Clinical trial NCT03397108: Assessing the Drug Exposure Risk of Infants Breastfed by Women With Inflammatory Bowel Disease
Official title: Assessing the Drug Exposure Risk of Infants Breastfed by Women With Inflammatory Bowel Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Crohn's Disease
Ulcerative Colitis
Healthy Controls
Keywords: Inflammatory Bowel Disease
Crohn disease
Colitis
TNF
Breast milk
monoclonal antibody
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: MOUNT SINAI HOSPITAL
name: Crohn's and Colitis Foundation
First posted: 2018-01-11
Enrollment: 79
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study participants are required to live in the Greater Toronto Area. The IBD group will be selected from IBD clinics, while the healthy controls will be selected from the community samples who volunteer to participate.

Brief summary: Breastfeeding is beneficial to both mother and baby. However, many breastfeeding women are affected by long-term health conditions and need to take medications.

Inflammatory Bowel Disease (IBD) is marked by an abnormal response of the body's immune system, and high levels of certain proteins that cause inflammation (Cytokines like Tumor Necrosis Factor-alpha or TNF). A group of drugs called "biologics" target and stop these proteins from causing inflammation, and have been successfully used to treat this condition. Inflammatory proteins may be present in breast milk of healthy women in variable levels, and may play a role in development of infant's brain and immune system.

This observational study is conducted to investigate:

* Concentration of some of the inflammatory proteins in breast milk of mothers with IBD and healthy controls
* Interaction between these proteins and biologics in breast milk of women with IBD
* Potential role of these proteins (and their interaction with biologics) on development of infant learning and memory function It has been presumed that concentrations of TNF and some other cytokines are higher in breast milk of women with IBD, and the biologics can normalize these high levels.

Note: Due to the pandemic, the study now consists of reduced number of study visits. The mandatory visits include two home visits in the first 4 months postpartum to complete a participant questionnaire and collect a small sample of breast milk at each visit. The optional study visits consist of two visits at the Hospital for Sick Children for evaluation of learning and memory function of the infant at the ages of 12 and 18 months. Additionally, mothers will be required to complete for their infant subscales of The Ages and Stages Questionnaires®, Third Edition (ASQ®-3) either in person or over the telephone at the ages of 12 months and 18 months.

Detailed description: The inflammatory bowel disease (IBD) shows the highest incidence among people of childbearing age. Indeed, it is not uncommon that pregnant or lactating women with IBD require drug therapy, including monoclonal antibodies against Tumor Necrosis Factor-alpha (TNF).

TNF and TNF-dependent chemokines are normally expressed in milk. Importantly, experimental data indicate enhanced brain growth and cognitive development in the mouse offspring given milk deficient in TNF and TNF-dependent chemokines. Patients with IBD are often treated with monoclonal antibodies against TNF (TNFmAb). Although TNFmAb is used during breastfeeding due to their minimal milk excretion, whether it affects endogenous TNF/chemokines in human milk is not known.

Our hypotheses are: 1) Women with IBD have higher TNF (and TNF-dependent chemokines) in milk than non-IBD control women, because of the inflammatory condition; and 2) Women with IBD receiving TNFmAb have lower TNF (and TNF-dependent chemokines) in milk than those with IBD who are not treated with TNFmAb.

We conduct an observational study of breastfeeding women with or without IBD. Some of these women with IBD are likely to be receiving TNFmAb. We measure milk concentrations of TNF and TNF-dependent chemokines in early (5-6 weeks postpartum) and mid-lactation period (13-14 weeks postpartum). Also, as an exploratory analysis, we assess their infant's cognitive and language development at 12 month and 18 months using Bayley-III tool.

Note:

Because there was no information at the outset of the study on cytokine profiles in milk of women with inflammatory conditions including IBD, a formal sample size could not be estimated. Although a provisional target was set, the study was designed to continue for the planned study duration as no stopping rule had been defined. Also, our original protocol included a population pharmacokinetic study of TNFmAb in milk. However, due to the pandemic and difficulty in developing the assay method, we were not able to start this part of the project.

Eligibility criteria: Inclusion Criteria:

* Breastfeeding women with IBD or healthy breastfeeding women in the first 4-month postpartum period

Exclusion Criteria:

* unable to communicate in English
* Present illness of chronic inflammatory conditions (except IBD)
* Mastitis
* Present acute or chronic infection
* use of a different anti-Tumor Necrosis Factor (TNF) drug within the last 2 months

Primary outcomes:
measure: Levels of TNF (Tumor Necrosis Factor Alpha) and TNF-dependent Chemokines (MCP1, MIP-1beta and IP10) in Breast Milk of Women With IBD and Healthy Controls by Multiplex Assay
timeFrame: Two points at early-lactation (median 5-6 postpartum weeks) and mid-lactation (median 13-14 postpartum weeks)
Secondary outcomes:
measure: Scores on Cognitive Subset of Bayley Scales of Infant and Toddler Development- Third Version (Bayley-III) in Infants of Healthy Controls and Women With IBD
timeFrame: At the infant age of 12 months and 18 months
Other outcomes:
measure: Population Pharmacokinetic Study of Anti-TNF Monoclonal Antibody in Milk
timeFrame: 1-2 months
measure: Milk Sampling Time Point in the Early Lactation Period
timeFrame: postpartum weeks until 10 weeks.
measure: Milk Sampling Time Point in the Mid Lactation Period
timeFrame: postpartum weeks of 10-20 weeks.
Locations:
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children
name: Shinya Ito, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Maron JL. The importance of investigating the effects of drug therapy on maternal breast milk composition. Pediatr Res. 2025 May;97(6):1765-1766. doi: 10.1038/s41390-024-03785-1. Epub 2024 Dec 13. No abstract available.
citation: Sepiashvili L, Brydon A, Koroshegyi C, Gold A, Dalvi P, Ghayoori S, Rahman M, Huang V, Maxwell C, Nguyen GC, Ito S. Reduction of tumor necrosis factor (TNF) in milk of women receiving anti-TNF antibody. Pediatr Res. 2025 May;97(6):1935-1942. doi: 10.1038/s41390-024-03672-9. Epub 2024 Nov 1.