AED use in pregnancy - management of babies exposed to anti-epileptic drugs in utero
Guidelines for the management of babies whose mothers are on anti-epileptic drugs
Summary
There is a 2-4 fold increase in the incidence of malformations and/or developmental disorders in infants of epileptic mothers on anti epileptic drugs (AED) as compared to epileptic mothers not taking drugs.¹
The overall risk of congenital malformation ranges from 2.2 to 11%.²
The highest risk is with valproate (congenital malformation in 7-12%).²
Overall, cardiac malformations are the most common anomalies seen.²
Some malformations are more common in association with certain drugs - see summary table below.
Rates of malformation are dose-dependent.³
Neonatal withdrawal symptoms such as irritability, jitteriness, hypertonia, tachypnoea, exaggerated startle reflex and vomiting have been reported in some infants, particularly in infants of mothers on valproate, phenytoin, or polytherapy.⁴,⁵
Asymptomatic neonatal hypoglycaemia has also been reported in infants of mothers on valproate.⁴
Table 1: Commonest malformations by AED
| AED | Commonest malformations | Neonatal side effects |
| Carbamazepine | Cardiac Orofacial clefts NTD | Withdrawal symptoms |
| Phenytoin | Cardiac Orofacial clefts | Withdrawal symptoms |
| Valproate | Cardiac NTD Facial dysmorphism Hypospadias Poor cognitive outcomes | Neonatal hypoglycaemia Withdrawal symptoms |
| Lamotrigine | Cardiac Cleft lip and/or palate | Withdrawal symptoms |
| Topiramate | Cleft lip and/or palate | Withdrawal symptoms |
| Gabapentin Levitiracetam | Little data on commonest malformations - lower rates than other | Withdrawal symptoms |
Management of infants exposed to AED in-utero
(even if exposure only during first or second trimester)
Admit to the postnatal ward (or NICU, if appropriate for other reasons) under paediatric care and observe for symptoms of withdrawal.
For infants of mothers on valproate: ensure early and adequate feeding and monitor glucose as per the infants at risk for hypoglycaemia.
Thorough physical examination by a paediatric registrar / consultant. Assess for facial dysmorphism particularly evidence of mid-facial hypoplasia. Look for hypoplastic nails or distal phalangeal hypoplasia
Arrange review in specialist or fellow clinic at 9 months and 18 months to check for developmental problems
Refer to CDU for assessment at 4 yrs if either polypharmacy or valproate exposure, as it is possible that such developmental problems may not be evident until pre-school age and risk is highest in these two groups.
The parents could be informed and encouraged to seek medical attention should they have concerns about their child's development.
Ensure that the baby has received the standard dose of Vitamin K at birth.
See also guideline for Neonatal Withdrawal
If an infant is identified with a problem secondary to maternal AED
Parents should be informed of an increased risk of recurrence with subsequent pregnancies.⁷ Quantification of the risk is difficult and advice could be obtained from the genetic service.
Periconceptual folic acid supplementation may be offered to the mother keeping in mind that there is no good evidence for protection at least with the standard 0.4 mg dose.⁸