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Serum Folate — Pregnancy Reference Values

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Serum Folate

Serum folate reflects recent dietary intake and short-term folate status. Unlike red cell folate, it can fluctuate rapidly with diet, supplementation, and hemolysis.

Units Nonpregnant Adult 1st Trimester 2nd Trimester 3rd Trimester
ng/mL 5.4 – 18 2.6 – 15 0.8 – 24 1.4 – 20.7
nmol/L 12 – 41 6 – 34 1.8 – 54 3 – 47
Physiology in pregnancy
  • Serum folate decreases through pregnancy due to hemodilution and increased placental transfer.
  • Maternal folate requirements rise substantially to support fetal neural tube and erythropoiesis.
  • Serum folate reflects short-term intake and supplementation status.
  • Low serum folate with normal RBC folate may reflect recent dietary fluctuation rather than true deficiency.
Causes of low serum folate
  • Poor dietary intake (leafy greens, legumes, fortified foods)
  • Malabsorption (celiac disease, Crohn’s disease, bariatric surgery)
  • Increased pregnancy requirement (especially multiple gestation)
  • Chronic hemolysis increasing folate utilization
  • Alcohol use disorder
  • Antifolate medications (methotrexate, phenytoin, sulfasalazine, trimethoprim)
  • Liver disease reducing folate storage
  • True folate-deficient megaloblastic anemia
Causes of elevated serum folate
  • High-dose folic acid supplementation (prenatal vitamins with added folate)
  • Fortified diet producing supraphysiologic folate levels
  • Vitamin B12 deficiency (functional folate trapping)
  • Laboratory artifact (sample hemolysis)
  • Reduced erythropoiesis
  • Renal failure (reduced metabolite clearance)
Special obstetric considerations
  • Low folate is associated with neural tube defects, fetal growth restriction, and macrocytic anemia.
  • WHO recommends maintaining adequate folate status throughout pregnancy.
  • High folate does not cause toxicity but may mask underlying vitamin B12 deficiency.
  • RBC folate is preferred to confirm chronic deficiency when serum folate is borderline.

References

  1. Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies. Obstet Gynecol. 2009.
  2. World Health Organization. Optimal serum and RBC folate concentrations in women of reproductive age. 2015.
  3. NIH Office of Dietary Supplements. Folate Fact Sheet for Health Professionals.
  4. Pfeiffer CM et al. Laboratory considerations for folate testing. Clin Chem Lab Med. 2013.
  5. O’Leary F, Samman S. Vitamin B12 and folate in pregnancy. Nutrition Reviews. 2010.
  6. Allen LH. Causes of folate deficiency. UpToDate (2025).
  7. ARUP Laboratories. Serum Folate Reference Interval Documentation.
  8. Mayo Clinic Laboratories. Folate, Serum Test ID: FOLS.