Author information

1 Division of Gastroenterology and Hepatology, Oregon Health & Science University, Portland, OR. Electronic address: matro@ohsu.edu.

2 Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC.

3 Atlanta Gastroenterology Associates, Atlanta, GA.

4 Division of Gastroenterology, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island.

5 Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, CA.

Abstract

BACKGROUND & AIMS: Exposure to biologic and immunosuppressant agents during breastfeeding is controversial and there are limited data on safety. We investigated whether biologics are detectable in breast milk from women receiving treatment for inflammatory bowel diseases (IBD) and whether breastfeeding while on treatment is associated with infections or developmental delays.

METHODS: We performed a multi-center prospective study of women with IBD and their infants, collecting breast milk samples (n=72) from patients receiving biologic therapy from October 2013 to November 2015. Drug concentrations were measured in all breast milk samples at several time points within 48 hrs of collection and within 168 hrs for some samples. Child development was assessed using the Ages and Stages Questionnaire 3 (ASQ3), completed by 824 women with IBD (treated or untreated) during pregnancy (620 breastfed and 204 did not). Data on childrens' health and development were obtained from mothers and pediatricians, along with information on mothers' medication exposure, IBD history, activity, and pregnancy, and post-partum complications. We used χ2 or Fisher's exact test to determine associations between categorical values, and compared differences in continuous outcomes between groups using ANOVA models. The primary outcome was drug concentration of biologic agents in breast milk (from 72 women) at 1, 12, 24, and 48 hours after dosing, and also at 72, 96, 120, and 168 hrs from available samples. Secondary outcomes were a range of infant infections and ASQ3-defined developmental delays among all breast-fed infants.

RESULTS: We detected infliximab in breast milk samples from 19 of 29 treated women (max 0.74 μg/mL), adalimumab in 2 of 21 treated women (max 0.71 μg/mL), certolizumab in 3 of 13 treated women (max 0.29 μg/mL), natalizumab in 1 of 2 treated women (max 0.46 μg/mL), and ustekinumab in 4 of 6 treated women (max 1.57 μg/mL); we did not detect golimumab in breast milk from the 1 woman receiving this drug. Rates of infection and developmental milestones at 12 months were similar in breastfed vs non-breastfed infants: any infection 39% vs 39% in controls (P=1.000) and milestone score 87 vs 86 in controls (P=.9992). Rates of infection and developmental milestones did not differ among infants whose mothers received treatment with biologics, immunomodulators, or combination therapy, compared to unexposed infants (whose mothers received treatment with mesalamines or steroids or no medication).

CONCLUSIONS: In a study of women receiving treatment for IBD and their infants, we detected low concentrations of infliximab, adalimumab, certolizumab, natalizumab, and ustekinumab in breast milk samples. We found breastfed infants of mothers on biologics, immunomodulators, or combination therapies to have similar risks of infection and rate of milestone achievement compared to non-breastfed or infants unexposed to these drugs. Maternal use of biologic therapy appears compatible with breastfeeding. Clinicaltrials.gov no: NCT00904878.