- Research article
- Open Access
- Open Peer Review
Increased risk of allergic rhinitis among children delivered by cesarean section: a cross-sectional study nested in a birth cohort
© Brandão et al. 2016
- Received: 11 April 2015
- Accepted: 21 April 2016
- Published: 27 April 2016
Few studies have evaluated the association between delivery by cesarean section (CS) and asthma, allergic rhinitis and chronic rhinitis and whether this association is different in children with and without a family history of asthma. This study aims to investigate whether children born by CS have a higher chance to develop asthma, allergic rhinitis and chronic rhinitis and to evaluate the influence of parental history of asthma on these associations.
This is a cross-sectional study of 672 children nested in a birth cohort evaluated at 6-years of age. Asthma and chronic/allergic rhinitis were identified by means of the mother’s responses to the ISAAC questionnaire. The association between CS, asthma, chronic rhinitis and allergic rhinitis was evaluated by multivariable logistic regression. The evidence of effect modification of parental history of asthma on the association CS and outcomes was examined by introducing interactions terms in the logistic regression models adjusting for confounders.
Asthma was not associated with birth by CS irrespective of parental history of asthma (odds ratio (OR) 1.03; 95 % CI 0.61–1.74). Chronic rhinitis and allergic rhinitis were both significantly associated with birth by CS but only in the subgroup of children with by parental history of asthma (OR 1.56; 95 % CI 1.04–2.34) and (OR 1.60; 95 % CI 1.01–2.55) respectively, after adjustment for confounders. The parental history of asthma was a effect modifier in the association between CS, chronic rhinitis and allergic rhinitis (p for effect modification = 0.10 and 0.02, respectively).
CS increases the risk of chronic rhinitis and allergic rhinitis in children at 6 years of age with parental history of asthma. Health professionals must be alerted with regard to the increased risk of allergic rhinitis and made aware this is another reason to avoid unnecessary CS.
- Allergic rhinitis
The prevalence of asthma and chronic rhinitis are high in Brazil [1, 2]. The average prevalence rate of symptoms of asthma in the age range 6 and 7 years is 24 % and for chronic rhinitis, 25.7 % . In Feira de Santana, State of Bahia, the prevalence of symptoms of chronic rhinitis and allergic rhinitis was 33 and 17 %, respectively, in the year of the 2003, among the highest in Brazil [2, 3]. The prevalence rate of asthma physician-diagnosed among adolescents is 12.4 and 6.4 % in children 6 to 7 years old [3, 4].
The frequency of birth by cesarean section (CS) is growing fast in the Brazilian public and private health services. The rate of CS among all births was 33.8 % in 2004 and increased to 45.9 % in 2008 , being considerated the highest in the world. The World Health Organization recommends a rate of CS of less than 15 %. However, in the majority of countries the actual rate exceeds this recommendation .
Several studies have demonstrated an association between symptoms of asthma and allergic rhinitis with CS, but there are controversial results reports . Some cohort studies demonstrated an association between CS and asthma in children, with odds ratio (OR) ranging from 1.09 to 1.82 [8, 9]; whereas other studies have found no association [10, 11]. In Brazil, the study of Menezes et al. evaluated the association between CS and asthma in children in two age ranges and did not find a significant association . A meta-analysis has favored a positive association with an estimate increased risk of 20 % for having asthma among children born by CS (Thavagnanam et al., 2008) .
There are a few studies that have evaluated the association between allergic rhinitis, asthma and birth by CS in children with genetic predisposition, and in those that have demonstrated a positive association, the OR ranged between 1.37 and 1.80 [14, 15]. Nevertheless, a meta-analysis have not demonstrated a significant increase in the risk of allergic rhinitis in children born by CS (Bager et al., 2003) .
The aim of the present study was to investigate whether children born by CS have a higher chance of developing asthma and allergic rhinitis at 6 years of age, looking for other potential risk factors in a birth cohort and evaluating family history of asthma as a possible effect modifier.
This is a cross-sectional study nested in a birth cohort.
A total of 684 mother-child dyads provided the basis for this study, as they were followed-up from birth and the children could be reviewed at 6 years of age. The births occurred in all public and private hospitals in the municipal district in the period from April 2004 to March 2005 in Feira de Santana, a city (608,000 inhabitants) located in Bahia, Northeast in Brazil.
The study was conducted in all ten hospitals of the city (namely, Emec, Cleriston Andrade, Inácia Pinto dos Santos, D. Pedro de Alcântara, São Mateus, Mater day, Santa Cecília, Stela Gomes, Unimed and Casa de Saúde Santana) in the period of 1 year, with the inclusion of all the children that were born in the period of two consecutive months in each hospital (n = 1.344).
The sample size calculation used for this study was estimated by the program OpenEpi (Open Source Epidemiologic Statistics for Public Health, version 2.3.1) adopting the following parameters: interval of confidence of 95 %, statistical power of 80 %, statistical significance α = 0.05, estimated risk of odds ratio equal to 2 for association of CS with asthma and a difference in prevalence of 7.9 %. The sample size estimated was 582 children, with 291 in each group (CS and vaginal delivery). However, considering the possibility of losses we included in the study all 684 children from the cohort we were able to find. There was no difference in baseline characteristics (gender of newborn, birth weight, gestational age) between participants and children lost to follow up. The losses were probably related to the frequent mobility of the low-income population of this region.
The following non-inclusion criteria were used upon enrollment for the study: children born of mothers who presented complications during gestation (eclampsia, placenta previa) or in the neonatal period (perinatal hyoxia, newborn respiratory distress syndrome). All women included in the study provided written informed consent.
The exposure of interest was delivery by CS (including elective and emergency CS) and vaginal delivery.
Definitions of asthma, chronic rhinitis and allergic rhinitis
The dependent variables analyzed were active asthma/severe asthma and chronic /allergic rhinitis. The criteria adopted in this study for the definition of asthma, chronic rhinitis and allergic rhinitis were same adopted from the ISAAC study questionnaires . A standard questionnaire was applied to the mothers at home visits when the child was 6 years old.
For the identification of active and severe asthma the following questions were considered: wheezing in the last 12 months (to identify active asthma symptoms) and episodes of wheezing that would prevent the child from speaking two or more words between one breath and the other (severe asthma episode). For the identification of rhinitis the following questions were considered: nasal symptoms of rhinorrhea (runny nose), obstruction, itching and sneezing in the last 12 months, without a flu or cold (to identify chronic rhinitis) and symptoms nasal accompanied by itchy or watery eyes in the last 12 months (as the indicator of allergic rhinitis).
The following factors that could influence on the association of asthma with CS were evaluated: mother's age (<20 years, ≥ 20 years); family income (up to 2 minimum wages, > 2 minimum wages); mother's educational level (up to 8 years of schooling, > 8 years of schooling); maternal smoking during gestation (yes, no); gestational age (<37 weeks, ≥37 weeks); gender of the newborn (male, female); birth weight (<2.500 kg, ≥2.500 kg); breastfeeding up to 4 month (yes, no); number of persons who sleep in the same room with the child (<4 people, ≥4 people); use of nursery before 2 years of age (yes, no); history of a clinical condition compatible with acute viral bronchiolitis in the 1st year of life (yes, no) and physician-diagnosed pneumonia ever (yes, no); type of hospital (private, public). Parental history of asthma was stratified into two groups as follows, parental history of asthma and no parental history of asthma.
Information related to the perinatal period was obtained in the first 72 h after birth, by means of a questionnaire applied to the mothers by trained interviewers, and confirmed by records on medical charts. Data related to the postnatal period were obtained in scheduled home visits during the period of follow-up of the children in cohort.
The samples characteristics were compared by the chi-square test and Student t test, according to the type of delivery. The prevalence estimate according to type of delivery for active/severe asthma, allergic/chronic rhinitis were calculated by dividing the number of positive responses to the given question in the ISSAC questionnaire by the total number of participants expressed as percentages.
The associations between CS, asthma, allergic and chronic rhinitis were evaluated by using a multivariate logistic regression test adjusting for potential confounders (family income, educational level; smoking during gestation; gestational age; birth weight; breastfeeding up to 4th month; number of persons who sleep in the same room as the child; use of nursery before age 2 years; physician-diagnosed pneumonia ever). A p-value of <0.05 was considered to be statistically significant. The effect modification of parental history of asthma on the association between CS, asthma, chronic rhinitis and allergic rhinitis was checked by including an interaction term between parental history of asthma and CS in the multivariable logistic regression models. Evidence for effect modification was assessed by the Likelihood Ratio Test (comparing the goodness of fit of models with and without the interaction term).
The data were analyzed with the Program SPSS version 4 (Statistical Package of Social Sciences) and by STATA 13 (StataCorp LP, College Station, Texas, USA).
The protocol and respective informed consent for the project were approved by the Research Ethics Committee of Feira de Santana State University (Report No. 04775012.8.0000.0053). Furthermore, all ten participating hospitals only allowed data collection in their respective units upon submission of approval by the Committee of Research Ethics. All women included in the study provided written informed consent.
In this study 672 mother-child dyads (98.2 %) of the 684 being currently followed-up in the cohort were included in analysis. The 12 remaining dyads were not identified because of recent change of their home addresses.
Characteristics of mothers and children delivered by cesarean and vaginal delivery
Total (n = 672)
Cesarean delivery (n = 325)
Vaginal delivery (n = 347)
Current age of the child in months (X ± SD) a
Age of the mother at the time of birth
< 20 years
≥ 20 years
Gender of newborn
Weight at birth
< 2.500 kg
≥ 2.500 kg
Up to 2 minimum wages
> 2 minimum wages
Mother’s schooling level
Up to 8 years of schooling
> 8 years of schooling
Exclusive breastfeeding up to the 4th month
Smoking during pregnancy
Number of persons who sleep in the room with the child
Frequency at nursery to the age of 2 years
Pneumonia ever in life
Bronchiolitis in the 1st year
The overall prevalence of asthma symptoms was 13.8 %, being 14.8 % and 13 % among subjects born by CS and vaginal delivery respectively. There was no statistically significant difference in the prevalence of symptoms of active asthma or severe asthma episodes between the children born by CS or vaginal delivery.
Association between type of delivery, asthma and rhinitis
OR (95 % CI); p value
(n = 347)
Active asthma a
48 (14.8 %)
45 (13 %)
1.16 (0.75–1.80); 0.499
1.03 (0.61–1.74); 0.883
27 (8.3 %)
22 (6.3 %)
1,31 (0.76–2.25); 0.327
1.15 (0.47–2.84); 0.746
Chronic rhinitis b
138 (42.5 %)
110 (31.7 %)
1.59 (1.16–2.18); 0.004
2.47 (1.56–3.89); <0.001
92 (28.4 %)
66 (19 %)
1.68 (1.17–2.42); 0.004
1.86 (1.18–2.93); 0.007
Active and severe asthma symptoms were not associated with delivery by CS, even after the adjustment for the following covariates: gestational age, birth weight, breastfeeding up to the 4th month, mother’s smoking during gestation, family income, mother's educational level, number of siblings, number of persons sleeping in the same room as the child, attendance to nursery before the age of 2 years and physician-diagnosed pneumonia ever. The frequency of CS section and vaginal delivery in children with active asthma was 51.6 % versus 48.4 % respectively (adjusted OR 1.16; 95%IC 0.75–1.80). Chronic and allergic rhinitis were associated with delivery by CS in the bivariate analysis as well as in the multivariate logistic regression adjusted for the same covariates as for asthma (Table 2).
Association between type of delivery, asthma and rhinitis according to parental history of asthma (n = 672)
No parental history of asthma (n = 496)
Parental history of asthma (n = 176)
OR (95 % CI)
OR (95 % CI)
OR (95 % CI)
OR (95 % CI)
29 (12.2 %)
19 (20.4 %)
27 (10.5 %)
18 (19,4 %)
18 (7.6 %)
11 (12.4 %)
11 (4.3 %)
9 (10.3 %)
99 (41.6 %)
39 (44.8 %)
72 (27.9 %)
38 (42.7 %)
63 (26.6 %)
29 (33.3 %)
45 (17.4 %)
21 (23.6 %)
Therefore the effect modifier of parental history of asthma was demonstrated in children born by CS, as they were significantly more likely to develop allergic rhinitis and chronic rhinitis, when exposed to the two variables combined (p value for Likelihood Ratio Test for effect modification = 0.02 and 0.10, respectively) (Table 3).
This study demonstrated a positive association between CS, chronic rhinitis and allergic rhinitis, after adjusting for potential confounders, but the association was significant only in children at higher risk of chronic rhinitis and allergic rhinitis as indicated by parental history of asthma. CS was not significantly associated with symptoms of asthma at age of 6 years in our study population. A cross-sectional study by Kolokrotoni et al.  found a positive association between CS, asthma and atopic sensitization in children aged 8–9 years. When children were stratified by family history of allergy, the association between CS and atopic sensitization was more pronounced but this was not the case for asthma outcomes. While more than a two-fold increase in the odds of being atopic was observed in children with a family history of allergy if born by CS, no association was observed in children without a family history of allergies.
The diagnosis criteria of active asthma considered in the present study was based on symptoms of the disease in the 12 months before the application of the ISAAC questionnaire, ruling out the cases of transient wheezing at an earlier age.
The possibility of selection bias doesn’t seem to be relevant in the present study, because children born by CS did not differ significantly from those born by vaginal delivery with regard to the main confounding variables (gestational age, birth weight, time of exclusive breastfeeding and mother smoking during gestation). Moreover, there were not differences between the proportions of exclusions due to complications during gestation or related to birth, such as differences in proportions of newborns who presented perinatal respiratory complications. The absence of association between CS and asthma may be explained because the majority of cases of symptoms of asthma related symptoms reported in urban centers in Brazil have not been attributed to atopy, as demonstrated in a study in children conducted in Salvador-Bahia, just 100 km from Feira de Santana, where the present study was conducted, by Cunha et al. .
Previous studies that assessed the association between CS and asthma presented different results. Roduit et al. , in a prospective cohort study of 2.917 children, found a significant association between delivery by CS and asthma (OR = 1.77) and the risk was increased in the presence of parental history of atopy. In a prospective cohort study of 12,367 children, Maitra et al.  found no association between delivery by CS and asthma (OR = 1.14; 95%CI 0.9–1.4). In two populations included in a cohort study conducted in Southern of Brazil by Menezes et al. , no significant association was found between the type of birth and dyspnea at 4 years of age (OR = 0.96), nor from 4 to 11 years (OR = 1.18) neither at 15 years (OR = 1.02). A meta-analysis conducted by Bager et al. , found a significant increase in the risk for asthma in children delivered by CS with (OR = 1.18;95%CI1.05–1.32) and risk for allergic rhinitis with (OR = 1.24;95%CI 1.08–1.43) . In another meta-analysis, Thavagnanam et al. also found an increased risk for asthma in children delivered by CS (OR = 1.22; 95%CI 1.14–1.29) . However, in these analyses there was high heterogeneity among the studies. They differed in many issues such as definition of asthma, age of the children when the diagnosis of asthma was made, in the study design, evaluation of environmental factors, time duration of exclusive breastfeeding and the use previous of BCG vaccination [21, 22].
The significant association between delivery by CS, chronic and allergic rhinitis observed in the present study was also identified in the studies carried out by Pistiner e et al. (OR = 1.80); Renz-Polster e et al. (OR = 1.37); Salam e et al. (OR = 1.57) [8, 14, 15]. Other studies found no association between delivery by CS and allergic rhinitis: Park e et al. (OR = 1.14); Xu e et al. (OR = 1.28); Mallen e et al. (OR = 2.82) [10, 23, 24]. Parental history of atopy is considered an important risk factor for the development of asthma and atopic diseases , and is a potential effect modifier in the evaluation of the association between delivery by CS, asthma, allergic rhinitis and atopic sensitization [14, 15, 17]. In our study, CS was associated allergic rhinitis and chronic rhinitis only in children with parental history of asthma, which suggests that the association between CS and allergic rhinitis and CS and chronic rhinitis could be dependent on the genetic predisposition. Our finding is consistent with the results of study of Pistiner e et al. which found increased risk of allergic rhinitis among children with a parental history of atopy but did not find any evidence of a positive association between CS and asthma in children with parental history of atopy.
The controversial reports on the association between allergic rhinitis and delivery by CS may be due to the different diagnostic criteria considered for the definition of allergic rhinitis, or the presence of confounding factors, such as maternal smoking during gestation, mother's history of asthma, and primiparity . In the present study, the inclusion of the main confounding variables in the multivariate analysis of the association between delivery by CS and allergic rhinitis might have contributed to a greater discrimination of the findings.
In the present study the birth rate by CS was higher in children born in private hospital, reproducing the current situation of the type delivery that occurs in Brazil . Therefore differences between children born by CS and vaginal delivery may be related to socioeconomic differences between children born in public health services versus private hospitals.
The possible biological mechanism that may explain the direct association between delivery by CS and allergic rhinitis could be related to the hygiene hypothesis: the characteristics of the intestinal microbiota in children born by CS is different from that found among children born by vaginal delivery . The intestinal microflora of children born by vaginal delivery is composed of bacteria from the vaginal flora by exposure while in the birth canal, whereas the intestinal biome of children born by CS is composed of bacteria from colonization of the skin and those related to the hospital environment . According to the hygiene hypothesis, there would be a predominance of the immunologic response of the Th2 type in children born by CS, due to the lack of physiological modulation of the immune system conferred by the natural biome. That condition entails the later development of atopic asthma, allergic rhinitis and other atopic diseases . Children born by CS present elevated levels of IL-13 and interferon γ in the umbilical cord and lower levels of IL-10, a regulatory cytokine .
The limitations of our study could be related to the lack of a multilevel approach analysis given the 10 institutions where participants were selection; the study design not robust enough to infer causation, as it did not allow the collection of biomarkers of atopy (skin prick tests or specific IgE), which could have reinforced the causality association by bringing in mechanistic evidence; we had no stool cultures to examine the type of intestinal microflora present in the children born by different methods, which could also bring further evidence to the theoretical explanation; possible misclassification due to self-reported of outcomes, as to parental history of asthma related to mothers; lack of classification of the CS type (emergency and elective), considering that babies born through emergency CS might be at less risk of allergies due to the exposure of the children to vaginal flora during labor. Despite these limitations, the results were similar to previous ones carried out in different settings and with different populations, and provide further evidence to fill the gap of knowledge on the association between, chronic and allergic rhinitis in children with parental history of asthma.
Our results indicate that elective CS increases significantly the risk of developing chronic rhinitis and allergic rhinitis, chronic diseases that imply in recurring discomfort and impaired quality of life among children with a family predisposition for asthma.
In conclusion, birth by CS was associated with both chronic rhinitis and allergic rhinitis in children with parental history of asthma, in this cross sectional study nested in a birth cohort.
The work was supported by grants from the Research Support Foundation of the State of Bahia (FAPESB).
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- Asher MI, Montefort S, Bjorkesten B, 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(9537):733–43.View ArticlePubMedGoogle Scholar
- Brandão HV, Batista W, Cruz CMS, et al. Prevalence and severity of asthma, rhinitis and atopic eczema among children and adolescents using the inernational study of asthma and allergies in childhood (ISAAC). Braz J Allergy Immunol. 2013;3:170–4.Google Scholar
- Solé D, Wandalsen GF, Camelo-Nunes IC, Naspitz C. ISAAC-grupo brasileiro. Prevalência de sintomas de asma, rinite e eczema atópico entre crianças e adolescentes brasileiros identificados pelo international study of asthma and allergies (ISAAC)-fase 3. J Pediatr. 2006;82(5):341–6.View ArticleGoogle Scholar
- Barreto ML, de Ribeiro-Silva R C, et al. Prevalence of asthma symptoms among adolescents in brazil: national adolescent school-based health survey (PeNSE 2012). Rev Bras Epidemiol. 2014;17 Suppl 1:106–15.View ArticlePubMedGoogle Scholar
- Patah LEM, Malik AM. Models of childbirth care and cesarean rates in different countries. Rev Saude Publ. 2011;451(1):185–94.View ArticleGoogle Scholar
- Bulletin of the World Health Organization. Available at: http://www.who.int/bulletin/volumes/91/12/13-117598/en/. published 2010. Accessed 23 April 2014.
- Kero J, Gessler M, Groulund MM. Mode of delivery and asthma-is there a connection? Pediatr Res. 2002;52(1):6–11.PubMedGoogle Scholar
- Renz-Polster H, David MR, Buist AS, et al. Caesarean section delivery and the risk of allergic disorders in childhood. Clin Exp Allergy. 2005;35:1466–72.View ArticlePubMedGoogle Scholar
- Tollânes MC, Moster D, Daltveit AK, Irgens LM. Cesarean section and risk and severe childhood asthma: a population based cohort study. J Pediatr. 2008;153(1):112–6.View ArticlePubMedGoogle Scholar
- Mallen CD, Mottran S, Winne-jones G, et al. Birth related exposure and asthma and allergy in adulthood. J Asthma. 2008;45:309–12.View ArticlePubMedGoogle Scholar
- Nathan AM, Bryne J, Knalid F, et al. Cesarean section and asthma in malasian children: a case–control study. Asian Pac J Allergy Immunol. 2012;30(3):204–8.PubMedGoogle Scholar
- Menezes AM, Hallal PC, Matijasevich AM, et al. Cesarean sections and risk of wheezing in childhood and adolescence: data from two birth cohort studies in brazil. Clin Exp Allergy. 2011;41(2):218–23.View ArticlePubMedPubMed CentralGoogle Scholar
- Thavagnanam S, Fleming J, Bromley A, et al. A meta-analysis of the association between caesarean section and childhood asthma. Clin Exp Allergy. 2008;38(4):629–33.View ArticlePubMedGoogle Scholar
- Pistiner M, Gold DR, Abdulkerim H, et al. Birth by caesarean section, allergic rhinitis, and allergic sensitization among children with a parental history of atopy. J Allergy Clin Immunol. 2008;122:274–9.View ArticlePubMedPubMed CentralGoogle Scholar
- Salam MT, Margolis HG, McConnell R. Mode of delivery is associated with asthma and allergy occurrences in children. Ann Epidemiol. 2006;16:341–6.View ArticlePubMedGoogle Scholar
- Bager P, Melbye M, Rortgaard K, et al. Mode of delivery and risk of allergic rhinitis and asthma. J Allergy Clin Immunol. 2003;111:51–6.View ArticlePubMedGoogle Scholar
- Kolokotroni O, Middleton N, Gavatha M, et al. Asthma and atopy in children born caesarean section: effect modification by family history of—a population based cross-sectional study. BMC Pediatr. 2012;12:179.View ArticlePubMedPubMed CentralGoogle Scholar
- Cunha SS, Barreto ML, Fiaccone RL, et al. Asthma cases in childhood attributed to atopy in tropical area in brazil. Rev Panam Salud Publica. 2010;28(6):405–11.View ArticleGoogle Scholar
- Roduit C, Scholtens S, Jongste JC, et al. Asthma at 8 years of age in children born by caesarean section. Thorax. 2009;64:107–13.View ArticlePubMedGoogle Scholar
- Maitra A, Sherriff A, Strachan D, et al. Mode of delivery is not associated with asthma or atopy in childhood. Clin Exp Allergy. 2004;34(9):1349–55.View ArticlePubMedGoogle Scholar
- Balicer RD, Grotto I, Mimouni M, et al. Is childhood vaccination associated with asthma? a meta-analysis of observations studies. Pediatrics. 2007;120(5):1269–77.View ArticleGoogle Scholar
- Oddy WH. A review of the effects of breastfeeding on respiratory infections, atopy, and childhood asthma. J Asthma. 2004;41(6):605–21.View ArticlePubMedGoogle Scholar
- Park YH, Kim KW, Choi BS. Relationship between mode of delivery in childbirth and prevalence of allergic diseases in Korean children. Allergy Asthma Immunol Resp. 2010;2(1):28–33.View ArticleGoogle Scholar
- Xu B, Pekkanen J, Hartkainen AL, et al. Risk of childhood asthma and allergic rhinithis in relation to pregnancy complications. J Allergy Clin Immunol. 2003;111(1):51–6.View ArticleGoogle Scholar
- Pinto LA, Stein R, Ribeiro JD. Genetic with asthma and virus—induced wheezing: associations: a systematic review. J Bras Pulmonology. 2009;35(12):1220–6.Google Scholar
- Sears MS, Holdaway MD, Flannery EM, et al. Parental and neonatal risk factors for atopy, airway hyper-responsiveness and asthma. Arch Dis Child. 1996;75:392–8.View ArticlePubMedPubMed CentralGoogle Scholar
- Strachan DP. Hay fever, hygiene, and household size. Br Med J. 1969;299:1259–60.View ArticleGoogle Scholar
- Penders JTC, van den Brandt PA. Gut microbiota composition and development of atopic manifestations in infancy: the KAOLA birth cohort study. Gut. 2007;56:661–7.View ArticlePubMedGoogle Scholar
- Gronlund MM, Lehtonen OP, Eerola E, Kero P. Fecal microflora in healty infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery. J Pediatr Gastroenterol Nutr. 1999;28:19–25.View ArticlePubMedGoogle Scholar
- Ly NP, Ruiz-Perez B, Onderdonk AB. Mode of delivery and cord blood cytokines a birth chort study. Clin Mol Alergy. 2006;4:13–26.View ArticleGoogle Scholar