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Please read this!

A reader recently e-mailed me, upset that this page made getting pregnant after a heart transplant sound like a bad idea - so I did further research. That research convinced me that getting pregnant after an organ transplant is very risky - but exactly how risky is impossible to know. The risks are worse for the baby than for the mother.

In Medpseak (doctor talk), "successful" has a different meaning. In Medspeak, if 100 heart recipients get pregnant and two of them have fairly healthy babies but the other 98 babies die, then "women heart recipients can successfully have children" is a valid statement. Doctors are trained to think this way. Please be aware of this when reading medical studies.

Pregnancy After Transplant

May, 2000 - Provided there is good organ function, pregnancy may be attempted. However, unpredictable problems can happen, raising concern among doctors and patients alike about the safety of pregnancy after heart transplant. Each group of organ recipients has its own issues and problems specific to the original disease and the specific transplanted organ. Immunosuppressive therapy must be maintained throughout pregnancy.
     Heart transplant recipients' children don't wind up with any specific deformity. However, new immunosuppressive drugs that are stronger and have new actions continue to be introduced. The older drugs' effect on unborn and born babies is unknown to a large degree, and these newer drugs effects are totally unknown. Male transplant recipients can father children successfully.
     Since even large transplant centers have limited experience with post-transplant pregnancies, hard facts are few and far between. In 1991, the National Transplantation Pregnancy Registry (NTPR) was established at Thomas Jefferson University. The registry attempts to track pregnancy outcomes for transplant recipients.
     As of January, 2001, data on only 2,000 pregnancies had been collected. However, less than 10% are heart transplant recipients - they are mostly kidney recipients. Also, please note that this registry is funded by the same drug companies that make the immunosuppressive drugs causing the complications. Honestly, I can't find detailed information online about this registry.
     The FDA has categories of risks for unborn children due to drugs, using the following classifications:

  • A = controlled studies, no risk
  • B = no proven risk in humans
  • C = risks cannot be ruled out
  • D = positive evidence of risk
  • X = contraindicated
Immunosuppressant drugs' safety in pregnancy
 Drug   FDA Safety Classification 
corticosteroids (prednisone, methylprednisolone) B - no evidence of risk in humans
cyclosporine (Sandimmune, Neoral) C - risks cannot be ruled out
cyclosporine (SangCya Oral Solution) C - risks cannot be ruled out
tacrolimus, FK506 (Prograf) C - risks cannot be ruled out
sirolimus, rapamycin (Rapamune) C - risks cannot be ruled out
azathioprine (Imuran) D - positive evidence of risk
mycophenolate mofetil, MMF (CellCept) C - risks cannot be ruled out
antithymocyte globulin (ATGAM, ATG) C - risks cannot be ruled out
antithymocyte globulin (Thymoglobulin) C - risks cannot be ruled out
muromonab-CD3 (orthoclone OKT3) C - risks cannot be ruled out
basiliximab (Simulect) B - no evidence of risk in humans
daclizumab (Zenapax) C - risks cannot be ruled out

None of the commonly used immunosuppressive drugs are Category A (risk-free). Steroids and basiliximab are Category B, while most immunosuppressives are Category C. On some Category C drugs, including daclizumab, orthoclone OKT3, thymoglobulin and ATGAM, there is no information on reproductive outcomes.

Both cyclosporine and tacrolimus, have shown fetal poisoning problems at higher than usual doses in animal trials. In contrast, animal studies with MMF (mycophenolate mofetil or CellCept) show deforming of the unborn baby animal at doses within the dose range used in humans, thus raising great concern.
     With combinations of newer drugs, it is hard to identify specific cause and effect. With lowered doses of multiple drugs, there will be less exposure to each specific drug, so the chance of birth defects might be lower. However, unknown interactions in multiple drug therapies may cause problems. These will only be discovered by pregnancies with bad outcomes for the newborn children.


Study Abstracts On Transplant & Pregnancy

Pregnancy Risks For Organ Recipients

September, 2001 - Pregnancy in heart transplant recipients carries the risk of cytomegalovirus infection and preeclampsia.
 
Title: Specific experiences in females receiving an organ transplant.
Author: di Filippo S.
Source: Presse Med 2001 Sep 1;30(24 Pt 2):27-8
PMID: 11577582

Pregnancy and Transplantation

2000 - Pregnancies in women recipients of all organ types must be considered high-risk. Management requires measuring transplant function, blood work, blood pressure control, diagnosis and treatment of rejection, treatment of any infections and fetal monitoring many times during pregnancy.
     Premature delivery (before 37 weeks) is common. Unless there are specific problems, however, spontaneous labor should be allowed. Vaginal delivery is the aim.
     Higher steroid dose is necessary to cover delivery, and very sterile technique must be used. Any surgical procedures - no matter how small - should be done only after giving antibiotics to prevent possible infections. Monitoring the unborn child is important.
     A wait of 18 months to 2 years after transplant is recommended before pregnancy. Then, if pre-pregnancy assessment is okay, pregnancy might be tried. By then, graft function should have stabilized and immunosuppression should be at maintenance levels.
     Couples who want a child should be encouraged to discuss all the implications, including the harsh realities of the mother's survival prospects. Please note that for kidney transplant recipients (there is more data on them than any other group), 13% (cyclosporine) to 29% (tacrolimus) of pregnancies ended in spontaneous abortion. Half the newborns were premature, with low birth weight.
 
Title: Pregnancy and Transplantation
Authors: Vincent T. Armenti, Michael J. Moritz, John S. Radomski, Gary A. Wilson, William J. Gaughan, Lisa A. Coscia and John M. Davison
Source: Graft 3(2):59-63, 2000

Pregnancy and Heart Transplant

December, 2000 - A 14 year old female became pregnant 6 years after heart transplant. The pregnancy went well and the infant was healthy. Even though the case reported here was a success, pregnancy after heart transplant is considered a high-risk condition and remains contraindicated.
 
Title: Pregnancy after cardiac transplantation. Report of one case and review.
Authors: Bordignon S, Aramayo AM, Nunes e Silva D, Grundler C, Nesralla I.
Source: Arq Bras Cardiol 2000 Dec;75(6):515-22
PMID: 11175475

Pregnancy, Drugs & Transplant

August, 1999 - Pregnancy causes profound changes of the water and electrolyte balance, with blood volume increasing 30 to 50%. This brings about a "hyperdynamic" state of heart and circulation, with the heart increasing rate by 10 to 20 beats per minute, and cardiac output increasing 30 to 50%. Vein pressure in the legs increases, encouraging edema.
     These cardiovascular changes develop over time with a plateau from the second trimester on, with even more strain during labor. High blood pressure may be aggravated. After heart transplant, successful pregnancies have been carried out. However, transplant coronary artery disease may be accelerated.
 
Source: Press Conference Release from XXIst Annual Congress of the ESC, Barcelona, Spain
Presenter: Dr. Hanjorg Just from Freiburg, Germany
From: Drug Therapy of Cardiovascular Problems in Pregnancy, August 30, 1999

Heart Recipients & Pregnancy

July, 1998 - We did a retrospective analysis on 35 heart transplant recipients with first pregnancies (P) and 12 who had one or two later pregnancies (LP). We checked the newborn infant records for premature birth, birth weight, and complications. The mothers' records included pregnancy outcome, post-birth complications including infection and rejection, current graft (organ) function, and survival.
     Forty-seven pregnancies (35 P and 12 LP) from 35 heart transplant recipients were studied. First pregnancy outcomes included 26 live births (one set of twins), 4 miscarriages, and 6 abortions for medical reasons. Later pregnancy outcomes included 11 live births (one set of twins), and 2 miscarriages.
     There were more post-birth complications in later pregnancies (40% versus 12%). No structural birth defects were seen. Complication rates for the mothers were the same in both groups - 40%. Of 28 mothers available for follow-up, the survival rate was 75% for the P group and 89% for the LP group. Average rejection rate per year was higher after more than one pregnancy.
     Post-heart transplant pregnancies may have successful outcomes, but there is a high rate of pre-birth infant death; premature births; and low birth weight in surviving babies. Subsequent pregnancies do not seem to significantly increase complications beyond that of first post-transplant birth.
 
Title: Risks of subsequent pregnancies on mother and newborn in female heart transplant recipients.
Authors: Branch KR, Wagoner LE, McGrory CH, Mannion JD, Radomski JS, Moritz MJ, Ohler L, Armenti VT.
Source: J Heart Lung Transplant 1998 Jul;17(7):698-702
PMID: 9703235

Kidney Recipients & Pregnancy 2

February, 1994 - Outcomes of pregnancies from 115 female kidney transplant recipients taking cyclosporine before and during pregnancy were obtained from questionnaires, hospital records, and telephone interviews. Average age when becoming pregnant was 29 years, with an average time after transplant of 2.2 years. There were 156 outcomes:

For mothers:

Mothers with drug-treated high blood pressure during pregnancy had significantly lower birth weight infants. Mothers with pre-pregnancy creatinine of 1.5 mg/dl or higher had smaller infants and diabetic mothers also had lower birth weight infants. Of 107 recipients interviewed, 12 (11%) lost their donor organ, one of them during pregnancy. Eight grafts were lost within 2 years of the pregnancy.
     We conclude that pre-pregnancy factors that increase risk to the baby of a female kidney transplant recipient include maternal drug-treated high blood pressure, diabetes, and blood level of creatinine at 1.5 mg/dl or higher.
 
Title: National transplantation Pregnancy Registry - outcomes of 154 pregnancies in cyclosporine-treated female kidney transplant recipients.
Authors: Armenti VT, Ahlswede KM, Ahlswede BA, Jarrell BE, Moritz MJ, Burke JF
Source: Transplantation 1994 Feb 27;57(4):502-6

Kidney Recipients & Pregnancy 3

August 1, 1995 - Female kidney transplant patients need increased cyclosporine doses during pregnancy, according to an article in the current issue of the journal Transplantation.
     We studied 197 pregnancies in 141 female kidney recipients. Of the 197 pregnancies, 137 (68.2%) resulted in live births. The information was evaluated by Dr. Vincent Armenti, with grant support from Sandoz Pharmaceuticals - a maker of immunosuppressant drugs.
     Patients in this study became pregnant while taking anti-rejection drugs. These medications were taken throughout pregnancy and during the follow-up period. Pregnant patients who took lower doses of cyclosporine before and during pregnancy had babies with lower birth weight. These patients were more likely to have failure of their transplanted kidney within two years of delivery. The investigators concluded that:

Title: Jefferson Study Evaluates Impact Of Transplants on Pregnancy
Presenter: Editor, JeffNews
Source: JeffNews, August 1, 1995

Heart Recipients & Pregnancy 4

August 1, 1995 - We surveyed 194 heart transplant centers and reviewed the literature for heart recipients who got pregnant. Thirty-two known pregnancies in heart (29) or heart-lung (3) recipients had resulted in 29 children, including 2 sets of twins. Caesarean section rate was 33%. Premature birth was common (41%).
     Onset of pregnancy from time of transplant averaged 2.6 years, with mother's age at conception ranging from 19 to 35 years. Complications were:

  1. high blood pressure - 44%
  2. premature labor - 30%
  3. preeclampsia - 22%
  4. rejection episodes requiring treatment during pregnancy - 22%
  5. chronic kidney dysfunction - 12%
  6. infections during pregnancy - 12%

No deaths soon after birth were reported; three later deaths occurred. Of the 29 children born to the heart transplant recipients, no birth defects or newborn deaths were reported. Forty-one percent were premature, and 17% were low birth weight.
     Most transplant recipients (59%) were being treated with triple-drug therapy of azathioprine (Imuran), steroids, and cyclosporine during pregnancy. The most common change to drug therapy during pregnancy (41%) was increasing cyclosporine dose.
 
Title: Immunosuppressive therapy, management, and outcome of heart transplant recipients during pregnancy
Authors: Wagoner LE, Taylor DO, Olsen SL, Price GD Sr, Rasmussen LG, Larsen CB, Scott JR, Renlund DG
Source: J Heart Lung Transplant 1993 Nov-Dec;12(6 Pt 1):993-9; discussion
Also, see Erratum: J Heart Lung Transplant 1994 Mar-Apr;13(2):342
PMID: 8312325

Pregnancy In Heart Recipients

September, 1993 - Thirty women who became pregnant after heart transplant were identified from cases managed personally, questionnaires sent to heart transplant centers, and review of the literature. Mothers' data was studied for evidence of rejection and pregnancy complications. The infants' data was studied for abnormalities and mortality.
     Frequent pregnancy complications included chronic high blood pressure (48%), preeclampsia (24%), and premature birth (28%). The rate of caesarean delivery was 32%. Six episodes of rejection required treatment, and 3 mothers died sometime after giving birth.
     Among the 27 live births, 5 babies were small for their actual age and 4 had complications. There were no birth defects. Our conclusion is that pregnancies in heart transplant recipients should be considered high risk.
 
Title: Pregnancy in heart transplant recipients: management and outcome
Authors: Scott JR, Wagoner LE, Olsen SL, Taylor DO, Renlund DG
Source: Obstet Gynecol 1993 Sep;82(3):324-7
PMID: 8355928

Kidney Recipients & Pregnancy 5

August 25, 1995 - As of 1995, the National Transplantation Pregnancy Registry (NTPR) currently contains data on over 500 pregnancies. Most of the pregnancies were in patients or wives of patients with kidney transplants (91%); the rest were in heart (6%) and liver (3%) recipients or their wives.

 premature infants = 129 babies or 58% of total births 
 Age in weeks 20 to 2324 to 2728 to 3132 to 3536
 % of infants 1%7%12%56%25%
 low birth weight infants = 85, or 38% of total births 
Weight in grams  less than 750  750 to 999  1000 to 1499  1500 to 1999  2000 to 2499 
% of infants1.2%7.1%18.8%15.3%57.6%
Effects of different drug protocols on premature birth
drug protocolnumber of mothers% of babies less than 37 weeks in womb% of babies less than 33 weeks in womb
cyclosporine, azathiaprine & steroids4357%16%
cyclosporine & steroids2861%17%
azathiaprine & steroids13058%19%
cyclosporine only0250%0
azathiaprine only0650%0
steroids only3067%13%
Total23959%17%

A number of women developed complications after giving birth, including high blood pressure, pyelonephritis, or uterine dystonia. Diabetes, epilepsy, brain structure changes, and hyperthyroid have also been reported.
     Immediate newborn problems included jaundice, thrombocytopenia, leukopenia, hypoglycemia, a mild blood clotting problem, and asphyxia in combination with bleeding in the brain of a premature baby. One newborn had convulsions on the third day and soon died. Another newborn needed oxygen for 2 days and was treated for cataracts in both eyes. Too-low thyroid function was seen in a newborn who also suffered from stomatitis and ophthalmia.

The rate of birth defects in these babies is 6%, which is about the same as in the general population. With the exception of one child with too-slow growth, and another with delayed speech development, all children seemed normal. The pregnant heart recipient mothers had more high blood pressure, preeclampsia, kidney dysfunction, infections, slow fetal growth, and premature labor.
     Babies born to organ transplant recipients often suffer from the conditions listed above, plus serious imflammation of both large and small intestinal walls. Despite the data we have, information on pregnancy in patients treated with anti-rejection drugs is too limited to draw universal conclusions.
     Facial changes have recently been linked to cyclosporine use in young children with kidney transplants. These drugs do cause birth defects in animals but this has not been proven in humans. However, there is an increased rate of complications in mothers and babies which apparently results from organ transplant. Therefore, female transplant recipients wishing to conceive should be informed of the risks.
 
Presenter: Mark Grebenau, MD, PhD - Sandoz Pharmaceuticals
Source: http://www.transweb.org/qa/askarchive/answers9507/95082501.htm


Material taken from manuals given to potential transplant recipients at transplant centers in the USA, and from heart transplant recipients - Updated April 27, 2002

All information on this site is opinion only. All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor. Use the reference information at the end of each article to search MedLine for more complete and accurate information. All original copyrights apply. No information on this page should be used by any person to affect their medical, legal, educational, social, or psychological treatment in any way. I am not a doctor. This web site and all its pages, graphics, and content copyright © 1997, 1998, 1999, 2000, 2001, 2002, 2003, 2004 Jon C.

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