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Does the sibling effect have its origin in utero? Investigating birth order, cord blood immunoglobulin E
W Karmaus1, H Arshad, J Mattes
1Department of Epidemiology, Michigan State University, East Lansing, MI 48823, USA. karmaus@msu.edu
Insights
Having siblings may protect against allergies. This study found lower cord blood immunoglobulin E (IgE) in later-born children, suggesting an in utero effect on allergy development.
Area of Science:
- Immunology
- Allergy Research
- Perinatal Epidemiology
Background:
- Siblings are known to have a protective effect against atopic diseases like asthma and eczema.
- The mechanisms behind this 'sibling effect' are not fully understood, with hypotheses including early childhood infections or in utero programming.
- The potential role of prenatal factors, specifically in utero programming, has been largely overlooked.
Purpose of the Study:
- To investigate the association between birth order and cord blood immunoglobulin E (IgE) levels.
- To determine if cord blood IgE and birth order predict allergic sensitization at age 4.
- To explore the hypothesis that the sibling effect on atopy may originate during pregnancy.
Main Methods:
- A cohort study of 981 newborns recruited on the Isle of Wight between 1989 and 1990.
- Measurement of cord blood IgE levels at birth.
- Assessment of allergic sensitization using skin prick tests at 4 years of age.
- Statistical analysis to evaluate the relationship between birth order, cord blood IgE, and allergic sensitization.
Main Results:
- Cord blood IgE levels decreased with increasing birth order (e.g., third-born children had lower IgE than first-born).
- Higher cord blood IgE levels were a significant predictor of positive skin prick tests (allergic sensitization) at age 4.
- Birth order itself was not a significant predictor of allergic sensitization at age 4, but cord blood IgE was.
Conclusions:
- The findings suggest that the protective 'sibling effect' against atopic diseases may begin before birth.
- Reduced cord blood IgE in later-born infants indicates a potential in utero programming mechanism influencing allergy risk.
- Further research into prenatal factors is warranted to understand and potentially prevent atopic manifestations.
Abstract:
There is a great body of evidence that siblings have a protective effect against atopic manifestations such as hay fever, atopic eczema, allergic sensitization, or asthma. Factors that may explain this association remain largely unknown. One hypothesis is that siblings promote early infections in childhood, and repeated infections protect against atopic disorders. Another hypothesis, the potential in utero programming, has been neglected. The authors investigated if cord blood immunoglobulin E (IgE) is dependent upon birth order and if both are associated with an increased incidence of allergic sensitization (skin prick test) at the age of 4 years in a cohort of 981 newborns recruited between January 1989 and February 1990 on the Isle of Wight, England. The authors found that IgE is reduced with increasing birth order (first child: odds ratio (OR) = 1; second child: OR = 0.78, 95% confidence interval (CI): 0.57, 1.05; third child: OR = 0.59, 95% CI: 0.41, 0.83). Cord IgE, but not birth order, is a significant predictor of skin prick test positivity at age 4 (IgE below detection limit: OR = 1; IgE of 0.2-<0.5 kilounits/liter: OR = 1.11, 95% CI: 0.73, 1.68; IgE of >or=0.5 kilounits/liter: OR = 2.63, 95% CI: 1.62, 4.29). The findings suggest that cord IgE is reduced in pregnancies with higher order, indicating that the sibling effect may have its origin in utero.
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