Phenytoin is not considered safe in pregnancy. The FDA warns that prenatal exposure increases the risk of birth defects, and the drug’s own label recommends that all women of childbearing age discuss alternative treatments with their healthcare provider. The rate of major malformations in babies exposed to phenytoin monotherapy ranges from about 3% to 7%, compared to a baseline risk of 1% to 3% in the general population. That translates to roughly a 2.4-fold increase in risk.
Types of Birth Defects Linked to Phenytoin
The pattern of abnormalities associated with prenatal phenytoin exposure has a name: fetal hydantoin syndrome, first described in 1975. The hallmark features include distinctive facial characteristics (a deep nasal bridge, low-set ears, short neck), cleft lip and palate, and underdeveloped fingertips and toenails. Some affected babies also have microcephaly, meaning a smaller-than-expected head size.
Heart defects are another recognized risk. These include holes between the heart’s chambers (ventricular septal defects), narrowing of blood vessels near the heart, and valve abnormalities. Growth restriction and hernias have also been documented. Not every exposed baby develops these problems, but the risk is meaningfully higher than in unexposed pregnancies.
Effects on Cognitive Development
The concerns extend beyond physical birth defects. In a controlled study comparing children exposed to phenytoin in utero with matched controls, the exposed children scored an average of 10 IQ points lower. They also performed significantly worse on language development assessments. A substantial number of phenytoin-exposed children scored 84 or below on cognitive tests, a threshold that indicates below-average intellectual functioning. The researchers concluded this effect was independent of the mother’s own intelligence or home environment.
For context, the American Academy of Neurology notes that phenytoin performs better than valproic acid on neurodevelopmental measures. Children exposed to valproic acid in utero show even larger drops in IQ. But phenytoin still carries meaningful cognitive risk compared to newer options like lamotrigine and levetiracetam.
Why Phenytoin Causes These Problems
The leading explanation involves folate, a B vitamin critical to fetal development. Phenytoin appears to interfere with how the body processes folate, lowering levels in the mother’s blood during key stages of pregnancy. Interestingly, animal research has shown that even when maternal folate drops, the embryo’s own folate levels may not change, suggesting the mechanism is more complex than simple folate deficiency. Phenytoin also reduces the activity of a specific enzyme involved in folate processing in the liver, which may disrupt the supply of folate-dependent building blocks the developing baby needs for normal organ formation.
How Pregnancy Changes Phenytoin Levels
Pregnancy itself makes phenytoin harder to manage. The body clears the drug roughly twice as fast during pregnancy compared to normal, meaning blood levels can drop significantly even if you’re taking the same dose. Lower drug levels increase the risk of breakthrough seizures, which carry their own serious dangers for both mother and baby, including falls, oxygen deprivation, and placental injury.
This creates a difficult clinical situation. Raising the dose to prevent seizures increases fetal exposure, while keeping the dose stable may leave seizures poorly controlled. Women who must remain on phenytoin during pregnancy typically need more frequent blood level monitoring so doses can be adjusted carefully throughout each trimester.
Bleeding Risk in Newborns
Phenytoin belongs to a group of medications that rev up certain liver enzymes in the fetus. This enzyme activity can accelerate the breakdown of vitamin K, which is essential for blood clotting. More than 40 case reports have linked maternal use of these types of anti-seizure drugs to bleeding problems in newborns. While routine vitamin K supplementation for the mother during the last month of pregnancy has been recommended based on these case reports, the evidence for this practice is not definitive. Vitamin K given to the baby at birth (which is standard practice) remains an important safeguard.
Safer Alternatives for Seizure Control
Current guidelines from the American Academy of Neurology and the American Epilepsy Society position phenytoin as a less favorable choice for pregnant women with epilepsy. Lamotrigine and levetiracetam are generally preferred because they carry lower rates of birth defects and have less evidence of cognitive harm to the developing baby. The FDA label for phenytoin itself states that alternative therapy should be considered for women of childbearing age.
Switching medications is not always straightforward, though. Some women have seizure types that respond best to phenytoin, or they may have tried and failed other drugs. In those cases, the risk of uncontrolled seizures has to be weighed against the risk of fetal harm. This decision is highly individual and depends on seizure frequency, severity, and how well other medications have worked in the past. The key point is that this conversation should happen before pregnancy whenever possible, since the highest risk period for birth defects is the first trimester, often before a woman knows she’s pregnant.
One practical consideration worth noting: high-dose folic acid supplementation, commonly recommended for women on anti-seizure drugs, can itself lower phenytoin blood levels. This interaction needs to be accounted for if phenytoin remains part of the treatment plan.
Breastfeeding on Phenytoin
In contrast to the pregnancy risks, phenytoin appears to be compatible with breastfeeding. Only small amounts pass into breast milk, typically ranging from about 0.3 to 4.5 mg/L depending on the dose and timing. These levels are low enough that breastfed infants generally tolerate the exposure without difficulty. One study found that breastfed infants of mothers on phenytoin actually had higher IQs and better verbal abilities at age 6 compared to formula-fed infants in the same situation. Rare allergic-type reactions in infants are possible but uncommon. If you need phenytoin after delivery, continuing to breastfeed is considered reasonable.