Skip to main content Accessibility help

Caesarean delivery, immune function and inflammation in early life among Ecuadorian infants and young children

  • A. L. Thompson (a1) (a2) (a3)


Caesarean delivery has been linked to a number of inflammatory conditions in childhood and adolescence. Yet the mechanisms underlying these associations and their generalizability across contexts with different postnatal feeding and pathogenic exposures remain unclear. This study tests the association between delivery type and three measures of immune function, inflammation, morbidity and leukocyte proportions, in Ecuadorian infants and children aged 6 months to 2 years. Data were collected from mother–child pairs participating in a nationally representative health and nutrition survey Encuesta Nacional de Salud y Nutricion (ENSANUT-ECU) conducted in 2012. The analytic sample includes 828 mothers and infants with delivery information and measured biomarkers. Poisson regression models were used to examine the association between delivery type and markers of immune function, controlling for maternal and infant characteristics, including age, sex, sociodemographic characteristics and medical indications. 40.8% (n=338) of sample infants and children were delivered by caesarean. Compared to those born vaginally, infants born by caesarean were less likely to have elevated C-reactive protein (CRP) [CRP>2 mg/l; risk ratio (RR): 0.76, 95% confidence interval (CI): 0.58–1.00] and more likely to have illness symptoms (RR: 1.22, 95% CI: 1.01–1.46) and elevated basophils (RR: 1.83, 95% CI: 1.03–3.25). No other immune cell proportions differed by delivery type. The results suggest that differences in the perinatal exposures accompanying caesarean delivery may alter immune development and function, particularly in the inflammatory response to infection and in cells involved in the allergic response, across infancy and early childhood. Understanding the pathways linking perinatal exposures to immune development is important for preventing the development of inflammatory conditions.


Corresponding author

*Address for correspondence: Amanda L. Thompson, 123W Franklin St, CB #8120, Chapel Hill, NC 27515, USA. E-mail:


Hide All
1. McDade, TW, Beck, MA, Kuzawa, C, Adair, LS. Prenatal undernutrition, postnatal environments, and antibody response to vaccination in adolescence. Am J Clin Nutr. 2001; 74, 543548.
2. McDade, TW, Beck, MA, Kuzawa, CW, Adair, LS. Prenatal undernutrition and postnatal growth are associated with adolescent thymic function. J Nutr. 2001; 131, 12251231.
3. McDade, TW, Kuzawa, CW, Adair, LS, Beck, MA. Prenatal and early postnatal environments are significant predictors of total immunoglobulin E concentration in Filipino adolescents. Clin Exp Allergy. 2004; 34, 4450.
4. McDade, TW, Rutherford, J, Adair, L, Kuzawa, CW. Early origins of inflammation: microbial exposures in infancy predict lower levels of C-reactive protein in adulthood. Proc Biol Sci. 2010; 277, 11291137.
5. Chen, W, Srinivasan, SR, Berenson, GS. Influence of birth weight on white blood cell count in biracial (black-white) children, adolescents, and young adults: the Bogalusa Heart Study. Am J Epidemiol. 2009; 169, 214218.
6. McDade, TW, Jones, MJ, Miller, G, et al. Birth weight and postnatal microbial exposures predict the distribution of peripheral blood leukocyte subsets in young adults in the Philippines. J Dev Orig Health Dis. 2018; 9, 198207.
7. Rautava, S, Ruuskanen, O, Ouwehand, A, Salminen, S, Isolauri, E. The hygiene hypothesis of atopic disease - An extended version. J Pediatr Gastr Nutr. 2004; 38, 378388.
8. Rook, GA, Lowry, CA, Raison, CL. Microbial ‘Old Friends’, immunoregulation and stress resilience. Evol Med Public Health. 2013; 2013, 4664.
9. Strachan, DP. Hay fever, hygiene, and household size. BMJ. 1989; 299, 12591260.
10. Blaser, MJ, Falkow, S. What are the consequences of the disappearing human microbiota? Nat Rev Microbiol. 2009; 7, 887894.
11. Gollwitzer, ES, Marsland, BJ. Impact of early-life exposures on immune maturation and susceptibility to disease. Trends Immunol. 2015; 36, 684696.
12. Kristensen, K, Henriksen, L. Cesarean section and disease associated with immune function. J Allergy Clin Immunol. 2016; 137, 587590.
13. Romero, R, Korzeniewski, SJ. Are infants born by elective cesarean delivery without labor at risk for developing immune disorders later in life? Am J Obstet Gynecol. 2013; 208, 243246.
14. Bager, P, Simonsen, J, Nielsen, NM, Frisch, M. Cesarean section and offspring’s risk of inflammatory bowel disease: a national cohort study. Inflamm Bowel Dis. 2012; 18, 857862.
15. Cardwell, CR, Stene, LC, Joner, G, et al. Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus: a meta-analysis of observational studies. Diabetologia. 2008; 51, 726735.
16. Leung, JY, Li, AM, Leung, GM, Schooling, CM. Mode of delivery and childhood hospitalizations for asthma and other wheezing disorders. Clin Exp Allergy. 2015; 45, 11091117.
17. Sevelsted, A, Stokholm, J, Bonnelykke, K, Bisgaard, H. Cesarean section and chronic immune disorders. Pediatrics. 2015; 135, e9298.
18. Thavagnanam, S, Fleming, J, Bromley, A, Shields, MD, Cardwell, CR. A meta-analysis of the association between Caesarean section and childhood asthma. Clin Exp Allergy. 2008; 38, 629633.
19. Thysen, AH, Larsen, JM, Rasmussen, MA, et al. Prelabor cesarean section bypasses natural immune cell maturation. J Allergy Clin Immunol. 2015; 136, 11231125 e1126.
20. Cho, CE, Norman, M. Cesarean section and development of the immune system in the offspring. Am J Obstet Gynecol. 2013; 208, 249254.
21. Dahlen, HG, Downe, S, Wright, ML, Kennedy, HP, Taylor, JY. Childbirth and consequent atopic disease: emerging evidence on epigenetic effects based on the hygiene and EPIIC hypotheses. BMC Pregnancy Childbirth. 2016; 16, 4.
22. Eisler, G, Hjertberg, R, Lagercrantz, H. Mimicking the stress of being naturally born improves the neonatal outcome after elective Caesarean section. Pediatr Res. 1998; 44, 442.
23. Duijts, L, Bakker-Jonges, LE, Labout, JA, et al. Perinatal stress influences lymphocyte subset counts in neonates. The generation R study. Pediatr Res . 2008; 63, 292298.
24. Dominguez-Bello, MG, Costello, EK, Contreras, M, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U A. 2010; 107, 1197111975.
25. Neu, J, Rushing, J. Cesarean versus vaginal delivery: long-term infant outcomes and the hygiene hypothesis. Clin Perinatol. 2011; 38, 321331.
26. Almanzar, G, Schonlaub, J, Hammerer-Lercher, A, et al. Influence of the delivery modus on subpopulations and replication of lymphocytes in mothers and newborns. Early Hum Dev. 2015; 91, 663670.
27. Weinberger, B, Vetrano, AM, Syed, K, et al. Influence of labor on neonatal neutrophil apoptosis, and inflammatory activity. Pediatr Res. 2007; 61, 572577.
28. Kaapa, P, Koistinen, E. Maternal and neonatal C-reactive protein after interventions during delivery. Acta Obstet Gynecol Scand. 1993; 72, 543546.
29. Logan, CA, Thiel, L, Bornemann, R, et al. Delivery mode, duration of labor, and cord blood adiponectin, leptin, and C-reactive protein: results of the population-based Ulm birth cohort studies. PLoS One. 2016; 11, e0149918.
30. Carrillo-Larco, RM, Miranda, JJ, Bernabé-Ortiz, A. Delivery by caesarean section and risk of childhood obesity: analysis of a Peruvian prospective cohort. Peer J. 2015; 3, e1046.
31. Veile, A, Kramer, KL. Childhood body mass is positively associated with cesarean birth in Yucatec Maya subsistence farmers. Am J Hum Biol. 2017; 29, e22920.
32. Betran, AP, Ye, J, Moller, AB, et al. The increasing trend in caesarean section rates: global, regional and national estimates: 1990–2014. PLoS One. 2016; 11, e0148343.
33. Pearce, N, Ait-Khaled, N, Beasley, R, et al. Worldwide trends in the prevalence of asthma symptoms: phase III of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax. 2007; 62, 758766.
34. Lavin, T, Franklin, P, Preen, DB. Association between caesarean delivery and childhood asthma in India and Vietnam. Paediatr Perinat Epidemiol. 2017; 31, 4754.
35. Nathan, AM, de Bruyne, J, Khalid, F, Arumugam, K. Caesarean section and asthma in Malaysian children: a case-control study. Asian Pac J Allergy Immunol. 2012; 30, 204208.
36. Al-Kubaisy, W, Ali, SH, Al-Thamiri, D. Risk factors for asthma among primary school children in Baghdad, Iraq. Saudi Med J. 2005; 26, 460466.
37. Garcia-Marcos, L, Mallol, J, Sole, D, Brand, PL, Group, ES. International study of wheezing in infants: risk factors in affluent and non-affluent countries during the first year of life. Pediatr Allergy Immunol. 2010; 21, 878888.
38. Prior, E, Santhakumaran, S, Gale, C, et al. Breastfeeding after cesarean delivery: a systematic review and meta-analysis of world literature. Am J Clin Nutr. 2012; 95, 11131135.
39. Freire, WB, Belmont, P, Rivas-Marino, G, et al. TOMO ii Encuesta Nacional de Salud y Nutricion. Salud Sexual y Reproductiva. 2015. Ministerio de Salud Publica/Instituto Nacional de Estadistica y Censos: Quito, Ecuador.
40. Orkin S, Nathan D, Ginsburg D, et al. Nathan and Oski’s Hematology of Infancy and Childhood. 2009 7th ed. Saunders Elsevier, Philadelphia.
41. Thompson, AL, Houck, KM, Adair, L, et al. Pathogenic and obesogenic factors associated with inflammation in Chinese children, adolescents and adults. Am J Hum Biol. 2014; 26, 1828.
42. Wander, K, Brindle, E, O’Connor, KA. Sensitivity and specificity of C-reactive protein and alpha(1)-acid glycoprotein for episodes of acute infection among children in Kilimanjaro, Tanzania. Am J Hum Biol. 2012; 24, 565568.
43. Greenland, S. Model-based estimation of relative risks and other epidemiologic measures in studies of common outcomes and in case-control studies. Am J Epidemiol. 2004; 160, 301305.
44. Spiegelman, D, Hertzmark, E. Easy SAS calculations for risk or prevalence ratios and differences. Am J Epidemiol. 2005; 162, 199200.
45. Magne, F, Puchi Silva, A, Carvajal, B, Gotteland, M. The elevated rate of cesarean section and its contribution to non-communicable chronic diseases in Latin America: the growing involvement of the microbiota. Front Pediatr. 2017; 5, 192.
46. WHO. WHO Statement on Caesarean Section Rates. 2015.
47. Huurre, A, Kalliomaki, M, Rautava, S, et al. Mode of delivery - effects on gut microbiota and humoral immunity. Neonatology. 2008; 93, 236240.
48. Mukai, K, Galli, S. Basophils. In: eLS. 2013. John Wiley and Sons, Ltd: Chichester.
49. Junge, KM, Hornig, F, Herberth, G, et al. The LINA cohort: cord blood eosinophil/basophil progenitors predict respiratory outcomes in early infancy. Clin Immunol. 2014; 152, 6876.
50. Almqvist, C, Oberg, AS. The association between caesarean section and asthma or allergic disease continues to challenge. Acta Paediatr. 2014; 103, 349351.
51. Collado, MC, Cernada, M, Bauerl, C, Vento, M, Perez-Martinez, G. Microbial ecology and host-microbiota interactions during early life stages. Gut Microbes. 2012; 3, 352365.
52. Andersson, Y, Hammarstrom, ML, Lonnerdal, B, et al. Formula feeding skews immune cell composition toward adaptive immunity compared to breastfeeding. J Immunol. 2009; 183, 43224328.
53. Belderbos, ME, Houben, ML, van Bleek, GM, et al. Breastfeeding modulates neonatal innate immune responses: a prospective birth cohort study. Pediatr Allergy Immunol. 2012; 23, 6574.
54. Bueso, A, Figueroa, M, Cousin, L, et al. Poverty-associated risk factors for wheezing in the first year of life in Honduras and El Salvador. Allergol Immunopathol (Madr). 2010; 38, 203212.
55. Jacomo, RH, Lozano, VF, da Cunha Neto, JG, Costa, SS. What’s the meaning of basophilia in Sysmex XE-2100? Arch Pathol Lab Med. 2011; 135, 415.
56. Becker, PH, Fenneteau, O, Da Costa, L. Performance evaluation of the Sysmex XN-1000 hematology analyzer in assessment of the white blood cell count differential in pediatric specimens. Int J Lab Hematol. 2016; 38, 5463.
57. Lee, BW, Yap, HK, Chew, FT, et al. Age- and sex-related changes in lymphocyte subpopulations of healthy Asian subjects: from birth to adulthood. Cytometry. 1996; 26, 815.
58. Lugada, ES, Mermin, J, Kaharuza, F, et al. Population-based hematologic and immunologic reference values for a healthy Ugandan population. Clin Diagn Lab Immunol. 2004; 11, 2934.
59. Georgountzou, A, Papadopoulos, NG. Postnatal innate immune development: from birth to adulthood. Front Immunol. 2017; 8, 957.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Journal of Developmental Origins of Health and Disease
  • ISSN: 2040-1744
  • EISSN: 2040-1752
  • URL: /core/journals/journal-of-developmental-origins-of-health-and-disease
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed