*3.1.2.3. Unconjugated estriol*

The presence of a low level of estriol in maternal urine in the case of a pregnancy with trisomy 21 was first reported by Jørgansen and Trolle [36]. Other studies confirmed this particularity and μE3 could be used as a marker in the prenatal screening of Down syndrome [37, 38].

The placenta uses 16 alpha-hydroxydehydroepiandrosterone sulfate (DHEAS) as the precursor of μE3. In Down syndrome pregnancies, both μE3 and DHEAS present lower levels in different tissues, including placenta [39]. During the second trimester the concentration of μE3 rises quickly and this marker can identify pregnancies with a small or underdeveloped fetus at the time of screening [27].
