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Keywords:

  • cesarean section;
  • cow's milk allergy;
  • food hypersensitivity;
  • hygiene hypothesis;
  • mode of delivery

Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

The present study provides support for a positive association between cesarean delivery and persistent cow milk allergy/cow's milk intolerance. Correspondingly, a negative association was seen between cesarean delivery and early outgrown cow milk allergy/intolerance. A possible explanation is that cesarean delivery, rather than increasing the overall risk of food allergy, increases the risk of persistency of disease among food allergic children.

Abbreviations:
SPT

skin prick test

CMA/CMPI

cow milk allergy/intolerance

Reduced microbial encounter has been hypothesized to play a role in the development of allergies. Cesarean delivery limits the input of maternal bacteria during birth and may thus be a risk factor.

Previously we reported a positive association between cesarean section and egg, fish and nut allergy (1). Here, the more complex associations with cow milk allergy/intolerance (CMA/CMPI) are reported.

Methods

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

The present study is based on 2656 participants in Oslo Birth Cohort, omitting children with reactions to egg, fish or nuts, and nonresponders to questionnaires used in the study. The outcomes chosen were parentally perceived reactions reported at 12, 18 and 24 months, and reactions objectively verified at the age of 2inline image. Confirmed and probable CMA/CMPI were grouped together as ‘verified’, because bivariate analysis revealed the same associations to cesarean delivery. All details of the study have been reported previously (2). Odds ratio (OR) were obtained by logistic regression (SPSS Release 11), adjusting for variables listed in Table 1, 95% confidence intervals (CI) are given.

Table 1.  Children with verified cow's milk allergy/intolerance (CMA/CMPI) in a population-based cohort of 2656 children, according to caesarean delivery, maternal allergy, or both caesarean delivery and maternal allergy
 HealthyCMA/CMPICrudeAdjusted
nn (%)P-valueOR (95% CI)P-valueOR (95% CI)P-value
  1. Adjusted for maternal age, education and smoking, children's birth weight, gestation length, pregnancy complications, short-term breast feeding (<1 month), being a firstborn child, maternal use of antibiotics during pregnancy and finally infant use of antibiotics during the first 6 months of life.

  2. About 255 children not included in the adjusted analysis due to missing values.

  3. CI, confidence interval.

All263422     
Maternal allergy ± caesarean
 None18687 (0.4)>0.0011 1 
 Only caesarean delivery2443 (1.2)3.3 (0.8–12.8)0.093.3 (0.8–14.1)0.10
 Only maternal allergy46710 (2.1)5.7 (2.2–15.1)0.0005.6 (2.1–15.0)0.001
 Both552 (3.6)9.7 (2.0–47.8)0.0059.6 (1.8–52.4)0.009

Results

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

There was no association between parentally perceived reactions to milk reported at three occasions and mode of delivery (crude OR, 0.5, CI: 0.2–1.4), or any interaction with maternal allergy, whether analyzed crude or adjusted.

In contrast ‘verified’ CMA/CMPI is twice as common among children who had been delivered by a cesarean section compared with children who had been vaginally delivered (adjusted OR: 2.5, CI: 0.8–7.5). Cesarean delivery is associated with a larger percentage increase in allergic children among allergic mothers than among nonallergic mothers, indicating an additive interaction (Table 1).

Among children classified as earlier CMA/CMPI grown tolerant, either based on parental reports or observed at the examination at 2inline image years, none had had a cesarean, indicating a negative association between becoming tolerant before the age of 2inline image year and cesarean section (P = 0.05).

Discussion

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

The association between cesarean section and verified CMA/CMPI is consistent with our previous study on egg allergy and with a study on sensitization to food allergens (3). For asthma, although more inconsistent results are reported, a pooled analysis favors an association (4). Furthermore, differences have been observed in the intestinal microflora between food allergic and healthy children (5). However, these differences may not be causal but rather a consequence of the disease. The results of the present study cannot be explained by differences between predisposed and not predisposed children and thus provides support for early intestinal colonization playing a role in the etiology of food allergy.

The lack of an association between cesarean delivery and reported reaction to milk was unexpected, as was the negative association with growing tolerant before 2inline image years. In order to investigate whether this could be explained by misclassification associated with parental reports, we performed a mathematic simulation. Only when assuming an extreme degree of differential misclassification, with all misclassification taking place among children without a cesarean was it possible to move OR below 1.

An alternative explanation is that cesarean delivery does not increase the risk of food allergy but the risk of persistent disease among food allergic children. This could explain the lack of association to parentally reported reactions to milk, because this is a mix of children with nonpersistent and persistent allergy. In contrast, all children with verified CMA/CMPI had persistent allergy, as the diagnosis was set when they were 2inline image years old. The finding of not one cesarean section among the children that had become tolerant, support this explanation.

The small sample size and the wide and overlapping CI limits the interpretation and larger studies are required to confirm these findings. However, the possibility that mode of delivery influences persistence of allergic disease, may be worth considering in future research.

Acknowledgment

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References

This project has been financed with the aid of EXTRA funds from the Norwegian Foundation for Health and Rehabilitation.

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgment
  7. References