Pregnancy outcome following maternal exposure to pregabalin may call for concern
Abstract
Objective:
To investigate pregnancy outcomes following maternal use of pregabalin.
Methods:
This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to pregabalin with those of matched controls (not exposed to any medications known to be teratogenic or to any antiepileptic drugs). Teratology Information Services systematically collected data between 2004 and 2013.
Results:
Data were collected from 164 exposed pregnancies and 656 controls. A significantly higher major birth defect rate in the pregabalin group was observed after exclusion of chromosomal aberration syndromes, and when cases with exposure during first trimester of pregnancy were analyzed separately (7/116 [6.0%] vs 12/580 [2.1%]; odds ratio 3.0, 95% confidence interval 1.2–7.9, p = 0.03). The rate of live births was lower in the pregabalin group (71.9% vs 85.2%, p < 0.001), primarily due to a higher rate of both elective (9.8% vs 5.0%, p = 0.02) and medically indicated (5.5% vs 1.8%, p = 0.008) pregnancy terminations. In the Cox proportional cause specific hazards model, pregabalin exposure was not associated with a significantly higher risk of spontaneous abortion.
Conclusions:
This study demonstrated a signal for increased risk of major birth defects after first trimester exposure to pregabalin. However, several limitations such as the small sample size, differences across groups in maternal conditions, and concomitant medication exposure exclude definitive conclusions, so these results call for confirmation through independent studies.
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© 2016 American Academy of Neurology.
Publication History
Received: October 15, 2015
Accepted: March 7, 2016
Published online: May 18, 2016
Published in print: June 14, 2016
Disclosure
The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.
Study Funding
No targeted funding reported.
Authors
Author Contributions
Dr. Winterfeld: study conception and design, acquisition of data, analysis and interpretation of data, drafting and revising the manuscript for intellectual content. Prof. Merlob, Dr. Baud, and Prof. Rousson: analysis and interpretation of data, drafting and revising the manuscript for intellectual content. Dr. Panchaud and Dr. Rothuizen: study conception and design, acquisition of data, drafting and revising the manuscript for intellectual content. N. Bernard, Dr. Vial, Dr. Yates, Dr. Pistelli, Dr. Ellfolk, Dr. Eleftheriou, Dr. de Vries, Dr. Jonville-Bera, and Dr. Kadioglu: acquisition of data, drafting and revising the manuscript for intellectual content. Prof. Biollaz: drafting and revising the manuscript for intellectual content. Prof. Buclin: study conception and design, analysis and interpretation of data, drafting and revising the manuscript for intellectual content, study supervision.
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I read with interest the study by Winterfeld et al. on pregnancy outcome after maternal exposure to pregabalin (Lyrica). [1] The authors found an increased risk of major birth defects after first trimester exposure to pregabalin. [1] In the United States, pregabalin is perscribed for neuropathic pain associated with diabetic peripheral neuropathy (DPN), postherpetic neuralgia (PHN), adjunctive therapy for adult patients with partial onset seizures, fibromyalgia, and neuropathic pain associated with spinal cord injury. It is unclear how and why pregabalin demonstrates efficacy across such diverse conditions of vastly different etiopathogenesis. When first launched, pregabalin was aggressively promoted as an antiepileptic drug (AED). Its use as an AED has considerably decreased owing to lack of efficacy and this is reflected in the manufacture's (Pfizer's) recent print campaign aimed at US healthcare professionals promoting it mainly for the treatment of painful DPN and PHN. For women of child bearing age with epilepsy, use of pregabalin for adjunctive therapy of partial onset seizures is hard to justify given its lack of efficacy and the authors reported risk of major birth defects. The risks clearly outweigh the benefits. Medications like lamotrigine, levetiracetam, and lacosamide are far safer during pregnancy.
1. Winterfeld U, Merlob P, Baud D, et al. Pregnancy outcome following maternal exposure to pregabalin may call for concern. Neurology Epub 2016 May 18.
For disclosures, please contact the editorial office at [email protected].