What causes elevated MSAFP during the first trimester?

Question

Hello doctor,

We had our first trimester bloodwork done, which screened negative for Down syndrome. That said, the MSAFP (maternal serum alpha-fetoprotein) level was elevated at 95 µg/L, or 7.28 MoM. The first trimester ultrasound went well; the nuchal translucency (NT) measured 1.8 mm. I understand that this is not typically a cause for concern since the test was done during the first trimester, around week 12. However, I am still curious, why would the MSAFP be elevated?

I am currently on artificial thyroid medication and taking prenatal multivitamins with folic acid.

Please advise.

Answer 1

Hello,

Welcome to icliniq.com.

I understand your concern.

You are absolutely right that an elevated MSAFP (maternal serum alpha-fetoprotein) in the first trimester is unusual and not typically part of the standard interpretation for enhanced first-trimester screening (eFTS), which primarily evaluates PAPP-A (pregnancy-associated plasma protein-A), free β-hCG (free beta-human chorionic gonadotropin), and the nuchal translucency (NT) measurement.

Key points about your case:

AFP is not typically assessed in the first trimester. It is more informative when measured in the second trimester (usually between 15 to 20 weeks) as part of the quad screen. First-trimester AFP levels are not well-established and are not routinely used to screen for neural tube defects or other fetal anomalies.
Your NT (nuchal translucency) measurement of 1.8 mm at 12w2d is completely normal, well below the commonly used 3.5 mm threshold for further evaluation.
A MoM of 7.28 is high, but if this AFP value was obtained from a sample taken during the first trimester, it is likely not clinically significant. AFP naturally rises with gestational age, and applying second-trimester reference ranges to a 12-week sample would result in an artificially elevated MoM.

Possible explanations for elevated MSAFP at week 12:

Reference range mismatch: If the laboratory used second-trimester MoM calculations for a first-trimester sample, this could falsely elevate the result.
Technical artifact: Errors such as incorrect gestational dating, maternal weight input, or analytical variation can all impact MoM results.
Maternal factors: Conditions like hypothyroidism (especially if not well controlled), certain autoimmune disorders, or (less likely in your case) twin pregnancy can elevate AFP levels.
Placental variations: In rare cases, abnormal placental function can lead to elevated AFP. However, with a normal ultrasound and NT, this is unlikely to be significant.

What to Expect:

Since your NT was normal and you are awaiting NIPT (non-invasive prenatal test) results, that will provide a more comprehensive view of chromosomal conditions. You will also likely be offered second-trimester serum screening or an anatomy scan, where AFP levels will be reassessed if needed.

You are asking the right question, and your instincts are correct; AFP is not clinically actionable at 12 weeks. This elevated value should not be a cause for concern. Just continue with your NIPT and routine follow-up. If necessary, your provider may repeat AFP testing during the appropriate timeframe.

I hope this helps answer your questions.

Thank you.