Breastfeeding and Immunosuppressive Therapy in Organ Transplant Recipients

Breastfeeding and Immunosuppressive Therapy in Organ Transplantation

On the occasion of the publication of my article "Breastfeeding Consultation in Organ Transplantation Recipients: Theoretical Background and a Case Report" in the journal "Breastfeeding & Lactation", I would like to offer a summary of the key points regarding breastfeeding and immunosuppressive treatments in the context of organ transplantation (organ graft).

Breastfeeding offers numerous benefits for both mother and child. Most health organisations recommend exclusive breastfeeding for at least six months, followed by continued breastfeeding for two years or until the mother or child decides to wean (WHO, LANCET).

Organ transplantation is a life-saving intervention in cases of organ failure. It requires the recipient to undertake lifelong immunosuppressive therapy so that the body accepts the transplanted organ. Pregnancies in transplanted women are becoming increasingly common.

An international registry documents cases of pregnancy in transplant recipients, tracking outcomes including delivery, observed complications, breastfeeding, and monitoring of children's health (NTPR 2022).

Breastfeeding after organ transplantation remains a rare situation, a source of confusion, as most immunosuppressive drugs carry package inserts advising against breastfeeding.

Breastfeeding was previously contraindicated due to immunosuppressive therapy, but compatible treatments now exist. However, for certain medications, breastfeeding is still discouraged due to insufficient data on their toxicity.

Breastfeeding rates are rising in this population: from less than 10% in the early 1990s, they increased to 35% in 2012, then to 44% in 2012 for renal transplantation (Anderson BMed 2020), and up to 80% more recently (NTPR REPORT).

Breastfeeding and Immunosuppressive Drugs

Transplant recipients require intensive treatment involving several medications to promote organ acceptance and prevent their immune system from reacting against and attacking the graft. These medications vary depending on the transplanted organ. Immunosuppressive therapy generally requires a combination of several drugs; for some, blood concentrations are monitored to adjust dosages.

These medications are generally used to prevent organ rejection and maintain graft tolerance.

An induction regimen is generally followed by a maintenance regimen for as long as the graft remains functional.

Sadonikova et al. report that some healthcare professionals are reluctant to support breastfeeding in transplant patients: several physicians in this study advised patients to pump and discard their milk until the safety of the medications was established, resulting in weaning for some mothers.

Other studies highlight mothers' lack of knowledge regarding the compatibility of their treatments with breastfeeding (Bartosz Korzeb et al., De Philippi et al.).

Following organ transplantation, pregnancies carry a high risk: preterm births are more frequent and the risk of low birth weight is higher (NTPR, McKINZIE). Regarding renal transplantation, rates of pre-eclampsia, gestational diabetes, caesarean section, and gestational hypertension are elevated (Shah et al.). These complications may have an impact on breastfeeding.

McKINZIE et al. also report on the early effects of immunosuppressive therapy in infants (due to in utero exposure): renal dysfunction caused by calcineurin inhibitors, myelosuppression from azathioprine, and a reduction in circulating immune cells with several agents. These effects are short-lived, but the decrease in immune cell counts may predispose the infant to an increased risk of infectious complications during the first year of life. This underscores the importance of breastfeeding in this context. Using relative infant dose estimates, almost all commonly used immunosuppressants are likely to be safe during breastfeeding, given the limited exposure to the infant.

Several immunosuppressive drugs are compatible with breastfeeding, with minimal transfer into breast milk, and the monitoring of children exposed in utero and during breastfeeding is reassuring:

• Ciclosporin

• Tacrolimus

• Azathioprine

• Long-term corticosteroids

Medications not recommended during breastfeeding include:

• Mycophenolate mofetil (MMF): it is contraindicated during pregnancy, therefore no information is available on its transfer into breast milk, and it should be avoided during breastfeeding.

• mTOR inhibitors: Sirolimus, Temsirolimus, Everolimus.

These drugs probably have low transfer into breast milk but have a long half-life. There is limited information on their use during breastfeeding; their use should therefore be avoided.

• Monoclonal antibodies such as basiliximab

These are very large protein molecules, and their quantity in breast milk is probably low. Their absorption is unlikely as they are destroyed in the infant's stomach. Some antibodies are insufficiently studied with regard to breastfeeding (e.g., antithymocyte globulin, basiliximab); it is therefore recommended to suspend breastfeeding during their use. Rituximab has more available data: the relative infant dose is 0.1% or less, several infants have been safely breastfed while their mothers were treated with rituximab, and the risk appears to be low.

• Belatacept: limited information is available regarding breastfeeding and its excretion into breast milk. Its very long half-life (8 to 10 days) also implies a potentially longer presence in breast milk. Breastfeeding is therefore discouraged during its use.

Role of the IBCLC with a Breastfeeding Transplant Recipient

In the context of a prenatal consultation with a transplant recipient, the role of the lactation consultant will be to:

• Provide information on drug compatibility and breastfeeding;

• Provide antenatal information: advise on breastfeeding management from the very first days, but also on the difficulties the mother may encounter in her particular context: breastfeeding a premature infant, breastfeeding after caesarean section, skin-to-skin contact, milk expression;

• Provide postnatal support and guidance.

The more detailed article, including a case report, written by Elise Armoiry, is available in the Lactation & Breastfeeding magazine published by the ELACTA association.

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Interested in this subject? Join the Pharmacology and Toxicology Professional Training course ( Replay )

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References:

• WHO.

• Lancet. Breastfeeding series. 2016.

• National Transplantation Pregnancy Registry 2022 Report.

• Philip O Anderson. Breastfeeding after organ transplantation, Breastfeeding Medicine Vol 15 n°2 Feb 2020 p 69-71.

• McKinzie CJ, Casale JP, Guerci JC, Prom A, Doligalski CT. Outcomes of Children with Fetal and Lactation Immunosuppression Exposure Born to Female Transplant Recipients. Paediatr Drugs. 2022 Sep;24(5):483-497. doi: 10.1007/s40272-022-00525-y. Epub 2022 Jul 23. PMID: 35870080.

• Bartosz Korzeb, et al. Level of Knowledge of Post-Transplant Women About Breastfeeding During Immunosuppression. Transplantation Proceedings, Volume 56, Issue 4, 2024, Pages 923-925, ISSN 0041-1345.

• DeFilippis EM, et al. Patient Perceptions and Knowledge Surrounding Pregnancy After Heart Transplantation: A Multicenter Study. Circ Heart Fail. 2024 Aug;17(8):e011741. doi: 10.1161/CIRCHEARTFAILURE.124.011741. Epub 2024 Aug 1. PMID: 39087365; PMCID: PMC11335446.

• Christina L. Klein and Michelle A. Josephson. Post-Transplant Pregnancy and Contraception. CJASN 17: 114-120, 2022.

• Anna Sadovnikova, et al. Comparison of Breastfeeding Practices in Mothers With Chronic Kidney Disease With or Without Kidney Transplantation. BREASTFEEDING MEDICINE Volume 18, Number 11, 2023. Mary Ann Liebert, Inc.