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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Microbial Colonization, Antibiotic Side Effect, Cesarean Section Complications

Intervention / Treatment
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* Drug: Cefazolin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Timing of umbilical cord clamping is different in the two arms. One gram of Cefazolin (once, intravenous) will be given to one group of women before skin incision compared to 1g cefazolin given to another group of women after umbilical cord clamping during an elective caesarean section.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cord clamped after antibiotic prophylaxis<br>Umbilical cord clamped after 1g of cephazolin | Drug: Cefazolin<br>* Cord clamping before or after antibiotic (cefazolin) prophylaxis<br>* Other names: J01DB04;|
| Experimental: Cord clamped before antibiotic prophylaxis<br>Umbilical cord clamped before 1g of cephazolin | Drug: Cefazolin<br>* Cord clamping before or after antibiotic (cefazolin) prophylaxis<br>* Other names: J01DB04;|

What is the study measuring?
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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 |