The lack of natural processes of delivery and neonatal intensive care treatment lead to impaired cytokine responses later in life

Martikainen, Maria-Viola; Keski‐Nisula, Leea; Jakupović, Hermina; Karvonen, Anne M.; Pekkanen, Juha; Hirvonen, Maija-Riitta; Roponen, Marjut

doi:10.1111/aji.12621

Cited by 8 publications

(7 citation statements)

References 25 publications

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“…A few studies regarding CRP have been described, that found similar differences in new-born levels depending on birth form as we describe (33,34). In a study among teenagers, whose mothers had entered the active phase of labour before CS, spontaneous and toll-like receptor-stimulated cytokine release was increased, compared to controls born by pre-labour CS (35). This concurs with another study showing that the risk for early childhood infections are higher in children born by pre-labour CS compared to children born by in-labour CS or VD (1,36).…”

Section: Discussionsupporting

confidence: 62%

Neonatal inflammation, stress and growth factors after vaginal delivery, pre-labour, and in-labour caesarean section: a retrospective cohort study

Kiilerich¹,

Cortes²,

Lausten-Thomsen³

et al. 2020

Preprint

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Objective To explore the effect of different delivery modes, vaginal delivery compared to caesarean section with or without initiation of labour, on the immune system and brain of the infants. Further, we aimed to elucidate gender and gestational ages' effect on these biomarkers. Design Retrospective case control study Setting Dried blood spots from new-born screening biobank drawn 2-4 days after birth Population or Sample Mature new-borns divided into delivery by pre-labour (n=714), inlabour caesarean section (n=655), and vaginally (n=5897). Method The samples were analysed for inflammatory markers (IL-18, MCP-1, CRP, sTNF RI), stress-(HSP-70), growth-(EGF, VEGF-A), and neurotrophic factors (BDNF, NT-3, S100B). Main Outcome Measures Delivery by caesarean section with or without initiation of labour Results The neonatal levels of inflammatory and stress-markers were significantly lower, while the levels of growth factors were higher after pre-labour caesarean section compared to vaginal delivery. The biomarker levels were similar after in-labour caesarean section and vaginal delivery. 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 biomarker levels indicates that the labour process has an important effect on the foetal immune system and level of stress, regardless if the delivery ends with caesarean section or vaginal birth. Funding "Laege Sofus Carl Emil Friis og hustru Olga Doris Friis' legat" and "Fonden til Laegevidenskabens Fremme". Keywords Inflammation; brain; CODIBINE; caesarean section; dried blood spot samples ObjectiveTo explore the effect of different delivery modes, vaginal delivery compared to caesarean section with or without initiation of labour, on the immune system and brain of the infants. Further, we aimed to elucidate gender and gestational ages' effect on these biomarkers. Design Retrospective case control study SettingDried blood spots from new-born screening biobank drawn 2-4 days after birth Population or SampleMature new-borns divided into delivery by pre-labour (n=714), in-labour caesarean section (n=655), and vaginally (n=5897).

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Section: Discussionsupporting

confidence: 62%

Neonatal inflammation, stress and growth factors after vaginal delivery, pre-labour, and in-labour caesarean section: a retrospective cohort study

Kiilerich¹,

Cortes²,

Lausten-Thomsen³

et al. 2020

Preprint

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“…Similar evidence has been brought regarding the mode of delivery on the composition of neonatal gut microbiota, and the maturation of the intestinal epithelium capable to control the immune system during early life (23). Newborns delivered by cesarean may have an early microbiota alteration and consequently different patterns of the immune response (24) even a long-lasting impairment of immune status (25). Our study provides evidence that birthweight may have a limited role in the risk to JIAPs knowing that fetal growth and timing of birth may be factors of the susceptibility to JIA (26).…”

Section: Discussionmentioning

confidence: 89%

Contribution of Genetic and Environmental Risk Factors in a Juvenile Idiopathic Arthritis Large Family With SERPINA1 Gene Mutations

Popescu

2021

Preprint

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Objectives Although the underlying mechanisms and mediators of arthritis in juvenile idiopathic arthritis (JIA) are not well understood, accumulated evidence supports the mixt role of genetic and environmental factors. Few reports of multiplex families with JIA were published until now. The aim of this study was to identify new genetic or environmental associations concerning the patients of a kindred with juvenile idiopathic arthritis and psoriatic features (JIAPs). Methods Here, we characterized an extended multiplex family of 5 patients with juvenile idiopathic arthritis and psoriatic features (PsA) at the clinical and genetic level, using whole exome sequencing. Results We did not confirm in our family the linkage with the genetic factors already described that might be associated with increase susceptibility to JIA. We found a carrier status of siblings who inherited a pathogenic allele of the SERPINA1 gene from their mother who herself has two heterozygous pathogenic variants in the SERPINA1 gene. Conclusions Our data showed that JIA results from pleiotropic effects of environmental background with an only minor monogenic contribution. Even that a monogenetic factor could not be proved, some genetic factor as SERPINA1 mutations which can sensitize for psoriatic arthritis development seems to be involved. Further investigation must be done to prove whether SERPINA1 mutations may have a potential JIA causality.

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“…A few studies regarding CRP have been described, which found similar differences in newborn levels depending on birth form as observed in the current study ( 30 ). In a study among teenagers, whose mothers had entered the active phase of labor before CS, spontaneous and toll-like receptor-stimulated cytokine release was increased, compared to controls born by pre-labor CS ( 31 ). This concurs with another study showing that the risk for early childhood infections is higher in children born by pre-labor CS compared to children born by in-labor CS or VD ( 32 ).…”

Section: Discussionmentioning

confidence: 98%

Delivery Modality Affect Neonatal Levels of Inflammation, Stress, and Growth Factors

et al. 2021

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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 lack of natural processes of delivery and neonatal intensive care treatment lead to impaired cytokine responses later in life

Abstract: The lack of natural processes of delivery and neonatal intensive care treatment might lead to long-lasting impairment of immune responses.

Cited by 8 publications

References 25 publications

Neonatal inflammation, stress and growth factors after vaginal delivery, pre-labour, and in-labour caesarean section: a retrospective cohort study

Neonatal inflammation, stress and growth factors after vaginal delivery, pre-labour, and in-labour caesarean section: a retrospective cohort study

Contribution of Genetic and Environmental Risk Factors in a Juvenile Idiopathic Arthritis Large Family With SERPINA1 Gene Mutations

Delivery Modality Affect Neonatal Levels of Inflammation, Stress, and Growth Factors

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