Breastfeeding by a mother taking cyclosporine for nephrotic syndrome

Cyclosporine is a crucial agent for treating nephrotic syndrome and is safe to use in pregnant women. However, mothers taking this drug are generally advised to avoid breastfeeding because cyclosporine may pass and enrich into breast milk, which may impair renal and liver function of breastfed infants, increase their susceptibility to hypertension, hypertrichosis, gingival hypertrophy, and cancer, and lead to infants` immune suppression [14, 15]. This traditional viewpoint has gradually changed as several cases of successful breastfeeding have been reported. Thiru et al. reported an infant whose mother took cyclosporine 3 mg/kg twice daily and breastfed was healthy at two years of age [16]. Nyberg et al. reported seven infants breastfed during maternal cyclosporine grew normally [17]. The National Transplantation Pregnancy Registry reported data on mothers who breastfed their infants following organ transplantation. From 1991 to 2013, a total of 43 mothers on treatment with cyclosporine had breastfed 55 infants with no apparent adverse effects in infants [7]. Cyclosporine is then considered compatible with breastfeeding by the European League Against Rheumatism if the infants do not have conditions that preclude it [2]. The decision on drug therapy during lactation should be based on an agreement between the internist, the obstetrician, the patient, and other healthcare providers. The American College of Rheumatology indicates using cyclosporine during breastfeeding is conditionally recommended since its amount transferred into breast milk seems low [18]. Although most of published cases and series of cyclosporine-treated mothers measured cyclosporine levels in breast milk, seldom of them monitored breast milk cyclosporine concentration consecutively [13]. Osadchy et al. reported cyclosporine concentration of 46 mcg/L in one milk sample two hours after a morning dose in a post renal transplantation mother taking 2.1 mg/kg daily (175 mg in total) [8]. Mazzuoccolo et al. tested milk levels of 128–364 mcg/L in a mother with plaque psoriasis taking cyclosporine 200 mg daily [12]. Milk samples were collected before morning doses on days 10 and 40, and two hours after morning doses on days 30 and 50 postpartum. It remains unclear whether infants are exposed to safe doses anytime throughout the day when they are breastfed, especially when infants` feeding time is close to when mothers take medicine. Consecutive milk level monitoring is thus essential. In our study, the mother`s milk was safe to the infants due to the low cyclosporine levels at all times of the day (0.443–5.307 mcg/L), indicating mothers with nephrotic syndrome also have the chances to sustain breastfeeding on their infants safely like mothers received renal transplantation [17]. It was also noticed that milk cyclosporine levels in our study were much lower than that in the previous studies. It can be partially attributed to the great variability of cyclosporine metabolism among individuals and the low blood cyclosporine concentration of the mother in our study. Since our study reported the first case of mother with NS taking cyclosporine and breastfeeding, more studies on mothers with NS taking cyclosporine are worth carrying out to determine whether the disease plays a role in the metabolism of cyclosporine and causes the low milk cyclosporine levels.

During clinical practice, obstetricians and parents are eager to know the safety of cyclosporine in lactation. They are also concerned if using other medications during lactation, including other immuno-suppressants, may elevate milk cyclosporine levels. Since consecutive cyclosporine levels are measured in breast milk, general concentrations of cyclosporine intake can be valuable references to optimize the decision-making process.

Existing limited literature suggested that cyclosporine excreted into breast milk had almost undetectable effects on exposed infants, with no adverse effects reported except one infant reached “therapeutic concentration”. Moretti et al. reported one infant had blood levels of 117 and 131 mcg/L on two occasions while the peak concentration in its mother`s milk was 521 mcg/L [5]. Thus, an infant blood test can be done if the milk level is relatively high. Long-term monitoring of those children, including their vaccination status, is still necessary [14].

Although the mother in our study did not exclusively breastfeed her infants due to insufficient breast milk for the twins, concentrations of cyclosporine in breast milk were consecutively monitored and were found to be low. It seemed that the absorption, distribution, metabolism, and excretion of cyclosporine did not significantly affect cyclosporine levels in breast milk throughout the day. The growth of the two babies was normal. The maternal blood level of cyclosporine was not consecutively monitored because it was undetectable (< 30 mcg/L) on the 8th day after parturition. Thus, we did not analyze the milk blood ratio and its peak. Maternal symptoms of NS were relieved, even though her blood levels seemed under normal therapeutic concentration.

Breastfeeding should not be discouraged when mothers are on cyclosporine treatment and decide on their infants’ feeding patterns. Levels of cyclosporine excreted into breast milk during breastfeeding should be monitored if possible. When maternal blood and milk cyclosporine levels were closely and regularly monitored, breastfeeding might still be a good option. However, mothers should be fully informed about the potential risks to their infants, including the increased risks associated with live vaccines. Mothers who choose to breastfeed their infants should observe the breastfed infants for signs of infection, vomiting and poor feeding. Infants` full blood count, renal and liver function, and blood cyclosporine level should be measured if any unusual conditions are noted in the breastfed infants.

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