Fetal Sensitization and Subsequent Immune Responses in Childhood

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Several groups have shown that responses set up during pregnancy can be predictive of subsequent allergic disease (Kondo et al. 1992; Prescott et al. 1998; Warner et al. 1994). Epidemiological data have been of particular importance in showing associations between various maternal factors and childhood asthma. Such maternal factors that are associated with an increased risk of childhood asthma include younger age (Anderson et al. 1986; Martinez et al. 1992; Schwartz et al. 1990), smoking (Martinez et al. 1992; Oliveti et al. 1996; Weitzman et al. 1990), lack of prenatal care, and weight gain of less than 20 pounds (9.1 Kg) during pregnancy (Oliveti et al. 1996; reviewed in: Donovan and Finn, 1999).

Experimental studies have shown that peripheral blood mononuclear cell sensitivity to allergens exists at birth (Kondo et al. 1992; Prescott et al. 1998; Warner et al. 1994; reviewed in: Warner and Warner 2000). In particular, specific allergen-induced responses can be measured in the peripheral blood mononuclear cells as early as 22 weeks into gestation (Jones et al. 1996). Moreover, events after birth are believed to modify the developing immune response in newborns; allergens, infections, diet, and gut microbial flora have all been implicated in the development, or not, of subsequent allergy (Warner and Warner 2000). The impact of diet on the development of allergies in newborns is now being recognized. The health benefits cited for breastfeeding include a reduction in childhood asthma (Oddy et al. 2002) and may be directly tied to gut microbial flora (Bjorksten et al. 1999; Holt et al.

1997; Kirjavainen and Gibson 1999). Moreover, it has been reported that allergic children are more likely to have a low colonization of Lactobacilli in their guts than non-allergic children (reviewed in: Warner and Warner 2000).

Finally, disease due to infection affects immune system maturation. The hygiene hypothesis proposed by Strachen (1989) is based on the inverse relationship between birth order in families and the prevalence of hay fever, as well as on an awareness that infections in early infancy brought home by older siblings might prevent sen-sitization. Further support comes from a recent report correlating reduced rates of asthma and wheezing among 812 rural European children with exposure to bacterial substances in dust from mattresses (Weiss 2002). The hygiene hypothesis and the gut microbial flora, diet, and allergen exposure issues likely all play roles in determining whether the events set up during pregnancy result in the development of allergic disease (Warner and Warner 2000). However, consideration must be taken of the unique intrauterine environment, which may actively dampen the neonate's immune system. One study demonstrates that birch and timothy grass pollen exposure via the mother sensitizes fetuses if it takes places in the first six months of pregnancy. Thus, exposure in later pregnancy appears to result in either immune suppression or tolerance (Van Duren-Schmidt et al. 1997). Obviously, much remains to be known about the myriad factors uniquely surrounding the development of the fetal and newborn immune system.

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