Clinical trial NCT03568734: Cesarean Section and Intestinal Flora of the Newborn
Official title: Cesarean Section and Intestinal Flora of the Newborn
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Intestinal Microbiome
Keywords: microbiome
transplant
infant
newborn
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
First posted: 2018-06-26
Enrollment: 7
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 12 mothers participating in the study (due for caesarean section) are screened for transmissible diseases. A transplant sample is gathered from the mother, processed, and given to the infant at delivery by caesarean section.
Primary purpose: PREVENTION

Brief summary: Mode of delivery affects gut microbiome of the infant. Infants born by caesarean section have a less heterogenous microbiome for the first weeks of life. This has been associated with an increased risk for atopy-related diseases, such as allergy and asthma. In this proof-of-principle study the investigators evaluate whether an orally delivered maternal fecal transplant to the infant during the first hours of life affects gut microbiome of the infant

Detailed description: Background

The immune system is affected by the colonizing microbiome. The gut microbiome has been associated with a multitude of inflammatory diseases, such as the development of autoimmune diseases. The association between microbiome and allergic diseases, asthma, type I diabetes and inflammatory bowel diseases have been demonstrated. Moreover, changes in gut microbiome during the first weeks of life have been associated with the development of atopy.

Already at birth, a low concentration of bacteria is present in the meconium of the vaginally delivered infant. Although the neonatal stool is not fully sterile, colonization of the intestinal tract takes place at delivery and throughout the first years of life. The gut microbiome of infants delivered vaginally (VD) and by cesarean section (CS) differs markedly from each other and this difference persists throughout the first years of life. The gut microbiome of infants born by CS have a lower total microbiota diversity and lower Th1 response than those born by VD. Infants delivered by CS been shown to be more likely to develop chronic inflammatory and allergic diseases, eg. inflammatory bowel disease, and systemic connective disorders, and asthma than those delivered vaginally.

Partial restoration of the microbiota of CS-infants was seen when introduced with vaginal microbial transfer. However, the vaginal microbiome is very limited to mainly Lactobacillus spp. and does not contain the microbes that are abundant in the gut microbiota of the mother. Fecal transplantation, or intestinal microbiota transfer, is used to treat chronic infections of Clostridium difficile. However, fecal transplantation has not been used to compensate for the low diversity of CS infants. In this pilot, proof-of-concept and safety evaluation study, the researchers aim to assess the feasibility of fecal transplantation after birth in infants delivered by CS.

Eligibility criteria: Inclusion criteria:

* healthy pregnancy
* planned cesarean section delivery

Exclusion criteria:

Maternal exclusion criteria:

* positive GBS status
* maternal refusal
* maternal antibiotic treatment within the last 3 months
* any travel outside of European Union within the last 3 months
* multiple pregnancy and CS after the onset of labor (non-elective CS)

Infant exclusion criteria:

* Apgar score of less than 8
* disturbances of neonatal adaptation (such as transient tachypnea of the newborn)
* antibiotic treatment of the newborn before discharge

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 0-3 postnatal days
Secondary outcomes:
measure: Attachment of transplant
timeFrame: 1 to 12 weeks of age
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Hospital
state: Uusimaa
Study officials:
affiliation: Professor of neonatology
name: Sture Andersson, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Korpela K, Helve O, Kolho KL, Saisto T, Skogberg K, Dikareva E, Stefanovic V, Salonen A, Andersson S, de Vos WM. Maternal Fecal Microbiota Transplantation in Cesarean-Born Infants Rapidly Restores Normal Gut Microbial Development: A Proof-of-Concept Study. Cell. 2020 Oct 15;183(2):324-334.e5. doi: 10.1016/j.cell.2020.08.047. Epub 2020 Oct 1.