FIGURE 44-1 Increments in fetal weight gain in grams per day from 24 to 42 weeks' gestation. The black line represents the mean and the outer blue lines depict ±2 standard deviations. (Data from pregnancies managed at Parkland Hospital.) levels below the threshold for diabetes. Overgrowth does occur in the fetuses of euglycemic women. Its etiology is thus likely more complicated than merely dysregulated glucose metabolism (Catalano, 2011). Genetic factors, including genomic imprinting and epigenetic modifications via gene methylation, are also important and emphasize the potential role of inheritance (Begemann, 2015; Nawathe, 2016).
Excessive transfer of lipids may also lead to fetal overgrowth (Higa, 2013). Free or nonesteriied fatty acids in maternal plasma may be transferred to the fetus via facilitated diusion or ater liberation of fatty acids from triglycerides by trophoblastic lipases (Gil-SGnchez, 2012). Generally speaking, lipolytic activity is augmented in pregnancy, and fatty acid levels are increased in nonobese women during the third trimester (Diderholm, 2005).
fetal-growth rates during these three phases are 5 g/d at 15 weeks' gestation, 15 to 20 g/d at 24 weeks', and 30 to 35 g/d at 34 weeks' (Williams, 1982). As shown in Figre 44-1, the velocity of fetal growth varies considerably.
Fetal development is determined by maternal provision of substrate and placental transfer of these, whereas fetal growth potentil is governed by the genome. The precise cellular and molecular mechanisms by which normal fetal growth ensues are incompletely understood. That said, considerable evidence support an important role for insulin and insulin-like growth factors (IGFs) in regulation offetal growth and weight gain (Luo, 2012). hese growth factors are produced by virtually all fetal organs and are potent stimulators of cell division and diferentiation.
Other hormones implicated in fetal growth have been identified, particularly hormones derived from adipose tissue. These hormones are known broadly as adipokines and include leptin, the protein product of the obesiy gene. Fetal leptin concentrations rise during gestation, and they correlate both with birthweight and with neonatal fat mass (Brifa, 2015; Logan, 2017; Simpson, 2017). Other adipokines possibly involved include adiponectin, ghrelin, follistatin, resistin, visfatin, vaspin, omentin-I, apelin, and chemerin.
Fetal growth is also dependent on an adequate supply of nutrients. As discussed in Chapter 7 (p. 138), both excessive and diminished maternal glucose availability afect fetal growth. Reduced maternal glucose levels may result in a lower birthweight. Still, growth-restricted neonates do not typically show pathologically low glucose concentrations in cord blood (Pardi, 2006). Fetal-growth restriction in response to glucose deprivation generally results only after long-term severe maternal caloric deprivation (Lechtig, 1975).
Conversely, excessive glycemia produces macrosomia. Varying levels of glucose afect fetal growth via insulin and its associated IGFs. he Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study Cooperative Research Group (2008) found that elevated cord C-peptide levels, which relect fetal hyperinsulinemia, are associated with greater birthweight. his relationship was noted even in women with maternal glucose