Diphenylhydantoin teratogenicity in man

Area of Science:

• Obstetrics and Gynecology
• Teratology
• Developmental Pediatrics

Background:

• Anticonvulsant medications, such as diphenylhydantoin, are frequently prescribed during pregnancy.
• Maternal dosage and pharmacokinetics can significantly influence fetal exposure and potential teratogenic effects.
• Understanding the risks associated with specific drug dosages is crucial for prenatal care.

Observation:

• A case study details fetal teratogenic damage in an infant exposed to an unusually high maternal dosage of diphenylhydantoin (600 mg daily).
• The mother weighed 40 kg and received the dosage throughout her pregnancy.
• The infant presented with a constellation of congenital anomalies.

Findings:

• Congenital anomalies included digital hypoplasia (narrowed digits, absent nails and distal phalanges), facial dysmorphism (broad nasal bridge, anteverted nostrils, prominent upper lip), and other features like coarse scalp hair and a pilonidal sinus.
• At 7 months, the infant exhibited delayed ossification of distal phalanges, a small anterior fontanel, retarded brain development, cranial asymmetry, and low arch dermal ridge patterns on fingertips.
• These findings are consistent with fetal hydantoin syndrome, associated with prenatal exposure to diphenylhydantoin.

Implications:

• This case underscores the critical need for careful monitoring and dose adjustment of diphenylhydantoin in pregnant women, especially those with lower body weight.
• It highlights the potential for severe teratogenic effects even with commonly used medications when dosages are unusually high.
• Further research into safer anticonvulsant alternatives or management strategies during pregnancy is warranted to minimize risks to the fetus.