From the Research
The most common cause of low estriol levels in pregnancy is fetal demise or congenital abnormalities, but recent evidence suggests that X-linked ichthyosis, a microdeletion syndrome causing steroid sulfatase (STS) deficiency, is a more prevalent genetic cause than previously thought. Estriol is primarily produced by the placenta using precursors from the fetal adrenal glands and liver, so its production depends on proper fetal development and placental function. When the fetus has certain genetic abnormalities, the production pathway for estriol can be disrupted, resulting in decreased maternal serum levels. Other potential causes include placental insufficiency, anencephaly (a neural tube defect), and fetal growth restriction. In some cases, maternal factors like certain medications (including steroids and antibiotics) or conditions affecting liver function can also influence estriol levels. Low estriol is often detected during maternal serum screening tests like the triple or quad screen, which are typically performed between 15-20 weeks of pregnancy. If low estriol is detected, further diagnostic testing such as amniocentesis or detailed ultrasound may be recommended to evaluate fetal health and development 1.
Some key points to consider when evaluating low estriol levels include:
- Fetal demise or congenital abnormalities are potential causes of low estriol levels 2, 3
- X-linked ichthyosis, a microdeletion syndrome causing STS deficiency, is a common genetic cause of low estriol levels 1
- Placental insufficiency, anencephaly, and fetal growth restriction are also potential causes of low estriol levels 4, 5
- Maternal factors, such as certain medications or conditions affecting liver function, can also influence estriol levels 4
It is essential to note that the most recent and highest quality study, published in 2022, recommends the addition of risk estimation for STS deficiency when a low uE3 level is detected in the screening test 1. This highlights the importance of considering STS deficiency as a potential cause of low estriol levels, rather than solely focusing on more severe and rare syndromes like Smith-Lemli-Opitz syndrome.