Therapeutic Immunosuppressant Levels In Mammary Gland Secretions

Many of the immunosuppressive drugs used during pregnancy are also found in breast milk. Currently, the American Academy of Pediatrics (AAP) provides guidelines for breastfeeding based on the excretion rate and potential teratogenic effects of each drug (Tendron et al. 2002). For example, limited concentrations (<10%) of prednisone and prednisolone have been measured in breast milk, levels perceived by the AAP as nonthreatening to the breastfed infant (Coulam et al. 1982; Ost et al. 1985). Thus, mothers on prednisone therapy are allowed to breastfeed since the maternal passive immunity outweighs the minimal perceived risks of prednisone. Azathioprine and its metabolites are also detectable at low concentrations in breast milk. Interestingly, due to a paucity of data regarding azathioprine, no guidelines by the AAP for breastfeeding have yet been established. Likewise, tacrolimus (FK506), which has also been detected in breast milk at concentrations reported to be comparable to maternal blood concentrations, is lacking AAP guidelines (Tendron et al. 2002). This is not the case for other immunosuppressants.

Ablactation has been recommended in women treated with cyclosporine A, cyclophosphamide, doxorubicin, and methotrexate, because these compounds have been shown to have high rates of transfer into breast milk (Wiernik and Duncan 1971; Johns et al. 1972; Amato and Niblett 1977; Flechner et al. 1985; Nyberg et al. 1998). Some drugs, including doxorubicin, concentrate beyond maternal blood levels in human milk (Egan et al. 1985). As much as 5% of an immunosuppressive dose of cyclosporine A can transfer from serum into the breast milk, with largely unknown side effects on the child's immune system being a significant concern (Behrens et al. 1989). The blood of newborns, prior to initiation of breastfeeding, can contain cyclosporine A concentrations up to 65 to 85% of maternal levels (Gunter et al. 1989). Notwithstanding, a recent case study described a 35-year-old woman who, while on cyclosporine A, breastfed her child for 10.5 months. The child showed no clinical developmental abnormalities nor were detectable levels of cyclosporine A found in the infant (Munoz-Flores-Thiagarajan et al. 2001). This may be in contrast to laboratory rodent data. For instance, newborn rat pups, suckling from the dams who were dosed with cyclosporine A at either 15 or 25 mg/kg for 20 days, displayed thymic hypocellularity, inhibition of T-cell maturation, and depressed lymphocyte proliferation (Padgett and Seelig 2002). It is important to note that cyclosporine A blood levels in the rats were higher than what is normally reported in humans. Collectively, these studies raise questions regarding the ability of transplacental cyclosporine A exposure to impair neonatal development of the human immune system. Further, the possibility of chemotherapeutics (other than cyclosporine A) transmitting via mammary secretions and negatively impacting the developing immune system needs evaluation.

New Mothers Guide to Breast Feeding

New Mothers Guide to Breast Feeding

For many years, scientists have been playing out the ingredients that make breast milk the perfect food for babies. They've discovered to day over 200 close compounds to fight infection, help the immune system mature, aid in digestion, and support brain growth - nature made properties that science simply cannot copy. The important long term benefits of breast feeding include reduced risk of asthma, allergies, obesity, and some forms of childhood cancer. The more that scientists continue to learn, the better breast milk looks.

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