Initiation of Gender-Affirming Testosterone Therapy in a Lactating Transgender Man

Introduction: Transgender and gender diverse individuals may choose to provide their infants with human milk. Lactating transgender men may experience gender dysphoria and desire to initiate or reinitiate gender-affirming testosterone therapy. However, there is limited safety data regarding use of testosterone during lactation. Main Issue: A 30-year-old G2P2 transgender man with gender dysphoria sought to initiate gender-affirming testosterone therapy while lactating. Management: Subcutaneous testosterone was self-administered beginning at 13 months post-partum. We prospectively collected data on circulating testosterone concentrations in parent serum, milk, and infant serum over 5 months until the infant self-weaned. The infant was monitored for growth and development at routine pediatric outpatient appointments. Parent serum testosterone concentrations rose with the initiation of testosterone therapy, reaching therapeutic concentrations by Day 14. Milk testosterone concentrations also increased with a maximum concentration of 35.9 ng/dl when the lactating parent was on a dose of 80 mg subcutaneous testosterone cypionate weekly. The calculated milk/plasma ratio remained under 1.0 and the calculated relative infant dose remained under 1%. The infant had no observable side effects, and his serum testosterone concentrations remained undetectable throughout the study period. Conclusion: This is the first study with data regarding human milk and infant serum testosterone concentrations during the initiation of gender-affirming testosterone therapy in a lactating individual. This evidence can help families and clinicians with decisions regarding lactation and testosterone use.

Maternal Transfer of Cetirizine Into Human Milk

Introduction Cetirizine hydrochloride is a second-generation H1 histamine antagonist with Food and Drug Administration approval for treatment of allergic rhinitis and urticaria. Currently, the Food and Drug Administration does not recommend use of cetirizine during breastfeeding, as there are insufficient studies on both the transference of cetirizine into human milk and the effects of cetirizine in infants. Main issue To determine the concentration of cetirizine in human milk, samples were analyzed using high performance liquid chromatography mass spectrometry. Management Based on calculations, relative infant dose was found to be 1.77% at 24 hr. In addition, there were no reported adverse effects seen in the infants. Conclusion We suggest that transfer of cetirizine into human milk is minimal and unlikely to pose a significant risk to the breastfeeding infant. This is the first report presenting the transfer of cetirizine in human milk.

Breastfeeding in a patient with chronic myeloid leukemia during tyrosine kinase inhibitor therapy

Introduction Although imatinib is the first-line of therapy for Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML), in Japan, it is recommended by the manufacturer that lactating women treated with imatinib mesylate for CML should discontinue breastfeeding their infants. Case A 32-year-old pregnant patient was diagnosed with Ph-positive CML at 13 weeks of gestation. She received imatinib (400 mg/day) after 28 weeks of gestation. A female infant was delivered at a gestational age of 35 weeks and 3/7 days after preterm premature rupture of membranes. It was decided to feed only colostrum to the infant and formula feeding was done subsequently because of the risk of the transfer of imatinib to breast milk. The milk/plasma (M/P) ratio and the relative infant dose (RID) for imatinib were calculated to be 0.35 and 1.4%, respectively at 5 days of life. Moreover, the serum level of imatinib in the child of age 5 days was 27 ng/mL, which was much lower than the target trough value for CML (1000 ng/mL). Conclusion The M/P ratio and RID values for maternally administered imatinib were within the safe range for breastfeeding, as reported in previous studies. In addition, it was found that the serum concentration of imatinib in the child was relatively low during short-term breastfeeding.

Cladribine transfer into human milk: A case report

Background: Cladribine is an antimetabolite used for the treatment of relapsing–remitting multiple sclerosis. At present, there are no data available on its use in breastfeeding mothers and its transfer in human milk. Objective: We present a case of a lactating mother who donated her milk samples to study the transfer of cladribine following a 20-mg oral dose. Methods: Analysis was done using liquid chromatography–mass spectrometry. Results: The relative infant dose calculated in this study was 3.06%. Conclusion: This is the first case report suggesting the transfer of cladribine in human milk in measurable quantities. However, caution should be advised during lactation.

DOSE ASSESSMENT FOR ATMOSPHERIC DISCHARGE OF LONG-LIVED RADIONUCLIDES IN NUCLEAR POWER PLANT DECOMMISSIONING

Decommissioning of nuclear power plants is a multistage process involving complex operations like radiological characterization, decontamination and dismantling of plant equipment, demolition of structures, and processing and disposal of waste. Radioactive effluents released into the environment may result in exposure of population through various exposure pathways. The present study estimates the public dose due to atmospheric discharge of important radionuclides during proposed decommissioning activities of Indian Pressurized Heavy Water Reactors. This study shows that major dose contributing radionuclides are 60Co followed by 94Nb, 134Cs, 154Eu, 152Eu, 133Ba, 99Tc, 93Mo and 41Ca. It is found that infant dose is higher than adult dose and major fraction of total dose (~98%) is through ground shine and ingestion; other pathways such as inhalation and plume shine contribute only a small fraction. This study will be helpful in carrying out radiological impact assessment for decommissioning operations which is an important regulatory requirement.

AB1294-HPR LOW CONCENTRATIONS OF BIOLOGIC DMARDS IN BREASTMILK OF PATIENTS TREATED DURING LACTATION

Background:There is very limited information about the passage of biologics into breast milk and into the peripheral blood of breastfed infants. However, based on pharmacological properties of biologic DMARDs (bDMARDs) lactation may not be discouraged in patients with chronic inflammatory rheumatic disease to treat or prevent postpartum relapses. We here report two cases treated with bDMARDs during lactation: one woman with Muckle-Wells syndrome (MWS) treated with canakinumab and one woman with microscopic polyangiitis (MPA) treated with rituximab.Objectives:To determine the level of rituximab and canakinumab in breast milk, in sera of breastfed infants as well as in sera of the mother and to calculate the average daily infant dose and the relative infant dose.Methods:Serum and milk levels of Rituximab were measured by ELISA using commercially available coating and detection antibodies. For Canakinumab an ELISA was established by coating of plates with recombinant human IL-1beta and detection of Canakinumab in samples by a polyclonal anti-human IgG coupled to HRP. In both cases separate standard curves for serum and milk were established. Serum samples and milk samples of unexposed healthy controls were used to determine the lower limit of quantification.Results:One patient with MWS received canakinumab 150 mg s.c. to treat a worsening of her disease ten days postpartum. She continued to breastfeed her child. The average concentration of canakinumab in milk samples collected on 10 consecutive days was 15.8 ng/ml. The average daily infant dose was 0.002 mg/kg/day. The relative infant dose, which refers infant to maternal exposure on a dose/weight basis, was 0.11%. There was no detectable canakinumab in the serum of the infant.One patient with MPA received rituximab 500 mg i.v. as a remission maintenance therapy four months postpartum. She continued to breastfeed her child. The average concentration of rituximab in milk samples collected on 4 consecutive days was 3.71 ng/ml. The average daily infant dose was 0.001 mg/kg/day. The relative infant dose was 0.01%. There was no detectable rituximab in the serum of the infant.Conclusion:Only minimal concentrations of canakinumab and rituximab can be detected in breastmilk. For both bDMARDs, the relative infant dose was below 1% of the maternal dose, which is considered unlikely to be of clinical concern. The lack of detectable levels of canakinumab and rituximab in the infants’ sera supports the notion of low oral bioavailability of large monoclonal antibodies. Together, the results are similar to those seen in TNF inhibitors which are regarded to be compatible with breastfeeding, yet more data are needed (1, 2, 3).References:[1]Götestam Skorpen C, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, da Silva J, Nelson-Piercy C, Cetin I, Costedoat-Chalumeau N, Dolhain R, Förger F, Khamashta M, Ruiz-Irastorza G, Zink A, Vencovsky J, Cutolo M, Caeyers N, Zumbühl C, Østensen M. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016 May;75(5):795-810. doi: 10.1136/annrheumdis-2015-208840. Epub 2016 Feb 17.[2]Clowse ME, Förger F, Hwang C, Thorp J, Dolhain RJ, van Tubergen A, Shaughnessy L, Simpson J, Teil M, Toublanc N, Wang M, Hale TW. Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study. Ann Rheum Dis. 2017 Nov;76(11):1890-1896. doi: 10.1136/annrheumdis-2017-211384. Epub 2017 Aug 16.[3]Matro R, Martin CF, Wolf D, Shah SA, Mahadevan U. Exposure Concentrations of Infants Breastfed by Women Receiving Biologic Therapies for Inflammatory Bowel Diseases and Effects of Breastfeeding on Infections and Development.Gastroenterology. 2018;155(3):696–704. doi:10.1053/j.gastro.2018.05.040Disclosure of Interests:Astrid Zbinden: None declared, Klara Eriksson: None declared, Frauke Förger Grant/research support from: Unrestricted grant from UCB, Consultant of: UCB, GSK, Roche, Speakers bureau: UCB, GSK

Dimethyl fumarate transfer into human milk

Dimethyl fumarate (DMF) is approved for the treatment of relapsing-remitting multiple sclerosis. It is unknown whether DMF or its primary metabolite monomethyl fumarate (MMF) are excreted into human milk. We present two cases of lactating patients who donated milk samples to study the transfer of MMF into human milk following a week of 2 × 240 mg daily oral dose. Samples were analyzed using liquid chromatography mass spectrometry. The calculated relative infant dose was 0.019% and 0.007%. This is the first study to demonstrate that MMF is transferred into human milk, with only limited exposure to an infant.

Minimal breast milk transfer of rituximab, a monoclonal antibody used in neurological conditions

ObjectiveTo determine the transfer of rituximab, an anti-CD20 monoclonal antibody widely used for neurologic conditions, into mature breast milk.MethodsBreast milk samples were collected from 9 women with MS who received rituximab 500 or 1,000 mg intravenous once or twice while breastfeeding from November 2017 to April 2019. Serial breast milk samples were collected before infusion and at 8 hours, 24 hours, 7 days, and 18–21 days after rituximab infusion in 4 patients. Five additional patients provided 1–2 samples at various times after rituximab infusion.ResultsThe median average rituximab concentration in mature breast milk was low at 0.063 μg/mL (range 0.046–0.097) in the 4 patients with serial breast milk collection, with an estimated median absolute infant dose of 0.0094 mg/kg/d and a relative infant dose (RID) of 0.08% (range 0.06%–0.10%). Most patients had a maximum concentration at 1–7 days after infusion. The maximum concentration occurred in a woman with a single breast milk sample and was 0.29 μg/mL at 11 days postinfusion, which corresponds with an estimated RID of 0.33%. Rituximab concentration in milk was virtually undetectable by 90 days postinfusion.ConclusionsWe determined minimal transfer of rituximab into mature breast milk. The RID for rituximab was less than 0.4% and well below theoretically acceptable levels of less than 10%. Low oral bioavailability would probably also limit the absorption of rituximab by the newborn. In women with serious autoimmune neurologic conditions, monoclonal antibody therapy may afford an acceptable benefit to risk ratio, supporting both maternal treatment and breastfeeding.

O31 Levetiracetam monitoring in breast-milk: high inter-individual variability

BackgroundAnti-epileptic drug therapy is a great challenge for the practitioners during pregnancy and lactation. Levetiracetam (LEV) is commonly prescribed to pregnant women, however, there are only few publications on its use during lactation with small number of participants.ObjectiveTo monitor LEV levels in breast-milk of epileptic mothers treated with LEV.MethodsBreastfeeding women treated with LEV during pregnancy and after delivery were recruited. Milk sample was collected before administration of the drug and other samples were collected at time points of 1,3,6,9, and 12 hours after drug administration. Breastmilk and blood LEV levels were measured using HPLC.ResultsFourteen breastfeeding women participated in the study: 9 infants were fully breastfed whereas 5 were partially breastfed. Maternal average daily dose of LEV was 2517 mg. Average infant´s age was 8 weeks (3–22w). Average infant´s weight 4368 gr (3300–7000 gr). Milk/Plasma LEV concentration ratio was 0.88 (0.23–1.1). Relative Infant Dose (RID) was 40% in partial breast feeding, and 61% in full breastfeeding. Estimated average daily dose that all infants received through milk was 158 mg/d (83–250 mg). The normalized dose for the average infant weight per day was 36 mg, which is 15% less than the maximal daily dose of LEV in infants (max. daily dose in infants 1–6 months in 42 mg/d). No adverse reactions were observed in the breastfeed infants.ConclusionsAlthough the RID of LEV were found to be high, no adverse reactions were observed in the infants; Nevertheless, further studies are needed to elucidate the high variability of LEV excretion into breastmilk.Disclosure(s)Nothing to disclose