In which condition is alpha-fetoprotein (AFP) level generally decreased?

Alpha-Fetoprotein Levels in Down Syndrome

Alpha-fetoprotein (AFP) levels are generally decreased in Down syndrome (trisomy 21). This finding is well-established in the medical literature and serves as an important marker in prenatal screening programs.

Mechanism and Evidence for Decreased AFP in Down Syndrome

• Maternal serum AFP (MSAFP) levels in pregnancies with Down syndrome fetuses are significantly reduced to approximately 70% of the levels found in normal pregnancies 1, 2
• The American Society of Human Genetics has documented that the average MSAFP level in Down syndrome pregnancies is 0.72 multiples of the median (MOM), which represents a statistically significant reduction 1
• This reduction in AFP levels appears to originate in the fetus itself, with studies showing significantly lower hepatic AFP levels in Down syndrome fetuses compared to normal controls 2
• The difference is most pronounced at earlier gestational ages (17-19 weeks), where median AFP levels differ by about 20% 2

Clinical Application in Prenatal Screening

• Low MSAFP values are used as a screening marker for Down syndrome in the second trimester of pregnancy 1, 3
• The optimal timing for MSAFP screening for Down syndrome is between 16-18 weeks' gestation, which coincides with the recommended timing for neural tube defect screening 3
• The American Society of Human Genetics recommends using the risk of Down syndrome in a 35-year-old woman (1/270 in the second trimester) as a reasonable cutoff point for defining low AFP values 1

Comparison with Other Conditions

In contrast to Down syndrome, AFP levels are typically:

• Elevated in:

  • Open neural tube defects (original purpose of AFP screening) 1
  • Hepatocellular carcinoma 1
  • Yolk sac tumors (which produce AFP) 1
  • Gastroschisis, omphalocele, and other fetal abdominal wall defects 1
  • Cystic hygroma 1
  • Congenital nephrosis 1

• Not consistently decreased in:

  • Other chromosomal abnormalities like trisomy 18,45,X, mosaics, 47,XXY, 47,XXX 4
  • Trisomy 13 and 47,XYY (which may actually show elevated AFP levels) 4

Clinical Implications and Caveats

• When counseling patients with low MSAFP, clinicians should emphasize that this finding increases risk for all chromosomal abnormalities, not just Down syndrome 5
• The risk for all chromosomal abnormalities is approximately twice the calculated risk for Down syndrome alone 5
• Amniotic fluid AFP levels are also significantly lower in Down syndrome pregnancies compared to controls, but this pattern is not seen in trisomies 13 and 18 6
• Selection of cases for karyotyping based solely on low AFP levels would miss other aneuploidies 4

Therefore, among the options presented (hepatocellular cancer, yolk sac tumors, Down syndrome, neural tube defects), Down syndrome is the condition in which alpha-fetoprotein levels are generally decreased.