Timing of Maternal Antibiotic Prophylaxis During a Cesarean Section and the Early Infant Gut Microbiome (CSBabyBiome)

Timing of Umbilical Cord Clamping During an Elective Caesarean Delivery and Its Association With Neonatal Gut Microbiome.

In this study, investigators seek to determine whether the timing of antibiotics given to mothers during an elective C-section affects the composition of their infant's gut microbiome. To do this, a randomized controlled trial (RCT) was carried out with women undergoing elective C-sections. These women were either given antibiotics before the skin incision (AB+) or after the umbilical cord was clamped (AB-).

Study Overview

• Status: Completed
• Conditions: Microbial Colonization; Cesarean Section Complications; Antibiotic Side Effect
• Intervention / Treatment: Drug: Cefazolin

Detailed Description

Rationale: During a caesarean delivery, umbilical cord clamping can occur before or after administering a perioperative prophylactic antibiotic to the mother. If the cord is clamped before the antibiotic administration, this antibiotic cannot reach the infant. Conversely, if the cord is clamped after the antibiotic administration, these maternal antibiotics cross the placenta and enter the infant's circulation. In this study, investigators hypothesize that such antibiotics modify the composition and functionality of the neonatal gut microbiome. A changed neonatal microbiome associates with the onset of asthma, allergies, type 1 diabetes, and obesity later in life. Such a small intervention could influence the future health of the infant significantly.

Objective: The primary aim of this study is to contrast the composition and functionality of the neonatal gut microbiome from mothers given antibiotic prophylaxis before skin incision with the microbiome of neonates from mothers given the antibiotic after umbilical cord clamping during an elective caesarean delivery.

Study design: Randomized controlled trial

Study population: Pregnant women at >38 weeks of gestation undergoing elective caesarean section at the UMCG will be randomized into two groups. The gut microbiome of the neonates from both groups will be analyzed.

Intervention: The timing of umbilical cord clamping differs between the two groups. One gram of Cefazolin (once, intravenous) will be administered to one group before skin incision, while 1g cefazolin will be given to another group after umbilical cord clamping during an elective caesarean section.

Main study parameters/endpoints: The primary endpoint of this study is the variance in the composition and functionality of the neonatal gut microbiome over a year, contrasting neonates from mothers given antibiotic prophylaxis before skin incision with neonates from mothers given the antibiotic after umbilical cord clamping.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Females undergoing elective CS at the UMCG
• Gestational age in weeks equal to or above 38 weeks

Exclusion Criteria:

• Cephalosporin allergy
• Exposure to antibiotic agent 2 weeks before CS
• Temperature >37.5 C before CS
• Pre-labour rupture of membranes
• Emergency CS
• No -20 freezer at home
• No command of the Dutch language

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cord clamped after antibiotic prophylaxis; Umbilical cord clamped after 1g of cephazolin	Drug: Cefazolin; Cord clamping before or after antibiotic (cefazolin) prophylaxis; Other Names: DB01327; J01DB04
Experimental: Cord clamped before antibiotic prophylaxis; Umbilical cord clamped before 1g of cephazolin	Drug: Cefazolin; Cord clamping before or after antibiotic (cefazolin) prophylaxis; Other Names: DB01327; J01DB04

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant microbial species level differences between two groups	Centered log ratio transformed relative abundance differences of bacterial species (relative abundance of > 0.05% and present in at least 2 infants) between two interventional groups	First 6 weeks of life
Infant Alpha Diversity differences between two groups	Alpha Diversity difference measured by the Shannon Diversity Index of infant microbiome at species level between two interventional groups	First 6 weeks of life
Infant Beta Diversity differences between two groups	Beta Diversity difference in Aitchison distances between the two intervention groups	First 6 weeks of life
Infant Antibiotic Resistance total gene load differences between two groups	Infant Antibiotic Resistance total gene load differenced measured in RPKM between the two interventional groups	First 6 weeks of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with post c-section maternal wound infection	Number of participants with early and late post C-section wound infection in mothers	First 6 weeks of life

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Principal Investigator: Trishla Sinha, MD, University Medical Center Groningen; Principal Investigator: Alexandra Zhernakova, MD/PhD, University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Actual): October 1, 2022
• Study Completion (Actual): March 1, 2023

Study Registration Dates

• First Submitted: August 25, 2023
• First Submitted That Met QC Criteria: September 1, 2023
• First Posted (Actual): September 11, 2023

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Anti-Infective Agents; Anti-Bacterial Agents; Cefazolin
• Other Study ID Numbers: CS_Baby_Biome_2017/240; NL61493.042.17 (Registry Identifier: ABR); METc 2017.240 (Other Identifier: METc)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The sequencing data of the microbiome will be available for other researchers via EGA
• IPD Sharing Time Frame: Data will become available upon publication
• IPD Sharing Access Criteria: Must fill in the form that the data will be used for research purposes.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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