components of maternal metabolism and may exert an indirect effect on GWG through their effects on maternal insulin sensitivity.

Leptin is produced in relatively large quantities by the placenta and is transferred primarily into the maternal circulation (Hauguel-de Mouzon et al., 2006), with maternal leptin concentrations increasing by 12 weeks’ gestation and having a significant positive correlation with both maternal body fat and BMR in both early and late gestation (Highman et al., 1998). Kirwan et al. (2002) used a stepwise regression analysis to show that, over the course of pregnancy, leptin also makes a significant contribution to changes in insulin sensitivity that occur during gestation. There may also be a relationship between circulating leptin and increased maternal fat oxidation (Okereke et al., 2004).

Adiponectin is a unique circulating cytokine that has a positive correlation with insulin sensitivity and negative correlation with adiposity (Cnop et al., 2003). In contrast to leptin and other cytokines, adiponectin is made exclusively in the maternal and fetal compartments, and not in the placenta (Pinar et al., 2008). There is no transfer of leptin from mother to fetus or vice versa. Lower adiponectin concentrations have been reported in women with previous GDM (Winzer et al., 2004), and leptin was shown to decrease over the course of pregnancy in women with GDM compared to women with normal glucose tolerance (Retnarkaran et al., 2004; Williams et al., 2004).

In summary both leptin and adiponectin are correlated with various components of maternal metabolism such as energy expenditure and adiposity. However, there are no direct mechanistic effects relating to the changes in maternal weight gain described in human pregnancy. Indirectly these cytokines through their effects on maternal insulin sensitivity may represent markers of other mechanisms effecting gestational weight changes.

Medical Factors

Pre-Existing Morbidities

The committee considered several maternal medical factors known to be related to pregnancy outcome that could have an impact on GWG: pre-existing chronic disease or other morbidities; hyperemesis gravidarium; anorexia nervosa and bulimia nervosa; bariatric surgery; and twins and higher order pregnancies. The committee was unable to identify studies that directly examined pre-existing morbidities as determinants of GWG. However, in general the pre-conceptional health status of a woman is important for optimal pregnancy outcome. This is particularly true for chronic diseases such as inflammatory bowel disease and systemic lupus erythematosus. In women with inflammatory bowel disease, and in particular Crohn’s disease, the level of disease activity during pregnancy is related to



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