USE OF DIAZEPAM IN PREGNANCY

Diazepam is a long-acting benzodiazepine used as a hypnotic, anxiolytic, anticonvulsant and muscle relaxant.  Its actions are mediated by enhancement of the activity of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.

Data on the risk of congenital malformation following use of diazepam in pregnancy are highly confounded by the research techniques employed in the majority of the available studies.  Evidence is therefore conflicting; with some older studies suggesting possible increased risks of congenital malformation, including orofacial clefts and cardiac malformations.  More recent, better designed studies, have failed to identify such associations.  Where clinically justifiable use of diazepam in the first trimester may be considered, ideally following discussion regarding these data with the patient.  The lowest effective dose should be used and only for as long as considered clinically necessary.  The potential effects of diazepam use at any stage of pregnancy on fetal neurodevelopmental outcome is unknown.

There are no data available relating specifically to the risk of spontaneous abortion (SA) following diazepam exposure in pregnancy, and although an increased risk of spontaneous abortion following exposure to benzodiazepines as a group has been reported, these data are considered too limited and confounded to be certain that a clinically relevant increased risk of spontaneous abortion exists.

Abrupt withdrawal of diazepam is not recommended as this may destabilise the maternal condition, or potentially lead to self-administration of other medications or drugs of abuse, like alcohol, which may confer a significant risk to the developing fetus.

Prolonged use of benzodiazepines near term, especially in high doses, is associated with a risk of neonatal withdrawal syndrome and/or “floppy infant syndrome” and monitoring for neonatal respiratory depression is advised.  Use of diazepam around term should therefore be avoided unless use can be clinically justified.

Exposure to diazepam during pregnancy would not usually be regarded as medical grounds for termination of pregnancy.  In light of conflicting data concerning the risk of congenital malformation, detailed fetal ultrasound scans may be considered following first trimester exposure.