third trimester. The concentration of the metabolically active free cortisol also progressively increases through gestation due to increased production and decreased clearance. Adrenocorticotropic hormone (ACTH) level is suppressed during pregnancy due to the action of estrogen and progesterone. The plasma concentration of dehydroepiandrosterone sulfate (DHEAS) declines during pregnancy due to an increase in metabolic clearance by the placenta and maternal liver.

The renin-angiotensin system changes dramatically during pregnancy. The adrenal gland remains responsive to the trophic action of angiotensin II, even though a refractory effect of pressors to angiotensin II develops early in pregnancy. This provides a probable explanation for the expansion of plasma volume during pregnancy. The secretion of prolactin from the pituitary and uterine decidua increases steadily during pregnancy. In contrast, luteinizing hormone and follicle-stimulating hormone are suppressed to levels similar to the luteal phase of ovulation. Growth hormone secretion is inhibited presumably by placental growth hormone production.

In normal pregnancy, thyroxine-binding globulin concentration is increased and the circulating pool of extrathyroidal iodide is decreased due to increased renal clearance. These changes cause the thyroid to enlarge and to synthesize and secrete the thyroid hormones T4 (thyroxine) and T3 (triiodothyronine) more actively. Despite elevated total T4 and T3, the concentrations of active hormones (free T4 and free T3) are unchanged during normal pregnancy, with the exception of a transient increase in the first trimester in some women (Gabbe et al., 1991; Glinoer, 2004).

Adipose tissue produces an array of adipokines known to have profound effects on metabolism and fertility, but their role in reproductive performance is yet to be fully understood. In addition to adipose tissue, leptin and its receptor, TNF-α, and resistin also are expressed in the placenta (Mitchell et al., 2005). Serum adiponectin is lower in the third trimester, a change that correlates with a decrease in insulin sensitivity (Catalano et al., 2006). Increases in maternal fat mass most likely are related to the decreases in circulating adiponectin concentrations.

Metabolic Changes

Many of the metabolic adjustments of pregnancy are well established in early pregnancy, when fetal nutrient demands are still minor. Minimal nutrient balances are usually positive, reflecting the anabolic state of the fetus and the mother. In the absence of nausea or “morning sickness,” most women experience an increase in appetite in the beginning of pregnancy (Gabbe et al., 1991). Several gastrointestinal changes occur during pregnancy, including decreased tone and motility of the stomach, reduced gastric acid secretion, delayed gastric emptying, and increased gastric mucous



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