Timing of antimicrobial prophylaxis for cesarean section is critical for gut microbiome development in term born infants
Open accessAbstract
Animal models imply that the perinatal exposure to antibiotics has a substantial impact on microbiome establishment of the offspring. We aimed to evaluate the effect of timing of antimicrobial prophylaxis for cesarean section before versus after cord clamping on gut microbiome composition of term born infants. We performed an exploratory, single center randomized controlled clinical trial. We included forty pregnant women with elective cesarean section at term. The intervention group received single dose intravenous cefuroxime after cord clamping (n = 19), the control group single dose intravenous cefuroxime 30 minutes before skin incision (n = 21). The primary endpoint was microbiome signature of infants and metabolic prediction in the first days of life as determined in meconium samples by 16S rRNA gene sequencing. Secondary endpoints were microbiome composition at one month and 1 year of life. In meconium samples of the intervention group, the genus Staphylococcus pre-dominated. In the control group, the placental cross-over of cefuroxime was confirmed in cord blood. A higher amino acid and nitrogen metabolism as well as increased abundance of the genera Cutibacterium, Corynebacterium and Streptophyta were noted (indicator families: Cytophagaceae, Lactobacilaceae, Oxalobacteraceae). Predictive models of metabolic function revealed higher 2'fucosyllactose utilization in control group samples. In the follow-up visits, a higher abundance of the genus Clostridium was evident in the intervention group. Our exploratory randomized controlled trial suggests that timing of antimicrobial prophylaxis is critical for early microbiome engraftment but not antimicrobial resistance emergence in term born infants.
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In a randomized control trial of 40 mother/infant pairs, the timing of prophylactic antibiotics before versus after clamping of the cord was found to be critical for microbiota development.
“In a RCT of 40 mother/infant pairs in which prophylactic antibiotics were administered before versus after clamping of the cord, the timing of the exposure was found to be critical for microbiota development (410).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [410]
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Bruchhage, K., Lupatsii, M., Möllenkolk, F., Leffers, D., Kurabi, A., Jürgens, T. P., Graspeuntner, S., Hollfelder, D., & Leichtle, A. (2023) · European Archives of Oto-Rhino-Laryngology · doi:10.1007/s00405-022-07795-9 · Cited by 14 · see citing works
“The patient’s stool samples were collected in Stool Collection Tubes with DNA Stabilizer (Invitek Molecular GmbH, Berlin, Germany) and were processed using PSP® Spin Stool DNA Plus Kit (Invitek Molecular GmbH, Berlin, Germany) Library preparation and Sequencing were carried out as described before [47, 48].”
MethodSchilling, A.-L., Rody, A., & Boßung, V. (2022) · Geburtshilfe und Frauenheilkunde · doi:10.1055/a-1934-1761 · Cited by 12 · see citing works
Graspeuntner, S., Lupatsii, M., van Zandbergen, V., Dammann, M.-T., Pagel, J., Nguyen, D. N., Humberg, A., Göpel, W., Herting, E., Rupp, J., et al. (2024) · Infection · doi:10.1007/s15010-024-02396-6 · Cited by 9 · see citing works
“The analyses of this study were conducted using the most recent version of SPSS software (Version 29.0; SPSS Inc., chain reaction (PCR) quantification of amplicons and library preparation were performed as described in previous work by our group [11, 25, 26].”
InfluentialTeuscher, J. L., Lupatsii, M., Graspeuntner, S., Jonassen, S., Bringewatt, A., Herting, E., Stichtenoth, G., Boßung, V., Rupp, J., Härtel, C., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1540979 · Cited by 9 · see citing works
Alrammaal, H. H., Abduljalil, K., Morton, V. H., Morris, R. K., Marriott, J. F., Chong, H. P., & Batchelor, H. K. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14061162 · Cited by 9 · see citing works
“the maternal/foetal safety should be considered [64].”
The impact of cefuroxime prophylaxis on human intestinal microbiota in surgical oncological patients
Văcărean-Trandafir, I.-C., Amărandi, R.-M., Ivanov, I. C., Iacob, Ș., Mușină, A.-M., Bărgăoanu, E.-R., & Dimofte, M. (2023) · Frontiers in Microbiomes · doi:10.3389/frmbi.2022.1092771 · Cited by 8 · see citing works
“which target the composition of the gut microbiota among newborns whose mothers had received Cefuroxime prior delivery, but provide confounding results (Kamal et al., 2019; Dierikx et al., 2019; Jokela et al., 2022; Bossung et al., 2022).”
BackgroundGraspeuntner, S., Lupatsii, M., Dashdorj, L., Rody, A., Rupp, J., Boßung, V., & Härtel, C. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.05254-22 · Cited by 7 · see citing works
“To detect the abundance of various previously explored (9) resistance genes in both sample types, the subset of 13 paired meconium samples and rectal swabs was screened using PCR with specific primers (see Table S1 in the supplemental material) (59–62).”
BackgroundMethodInfluentialPerinatal Antibiotic Exposure and Respiratory Outcomes in Children Born Preterm
Fortmann, M. I., Welp, A., Hoffmann, N., Faust, K., Silwedel, C., Retzmann, J., Gembicki, M., Köstlin‐Gille, N., Häfke, A., Zemlin, M., et al. (2025) · JAMA Network Open · doi:10.1001/jamanetworkopen.2025.9647 · Cited by 6 · see citing works
Prophylactic antibiotics to prevent postcesarean infection: which antimicrobial, when, how, and why?
Sanchez‐Ramos, L., Preis, R., & Romero, R. J. (2025) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2025.09.044 · Cited by 3 · see citing works
Use of Macrogol to Accelerate Feeding Advancement in Extremely Preterm Infants
Faust, K., Lupatsii, M., Rømer, F., Graspeuntner, S., Waschina, S., Zimmermann, S., Humberg, A., Fortmann, M. I., Hanke, K., Böckenholt, K., et al. (2025) · Neonatology · doi:10.1159/000543050 · Cited by 2 · see citing works
Horwell, E., Bearn, P. E., & Cutting, S. M. (2024) · Microbiome Research Reports · doi:10.20517/mrr.2024.32 · Cited by 3 · see citing works
Walter, J. M., Choe, J., Parajon, T., McDonough, E., Dambly, N., & Chowdhury, D. (2023) · Side effects of drugs annual · doi:10.1016/bs.seda.2023.07.010 · Cited by 1 · see citing works
Probiotics - should pediatricians and neonatologists use them? A literature review
Marcicka, J., Mądry, W., Mazurkiewicz, A., Kołodziej, M., Męczyńska, J., Saiuk, N., Kozicz, M. A., Seredyński, T., Wojciechowska, A., & Salasa, W. (2024) · Quality in Sport · doi:10.12775/qs.2024.15.52273 · Cited by 1 · see citing works
“%) or ADHD (Attention Deficit Hyperactivity Disorder) [6][9][10][11].”
BackgroundPräventionskonzepte in der Frühgeborenenmedizin
Härtel, C., Spiegler, J., Hanke, K., Herting, E., & Göpel, W. (2022) · Monatsschrift Kinderheilkunde · doi:10.1007/s00112-022-01486-9
Vaginale Geburt – Vor- und Nachteile für Mutter und Kind
Schrey-Petersen, S., & Härtel, C. (2024) · Die Gynäkologie · doi:10.1007/s00129-024-05197-y
Infektprophylaxe bei Sectio – wie und wann?
Boßung, V., & Härtel, C. (2024) · Die Gynäkologie · doi:10.1007/s00129-024-05254-6
Antibiotika in der Geburtshilfe – wie viel ist zu viel?
Boßung, V. (2024) · Hebamme · doi:10.1055/a-2340-1045
The neonatal gut microbiome in health and disease
Preidis, G. A. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2457499
“18 This section concludes with a review by Samarra and coauthors from the laboratory of Maria Carmen Collado that outlines the current state of knowledge of vertical transfer of antibiotic resistance genes (ARGs).”
Boßung, V., & Härtel, C. (2025) · Die Gynäkologie · doi:10.1007/s00129-025-05387-2
Development of Infant Microbiome and Its Long‐Term Health Impacts
Adeboye, S. O., Olarewaju, V. O., Allen, O. V., Oyegbade, S. A., & Adeboye, B. J. (2026) · Advanced Gut & Microbiome Research · doi:10.1155/agm3/3719969
Coșovanu, E. T., Ursu, R. G., Coșovanu, E. O., Minciună, D. A., Cărăuleanu, A., Socolov, D. G., Iancu, L. S., & Caruntu, I. D. (2026) · Microbiology Research · doi:10.3390/microbiolres17100200
- Authors
- Bossung, V., Lupatsii, M., Dashdorj, L., Tassiello, O., Jonassen, S., Pagel, J., Demmert, M., Wolf, E. A., Rody, A., Waschina, S., Graspeuntner, S., Rupp, J., & Härtel, C.
- Affiliations
- University Hospital Schleswig-Holstein (DE)
- German Center for Infection Research (DE)
- Christian-Albrechts-Universität zu Kiel (DE)
- University of Lübeck (DE)
- Corresponding author
- Bossung, Verena
- ORCID
- Venue
- Gut Microbes
- Publisher
- Informa UK Limited
- Published
- 2022-02-20
- Volume
- 14
- Issue
- 1
- Pages
- 2038855-2038855
- ISSN
- 1949-0976 (ISSN-L)
- 1949-0984
- PMC
- PMC8865290
- OpenAlex
- W4212930045
- Cited by
- 28
- References
- 75
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 8 · 2023: 7 · 2022: 4
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Gut Microbes (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
- Health Sciences › Medicine › Obstetrics and Gynecology › Maternal and Perinatal Health Interventions
- Keywords
- cesarean section, antibiotic prophylaxis, timing of prophylaxis, gut microbiota, term infants, cefuroxime, umbilical cord clamping, meconium, Staphylococcus, Clostridium, antimicrobial resistance
- MeSH terms
- Gastrointestinal Microbiome, Anti-Bacterial Agents, Cefuroxime, Cesarean Section, Feces, Female, Humans, Placenta, Pregnancy, RNA, Ribosomal, 16S
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