Should breastfeeding be withheld in infants of mothers receiving azathioprine?/nThe question relate

Fråga: Should breastfeeding be withheld in infants of mothers receiving azathioprine? The question relates to an infant born at week 33 +6. The mother suffers from inflammatory bowel disease and has been treated with azathioprine (200 mg/day) during the pregnancy. Her gastroenterologist wants to continue her treatment with azathioprine and the mother wants to breastfeed her baby.

Sammanfattning: There is a limited amount of data concerning the use of azathioprine during breastfeeding, but the existing data indicate that breast-fed babies are exposed to a negligible dose. No increased risk for immunosuppression in the babies of mothers being treated with azathioprine has been detected. However, this is based only on clinical observation. Breastfeeding should not routinely be withheld in infants of mothers receiving azathioprine.

Svar: This question has earlier been answered in a few Drugline documents and the risk for the baby has generally been considered low, even though this has been based on only three case reports (1,2,3,4). There has now been published new data, adding more information to this subject (5,6,7).

In one study on 10 women treated with azathioprine in a dosage of 75-150 mg/day, breast milk samples were taken on day 3-4, day 7-10 and day 28 (5). Additionally, blood samples were obtained from 7 neonates on days 1-6 of life if other tests were indicated clinically, days 7-10 and day 28. 6-mercaptopurine (6-MP) levels were measured in breast milk samples and in blood samples both 6-MP levels and 6-thiogunaine nucleotides (6-TGN) were measured. The timings of collection of breast milk samples varied between just prior to azathioprine intake and 3-18 hours after the azathioprine intake. 6-MP were only detected in one case (1.2 and 7.6 ng/mL at 3 and 6 hours after ingestion of azathioprine respectively). Eleven blood samples were obtained from the 7 neonates and 6-MP and 6-TGN were undetectable in neonatal blood. There were no clinical signs of immunosuppression in any of the ten neonates, three of whom were preterm.

In another study on 4 patients treated with azathioprine (50-100 mg /day) while lactating, breast milk samples were analyzed for 6-MP in two of the mothers (6). Several milk samples per patient were obtained and 6-MP were undetectable by HPLC (detection limit 5 ng/mL). The authors concluded that the infant dose would have been less than 0.09% of the maternal weight adjusted dose. No adverse effects were seen in any of the 4 infants.

In a third study on four women treated with azathioprine (1.2-2.1 mg/kg/day), neither 6-TGN nor 6-methylmercaptopurine nucleotides (6-MMP) were detected in blood samples from any of the infants (7). All mothers and babies had the wild-type TPMT genotype and maternal blood concentrations of 6-TGN and 6-MMP were in a range normally considered to be therapeutic and non-toxic (6-TGN 234-291 pmol/8*10(8) rbc´s; 6-MMP 284-1178 pmol/8*10(8) rbc´s).