scholarly journals Risks of 23 specific malformations associated with prenatal exposure to 10 antiepileptic drugs

Neurology ◽  
2019 ◽  
Vol 93 (2) ◽  
pp. e167-e180 ◽  
Author(s):  
Pierre-Olivier Blotière ◽  
Fanny Raguideau ◽  
Alain Weill ◽  
Elisabeth Elefant ◽  
Isabelle Perthus ◽  
...  
Keyword(s):  
Health Care ◽  
Valproic Acid ◽  
Antiepileptic Drugs ◽  
Congenital Malformations ◽  
Cleft Lip ◽  
Reference Group ◽  
The Other ◽  
Increased Risk ◽  
Exact Confidence Intervals ◽  
Major Congenital Malformations

ObjectiveTo assess the association between exposure to monotherapy with 10 different antiepileptic drugs (AEDs) during the first 2 months of pregnancy and the risk of 23 major congenital malformations (MCMs).MethodsThis nationwide cohort study, based on the French health care databases, included all pregnancies ≥20 weeks and ending between January 2011 and March 2015. Women were considered to be exposed when an AED had been dispensed between 1 month before and 2 months after the beginning of pregnancy. The reference group included pregnant women with no reimbursement for AEDs. MCMs were detected up to 12 months after birth (24 months for microcephaly, hypospadias, and epispadias). Odds ratios (ORs) were adjusted for potential confounders for MCMs with at least 5 cases. Otherwise, we calculated crude ORs with exact confidence intervals (CIs).ResultsThe cohort included 1,886,825 pregnancies, 2,997 of which were exposed to lamotrigine, 1,671 to pregabalin, 980 to clonazepam, 913 to valproic acid, 579 to levetiracetam, 517 to topiramate, 512 to carbamazepine, 365 to gabapentin, 139 to oxcarbazepine, and 80 to phenobarbital. Exposure to valproic acid was associated with 8 specific types of MCMs (e.g., spina bifida, OR 19.4, 95% CI 8.6–43.5), and exposure to topiramate was associated with an increased risk of cleft lip (6.8, 95% CI 1.4–20.0). We identified 3 other signals. We found no significant association for lamotrigine, levetiracetam, carbamazepine, oxcarbazepine, and gabapentin.ConclusionsThese results confirm the teratogenicity of valproic acid and topiramate. Because of the small numbers of cases and possible confounding, the other 3 signals should be interpreted with appropriate caution.

Paternal exposure to antiepileptic drugs and offspring outcomes: a nationwide population-based cohort study in Sweden

2020 ◽  
Vol 91 (9) ◽  
pp. 907-913
Author(s):  
Torbjörn Tomson ◽  
Giulia Muraca ◽  
Neda Razaz
Keyword(s):  
Intellectual Disability ◽  
Antiepileptic Drugs ◽  
Congenital Malformations ◽  
Population Based ◽  
Autism Spectrum ◽  
Adverse Outcomes ◽  
Neurodevelopmental Outcomes ◽  
Hyperactivity Disorder ◽  
Increased Risk ◽  
Major Congenital Malformations

ObjectivesTo investigate the association between paternal use of antiepileptic drugs (AEDs) and adverse neurodevelopmental outcomes and major congenital malformations (MCM) in the offspring.MethodsUsing nationwide Swedish registries, we included 1 144 795 births to 741 726 fathers without epilepsy and 4544 births to 2955 fathers with epilepsy. Of these, 2087 (45.9%) were born to fathers with epilepsy who had dispensed an AED during the conception period. Children who had both parents with epilepsy were excluded. The incidence rate of MCM, autism spectrum disorder, attention deficit hyperactivity disorder (ADHD) and intellectual disability in offspring was analysed.ResultsOffspring of fathers exposed to AEDs did not show an increased risk of MCM (adjusted OR 0.9, 95% CI 0.7 to 1.2), autism (adjusted HR (aHR) 0.9, 95% CI 0.5 to 1.7), ADHD (aHR 1.1, 95% CI 0.7 to 1.9) or intellectual disability (aHR 1.3, 95% CI 0.6 to 2.8) compared with offspring of fathers with epilepsy not exposed to AEDs. Among offspring of fathers with epilepsy who used valproate in monotherapy during conception, rates of autism (2.9/1000 child-years) and intellectual disability (1.4/1000 child-years) were slightly higher compared with the offspring of fathers with epilepsy who did not use AEDs during conception (2.1/1000 child-years autism, 0.9/1000 child-years intellectual disability), but in the propensity-score adjusted analyses, no statistically significant increased risk of adverse outcomes was found.ConclusionsPaternal AED use during conception is not associated with adverse outcomes in the offspring.

scholarly journals Congenital Malformations and Perinatal Deaths among the Children of Atomic Bomb Survivors: A Reappraisal

2021 ◽  
Author(s):  
Michiko Yamada ◽  
Kyoji Furukawa ◽  
Yoshimi Tatsukawa ◽  
Keiko Marumo ◽  
Sachiyo Funamoto ◽  
...  
Keyword(s):  
Pregnancy Outcomes ◽  
Congenital Malformations ◽  
Radiation Effects ◽  
Atomic Bomb ◽  
Perinatal Deaths ◽  
Neonatal Deaths ◽  
Atomic Bomb Survivors ◽  
Parental Exposure ◽  
Increased Risk ◽  
Major Congenital Malformations

Abstract From 1948 to 1954, the Atomic Bomb Casualty Commission conducted a study of pregnancy outcomes of children of atomic bomb survivors who had received radiation doses from zero to near-lethal levels. Past reports (1956, 1981, and 1990) on the cohort did not identify significant associations of radiation exposure with untoward pregnancy outcomes such as major congenital malformations, stillbirths, or neonatal deaths, individually or in aggregate. We have re-examined the risk of major congenital malformations and perinatal deaths in the children of the atomic bomb survivors (N=71,603) using fully reconstructed data to minimize the potential for bias, with refined estimates of the gonadal dose from the Dosimetry System 2002 and refined analytical methods for characterizing dose-response relationships. The analyses show that parental exposure is associated with increased risk for major congenital malformations and perinatal deaths, but the estimates are imprecise for direct radiation effects and most are not statistically significant. Nonetheless, the uniformly positive estimates for untoward pregnancy outcomes among children of both maternal and paternal survivors are useful for risk assessment purposes, although extending them to circumstances other than atomic bomb survivors comes with uncertainty as to the generalizability of the Hiroshima and Nagasaki populations.

scholarly journals Antiepileptic drugs and suicide-related outcomes in bipolar disorder: A descriptive review of published data

2018 ◽  
Vol 8 (3) ◽  
pp. 138-147 ◽  
Author(s):  
Charles F. Caley ◽  
Emily Perriello ◽  
Julia Golden
Keyword(s):  
Bipolar Disorder ◽  
Antiepileptic Drugs ◽  
Suicide Attempts ◽  
Reference Group ◽  
Lithium Treatment ◽  
Reporting Rate ◽  
Published Data ◽  
Suicide Death ◽  
Suicidal Thinking ◽  
Increased Risk

Abstract Introduction: In January 2008 the US Food and Drug Administration issued a warning to healthcare professionals about the potential for an increased risk of suicidal thinking and behavior associated with antiepileptic drugs (AEDs). Given that AEDs are important for treating bipolar disorder (BD), a better understanding of suicide-related events is necessary. Methods: A PubMed search was performed using the following search terms: anticonvulsant OR valpro* OR carbamazepine OR lamotrigine OR oxcarbazepine OR topiramate AND bipolar AND suicid*. The objective was to identify published investigations reporting rate and/or risk data of suicide-related outcomes in BD patients treated with AED monotherapy. Results: The search identified 323 reviewable citations, with 13 of these studies (4.0%) being reviewed. Valproate was studied most often, and lithium treatment was frequently used as a reference group. Carbamazepine and lamotrigine had small treatment exposure durations. Suicide attempts and suicide deaths were studied the most; a few trials investigated suicidal thinking and/or hospitalizations for suicidal behavior. Suicide attempt rates occurred in the following order: no treatment > carbamazepine > valproate > lithium, while suicide death rates were: no treatment > valproate > lithium > carbamazepine. For valproate, the risk of suicide attempts and suicide death appeared higher than lithium, but lower than no treatment. Discussion: Investigating suicide-related events for AEDs in BD is difficult; more data are necessary for valproate, carbamazepine, and lamotrigine. An improved understanding of AED treatment and suicide-related events in BD may help pharmacists become more effective at supporting their patients with BD.

scholarly journals Antiepileptic drugs prescribed in pregnancy and prevalence of major congenital malformations: comparative prevalence studies

2017 ◽  
Vol Volume 9 ◽  
pp. 95-103 ◽  
Author(s):  
Irene Petersen ◽  
Shuk-Li Collings ◽  
Rachel L McCrea ◽  
Irwin Nazareth ◽  
David P Osborn ◽  
...  
Keyword(s):  
Antiepileptic Drugs ◽  
Congenital Malformations ◽  
Prevalence Studies ◽  
Major Congenital Malformations ◽  
In Pregnancy

scholarly journals Birth outcomes following antiretroviral exposure during pregnancy: Initial results from a pregnancy exposure registry in South Africa

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Ushma C. Mehta ◽  
Cari Van Schalkwyk ◽  
Prineetha Naidoo ◽  
Arthi Ramkissoon ◽  
Otty Mhlongo ◽  
...  
Keyword(s):  
Birth Outcomes ◽  
Congenital Malformations ◽  
First Trimester ◽  
First Year ◽  
Increased Risk ◽  
Bivariable Analysis ◽  
Major Congenital Malformations ◽  
Clinical Records ◽  
Surface Examination ◽  
The Impact

Background: In 2013, a pregnancy exposure registry and birth defects surveillance (PER/BDS) system was initiated in eThekwini District, KwaZulu-Natal (KZN), to assess the impact of antiretroviral treatment (ART) on birth outcomes.Objectives: At the end of the first year, we assessed the risk of major congenital malformations (CM) and other adverse birth outcomes (ABOs) detected at birth, in children born to women exposed to ART during pregnancy.Method: Data were collected from women who delivered at Prince Mshiyeni Memorial Hospital, Durban, from 07 October 2013 to 06 October 2014, using medicine exposure histories and birth outcomes from maternal interviews, clinical records and neonatal surface examination. Singleton births exposed to only one ART regimen were included in bivariable analysis for CM risk and multivariate risk analysis for ABO risk.Results: Data were collected from 10 417 women with 10 517 birth outcomes (4013 [38.5%] HIV-infected). Congenital malformations rates in births exposed to Efavirenz during the first trimester (T1) (RR 0.87 [95% CI 0.12–6.4; p = 0.895]) were similar to births not exposed to ART during T1. However, T1 exposure to Nevirapine was associated with the increased risk of CM (RR 9.28 [95% CI 2.3–37.9; p = 0.002]) when compared to the same group. Other ABOs were more frequent in the combination of HIV/ART-exposed births compared to HIV-unexposed births (29.9% vs. 26.0%, adjusted RR 1.23 [1.14–1.31; p 0.001]).Conclusion: No association between T1 use of EFV-based ART regimens and CM was observed. Associations between T1 NVP-based ART regimen and CM need further investigation. HIV- and ART-exposed infants had more ABOs compared to HIV-unexposed infants.

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