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

Not Applicable

Completed

• Conditions: Cesarean Section Complications; Microbial Colonization; Antibiotic Side Effect
• Interventions: Drug: Cefazolin

• Registration Number: NCT06030713
• Lead Sponsor: University Medical Center Groningen

Brief Summary

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-).

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 Timeline

• Study Start: 2019-03-01
• Primary Completion: 2022-10-01
• Study Completion: 2023-03-01
• Study First Submitted: 2023-08-25
• Status Verified: 2023-09
• Study First Submitted QC: 2023-09-01
• Study First Posted: 2023-09-11
• Last Update Submitted: 2023-09-11
• Last Update Posted: 2023-09-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cord clamped before antibiotic prophylaxis	Cefazolin	Umbilical cord clamped before 1g of cephazolin
Cord clamped after antibiotic prophylaxis	Cefazolin	Umbilical cord clamped after 1g of cephazolin

Primary Outcome Measures

Name	Time	Method
Infant Beta Diversity differences between two groups	First 6 weeks of life	Beta Diversity difference in Aitchison distances between the two intervention groups
Infant Antibiotic Resistance total gene load differences between two groups	First 6 weeks of life	Infant Antibiotic Resistance total gene load differenced measured in RPKM between the two interventional groups
Infant microbial species level differences between two groups	First 6 weeks of life	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
Infant Alpha Diversity differences between two groups	First 6 weeks of life	Alpha Diversity difference measured by the Shannon Diversity Index of infant microbiome at species level between two interventional groups

Secondary Outcome Measures

Name	Time	Method
Number of participants with post c-section maternal wound infection	First 6 weeks of life	Number of participants with early and late post C-section wound infection in mothers

Trial Locations

Locations (1)

University Medical Center Groningen; 🇳🇱 Groningen, Netherlands