Estrogens are involved in development and maintenance of the female phenotype, germ cell maturation, and pregnancy.During pregnancy E3 becomes the dominant estrogen. The fetal adrenal gland secretes dehydroepiandrosterone-sulfate (DHEAS), which is converted to E3 in the placenta and diffuses into the maternal circulation. E3 levels increase throughout the course of pregnancy, peaking at term.Decreased second trimester uE3 has been shown to be a marker for Down and trisomy-18 syndromes. Low levels of uE3 also have been associated with pregnancy loss, Smith-Lemli-Opitz syndrome (defect in cholesterol biosynthesis), X-linked ichthyosis and contiguous gene syndrome (placental sulfatase deficiency disorders), aromatase deficiency, and primary or secondary fetal adrenal insufficiency.