The precise biomolecular events in the pathophysiology of fetal macrosomia are not deined. Nonetheless, fetal hyperinsulinemia is clearly one driving force (Luo, 2012). As discussed in Chapter 44 (p. 845), insulin-like growth factor, fibroblast growth factor, and corticotropin-releasing hormone (CRH) and are important regulators of placental development and function (Gao, 2012; Giudice, 1995). Maternal obesity begets fetal macrosomia (Chap. 44, p. 857). In addition, it is hypothesized that maternal obesity afects fetal cardiomyocyte growth that may result in fetal cardiomyopathy or even congenital heart disease (Roberts, 2015).
This polypeptide hormone was originally identified as a product of adipocytes and a regulator of energy homeostasis by curbing appetite. It also contributes to angiogenesis, hemopoiesis, osteogenesis, pulmonary maturation, and neuroendocrine, immune, and reproductive functions (Brifa, 2015; Maymo, 2009). Leptin is produced by the mother, fetus, and placenta. It is expressed in syncytiotrophoblast and fetal vascular endothelial cells. Of placental production, 5 percent enters the fetal circulation, whereas 95 percent is transferred to the mother (Hauguel-de vlouzon, 2006). Leptin concentrations peak in amnionic fluid at midpregnancy (Scott-Finley, 2015).
Fetalileptin levels begin rising at approximately 34 weeks and are correlated with fetal weight. This hormone is involved in the development and maturation of the heart, brain, kidneys, and pancreas, and its levels are decreased with fetal growth restriction (Brifa, 2015). Abnormal levels have been associated with fetal growth disorders, gestational diabetes, and preeclampsia (Fasshauer, 2014). Postpartum, leptin levels decline in both the newborn and mother. Perinatal leptin is associated with the development of metabolic syndromes later in life (Brifa, 2015; Granado, 2012).
The newborn has a large proportion of fat, which averages 15 percent of body weight (Kimura, 1991). Thus, late in pregnancy, a substantial part of the substrate transferred to the human fetus is stored as fat. Although maternal obesity raises placental fatty acid uptake and fetal fat deposition, it does not appear to afect fetal organ growth (Dube, 2012). Neutral fat in the form of triglycerides does not cross the placenta, but glycerol does. Despite this, evidence supports that abnormal maternal concentrations of triglycerides-both low and high levels-are associated with major congenital anomalies (Nederlof, 2015).
There is preferential placental-fetal transfer of long-chain polyunsaturated fatty acids (Gil-Sanchez, 2012). Lipoprotein lipase is present on the maternal but not on the fetal side of the placenta. his arrangement favors hydrolysis of triacylglycerols in the maternal intervillous space yet preserves these neutral lipids in fetal blood. Fatty acids transferred to the fetus can be converted to triglycerides in the fetal liver.