Pregnancy Outcomes Following In Utero Exposure to Lamotrigine: A Systematic Review and Meta-Analysis

Pariente, Gali; Leibson, Tom; Shulman, Talya; Adams‐Webber, Thomasin; Barzilay, Eran; Nulman, Irena

doi:10.1007/s40263-017-0433-0

Cited by 57 publications

(32 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In 2009, an increased risk of cleft palate and lip was reported after an exposure during the first trimester of pregnancy . However, this risk was not confirmed by other studies …”

Section: Discussionmentioning

confidence: 93%

See 1 more Smart Citation

Prescription of antiepileptic medicines including valproate in pregnant women: A study in three European countries

Hurault‐Delarue

Morris

Charlton

et al. 2019

Pharmacoepidemiology and Drug

View full text Add to dashboard Cite

Purpose To study patterns of antiepileptic drugs (AED) prescribing, particularly valproate, during pregnancy over a 10‐year period in the UK, Italy, and France. Methods Data on pregnancies conceived after 1 January 2007 with outcomes before 31 December 2016 were extracted from four European electronic health care databases (380 499 in the United Kingdom (UK), 66 681 in France, and 649 918 in Italy [355 767 in Emilia Romagna and 294 151 in Tuscany]). Prevalence of AEDs with an ATC code starting N03A and clobazam (N05BA09) were stratified by country and calendar year. Results AED prescribing during pregnancy varied from 3.0 (2.8‐3.1) per 1000 pregnancies in Emilia Romagna to 7.8 (7.5‐8.0) in the UK, 5.9 (5.6‐6.1) in Tuscany, and 6.3 (5.7‐6.9) in France. Lamotrigine was commonly prescribed in all regions with a third of women exposed to an AED during pregnancy taking lamotrigine in the UK and France. Valproate was prescribed to 28.6% of AED exposed pregnant women in Tuscany, 21.6% in France, 16.7% in Emilia Romagna, and 11.9% in the UK. Over the study period, the prevalence of AED prescribing increased in the UK mainly due to increases in pregabalin and gabapentin, declined in France mainly related to decreases in clonazepam, and remained constant in Italy. Valproate prescriptions declined to a prevalence <1 per 1000 pregnancies in 2015 to 2016 in the UK, France, and Emilia Romagna. Conclusions Variations in AED prescribing during pregnancy indicate the potential for further reductions, particularly of valproate. Increases in pregabalin/gabapentin prescribing, for which risks are not well known, are a cause for concern.

show abstract

“…In 2009, an increased risk of cleft palate and lip was reported after an exposure during the first trimester of pregnancy . However, this risk was not confirmed by other studies …”

Section: Discussionmentioning

confidence: 93%

“…38 However, this risk was not confirmed by other studies. 39 During the first years of the study period, carbamazepine was the most frequently prescribed AED in Emilia Romagna, with more than 20% of pregnant women exposed to AEDs receiving carbamazepine.…”

Section: Drug Choice Differs According To Countriesmentioning

confidence: 99%

Prescription of antiepileptic medicines including valproate in pregnant women: A study in three European countries

Hurault‐Delarue

Morris

Charlton

et al. 2019

Pharmacoepidemiology and Drug

View full text Add to dashboard Cite

show abstract

“…Of utmost importance, the risk of major congenital malformations among children who were exposed to LTG appears null in a prospective registry of 18 years . In addition, among 96 studies including 58,461 individuals, the risk observed under LTG did not differ from that reported in healthy individuals in contrast with findings obtained with most other antiepileptic drugs . Moreover, a large prospective cohort study shows that fetal exposure to LTG does not affect IQ or any detectable neuropsychological ability in children up to 6 years of age .…”

Section: The Safety and Tolerance Of Lamotrigine Appears Among The Himentioning

confidence: 64%

Lamotrigine in the Prevention of Migraine With Aura: A Narrative Review

Buch

Chabriat

2019

Headache

View full text Add to dashboard Cite

Background Lamotrigine is not recommended in the prevention of migraine in general but some reports suggest that it might be effective for treating specifically migraine with aura (MA). This review aims to summarize the related data from the literature and to better understand this discrepancy. Methods All reports from the literature related to the use of lamotrigine in migraine with or without aura published prior to February 2019 found using PUBMED and the 2 keywords “migraine” AND “lamotrigine” were reviewed. Original studies, published in full, systematic reviews, and all case reports were synthetized. We also examined the risk profile, pharmacokinetics, and mode of action of lamotrigine in view of the presumed mechanism of MA. Results Lamotrigine was tested in different populations of migraineurs, but previous studies had small sample sizes (n < 35) and might not have been powered enough for detecting a potential benefit of lamotrigine in MA. Accumulating data suggest that the drug can reduce both the frequency and severity of aura symptoms in multiple conditions and is well tolerated. Conclusion Lamotrigine appears promising for treating attacks of MA and related clinical manifestations because of its high potential of efficacy, low‐risk profile, and cost. Additional studies are needed for testing lamotrigine in patients with MA.

show abstract

“…In comparisons of women exposed to lamotrigine with those unexposed, published studies reported null or adverse effects on pregnancy duration and birth weight [14,20,23], protective or null effects on SGA [14,20,24], and null effects on head circumference [13,20]. A recent systematic review that focused on lamotrigine concluded that there was no association between lamotrigine in monotherapy and congenital malformations, preterm delivery, or SGA [28,29]; but a dose dependency was reported for congenital malformations. [5].…”

Section: Lamotriginementioning

confidence: 99%

“…Overview 90 We conducted a cohort study based on nationwide Swedish register data from 1996 through 2013 91 to explore the association between maternal use of individual AEDs and pregnancy duration and 92 fetal size. Lamotrigine was the reference AED because it is commonly used and has been 93 considered to have fewer adverse fetal effects than other AEDs [2,12,28,29]. 94 Data sources 95 In Sweden, tax-funded health care is provided to all citizens.…”

mentioning

confidence: 99%

Relation of in-utero exposure to antiepileptic drugs to pregnancy duration and size at birth

Margulis

Hernández–Dı́az

McElrath

et al. 2019

Preprint

View full text Add to dashboard Cite

38 Background: The associations of individual antiepileptic drugs (AEDs) with pregnancy duration 39 and size at birth, and potential dose relations, are not well characterized.40 Methods: This cohort study used nationwide Swedish register data (1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013). Adjusting for 41 smoking, epilepsy and other AED indications, we used linear and quantile regression to explore 42 associations with pregnancy duration, and birth weight, length, and head circumference (the last 43 three operationalized as z-scores). We used logistic regression for preterm delivery, small for 44 gestational age, and microcephaly. Lamotrigine was the reference drug.45 Results: 6,720 infants were exposed to AEDs in utero; AED exposure increased over the study 46 period. Relative to lamotrigine-exposed infants, carbamazepine-exposed infants were born, on 47 average, 1.3 days earlier (mean [95% confidence interval]: -1.3 [-2.3 to -0.3]); were 0.1 standard 48 deviations (SDs) lighter (-0.1 [-0.2 to 0.0]); and had a head circumference that was 0.2 SDs 49 smaller (-0.2 [-0.3 to -0.1]). Pregabalin-exposed infants were born, on average, 1.1 days earlier (-50 1.1 [-3.0 to 0.8]); were 0.1 SDs lighter (-0.1 [-0.3 to 0.0]); and had the same head circumference. 51 Levetiracetam-exposed infants were born, on average, 0.5 days earlier (-0.5 [-2.6 to 1.6]); were 52 0.1 SDs lighter (-0.1 [-0.3 to 0.0]); and were 0.1 SDs smaller (-0.1 [-0.3 to 0.1]) in head 53 circumference. Valproic acid-exposed infants had, on average, the same duration of gestation 54 and birth weight z-score, but were 0.2 SDs smaller (-0.2 [-0.2 to -0.1]) in head circumference. 55 More negative associations at the left tail of pregnancy duration and birth weight z-score, effect-56 measure modification, and dose-response relations were noted for some of the associations.57 Observed associations were generally of smaller magnitude than that of smoking, assessed as a 58 potential confounder in the same models. 4 59 Conclusions: In comparison with lamotrigine, valproic acid and carbamazepine had a more 60 negative association with head circumference than other study AEDs. 5 INTRODUCTION63 Epilepsy and antiepileptic drugs (AEDs) have been associated with adverse pregnancy, fetal, and 64 neonatal outcomes [1]. AEDs differ in their risk for congenital malformations [2][3][4], and some 65 associations have been found to be dose dependent [4][5][6]. Newer AEDs are generally considered 66 safer than the older drugs, with the possible exception of topiramate [7]. Antiepileptic drugs also 67 differ in the magnitude of their associations with adverse neurodevelopmental outcomes in the 68 offspring, which also appear to be dose dependent [8][9][10]. The exploration of indication and dose 69 is important because confounding by indication has been a concern and AED doses are often 70 higher in epilepsy than in other conditions [11]. 71 A meta-analysis has shown elevated point estimates for the association of AEDs...

show abstract

Pregnancy Outcomes Following In Utero Exposure to Lamotrigine: A Systematic Review and Meta-Analysis

Abstract: No association was found between prenatal lamotrigine monotherapy and increased rates of birth defects and other explored variables related to adverse pregnancy outcomes.

Cited by 57 publications

References 61 publications

Prescription of antiepileptic medicines including valproate in pregnant women: A study in three European countries

Prescription of antiepileptic medicines including valproate in pregnant women: A study in three European countries

Lamotrigine in the Prevention of Migraine With Aura: A Narrative Review

Relation of in-utero exposure to antiepileptic drugs to pregnancy duration and size at birth

Contact Info

Product

Resources

About