Asthma and Cesarean Section

Editorial

Asthma is chronic disease of multifactorial etiologic and exposure perinatal factors can determine the development of airway inflammation. High prevalence of asthma in developing countries accompanies the increase in the Cesarean Section (CS) rate in the same period [1,2]. Cesarean births in some countries of Latin America reach the 50% prevalence, in the Brazilian, public and private health services the rate CS is considerate highest in the world [3,4 ]. However, the association between CS and asthma is still a controversial issue with conflicting data in the literature due to potential confounding of several other determinants of asthma [5].

The mechanism to explain its association between CS and asthma refers to the hygiene hypothesis. Decrease exposure to certain types of microorganisms early in life would lead to insufficient stimulation of T1 lymphocytes and consequences predominance of allergic response of the type T2, responsible for the development of asthma and allergic reactions [6]. In children born CS the initial colonization of intestinal micro flora is composed by bacteria from colonization of the skin and those related to the hospital environment and these bacteria are capable of modulating the type of immune response to the type T2 [7].

The EPIC hypothesis (Epigenetic Impact of Childbirth) has also been proposed for explain the association between CS and asthma; this suggests that the genome of fetus undergoes remodelling in chromantin architecture and DNA methylation during the intrapartum period and cause susceptibility to diseases. Children born CS have higher DNA methylation than children born of vaginal delivery [8]. The third hypothesis to explain the association between CS and asthma is the lowest rate of onset and duration of exclusive breastfeeding in children born cesarean, the maternal milk would have a protective effect for asthma due to the immunomodulators, low proportion of IL10 and more of IL13 and gamma interferon [9].

Studies that assessed the association between CS and asthma presented different results. Association between asthma and CS was reported by Roduit, et al. [10], in a prospective cohort study of 2.917 children, found a significant association between delivery by CS and asthma OR = 1.77 CI 95% (1.03-1.32) and the risk was increased in the presence of parental history of atopy. Almqvist, et al. [11] evaluated a retrospective cohort of 87,500 cesarean births and risk of asthma in children and adolescents CS was associated with the use of asthma drugs OR: 1.13; 95% CI (1.04-1.24) and diagnosis of asthma OR: 1.20 95% CI (1.05-1.37), adjusted by family history of atopy, weight at birth, gestational age, gender, Apgar score and age maternal. Tollanes, et al. [12] found a high risk for asthma in children born of emergency CS with OR: 1.42; CI 95 (1.12-1.62) and elective CS with OR 1.59; 95% CI (1.44-1.55) being the highest risk for asthma in preterm infants. Kero, et al. [13] evaluated records of 59,927 children and found association between CS and asthma with OR: 1.21; CI 95% (1.08-1.36) and atopic asthma OR: 2.2; 95% CI (1.06-4.64), adjusted for maternal age, gender and born. Salam et al. [14]. Evaluated a cohort of 3,464 children born =37 weeks of gestation and birth weight =2,500 kg and a structured asthma questionnaire was applied. CS represented risk factor for asthma OR: 1.33; CI 95% (1.01-1.75). Bager, et al. [15] evaluated 9,722 women from a cohort in the Denmark for type of delivery, gestational age, weight and height at birth, asthma and rhinitis obtained by the local registry system and CS associated with asthma OR: 1.33;CI 95% (1.2-1.74) but not allergic rhinitis OR: 1.16; 95% CI (0.90-1.49). Gessner and Chimonas 23 evaluated 37,349 children aged 5-9 years of a retrospective birth cohort. Asthma was confirmed by the Standard International Classification of Diseases 9th Revision codes. Asthma was associated with preterm birth but not with small for gestational age status. CS represented risk factor for asthma or hospitalizations for asthma OR: 1.4; 95% CI (1.08-2.2).

In a prospective cohort study of 12,367 children Maitra, et al. [16]. Found no association between delivery by CS and asthma (OR= 1.14; 95% CI 0.9–1.4). Brandão, et al. [17] evaluated 672 children with asthma and allergic rhinitis found no association between CS and asthma however there was association between CS and allergic rhinitis, adjusted for the main confounding variables for asthma. Mallen, et al. [18] using population-based registers evaluated conditions of birth and asthma, allergic rhinitis, eczema and hay fever in 567 adults. CS was not associated with asthma OR: 1.71; 95% CI (0.76-6.84), rhinitis, eczema or hay fever. Vonk, et al. [19] evaluated 597 adults using birth data on labour for delivery type and diagnosis for asthma and atopy after 20-year follow-up, CS was not risk factor for asthma OR: 1.77; 95% CI (0.98-3.51). Bernsen, et al. [20] evaluated 1,797 children in a cohort through birth data records on type of birth and asthma, eczema and allergy at six years of age. CS was not a risk for asthma OR: 1.03; 95% CI (0.51-2.08). Nathan, et al. [21] evaluated 156 children in a control case study at the age of 3-15 years. Seventyeight children with diagnosis of asthma and seventy-eight controls were evaluated for CS. There was no association between CS and asthma OR: 1.21; 95% CI (0.6-2.41). Rusconi, et al. [22] performed a cross-sectional study in 15,609 children diagnosed with asthma less than five years old of age. CS was associated with asthma and atopy. The association was of greater magnitude in children of no atopic parent. The perinatal variables, gestational age and low birth weight had low frequency in children of the CS.

A meta-analysis study [24] found association between CS and atopy, the proportion of cases attributed the CS was 1% to 4%, suggesting that the increase in CS in the last decades may have contributed to high prevalence of allergic diseases. Gestational age is an important confounding variable to be considered in the association between CS and asthma. Children born premature have a higher risk of asthma compared to children born to term. The frequency of gestational age <37 weeks was evaluated in several studies in children born cesarean and vaginal delivery. Some of these studies [10,15] verified the relationship between prematurity and risk of asthma, while others studies [23,25] evaluated the association between CS, asthma and gestational age. Children born of low age gestational, disorders present early respiratory distress and risk of respiratory infection and asthma [23]. Maternal smoking in pregnancy or environmental smoking is a risk factor to asthma [26].

CS was associated with asthma and atopy in most studies and the low gestational age, smoking during pregnancy, breastfeeding and low birth weight are associated risk factors to asthma but were not evaluated together as confounding variables in studies. The positive association between CS and asthma, remaining controversial.

References

1. Asher MI, Montefort S, Björkstén B, Lai CK, Strachan DP, Weiland SK, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC phases one and three repeat multicountry cross-sectional surveys. Lancet. 2006; 368:733-743.
2. Brandão HV, Batista W, Cruz CMS, et al. Prevalence and severity of asthma, rhinitis and atopic eczema among children and adolescents using the international study of asthma and allergies in childhood (ISAAC). Braz J Allergy Immunol. 2013; 3: 170-174.
3. Patah LEM, Malik AM. Models of childbirth care and cesarean rates in different countries. Rev Saude Publ. 2011; 451: 185-194.
4. Bulletin of the World Health Organization.
5. Kero J, Gissler M, Grönlund MM, Kero P, Koskinen P, Hemminki E, et al. Mode of delivery and asthma-is there a connection? Pediatr Res. 2002; 52: 6-11.
6. Strachan DP. Hay fever, hygiene and household size. BMI. 1989; 299: 1259-1260.
7. Gronlund MM, Lehtonen OP, Eerola E, Kero P. Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after caesarean delivery. J Pediatr Gastroenterol Nutr. 1999; 28:19-25.
8. Dahlen HG, Kennedy HP, Anderson CM, Bell AF, Clark A, Foureur M, et al. The EPIIC hypothesis: Intrapartum effects on the neonatal epigenome and consequent health outcomes. Med Hypotheses. 2013; 80: 656-662.
9. Chien LY, Tai CJ. Effect of delivery method and timing of breafeeding initiation on breafeeding outcome in Taiwan. Birth. 2007; 34: 123-130.
10. Roduit C, Scholtens S, de Jongste JC, Wijga AH, Gerritsen J, Postma DS, et al. Asthma at 8 years of age in children born by caesarean section. Thorax. 2009; 64: 107-113.
11. Almqvist C, Cnattingius S, Lichtenstein P, Lundholm C. The impact of birth mode of delivery on childhood asthma and allergic diseases-a sibling study. Clinical Exp Allergy. 2012; 42: 1369-1376.
12. Tollanes MC, Moster D, Daltveit AK, Irgens LM. Cesarean section and risk and severe childhood asthma: a population based cohort study. J Pediatr. 2008; 153: 112-116.
13. Kero J, Gissler M, Grönlund MM, Kero P, Koskinen P, Hemminki E, et al. Mode of delivery and asthma is there a conection? Pediatr Res. 2002; 52: 6-11.
14. Salam MT, Margolis HG, McConnell R, McGregor JA, Avol EL, Gilliland FD. Mode of delivery is associated with asthma and allergy occurrences in children. Ann Epidemiol. 2006; 16: 341-346.
15. Bager P, Wohlfahrt J, Westergaard T. Cesearean delivery and risk of atopy and allergic disease: meta-analyses.Clin Exp Allergy. 2008; 38: 634-642.
16. Maitra A, Sherriff A, Northstone K, Strachan D, Henderson U. Mode of delivery is not associated whaberg ith asthma or atopy in childhood. Clin Exp Allergy. 2004; 34: 1349-1355.
17. Brandão HV, Vieira GO, de Oliveira Vieira T, Camargos PA, de Souza Teles CA, Guimarães AC, Cruz AA, et al. Increased risk of allergic rhinitis among children delivered by cesarean section: a cross-sectional study nested in a birth cohort. BMC Pediatrics. 2016; 16: 57.
18. Mallen CD, Mottram S, Wynne-Jones G, Thomas E. Birth related exposure and asthma and allergy in adulthood. J Asthma. 2008; 45: 309-312.
19. Vonk JM, Boezen HM, Postma DS, Schouten JP, van Aalderen WM, Boersma ER. perinatal risk factors for bronchial hyperresponsiveness and atopy after a follow-up of 20 years. J Allergy Clin Immunol. 2004; 114: 270-276.
20. Bernsen RM, de Jongste JC, Koes BW, Aardoom HA, van der Wouden JC. Perinatal characteristics and obstetric complications as risk factors for asthma, allergy and eczema at the age 6 years. Clin Exp Allergy. 2005; 35: 1135-1140.
21. Nathan AM, Bryne J, Knalid F, Arumugan K. Cesarean section and asthma in Malasian children: a case-control study. Asian Pac J Allergy Immunol. 2012; 30: 204-208.
22. Rusconi F, Galassi C, Forastiere F, Bellasio M, De Sario M, Ciccone G, et al. Maternal complications and procedures in pregnancy and at birth and wheezing phenotypes in children. Am J Respir Crit Care Med. 2007; 175: 16-21.
23. Gessner BD, Chimonas MA. Astham is associated with preterm birth but not small for gestational age status among a population based cohort of Medicaid-enrolled children < 10 years of age. Thorax. 2007; 62: 231-236.
24. Thavagnanam S, Fleming J, Bromley A, Shields MD, Cardwell CR. A meta-analysis of the association between cesarean section and childhood asthma. Clin Exp Allergy. 2008; 38: 629-633.
25. Metsälä J, Kilkkinen A, Kaila M, Tapanainen H, Klaukka T, Gissler M, et al. Perinatal factors and risck of asthma in childhood-A population based register study in Finland. Am J Epidemiol. 2008; 168: 170-178.
26. Joad JP. Smoking and pediatric respiratory health. Clin Chest Med. 2000; 21: 37-46.