Cross-sectional observational study protocol: missing microbes in infants born by caesarean section (MiMIC): antenatal antibiotics and mode of delivery

Alicja K Warda, Eugene M Dempsey, Sofia D Forssten, C Anthony Ryan, John F Cryan, Elaine Patterson, Mairead N O'Riordan, Carol-Anne O'Shea, Finola Keohane, Grainne Meehan, Orlagh O'Connor, R Paul Ross, Catherine Stanton, Alicja K Warda, Eugene M Dempsey, Sofia D Forssten, C Anthony Ryan, John F Cryan, Elaine Patterson, Mairead N O'Riordan, Carol-Anne O'Shea, Finola Keohane, Grainne Meehan, Orlagh O'Connor, R Paul Ross, Catherine Stanton

Abstract

Introduction: The intestinal microbiome in early life plays a major role in infant health and development. Factors like antibiotic exposure, breast/formula feeding and mode of delivery are known to affect the microbiome. The increasing occurrence of caesarean section (C-section) deliveries and antibiotic exposure warrants further insight into the potential missing microbes in those infants. The study objective is to study the effect of maternal antibiotic administration during pregnancy and/or C-section mode of delivery on the development of the infant's intestinal microbiome until the age of 2 years.

Methods and analysis: A single site, cross-sectional observational study of C-section and vaginally delivered infants being either exposed to maternal antibiotic treatment or not during the third trimester of pregnancy. Throughout the nine visits, stool, urine, saliva, hair, breast milk and vaginal swabs will be collected from either mother and/or infant for microbiome and metabolomic analysis.

Ethics and dissemination: The protocol was approved by the Clinical Research Ethics Committee of the Cork Teaching Hospitals. The trial has been registered at ClinicalTrials.gov.The findings from this study will be disseminated in peer-reviewed journals, during scientific conferences, and directly to the study participants. Sequencing data will be deposited in public databases.

Trial registration number: NCT04134819.

Keywords: MICROBIOLOGY; OBSTETRICS; PAEDIATRICS.

Conflict of interest statement

Competing interests: JFC has been an invited speaker at meetings organised by Mead Johnson, Yakult, Nutricia, Pepsi and Friesland Campina and has received research funding from Cremo, IFF, Pharmavite, Mead Johnson and Nutricia; and has been a consultant for Nestle. SDF is an employee of IFF Health & Biosciences that manufactures and commercialises probiotics, while EP was an employee of IFF Health & Biosciences at the time this manuscript was prepared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Study design, representing four comparative arms and the approximate number of infants per group (group 1 - 168, group 2 - 112, group 3 - 72, group 4 - 48) assuming that the probability for a mother to receive antibiotics during pregnancy is the same for the two delivery modes. Nonetheless, note that every baby born by C-section indirectly receives antibiotics at birth. Copyright Pinja Kettunen/SciArt & IFF Health & Biosciences, with permission. C-section, caesarean section.
Figure 2
Figure 2
Visit schedule, biological sample and data collection points during the study (ClinicalTrials.gov, NCT04134819). Copyright Pinja Kettunen/SciArt & IFF Health & Biosciences, with permission.
Figure 3
Figure 3
Effect of COVID-19 on participant recruitment showing the targeted (grey) and actual recruitment (black) rate.

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