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Trial registered on ANZCTR


Registration number
ACTRN12617000718347p
Ethics application status
Not yet submitted
Date submitted
3/03/2017
Date registered
17/05/2017
Date last updated
22/05/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Early life exposure to antibiotics and mental health disorders later in life
Scientific title
Early life exposure to antibiotics and mental health disorders in childhood and adolescence
Secondary ID [1] 291344 0
None
Universal Trial Number (UTN)
None
Trial acronym
None
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Mood and anxiety disorders 302327 0
Behavioral disorders 302770 0
Psychotic disorders 302771 0
Developmental disorders 302772 0
Condition category
Condition code
Mental Health 301911 301911 0 0
Depression
Mental Health 302191 302191 0 0
Anxiety
Mental Health 302284 302284 0 0
Other mental health disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Within a retrospective cohort design, exposure to antibiotics during pregnancy and the first 3 years of life were evaluated with respect to the frequency of exposure, gestational and postnatal age at exposure, antibiotic class, and type. The participants have already been followed up for at least 10 years. Data will be collected from medical records, hospital discharge abstracts and drug information network.
Intervention code [1] 297371 0
Not applicable
Comparator / control treatment
The control group consists of all children who have not been exposed to any antibiotics during fetal period and after birth.

The sources of data for this cohort study will come from the Manitoba Population Research Data Repository which is a comprehensive collection of data related to patterns of heath care and profiles of heath and illness for Manitoba residents. We focus on data collected from April1, 1995 to May 31, 2014.
Data on primary outcome measures from birth between January 1995 and December 2014 will be included in the analyses.
Control group
Historical

Outcomes
Primary outcome [1] 301342 0
The outcome measure, depression will be treated as an individual disease based on antidepressant, prescriptions derived from hospital discharges, physician billing claims using ICD diagnostic codes.
Timepoint [1] 301342 0
Using prescriptions and diagnostic codes housed at Manitoba center for health policy repository, the outcomes are assessed from birth to 10 -18 years of age.
Primary outcome [2] 301946 0
The outcome measure, anxiety will be treated as individual diseases based on anxiolytic prescriptions derived from hospital discharges, physician billing claims using ICD diagnostic codes.
Timepoint [2] 301946 0
Using prescriptions and diagnostic codes housed at Manitoba center for health policy repository, the outcomes are assessed from birth to 10 -18 years of age.
Primary outcome [3] 302060 0
The outcome measure, ADHD will be treated as individual diseases based on psychostimulant prescriptions derived from hospital discharges, physician billing claims using ICD diagnostic codes.
Timepoint [3] 302060 0
Using prescriptions and diagnostic codes housed at Manitoba center for health policy repository, the outcomes are assessed from birth to 10 -18 years of age.
Secondary outcome [1] 333286 0
Age of developing depression which is assessed based on data available at Manitoba center for health policy repository.
Timepoint [1] 333286 0
Assessment is done at 10-18 years of age using databases from Manitoba center for health policy repository.
Secondary outcome [2] 334312 0
Age of developing anxiety which is assessed based on data available at Manitoba center for health policy repository.
Timepoint [2] 334312 0
Assessment is done at 10-18 years of age using databases from Manitoba center for health policy repository.
Secondary outcome [3] 334313 0
Age of developing ADHD which is assessed based on data available at Manitoba center for health policy repository.
Timepoint [3] 334313 0
Assessment is done at 10-18 years of age using databases from Manitoba center for health policy repository.

Eligibility
Key inclusion criteria
All children who were exposed to antibiotics during fetal period and the first 3 years of life
Minimum age
10 Years
Maximum age
18 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
No exclusion criteria

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Retrospective
Statistical methods / analysis
Multivariate logistic regression analyses

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 8709 0
Canada
State/province [1] 8709 0
Manitoba

Funding & Sponsors
Funding source category [1] 295814 0
Charities/Societies/Foundations
Name [1] 295814 0
Dr. Geert ‘t Jong’s Establishment Grant from the Children’s Hospital Research Foundation of Manitoba
Address [1] 295814 0
513 – 715 McDermot Avenue
Winnipeg MB R3E 3P4
Country [1] 295814 0
Canada
Primary sponsor type
Individual
Name
Dr. Geert ‘t Jong
Address
Children’s Hospital Research institution of Manitoba
513 – 715 McDermot Avenue
Winnipeg MB R3E 3P4
Country
Canada
Secondary sponsor category [1] 294664 0
None
Name [1] 294664 0
None
Address [1] 294664 0
None
Country [1] 294664 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 297102 0
University of Manitoba Health Research Ethics Board
Ethics committee address [1] 297102 0
208-194 Dafoe Road
Winnipeg, MB R3T 2N2
Ethics committee country [1] 297102 0
Canada
Date submitted for ethics approval [1] 297102 0
16/05/2017
Approval date [1] 297102 0
Ethics approval number [1] 297102 0

Summary
Brief summary
While mental illness affects 20% of Canadians of all ages, youth and children are at greater risk with a total number of staggering 3.2 million children at risk of developing depression. Seventy percent of mental health problems have their onset during childhood or adolescence. According to the Manitoba Center for Health Policy (MCHP), 11 % of children in Manitoba is prescribed at least one antidepressant over the course of a year.The rate of anxiolytic, antipsychotic and psychostimulant prescriptions in Manitoba’s children has been increasing over the last decades, and the prevalence of pervasive development disorders doubled during a ten-year study period. While a complex interplay of genetic, biological, personality and environmental factors have been identified for the etiology, the role of gut-brain axis and microbiota composition in psychiatric pathology is remarkable. Animal models show the effect of gut microbiota on brain function through neural, endocrine, immune, and metabolic pathways. Several factors including antibiotics can alter gut microbiota (dysbiosis) starting from very early life including fetal period and delivery. Childbirth exposes the human gut to a complex microflora, but the initial microbiome has a maternal signature. The linkage between dysbiosis and abnormal behavior has been documented in animal models, but limited studies in humans have supported this idea. A large Canadian cohort showed long lasting dysbiosis in infants born to mothers who received intrapartum antibiotic prophylaxis. This idea was supported in a European cohort of infants who were exposed to antibiotics perinatally. A large provincial study also revealed that 37 % of children in Manitoba were exposed to antibiotics during the prenatal period indicating that these children might be at risk of developing psychiatric diseases.To date, no animal or human study has been conducted to assess the effect of early life exposure to antibiotics on mental health despite the evidence that early life period is a key time window in the establishment of the initial microbiome. To bridge the gap in the literature, our study is aimed to provide insight into the role of antibiotics in the development of psychiatric and behavioral disorders in later childhood. Proving a clear association between the use of antibiotics in pregnant women and their offsprings, and development of psychological and behavioral disorders later in life will send a paradigm-shifting message to mothers and physicians to be cautious about prescribing and using antibiotics in pregnancy and early childhood.
Trial website
None
Trial related presentations / publications
None
Public notes

Contacts
Principal investigator
Name 72978 0
Dr Mahin Delara
Address 72978 0
Children Hospital Research Insitute of Manitoba (CHRIM)
654 – 715 McDermot Avenue
Winnipeg MB R3E 3P4
Country 72978 0
Canada
Phone 72978 0
+1 -204-480-1386
Fax 72978 0
Email 72978 0
delaram@myumanitoba.ca
Contact person for public queries
Name 72979 0
Dr Mahin Delara
Address 72979 0
Children Hospital Research Insitute of Manitoba (CHRIM)
654 – 715 McDermot Avenue
Winnipeg MB R3E 3P4
Country 72979 0
Canada
Phone 72979 0
+1 -204-480-1386
Fax 72979 0
Email 72979 0
delaram@myumanitoba.ca
Contact person for scientific queries
Name 72980 0
Dr Mahin Delara
Address 72980 0
Children Hospital Research Insitute of Manitoba (CHRIM)
654 – 715 McDermot Avenue
Winnipeg MB R3E 3P4
Country 72980 0
Canada
Phone 72980 0
+1 -204-480-1386
Fax 72980 0
Email 72980 0
delaram@myumanitoba.ca

No information has been provided regarding IPD availability
Summary results
No Results