Anticonvulsants during Pregnancy and Lactation

Nau, Heinz; Kuhnz, W.; Egger, H; Rating, D.; Helge, H

doi:10.2165/00003088-198207060-00003

Cited by 149 publications

(3 citation statements)

References 63 publications

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“…However, VPA is teratogenic (Nau et al, 1982; Ornoy, 2009), where exposure during gestation increases the risk for various congenital malformations in the child, grouped as Fetal Valproate Syndrome (FVS; Kozma, 2001; Kini, 2006; Ornoy, 2009). FVS features also include decreased verbal intelligence and an association between VPA exposure in utero and autism has been consistently reported (reviewed in Ornoy, 2009; Roullet et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

General developmental health in the VPA-rat model of autism

Favre¹,

Barkat²,

LaMendola³

et al. 2013

Front. Behav. Neurosci.

105

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Autism is a neurodevelopmental condition diagnosed by impaired social interaction, abnormal communication and, stereotyped behaviors. While post-mortem and imaging studies have provided good insights into the neurobiological symptomology of autism, animal models can be used to study the neuroanatomical, neurophysiological and molecular mediators in more detail and in a more controlled environment. The valproic acid (VPA) rat model is an environmentally triggered model with strong construct and clinical validity. It is based on VPA teratogenicity in humans, where mothers who are medicated with VPA during early pregnancy show an increased risk for giving birth to an autistic child. In rats, early embryonic exposure, around the time of neural tube closure, leads to autism-like anatomical and behavioral abnormalities in the offspring. Considering the increasing use of the VPA rat model, we present our observations of the general health of Wistar dams treated with a single intraperitoneal injection of 500 or, 600 mg/kg VPA on embryonic day E12.5, as well as their male and female offspring, in comparison to saline-exposed controls. We report increased rates of complete fetal reabsorption after both VPA doses. VPA 500 mg/kg showed no effect on dam body weight during pregnancy or, on litter size. Offspring exposed to VPA 500 mg/kg showed smaller brain mass on postnatal days 1 (P1) and 14 (P14), in addition to abnormal nest seeking behavior at P10 in the olfactory discrimination test, relative to controls. We also report increased rates of physical malformations in the offspring, rare occurrences of chromodacryorrhea and, developmentally similar body mass gain. Further documentation of developmental health may guide sub-grouping of individuals in a way to better predict core symptom severity.

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Section: Introductionmentioning

confidence: 99%

General developmental health in the VPA-rat model of autism

Favre¹,

Barkat²,

LaMendola³

et al. 2013

Front. Behav. Neurosci.

105

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“…In the next 20 years, the awareness of the importance of development on drug disposition rose among pharmacologists, leading to a new research field: neonatal PK [114][115][116]. Since then, the efforts to better understand drug metabolism and safety in pediatric populations have augmented and so has the use of animal, in vitro and in silico models for this sensitive age group.…”

Section: History Of Pharmacological Studies In Pigsmentioning

confidence: 99%

The Neonatal and Juvenile Pig in Pediatric Drug Discovery and Development

et al. 2020

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Pharmacotherapy in pediatric patients is challenging in view of the maturation of organ systems and processes that affect pharmacokinetics and pharmacodynamics. Especially for the youngest age groups and for pediatric-only indications, neonatal and juvenile animal models can be useful to assess drug safety and to better understand the mechanisms of diseases or conditions. In this respect, the use of neonatal and juvenile pigs in the field of pediatric drug discovery and development is promising, although still limited at this point. This review summarizes the comparative postnatal development of pigs and humans and discusses the advantages of the juvenile pig in view of developmental pharmacology, pediatric diseases, drug discovery and drug safety testing. Furthermore, limitations and unexplored aspects of this large animal model are covered. At this point in time, the potential of the neonatal and juvenile pig as nonclinical safety models for pediatric drug development is underexplored.

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“…Virtually all AEDs cross into breast milk (381, with breast milk concentrations ranging from 10 to 100% of maternal plasma concentrations (48, 85,86). Although concentrations of most AEDs in breast milk are usually low, concentrations in the neonate may exceed those of the mother because of reduced protein binding and longer drug elimination half-lives in neonates (48).…”

Section: Postpartum Managementmentioning

confidence: 99%

Obstetric and Gynecologic Care of Women with Epilepsy

El‐Sayed

1998

Epilepsia

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Summary: Optimal gynecologic and obstetric care for women with epilepsy requires a multidisciplinary approach throughout the various life stages. Epilepsy has important effects on puberty, contraceptive efficacy, pregnancy and fetal development, and menopause. This article discusses these effects and makes recommendations for gynecologic and obstetric care of patients with epilepsy, with particular focus on pregnancy. Despite very real risks to both the developing fetus and the mother, the majority of women with epilepsy-with appropriate pregnancy planning and management-have good pregnancy outcomes. Key Words: Epilepsy-Pregnancy-Puberty-Contraception-Menopause.It is estimated that there are 1 million women of childbearing age with epilepsy in the United States (1). Optimal gynecologic and obstetric care of these and other women with epilepsy requires the close collaboration of the obstetrician-gynecologist, neurologist, nurse educator, genetic counselor, and pediatrician. Using this team approach, the true spectrum of management issues in the female patient with epilepsy can be effectively addressed and coordinated. These issues broadly include the effects of epilepsy on puberty, contraceptive efficacy, pregnancy and fetal development, and menopause, and the effect of these reproductive life stages on the course of epilepsy. The use of antiepileptic drugs (AEDs) in pregnancy, their variable pharmacokinetics, and their associated risks for congenital malformations and neonatal side effects requires input from multiple specialties to help optimize maternal and neonatal outcomes. As always, the active involvement of a well-informed patient is crucial. EFFECTS OF EPILEPSY ON REPRODUCTIVE HEALTH PubertyAlthough dysfunction of the hypothalamic-pituitarygonadal axis has been reported in epilepsy, the exact effect of epilepsy on puberty is unclear. Regardless of a diagnosis of epilepsy, delayed puberty in an adolescent

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Anticonvulsants during Pregnancy and Lactation

Cited by 149 publications

References 63 publications

General developmental health in the VPA-rat model of autism

General developmental health in the VPA-rat model of autism

The Neonatal and Juvenile Pig in Pediatric Drug Discovery and Development

Obstetric and Gynecologic Care of Women with Epilepsy

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