Fetal Hydantoin Syndrome

What is Fetal Hydantoin Syndrome?

Fetal Hydantoin Syndrome or Fetal Dilantin Syndrome is a rare disease that is caused when a fetus is exposed to Phenytoin, an anticonvulsant drug in the form of Dilantin. Some of the principal syndromes of this disorder include microcephaly or developing an unusually small head, brain malfunctions, developmental delays, growth deficiencies, skull deformities, abnormal facial features, etc.

The drug Dilantin is commonly administered to epilepsy patients. Fetal Hydantoin Syndrome comprises the entire range of abnormalities caused by the teratogenicity of this drug.

Some of the other names for this disease include Congenital Hydantoin Syndrome, Phenytoin Embryopathy or Dilantin Embryopathy.

Fetal Hydantoin Syndrome Symptoms

Children born with Fetal Hydantoin Syndrome may show developmental problems at birth. They may have an abnormally small size at birth, have an increased growth of hair on the face and body and show poor muscle tone. They may also display impaired development of fingernails and toenails.

The developmental delays reduce in effect as the children grow up. However, the children still lag behind in their development compared to their unexposed siblings. Signs of growth delays are evident throughout life, as are the tendencies to grow increased body hair.

Almost around 3% of infants who are exposed to Dilantin tend to have severe developmental delays, cleft lip and palate and brain malformations.

A detailed list of the various symptoms of this disease is given below:

Craniofacial symptoms – Wide anterior fontanelle, broad nasal bridge, broad alveolar ridge, short neck, hypertelorism, microcephaly, cleft lip/palate, low set ears, low hairline, coarse scalp hair, epicanthal folds, coloboma, ptosis, strabismus

Performance: Mild mental deficiency or occasional borderline tendencies can be found in children. A child normally performs better than what is predicted or expected of him or her in infancy.

Growth: Moderate growth deficiency is found at the prenatal stages.

Gastrointestinal Disorders: Possible symptoms of gastrointestinal disorders include anal atresia, duodenal atresia and Pyloric stenosis.

Cardiovascular abnormalities: Cardiovascular problems can occasionally emerge. The common symptoms of such occurrences are coarctation of aorta, aortic valvular stenosis, septal defects and PDA.

Limbs: Hypoplasia or under-development of distal phalanges, small or absent nails, digital thumb, altered palmar crease, dislocated hip

Other Symptoms: Some of the other symptoms of Fetal Hydantoin Syndrome include inguinal and umbilical hernia as well as widely spaced small nipples.

Fetal Hydantoin Syndrome Causes

Fetal Hydantoin Syndrome is caused by the exposure of the fetus to phenytoin or Dilantin, an anticonvulsant drug which is prescribed for epilepsy cases. It is important to remember that of all the infants exposed to this drug only a few will be affected by this disorder.

Cases have been documented where it was found that both the unaffected and affected siblings were exposed to this drug in the same proportions. Certain other factors might make it more likely that the infant will exhibit symptoms of this syndrome, such as decreased levels of folic acid in the mother’s body.

Connection between Dilantin and Fetal Hydantoin Syndrome

The Dilantin drug is quite popularly used in the treatment of epilepsy and seizure-oriented disorders. However, use of this drug has been controversial and seriously debated over. The anticonvulsant property of this drug is linked with major birth injuries and several adverse side effects. Questions have been raised regarding the safe use of this drug mainly due to its use of Phenytoin, a well-known teratogen as a constituent. Phenytoin is capable of hampering the development of the fetus. The drug may also disrupt the absorption of folic acid, otherwise a normal bodily function. Folic acid is an essential ingredient in the production of blood cells. It has been seen that those infants who are deprived of proper amount of folic acid at the beginning stages of their fetal development runs the risk of developing serious birth injuries. Generally for most women, a daily dosage of 400 micrograms of folic acid before and during pregnancy is sufficient for preventing birth injuries up to 70%. It is advisable for epileptic women to consume around 4 milligrams of folic acid daily as the anti-seizure drugs they take tend to restrict folic acid absorption.

The birth injuries commonly associated with Fetal Hydantoin Syndrome and Dilantin syndrome such as heart malformations, cleft lip and palate, usually occurs in around 2% to 3% of all pregnancies. However, around 4% to 7% infants affected by these symptoms have mothers who regularly take Phenytoin. The potential risks associated with the use of Phenytoin and Dilantin has been known for several years. The New England Journal of Medicine published a paper in 2001 which stated that anticonvulsant drugs are among the most commonly known threats to a fetus in uteri. Researchers presenting the paper also suggested that the frequency of birth defects in newborn children is closely related with the use of administered anticonvulsant drugs rather than the disorder of epilepsy itself. In the year 2008, FDA included Dilantin in its list of drugs having “Potential Signs of Serious Risks,” thus marking the drug as a potentially dangerous one which requires further study.

Risks associated with Fetal Hydantoin Syndrome

The risks associated with the intake of Dilantin or Phenytoin are:

  • Women taking Dilantin for the treatment of epilepsy runs the risk of delivering a child who is 2 to 3 times more prone to suffer from congenital defects. Increased risks of Fetal Hydantoin Syndrome could result from epilepsy or the drugs or a combination of both. The drugs are considered to be the essential cause behind the birth defects.
  • The chances of seeing full effectiveness of the syndrome in a child is almost 10%. The probability of a child displaying some of the characteristics of the disorder is an additional 33%.
  • Some researchers suggest that Phenytoin is a transplacental carcinogen. In some cases, tumors have been reported to develop in uterus exposed to Phenytoin.
  • Phenytoin increases hepatic metabolism in the body. It also impairs GI absorption. These results in the deficiency of folic acid in the epileptic woman which increases the risk of giving birth to a baby having spinal abnormalities.
  • In some cases, the newborn child runs the risk of having early hemorrhagic disease. This usually happens in the first 24 hours after birth and can prove to be fatal. The exact factors causing this are unknown. It is believed that Phenytoin depletes the already low levels of fetal vitamin K and suppresses the coagulation factors II, VII, IX, and X which are dependent on vitamin K. To combat such tendencies, it is recommended that the pregnant woman takes an oral dosage of vitamin K during the last 2 months of her pregnancy. If trauma or difficult labor is suspected, C section procedure is to be carried out while intravenously administering vitamin K to the newborn child in the delivery room.
  • If the epileptic woman avoids taking Phenytoin while she is pregnant, she can have seizures which can result in the baby having fetal hypoxia.

Phenytoin and Breast Feeding

The risks associated with breast feeding while consuming Phenytoin are:

  • Phenytoin can easily get combined with breast milk. The ratio between milk and plasma usually ranges between 0.18 and 0.54.
  • The infant runs little risk of getting affected if the Phenytoin levels in the mom’s body are kept within therapeutic range.
  • Decreased sucking and drowsiness were observed and reported in one infant. Other than that, no ill effects have been recorded.
  • The American Academy of Pediatrics believes the drug Phenytoin causes no adverse effects to breast feeding.

Populations affected by Fetal Hydantoin Syndrome

Almost 2 million women around the world are exposed to Dilantin or Phenytoin while they are pregnant. There is a 7% to 10% risk that the fetus of an epileptic woman exposed to Phenytoin will have some or all the symptoms of the Fetal Hydantoin Syndrome.

Fetal Hydantoin Syndrome Related Disorders

Some disorders may have symptoms which are closely related to those of Fetal Hydantoin Syndrome. A proper diagnosis is required to identify these different diseases which have similar symptoms. Some of these diseases are

  • Aarskog Syndrome
  • Noonan Syndrome
  • Fetal Alcohol syndrome (FAS)

Fetal Hydantoin Syndrome Prevention

A pregnant woman should be treated with a single anticonvulsant before conception and during her pregnancy as it seems that children who are exposed to several anticonvulsants are significantly more prone to develop serious birth defects.

It is also important for all women to consume adequate quantities of folic acid in their diet both prior to conception and throughout pregnancy. Habits such as drinking alcohol and smoking are harmful and should be strictly avoided during pregnancy.

Fetal Hydantoin Syndrome Treatment

In case of a cleft lip/palate, a team of specialists including pediatricians, surgeons, dental specialists, psychologists and speech pathologists can help in planning the child’s medical treatment and rehabilitation. Surgical procedures can cure cleft lip. These surgeries are usually conducted when the child is still quite young. After a surgery conducted when the child is an infant, a second surgery may sometimes be undertaken for cosmetic reasons when the child grows a bit older.

Cleft palates can be cured by surgeries that can be conducted in a single operation or in stages, depending on the severity of the case. The first palate surgery is normally conducted when the child is still a toddler.

Children with learning disabilities can be helped by special forms of education and related services. The treatment is carried out in a symptomatic and supportive manner.

So if you are a pregnant woman taking Phenytoin due to your epilepsy, you should consult your doctor immediately to ensure the birth of a healthy baby.