Prephage - Faecal Bacteriophage Transfer for Enhanced Gastrointestinal Tract Maturation in Preterm Infants - Donor Study

Detailed Description:

PrePhage - Fecal bacteriophage transfer for enhanced gastrointestinal tract maturation in preterm infants

This pilot trial aims to investigate if fecal filtrate transfers (FFT) to preterm infants is safe and tolerable. To investigate this, the investigators will recruit 20 donor infants and their mothers from time of delivery, and both will be subjected to a novel screening program including blood, urine, breastmilk, fecal screening and standard clinical investigation. Donor fecal samples will be collected from time of birth and with varying intervals for consecutive 3 years for 3 purposes: 1) to conduct safety studies in preterm piglets before transfer to preterm recipient infants, 2) to conduct FFT to preterm infants, and 3) to map normal microbiota development in healthy infants. The feces used for donation will be collected between 2-4 weeks after birth. After 1 year, donated feces will be released for FFT to preterm, but only if the donor infant at this time has been healthy and normally developed. Donors are followed up for consecutive 3 years after birth. Maternal fecal samples will be compared to infant samples, to investigate maternal to infant transfer of microbiota, as well as changes in infant microbiota in response to environment.

20 preterm infants with gestational age between 26 +0 - 30+6 weeks + days, are block randomized to either FFT or saline placebo within 24 hours after birth and the following 3 days, in total 4 donations. The recipients are clinically and biochemically closely monitored by attending staff and the group of investigators according to best clinical practice and predefined clinical observation. The recipients are followed up for consecutive 3 years to evaluate potential late side-effects and to monitor change in fecal microbiome after transplant or placebo.

The primary endpoint is to assess safety of FFT to preterm infants with expected no increase in necrotizing enterocolitis (NEC), sepsis and death in the intervention group. The secondary endpoint is to assess if, FFT treatment will reduce incidence of feeding tolerance and improve healthy gut development in recipient preterm infants. The investigators expect to find FFT safe and with fewer cases of NEC and sepsis. The investigators do not expect to prove the effect of the intervention in this study. However, the investigators aim to follow up with a double-blinded multicenter randomized control trial - powered to document our hypothesis - that when colonizing with a healthy microbiome, it is possible decrease incidence of NEC in premature infants.

Inclusion criteria

for infants

• The donor must be of term (>37+0 weeks GA, < 41+0 weeks GA),
• Be born vaginally with no maternal pre-birth infection,
• Be exclusively breastfed un till fulfilled donation at 4 weeks of age,
• Have no known predisposition for disease.

Exclusion criteria

for infants

• Antibiotic exposure before collection of faecal material for donation,
• Disease between time of birth and collection of feces for donation,
• Major congenital anomalies or birth defects, perinatal asphyxia, need for mechanical ventilation or cardiovascular support before time of inclusion.
• Positive stool sample for C. difficile toxin, parasites or other pathogens
• Positive HIV, HBV, or HCV or CMV
• Parents who do not want to know the HIV, HBV or HCV status of the child

Inclusion criteria

for mothers

• Women aged 18-45 and currently healthy
• No continuous medical consumption with effects on microbiome
• Non-smoking
• Ability to give informed consent

Exclusion criteria

for mothers

• Known or high risk of infectious disease such as HIV, HBV, or HCV
• Positive CMV IgM during pregnancy
• Positive stool sample for C. difficile toxin, parasites or other pathogens
• Systemic antibiotic treatment < 1 months prior to study
• New tattoo < 1 month prior to study
• Risky sexual behavior
• Gestational diabetes
• Family history of inflammatory bowel disease