Nearly 20 percent of the almost 4 million infants born in the United States are at the low and high extremes of fetal growth. In 2010, 8.2 percent of infants weighed < 2500 g at birth, whereas 7.6 percent weighed > 4000 g. And although most low-birthweight infants are born preterm, approximately 3 percent are term. The proportion of infants with birthweight < 2500 g has increased by more than 20 percent since 1984, and at the same time, the incidence of birthweight > 4000 g continues to decline (Martin, 2012). This shift away from the upper extreme is difficult to explain because it coincides with the epidemic prevalence of obesity (Morisaki, 2013).
Human fetal growth is characterized by sequential patterns of tissue and organ growth, differentiation, and maturation. However, the “obstetrical dilemma” postulates a conflict between the need to walk upright—requiring a narrow pelvis—and the need to think—requiring a large brain, and thus a large head. Some have speculated that there may be evolutionary pressure to restrict growth late in pregnancy (Dunsworth, 2012; Espinoza, 2012). Thus, the ability to growth restrict may be adaptive rather than pathological.
Fetal growth has been divided into three phases. The initial phase of hyperplasia occurs in the first 16 weeks and is characterized by a rapid increase in cell number. The second phase, which extends up to 32 weeks’ gestation, includes both cellular hyperplasia and hypertrophy. After 32 weeks, fetal growth is by cellular hypertrophy, and it is during this phase that most fetal fat and glycogen are accumulated. The corresponding fetal-growth rates during these three phases are 5 g/day at 15 weeks’ gestation, 15 to 20 g/day at 24 weeks, and 30 to 35 g/day at 34 weeks (Williams, 1982). As shown in Figure 44-1, there is considerable biological variation in the velocity of fetal growth.
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. (Image courtesy of Dr. Don McIntire.)
Fetal development is determined by maternal provision of substrate, placental transfer of these substrates, and fetal growth potential governed by the genome. However, the precise cellular and molecular mechanisms by which normal fetal growth ensues are incompletely understood. That said, there is considerable evidence that insulin and insulin-like growth factors, particularly insulin-like growth factor-I (IGF-I), have an important role in regulation of fetal growth and weight gain (Luo, 2012; Murray, 2013). These growth factors are produced by virtually all fetal organs and are potent stimulators of cell division and differentiation.
Other hormones implicated in fetal growth have been identified in recent years, particularly hormones derived from adipose tissue. These hormones are known broadly as adipokines and include leptin, the protein product of the obesity gene. Fetal leptin ...