Transplant and pregnancy

Updated: May 4, 2023

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In 1956, Edith Helm received a kidney transplant from her identical twin sister. Two years later, she became the first woman to give birth post-kidney transplantation successfully. She was also the longest-surviving kidney transplant recipient passing away in April 2011 at 76 from a non-transplant-related illness with a functioning graft. Female kidney transplant recipients might consider having a family and want to get pregnant as Edith did.

The diminished fertility for patients with kidney failure begins to recover after receiving a kidney transplant with normalization of the hypothalamic-pituitary-gonadal axis by six months. Navigating pregnancy requires a multi-disciplinary approach, thereby minimizing the risk to the mother, fetus, and transplanted kidney. This blog post aims to provide an overview of the general management of family planning for kidney transplant recipients to achieve favorable outcomes.

Planning is Key

Timing: The Kidney Disease: Improving Global Outcomes (KDIGO), and European Best Practice recommend delaying pregnancy until one and two years after the transplant, respectively. Thus, it is essential to counsel patients on using safe and effective contraception methods early, preceding transplant, as the risk of unintended pregnancy could exceed that of adverse contraception-related events.

Contraception: Patients are advised to use two reliable contraception methods, with consistent condom use being one of them. The choice of a contraception method should be tailored to the patient's needs, lifestyle, and comorbidities. Further information about contraception can be found (link to the contraception blog)

Medication adjustments: Another critical aspect of planning is the avoidance of teratogenic medications. Patients can be transitioned to a safer immunosuppression regimen where azathioprine replaces mycophenolate at least six weeks before pregnancy due to its teratogenic effects. Calcineurin inhibitors, steroids, and azathioprine are considered safe during pregnancy and breastfeeding. Rapamycin inhibitors and belatacept do not have enough data to support their use.

Since the implementation of the Pregnancy and Lactation Labeling Final Rule (PLLR) on June 30, 2015, the FDA pregnancy risk letter categories (A, B, C, D, X) have been replaced with a new narrative pregnancy risk categories to allow better patient counseling and an improved shared decision making. These sections include information about pregnancy (pregnancy exposure registry, risk summary, clinical considerations, data), lactation (risk summary, clinical considerations, and data), and females and males of reproductive potential (pregnancy testing, contraception, infertility).

Predictors of Good Outcomes

The reported live-birth rate for kidney transplant recipients is 72.9-75%, but it is associated with high maternal and fetal risks. The high live birth rate could also indicate selection bias since it is higher than the general population of 62%. There are predictors of good outcomes for pregnancy as listed below, and delaying pregnancy until they are achieved is desirable.

Younger maternal age
- A systematic review reported higher live birth outcomes with a maternal age < 29 years vs 29–34 (74% vs. 76%)
Stable graft function with no recent episodes of graft rejection
Adequate graft function
- Serum creatinine level of <1.5 mg/dl
- Proteinuria of <500 mg/day
Normal or well-controlled hypertension

Pregnancy outcomes

Maternal outcomes: There appears to be a high rate of pregnancy-induced hypertension (24.1-54.2%), preeclampsia (21.5-31% vs 3.8% US population), and patients tend to undergo cesarean section more commonly (52-62.6% vs 31.9% US population).

Fetal outcomes: Babies are more commonly delivered preterm with a mean gestational age of 34.9-35.9 wk, have a low-mean-birth-weight of 2470-2571 g, but no increased risk of congenital disabilities. The rates of neonatal death and stillbirths are 1.4-3.8% and 2-5.1%, respectively, vs. 0.4% and 0.6% in the US population.

Follow-up and Delivery

Patients should follow up in a high-risk pregnancy clinic and be seen regularly by their nephrologist every 1-2 months. Routine kidney function and drug levels should be measured every four weeks during the first trimester and every two weeks afterwards. It is essential to be cognizant of the normal physiological changes during pregnancy. Normally, pregnancy leads to a hyperfiltration state with a concordant creatinine decrease and proteinuria increase. Thus, careful monitoring of creatinine levels, proteinuria, and blood pressure measurements are vital to evaluate hypertension, preeclampsia, and graft loss. eGFR changes affect drug metabolism during pregnancy and patients might need to increase their tacrolimus dose by 20-25%.

Normal vaginal delivery is possible and does not affect graft function. If patients undergo a cesarean section, careful identification of the renal artery anatomy is important to avoid injury. Breastfeeding is generally encouraged, and the combination of tacrolimus, azathioprine, and steroids are felt to be safe. Further information about medication safety for breastfeeding can be found here.

Graft Function and Pregnancy

A significant concern for transplant recipients considering pregnancy is graft function during and after pregnancy. It is, of course, essential to have stable and adequate kidney function with no acute rejection episodes. In a systematic review, the reported rate of acute rejection during pregnancy was 9.4%, and the 2-year post-pregnancy graft loss was 9.2%. Another systematic review focusing on the long-term effects of pregnancy on graft loss and creatinine level reported that graft loss was 9.2% within 2–5 years, 22.3% within 5–10 years, and 38.5% >10 years postpartum, while serum creatinine level was stable with marginal elevation in the first two years (0.18mg/dL). This rate is reassuring compared to the deceased donor recipients' 5 and 10-year overall graft survival rates in the US of 72% and 53.6%, respectively, although the US graft survival rate is lower than in other countries.

Conclusion

Pregnant kidney transplant recipients are considered high-risk pregnancies that require a multi-disciplinary approach, and planning is critical for favorable outcomes—delaying pregnancy until at least one year post-transplantation is recommended with avoidance of all teratogenic medications. There is a high rate of successful pregnancies, but maternal and fetal adverse events remain common. Careful attention to the normal physiological changes during pregnancy is needed to adjust the immunosuppression regimen and detect graft dysfunction. There does not appear to be an increased risk for graft loss.

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