In the literature on the safety of ursodeoxycholic acid (UDCA) during breastfeeding, insufficient data has been reported to date. Thus, the aim of our study was to analyze bile acid (BA) concentrations in breast milk in a cohort of patients, treated with UDCA, and with various cholestatic liver diseases. The study was carried out on a cohort of 20 patients with various cholestatic diseases. All the patients were treated with UDCA (500-1500 mg daily). Concentrations of BA, sampled on day 3 after delivery were analyzed using the GS-MS technique, and then compared to untreated women. Total BA concentrations in the breast milk of the UDCA-treated patients were equal to those of the untreated women controls (3.2 ± 1 vs. 3.2 ± 0.2 µmol/L, respectively). The UDCA concentrations in breast milk remained negligible in UDCA-treated patients (0.69 µmol/L), and in any event did not contribute to the newborn BA pool. No apparent side-effects of the maternal UDCA treatment were observed in any newborn infant, and no deterioration in postnatal development was observed during the routine 1-year follow-ups. Therapeutic administration of UDCA during lactation is safe for breastfed babies since UDCA only gets into breast milk in negligible amounts. UDCA treatment should be allowed and included into the guidelines for the therapy of cholestatic diseases in breastfeeding mothers.

4th Department of Internal Medicine General University Hospital Prague and 1st Faculty of Medicine Charles University Prague U Nemocnice 2 Prague 2 128 08 Czech Republic

Department of Gynecology and Obstetrics General University Hospital Prague and 1st Faculty of Medicine Prague Czech Republic

Department of Internal Medicine University Hospital in Hradec Králové and Faculty of Medicine in Hradec Králové Hradec Králové Czech Republic

Institute of Medical Biochemistry and Laboratory Diagnostics General University Hospital Prague and 1st Faculty of Medicine Prague Czech Republic

Sci Rep. 2022 Dec 16;12(1):21785. doi: 10.1038/s41598-022-26431-4. PubMed

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European Association for the Study of the Liver EASL Clinical Practice Guidelines: Management of cholestatic liver diseases. J. Hepatol. 2009;51:237–267. doi: 10.1016/j.jhep.2009.04.009. PubMed DOI

Lindor KD, Gershwin ME, Poupon R, et al. Primary biliary cirrhosis. Hepatology. 2009;50:291–308. doi: 10.1002/hep.22906. PubMed DOI

European Association for the Study of the Liver EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J. Hepatol. 2017;67:145–172. doi: 10.1016/j.jhep.2017.03.022. PubMed DOI

Ursodiol. Drugs and Lactation Database (LactMed) (2021) https://www.ncbi.nlm.nih.gov/books/NBK501389/ (Accessed 14 July 2022).

de Vries E, Beuers U. Ursodeoxycholic acid in pregnancy? J. Hepatol. 2019;71:1237–1245. doi: 10.1016/j.jhep.2019.08.020. PubMed DOI

Rudi J, Schonig T, Stremmel W. Therapy with ursodeoxycholic acid in primary biliary cirrhosis in pregnancy. Z. Gastroenterol. 1996;34:188–191. PubMed

Brites D, Rodrigues CM. Elevated levels of bile acids in colostrum of patients with cholestasis of pregnancy are decreased following ursodeoxycholic acid therapy [see comemnts] J. Hepatol. 1998;29:743–751. doi: 10.1016/S0168-8278(98)80255-9. PubMed DOI

Vitek L, Zelenkova M, Bruha R. Safe use of ursodeoxycholic acid in a breast-feeding patient with primary biliary cirrhosis. Digest Liver Dis. 2010;42:911–912. doi: 10.1016/j.dld.2010.06.002. PubMed DOI

Binder T, Duskova M, Hill M, et al. Intrahepatální cholestáza v těhotenství. Doporučený postup. Ceska Gynekol. 2017;82:168–169.

Setchel KDR, Lawson AM. Bile acids. In: Lawson AM, editor. Mass Spectrometry. Walter de Gruyter; 1999. pp. 53–125.

Kavalkova P, Mraz M, Trachta P, et al. Endocrine effects of duodenal-jejunal exclusion in obese patients with type 2 diabetes mellitus. J. Endocrinol. 2016;231:11–22. doi: 10.1530/JOE-16-0206. PubMed DOI

Hirano S, Masuda N, Oda H. In vitro transformation of chenodeoxycholic acid and ursodeoxycholic acid by human intestinal flora, with particular reference to the mutual conversion between the two bile acids. J. Lipid Res. 1981;22:735–743. doi: 10.1016/S0022-2275(20)37344-2. PubMed DOI

Bazzoli F, Fromm H, Sarva RP, Sembrat RF, Ceryak S. Comparative formation of lithocholic acid from chenodeoxycholic and ursodeoxycholic acids in the colon. Gastroenterology. 1982;83:753–760. doi: 10.1016/S0016-5085(82)80003-6. PubMed DOI

White BA, Fricke RJ, Hylemon PB. 7 Beta-dehydroxylation of ursodeoxycholic acid by whole cells and cell extracts of the intestinal anaerobic bacterium, Eubacterium species V.P.I. 12708. J. Lipid Res. 1982;23:145–153. doi: 10.1016/S0022-2275(20)38183-9. PubMed DOI

Erol-Coskun H, Karagur N, Akyol F, Karadas B, Kaya-Temiz T, Kaplan YC. Ursodiol use during breastfeeding: A case report. Reprod. Toxicol. 2018;80:159. doi: 10.1016/j.reprotox.2018.07.070. DOI

Watkins JB, Ingall D, Szczepanik P, Klein PD, Lester R. Bile-salt metabolism in the newborn. Measurement of pool size and synthesis by stable isotope technic. N. Engl. J. Med. 1973;288:431–434. doi: 10.1056/NEJM197303012880902. PubMed DOI

Attili AF, Angelico M, Cantafora A, Alvaro D, Capocaccia L. Bile acid-induced liver toxicity: Relation to the hydrophobic-hydrophilic balance of bile acids. Med. Hypotheses. 1986;19:57–69. doi: 10.1016/0306-9877(86)90137-4. PubMed DOI

Goh SK, Gull SE, Alexander GJ. Pregnancy in primary biliary cirrhosis complicated by portal hypertension: Report of a case and review of the literature. BJOG. 2001;108:760–762. PubMed

Efe C, Kahramanoglu-Aksoy E, Yilmaz B, et al. Pregnancy in women with primary biliary cirrhosis. Autoimmun Rev. 2014;13:931–935. doi: 10.1016/j.autrev.2014.05.008. PubMed DOI

Catzola A, Vajro P. Management options for cholestatic liver disease in children. Exp. Rev. Gastroenterol. Hepatol. 2017;11:1019–1030. doi: 10.1080/17474124.2017.1359538. PubMed DOI

Pakarinen MP, Johansen LS, Svensson JF, et al. Outcomes of biliary atresia in the Nordic countries—A multicenter study of 158 patients during 2005–2016. J. Pediatr. Surg. 2018;53:1509–1515. doi: 10.1016/j.jpedsurg.2017.08.048. PubMed DOI

Thibault M, McMahon J, Faubert G, et al. Parenteral nutrition-associated liver disease: A retrospective study of ursodeoxycholic acid use in neonates. J. Pediatr. Pharmacol. Ther. 2014;19:42–48. PubMed PMC

Simic D, Milojevic I, Bogicevic D, et al. Preventive effect of ursodeoxycholic acid on parenteral nutrition-associated liver disease in infants. Srp. Arh. Celok Lek. 2014;142:184–188. doi: 10.2298/SARH1404184S. PubMed DOI

Arslanoglu S, Moro GE, Tauschel HD, Boehm G. Ursodeoxycholic acid treatment in preterm infants: A pilot study for the prevention of cholestasis associated with total parenteral nutrition. J. Pediatr. Gastroenterol. Nutr. 2008;46:228–231. doi: 10.1097/MPG.0b013e3181560524. PubMed DOI

Liu SY, Chang LW, Wang J, Xie M, Chen LL, Liu W. Ursodeoxycholic acid prevention on cholestasis associated with total parenteral nutrition in preterm infants: A randomized trial. World J. Pediatr. 2022;18:100–108. doi: 10.1007/s12519-021-00487-0. PubMed DOI

Lewis T, Kuye S, Sherman A. Ursodeoxycholic acid versus phenobarbital for cholestasis in the Neonatal Intensive Care Unit. BMC Pediatr. 2018;18:197. doi: 10.1186/s12887-018-1167-y. PubMed DOI PMC

Chen CY, Tsao PN, Chen HL, Chou HC, Hsieh WS, Chang MH. Ursodeoxycholic acid (UDCA) therapy in very-low-birth-weight infants with parenteral nutrition-associated cholestasis. J. Pediatr. 2004;145:317–321. doi: 10.1016/j.jpeds.2004.05.038. PubMed DOI

Al-Hathlol K, Al-Madani A, Al-Saif S, Abulaimoun B, Al-Tawil K, El-Demerdash A. Ursodeoxycholic acid therapy for intractable total parenteral nutrition-associated cholestasis in surgical very low birth weight infants. Singap. Med. J. 2006;47:147–151. PubMed

Levine A, Maayan A, Shamir R, Dinari G, Sulkes J, Sirotta L. Parenteral nutrition-associated cholestasis in preterm neonates: Evaluation of ursodeoxycholic acid treatment. J. Pediatr. Endocrinol. Metab. 1999;12:549–553. doi: 10.1515/JPEM.1999.12.4.549. PubMed DOI

Zapata R, Sandoval L, Palma J, et al. Ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy. A 12-year experience. Liver Int. 2005;25:548–554. doi: 10.1111/j.1478-3231.2004.0996.x. PubMed DOI

Evans WRH, Nicoli ER, Wang RY, Movsesyan N, Platt FM. Case Report: Ursodeoxycholic acid treatment in Niemann-Pick disease type C; clinical experience in four cases. Wellcome Open Res. 2017;2:75. doi: 10.12688/wellcomeopenres.11854.1. PubMed DOI PMC

Cuperus FJ, Hafkamp AM, Havinga R, et al. Effective treatment of unconjugated hyperbilirubinemia with oral bile salts in Gunn rats. Gastroenterology. 2009;136:673–682. doi: 10.1053/j.gastro.2008.10.082. PubMed DOI

van der Schoor LWE, Verkade HJ, Bertolini A, et al. Potential of therapeutic bile acids in the treatment of neonatal hyperbilirubinemia. Sci. Rep. 2021;11:11107. doi: 10.1038/s41598-021-90687-5. PubMed DOI PMC

Honar N, Ghashghaei Saadi E, Saki F, Pishva N, Shakibazad N, Hosseini TS. Effect of ursodeoxycholic acid on indirect hyperbilirubinemia in neonates treated with phototherapy. J. Pediatr. Gastroenterol. Nutr. 2016;62:97–100. doi: 10.1097/MPG.0000000000000874. PubMed DOI

Ughasoro MD, Adimorah GN, Chukwudi NK, Nnakenyi ID, Iloh KK, Udemba CE. Reductive effect of ursodeoxycholic acid on bilirubin levels in neonates on phototherapy. Clin. Exp. Gastroenterol. 2019;12:349–354. doi: 10.2147/CEG.S207523. PubMed DOI PMC

Rezaie M, Gholami R, Jafari M, Haghighinejad H. Evaluating the effect of ursodeoxycholic acid on total bilirubin of neonates with glucose-6-phosphate dehydrogenase deficiency complicated by indirect hyperbilirubinaemia. J. Paediatr. Child Health. 2021;57:1175–1181. doi: 10.1111/jpc.15411. PubMed DOI

Gharehbaghi MM, Sani AM, Refeey M. Evaluating the effects of different doses of ursodeoxycholic acid on neonatal jaundice. Turk. J. Pediatr. 2020;62:424–430. doi: 10.24953/turkjped.2020.03.009. PubMed DOI

Akefi, R., Hashemi, S. M., Alinejad, S. & Almasi-Hashiani, A. The effect of ursodeoxycholic acid on indirect hyperbilirubinemia in neonates treated with phototherapy: A randomized clinical trial. J. Matern. Fetal Neonatal Med.35, 4075–4080 (2022). PubMed

Hulzebos CV, van Zoonen AG, Hulscher JB, et al. Fecal bile salts and the development of necrotizing enterocolitis in preterm infants. PLoS ONE. 2017;12:e0168633. doi: 10.1371/journal.pone.0168633. PubMed DOI PMC

Schanler RJ, Lau C, Hurst NM, Smith EO. Randomized trial of donor human milk versus preterm formula as substitutes for mothers' own milk in the feeding of extremely premature infants. Pediatrics. 2005;116:400–406. doi: 10.1542/peds.2004-1974. PubMed DOI