Cesarean section and disease associated with immune function

doi:10.1016/j.jaci.2015.07.040

Journal of Allergy and Clinical Immunology

Volume 137, Issue 2, February 2016, Pages 587-590

https://doi.org/10.1016/j.jaci.2015.07.040 Get rights and content

Background

Earlier studies have shown that delivery by cesarean section (CS) is associated with an increased risk of disease associated with immune function in the offspring, but these studies have generally not discriminated between the effect of acute and elective CS.

Objective

We sought to further explore these associations using discrimination between the effects of acute versus elective CS.

Methods

We performed a population- and national register–based cohort study including all children born in Denmark from January 1997 through December 2012. Hazard ratios for diseases associated with immune function in children delivered by acute and elective CS with vaginal delivery as the reference were calculated by using Cox regression. All analyses were adjusted for gestational age, sex, birth weight, maternal age, maternal smoking during pregnancy, and complications during pregnancy (preeclampsia, eclampsia, hemorrhage, and hyperemesis).

Results

A total of 750,569 children aged 0 to 14 years were included. Children delivered by both acute and elective CS had an increased risk of asthma, laryngitis, and gastroenteritis. Children delivered by acute CS had an increased risk of ulcerative colitis and celiac disease, whereas children delivered by elective CS had an increased risk of lower respiratory tract infection and juvenile idiopathic arthritis. The effect of elective CS was higher than the effect of acute CS on the risk of asthma.

Conclusion

Children delivered by CS are at increased risk of disease associated with immune function. The effect is mainly on diseases involving the mucosal immune system.

Section snippets

Methods

This was a population- and register-based cohort study based on all children born in Denmark from January 1997 through December 2012. Data on maternal age, maternal smoking during pregnancy, complications during pregnancy (preeclampsia, eclampsia, hemorrhage, and hyperemesis), mode of delivery, sex, gestational age at birth, birth weight, neonatal respiratory morbidity, and diagnoses associated with immune function, including gastrointestinal and respiratory tract infections and autoimmune and

Results

During the study period, a total of 1,031,424 children were born in Denmark. Of these, 92,062 (8.9%) were delivered by acute CS, and 109,022 (10.6%) were delivered by elective CS. The number of children delivered by CS (both elective and acute) increased from 9,198 (13.6%) in 1997 to 12,704 (21.8%) in 2012. Of the total population, 67,093 children with gestational ages of less than 37 weeks at birth; 73,402 children with congenital chronic conditions, including all with congenital

Discussion

To our knowledge, this is the first study that discriminates between the effect of acute and elective CS when looking at the associations between CS and disease associated with immune function in the offspring. We show that both acute and elective CS are associated with laryngitis, asthma, and gastroenteritis; that acute CS is associated with ulcerative colitis and celiac disease; and that elective CS is associated with lower respiratory tract infection and juvenile idiopathic arthritis. In

References (26)

V. Vestermark et al.
Influence of the mode of delivery on initiation of breast-feeding
Eur J Obstet Gynecol Reprod Biol
(1991)
E. Prior et al.
Breastfeeding after cesarean delivery: a systematic review and meta-analysis of world literature
Am J Clin Nutr
(2012)
C. Macaubas et al.
Association between antenatal cytokine production and the development of atopy and asthma at age 6 years
Lancet
(2003)
J.A. Martin et al.
Births: final data for 2009
Natl Vital Stat Rep
(2011)
A.K. Hansen et al.
Risk of respiratory morbidity in term infants delivered by elective caesarean section: cohort study
BMJ
(2008)
K. Kristensen et al.
Caesarean section and hospitalization for respiratory syncytial virus infection: a population based study
Pediatr Infect Dis J
(2015)
H.C. Moore et al.
Hospitalisation for bronchiolitis in infants is more common after elective caesarean delivery
Arch Dis Child
(2012)
P. Bager et al.
Caesarean delivery and risk of atopy and allergic disease: meta-analyses
Clin Exp Allergy
(2008)
S. Thavagnanam et al.
A meta-analysis of the association between Caesarean section and childhood asthma
Clin Exp Allergy
(2008)
S. Hakansson et al.
Caesarean section increases the risk of hospital care in childhood for asthma and gastroenteritis
Clin Exp Allergy
(2003)

P. Bager et al.

Cesarean section and offspring's risk of inflammatory bowel disease: a national cohort study

Inflamm Bowel Dis

(2012)

E. Decker et al.

Cesarean delivery is associated with celiac disease but not inflammatory bowel disease in children

Pediatrics

(2010)

A. Sevelsted et al.

Cesarean section and chronic immune disorders

Pediatrics

(2015)

Cited by (147)

Short-term and long-term effects of cesarean section on asthma and wheezing: A cohort study and meta-analysis
2023, Respiratory Medicine
To describe the short-term and long-term effects of cesarean section on childhood asthma and wheezing.
Firstly, in the cohort study, 6640 infants were included in the cohort baseline from January 2018 to December 2019, in which 6501 children completed the follow-up study for respiratory diseases at age 2 years. The effect of cesarean section on asthma and wheezing was estimated by the logistic regression model. Secondly, we conducted a meta-analysis of studies with outcomes of childhood asthma and wheezing under 2 years of age and over 2 years of age, respectively, to investigate the short-term and long-term effects of cesarean section on asthma and wheezing.
In our cohort study, the cumulative incidence of asthma and wheezing was 1.3% (84/6501). 45.5% of children (2961/6501) were born by cesarean section. The adjusted odds ratio for the effect of cesarean section on asthma and wheezing in children under 2 years of age was 1.14 (95%CI 0.73–1.78). Combining previous studies (outcomes of asthma and wheezing under 2 years of age) with our results for a meta-analysis, the odds ratio was 1.15 (95%CI 1.05–1.25, I² = 46.82%). Meanwhile, cesarean section had a long-term effect on asthma and wheezing in the child population over 2 years of age (OR = 1.17, 95%CI 1.11–1.24, P < 0.001, I² = 79.38%).
Cesarean section had a short-term effect on asthma and wheezing before the age of 2, in addition, the long-term effect of cesarean section on asthma and wheezing persisted in the child population (under 18).
Infant gut microbiota and environment associate with juvenile idiopathic arthritis many years prior to disease onset, especially in genetically vulnerable children
2023, eBioMedicine
The etiology of juvenile idiopathic arthritis (JIA) is poorly understood. This study investigated genetic and environmental factors and infant gut microbiota in a prospective birth cohort to assess disease risk.
Data was collected from the All Babies in Southeast Sweden (ABIS) population-based cohort (n = 17,055), 111 of whom later acquired JIA (ABIS_JIA). Stool samples were collected at one year of age for 10.4%. To determine disease association, 16S rRNA gene sequences were analyzed, with and without confound adjustment. Genetic and environmental risks were assessed.
ABIS_JIA had higher abundance of Acidaminococcales, Prevotella 9, and Veillonella parvula and lower abundance of Coprococcus, Subdoligranulum, Phascolarctobacterium, Dialister spp., Bifidobacterium breve, Fusicatenibacter saccharivorans, Roseburia intestinalis, and Akkermansia muciniphila (q’s < 0.05). Parabacteroides distasonis greatly increased the odds of later contracting JIA (OR = 6.7; 1.81–24.84, p = 0.0045). Shorter breastfeeding duration and increased antibiotic exposure compounded risk in a dose-dependent manner, especially in those with genetic predisposition.
Microbial dysregulation in infancy may trigger or accelerate JIA development. Environmental risk factors have a stronger impact on genetically predisposed children. This study is the first to implicate microbial dysregulation in JIA at such an early age, with many bacterial taxa associated with risk factors. These findings provide opportunities for intervention or early screening and offer new insights into JIA pathogenesis.
Barndiabetesfonden; Swedish Council for Working Life and Social Research; Swedish Research Council; Östgöta Brandstodsbolag; Medical Research Council of Southeast Sweden; JDRF-Wallenberg Foundation; Linköping.
Microbiota dysbiosis and myasthenia gravis: Do all roads lead to Rome?
2023, Autoimmunity Reviews
Dysregulated immune system with a failure to recognize self from non-self-antigens is one of the common pathogeneses seen in autoimmune diseases. The complex interplay of genetic and environmental factors is important for the occurrence and development of the disease. Among the environmental factors, disturbed gut microbiota (gut dysbiosis) has recently attracted particular attention, especially with advancement in human microbiome research. Although the alterations in microbiota have been seen in various autoimmune diseases, including those of nervous system, there is paucity of information on neuromuscular system diseases. Myasthenia gravis (MG) is one such rare autoimmune disease of neuromuscular junction, and is caused by generation of pathogenic autoantibodies to components of the postsynaptic muscle endplate. In the recent years, accumulating evidences have endorsed the key role of host microbiota, particularly those of gut, in the pathogenesis of MG. Differential microbiota composition, characterized by increased abundance of Fusobacteria, Bacteroidetes, and Proteobacteria, and decreased abundance of Actinobacteria and Firmicutes, has been seen in MG patients in comparison to healthy subjects. Disturbance of microbiota composition, particularly reduced ratio of Firmicutes/Bacteroidetes, alter the gut permeability, subsequently triggering the immunological response. Resultant reduction in levels of short chain fatty acids (SCFAs) is another factor contributing to the immunological response in MG patients. Modulation of gut microbiota via intervention of probiotics, prebiotics, synbiotics, postbiotics (metabiotics), and fecal microbiota transplantation (FMT) is considered to be the futuristic approach for the management of MG. This review summarizes the role of gut microbiota and their metabolites (postbiotics) in the progression of MG. Also, various bacteriotherapeutic approaches involving gut microbiota are discussed for the prevention of MG progression.
Functional constipation symptoms and complementary feeding methods: A randomized clinical trial
2023, Anales de Pediatria
El objetivo del estudio fue investigar el impacto de diferentes métodos de alimentación complementaria en la prevalencia de síntomas de estreñimiento funcional en lactantes a los 12 meses de edad.
Ensayo clínico aleatorizado realizado en díadas madre-lactante sometidas a intervención a los 5,5 meses del nacimiento, con asignación aleatoria a uno de los tres métodos de introducción de sólidos: destete dirigido por la madre, o parent-led weaning (PLW), método Baby-Led Introduction to Solids (BLISS) dirigido por el lactante, y mixto. Los síntomas de estreñimiento se evaluaron a los 12 meses mediante un cuestionario en línea basado en los criterios diagnósticos de Roma IV y adaptado a la muestra. Los análisis se realizaron mediante la prueba χ² y los datos se expresaron como frecuencias absolutas y porcentajes. El proyecto fue aprobado por el comité de ética del Hospital de Clínicas de Porto Alegre con el número 2019-0230.
Se analizaron los datos de 135 lactantes, 45 asignados al método PLW, 48 al BLISS y 42 al método mixto. La prevalencia de síntomas de estreñimiento fue del 49,6% en la muestra global (n = 67), siendo del 60% (n = 27) en el método PLW, 47,9% (n = 23) en el BLISS y 40,5% (n = 17) en el mixto. No hubo asociación entre los síntomas de estreñimiento funcional y el método de introducción de la alimentación complementaria (p = 0,183).
La prevalencia de estreñimiento y sus síntomas fue alta en la población estudiada. La prevalencia de los síntomas de estreñimiento funcional no se asoció con el método de alimentación complementaria.
The aim of the study was to investigate the impact of different complementary feeding methods on the prevalence of functional constipation symptoms in infants at 12 months of age.
Randomized clinical trial in mother–infant dyads that underwent the intervention at 5.5 months post birth, randomly allocated to one of three complementary food introduction methods: PLW (parent-led weaning), baby-led introduction to solids (BLISS) and a mixed approach. The symptoms of constipation were assessed at 12 months with an online questionnaire based on the Rome IV diagnostic criteria and adapted to our sample. The data were summarised as absolute frequencies and percentages and compared by means of the χ² test. The project was approved by the ethics committee of the Hospital de Clínicas de Porto Alegre under number 2019-0230.
We analysed data corresponding to 135 infants, 45 allocated to PLW, 48 to BLISS and 42 to the mixed approach. The prevalence of constipation symptoms was 49.6% in the overall sample (n = 67), 60% (n = 27) in the PLW group, 47.9% (n = 23) in the BLISS group and 40.5% (n = 17) in the mixed approach group. We found no association between functional constipation symptoms and the method used to introduce complementary foods (P = .183).
The prevalence of functional constipation symptoms was high in the study population. The presence of constipation symptoms was not associated with the complementary feeding approach.
Association between Cesarean section delivery and increased risk of childhood Kawasaki disease
2023, Journal of the Formosan Medical Association
Cesarean section delivery is associated with microbiota disruption and immuno-dysregulation during childhood, but the association with Kawasaki disease remains uncertain. We aimed to evaluate the association between Cesarean section and Kawasaki disease.
We examined the association between Kawasaki disease between six and eighteen months and Cesarean section within a birth cohort of 15,796 mother-infant pairs in Taiwan. The associations were assessed with Poisson regression in the study population, in the 1:2 propensity score-matched subpopulation, and compared with febrile convulsion, trauma and accidents during the same interval as negative control outcomes.
Cesarean section was found to increase the risk of Kawasaki disease among overall population (adjusted relative risk [aRR]: 2.22, 95 % confidence interval (CI): 1.14–4.34) and the matched subpopulation (aRR: 2.29, 95 % CI: 1.14–4.68 in PS-matched subpopulation). Meanwhile, there was no association between Cesarean section and the clinic visits for febrile convulsion, trauma and accidents.
In conclusion, this study identified a potential association between Cesarean section delivery and a higher risk of Kawasaki disease during six-to eighteen months of the prospective birth cohort in Taiwan.
Effects of vaginal seeding on gut microbiota, body mass index, and allergy risks in infants born through cesarean delivery: a randomized clinical trial
2023, American Journal of Obstetrics and Gynecology MFM
Vaginal seeding—exposure of neonates to maternal vaginal fluids—has been proposed to improve the microbiota of infants born through cesarean delivery, but its impacts on the infants' subsequent health outcomes remain unclear.
This study aimed to examine the impacts of vaginal seeding on gut microbiota, growth, and allergy risks in infants born through cesarean delivery.
This randomized controlled trial was conducted at Liuyang Maternal and Child Health Care Hospital in Hunan, China. We estimated that a minimum sample size of 106 was needed by assuming a standardized effect size of 0.6 for the primary outcomes, with a statistical power of 80%, a 2-sided type I error of 0.05, and an expected loss to follow-up rate of 15%. Finally, 120 singleton term pregnant women scheduled for cesarean delivery were enrolled from November 2018 to September 2019. Infant follow-up was completed in September 2021. The participants were randomized in a 1:1 ratio to the vaginal seeding group (n=60; infants were swabbed immediately after birth using gauze preincubated in maternal vagina) or the control group (n=60; routine standard care). The first set of primary outcomes was infant body mass index and body mass index z-scores at 6, 12, 18, and 24 months of age. The other primary outcome was the total allergy risk score at 18 months for 20 common allergens (each scored from 0–6 points). Characteristics of gut microbiota, overweight/obesity, and allergic diseases and symptoms were included as secondary outcomes. The main analyses were performed according to the modified intention-to-treat principle.
Of 120 infants, 117 were included in the analyses. Infant body mass index and body mass index z-scores did not significantly differ between the 2 groups at any of the 4 time points, with the largest difference in point estimates occurring at 6 months: the mean (standard deviation) body mass index was 17.5 (1.4) kg/m² and 17.8 (1.8) kg/m² in the vaginal seeding and control groups, respectively (mean difference, −0.31 kg/m² [95% confidence interval, −0.91 to 0.28]; P=.30), and body mass index z-score was 0.2 (1.0) and 0.4 (1.1), respectively (mean difference, −0.20 [95% confidence interval, −0.58 to 0.18]; P=.31). The median total allergy risk score was 1.5 (interquartile range, 0.0–4.0) in the vaginal seeding group and 2.0 (interquartile range, 1.0–3.0) in the control group (median difference, 0.00 [95% confidence interval, −1.00 to 1.00]; P=.48). For infants from the vaginal seeding group, the relative abundance of genera Lactobacillus and Bacteroides in the gut microbiota was slightly yet nonsignificantly elevated at birth and 6 months, and the risk of overweight/obesity was lower at 6 months (0/57 vs 6/59; relative risk, 0.03 [95% confidence interval, 0.00–0.57]; P=.03) though not at subsequent time points. Other secondary outcomes did not differ between groups. No adverse events related to the intervention were reported.
For infants born through cesarean delivery, vaginal seeding has no significant impacts on the gut microbiota, growth, or allergy risks during the first 2 years of life.

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: Supported by Edith og Henrik Henriksens Mindelegat.

: Disclosure of potential conflict of interest: The authors received research support from Edith og Henrik Henriksens Mindelegat. L. Henriksen participated in an AbbVie safety study on palivizumab.

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Mechanisms of allergy and clinical immunologyCesarean section and disease associated with immune function

Background

Objective

Methods

Results

Conclusion

Section snippets

Methods

Results

Discussion

Eur J Obstet Gynecol Reprod Biol

Am J Clin Nutr

Lancet

Births: final data for 2009

Natl Vital Stat Rep

Risk of respiratory morbidity in term infants delivered by elective caesarean section: cohort study

BMJ

Caesarean section and hospitalization for respiratory syncytial virus infection: a population based study

Pediatr Infect Dis J

Hospitalisation for bronchiolitis in infants is more common after elective caesarean delivery

Arch Dis Child

Caesarean delivery and risk of atopy and allergic disease: meta-analyses

Clin Exp Allergy

A meta-analysis of the association between Caesarean section and childhood asthma

Clin Exp Allergy

Caesarean section increases the risk of hospital care in childhood for asthma and gastroenteritis

Clin Exp Allergy

Cesarean section and offspring's risk of inflammatory bowel disease: a national cohort study

Inflamm Bowel Dis

Cesarean delivery is associated with celiac disease but not inflammatory bowel disease in children

Pediatrics

Cesarean section and chronic immune disorders

Pediatrics

Mechanisms of allergy and clinical immunology
Cesarean section and disease associated with immune function