Malformation risk of antiepileptic drug exposure during pregnancy in women with epilepsy: Results from a pregnancy registry in South India

Thomas, Sanjeev V; Jose, Manna; Divakaran, Srividya; Sarma, P. Sankara

doi:10.1111/epi.13632

Cited by 74 publications

(91 citation statements)

References 13 publications

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“…In women with epilepsy, it is known that the risk of birth defects in general and orofacial clefts in their offspring is significantly elevated. Present results are in accordance with the literature data . It is important to note that the possible teratogenic effect of antiepileptic drugs in these cases must also be taken into consideration .…”

Section: Discussionsupporting

confidence: 91%

Maternal‐related factors in the origin of isolated cleft palate—A population‐based case‐control study

Ács

Bányai

Nemes

et al. 2020

Orthod Craniofacial Res

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Objects Isolated cleft palate (CPO) is the rarest form of oral clefting affecting 1‐25 per 10 000 newborns worldwide. There is increasing evidence for the different pathogenetic backgrounds of CPO and cleft lip with or without cleft palate. The role of environmental factors in the origin of non‐syndromic and syndromic CPO is unclear in most patients. The aim of this study was to estimate possible maternal risk factors in the origin of CPO. Setting and Sample Population The Hungarian Case‐Control Surveillance of Congenital Abnormalities contains data of 32 345 birth defect cases and 57 231 control newborns. The study samples included 751 cases with isolated CPO, 1196 matched controls and 57 231 population controls. Material and Methods Maternal diseases during pregnancy in cases and population controls were compared, and adjusted ORs with 95% CI were calculated in a multivariable unconditional logistic regression model. Results Beyond the well‐known robust female excess (58.9%)—maternal smoking (OR with 95% CI: 2.34, 1.94‐2.81) medically recorded maternal anaemia, threatened abortion and excessive vomiting in pregnancy were associated with a higher risk for CPO in the offspring. An elevated risk was found in Graves’ disease (OR: 4.30, 1.74‐10.62), epilepsy (OR: 4.64, 2.44‐8.82), migraine (OR: 2.82, 1.18‐6.76) and essential hypertension (OR: 2.33, 1.32‐4.10). Among acute diseases common cold (OR: 4.94, 3.48‐7.03), acute respiratory infections (OR: 4.20, 1.49‐11.82), influenza (OR: 2.95, 1.75‐4.95), pulpitis (OR: 7.85, 2.80‐22.03), cholecystitis (OR: 3.15, 1.16‐8.60), acute urinary tract infections (OR: 4.08, 2.22‐7.49) and pelvic inflammatory diseases (OR: 3.93, 1.62‐9.53) during pregnancy also were associated with an increased risk for developing CPO. Conclusion The findings of this study suggest that maternal diseases and lifestyle factors during the first trimester play a significant role in the development of isolated cleft palate.

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Section: Discussionsupporting

confidence: 91%

Maternal‐related factors in the origin of isolated cleft palate—A population‐based case‐control study

Ács

Bányai

Nemes

et al. 2020

Orthod Craniofacial Res

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“…It is now well demonstrated that exposure to some AEDs during pregnancy increases the risk of major congenital malformations in the offspring, such as neural tube defects and cleft palate, from two‐fold to three‐fold . The risk varies by AED: valproate is known to have the highest risk whereas lamotrigine may represent the safest AED during pregnancy .…”

Section: Introductionmentioning

confidence: 99%

“…1 It is now well demonstrated that exposure to some AEDs during pregnancy increases the risk of major congenital malformations in the offspring, such as neural tube defects and cleft palate, from two-fold to three-fold. [2][3][4][5] The risk varies by AED 6 : valproate is known to have the highest risk 2 whereas lamotrigine may represent the safest AED during pregnancy. 5 Furthermore, since the early 2000s, several studies have suggested a risk of neurodevelopmental problems in children exposed in utero to valproate 7 including delayed walking and talking or difficulty with language.…”

Section: Introductionmentioning

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

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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.

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“…The chronic and serious nature of some of the indications for which they are prescribed means that it is not always possible for women to discontinue their treatment in advance of and during pregnancy . For some time, there has been evidence that certain AEDs, when taken by women during their pregnancy, are associated with a two‐ to three‐fold increase in risk of major congenital malformations in the offspring . The risk varies by AED, with sodium valproate often reported as having the highest risk and lamotrigine and levetiracetam the lowest risk, although for many of the other newer AEDs, the number of exposures during pregnancy available for study is low.…”

Section: Introductionmentioning

confidence: 99%

“…[11][12][13] For some time, there has been evidence that certain AEDs, when taken by women during their pregnancy, are associated with a two-to three-fold increase in risk of major congenital malformations in the offspring. [14][15][16][17] The risk varies by AED, with sodium valproate often reported as having the highest risk 14 and lamotrigine and levetiracetam the lowest risk, 17 although for many of the other newer AEDs, the number of exposures during pregnancy available for study is low. In recent years, there has been a growing body of evidence of negative neurodevelopmental outcomes in children exposed to sodium valproate in utero.…”

mentioning

confidence: 99%

Did advice on the prescription of sodium valproate reduce prescriptions to women? An observational study in three European countries between 2007 and 2016

Charlton

Damase‐Michel

Hurault‐Delarue

et al. 2019

Pharmacoepidemiology and Drug

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Objectives In November 2014, the CMDh (a regulatory body representing EU Member States) advised doctors not to prescribe sodium valproate for epilepsy or bipolar disorder in preg nant women, in women who can become pregnant, or in girls unless other treatments are ineffective or not tolerated. This study aimed to determine if this warning led to changes in prescription patterns. Design and setting Cohort of 5.4 million women aged between 10 and 50 years identified in electronic health care data from United Kingdom, France, and Italy (2007–2016). Main outcome measures Anti‐epileptic drug (AED) prescriptions. Results The prevalence of women receiving AED prescriptions in 2016 varied from 12.2 per 1000 to 29 per 1000 in the four regions. The incidence of prescribing any AED (excluding clonazepam, gabapentin, and pregabalin) fell each year on average by 7.5% (95% CI, 7.0%‐8.0%; Emilia Romagna), 9.6% (8.3%‐11.0%; France), 7.1% (6.7%‐7.6%; Tuscany), and 0.4% (0.2%‐1.0%; United Kingdom). The relative odds of prescribing sodium valproate rather than any other AED decreased more after 2014 compared with before the end of 2014 in France (OR = 0.77; 95% CI, 0.60‐0.98), Tuscany (0.81; 0.76‐0.86), Emilia Romagna (0.83; 0.76‐0.90), and the United Kingdom (0.92; 0.80‐1.06; not statistically significant). Conclusions There is evidence that the CMDh warning did lead to changes in prescription patterns of sodium valproate in women of childbearing age. There were considerable differences in prescribing practice amongst regions of Europe.

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Malformation risk of antiepileptic drug exposure during pregnancy in women with epilepsy: Results from a pregnancy registry in South India

Cited by 74 publications

References 13 publications

Maternal‐related factors in the origin of isolated cleft palate—A population‐based case‐control study

Maternal‐related factors in the origin of isolated cleft palate—A population‐based case‐control study

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

Did advice on the prescription of sodium valproate reduce prescriptions to women? An observational study in three European countries between 2007 and 2016

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