Neurological disease in pregnancy

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Chapter 52 Neurological disease in pregnancy

Epilepsy and pregnancy

Incidence. Epilepsy occurs in 0.5%–1% of the population. Over 90% of women with epilepsy have a normal pregnancy.

Effects of epilepsy on pregnancy

• reports of fetal bradycardia after generalised seizure

• increased risk of childhood epilepsy of 3%–4% if one parent has epilepsy

• increased association with pre-eclampsia, preterm delivery, low birthweight, higher perinatal mortality and congenital malformations due to the epilepsy and the anticonvulsant drugs; fetal effects include cerebral palsy, seizures and mental retardation

Effect of pregnancy on epilepsy

• About 50% remain stable, with improvement in seizure frequency in 25% and deterioration in 25% of women.

• The deterioration is attributed to hormonal and metabolic changes and diminished compliance with drug therapy.

• In about 70% of patients, serum levels of anticonvulsants fall in early pregnancy and return to prepregnancy levels by 4 weeks postpartum; so if seizure activity increases, it is often in the first two trimesters.

• If epilepsy presents for the first time in pregnancy, rigorous investigation is required to exclude other neurological abnormalities.

Pharmacokinetics of anticonvulsants in pregnancy

• Drug absorption may be lowered with vomiting in early pregnancy.

• Volume of distribution is increased due to raised plasma volume and total body water, and results in a reduced steady state of plasma levels.

• Increased fat stores will lower lipid-soluble drug excretion.

• Phenytoin and valproate are highly protein-bound. With the reduction of albumin in pregnancy, there is a lower percentage of bound drug. Therefore, unbound levels in plasma remain constant, but total plasma levels are reduced.

• The glomerular filtration rate rises, raising the clearance of renally excreted drugs.

• Hepatic hydroxylation of phenytoin is increased, and this causes a reduction in free drug.

• Non-compliance due to maternal fears of teratogenicity often reduces plasma levels of drug.

Teratogenicity of anticonvulsants

• In a woman with epilepsy treated with a single anticonvulsant, the fetus has a risk of congenital malformation of 7%, compared with 3% in non-epileptics. There may be a higher incidence with polypharmacy.

• The defects include orofacial clefts, cardiovascular anomalies, neural tube defects (which are commonly primary myelomeningocele and anencephaly, and especially if valproate is taken in the first trimester), microcephaly and digital hypoplasia.

• Epilepsy pregnancy registries indicate valproate at doses >1100 mg/day confer significant risk compared to other doses and other drugs.

Other maternal effects of anticonvulsants

• reduced folate levels

• increased vitamin D metabolism with phenytoin and phenobarbitone, and risk of hypocalcaemia

Fetal/neonatal effects of anticonvulsants

• reduced fetal thyroxine as phenytoin competes for thyroxine-binding sites

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