Could Caesarean births be responsible for childhood allergies?

By Katherine Bethell 

In the last several decades the number of births by caesarean section has increased dramatically to approximately 30% of all deliveries (Bager P et al., 2008). Whilst this rate has been increasing, so has the incidence of allergic diseases including food allergy, eczema, allergic rhinitis and asthma (Bjorksten B, 2004). It has been suggested that there is a potential link between caesarean deliveries and the risk of developing allergies, which will be explored in this article. 

The intestinal microbiome, composed of trillions of microorganisms and their genes residing in the intestines, has a pinnacle role in the development of the immune system, absorption of nutrients and maintaining homeostasis (Frost F et al., 2020). However, before birth, the foetus is isolated from the environment and has a largely sterile gastrointestinal tract; this will quickly change once the baby is born and exposed to microorganisms which colonise their intestine (Kirjavainen P and Gibson G, 1999).

Mode of delivery is an important factor which will influence the newborn’s intestinal microbiome as birth is likely to be the first time the baby comes into contact with microorganisms. In a typical vaginal delivery, the baby is instantly exposed to the maternal vaginal microbiome which seeds the baby’s intestinal microbiome (Adlerberth I and Wold A, 2009.); this is an important event as the mother’s reproductive tract contains commensal bacteria which are also important in the gut. Whereas babies born via caesareans lack the contact with the maternal vaginal microbiota and their intestinal microbiome is instead seeded by microorganisms present on the mother skin through breastfeeding and bacteria present in the environment (Renz-Polster et al., 2005). One of the most common commensal bacteria types found in both the vaginal and intestinal microbiome, and is essential for both, are Lactobacilli – several studies have shown that vaginally delivered infants are likely to have intestines colonised with Lactobacillus species 10 days earlier than those born by caesareans (Gronlund M et al., 1999). 

It is widely accepted that exposure to microbes and their products helps to develop tolerance to antigens, vital for developing a healthy working immune system (Bjorksten B. 2004). The colonising bacteria have constant communication with the newborns intestinal epithelial cells through the gut mucosa and surface molecules, which allows the immune system to become tolerant to these antigens (Weng M and Walker W, 2013). The differences observed in the intestinal microbiota of babies born either through caesareans or vaginal delivery could affect the development and maturation of the immune system as different bacteria will be interacting with the baby’s epithelial cells. This could be vital for allergy development since babies born by caesareans may lack the tolerance to commensal antigens and instead develop allergic reactions to typically harmless environmental material (Bjorksten B. 2004).

Currently the evidence regarding caesareans’ influence on the development of childhood allergies is contrasting. Papers have been published which show caesareans moderately increasing the risk of allergic rhinitis and asthma, despite the overall proportion of these allergy cases attributable to caesareans only being 1-4% (Bager P et al., 2008). However, there is a large contrast between papers studying specific allergies: one study found children born by caesareans has a significantly increased risk of developing allergic rhinitis but not asthma (Pistiner M et al., 2008), whilst another found no association between mode of delivery and allergic rhinitis and instead reported a positive link between caesareans and asthma (Bager P et al., 2003). In some studies, there has been no statistically convincing data to suggest that children born by caesareans had an increased risk of allergy and asthma (Maitra A et al., 2004).

The mode of delivery is not the only factor which can influence a baby’s gut microbial composition, however. The place of birth will have an effect on the microbiota profile of a newborn’s intestine as the environment is different and is likely to contain different bacterial species (Selma-Royo M, 2020). Furthermore, the infant’s diet can also determine initial bacterial colonisation of their intestine as breast milk contains a variety of oligosaccharides that selectively stimulate the proliferation of certain bacteria types whereas formula milk is unable to contain some of these complex sugars, so a different intestinal microbiome is developed (Walker A, 2013). If antibiotic administration is necessary due to a premature birth or infection it can have a significant effect on the infant’s microbial composition as well, by reducing the levels of bacteria and altering its composition (O’Neill et al., 2020). Each of these factors may play a role in changing the newborns microbiome and hence affecting their immune system and likelihood of developing allergies. 

The link between mode of delivery, specifically caesareans, and the increase in allergy prevalence has not been proven despite several studies investigating this. Although some studies have shown convincing evidence of allergies attributable to caesareans (Bager P et al., 2008) there have equally been studies showing no link at all (McKeever T et al., 2002). It has been confirmed caesareans influence the newborns intestinal microbiome (Gronlund M et al., 1999) which could increase the risk of allergy alongside other factors such as antibiotic usage and formula feeding. Most papers investigating this area have underpinned how the connection between caesareans and allergy is tentative and not strong enough to advise against this mode of delivery, but it is an interesting link to consider and further investigate. 

References:

Adlerberth I, Wold A. 2009. Establishment of the gut microbiota in Western Infants. Acta Paediatrica. 98(2). Available from: DOI: 10.1111/j.1651-2227.2008.01060.x

Bager P, Melbye M, Rostgaard K, Benn C. 2003. Mode of delivery and risk of allergic rhinitis and asthma. The Journal of Allergy and Clinical Immunology. 111(1): 51-56. Available from: DOI: 10.1067/mai.2003.34

Bager P, Wohlfahrt J, Westergaard T. 2008. Caesarean delivery and risk of atopy and allergic disease: meta-analyses. Clinical and Experimental Allergy. 38 (4). Available from: DOI: 10.111/j.1365-2222.2008.02939.x

Bjorksten B. 2004. Effects of intestinal microflora and the environment on the development of asthma and allergy. Springer Seminars in Immunopathology. 25: 257-270. Available from: DOI: 10.1007/s00281-003-0142-2

Frost F, Kacprowski T, Rhlemann M, Pietzner M, Bang C, Franke A et al. 2020. Long-term instability of the intestinal microbiome is associated with metabolic liver diseases, low microbiota diversity, diabetes mellitus and impaired exocrine pancreatic function. Gut. 0: 1-9. Available from: DOI: 10.1136/gutjnl-2020-322753

Gronlund M, Lehtonen O, Eerola E, Kero P. 1999. Faecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after caesarean delivery. Journal of Paediatric Gastroenterology and Nutrition. 28(1): 19-25. Available from: DOI: 10.1097/00005176-199901000-00007

Kirjavainen P, Gibson G. 1999. Healthy gut microflora and allergy: factors influencing development of the microbiota. Annals of Medicine. 31(4). Available from: DOI: 10.3109/07853899908995892

Maitra A, Sherriff A, Strachan D, Henderson J. 2004. Mode of delivery is not associated with asthma or atopy in childhood. Clinical and Experimental Allergy. 34(9). Available from: DOI: 10.1111/j.1365-2222.2004.02048.x

McKeever T, Lewis S, smith C, Hubbard R. Mode of delivery and risk of developing allergic disease. The Journal of Allergy and Clinical Immunology. 109(5): 800-802. Available from: DOI: 10.1067/mai.2002.124046

O’Neill I, Galardon R, Saldova R, Murphy E, Cotter P, McAuliffe F. 2020. Maternal and Infant factors that shape neonatal gut colonisation by bacteria. Expert review of gastroenterology and Hepatology. 14(8). Available from: DOI: 10.1080/17474124.2020.1784725

Pistiner M, Gold D, Abdulkerim H, Hoffman E, Celedon J. 2008. Birth by caesarean section, allergic rhinitis, and allergic sensitisation among children with parental history of atopy. Journal of Allergy and Clinical Immunology. 122(2): 274-279. Available from: 10.1016/j.jaci.2008.05.007

Renz-Polster H, David M, Buist A, Vollmer W, O’Connor E, Frazier E, Wall M. 2005. Caesarean section delivery and the risk of allergic disorders in childhood. Clinical and Experimental Allergy. 35(11). Available from: DOI: 10.1111/j.1365-2222.2005.02356.x

Selma- Royo M, Arroyo M, Garcia-Mantrana I, Llorca P, Escuriet R, Martinez-Costa C, Collado M. 2020. Perinatal environment shapes microbiota colonisation and infant growth: impact on host response and intestinal function. Microbiome. 8(167). Available from: DOI: 10.1186/s40168-020-00940-8

Walker A. 2013. Initial intestinal colonisation in the human infant and immune homeostasis. Annales Nestle. 63(2): 8-15. Available form: DOI: 10.1159/000354907

Weng M, Walker W. 2013. The role of gut microbiota in programming the immune phenotype. Journal of Developmental origins of Health and Disease. 4(3): 203-214. Available from: DOI: 10.1017/S2040174412000712

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