Cesarean Section and Intestinal Flora of the Newborn (SECFLOR)

• ClinicalTrials.gov Identifier: NCT03568734
• Recruitment Status: Completed
• First Posted: June 26, 2018
• Last Update Posted: February 11, 2019
• Sponsor: Sture Andersson
• Information provided by (Responsible Party): Sture Andersson, Helsinki University Central Hospital

Study Description

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

Condition or disease	Intervention/treatment	Phase
Intestinal Microbiome	Other: Fecal transplant	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• 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.
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Cesarean Section and Intestinal Flora of the Newborn
• Actual Study Start Date: October 27, 2017
• Actual Primary Completion Date: September 1, 2018
• Actual Study Completion Date: December 31, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Transplant arm; Fecal transplant sample given to child at delivery	Other: Fecal transplant; At delivery, i.e. 39-40 weeks of gestation, the newborn infant is given 0.1 g maternal fecal sample (in 0.5 ml of the isotonic saline+10 % glycerol) dissolved in 10 ml of bank milk orally. The sample is given within 2 h of birth. Milk containing fecal sample (2 ml) is given as a part of a total feeding of 5-10 ml.

Outcome Measures

Primary Outcome Measures :

1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 0-3 postnatal days ]
   Clinical condition, inflammatory markers

Secondary Outcome Measures :

1. Attachment of transplant [ Time Frame: 1 to 12 weeks of age ]
   Evaluation of microbiome in comparison to transplant from samples taken from infants weekly at 1-4 weeks of life and at 3 months of age.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Pregnant women only
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

Finland

Helsinki University Hospital

Helsinki, Uusimaa, Finland, 00029

Sponsors and Collaborators

Sture Andersson

Investigators

• Principal Investigator: Sture Andersson, Prof; Professor of neonatology

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Sture Andersson, Professor, Helsinki University Central Hospital
• ClinicalTrials.gov Identifier: NCT03568734
• Other Study ID Numbers: SECFLOR
• First Posted: June 26, 2018
• Last Update Posted: February 11, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sture Andersson, Helsinki University Central Hospital:

microbiome; transplant; infant; newborn