TERATOGENICITY AND DRUGS THAT AFFECT THE FETUS (Part three)
4 - ANTIEPILEPTIC DRUGS
A - Carbamazepine
- Used for the treatment of epilepsy and trigeminal neuralgia.
- Included in category D medications.
- Affects 1-2% of pregnancies.
- The most common anomalies are neural tube defects, orofacial defects, cardiac defects.
B - Gabapentin
- Used for the treatment of neuropathic pain.
- Major congenital anomalies occur in both monotherapy and polytherapy.
- The most common anomalies are unilateral renal agenesis, hypospadias, ventricular septal defects.
C - Lamotrigine
- Is less teratogenic than other drugs in this group.
- Included in category C medications.
- Increases the risk 4 times for congenital anomalies when used as monotherapy and up to 10 times as polytherapy.
- Acts by inhibiting dihydrofolate reductase and leads to a decrease in fetal folate levels.
- The most common anomalies are orofacial defects.
D - Levetiracetam
- Used more than other preparations as monotherapy due to its broader tolerance and higher safety.
- Included in category C medications.
- Data on congenital anomalies are not certain but theoretically have a risk for skeletal anomalies and growth disorders in animals at therapeutic or higher doses.
E - Phenobarbital
- Included in category D medications.
- The most common congenital anomalies are cardiac, less frequently urinary tract malformations.
F - Phenytoin
- Included in category D medications.
- Congenital anomalies include in the fetal hydantoin syndrome (hypoplasia and irregular ossification of the distal phalanges, facial dysmorphism, growth and developmental disorders, cardiac defects, developmental delay).
G - Topiramate
- Included in category C medications.
- Used for the treatment of epilepsy and as a prophylactic in migraines.
- The risk as monotherapy for congenital anomalies is 4.8% and triples in polytherapy (11.2%).
- Studies show an increased risk for cleft palate.
H - Valproic acid
- Included in category D medications.
- Used as an anticonvulsant, for migraine pain, and in schizophrenia.
- Fetal outcome is poor and depends on the dose of the medication used.
- Congenital anomalies include neural tube defects, cleft palate, skeletal anomalies, developmental disorders.
5 - ANTIHYPERTENSIVE DRUGS
A - Angiotensin-Converting Enzyme Inhibitors (ACE-I)
- The most used drugs in this group are: enalapril, captopril, and lisinopril.
- The changes they cause occur after organogenesis, i.e., during the fetal period and cause what is called ACE-Inhibitor fetopathy.
- The drugs cause disruption of the renin-angiotensin system which is essential for normal renal development.
- They provoke prolonged fetal hypoperfusion and hypotension - this leads to renal ischemia, renal tubular dysgenesis, and anuria - leads to oligohydramnios which prevents normal pulmonary development and leads to limb contractures.
- Reduction of perfusion causes IUGR, relative shortening of limbs, and abnormal development of the calvarium.
- They cause major congenital malformations: central nervous system, cardiovascular system.
- During pregnancy, the use of ACE-I is discontinued and another alternative for treating hypertension is chosen.
B - Angiotensin-II Receptor Antagonists
- The most used drugs in this group are: losartan, irbesartan, candesartan, and valsartan.
- The most common congenital anomalies are: renal dysgenesis, acute perinatal renal failure, various limb deformities, Potter syndrome, patent ductus arteriosus.
- Their use is discontinued in a pregnant woman or one planning a pregnancy.