Plain English Summary
Background and study aims
The healthy development and maturation of a newborn baby depends not only on the genetic information inherited from both parents, but also on the bacteria which come to live in their gut. These bacteria are collectively known as the microbiota and are passed mainly from mother to baby at the time of birth, and some additional bacteria come from the environment. This study will focus on a specific group of bacteria called bifidobacteria as these are the dominant bacteria in healthy infants’ guts and are associated with positive health outcomes. This study investigates whether a daily bifidobacterial probiotic capsule taken during pregnancy and breastfeeding results in transfer of these beneficial bacteria from mother to baby. This study also explores whether the probiotichas a beneficial effect on the mother’s blood sugars and lipid levels.
Who can participate?
Pregnant women with a body mass index (BMI) of ≥20kg/m2 and ≤35kg/m2, who are otherwise healthy
What does the study involve?
Participants are asked to avoid food and yoghurts that contain probiotics for the duration of the study. When they are 16 weeks pregnant they are asked to provide a stool sample, complete a 3-day food diary, provide blood samples, and have a skin swab, mouth swab/rinse and a vaginal swab. Participants are also offered a fetal ultrasound at this visit. They are then randomly allocated to receive either probiotic or placebo (dummy) capsules, which they take daily from 16 weeks of pregnancy until the baby is 3 months old. The research doctor/midwife meets them at regular antenatal appointments to ensure they have enough capsules and that they are having no difficulties. When they are 34 weeks pregnant participants are again asked to provide a stool sample, complete a 3-day food diary, provide blood samples, and have a skin swab, mouth swab/rinse and a vaginal swab. At this time participants have an additional growth scan of their baby. At the time the baby is born, a sample of blood is taken from the umbilical cord and a sample of the placenta and membranes (afterbirth) is taken if they deliver by elective caesarean section. Participants are also asked to take a sample of their baby’s first bowel movement, and to provide a small sample of breast milk and a swab from the skin of the breast. When the baby is 1 month old participants are asked to complete a 3-day food diary, provide stool samples (both mother and baby), and provide a sample of breast milk. This is repeated when the baby is 3 months old.
What are the possible benefits and risks of participating?
There are no health benefits from participating in the study but the knowledge gained may influence future medical care. There are no known risks associated with this study. Probiotics have been shown to be safe to take during pregnancy, with no risks for mother or baby. Participants may experience some discomfort in providing the requested samples but this will be brief and minimised as much as possible. Remembering to take the probiotic or placebo capsules each day may also be a minor inconvenience for participants.
Where is the study run from?
The National Maternity Hospital (Ireland)
When is the study starting and how long is it expected to run for?
December 2015 to December 2018
Who is funding the study?
National Maternity Hospital Ireland Medical Fund
Who is the main contact?
Prof. Fionnuala McAuliffe
Trial website
Contact information
Type
Public
Primary contact
Prof Fionnuala McAuliffe
ORCID ID
http://orcid.org/0000-0002-3477-6494
Contact details
UCD Department of Obstetrics & Gynaecology
65-66 Lower Mount Street
Dublin 2
Dublin
None
Ireland
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
EC 35.2015
Study information
Scientific title
To study the transit of bifidobacteria from mother to infant: a randomised controlled trial
Acronym
Study hypothesis
Maternal dietary supplementation with a specific bifidobacterial strain during pregnancy and lactation will result in colonization of the neonatal gut with that specific strain.
Ethics approval
The Research Ethics Committee at The National Maternity Hospital, Holles St, Dublin 2, 15/02/2016, ref: EC 35.2015
Study design
Single-centre double-blind interventional randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
See additional files
Condition
Probiotics, pregnancy, Bifidobacteria, microbiome
Intervention
Eligible participants will be recruited from the outpatients’ department of the hospital at approx. 12 weeks’ gestation. Once a patient has given written informed consent to participate in the trial, she will be randomised to receive one of the following: daily Bifidobacteria probiotic capsule or daily placebo capsule. The study statistician, who will not be involved in data collection, will produce computer-generated sets of random allocations before the study starts. This will be done by block randomisation with randomly permuted block sizes, with the group allocation linked to a unique study identifier for each participant, the allocation and identifier will be communicated to the capsule manufacturer.
All study products will be manufactured under Good Manufacturing Practice conditions. The trial products, both probiotic and placebo will be provided as identical white, size #1 hydroxypropylmethylcellulose capsules. The probiotic capsules will contain approx. 10 mg of probiotic as freeze-dried powder blended with standard excipients at a dose of approx. 1 x 10 to the power of 9 colony forming units (CFU). Identical placebo capsules will contain standard excipient only. They will be prepacked in tubes and consecutively numbered for each woman according to the randomisation schedule, thereby concealing allocation from the trial staff and the participants. The consecutively numbered tubes will be allocated in sequence to each woman on recruitment. Treatment allocation will be concealed from the investigators until the data analysis is complete.
Participants will be provided with a 1-month supply of capsules at 16 weeks’ gestation and will be requested to bring the empty bottles to their next appointment. This will enable us to monitor compliance with the intervention. Presence of the specific bacterial strain in faecal samples of the expecting mother will also serve to demonstrate compliance. Participants will advised to take 1 capsule per day from 16 weeks’ gestation until 3 months postpartum. We have previously reported that this type of supplementation intervention is acceptable and that compliance is high among pregnant women (Lindsay et al, 2014).
Baseline blood samples, an oral rinse, a high vaginal swab, a stool sample and a nutritional assessment (3-day food diary) will be collected at 16 weeks’ gestation (pre-supplementation) and again at 34 weeks’ gestation. At delivery cord blood will be collected. At one point on days 2-5 postpartum, a small sample (< 5 ml) of breast milk and a sample of baby’s stool will be collected.
At 1 month and 3 months postpartum a maternal 3-day food diary, a sample of breast milk, mother’s stool and baby’s stool will be collected.
Intervention type
Supplement
Phase
Drug names
Primary outcome measure
Presence of the supplemented bifidobacterial strain in the infant’s stool in the 1st week postpartum, at 1 month postpartum and at 3 months postpartum. To measure this the infant stool will be analysed for the presence of the supplemented bifidobacterial strain.
Secondary outcome measures
Differences in the following between the probiotic and placebo groups:
1. Maternal lipids
2. Maternal insulin resistance as measured by fasting glucose and HOMA-IR
3. Maternal C Reactive Peptide
Maternal bloods will be taken in early (approx. 16 weeks gestation) and late (approx. 34 weeks gestation) pregnancy and will be analysed for these metabolic parameters.
Overall trial start date
01/12/2015
Overall trial end date
31/12/2019
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Participant inclusion criteria as of 14/11/2018:
1. Pregnant women over the age of 18, capable of giving informed consent
2. With adequate understanding of the English language and an understanding of the study to enable them to give informed consent to participate
3. With a Body Mass Index of ≥18.5kg/m2 and ≤35kg/m2
Previous participant inclusion criteria:
1. Pregnant women over the age of 18, capable of giving informed consent
2. With adequate understanding of the English language and an understanding of the study to enable them to give informed consent to participate
3. With a Body Mass Index of ≥20kg/m2 and ≤35kg/m2
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
Our sample size was estimated based on colonization of the neonatal gut at any time point. A target power of 80% will be used, at a type I error rate of 0.05. The default (placebo) colonization rate will be 0% as the strain we are using is not present in the maternal diet. In the intervention group, a minimal clinically relevant difference was not possible to obtain from the literature, thus, we took 15% as a target. The sample size required to show at least this difference between arms (0% versus 15%) is 60 per group. We will therefore need 120 participants to complete the study.
Participant exclusion criteria
1. A history of gestational diabetes in a previous pregnancy
2. Pre-gestational diabetes e.g. Type 1 or Type 2 diabetes
3. A multiple pregnancy or fetal anomaly
5. A poor standard of English
6. A previous perinatal death
Recruitment start date
29/08/2016
Recruitment end date
31/12/2018
Locations
Countries of recruitment
Ireland
Trial participating centre
The National Maternity Hospital
Holles Street
Dublin
-
Ireland
Funders
Funder type
Government
Funder name
Science Foundation Ireland
Alternative name(s)
SFI
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
Ireland
Funder name
Alimentary Health
Alternative name(s)
Alimentary Health Ltd., AH
Funding Body Type
private sector organisation
Funding Body Subtype
professional associations and societies
Location
Ireland
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer-reviewed journal.
IPD sharing statement: the data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
31/12/2019
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list
Publication citations
Additional files
- ISRCTN53023014_PIS_16Aug16.doc Uploaded 15/09/2016