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Alpha-fetoprotein (AFP, α-fetoprotein) — Pregnancy Reference Values

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Alpha-fetoprotein (serum)

Alpha-fetoprotein (AFP) is produced by the fetal liver and yolk sac. Maternal serum AFP (MSAFP) rises through the 1st–2nd trimesters, peaking around 32 weeks. In screening, AFP is interpreted as multiples of the median (MoM) for gestational age.

Units Nonpregnant Adult 1st Trimester* 2nd Trimester* 3rd Trimester*
ng/mL < 15 18 – 119 96 – 302 160 – 550
µg/L < 15 18 – 119 96 – 302 160 – 550

* Minimum and maximum values. Small sample size.

Clinical note: AFP interpretation relies primarily on MoM rather than absolute values. Dating, maternal weight, ethnicity, diabetes status, and plurality significantly influence MoM calculations.

Causes of Elevated Maternal Serum AFP
  • Incorrect gestational dating (most common cause)
  • Multiple gestation (AFP roughly doubles with twins)
  • Open neural tube defects
    • Anencephaly
    • Open spina bifida
  • Ventral wall defects
    • Gastroschisis
    • Omphalocele
  • Other fetal conditions
    • Sacrococcygeal teratoma
    • Skin or soft tissue disruption
    • Certain renal or GI disorders with protein leakage
  • Placental or pregnancy complications
    • Fetal demise
    • Placental abruption
    • Chorioangioma
  • Maternal causes
    • Hepatocellular carcinoma
    • Germ cell tumors (yolk sac tumors)
    • Chronic hepatitis / cirrhosis
    • Hereditary persistence of AFP

Markedly elevated MSAFP → confirm gestational age and plurality → targeted ultrasound → evaluate fetal anatomy and placenta.

Causes of Low Maternal Serum AFP
  • Incorrect gestational dating (overestimated GA)
  • Aneuploidy
    • Trisomy 21 (Down syndrome)
    • Trisomy 18
  • Maternal diabetes (especially pregestational)
  • MoM calculation errors
    • Incorrect weight entry
    • Incorrect race/ethnicity factor
    • Incorrect gestational dating method
  • Nonpregnant adults
    • Very low AFP is generally not diagnostic

Low AFP is interpreted in combination with other serum markers as part of aneuploidy screening (e.g., quad screen).

References

  1. Seppälä M, Ruoslahti E. Radioimmunoassay of maternal serum AFP during pregnancy and delivery. Am J Obstet Gynecol. 1972;112:208–12.
  2. Kratz A, Ferraro M, Sluss PM, Lewandrowski KB. Laboratory reference values. N Engl J Med. 2004;351:1548–63.