Restoration of Microbiota in Neonates (RoMaNs)

Restoration of Microbiota in Neonates - a Randomized Controlled Trial

The aim of the study is to examine the effect of exposure of cesarean section (CS) delivered neonates to a natural condition of birth, i.e. to the microbiota of the birth canal, on the acquisition of microbial genes during development of the microbiome at multiple body sites, immune system maturation and allergy risk in childhood

Study Overview

• Status: Recruiting
• Conditions: Atopic Dermatitis; Immunologic Activity Alteration; Atopic Asthma
• Intervention / Treatment: Other: Maternal microbiota

Detailed Description

The primary outcome is to examine if exposure to the maternal vaginal and fecal microbiota directly after birth will halfen the cumulative incidence of Immunoglubulin E (IgE)-associated allergic disease at 2 years of age in CS delivered infants, compared with non-treated CS-delivered infants.

The secondary outcomes are to compare the community structure of microbes from mothers and their infants and immunological programming of infants delivered via scheduled CS, with or without exposure to the maternal vaginal and fecal microbiota, from birth until two years of age. The primary and secondary outcomes will also be compared with a reference group of vaginally delivered infants. Sex differences in the incidence and prevalence of allergic diseases have been described. The anticipated benefit of the intervention can be implemented in clinical practice regardless of sex, so that improved conditions for good health are created.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lars G Engstrand, MD; Phone Number: +46706780318; Email: lars.engstrand@ki.se
• Study Contact Backup: Name: Marica C Hamsten, MSc; Phone Number: +46675555872; Email: marica.hamsten@ki.se

Study Locations

• Sweden
  • Stockholm, Sweden, 171 65
    • Recruiting
    • Karolinska Institutet
    • Contact: Marica C Hamsten, MSc; Phone Number: +46765555872; Email: marica.hamsten@k.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 minutes to 15 minutes (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infants of healthy mothers with uncomplicated pregnancies at term, mothers of any ethnic or social background that can speak, read, and understand Swedish to the extent that they can consent in Swedish. An additional inclusion criterion for mothers in the CS groups is vaginal pH ≤ 4 at the time of birth.

Exclusion Criteria:

• Infants of mothers with pre-eclampsia or complicated pregnancies, mothers <18 years or >40 years of age, genital herpes simplex, genital warts, HIV, Hepatitis B or complications during delivery, infants delivered prior to 37 weeks of gestation. Additional exclusion criteria for mothers in the CS group: Mothers positive to Group B Streptococcus, Group A Streptococcus, bacterial vaginosis, vaginal pH > 4 at the time of birth. Mothers with fecal samples positive for Salmonella, Shigella, Campylobacter or Yersinia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: vaginally delivered; A non-randomized reference group of vaginally delivered infants.
Active Comparator: CS intervention; A piece of gauze soaked with saline (0.9%) will be placed in the birth canal 2 hours before the CS by the study midwife, using sterile glows. Before the CS procedure begins, the gauze will be removed from the vagina and then immediately "contaminated" by a swab carrying maternal fecal microbiota. The swab is contaminated by introducing it 3 cm into the anal canal and by rotating it for 10-20 s. Immediately after birth, the study midwife will swab the neonate with the gauze in multiple body sites by a standardized manner and then swab maternal breasts and chest skin. The neonate will then be placed on the maternal chest to initiate breast-feeding.	Other: Maternal microbiota; See arm descriptions
Placebo Comparator: CS placebo; See above - the gauze will be exchanged to a clean gauze (soaked with saline). Immediately after birth, the study midwife will swab the neonate with the gauze in multiple body sites by a standardized manner and then swab maternal breasts and chest skin. The neonate will then be placed on the maternal chest to initiate breast-feeding.	Other: Maternal microbiota; See arm descriptions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IgE-associated allergic disease	Incidence of Immunoglubulin E (IgE)-associated allergic disease at 2 years of age in CS delivered infants, compared with non-treated CS-delivered infants and vaginally delivered controls. Skin-puncture tests will be performed at infant age 6 months, 12 months and child age 24 months.	Two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunological programming	Immunological programming will be assessd via blood cell count from blood tests at 6,12 nad 24 months in infants delivered via scheduled CS, with or without exposure to the maternal vaginal and fecal microbiota in comparison to infants born vaginally.	Two years
Development of the microbiota	To compare microbial composition between groups, using shotgun metagenomics.	Two years

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: Uppsala University; Umeå University; Linkoeping University; Örebro University, Sweden; Jonkoping University
• Investigators: Study Chair: Susanne Nylén, PhD, Dept Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Anticipated): December 15, 2024
• Study Completion (Anticipated): December 15, 2026

Study Registration Dates

• First Submitted: April 24, 2019
• First Submitted That Met QC Criteria: April 24, 2019
• First Posted (Actual): April 26, 2019

Study Record Updates

• Last Update Posted (Actual): April 5, 2023
• Last Update Submitted That Met QC Criteria: April 3, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: cesarean section; microbiota; allergy; vaginal delivery; immunological programming
• Additional Relevant MeSH Terms: Skin Diseases; Dermatitis
• Other Study ID Numbers: 2017/1298-31/1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Samples will be stored at Karolinska Biobank and metadata will be linked to these samples with access for all researchers in the study. No data will be available for researchers outside the consortium.

Drug and device information, study documents

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