to controls with adequate GWG. In that study, maternal smoking (OR = 18) was the major determinant of the response.

Cancer

Whether associations exist between GWG, birth weight, and risk for childhood cancers is not clear; however, there are a few studies that have examined the possibility.


Childhood leukemia Two lines of evidence link GWG to cancer: First, a recent meta-analysis (Hjalgrim et al., 2003) estimated that the odds for acute lymphoblastic childhood leukemia (ALL) were higher (OR = 1.26, 95% CI: 1.17-1.37) for infants with birth weight over 4,000 g compared to those under 4,000 g. Although not statistically significant, results were of similar magnitude for acute myelogenous leukemia (AML). McLaughlin et al. (2006) examined the association between pregnancy outcomes and leukemia cases registered in the state of New York and diagnosed before 10 years of age. The authors obtained information on prepregnancy weight (BMI not generally available) and GWG from birth certificates. Using multivariate regression analyses, the researchers found that total GWG greater than 14 kg conferred an increased risk for ALL (OR = 1.31, 95% CI: 1.07, 1.60). Maternal prepregnancy weight did not affect the impact of GWG on ALL; nor was there any association between GWG and AML. The authors speculated that higher GWG could result in higher fetal exposure to insulin-like growth factor I (IGF-I), which in turn may increase the risk of childhood ALL. Based on these results and because of the established relationship between higher GWG and macrosomia (see discussion in Fetal Growth section in this chapter), it is plausible that GWG may be related to childhood leukemia.


Breast cancer Almost two decades ago, Trichopoulos (1990) hypothesized that breast cancer originates from alterations in the prenatal endocrine milieu, in particular higher estrogen levels. Although longitudinal studies needed for definitively testing this hypothesis have yet to be conducted, observational studies showing direct associations between birth weight and breast cancer provide some support for an association (Michels et al., 1996; Vatten et al., 2002; Ahlgren et al., 2007). Therefore, the committee deemed it of interest to examine determinants of hormone levels in the maternal-placental-fetal unit. In a sample of 270 white women from Boston, Lagiou et al. (2006) examined the association between GWG and maternal sex hormones at 16 and 27 weeks of gestation. After adjusting for prepregnancy BMI and other covariates the authors did not detect any associations between GWG and maternal estradiol, estriol, or prolactin



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