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

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

doi:10.1007/s40263-017-0439-7

Cited by 17 publications

(4 citation statements)

References 57 publications

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“…In comparisons of women exposed to lamotrigine with those unexposed, published studies estimated 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: Discussionmentioning

confidence: 99%

“…We conducted a cohort study based on nationwide Swedish register data from 1996 through 2013 to explore the association between maternal use of individual AEDs and pregnancy duration and fetal size. We chose lamotrigine as the reference AED because it is commonly used, providing a statistical advantage as well as a reasonable clinical comparison, and has been considered to have fewer adverse fetal effects than other AEDs based on information available at the time this study was conducted [2, 12, 28, 29].…”

Section: Methodsmentioning

confidence: 99%

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

Margulis¹,

Hernández–Dı́az

McElrath

et al. 2019

PLoS ONE

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Background The associations of individual antiepileptic drugs (AEDs) with pregnancy duration and size at birth, and potential dose relations, are not well characterized. Methods This cohort study used nationwide Swedish register data (1996–2013). Adjusting for smoking, epilepsy and other AED indications, we used linear and quantile regression to explore associations with pregnancy duration, and birth weight, length, and head circumference (the last three operationalized as z-scores). We used logistic regression for preterm delivery, small for gestational age, and microcephaly. Lamotrigine was the reference drug. Results 6,720 infants were exposed to AEDs in utero; AED exposure increased over the study period. Relative to lamotrigine-exposed infants, carbamazepine-exposed infants were born, on average, 1.3 days earlier (mean [95% confidence interval]: -1.3 [-2.3 to -0.3]); were 0.1 standard deviations (SDs) lighter (-0.1 [-0.2 to 0.0]); and had a head circumference that was 0.2 SDs smaller (-0.2 [-0.3 to -0.1]). Pregabalin-exposed infants were born, on average, 1.1 days earlier (-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 as lamotrigine-exposed infants. Levetiracetam-exposed infants were born, on average, 0.5 days earlier (-0.5 [-2.6 to 1.6]); were 0.1 SDs lighter (-0.1 [-0.3 to 0.0]); and had a head circumference 0.1 SDs smaller (-0.1 [-0.3 to 0.1]). Valproic acid–exposed infants had, on average, the same duration of gestation and birth weight z-score as lamotrigine-exposed infants, but had a head circumference 0.2 SDs smaller (-0.2 [-0.2 to -0.1]). Associations between carbamazepine exposure and pregnancy duration and between valproic acid exposure and pregnancy duration and birth weight z-score were more negative at the left than at the right tails of the outcome distributions. Effect-measure modification and dose-response relations were noted for some of the associations. Conclusions Relative to lamotrigine, valproic acid and carbamazepine were associated with smaller head circumference.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

Margulis¹,

Hernández–Dı́az

McElrath

et al. 2019

PLoS ONE

View full text Add to dashboard Cite

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

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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...

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Lamotrigine in the maintenance treatment of bipolar disorder

Hashimoto

Kotake

Watanabe

et al. 2021

Cochrane Database of Systematic Reviews

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

Cited by 17 publications

References 57 publications

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

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

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

Lamotrigine in the maintenance treatment of bipolar disorder

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