Folic Acid Dose for Pregnant Women on Phenytoin
A pregnant woman taking phenytoin should receive 5000 micrograms (5 mg) of folic acid daily, starting immediately (ideally 3 months before conception) and continuing through the first trimester.
Risk Stratification
Women with epilepsy taking antiepileptic medications like phenytoin are classified as high-risk for neural tube defects (NTDs) by the American College of Medical Genetics 1. This elevated risk stems from:
- The teratogenic effects of phenytoin and other antiepileptic drugs, which are established human teratogens 2
- Anticonvulsant interference with folic acid metabolism, leading to increased NTD risk 2
- A baseline NTD risk that is significantly higher than the general population 1
Dosing Algorithm
High-risk women (including those on phenytoin) require 4-5 mg (4000-5000 μg) of folic acid daily 1, 3. The specific regimen is:
- Start immediately (ideally 3-6 months before conception) at 5 mg daily 1
- Continue through 12 weeks of gestation at 5 mg daily 1
- Reduce to 0.4-1.0 mg daily after 12 weeks of gestation 1
This contrasts sharply with standard-risk women, who only need 0.4-0.8 mg (400-800 μg) daily 1, 3.
Practical Prescribing Considerations
- Prescribe a single 5 mg prescription-strength folic acid tablet rather than multiple over-the-counter multivitamins to avoid excessive intake of other vitamins, particularly vitamin A, which is teratogenic at high doses 1
- Rule out vitamin B12 deficiency before initiating high-dose folic acid (>1 mg), as high-dose folic acid can mask pernicious anemia while neurologic damage progresses 1, 4
- Start supplementation immediately rather than waiting for planned conception, since more than 50% of pregnancies are unplanned and neural tube closure occurs within the first 28 days after conception 1
Critical Clinical Caveats
- Maintain seizure control: Phenytoin should generally be continued if it provides good seizure control, as uncontrolled seizures pose significant risks to both mother and fetus 1
- Limitations of prevention: Even with adequate 5 mg folic acid supplementation, not all NTDs can be prevented due to their multifactorial or monogenic etiology, though supplementation prevents approximately 50-72% of cases 1
- Monitoring required: Women taking phenytoin should undergo perinatal diagnostic ultrasound to rule out NTDs, even with supplementary folic acid 1
- Therapeutic drug monitoring: Phenytoin levels should be monitored during pregnancy, as pregnancy increases clearance and decreases drug concentrations 5, 6
Safety Monitoring
Vitamin B12 deficiency is uncommon in young women (affecting fewer than 1% of this population), but screening before initiating doses exceeding 1 mg daily remains prudent to prevent masking pernicious anemia 1. The FDA label confirms that doses greater than 0.1 mg should not be used unless vitamin B12 deficiency has been ruled out or is being adequately treated 4.
Answer: C - 5000 Microgram