combined transplants eration of pregnancy in transplant recipients and adherence to
(heart“lung(s), liver“kidney, liver“heart, and liver“lung). Despite the recommended waiting period of at least one year following
the inherent increased risk to the mother and concerns about the transplantation will alert the reader to those patients who, not
effects of immunosuppressive drugs on fetal development, and satisfying these prerequisites, may anticipate a prohibitively
the effects of pregnancy on transplant function, a successful high-risk antenatal and peripartum course (see Tables 22.2,
22.3, and 22.4).3,4,5,9
outcome in such pregnancies is achievable. Consensus is that
in the presence of good graft function and with stable mainten- Despite good preconception and peripartum graft function and
ance immunosuppressive drug therapy, pregnancy is well toler- minimal morbidity from immunosuppressive therapy, life expec-
ated, with most pregnancies resulting in successful outcomes for tancy following transplantation is uncertain, and pregnancy
mother and newborn.2,3,4,5 In addition, multiple pregnancies in a should be considered as high risk. Collaborative interdisciplinary
transplant recipient do not seem to increase the incidence of management between transplant specialists, obstetricians, peri-
complications in the newborn or mother or augment graft dys- natologists, and anesthesiologists is essential.
function and failure.6 Issues that must be considered in every transplant parturient
include: timing and mode of delivery; increased risk of preeclamp-
sia; adverse effects of immunosuppressive drugs (hypertension,
Statistics
hyperglycemia, renal insufficiency), immunosuppressive drug
Organ transplantation has become a relatively common surgical levels and dosing; surveillance of graft function; maternal infec-
procedure performed in over 250 centers worldwide, with tion; residual physiologic alterations of end-stage organ disease;
improvement in both patient and graft survival rates reported and coexisting disease effecting other organ systems.
over the past two decades. As such, many of these recipients are
healthy and live a relatively normal life, with an excellent chance
Kidney and pancreas“kidney recipient
of survival during and beyond their reproductive years. The
National Transplantation Pregnancy Registry (NTPR), estab- The age range of renal transplant patients who have completed
successful pregnancies is 18 to 46 years.7,10 Most studies conclude
lished in the US in 1991, is a voluntary reporting, retrospective
database analyzing the long-term outcomes of female transplant that pregnancy does not have an adverse long-term effect on
recipients who have had pregnancies, graft function within two patient survival or on renal graft function, if the glomerular filtra-
years of pregnancy, and the health of their offspring. The total tion rate (GFR) is well preserved and the patient is normoten-
sive.10,11,12,13 Contrary to these findings, an estimated 12% of
number of pregnancies in female recipients reported to the reg-
istry as of January 2003 is shown in Table 22.1.2 The number of these women have been reported to develop new long-term med-
outcomes exceeding pregnancies indicates multiple gestations. ical problems following pregnancy, which doubles if uncon-
In general, reports have not distinguished between recipients trolled hypertension, renal deterioration, or rejection occurs
prior to 28 weeks™ gestation.14 It is uncertain whether such prob-
of transplants as adults and those who received transplants dur-
ing childhood and adolescence. No information is available on lems are pregnancy-induced or follow the natural time course for
pregnancy following small bowel transplantation. kidney recipients and graft survival.


Obstetric Anesthesia and Uncommon Disorders, eds. David R. Gambling, M. Joanne Douglas and Robert S. F. McKay. Published by Cambridge University Press.
# Cambridge University Press 2008.
5 Other disorders



Table 22.1 NTPR: Pregnancies in all female transplant Table 22.4 Criteria for consideration of pregnancy in heart and
recipients (1991“2002) heart“lung transplant recipients

Organ Recipients Pregnancies Outcomes 1. Pregnancy is generally not recommended in the first year after
heart transplantation, and ideally not for two years posttransplant,
Kidney 691 1058 1089
to allow for recovery from primary and secondary disease
Liver 102 175 176
processes
Liver“kidney 3 5 6
2. Asymptomatic, normal exercise tolerance, New York Heart
Pancreas“kidney 35 48 50
Association Functional Class I
Heart 31 52 52
3. Well preserved ventricular function (echocardiography and cardiac
Heart“lung 3 3 3
catheterization)
Lung 13 14 14
4. No evidence of coronary atherosclerosis by angiography
Totals 878 1355 1390
5. Stable immunosuppressive regimen
6. No evidence of rejection on endomyocardial biopsy
7. Normal or near normal renal function
Table 22.2 Criteria for consideration of pregnancy in kidney
and pancreas“kidney transplant recipients

1. Good general health Table 22.5 Hallmarks of clinical rejection in the transplanted
2. Elapsed time from cadaveric transplant surgery 24 months, possibly kidney
one year for a living donor recipient, and <5 years from
1. Fever
transplantation
2. Diminishing urine output
3. Proteinuria <500 mg/24hr
3. Fluid retention
4. Hypertension, if present, BP 140/90 mmHg on minimal drugs and
4. Hypertension
easily controlled
5. Worsening renal function (i.e. increased blood urea nitrogen,
5. No recent episodes of acute rejection in the preceding 6 to
creatinine, beta-2 microglobulins)
12 months and no evidence of ongoing rejection
6. Enlargement and tenderness of the ectopic kidney
6. Mild renal dysfunction with a serum creatinine of less than
1.8 mmol/l (2 mg/dl) or preferably less than 1.25 mmol/l (1.5 mg/dl)
7. Stable maintenance level of immunosuppressive therapy:
 Prednisone 15 mg/day Table 22.6 Causes of functional impairment of the
 Azathioprine 2 mg/kg/day transplanted kidney during pregnancy
 Cyclosporine and tacrolimus at therapeutic levels
1. Functional stress of pregnancy (glomerular hyperfiltration and
 Mycophenolate mofetil and sirolimus are contraindicated and
sclerosis)
have to be stopped 6 weeks preconception
2. Accelerated progression of an underlying disease process
8. Normal graft ultrasound (absence of pelvicalyceal distension)
3. Preeclampsia
9. Rubella vaccine should be administered pretransplantation
4. Cyclosporine A nephrotoxicity
5. Rejection (acute or chronic)
6. Hypertension
Table 22.3 Criteria for consideration of pregnancy in liver
transplant recipients

the third trimester and return to normal by 8 to 12 weeks postpar-
1. Pregnancy should be avoided for at least the first 6 months and
tum, without permanent sequelae.15 Proteinuria, frequently more
preferably 9 to 12 months after transplantation
than 500 mg/24 hours and as remarkable as 2“3 g/24 hours,16 is
2. Evidence of stabilization of liver function and recovery from
seen in the third trimester in 30“40% of patients.17 However, in the
surgical complications
absence of hypertension or renal dysfunction, proteinuria is not
3. Completion of posttransplant prophylactic treatment of
significant and usually resolves postpartum.18
opportunistic infections, with no evidence of active
Rejection during pregnancy is a rare phenomenon but post-
viral infection
partum rejection and deterioration in renal function has been
4. Maintenance immunosuppressive therapy
observed. There are no predictive risk factors for which patients
5. No evidence of acute rejection
will develop acute rejection and the diagnosis may be difficult
(see Table 22.5). If deterioration in renal function occurs at any
Adaptations of the kidney to pregnancy are paralleled by the stage of pregnancy, treatable causes should be excluded (see
denervated renal graft, although to a lesser degree. A sustained Table 22.6). The impact of pregnancy on graft loss is difficult to
increase in GFR and renal plasma flow is seen in the first and evaluate. Recipients with graft dysfunction (serum creatinine
second trimester, with a transient reduction of up to 30% during >1.5 mg/dl) or rejection during pregnancy and the postpartum



382
Chapter 22


period are more likely to deliver earlier as well as suffer eventual
Table 22.7 Physiologic alterations in end-stage renal disease
graft loss.19,20
Hypertension and preeclampsia are common and frequently 
Neurologic Central: lethargy, seizures, personality traits
severe. A blood pressure (BP) greater than 140/90 mmHg in the  Peripheral: sensory and motor neuropathy
kidney transplant patient should be treated early and aggres-  Autonomic dysfunction
sively.21 Maintaining a diastolic BP between 80“85 mmHg may 
Respiratory Hypocarbia
preserve graft function and prevent the occurrence of a life-  Pleural effusion, edema, pneumonitis, infection
threatening hypertensive crisis or eclampsia. In general, hyper- 
Cardiovascular Indeterminate volume status, susceptible to fluid
tension, particularly before 28 weeks™ gestation, is associated with overload
adverse perinatal outcome.22 Antihypertensive medications con-  High cardiac output
sidered relatively safe during pregnancy include: a-methyldopa,  Hypertension, left ventricular hypertrophy
beta-adrenergic antagonists, labetalol, clonidine, hydralazine,  Accelerated peripheral and coronary
nifedipine, and diuretics.8,10 Angiotensin-converting enzyme atherosclerosis
inhibitors should be discontinued because of potential adverse  Tachycardia, dysrhythmias, and conduction
effects on the fetus, including oligohydramnios, pulmonary disorders
hypoplasia, and long-lasting neonatal anuria.23 Delivery of the  Attenuated reactivity of the sympathetic nervous
infant, regardless of gestational age, should be considered if the system
patient develops a hypertensive crisis, seizures, or diastolic BP  Reduced oxygen carrying capacity, increased
over 110 mmHg, which is refractory to optimum therapy, and peripheral extraction of O2
when no reversible aggravating factor can be found.15 Due to  Pericarditis, cardiac tamponade
the high incidence of hypertension in transplant patients, pro-  Electrolyte disorders (hyperkalemia,
Endocrine
phylactic low-dose aspirin has been proposed to decrease the hyperphosphatemia, hypermagnesemia,
incidence of preeclampsia.24 There is an increased incidence hypercalcemia, hyponatremia)
of preeclampsia of 25“40%, compared with 8% in the nontrans-  Metabolic acidosis
plant patient.3,25,26 Diagnosis is difficult without a renal biopsy,  Secondary hyperparathyroidism
because edema, proteinuria, hypertension, and increased serum  Glucose intolerance
uric acid levels may also indicate exacerbation of preexisting Gastrointestinal  Delayed gastric emptying and increased volume
renal disease, drug toxicity, or acute rejection.21 Abnormalities and acidity of gastric contents, aspiration risk
in the platelet count or liver function tests (LFTs) may be consis- Musculoskeletal  Osteodystrophy, muscle wasting
tent with a diagnosis of preeclampsia, or immunosuppression-  Chronic anemia, right shift of hemoglobin
Hematologic
induced changes in an otherwise uncomplicated pregnancy. dissociation curve
The risk of bacterial infections of the genitourinary tract may be  Platelet dysfunction, coagulopathy
as high as 40%. Less frequently opportunistic viral and fungal  Increased susceptibility to infection, carrier state
infections may result from chronic immunosuppression and for hepatitis B antigen and HIV
exposure to blood products during years on hemodialysis.  Reduced serum protein and abnormal binding
Diagnosis and treatment is dictated by verification of infection  Decreased drug or metabolite clearance
with culture and sensitivity and/or serological monitoring, as  Abnormal electrolyte and acid-base status
uncommon organisms are frequently seen. Potential risks to the  Altered permeability of the blood“brain barrier
mother and fetus include: pulmonary, liver, and renal dysfunc-  Increased sensitivity to central nervous system
tion, spontaneous abortion, intrauterine and perinatal infections, depressants
intrauterine growth restriction (IUGR), and preterm delivery.  Reduced serum cholinesterase level
Cesarean section (C/S) is indicated if a cervical culture is positive  Altered end-organ sensitivity or response or both
for herpes simplex virus at term, as the incidence of neonatal  Altered volume of distribution
Altered drug
infection resulting from vaginal delivery is at least 50%. With effects
premature rupture of membranes, waiting for greater fetal matur-
ity may not be desirable in view of this enhanced susceptibility to
infection. hypercalcemia due to hyperparathyroidism occurs in up to 20%
Causes of maternal death postpartum include infection, renal of women, with the possibility of exacerbation at the beginning of
failure, uterine rupture, gastroenteritis, cerebrovascular and car- the third trimester. This is associated with an increase in 1,25
dihydroxy vitamin D of placental origin.28 Patients with moderate
diac disease. Few deaths have been reported during or shortly
hypercalcemia (total serum calcium [Ca2 þ] 11.5“13 mg/dl) have
after pregnancy: the majority occurring six to eight years later. In
several small series, 5% to 30% of renal transplant recipient lethargy, and hypotension from polyuria and/or nausea and
vomiting with hypovolemia. A total serum Ca2 þ exceeding
mothers died during their offspring™s childhood.10,27
Residual physiologic alterations of end-stage renal disease (see 14 mg/dl represents a medical emergency from hypertension,
Table 22.7) may have a potential negative impact on obstetrical dysrhythmias, complete heart block, severe neuromyopathic
symptoms, and renal failure.29
outcome and vice versa. After kidney transplantation, persistent



383
5 Other disorders


Successful pregnancies have been reported in a number of
Table 22.8 Biochemical alterations in liver function in normal
kidney transplant patients with coexisting systemic disease, put-
pregnancy
ting them at high risk, independent of transplant-related consid-
erations. These coexisting conditions include: juvenile-onset DM, Alkaline phosphatase Increases up to 200% (placental > fetal
systemic lupus erythematosus, scleroderma, type 1 primary bone isoenzymes)
hyperoxaluria, sickle cell disease, Wegener syndrome, and Good- Gamma glutamyl Normal or increased, reduced response
pasture syndrome. transpeptidase to hepatocellular injury
In the kidney transplant recipient with juvenile-onset DM, Aminotransferases (AST, No change with slight increase, usually
there is a two fold increase in the pregnancy complication rate ALT) within the normal range, near term
compared with recipients having other causes of chronic renal Lactate dehydrogenase Increased
failure (CRF). This is likely related to the preexisting vascular (LDH)
complications seen with severe longstanding DM.30,31,32 In addi- Bilirubin Unchanged, or mild decrease or
tion, immunosuppression can increase the risk of infection, increase, rarely greater than 2 mg/dl
worsen diabetic control, accelerate vascular atherosclerotic dis- Total protein Mild progressive decline
ease, and increase rates of hypertension and thromboembolism. Alpha and beta globulins Tend to increase
Bone fractures may be associated with steroid-induced osteo- Gamma globulins Tend to decrease
porosis, neuropathy, and vascular insufficiency compounded by Albumin Decrease 20“50%
increased Ca2 þ requirements and weight gain during pregnancy. Albumin-to-globulin ratio Decreases
Pelvis osteodystrophy may be present as a result of CRF, dialysis, Triglyceride and Increase substantially (300% and
and prolonged steroid therapy, particularly if renal failure started cholesterol 50%“100% respectively)
in childhood. This may necessitate delivery by C/S due to cepha- Ceruloplasmin Gradually increased to term
lopelvic disproportion. Serum cholinesterase Decreases by 30% at three days
Maintaining normal glucose control may be challenging since activity postpartum, rarely clinically
the risk of developing gestational DM in the normal population is significant prolongation of
in the range of 0.15“12.30%.33 In normal pregnancy, glucosuria is succinylcholine
a common finding due to an increase in the filtered glucose load PT and aPTT, bleeding Unchanged
(increased GFR) and less efficient tubular reabsorption of glu- time, platelet function
cose. Pregnancy outcomes in women with diabetic nephropathy Fibrinolytic activity Slightly reduced
may be better after a combined pancreas“kidney transplantation, Fibrinogen Increases 50%, accounting for a
than with a single kidney transplant.33 hypercoagulable state
After total pancreatectomy and islet transplantation, parturi- Factors VII, VIII, IX, and X Increase
ents are not at increased risk for gestational DM or insulin depen- Platelet count Decreases by 20% due to plasma volume
dency postpartum. Even segmental grafts appear able to produce expansion
enough insulin to overcome the peripheral insulin resistance Glucose Fasting, decreased 10% or no change
found during the second and third trimesters.34 Consequently,
PT ¼ prothrombin time; aPTT ¼ activated partial thromboplastin
hyperglycemia may herald an ischemic insult, graft rejection, or a
time
drug effect (steroids, CyA, tacrolimus).
Acute rejection and loss of a pancreas graft immediately after
delivery has been reported.33 With surgical placement of the pan-
creatic graft in the pelvis, the potential exists for compression- (ALT or SGPT) and glutamic oxaloacetic transaminase (AST or
induced injury by the enlarging uterus or vaginal delivery. Graft SGOT) are considered the standard serological markers and most
pancreatitis caused by reflux of jejunal contents into the pancrea- sensitive indicators of liver damage during pregnancy. During
tic duct should be suspected with the onset of abdominal pain pregnancy, liver blood flow is essentially unchanged as the
and elevation of serum amylase and lipase levels. Confirmation increase in blood volume and cardiac output (CO) is balanced
by a decrease in the proportion of CO directed to the liver.36
requires ultrasound imaging of the uterus and kidney“pancreas
grafts. The following mild-to-moderate complications have been Alterations in drug distribution and metabolism are attributable
reported: elevated amylase (that normalizes after delivery), pre- to changes in protein binding, increases in plasma volume, extra-
eclampsia, pancreatitis, hypertension, and urinary tract infection. cellular water and adipose tissue mass, as well as a competitive
inhibitory effect of estrogen on liver enzyme systems.
The incidence of hepatic dysfunction causing jaundice during
Liver recipients
normal pregnancy varies from 1:1500 to 1:5000, with viral hepatitis
accounting for 50% of cases.37 Derangements in liver and biliary
The biochemical alterations in liver function found in normal
pregnancy are summarized in Table 22.8.35 All changes in LFTs function specific to pregnancy include: hemolysis, elevated liver
are maximal in the third trimester except the decrease in albu- enzymes, and low platelets (HELLP) syndrome and rarely hep-
min/total serum proteins and increase in fibrinogen occurring atic infarction or rupture, acute fatty liver of pregnancy, intrahep-
in the second trimester. Serum glutamic pyruvic transaminase atic cholestasis of pregnancy, and possibly acute cholelithiasis



384
Chapter 22



Table 22.9 Hallmarks of clinical rejection in the transplanted Table 22.10 Cardiovascular, pulmonary, and renal
liver complications of advanced cirrhosis
 Jaundice
1. Clinical signs Cardiovascular ˜˜Hyperdynamic circulation™™
 Tenderness of the right upper quadrant of the  High cardiac index and stroke volume
abdomen  Low systemic vascular resistance
 Asterixis  Low-to-normal mean arterial pressure
 Increased aminotransferases, alkaline phospha-
2. Biologic (widened pulse pressure)
parameters tase, bilirubin  Mild tachycardia
 Decreased serum albumin, coagulation factors Central hypovolemia

3. Liver biopsy Perivascular lipid accumulation  Increased total blood volume
 Periportal fibrosis  Decreased effective plasma volume
 Cholestasis  Increased sympathetic tone
Hyporesponsiveness of the vasculature to
pressor therapy
(see Chapter 14). Hyperemesis gravidarum may result in a mild
Flow-dependent oxygen consumption
transient elevation in bilirubin and abnormal LFTs in up to 50% of
Hepatic and splanchnic vasculature
patients, without chronic sequelae. In general, pregnancy does not
 Portal hypertension
appear to hasten the natural course of chronic liver disease, unless
 Portal-systemic collateral circulation
metabolic decompensation occurs early in the pregnancy.35
 Decreased hepatic blood flow
Following liver transplantation, recurrence of the original disease
Pulmonary Arterial hypoxemia (PaO2 <70 mmHg)
is most frequently seen with hepatitis C. Recurrence of primary
Intrapulmonary vascular abnormalities
biliary cirrhosis and primary sclerosing cholangitis are still con-
 Intrapulmonary shunting (precapillary or
troversial. In patients with cirrhosis and portal hypertension, mas-
arteriovenous intrapulmonary vascular
sive variceal bleeding in pregnancy is considered a significant risk,
dilatations)
accounting for the majority of maternal deaths. In these patients,
 Portal-pulmonary or pleural shunting
the incidence of premature delivery, placental insufficiency, and
 Ventilation-perfusion mismatch (pleural
perinatal mortality is increased.
effusions, ascites and diaphragm dysfunction,
As limited information is available regarding the impact of
increased closing capacities, and/or aspiration
pregnancy on graft function in the liver transplant patient, close
pneumonitis)
surveillance of liver function with serial measurements of immu-
 Diffusion-perfusion defect (interstitial
nosuppressive drug levels is imperative. Graft rejection does not
pneumonitis, fibrosis, or pulmonary
appear to be accelerated by pregnancy,4,38,39 although mild to
hypertension)
moderate increases in liver transaminases, progression of chronic
 Impaired hypoxic pulmonary vasoconstriction
rejection, and acute rejection episodes have been documented
 Pulmonary hypertension
(see Table 22.9).39 In the largest reported single center series, the
 Hepatopulmonary syndrome
incidence of elevated liver enzymes during pregnancy was 35%,
Parenchymal abnormalities
with spontaneous resolution in greater than 80% of these patients
 Restrictive ventilatory pattern due to ascites
without treatment.40 The cause of persistently abnormal LFTs,
limiting diaphragmatic excursion, pleural
unrelated to rejection, may be due to hepatotoxicity from
effusions, or chest wall deformity due to
azathioprine, CyA, and tacrolimus. Rejection may be successfully
osteoporosis
treated with steroid pulse therapy or adjustments in drug therapy,
 Obstructive airway disease, emphysema,
as it is common for drug levels to drop during pregnancy.
bronchitis-bronchiectasis
Obstetric and medical complications described in liver trans-
 Interstitial lung disease (infection, pneumonitis,
plant recipients treated with CyA or tacrolimus and prednisone
pulmonary edema)
include renal insufficiency, preeclampsia, anemia, hyperbili-
 Renin-angiotensin-aldosterone activation:
Renal
rubinemia, and cytomegalovirus infection. The incidence of
impaired sodium handling, water excretion,
preeclampsia is 10“20%, and more frequent in women with pre-
potassium metabolism, and concentrating
existing renal dysfunction.39
ability
End-stage liver disease is associated with unique systemic
 Impaired renal acidification
physiologic alterations (see Table 22.10). Liver transplantation
 Prerenal insufficiency (ascites or diuretics)
does not fully correct the splanchnic and hyperdynamic sys-
 Acute renal failure (acute liver failure, biliary
temic hemodynamic changes seen in advanced cirrhosis.
obstruction, sepsis)
Hepatic denervation after liver transplantation has no major
 Hepatorenal syndrome
deleterious effects on bile secretion, liver regeneration, or hepa-
 Glomerulopathies
tic blood flow.41 Total liver blood flow is increased, despite the



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