Infant gut microbiome Digestive System
Conditions
Interventions
Approximately 70 women will be recruited to provide vaginal and rectal swabs for baseline assessment of the maternal microbiome prior to Caesarean section. Newborn infants will be randomised to receiv
Sponsors
Evolve BioSystems, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 17/12/2020: 1. Singleton pregnancies (primip or multi) 2. Pregnant women age 18 and above 3. Elective Caesarean section =37 weeks gestation 4. Maternal pre-pregnancy BMI < 35kg/m² 5. Intention to exclusively breastfeed for at least 35 days, preferably for 6 months 6. Non-smoker (gave up prior to pregnancy) 7. Intention to exclusively breastfeed for at least 3 months 8. Non-smoker (never smoked or gave up prior to enrolment) _____ Previous inclusion criteria: 1. Singleton pregnancies (primip or multi) 2. Pregnant women age 18 and above 3. Elective Caesarean section =37 weeks gestation 4. Maternal pre-pregnancy BMI < 35kg/m² 5. Resident in UK for 3 years or more 6. Intention to exclusively breastfeed for at least 35 days, preferably for 6 months 7. Non-smoker (gave up prior to pregnancy) Added 15/07/2020: 8. Willingness to vaccinate infant with BCG vaccine no later than Day 4 9. Intention to exclusively breastfeed for at least 3 months 10. Non-smoker (never smoked or gave up prior to enrolment)
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 17/12/2020: At antenatal screening 1. Multiple pregnancy 2. Vaginal deliveries 3. Fetus has a known medical condition that would preclude breastfeeding or alter gut microbiota 4. Maternal breast surgery or injury within the past 5 years that would reduce the likelihood of successful exclusive breastfeeding (not exclusionary if mother can evidence successful breastfeeding of a previous infant after the surgery or injury) 5. Plan to administer non-study probiotics to infant any time throughout the study 6. Plan to apply maternal vaginal swab to infant’s mouth 7. Maternal infection with HIV or Hepatitis C or experiencing symptoms of COVID-19 8. Maternal smoking (current) 9. Maternal medication use that may alter infant’s gut microbiotia (e.g. daily antibiotics) At Day 7 postnatal screen, pre-randomization: 1. Infants who have taken antibiotics for more than 3 days 2. Intake of formula within 24 hours of the Postnatal Eligibility Screen 3. Infants born with medical complications such as: respiratory distress syndrome, birth defects, and infection 4. Mothers who experienced medical complications that would preclude them from breastfeeding 5. Infants who had exposure to maternal vaginal microbiome via oral swab 6. Infants who have received the BCG vaccine 7. Infants whose caregivers intend to vaccinate their infant with the BCG vaccine prior to 3 months of life 8. Infants with known exposure to an individual testing positive for, or experiencing symptoms of, COVID-19 _____ Previous exclusion criteria: At antenatal screening 1. Multiple pregnancy 2. Recent arrival in UK (< 3 years) 3. Vaginal deliveries 4. Mothers with another child < 14 months of age at recruitment 5. Fetus has a known medical condition that would preclude breastfeeding or alter gut microbiota 6. Maternal breast surgery or injury within the past 5 years that would reduce the likelihood of successful exclusive breastfeeding (not exclusionary if mother can evidence successful breastfeeding of a previous infant after the surgery or injury) 7. Plan to administer non-study probiotics to infant any time throughout the study 8. Plan to apply maternal vaginal swab to infant’s mouth 9. Maternal infection with HIV or Hepatitis C 10. Maternal type 1 or type 2 diabetes (gestational diabetes is not exclusionary) 11. Maternal pre-eclampsia 12. Smoking this pregnancy 13. Plan to leave UK in < 6 months (added 01/08/2019) 14. Maternal medication use that may alter infant’s gut microbiotia (e.g. daily antibiotics) (added 01/08/2019) At Day 7 postnatal screen, pre-randomization: 1. Infants who have taken antibiotics for more than 3 days 2. Intake of formula within 24 hours of the Day 7-9 visit 3. Infants born with medical complications such as: respiratory distress syndrome, birth defects, and infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.The change in infant faecal microbiota before, during and after probiotic or placebo supplementation by shotgun sequencing or next generation sequencing (NGS, e.g. Illumina MISeq or HiSeq) Added 01/08/2019: 2. Continuation study: The change in levels of immune cells and markers from baseline (Day 0 – Day 4) to 3 months (Day 84 – Day 104) Added 15/07/2020: 3. Extension study: The change in infant faecal B. infantis colonization levels from baseline during B. infantis supplementation as measured by quantitative PCR | — |
Secondary
| Measure | Time frame |
|---|---|
| 1.Biochemistry of infant stools by assessing pH levels, HMO and short-chain fatty acids using liquid chromatography-mass spectrometry may be performed on samples collected at Baseline (Day 4-7), 1 month, 3 months, 6 months, 12 months, 18 months and 24 months. 2. Comparison of the composition of the maternal and infant microbiome at baseline using shotgun sequencing or next generation sequencing. 3.Adverse events will be recorded on daily and weekly adverse event logs, as well as infant health surveys, for the duration of the study. Medical records will be reviewed as needed for confirmation. Added 01/08/2019: 4. Continuation study: The correlation between gut microbiota composition and abundance and levels of immune cells and markers 5. Continuation study: The differences between B. infantis and placebo supplementation on levels of immune cells and markers 6. Continuation study: The differences between B. infantis and placebo supplementation on vaccine response (antibody titres) Added 15/07/2020: 7. Extension study: The differences between probiotic and control infants with respect to: 7.1. The infant faecal microbiome composition as measured by shotgun metagenomics, and 7.2. Levels of enteric inflammation as measured by inflammatory cytokines in infant stool. Exploratory Endpoints for the Extension Study Include: • The differences between treatment and control infants with respect to: Immune and inflammatory responses as measured by calprotectin, lipocalin-2, and soluble faecal IgA and IgG in infant stool • Immune-sensing of the microbiome as measured by IgA-seq in infant stool • Stool metabolomics • The development of immune cell populations in whole blood by mass cytometry • Plasma proteins by immunoassays | — |
Countries
England, United Kingdom
Contacts
Public ContactAnnette Briley
Outcome results
None listed