Assessing the Drug Exposure Risk of Infants Breastfed by Women With Inflammatory Bowel Disease

NCT03397108 | Completed Results

• 1 other identifier: 1000056982
• Study Type: observational
• Target: 79
• Locations: 1 country
• Sites: 2

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.

Conditions

Crohn's Disease; Ulcerative Colitis; Healthy Controls

Keywords

Inflammatory Bowel Disease; Crohn disease; Colitis; TNF; Breast milk; monoclonal antibody

Outcome Measures

Primary Outcomes (1)

• 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

  This observational study collected milk samples during the defined study periods: early-lactation and mid-lactation. To capture a temporal profiles of Tumour Necrosis Factor (TNF) and TNF-dependent chemokine levels, we analyzed these 2 sampling periods separately, instead of pooling them per sampling period. Multiplex assay was used to measure TNF and TNF-dependent downstream chemokines including MCP-1 (CCL2), MIP-1beta (CCL4) and IP10 (CXCL10) in breast milk of two groups of participants (women with IBD and healthy controls) at two sampling periods (early- and mid-lactation). Our original plan included MCP-3 (CCL7) as well, but an average quantification rate for this chemokine was only 33%, and therefore we excluded MCP-3 from our analyses.

  Two points at early-lactation (median 5-6 postpartum weeks) and mid-lactation (median 13-14 postpartum weeks)

Secondary Outcomes (1)

• 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

  At the infant age of 12 months and 18 months

Other Outcomes (3)

• Population Pharmacokinetic Study of Anti-TNF Monoclonal Antibody in Milk

  1-2 months

• Milk Sampling Time Point in the Early Lactation Period

  postpartum weeks until 10 weeks.

• Milk Sampling Time Point in the Mid Lactation Period

  postpartum weeks of 10-20 weeks.

Study Arms (2)

Women with IBD

This group is composed of breastfeeding women aged over 18 years and in their first 4-month postpartum period, who are diagnosed with Crohn's disease or Ulcerative Colitis. Some of them were receiving anti-TNF monoclonal antibody prescribed by their prescribers (outside this observational study) at a standard dose and interval.

Other: The IBD group was divided into 2 subgroups: with or without anti-TNF antibody use

Healthy breastfeeding women

This group is composed of healthy breastfeeding women aged over 18 years and in their first 4-month postpartum period.

Interventions

The IBD group was divided into 2 subgroups: with or without anti-TNF antibody use OTHER

This observational study enrolled women with IBD, and some of them were receiving a treatment with anti-TNF monoclonal antibody, which was prescribed by their responsible prescribers at a standard dose and dosing interval.

Women with IBD

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• MOUNT SINAI HOSPITAL: collaborator
• Crohn's and Colitis Foundation: collaborator

Study Sites (2)

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Related Publications (2)

• 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.

  PMID: 39672826 BACKGROUND

• 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.

  PMID: 39487320 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Human milk samples will be collected and analyzed for TNF alpha, TNF alpha-dependent chemokines, and infliximab/adalimumab levels.

MeSH Terms

Conditions

Crohn Disease; Colitis, Ulcerative; Inflammatory Bowel Diseases; Colitis

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colonic Diseases

Limitations and Caveats

This observational cohort study continued throughout the pandemic restrictions in person-to-person contact. This posed significant challenges to us. Despite this, the participating mother-infant pairs volunteered for the study. This may be the reason why many women in our IBD cohort were in remission, and those women on a severe end of IBD spectrum were not represented by our cohort, limiting the generalizability of our findings.

Results Point of Contact

• Title: Dr. Shinya Ito
• Organization: The Hospital for Sick Children

shinya.ito@sickkids.ca

4168135776

Study Officials

• Shinya Ito, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Head of Clinical Pharmacology & Toxicology

Study Record Dates

• First Submitted: December 19, 2017
• First Posted: January 11, 2018
• Study Start: August 31, 2017
• Primary Completion: November 30, 2022
• Study Completion: November 5, 2024
• Last Updated: March 4, 2025
• Results First Posted: March 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be available from February 2025 to January 2028
• Access Criteria: 1. Request deemed reasonable by the study team 2. No objection from the research ethics board of the Hospital for Sick Children 3. No objection from the legal department of the Hospital for Sick Children

Locations

CA (2)