Estriol (E3) is one of the three main estrogen hormones, and unlike estrone and estradiol, it is the form most closely associated with pregnancy. While virtually undetectable in non-pregnant women, its concentration increases significantly during gestation, making it a unique marker for monitoring a developing pregnancy. Measuring estriol is a routine component of prenatal screening tests, typically performed during the second trimester. A low result is not a definitive diagnosis but rather an indicator that further investigation is required to assess the health of the fetus and the placenta.
The Role of Estriol (E3) in Pregnancy
Estriol is often referred to as the “pregnancy hormone” because its production dramatically increases, becoming the dominant estrogen in the maternal bloodstream. It supports fetal development, helps the uterus expand, and prepares the body for labor and breastfeeding. The production of estriol increases up to 1,000-fold during pregnancy, underscoring its importance in maintaining a healthy gestation.
The synthesis of estriol requires cooperation between the fetus and the placenta, collectively known as the fetoplacental unit. The process begins when the fetal adrenal glands produce dehydroepiandrosterone sulfate (DHEAS), which the fetal liver then modifies before it travels to the placenta.
The placenta acts as the final processing center, converting this modified precursor into unconjugated estriol (uE3). Since the fetus provides the initial building blocks, the estriol level in the mother’s blood indicates how well both the fetus and the placenta are functioning. A decline in this hormone’s level can signal a potential compromise in the health of this cooperative system.
Understanding Low Estriol Test Results
Estriol is typically measured as part of a multiple marker screening test, such as the Triple or Quad screen, offered to pregnant women between 15 and 20 weeks of gestation. The test specifically measures the level of unconjugated estriol (uE3) in the maternal serum. A result is deemed “low” when the measured level falls significantly below the median value established for that specific week of pregnancy.
The measurement is reported in Multiples of the Median (MoMs), a standardized way to compare an individual’s result to the average for that gestational age. A low estriol result is defined as a value below 0.5 or 0.75 MoM, depending on the specific laboratory protocol. A result outside the normal range does not automatically mean a problem exists, as these tests are designed to screen for risk, not to diagnose a condition.
Several non-clinical factors can influence the numerical result and lead to a falsely low reading. The most common factor is an inaccurate determination of the pregnancy’s gestational age. Maternal weight can also affect the hormone concentration, and certain medications, including corticosteroids and some antibiotics, are known to interfere with E3 production or measurement.
Potential Causes Associated with Low E3 Levels
When a low estriol result is confirmed and not attributed to a dating error, it suggests a disruption in the fetoplacental estriol production pathway. Since both the fetus and the placenta are involved in E3 synthesis, a reduced level can point toward issues with either component. A primary concern is placental insufficiency, where the placenta is not effectively converting the fetal precursors, leading to insufficient nutrient and oxygen transfer.
Low E3 levels are also a recognized marker for an increased risk of certain chromosomal abnormalities, most notably Down syndrome (Trisomy 21). In these cases, the reduced estriol is typically seen in combination with abnormal levels of other markers on the screening test. Specific genetic conditions that interfere with the body’s ability to process or synthesize the precursor hormones can also cause a drop in estriol.
One such genetic condition is X-linked ichthyosis, caused by a steroid sulfatase (STS) deficiency, which prevents the placenta from properly converting the DHEAS precursor. Another is Smith-Lemli-Opitz Syndrome (SLOS), an autosomal recessive disorder of cholesterol metabolism that results in very low estriol levels. Issues related to the fetal adrenal glands, such as congenital adrenal hypoplasia or isolated adrenocorticotropic hormone (ACTH) deficiency, can also reduce the supply of DHEAS, lowering the final E3 level.
Next Steps After a Low Estriol Result
A low estriol result prompts the healthcare team to recommend further diagnostic testing to clarify the risk. The initial step often involves a high-resolution ultrasound examination to confirm gestational age and assess fetal growth and anatomy. This specialized imaging helps rule out major structural anomalies and confirms that the baby is growing at the expected rate.
Depending on the overall risk profile and the levels of other screening markers, a physician may recommend more invasive diagnostic procedures, such as amniocentesis or chorionic villus sampling (CVS). These tests provide a definitive karyotype to confirm or rule out chromosomal conditions like Down syndrome. For pregnancies beyond the second trimester, Non-Stress Tests (NSTs) or Biophysical Profiles (BPPs) may be used to monitor the baby’s well-being and placental function.
Genetic counseling is an important part of the process, providing a comprehensive review of all screening results and family history to determine a personalized risk assessment. Consultation with a maternal-fetal medicine specialist can help develop a surveillance plan tailored to the concerns raised by the low estriol level. Many low estriol results are ultimately deemed false positives or are corrected by more accurate dating, and a majority of women with an abnormal screen go on to have healthy pregnancies.