The current study found a significant inverse exposure-response relationship between the number of older siblings and the prevalence of rhinoconjunctivitis, but not wheeze, asthma, or eczema. Total sibship size and number of younger siblings were not materially associated with the prevalence of wheeze, asthma, eczema, or rhinoconjunctivitis.
Epidemiological evidence for the sibling effect on allergic disorders among adults is limited. A cross-sectional study of men and women in the UK aged 16-30 years found significant inverse exposure-response associations of sibship size and birth order with the prevalence of hay fever whereas larger sibship size, but not birth order, was significantly inversely related to the prevalence of eczema-urticaria . In a cross-sectional study of pregnant women in Denmark, larger sibship size was significantly associated with a lower prevalence of allergic rhinitis and asthma with allergic rhinitis, but not asthma without allergic rhinitis; the inverse associations between having older siblings and allergic rhinitis and asthma with allergic rhinitis were more pronounced than the inverse associations between having younger siblings and these disorders . Having 4 or more older siblings was significantly related to a lower prevalence of allergic rhinitis and/or allergic conjunctivitis, but not asthma or atopic dermatitis, over the lifetime of the subjects in a cross-sectional study of Finnish young adults aged 18-24 years . In a retrospective cohort study of Swedish male conscripts, number of older siblings was significantly inversely associated with the prevalence of allergic rhinitis, but not asthma .
Turning to the evidence concerning Japanese children, having 2 or more older siblings was significantly related to a lower prevalence of rhinoconjunctivitis, but not wheeze or eczema, in a cross-sectional study of children aged 12-15 years . Another cross-sectional study of Japanese children aged 6-15 years reported significant exposure-response relationships between larger sibship size and the prevalences of wheeze, asthma, eczema, and rhinoconjunctivitis, and demonstrated that having older siblings reduces the prevalences of eczema and rhinoconjunctivitis while having younger siblings reduces only the prevalence of eczema . These findings, which demonstrate an inverse association between the number of older siblings and allergic rhinitis and null associations between sibship size and wheeze, asthma, or eczema, are in agreement with the current results.
Karmaus and colleagues have found that the level of cord blood IgE was reduced with increasing birth order and that elevated cord blood IgE values were significantly related to an increased risk of allergic sensitization at 48 months of age, though there was no association between birth order and allergic sensitization . Karmaus and colleagues have also shown that maternal IgE levels are significantly reduced with increasing numbers of live offspring . In a study in the UK, women with more pregnancies over a seven-year period were more likely to have lost atopy and symptoms of hay fever, but not asthma, during that period . The fact that maternal immune tolerance against allergens increases as more live offspring are born, and the fact that maternal immune status is communicated to the fetus, might explain the inverse association between the number of older siblings and rhinoconjunctivitis in the current study. Another version of the intrauterine programming hypothesis suggests a potential role of hormones; progesterone and testosterone seem to promote the preferential development of Th2-like cells . In addition, the potential role of endocrine disruptors should be discussed. Parity was significantly associated with decreasing levels of organochlorines in breast milk of Norwegian women . Higher levels of cord blood dichlorodiphenyldichloroethylene were significantly related to an increased risk of asthma at 6.5 years in a cohort study in Spain . Nevertheless, a UK study cited above showed a significant inverse association between sibship size and the prevalence of combined allergies, asthma, eczema-urticaria, and hay fever among people born between 1918 and 1930 when organochlorines had not come into widespread use .
The absence of a sibling effect on wheeze, asthma, or eczema in this study might be ascribed to the attenuation of the sibling effect with advancing age. In our previous study, larger sibship size was significantly associated with the prevalences of wheeze, asthma, eczema, and rhinoconjunctivitis among children aged 6-10 years, but only with the prevalence of eczema among subjects aged 11-15 years . It should be noted that the results of that study, specifically, the findings concerning eczema and rhinoconjunctivitis in the older age group, are at variance with the present findings.
This study had certain methodological advantages. Study subjects were homogeneous in that they were all pregnant. Definitions of wheeze and asthma were based on the questions in the European Community Respiratory Health Survey. Likewise, definitions of eczema and rhinoconjunctivitis were based on the questions in the International Study of Asthma and Allergies in Childhood, although validation tests of such questions have not been performed for young Japanese adults. Several potential confounders were adjusted for, though we could not control for breastfeeding, early day care center attendance, and external factors as aeroallergens and air pollution.
This study also had certain limitations. The participation rate could not be calculated because the exact number of eligible pregnant women who were provided with the KOMCHS documents and application form by the 423 collaborating obstetric hospitals is not available. Nevertheless, the participation rate must have been fairly low, given that the present study used data from only 970 pregnant women who lived in Fukuoka Prefecture, while, according to the government of Fukuoka Prefecture, the number of childbirths was 46,393 in 2007 and 46,695 in 2008. We were not able to assess differences between participants and non-participants because information on personal characteristics such as age, socioeconomic status, and history of allergic disorders was not available for non-participants. Our subjects were probably not a representative sample of Japanese women in the general population. For example, educational levels were higher in the current study population than in the general population. According to the 2000 population census of Japan, the proportions of women aged 30 to 34 years in Fukuoka Prefecture with years of education of < 13, 13-14, ≥ 15, and unknown were 52.0%, 31.5%, 11.8%, and 4.8%, respectively . The corresponding figures for the current study were 24.6%, 33.0%, 42.4%, and 0.0%, respectively. The present population therefore might have had greater awareness about health issues compared to the general population. The lack of significant inverse relationships between total sibship size and the prevalences of wheeze and eczema might be attributable to an insufficient statistical power.
The interface between allergy/immunology and pregnancy should be discussed, as it may have an influence on the association of interest. It has been suggested that pregnancy involves a shift to the Th2 side of the immune response  although Chaouat et al. have pointed out the importance of the role of natural killer cells and IL-12, IL-15, and IL-18 tripods in successful or failed pregnancies in humans beyond the Th1/Th2 paradigm . The hormonal changes in pregnancy are often invoked to explain the apparent association between rhinitis symptoms and pregnancy. However, rhinitis ascribed solely to pregnancy may not be a distinct entity because most pregnant women do not have significant nasal symptoms .