Cesarean Section and Intestinal Flora of the Newborn (SECFLOR)

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

Study Overview

• Status: Completed
• Conditions: Intestinal Microbiome
• Intervention / Treatment: Other: Fecal transplant

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 Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Uusimaa
    • Helsinki, Uusimaa, Finland, 00029
      • Helsinki University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Clinical condition, inflammatory markers	0-3 postnatal days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Attachment of transplant	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.	1 to 12 weeks of age

Collaborators and Investigators

• Sponsor: Sture Andersson
• Investigators: Principal Investigator: Sture Andersson, Prof, Professor of neonatology

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2017
• Primary Completion (Actual): September 1, 2018
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: June 14, 2018
• First Posted (Actual): June 26, 2018

Study Record Updates

• Last Update Posted (Actual): February 11, 2019
• Last Update Submitted That Met QC Criteria: February 8, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: transplant; microbiome; infant; newborn
• Other Study ID Numbers: SECFLOR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No