Johns Hopkins University School of Medicine, Baltimore, MD 21205
The recent article by Scholl et al. (1) explores the role of maternal plasma levels of glucose as a contributing factor in birth weight. However, failing to account for small-for-gestational-age (SGA) birth rate disparities, Scholls work ultimately reveals the limitations of plasma glucose in explaining birth outcomes. In this study, 2,072 Hispanic, White, and African-American nondiabetic gravidas of similar socioeconomic status were screened for plasma glucose levels at the 28th week of pregnancy. Researchers examined the correlation of plasma glucose with ethnicity and pregnancy outcomes, controlling for demographic and confounding variables. Their analysis reveals a significant difference in average maternal plasma glucose levels (5 percent) between African-American and White women while White and Hispanic women show similar levels. Using multiple logistic regression analysis, researchers found that this disparity accounts for 11 g of the 178-g difference between average African-American and White birth weights. Furthermore, the inclusion of maternal plasma glucose in the regression model examining large-for-gestational-age (LGA) birth weights significantly accounted for African-American gravidas more than twofold decreased risk (1).
Although Scholl et al. elucidate the role of plasma glucose level in LGA risk, they fail to explain its role in low-birth-weight disparities among African-American, Hispanic, and White women. As they expound, "reduced glucose transfer from mother to fetus ... is linked to slower fetal growth, smaller birth size, a reduced risk of LGA birth, and an increased risk of fetal growth restriction" (1, p. 502). While it explains the reduced LGA risk, maternal plasma glucose levels fail to account for African-American gravidas nearly fourfold increased risk of SGA births (1). This unanswered question may reflect the confounding role of placental growth hormone and its role in fetal growth and maternal metabolism.
Placental growth hormone replaces pituitary growth hormone during the 12th and 20th weeks of gestation and controls important aspects of maternal metabolism, particularly insulin levels. In healthy pregnancies, during weeks 2838, the maternal plasma level of glucose increases to accommodate the rapid growth of the fetus during this time (2). Studies using transgenic mice have shown that increased resistance to insulin is a result of increased plasma placental growth hormone levels. Mice that expressed the placental growth hormone gene had plasma glucose levels four times that of wild-type mice (3). However, in the case of in utero growth retardation, low levels of placental growth hormone may not only cause SGA births but also be a result. SGA infants have lower placental weights than average-for-gestational-age infants, resulting in a decreased concentration of cells producing placental growth hormone (4). Furthermore, placental tissues of SGA births may also be abnormal, resulting in a decreased concentration of cells producing placental growth hormone (5). The low level of placental growth hormone causes decreased levels of insulin resistance and gluconeogenesis, resulting in lower plasma glucose levels (2). Thus, it is unclear whether the variations of glucose levels across ethnic boundaries are a result or cause of low birth weights.
Variations in plasma glucose levels fail to explain the pressing question of SGA birth weight disparities between African Americans and Whites, possibly because of confounding variables. However, placental growth hormone may serve as an important indicator of in utero growth retardation, answering the questions presented by Scholl et al. Unlike the variation of plasma glucose levels throughout the day, placental growth hormone is nonpulsatile in maternal circulation, making it ideal for screenings (5). Further studies are needed to explore the role of placental growth hormone and other maternal metabolic regulators in fetal growth and birth outcomes.
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