Overview

Fetal hydantoin syndrome (FHS) refers to a known collection of characteristic mental and physical defects which occur in babies who were exposed to certain anti-seizure medications during pregnancy. The specific medication is Dilantin (or phenytoin) and is usually prescribed to help prevent and control seizures in people with epilepsy by calming the overactive nerves in the body.¹

Understanding fetal hydantoin syndrome 

Fetal hydantoin syndrome (FHS) is a rare condition which impacts babies who were exposed to certain anti-seizure medications during pregnancy. Healthcare professionals are not yet completely sure of the mechanism which results in fetal hydantoin syndrome, but are confident that other factors, such as genetics, can play a part in determining which fetuses are affected. 

More research and funding are required to completely understand the mechanisms and risk factors of fetal hydantoin syndrome as much of the disorder is not yet fully understood.

Causes

Fetal hydantoin syndrome is a result of genetic mutations in the DNA. This can happen as a result of medication or genetic causes, and other external factors.²

Medication 

Not all babies exposed to the drug, phenytoin, develop fetal hydantoin syndrome; the risk is around 5-10% of exposed fetuses. It is not known exactly how much phenytoin is required to be present for fetal hydantoin syndrome to occur. It is also not yet known if it is phenytoin itself which causes fetal hydantoin syndrome, or one of its metabolites following its breakdown in the body. 

Healthcare providers stress that pregnant parents should not stop taking anti-seizure medication without first consulting their healthcare provider, who will discuss their individual risks. 

Genetic causes 

Fetal hydantoin syndrome is known to be caused by genetic mutations (changes in the DNA), so it is not just taking phenytoin that can cause it. Genetic mutations can be hereditary, so parents can pass them down to their children, or they can develop independently when the cells are dividing. 

There are many causes of genetic mutations, such as UV damage from excessive UV exposure from places like the sun, or contracted viruses and other environmental factors, e.g. smoking. This means that all in all, fetal hydantoin syndrome cannot be specifically targeted to be prevented, but there are steps you can take to determine if your child is more at risk.²

Healthcare professionals may ask you to collect family healthcare data to determine if other family members have experienced any symptoms. If you suspect you or your child could have fetal hydantoin syndrome, discuss this with your healthcare provider. 

Prevention 

A complete cure of fetal hydantoin syndrome is not possible; therefore, prevention strategies are essential.  Individual cases and risks can be discussed with healthcare professionals and doctors to see if alternative medications can be tried or stopped altogether. Do not stop taking any medication without first consulting your doctor. 

Your healthcare provider may suggest taking folic acid supplements before and after pregnancy to help protect against congenital malformations. If the medication is continued throughout pregnancy, your healthcare provider will ensure regular appointments to monitor both your and the baby's health. 

Physical symptoms and signs 

The characteristic features of fetal hydantoin syndrome include:²

• Crossed  eyes
• Cleft  lip or cleft palate 
• Flatter  or wider nasal bridge compared to expected 
• Smaller  head size than expected 
• Underdeveloped  or malformed fingers, toes and nails 
• Further distance between eyes than expected 

These are not all the potential symptoms, as they vary from child to child. Not all signs are noticeable from birth, with many developing later on as the child grows and develops. This is especially true with signs of intellectual disability, which many show in terms of slower progression compared to other babies of similar age. For example, the child may be affected in terms of how they interact with their environment. 

Effect on cognitive development 

Some affected children or infants may show signs of slower cognitive development, which sometimes improve as the child grows up. This is usually seen when they are learning to crawl or sit up by themselves. 

Studies have not yet determined the full cognitive effects of fetal hydantoin syndrome, but research has suggested that there is an increased risk of developing some learning disabilities, particularly in their verbal development.²

A lot is still unknown about the cognitive development impacts of fetal hydantoin syndrome, so much more research is required. 

Assessing risk before birth

Unfortunately, the damage caused by phenytoin to the fetus during pregnancy is irreversible; therefore, prevention strategies are the best way forward. 

Genetic counseling 

Genetic mutations, or changes in the DNA, are the underlying cause of fetal hydantoin syndrome, and although this is typically associated with external factors such as smoking or UV damage, it can be hereditary. This means it can be passed down by parents to their child. Because of this,  researchers recommend genetic counselling prior to pregnancy to determine your risk. 

Genetic counselling helps to identify their risk of a variety of genetic conditions, not just fetal hydantoin syndrome. It involves gathering and analysing the parents' families' genetic history and calculating any patterns and chances of occurrence. The counsellor will provide advice and signpost if necessary, according to each family's specific cases.⁴

The genetic counsellor will give you options if you have a child with fetal hydantoin syndrome and do not want your next child to inherit it. If you are genetically at risk but still want to have a baby, there are options to consider; please discuss your results with a professional to assess all possible options.

Health assessments pre-pregnancy

Undergoing health assessments prior to pregnancy is not only beneficial for the fetus, but for the mother too. They can range from assisting in conception to helping determine the best practices during pregnancy for the babies' and mothers' optimum health.⁵

A preconception test helps determine if the body is ready for pregnancy, and, like genetic counselling, the provider will look for health conditions that could affect the baby. The healthcare provider may talk to you about a variety of things:

• Taking folic acid to assist in healthy growth and development
• Quitting smoking, drinking or overusing medications or drugs
• Medications you may be taking - especially phenytoin
• Vaccinations to make sure you are up-to-date

Medication during pregnancy 

Alternative treatments for epilepsy 

If you are taking phenytoin for your epilepsy management and you are planning on becoming pregnant or already are pregnant, immediately contact your healthcare provider to discuss your options. Do not stop taking the medication without first consulting a doctor, as you may be putting yourself at an elevated risk. Healthcare providers recommend always having a preconception appointment. 

Your healthcare provider may change your medication to one with lower risks or try to get the seizures under better control. Their advice will vary depending on your individual case as well as how you feel about making any of the changes they suggest. 

A review in the UK determined which epilepsy medications are safer to use during pregnancy than phenytoin; these include Lamotrigine (Lamictal) and Levetiracetam (Keppra). The studies showed that these two medications did not increase the risk of physical birth abnormalities.⁶  Epilepsy medication affects each individual differently, so it is important to discuss this with your general practitioner or a specialist so they can monitor your symptoms and any concerns you may have. 

Support for expectant mothers 

Many expectant or new mums with epilepsy find pregnancy especially daunting, but there is support available and steps you can take to make sure you are prepared. 

If you have seizures, your healthcare provider will advise you to keep taking your anti-seizure medication throughout your pregnancy as long as the specific medication is suitable. 

Prenatal screening

To monitor the growth and development of the fetus, you can undergo prenatal screening, which involves a combination of checks. 

• Ultrasound - At particular intervals throughout the pregnancy, usually 12 weeks and 18-20 weeks. This helps the healthcare provider to see how the fetus is developing. It can also help to provide some peace of mind to the mother if they are concerned
• Blood tests - Used to measure levels of a number of things, such as alpha-fetoprotein which indicates the risk of the baby being born with specific disorders

More information 

Visit the following links for more information and support. 

The UK Epilepsy and Pregnancy Register - Conducts research aiming to make pregnancy safer for people with epilepsy. 

Epilepsy in Pregnancy - The Royal College of Obstetricians and Gynecologists - Provides information for the mother and those around them. 

Epilepsy Medicines and Pregnancy - This leaflet, produced by The Medicines and Healthcare Regulatory Authority (MHRA), offers support in understanding the risks of some epilepsy medicines when used during pregnancy. 

Epilepsy and Seizures 24/7 helpline - Has trained information specialists on hand to answer questions, provide support and guidance, as well as signpost to other national or local resources. 

Summary 

Fetal hydantoin syndrome results from genetic mutations during pregnancy, usually caused by the anti-seizure medication Phenytoin. The severity of FHS varies from pregnancy to pregnancy, and there is no current cure; therefore, prevention is the best option. If you are trying to conceive or are pregnant and have epilepsy, consult a medical professional for advice and support - do not stop taking any medication without consultation first.