Optimizing Mastitis Identification and Treatment

NCT05794945 | Recruiting

• 1 other identifier: 2023/578416 (REK)
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this observational study is to gain more information about the aetiology and progression of mastitis and breast inflammation, in order to develop evidence-based clinical guidelines and treatment plans, especially concerning judicious use of antibiotics. The main questions it aims to answer are:

• Do clinical symptoms differ between inflammatory and infectious mastitis?
• What is the microbial composition in human milk, and does it change before, during, and after episodes of mastitis?
• Does the bacterial composition change due to antibiotic treatment?
• Are all mastitis episodes treated with antibiotics bacterial mastitis?
• Do mothers with recurrent mastitis have a distinct microbial composition?
• Are there immunological markers that can differentiate between bacterial and inflammatory mastitis? Researchers will compare breastfeeding women with and without mastitis to see if the microbiological composition in milk and on the skin of the breast and breast nipple differs.

Conditions

Mastitis Postpartum

Keywords

Breast inflammation; Clinical mastitis; Sub-clinical mastitis

Outcome Measures

Primary Outcomes (7)

• Determination of the microbial composition in human milk from mothers without mastitis by MALDTI-TOF and Illumina sequencing

  In order to investigate if there is a particular microbial composition of the human milk that leads to mastitis, the microbial composition in human milk from mothers without mastitis will be assessed. The investigators will collect milk samples from all enrolled mothers at day 6-7 after birth. Milk samples will be stored at -20 until further processing. Mothers who develop mastitis will be further sampled as described in outcome 2. Samples will be analyzed using culture dependent and culture independent methods. Following culturing of the milk samples, colonies will be analysed by Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) to identify bacterial species. DNA will be isolated from the same milk sample.16S rRNA amplicon sequencing of DNA from milk samples will be performed using the Illumina technology, in order to get an overview of the total bacterial composition.

  18 months

• Determination of the microbial composition in human milk from mothers at onset of mastitis by MALDTI-TOF and Illumina sequencing

  The investigators will investigate if the microbial composition in human milk changes at onset of mastitis. By analysing possible changes in microbial composition the investigators will assess if the mastitis symptoms are caused by microorganisms, or if the symptoms of mastitis are inflammatory. Milk samples will be collected by the mother at onset of mastitis, 24 hours after onset of symptoms and after resolution of symptoms. If the mastitis episode is treated with antibiotics, a new sample will be taken 24 hours after cessation of antibiotic treatment. Milk samples will be stored at -20 until further processing. Samples will be analyzed using culture dependent, and culture independent methods. Following culturing of the samples, colonies will be analysed by MALDI-TOF to identify bacterial species. 16S rRNA amplicon sequencing of DNA from milk samples will be performed using the Illumina technology, in order to get an overview of the total bacterial composition.

  18 months

• Assessment of the microbial composition on nipples of mothers without mastitis

  It is no agreement on if mastitis causing bacteria originate from the breast nipple, or if they are part of the milk microbiome. We will sample the breast nipples in order to investigate if microorganisms colonizing the breast skin enter the mammary glands, and potentially cause mastitis. A skin swab of the nipple (both breasts) will be taken at day 6-7 after birth. Following culturing of the swab, bacterial colonies will be analysed by MALDI-TOF to identify bacterial species. The skin swabs will be collected at the same timepoints as collection of milk samples.

  18 months

• Assessment of the microbial composition on nipples of mothers with mastitis

  It is no agreement on if mastitis causing bacteria originate from breast nipple, or if they are part of the milk microbiome. We will sample the breast nipples in order to investigate if microorganisms colonizing the breast skin enter the mammary glands, and potentially cause mastitis. When the mother experiences symptoms of mastitis the mother will collect a skin swab sample. Following culturing of the swab, bacterial colonies will be analysed by MALDI-TOF to identify bacterial species. The skin swabs will be collected at the same timepoints as collection of milk samples.The microbial composition on nipples of mothers with mastitis will also be compared to the nipple microflora of mothers without mastitis in order to see if there is a correlation between particular skin colonizing bacteria that cause mastitis.

  18 months

• The concentration of immunological markers in milk from mothers without mastitis

  A milk sample will be collected at day 6-7 after birth, and the concentration of immunological markers will be assessed in the milk of mothers without mastitis. The concentration (pg/ml) of 8 immune factors, including innate immune factors (IL6, IFNγ, TNFα), acquired immune factors (IL2, IL4, IL10), chemokines (IL8), and growth factor (GMCSF), will be determined by magnetic bead-based multi- plex immunoassays, using a Bioplex 200 instrument (Bio-Rad, Hercules, CA, USA).

  18 months

• The concentration of immunological markers in milk from mothers with mastitis

  In order to determine if there is an increase in the immunological markers present in milk from mothers with mastitis, milk samples will be collected at onset of mastitis symptoms and 24 hours after cessation of symptoms. If the mother requires antibiotic treatment , samples will be collected at onset of treatment and 24 hours after cessation of antibiotic treatment. The concentration (pg/ml) of 8 immune factors, including innate immune factors (IL6, IFNγ, TNFα), acquired immune factors (IL2, IL4, IL10), chemokines (IL8), and growth factor (GMCSF), will be determined by magnetic bead-based multi- plex immunoassays, using a Bioplex 200 instrument (Bio-Rad, Hercules, CA, USA).The investigators will assess if the concentration of immunological markers differs in bacterial mastitis and inflammatory mastitis.

  18 months

• Mapping of mastitis symptoms by detailed Questionnaires

  The mothers will be asked to fill in a detailed questionnaire regarding breastfeeding practice and symptoms of mastitis. The questionnaire will accompany the collection of milk samples as described in outcome 1and 2.

  18 months

Study Arms (1)

Breastfeeding mothers

In this study breastfeeding mothers will be included. Samples will be collected from breast-feeding mothers experiencing mastitis Samples will be collected from breast-feeding mothers after the mastitis episode is resolved Breastfeeding mothers will be sampled at each mastitis episode, and with the final sample collected after a maximum of 12 months

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: This study will include breastfeeding mothers
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Pregnant mothers aged \> 18 years planning to give birth at University Hospital Noth Norway (UNN), with the intention to breastfeed and with an address in Tromsø municipality.

You may qualify if:

• Pregnant mothers aged \> 18
• mothers must understand information given in Norwegian or English
• participants must be willing to complete study questionnaires
• participants must be willing to and provide biological samples

Sponsors & Collaborators

• University of Tromso: lead
• Norwegian Institute of Public Health: collaborator
• The University of Western Australia: collaborator
• Helse Nord: collaborator

Study Sites (2)

Tromsø municipality, health centre

Tromsø, Troms, 9019, Norway

RECRUITING

UiT-The Arctic University of Norway

Tromsø, 9019, Norway

RECRUITING

Related Publications (4)

• Wilson E, Woodd SL, Benova L. Incidence of and Risk Factors for Lactational Mastitis: A Systematic Review. J Hum Lact. 2020 Nov;36(4):673-686. doi: 10.1177/0890334420907898. Epub 2020 Apr 14.

  PMID: 32286139 RESULT

• Mitchell KB, Johnson HM, Rodriguez JM, Eglash A, Scherzinger C, Zakarija-Grkovic I, Cash KW, Berens P, Miller B; Academy of Breastfeeding Medicine. Academy of Breastfeeding Medicine Clinical Protocol #36: The Mastitis Spectrum, Revised 2022. Breastfeed Med. 2022 May;17(5):360-376. doi: 10.1089/bfm.2022.29207.kbm.

  PMID: 35576513 RESULT

• Grzeskowiak LE, Saha MR, Ingman WV, Nordeng H, Ystrom E, Amir LH. Incidence, antibiotic treatment and outcomes of lactational mastitis: Findings from The Norwegian Mother, Father and Child Cohort Study (MoBa). Paediatr Perinat Epidemiol. 2022 Mar;36(2):254-263. doi: 10.1111/ppe.12824. Epub 2021 Nov 28.

  PMID: 34841537 RESULT

• Castro I, Garcia-Carral C, Furst A, Khwajazada S, Garcia J, Arroyo R, Ruiz L, Rodriguez JM, Bode L, Fernandez L. Interactions between human milk oligosaccharides, microbiota and immune factors in milk of women with and without mastitis. Sci Rep. 2022 Jan 25;12(1):1367. doi: 10.1038/s41598-022-05250-7.

  PMID: 35079053 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Researchers will collect human milk samples and skin swabs. Samples will be used for culture dependent assessment of the microbiological composition in milk and on breast skin and breast nipple. Researchers will isolate microbial DNA in order to perform whole genome sequencing and amplicon sequencing to map the microbial community in breastmilk.

MeSH Terms

Conditions

Mastitis

Condition Hierarchy (Ancestors)

Puerperal Disorders; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Jorunn Pauline Cavanagh, PhD

  The Arctic university of Norway-UiT

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jorunn Pauline Cavanagh, PhD

CONTACT

40498490; pauline.cavanagh@uit.no

Claus Klingenberg, MD, PhD

CONTACT

91563167; claus.klingengerg@unn.no

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2023
• First Posted: April 3, 2023
• Study Start: October 1, 2023
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will become available after publication
• Access Criteria: Access upon request

Locations

NO (2)