USE OF GABAPENTIN IN PREGNANCY

Gabapentin is an antiseizure medication drug indicated as monotherapy or adjunctive therapy in the treatment of partial seizures with or without secondary generalisation, and for the treatment of peripheral neuropathic pain. It is also used off-licence for migraine prophylaxis, for the treatment of oscillopsia and spasticity in multiple sclerosis, and to ameliorate hot flushes in women receiving treatment for breast cancer.

Much of the available epidemiological data relate to gabapentin use in pregnancy for the treatment of epilepsy. A few case reports/series describe use of gabapentin in the treatment of neuropathic pain or hyperemesis gravidarum, but studies have not assessed fetal outcomes following use in pregnancy for these indications.

The available data do not provide robust evidence of an increased risk of congenital malformation, either overall or for specific anomalies, following first trimester gabapentin exposure in pregnancy. However, the evidence is conflicting, and therefore further studies are required. Data regarding risk of cardiac malformation are conflicting and likely confounded. However, the highest quality data do not indicate an increased risk.

Data regarding the risk of miscarriage are conflicting but do not provide reliable evidence of an increased risk following gabapentin exposure in early pregnancy. A single small study did not find an association with intrauterine death. Conflicting results regarding possible increased risks of preterm delivery and low birth weight have been described in a small number of studies but these data may be confounded. Data relating to neurodevelopment following in utero gabapentin exposure are limited and conflicting; further research is required before evidence-based conclusions can be drawn.

Exposed infants have seen an increase in NICU admissions, with documented indications including neonatal withdrawal, neonatal jaundice, bradycardia, hypotonia, hypoglycaemia, apnoea, respiratory distress, jitteriness, diarrhoea, fever and arrhythmia. Use of any centrally acting drug throughout pregnancy or near delivery may be associated with withdrawal symptoms in the neonate and/or poor neonatal adaptation syndrome (PNAS). These symptoms are likely to be more severe in infants exposed in utero to more than one CNS acting drug. Delivery should be planned in a unit with neonatal intensive care facilities.

Gabapentin may impact upon maternal folate status. UK guidelines state that women who take any anti-epileptic medication should be prescribed high-dose folic acid (5mg), although it is currently not known whether high-dose folic acid supplementation offers any additional benefit or protective effects over standard dose regimes when taking gabapentin pre-conceptually or during pregnancy.

More research is required to define the pregnancy safety profile of gabapentin. Pregnant women and women of childbearing potential should be made aware that data for most pregnancy outcomes are conflicting, and although the highest quality evidence does not indicate an association with adverse outcomes, further studies are still required. Gabapentin should only be used during pregnancy where benefits of treatment are considered to outweigh any potential risks. In view of the limited human pregnancy data, close monitoring of mother and fetus should be considered with use of gabapentin in pregnancy. Other risk factors may also be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.