From the Guidelines
Trisomy 18 typically causes maternal serum alpha-fetoprotein (MSAFP) levels to be low during pregnancy screening. This is based on the findings of a study published in the journal Genetics in Medicine in 2004 1, which reported that in most cases of trisomy 18, the levels of MSAFP are low. The study also noted that serum screening using multiple analytes, including AFP, hCG, and uE3, can identify women at risk for having a fetus with trisomy 18, with a detection rate of at least 70%.
Some key points to consider when interpreting MSAFP levels in the context of trisomy 18 include:
- The biological reason for the reduction in MSAFP levels is thought to be related to abnormal placental function and fetal development associated with trisomy 18.
- Unlike conditions such as neural tube defects, which cause elevated MSAFP levels, chromosomal abnormalities like trisomy 18 often present with reduced MSAFP.
- MSAFP screening alone is not diagnostic for trisomy 18, and abnormal results require follow-up with more definitive testing such as cell-free DNA screening, amniocentesis, or chorionic villus sampling to confirm the diagnosis.
- Multiple marker screening (quad screen) that includes MSAFP along with human chorionic gonadotropin (hCG), unconjugated estriol, and inhibin-A provides better detection rates for trisomy 18 than MSAFP alone, as reported in the study 1.
It's essential to inform patients that MSAFP screening is only a screening test for trisomies 21 and 18 and not a replacement for more invasive diagnostic tests like CVS or amniocentesis, as noted in the study 1.
From the Research
Trisomy 18 and MSAFP Levels
- Trisomy 18 is generally associated with low maternal serum alpha-fetoprotein (MSAFP) levels 2, 3, 4, 5, 6.
- The median MSAFP levels in trisomy 18 pregnancies without complications are typically lower than those in normal pregnancies, with reported median values ranging from 0.6 to 0.65 multiples of the median (MoM) 2, 3, 6.
- However, the presence of complications such as exomphalos or neural tube defects can lead to higher MSAFP levels, even within the normal range or elevated 2, 3.
- Studies have consistently shown that low MSAFP levels are associated with an increased risk of trisomy 18, making MSAFP a useful marker in prenatal screening 2, 3, 4, 5, 6.
Screening for Trisomy 18
- A two-step screening strategy using MSAFP, free beta-human chorionic gonadotrophin (beta-hCG), and pregnancy-associated plasma protein A (PAPP-A) has been proposed for detecting trisomy 18 3.
- This approach can detect a high percentage of trisomy 18 cases with a low false-positive rate, making it a valuable tool for prenatal screening 3.
- Other studies have also explored the use of additional markers, such as unconjugated oestriol (uE3) and human chorionic gonadotropin (hCG), to improve the detection of trisomy 18 6.