Delivery modality affect neonatal levels of inflammation, stress, and growth factors
Open accessAbstract
Introduction: As part of the study CODIBINE, Correlations and Diagnoses for Biomarkers in New-borns, the main objective of the study was to explore neonatal inflammation, stress, neurodevelopment, and growth factors after in-labor and pre-labor cesarean section compared to vaginal delivery. Increasing evidence has shown that birth delivery mode has an impact on imminent and long-term child health. However, the effect of the timing of cesarean section is insufficiently elucidated. The main objective of the study was to explore the effect of different delivery modes, vaginal delivery compared to cesarean section with or without initiation of labor, on the infants. Methods: We designed a retrospective cohort study, including dried blood spot samples from mature (gestational age ≥ 37) newborns delivered in the years 2009-2011. The newborns were divided into three groups after delivery mode: (1) pre-labor cesarean section ( n = 714), i.e., cesarean delivery without initiation of labor, (2) in-labor cesarean section ( n = 655), i.e., cesarean section after initiation of labor, and (3) vaginal delivery ( n = 5,897). We measured infant levels of inflammatory (IL-18, MCP-1, CRP, sTNF RI), stress (HSP-70), growth (EGF, VEGF-A), and neurotrophic factors (BDNF, NT-3, S100B) 2–4 days after birth. Results: The neonatal levels of inflammatory and stress markers were significantly lower, while the levels of growth factors were higher after pre-labor cesarean section compared to vaginal delivery. The biomarker levels were similar after in-labor cesarean section and vaginal delivery. Removing cases with pre-labor rupture of membranes and artificial rupture of membranes in the calculations did not change the results. The levels of neurotrophic factors were unaffected by delivery form. Males had generally higher levels of inflammation and lower levels of growth and neurotrophic factors. Overall, the levels of inflammatory markers increased, and the growth factors decreased with increasing gestational age. Conclusion: The present study of the biomarker levels after birth suggests that the labor process has an important effect on the fetal immune system and level of stress, regardless if the delivery ends with cesarean section or vaginal birth.
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The differences in inflammatory and stress markers between C-section and vaginal delivery were not significant if C-section was performed during labor, suggesting that the labor process itself initiates important endocrine, physiological, and biochemical processes relevant to the neonatal immune system and stress response.
“Interestingly, these differences were not significant if C-section was performed during labor, suggesting that the labor process itself initiates important endocrine, physiological, and biochemical processes relevant to the neonatal immune system and stress response.”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [403]
In a cohort of more than 7,000 neonates, levels of inflammatory and stress markers were lower, and growth factor levels higher, in infants delivered via pre-labor C-section when compared to those delivered vaginally.
“In a cohort of more than 7,000 neonates, Kiilerich et al. found that levels of inflammatory and stress markers were lower, and growth factor levels higher, in infants delivered via pre-labor C-section when compared to those delivered vaginally (403).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [403]
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- Authors
- Kiilerich, P., Cortes, R., Lausten-Thomsen, U., Borbye-Lorenzen, N., Holmgaard, S., & Skogstrand, K.
- Affiliations
- Statens Serum Institut (DK)
- Corresponding author
- Skogstrand, Kristin
- Venue
- Frontiers in Pediatrics
- Publisher
- Frontiers Media SA
- Published
- 2021-09-22
- Volume
- 9
- Pages
- 709765-709765
- ISSN
- 2296-2360 (ISSN-L)
- PMC
- PMC8492985
- OpenAlex
- W3199212654
- Cited by
- 19
- References
- 43
- Citations by year
- 2026: 8 · 2025: 2 · 2024: 7 · 2023: 1 · 2021: 1
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Pediatrics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fonden til Lægevidenskabens Fremme
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Maternal and Perinatal Health Interventions
- Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Keywords
- mode of delivery, cesarean section, vaginal delivery, neonatal inflammation, neonatal stress, growth factors, neurotrophic factors, inflammatory markers, HSP70, brain-derived neurotrophic factor, S100B, epidermal growth factor, VEGF-A, IL-18, MCP-1, C-reactive protein, soluble TNF receptor 1, fetal immune system, sex differences, gestational age
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