Unit Converter
Estriol Unconjugated (E3)
(Placental/Fetal Estrogen – Marker for Fetal Well-being & Prenatal Screening)
Synonyms
- Estriol (unconjugated)
- uE3
- Free estriol
- Free E3
- 16α-hydroxyestradiol (metabolite origin)
- Fetal–placental estrogen
Units of Measurement
- nmol/L
- ng/mL
- ng/dL
- ng/100 mL
- ng%
- ng/L
- µg/L
Unit Conversions
1 ng/mL = 3.47 nmol/L
1 ng/mL = 100 ng/dL
1 ng/mL = 1000 ng/L
1 ng/mL = 1 µg/L
ng/dL = ng% = ng/100 mL
Description
Unconjugated estriol (uE3) is a major estrogen produced during pregnancy, synthesized through a unique fetal–placental collaboration:
- Fetal adrenal → DHEA-S
- Fetal liver → 16α-hydroxylation
- Placenta → Aromatization → Estriol (E3)
uE3 reflects fetal adrenal activity, placental function, and fetal liver function.
It is a key analyte in:
- Second-trimester prenatal screening (Triple & Quad tests)
- Assessment of fetal well-being
- Evaluation of fetal growth, adrenal, and liver function
uE3 is not a useful marker outside pregnancy.
Physiological Role
- Increases steadily from early pregnancy to term
- Regulates uteroplacental perfusion
- Supports cervical softening
- Indicates health of fetal–placental steroidogenic pathways
Clinical Significance
Low uE3 (Most Important Clinical Use)
Low estriol may indicate significant fetal abnormalities.
1. Down Syndrome (Trisomy 21)
- Low uE3 is one of the key findings in the triple/quad screen
2. Trisomy 18 (Edwards Syndrome)
- Very low uE3
3. Smith-Lemli-Opitz Syndrome (SLOS)
- Extremely low or undetectable uE3
- Due to cholesterol synthesis defect (DHCR7 deficiency)
4. Fetal Demise or Severe Placental Dysfunction
- Very low estriol
- No appropriate rise with gestational age
5. Fetal Growth Restriction (FGR)
- Reflects reduced placental metabolism
6. Congenital Adrenal Hypoplasia
- Low DHEA-S → low estriol
7. Anencephaly
- Very low due to impaired fetal steroidogenesis
High uE3
Less clinically specific.
Causes:
- Multiple gestation
- Large placental mass
- Maternal liver disease
- Certain drugs (phenytoin ↑ estriol metabolism)
Generally not associated with pathology.
Reference Intervals
(Tietz 8E + ACOG + SMFM + Mayo + ARUP)
Estriol levels vary strongly with gestational age.
Typical Ranges During Pregnancy (ng/mL)
| Gestational Age | Unconjugated Estriol (uE3) |
| 10–12 weeks | 0.1 – 1.0 ng/mL |
| 14–16 weeks | 0.3 – 2.0 ng/mL |
| 17–19 weeks | 0.6 – 3.5 ng/mL |
| 20–22 weeks | 1.0 – 5.0 ng/mL |
| 26–30 weeks | 2.0 – 10.0 ng/mL |
| Term | 5 – 30 ng/mL |
(Values depend on assay and pregnancy stage.)
Non-Pregnant
- Very low (<2 ng/dL) or undetectable
Estriol is not clinically useful outside pregnancy.
Diagnostic Uses
1. Prenatal Screening (Triple/Quad Test)
uE3 is used with:
- AFP
- hCG
- Inhibin A
Low uE3 suggests:
- Trisomy 21
- Trisomy 18
- SLOS
- Fetal jeopardy
2. Fetal-Placental Function Assessment
Decreasing levels signal:
- Placental insufficiency
- Growth restriction
- Fetal stress
3. Monitoring High-Risk Pregnancies
Serial estriol interpretations may indicate:
- Maternal–fetal compromise
- Abnormal fetal adrenal activity
4. Rarely for Fetal Adrenal Disorders
Helps assess steroidogenic defects.
Analytical Notes
- Serum sample
- Must be interpreted with gestational age
- Diurnal variation: estriol peaks in the evening
- Immunoassay used in screening panels
- LC-MS/MS may be used for research or special cases
Clinical Pearls
- Extremely low uE3 is a hallmark of Smith–Lemli–Opitz syndrome.
- A falling estriol late in pregnancy may precede fetal compromise.
- uE3 is crucial in maternal serum screening between 15–20 weeks.
- Estriol is a pure fetal–placental marker, unlike estradiol.
- Normal estriol increase across gestation indicates a healthy fetal adrenal axis.
Interesting Fact
Estriol becomes the dominant estrogen in pregnancy, rising up to 1000-fold, but remains almost absent in non-pregnant women.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Steroid Hormones.
- ACOG Guidelines - Prenatal Genetic Screening.
- SMFM Maternal Serum Screening Standards.
- Mayo Clinic Laboratories - Unconjugated Estriol.
- ARUP Consult - Maternal Serum Screening.
- MedlinePlus / NIH - Estriol Test.