Fetal Hydantoin Syndrome: Causes, Symptoms, and Support

Medically reviewed by Dr. Baraa Alnahhal, MD · Last reviewed: October 2026

Quick Answer: What is fetal hydantoin syndrome?

Fetal hydantoin syndrome is a condition caused by prenatal exposure to the antiseizure medication phenytoin. [3] It can cause malformations such as cleft lip, widely spaced eyes or underdeveloped fingers and nails, and some children have developmental delays. [3] Treatment is tailored and may include surgery and therapy. [3] Prevention relies on careful medication management and folic acid under medical guidance. [2] [3]

What the research says

• Phenytoin raises the risk of major malformations, but most exposed children are not affected. A Cochrane review of 49 studies found that the prevalence of major congenital malformations after phenytoin exposure was 5.4% (95% CI 3.6–8.1) in cohort studies, compared with 2.1% (95% CI 1.5–3.0) in children of women without epilepsy; the risk ratio was 3.81 (95% CI 1.91–7.57) versus women without epilepsy and 2.01 (95% CI 1.29–3.12) versus women with untreated epilepsy (PubMed: Bromley et al., Cochrane Database Syst Rev, 2023 [1]).

• Plan before pregnancy, don’t stop effective medication, and take folic acid. A 2024 AAN, AES and SMFM practice guideline recommends choosing medicines and doses that balance seizure control and fetal outcomes as early as possible before conception, exercising caution in removing or replacing an effective medicine once pregnant, and prescribing at least 0.4 mg of folic acid daily before and during pregnancy to people treated with antiseizure medication to decrease neural tube defect risk and possibly improve neurodevelopmental outcomes (PubMed: Pack et al., Neurology, 2024 [2]).

Overview of Fetal Hydantoin Syndrome

Fetal hydantoin syndrome refers to a specific pattern of features observed in infants who were exposed to hydantoin-based antiseizure medications, most notably phenytoin (Dilantin), while in the womb. [3] Phenytoin is classified as a teratogen, a substance capable of disrupting normal fetal development. [3]

Feature	Description
Primary Cause	Prenatal exposure to phenytoin (Dilantin) [3]
Prevalence	5% to 11% of exposed fetuses [3]
Timing of Signs	Some visible at birth; others appear in early childhood [3]
Core Components	Facial malformations, limb defects, and developmental delays [3]

Figure 1: How teratogens like phenytoin can reach the developing fetus.

It is important for expectant parents to understand that the majority of babies exposed to these medications are born without the syndrome. [3] However, because the risk exists, healthcare providers prioritize close monitoring and medication adjustments during pregnancy.

Recognizing the Signs and Symptoms

The features of fetal hydantoin syndrome can be categorized into physical malformations present at birth and developmental or intellectual challenges that become apparent as the child grows. [3]

Physical Features at Birth

Many of the physical signs are related to the development of the face, head, and extremities. These may include:

• Facial Structure: Widely spaced eyes (hypertelorism), a flatter or wider nasal bridge, and crossed eyes (strabismus). [3]

• Oral Health: The presence of a cleft lip or cleft palate. [3]

• Head Size: A head that is smaller than expected for the baby’s age (microcephaly). [3]

• Limb Development: Underdeveloped or malformed fingers, toes, and fingernails. [3]

Developmental and Intellectual Signs

As the child reaches early childhood, other symptoms may become noticeable:

• Developmental Delays: Being slow to reach milestones such as smiling, rolling over, sitting up, or walking. [3]

• Intellectual Disability: Challenges with learning, self-care, toilet training, or understanding complex concepts like time and money management. [3]

Category	Common Signs
Facial	Hypertelorism, flat nasal bridge, cleft lip/palate [3]
Limbs	Hypoplastic (underdeveloped) nails and distal phalanges [3]
Cognitive	Learning difficulties, developmental milestone delays [3]

Causes and Mechanisms

The syndrome is caused by the transfer of antiseizure medications through the placenta to the developing fetus. [3] While researchers know that phenytoin is the primary trigger, the exact biological mechanism of how it causes these specific malformations is not yet fully understood. [3]

Genetics likely play a significant role in determining which babies are affected. For example, a mother’s genetic makeup may influence how her body breaks down the medication, which in turn affects the level of exposure the fetus receives. Taking multiple types of antiseizure medications simultaneously also increases the risk compared to taking a single medication. [3]

Figure 2: Multiple factors contribute to fetal hydantoin syndrome, including medication exposure, genetics, maternal metabolism and placental transfer.

Diagnosis and Clinical Evaluation

There are no specific laboratory or genetic tests that can definitively confirm fetal hydantoin syndrome. [3] Instead, the diagnosis is made clinically by a healthcare provider based on two main factors:

1. Clinical Presentation: The presence of characteristic physical features or developmental delays in the child. [3]

2. Medical History: A confirmed history of the birth mother taking phenytoin or similar medications during pregnancy. [3]

In some cases, healthcare providers may suspect the condition during the prenatal period if significant birth defects are visible on a high-resolution ultrasound. However, a formal diagnosis is typically deferred until after birth. [3]

Management and Treatment Options

Treatment for fetal hydantoin syndrome is highly individualized, focusing on the specific needs and symptoms of each child. [3] Because the condition affects multiple systems, a multi-disciplinary team of specialists is usually required.

Surgical Interventions

Surgery may be necessary early in life to address physical malformations, such as:

• Repairing a cleft lip or cleft palate. [3]

• Other surgeries, depending on your child’s specific needs. [3]

Specialized Therapies

Therapy is a cornerstone of management for children with developmental or intellectual challenges:

• Physical Therapy: To help with motor skills and physical development. [3]

• Occupational Therapy: To assist with daily living skills and self-care. [3]

• Speech Therapy: To support language development and communication. [3]

Educational Support

Children may benefit from an Individualized Family Service Plan (IFSP), which outlines specific services and assistive technologies to help them reach their full potential in learning and social environments. [3]

Specialist	Role in Care
Pediatrician [3]	Primary care and coordination of specialists
Plastic Surgeon [3]	Repair of facial and limb malformations
Neurologist [3]	Monitoring brain development and seizure health
Psychologist [3]	Support for cognitive and emotional development

Prevention and Risk Management

Preventing fetal hydantoin syndrome involves careful planning and communication between the patient and their healthcare provider, ideally before pregnancy begins. [2] [3]

Medication Management

The most effective way to lower the risk is to optimize antiseizure treatment:

• Pre-Pregnancy Planning: Adjusting medication types and dosages before conception. [2] [3]

• Monotherapy: Aiming to use a single medication at the lowest effective dose rather than multiple drugs.

• Switching Medications: Moving to newer antiseizure medications that may have a lower risk of teratogenic effects. [2] [3]

Critical warning: You should never stop taking your antiseizure medication unless specifically instructed by your doctor. [3] Uncontrolled seizures during pregnancy can be life-threatening for both the mother and the developing fetus.

Nutritional Support

Healthcare providers often recommend folic acid supplements before and during pregnancy, as this has been shown to help protect against certain congenital malformations. [2] [3] Your provider will advise you on the right dose.

Figure 3: Management and prevention pathway, from pre-pregnancy planning to post-birth support.

Conclusion

While fetal hydantoin syndrome presents significant challenges, early diagnosis and a comprehensive support system can help children lead fulfilling lives. By working closely with a medical team to manage medications and utilizing available therapeutic resources, families can effectively navigate the complexities of this condition.

Next step: If you are taking antiseizure medication and are planning a pregnancy or have recently become pregnant, schedule a consultation with your neurologist and obstetrician immediately to discuss a safe management plan.

Further reading: Cleveland Clinic — Fetal Hydantoin Syndrome

Frequently Asked Questions

1. What is the primary cause of fetal hydantoin syndrome?

The primary cause is the exposure of a developing fetus to the antiseizure medication phenytoin (brand name Dilantin) during pregnancy. [3] This medication can interfere with normal fetal growth and development. [3]

2. Does every baby exposed to phenytoin develop this syndrome?

No. Statistics show that only about 5% to 11% of babies exposed to phenytoin develop the syndrome. [3] Most babies exposed to these medications are born without these specific birth defects. [3]

3. What are the most common physical signs visible at birth?

Common signs include widely spaced eyes, a flat nasal bridge, a cleft lip or palate, a smaller-than-average head size (microcephaly), and underdeveloped fingernails or toes. [3]

4. Can fetal hydantoin syndrome be diagnosed during pregnancy?

While there is no specific test, a high-resolution ultrasound during pregnancy may reveal certain physical birth defects that lead a doctor to suspect the syndrome, especially if there is a known history of phenytoin use.

5. Is there a cure for fetal hydantoin syndrome?

There is no single “cure” for the syndrome, as it involves physical and developmental changes that occurred during gestation. However, many of the physical issues can be corrected with surgery, and developmental delays can be managed with specialized therapies. [3]

6. Should I stop my epilepsy medication if I find out I’m pregnant?

Absolutely not. Stopping antiseizure medication abruptly can cause severe, prolonged seizures that are dangerous for both you and your baby. Always consult your doctor before making any changes to your medication.

7. How does folic acid help in these cases?

Folic acid is essential for proper fetal development, particularly of the neural tube. Supplementation can help reduce the risk of some birth defects associated with antiseizure medications. [2] [3] Your provider will advise you on the right dose.

8. What is an Individualized Family Service Plan (IFSP)?

An IFSP is a specialized document created by a team of professionals and the family to outline the specific services, therapies, and support a child with developmental delays needs to thrive.

9. Can other antiseizure medications cause similar issues?

Yes, other medications can also affect fetal development. For example, valproate products are known to carry a higher risk of serious effects than some other antiseizure drugs. [2] [3] This is why medication management is so personalized.

10. What is the long-term outlook for a child with this syndrome?

The outlook varies depending on the severity of the symptoms. [3] With early surgical intervention and ongoing physical, occupational, and educational therapy, many children are able to reach their milestones and live productive lives.

References

1. Bromley R, Adab N, Bluett-Duncan M, et al. Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child. Cochrane Database Syst Rev. 2023;8(8):CD010224. doi:10.1002/14651858.CD010224.pub3. PMID: 37647086.

2. Pack AM, Oskoui M, Williams Roberson S, et al. Teratogenesis, perinatal, and neurodevelopmental outcomes after in utero exposure to antiseizure medication: practice guideline from the AAN, AES, and SMFM. Neurology. 2024;102(11):e209279. doi:10.1212/WNL.0000000000209279. PMID: 38748979.

3. Cleveland Clinic. Fetal hydantoin syndrome. Cleveland Clinic Health Library. Medically reviewed; last updated April 2, 2024. https://my.clevelandclinic.org/health/diseases/fetal-hydantoin-syndrome

Medical Disclaimer

This article is for informational purposes only and does not constitute medical advice. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read here.