Please note, this document considers the study which was communicated by the MHRA in their April 2022 Drug Safety Update in addition to all other published evidence regarding the fetal risks associated with pregabalin use in pregnancy.
Pregabalin is an anticonvulsant used as adjunctive therapy in adults with partial seizures, with or without secondary generalisation, and in the treatment of neuropathic pain and generalised anxiety disorder.
The available data do not currently provide conclusive evidence that maternal pregabalin use in the first trimester, or at any stage of pregnancy, is associated with increased risks of either overall malformation or any specific malformations. Although some studies have described increased risks of malformation overall and for specific anomalies (including central nervous system (CNS), eye, genital and urinary anomalies, and orofacial clefts), these results may have been influenced by data confounding and methodological limitations. Furthermore, the absolute risks indicated by those studies describing increased risks were generally small and therefore do not preclude the use of pregabalin in pregnancy where the indication for treatment is compelling.
Collectively, the available data do not conclusively indicate that maternal pregabalin use in pregnancy is associated with increased risks of miscarriage, stillbirth, preterm delivery, fetal growth restriction or neurodevelopmental impairment.
Although controlled studies have not identified increased risks of poor neonatal adaptation following prenatal pregabalin exposure, one uncontrolled study has described a small number of affected infants, including one case of neonatal withdrawal. Use of any centrally acting drug throughout pregnancy or near delivery may potentially 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 to more than one CNS-acting drug. For all pregnancies with exposure to CNS-acting medication, delivery should be planned in a unit with adequate neonatal facilities.
Pregabalin is not known to impact maternal folate status. However, guidelines in the UK state that women who take any anti-epileptic medication should be prescribed high dose folic acid (5mg). Women should be made aware that it is not known whether high dose folic acid supplementation offers any benefit or protective effects over standard dose regimes when taking pregabalin pre-conceptually or during pregnancy.
Exposure to pregabalin at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy or any additional fetal monitoring. However, other risk factors may 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.
This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.
If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.
If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.