Trial Outcomes & Findings for Assessing the Drug Exposure Risk of Infants Breastfed by Women With Inflammatory Bowel Disease (NCT NCT03397108)
NCT ID: NCT03397108
Last Updated: 2025-03-04
Results Overview
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.
Recruitment status
COMPLETED
Target enrollment
79 participants
Primary outcome timeframe
Two points at early-lactation (median 5-6 postpartum weeks) and mid-lactation (median 13-14 postpartum weeks)
Results posted on
2025-03-04
Participant Flow
Participants enrolled between August 2017 to November 2022
Participant milestones
| Measure |
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.
|
Healthy Breastfeeding Women
This group is composed of healthy breastfeeding women aged over 18 years and in their first 4-month postpartum period.
|
|---|---|---|
|
Overall Study
STARTED
|
46
|
33
|
|
Overall Study
COMPLETED
|
26
|
31
|
|
Overall Study
NOT COMPLETED
|
20
|
2
|
Reasons for withdrawal
| Measure |
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.
|
Healthy Breastfeeding Women
This group is composed of healthy breastfeeding women aged over 18 years and in their first 4-month postpartum period.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
15
|
0
|
|
Overall Study
Insufficient milk production
|
3
|
2
|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Women With IBD
n=26 Participants
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.
|
Healthy Breastfeeding Women
n=31 Participants
This group is composed of healthy breastfeeding women aged over 18 years and in their first 4-month postpartum period.
|
Total
n=57 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
34 years
n=26 Participants
|
34 years
n=31 Participants
|
34 years
n=57 Participants
|
|
Sex/Gender, Customized
Female
|
26 participants
n=26 Participants
|
31 participants
n=31 Participants
|
57 participants
n=57 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Canada
|
26 participants
n=26 Participants
|
31 participants
n=31 Participants
|
57 participants
n=57 Participants
|
|
Maternal Weight
|
68 kg
n=26 Participants
|
66 kg
n=31 Participants
|
67 kg
n=57 Participants
|
|
Maternal BMI
|
25 kg/m^2
n=26 Participants
|
24 kg/m^2
n=31 Participants
|
24.5 kg/m^2
n=57 Participants
|
|
Pregnancy period
|
39 week
n=26 Participants
|
39 week
n=31 Participants
|
39 week
n=57 Participants
|
|
Mode of Delivery
Vaginal
|
16 participants
n=26 Participants
|
27 participants
n=31 Participants
|
43 participants
n=57 Participants
|
|
Mode of Delivery
C-section
|
10 participants
n=26 Participants
|
4 participants
n=31 Participants
|
14 participants
n=57 Participants
|
|
Infant Sex: Female
|
15 participants
n=26 Participants
|
13 participants
n=31 Participants
|
28 participants
n=57 Participants
|
|
Infant birth weight
|
3351 grams
n=26 Participants
|
3402 grams
n=31 Participants
|
3376.5 grams
n=57 Participants
|
|
Smoking during pregnancy
|
0 participants
n=26 Participants
|
0 participants
n=31 Participants
|
0 participants
n=57 Participants
|
|
Breastfeeding status
Exclusive breastfeeding
|
16 participants
n=26 Participants
|
23 participants
n=31 Participants
|
39 participants
n=57 Participants
|
|
Breastfeeding status
Predominant (>80% of time)
|
8 participants
n=26 Participants
|
6 participants
n=31 Participants
|
14 participants
n=57 Participants
|
|
Breastfeeding status
Usual (<80% of time)
|
2 participants
n=26 Participants
|
2 participants
n=31 Participants
|
4 participants
n=57 Participants
|
PRIMARY outcome
Timeframe: Two points at early-lactation (median 5-6 postpartum weeks) and mid-lactation (median 13-14 postpartum weeks)Population: Control is non-IBD breastfeeding women. IBD group was divided into 2 subgroups based on the status of their treatment with anti-TNF antibody (TNFmAb). Participants were tested twice: first, during early lactation period and second, later during mid-lactation period. Six women in IBD group could not provide milk samples during the mid-lactation period. MCP-3 (CCL7) detection rate was 33% of all samples and therefore excluded from the analyses.
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.
Outcome measures
| Measure |
Healthy Breastfeeding Women
n=31 Participants
This group is composed of healthy breastfeeding women aged over 18 years and in their first 4-month postpartum period.
|
Women With IBD
n=26 Participants
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.
|
IBD Subgroup "On TNFmAb Treatment"
n=9 Participants
Those women in the IBD group were further stratified into two subgroups based on the use of anti-TNF monoclonal antibody (TNFmAb): 1) "on TNFmAb treatment" if they received either infliximab within 8 weeks or adalimumab within 2 weeks of sample collection dates, which are usual dosing intervals of TNFmAb maintenance regimens; 2) otherwise "off TNFmAb treatment".
|
IBD Subgroup "Off TNFmAb Treatment"
n=17 Participants
Those women in the IBD group were further stratified into two subgroups based on the use of anti-TNF monoclonal antibody (TNFmAb): 1) "on TNFmAb treatment" if they received either infliximab within 8 weeks or adalimumab within 2 weeks of sample collection dates, which are usual dosing intervals of TNFmAb maintenance regimens; 2) if they were not receiving them during the sampling periods, "off TNFmAb treatment".
|
|---|---|---|---|---|
|
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
Early-lactation: TNF
|
12.5 pg/ml
Interval 9.6 to 28.5
|
19.8 pg/ml
Interval 5.7 to 34.0
|
7.1 pg/ml
Interval 3.1 to 15.8
|
23.5 pg/ml
Interval 9.8 to 49.3
|
|
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
Early-lactation: MCP1
|
1078.0 pg/ml
Interval 398.3 to 3383.0
|
1325.0 pg/ml
Interval 317.9 to 2761.0
|
339.6 pg/ml
Interval 201.2 to 1949.0
|
1352.0 pg/ml
Interval 879.1 to 3694.0
|
|
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
Early-lactation:MIP1beta
|
13.4 pg/ml
Interval 6.6 to 17.9
|
12.6 pg/ml
Interval 6.0 to 27.5
|
7.1 pg/ml
Interval 2.6 to 13.5
|
17.7 pg/ml
Interval 9.2 to 47.6
|
|
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
Early-lactation: IP10
|
3985.0 pg/ml
Interval 1355.0 to 6952.0
|
2302.0 pg/ml
Interval 853.5 to 5429.0
|
898.8 pg/ml
Interval 273.7 to 2014.0
|
3360.0 pg/ml
Interval 1511.0 to 10549.0
|
|
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
Mid-lactation: TNF
|
11.1 pg/ml
Interval 5.6 to 18.6
|
16.4 pg/ml
Interval 6.5 to 21.5
|
7.3 pg/ml
Interval 3.6 to 14.7
|
18.8 pg/ml
Interval 8.1 to 43.6
|
|
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
Mid-lactation: MCP1
|
513.1 pg/ml
Interval 403.4 to 1802.0
|
679.5 pg/ml
Interval 403.4 to 1802.0
|
305.8 pg/ml
Interval 183.8 to 1753.0
|
693.8 pg/ml
Interval 522.3 to 1981.0
|
|
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
Mid-lactation: MIP1beta
|
8.2 pg/ml
Interval 3.7 to 16.9
|
16.4 pg/ml
Interval 6.7 to 31.0
|
6.9 pg/ml
Interval 1.0 to 20.6
|
18.1 pg/ml
Interval 7.0 to 35.1
|
|
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
Mid-lactation: IP10
|
2041.0 pg/ml
Interval 970.3 to 3681.0
|
1277.0 pg/ml
Interval 748.2 to 2785.0
|
981.9 pg/ml
Interval 578.0 to 1758.0
|
1820.0 pg/ml
Interval 745.4 to 4024.0
|
|
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
Early-lactation MCP-3
|
NA pg/ml
67% of MCP-3 (CCL7) were below quantitation limit and was judged inappropriate to derive sample statistics.
|
NA pg/ml
67% of MCP-3 (CCL7) were below quantitation limit and was judged inappropriate to derive sample statistics.
|
NA pg/ml
67% of MCP-3 (CCL7) were below quantitation limit and was judged inappropriate to derive sample statistics.
|
NA pg/ml
67% of MCP-3 (CCL7) were below quantitation limit and was judged inappropriate to derive sample statistics.
|
|
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
Mid-lactation MCP-3
|
NA pg/ml
67% of MCP-3 (CCL7) were below quantitation limit and was judged inappropriate to derive sample statistics.
|
NA pg/ml
67% of MCP-3 (CCL7) were below quantitation limit and was judged inappropriate to derive sample statistics.
|
NA pg/ml
67% of MCP-3 (CCL7) were below quantitation limit and was judged inappropriate to derive sample statistics.
|
NA pg/ml
67% of MCP-3 (CCL7) were below quantitation limit and was judged inappropriate to derive sample statistics.
|
SECONDARY outcome
Timeframe: At the infant age of 12 months and 18 monthsPopulation: Language test was introduced to the project for completeness after the study had started. This created lower sample numbers at the 12 month point.
We used Bayley Scales of Infant and Toddler development- Third Version (Bayley-III): which is used widely to measure child's cognitive and language development. In this scale, for both cognitive and language scores, minimum standard score is 45 and maximum standard score is 155: Higher standard scores indicates stronger/better performance. Children of the participating mothers were tested at the age of 12 months and 18 months. The language assessment is also used for comprehensiveness, but this has been added after the study was started. The test is performed as a single-blinded assessment in a controlled environment at the Hospital for Sick Children by a trained psychometrist supervised by a psychologist.
Outcome measures
| Measure |
Healthy Breastfeeding Women
n=15 Participants
This group is composed of healthy breastfeeding women aged over 18 years and in their first 4-month postpartum period.
|
Women With IBD
n=28 Participants
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.
|
IBD Subgroup "On TNFmAb Treatment"
Those women in the IBD group were further stratified into two subgroups based on the use of anti-TNF monoclonal antibody (TNFmAb): 1) "on TNFmAb treatment" if they received either infliximab within 8 weeks or adalimumab within 2 weeks of sample collection dates, which are usual dosing intervals of TNFmAb maintenance regimens; 2) otherwise "off TNFmAb treatment".
|
IBD Subgroup "Off TNFmAb Treatment"
Those women in the IBD group were further stratified into two subgroups based on the use of anti-TNF monoclonal antibody (TNFmAb): 1) "on TNFmAb treatment" if they received either infliximab within 8 weeks or adalimumab within 2 weeks of sample collection dates, which are usual dosing intervals of TNFmAb maintenance regimens; 2) if they were not receiving them during the sampling periods, "off TNFmAb treatment".
|
|---|---|---|---|---|
|
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
Cognitive at 12 month
|
103.0 score on a scale
Standard Deviation 7.0
|
107.1 score on a scale
Standard Deviation 8.8
|
—
|
—
|
|
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
Language at 12 month
|
105.4 score on a scale
Standard Deviation 9.7
|
107.7 score on a scale
Standard Deviation 8.3
|
—
|
—
|
|
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
Cognitive at 18 month
|
108.8 score on a scale
Standard Deviation 8.6
|
114.7 score on a scale
Standard Deviation 10.8
|
—
|
—
|
|
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
Language at 18 month
|
107.0 score on a scale
Standard Deviation 15.6
|
105.3 score on a scale
Standard Deviation 13
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 1-2 monthsConcentrations of anti-TNF monoclonal antibody in milk will be measured once the method is validated. The data will be analyzed using population pharmacokinetic modeling.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: postpartum weeks until 10 weeks.This is the early lactation sampling points: one of the two milk sampling time points (post-partum weeks). The milk samples were analyzed for their TNF and chemokine levels.
Outcome measures
| Measure |
Healthy Breastfeeding Women
n=31 Participants
This group is composed of healthy breastfeeding women aged over 18 years and in their first 4-month postpartum period.
|
Women With IBD
n=26 Participants
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.
|
IBD Subgroup "On TNFmAb Treatment"
n=9 Participants
Those women in the IBD group were further stratified into two subgroups based on the use of anti-TNF monoclonal antibody (TNFmAb): 1) "on TNFmAb treatment" if they received either infliximab within 8 weeks or adalimumab within 2 weeks of sample collection dates, which are usual dosing intervals of TNFmAb maintenance regimens; 2) otherwise "off TNFmAb treatment".
|
IBD Subgroup "Off TNFmAb Treatment"
n=17 Participants
Those women in the IBD group were further stratified into two subgroups based on the use of anti-TNF monoclonal antibody (TNFmAb): 1) "on TNFmAb treatment" if they received either infliximab within 8 weeks or adalimumab within 2 weeks of sample collection dates, which are usual dosing intervals of TNFmAb maintenance regimens; 2) if they were not receiving them during the sampling periods, "off TNFmAb treatment".
|
|---|---|---|---|---|
|
Milk Sampling Time Point in the Early Lactation Period
|
5.3 postpartum weeks
Interval 4.5 to 7.3
|
5.5 postpartum weeks
Interval 5.0 to 6.5
|
6.0 postpartum weeks
Interval 5.0 to 6.9
|
5.4 postpartum weeks
Interval 4.7 to 6.7
|
OTHER_PRE_SPECIFIED outcome
Timeframe: postpartum weeks of 10-20 weeks.This is the second milk sampling point corresponding to the mid-lactation period.
Outcome measures
| Measure |
Healthy Breastfeeding Women
n=31 Participants
This group is composed of healthy breastfeeding women aged over 18 years and in their first 4-month postpartum period.
|
Women With IBD
n=20 Participants
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.
|
IBD Subgroup "On TNFmAb Treatment"
n=5 Participants
Those women in the IBD group were further stratified into two subgroups based on the use of anti-TNF monoclonal antibody (TNFmAb): 1) "on TNFmAb treatment" if they received either infliximab within 8 weeks or adalimumab within 2 weeks of sample collection dates, which are usual dosing intervals of TNFmAb maintenance regimens; 2) otherwise "off TNFmAb treatment".
|
IBD Subgroup "Off TNFmAb Treatment"
n=15 Participants
Those women in the IBD group were further stratified into two subgroups based on the use of anti-TNF monoclonal antibody (TNFmAb): 1) "on TNFmAb treatment" if they received either infliximab within 8 weeks or adalimumab within 2 weeks of sample collection dates, which are usual dosing intervals of TNFmAb maintenance regimens; 2) if they were not receiving them during the sampling periods, "off TNFmAb treatment".
|
|---|---|---|---|---|
|
Milk Sampling Time Point in the Mid Lactation Period
|
13.9 postpartum weeks
Interval 12.3 to 15.1
|
13.3 postpartum weeks
Interval 12.3 to 14.2
|
13.2 postpartum weeks
Interval 11.7 to 13.7
|
13.5 postpartum weeks
Interval 12.3 to 14.3
|
Adverse Events
Women With IBD
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Healthy Breastfeeding Women
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place