Unconjugated Estriol(E3)

Pregnancy

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Maternal serum marker.

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Unconjugated Estriol (E3) Test Information Guide

Why is it done?
- Test Purpose: Unconjugated estriol (uE3) is a form of estrogen produced primarily by the placenta during pregnancy. This test measures the level of free, unbound estriol in maternal blood to assess fetal and placental health.
- Primary Indications: Second and third trimester prenatal screening for chromosomal abnormalities (Down syndrome, Edwards syndrome, Patau syndrome) and neural tube defects
- Component of Screening: Part of the 'Triple Screen' (estriol, hCG, AFP) or 'Quadruple Screen' (adds inhibin A) during second trimester
- Typical Timing: Performed between 15-22 weeks of gestation, ideally between 16-18 weeks for optimal detection rates
- Clinical Circumstances: Maternal age >35 years, abnormal first trimester screening, family history of chromosomal abnormalities, or previous pregnancy with genetic disorder
Normal Range
- Reference Values by Gestational Age:
- 15 weeks: 0.5-1.5 ng/mL (multiples of median - MoM: 0.5-1.5)
- 16 weeks: 0.6-2.0 ng/mL (MoM: 0.5-1.5)
- 17 weeks: 0.7-2.7 ng/mL (MoM: 0.5-1.5)
- 18 weeks: 0.8-3.2 ng/mL (MoM: 0.5-1.5)
- 19 weeks: 0.9-3.8 ng/mL (MoM: 0.5-1.5)
- 20 weeks: 1.0-4.5 ng/mL (MoM: 0.5-1.5)
- Units of Measurement: ng/mL (nanograms per milliliter) or pmol/L (picomoles per liter)
- MoM Standard: Results are often reported as 'Multiples of Median' (MoM). Normal range = 0.5-1.5 MoM regardless of gestational age
- Interpretation Guide:
- • Normal/Negative: 0.5-1.5 MoM - Low risk for chromosomal abnormalities
- • Low: <0.5 MoM - May indicate Down syndrome, Edwards syndrome, or other genetic conditions
- • High: >1.5 MoM - May indicate placental abnormalities or certain complications
Interpretation
- Low Unconjugated Estriol (<0.5 MoM):
- Associated with increased risk for Down syndrome (Trisomy 21), Edwards syndrome (Trisomy 18), Patau syndrome (Trisomy 13), and placental insufficiency; may indicate fetal distress or poor prognosis
- Normal Unconjugated Estriol (0.5-1.5 MoM):
- Indicates lower risk for chromosomal abnormalities and suggests normal placental function; does not completely exclude genetic disorders
- High Unconjugated Estriol (>1.5 MoM):
- May indicate pregnancies at higher risk for adverse outcomes, preeclampsia, or fetal stress; can also be seen in multiple gestations or maternal diabetes
- Factors Affecting Interpretation:
- • Accurate dating of pregnancy - Gestational age is critical; even 1-week discrepancy significantly affects result interpretation
- • Maternal diabetes - Produces lower estriol levels independent of fetal condition
- • Maternal weight - Can affect hormone levels and test results
- • Multiple gestations - Estriol levels are naturally higher; results difficult to interpret
- • Maternal age - Results may be adjusted for advanced maternal age
- • Ethnic background - Some populations have different baseline values
- Clinical Significance:
- Estriol is used as a screening marker, not diagnostic test; abnormal results require confirmation with additional testing (ultrasound, amniocentesis, cell-free DNA testing); false positives are common; risk assessment is based on combination of all markers in triple/quadruple screen
Associated Organs
- Primary Organ Systems:
- • Placenta - Primary source of estriol production during pregnancy
- • Fetal adrenal glands - Produce DHEA-S that is converted to estriol by placenta
- • Fetal liver - Contributes to estriol metabolism and production
- • Maternal circulation - Transport and storage of estriol
- Associated Conditions with Abnormal Results:
- • Down Syndrome (Trisomy 21) - Low estriol levels
- • Edwards Syndrome (Trisomy 18) - Significantly low estriol
- • Patau Syndrome (Trisomy 13) - Markedly reduced levels
- • Neural tube defects - May show abnormal levels
- • Placental insufficiency - Low levels indicating compromised placental function
- • Preeclampsia - Can be associated with altered estriol levels
- • Fetal distress - May result in abnormal estriol values
- • Intrauterine growth restriction (IUGR) - Often associated with low estriol
- • Adrenal hypoplasia - Severely low estriol due to inadequate fetal adrenal function
- Potential Complications Associated with Abnormal Results:
- • Psychological distress from abnormal prenatal screening results
- • Need for invasive testing (amniocentesis) to confirm diagnosis
- • Risk of pregnancy loss if invasive procedures are performed
- • Maternal anxiety and stress related to fetal prognosis concerns
Follow-up Tests
- Recommended if Results are Abnormal:
- • Ultrasound evaluation - Detailed fetal anatomy scan, assessment of placental structure, amniotic fluid volume, and fetal measurements for dating
- • Cell-free DNA testing (Non-invasive Prenatal Testing - NIPT) - Analyzes fetal DNA fragments in maternal blood for chromosomal abnormalities
- • Amniocentesis - Invasive test for definitive diagnosis of chromosomal abnormalities; generally performed after 15 weeks
- • Chorionic villus sampling (CVS) - Invasive test for genetic diagnosis; performed at 10-13 weeks
- Complementary Marker Testing (Part of Comprehensive Screening):
- • Human chorionic gonadotropin (hCG) - Elevated in Down syndrome, decreased in Edwards and Patau syndromes
- • Alpha-fetoprotein (AFP) - Elevated in neural tube defects and some chromosomal abnormalities
- • Inhibin A - Part of Quadruple Screen; elevated in Down syndrome
- First Trimester Screening (if abnormal results prompt review):
- • PAPP-A (pregnancy-associated plasma protein A) - Low levels associated with chromosomal abnormalities
- • First trimester hCG - Combined with PAPP-A for early risk assessment
- • Nuchal translucency (NT) measurement - Ultrasound measurement at 11-14 weeks for chromosomal abnormality risk
- Monitoring Frequency:
- If high-risk result identified, close monitoring with serial ultrasounds may be recommended every 2-4 weeks for assessment of fetal growth and well-being
- Non-stress testing (NST) may be initiated in third trimester for pregnancies with concerning estriol results
Fasting Required?
- Fasting Requirement: No
- Fasting is not required for unconjugated estriol testing; the test can be performed at any time of day
- Patient Preparation Requirements:
- • No special dietary restrictions
- • Patient may eat and drink normally before the test
- • Accurate knowledge of gestational age is essential (confirm via ultrasound dating)
- • Patient should be well-hydrated for easier blood draw
- • Inform healthcare provider of current medications and health conditions
- Medications to Avoid:
- • No medications need to be withheld specifically for this test
- • Continue all regularly prescribed prenatal vitamins and medications
- • Inform provider of any hormonal medications (e.g., corticosteroids, hormone replacement), as these may affect results
- Collection Method:
- • Simple venipuncture (blood draw); typically 5-10 mL of blood is collected in a serum separator tube
- • Sample should be labeled with patient identifiers and time of collection
- • Usually processed within 2 hours and refrigerated if delayed; results available within 24-48 hours

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