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

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

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-).

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.

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.

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

Alpha Diversity difference measured by the Shannon Diversity Index of infant microbiome at species level between two interventional groups

Infant Antibiotic Resistance total gene load differenced measured in RPKM between the two interventional groups

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