Abstract:
:Most epileptic women delivering children each year take anticonvulsants throughout pregnancy. The teratogenic potential of anticonvulsants is most notable for phenytoin, trimethadione, valproic acid, and carbamazepine. This review focuses on the human and animal evidence for the teratogenicity of phenytoin, with emphasis on neurobehavioral end points. The Fetal Hydantoin Syndrome (FHS) consists of craniofacial defects and any two of the following: pre/postnatal growth deficiency, limb defects, major malformations, and mental deficiency. Available data suggest a prevalence of FHS of 10-30% in infants of women ingesting 100-800 mg/kg of phenytoin during the first trimester or beyond. Unfortunately, data on neurobehavioral development in FHS children is limited. Animal models of FHS have been developed and those focusing on neurobehavioral effects are reviewed. Phenytoin produces multiple behavioral dysfunctions in rat offspring at subteratogenic and nongrowth retarding doses. These behaviorally teratogenic doses produce maternal serum phenytoin concentrations in rats comparable to those found in humans. The dysfunctions in rats are dose-dependent and exposure-period-dependent, but independent of nutritional, maternal rearing, or seizure disorder confounds. Effects include vestibular dysfunction, hyperactivity and deficits in learning and memory. General comparability between the human and animal findings for phenytoin are apparent, however, difficulties with existing studies prevent precise comparisons. Animal studies have not dealt satisfactorily with the potential contribution of epileptic disease state to the FHS, with fetal brain drug concentration determinations, a complete dose-effect range, effects in multiple species (although limited nonhuman primate data exist), site of CNS injury, and the comparability of end points assessed. Human studies have not dealt satisfactorily with issues of the need for prospective study designs, separation of the effects of different anticonvulsants, or adequate long-term follow-up of cases, especially with attention to neuropsychological assessment.
journal_name
Neurotoxicol Teratoljournal_title
Neurotoxicology and teratologyauthors
Adams J,Vorhees CV,Middaugh LDdoi
10.1016/0892-0362(90)90092-qsubject
Has Abstractpub_date
1990-05-01 00:00:00pages
203-14issue
3eissn
0892-0362issn
1872-9738pii
0892-0362(90)90092-Qjournal_volume
12pub_type
杂志文章,评审abstract::The reduction in growth resulting from lead (PB) exposure in weanling rats is consistent with a lowering of the biological set-point for food intake. In this study the effects of lead on the patterns of food intake were examined. For 10 days (from ages 26 to 36 days), female rats were provided with drinking water cont...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/0892-0362(94)90040-x
更新日期:1994-11-01 00:00:00
abstract::Zebrafish provide a powerful model of the impacts of embryonic toxicant exposure on neural development that may result in long-term behavioral dysfunction. In this study, zebrafish embryos were treated with 1.5mM strychnine for short embryonic time windows to induce transient changes in inhibitory neural signaling, an...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2012.08.001
更新日期:2012-11-01 00:00:00
abstract::Measures of visual contrast sensitivity (VCS), rather than traditional measures of visual acuity using high-contrast stimuli, have been presented as better appraisals of visual dysfunction resulting from chemical exposures. The present study sought to determine if differences exist between two available measures of co...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2003.10.007
更新日期:2004-03-01 00:00:00
abstract::We examined the relationship between acquired color vision loss and exposure to toluene and total hydrocarbons among 125 male workers. Seventy-two toluene-exposed printers were compared with 34 workers from the same photogravure plant with ambient background exposure, and with 19 workers from a bookbinding plant locat...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/s0892-0362(01)00163-5
更新日期:2001-09-01 00:00:00
abstract::Pregnant C57BL/6 mice were chronically treated with 0, 4, 6, or 8 ppm of methylmercury chloride (MeHg) in drinking water during fetal and early postnatal development. Four behavioral functions were analyzed in female and male offspring between the age of 6 and 12 weeks: motor coordination learning on the rotarod; trai...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/s0892-0362(03)00007-2
更新日期:2003-05-01 00:00:00
abstract::Maternal smoking during pregnancy greatly enhances perinatal morbidity/mortality and is the major risk factor for Sudden Infant Death Syndrome (SIDS). Studies in developing rodents indicate that nicotine is a neuroteratogen that targets monoamine pathways involved in the responses to hypoxia that are in turn, hypothes...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2011.02.001
更新日期:2011-05-01 00:00:00
abstract::This study examined the effects of chronic postweaning lead (Pb) exposure in Long-Evans rats on a series of spatial alternation tasks. All tasks were administered in automated testing chambers, with a nosepoke as the critical response. While neither Pb-exposed group (median blood lead levels: 19 and 39 micrograms/dl, ...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/0892-0362(95)02026-8
更新日期:1996-01-01 00:00:00
abstract::Monensin, a growth-promoting agent and coccidiostat used in veterinary medicine, was studied in terms of its effects on the development of female rats and their offspring when added to the diet. Young female rats received 100 or 300 ppm monensin mixed with powdered chow diet until adulthood, when they were mated and t...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/s0892-0362(99)00012-4
更新日期:1999-07-01 00:00:00
abstract::A variety of behavioral instruments are available for assessing important aspects of cognition in both animals and humans and, in many cases, the same instruments can be used in both. While nonhuman primates are phylogenetically closest to humans, rodents, pigeons and other animals also offer behaviors worthy of note....
journal_title:Neurotoxicology and teratology
pub_type:
doi:10.1016/j.ntt.2012.01.008
更新日期:2012-03-01 00:00:00
abstract::The present study was designed to investigate the possible involvement of TLR4 pathway in the mouse hippocampus following toluene exposure. Male C3H/HeN and C3H/HeJ (TLR4 defective) mice were exposed to 0, 5, 50 or 500 ppm of toluene for 6 weeks. The expressions of TLR4-related signal transduction pathway mRNAs in the...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2011.07.005
更新日期:2011-09-01 00:00:00
abstract::The effects of administration by inhalation of metallic mercury vapour (Hg0) to pregnant rats, approximately corresponding to doses of 0.2 mg Hg0/kg/day (high dose) or 0.07 mg Hg0/kg/day (low dose), on the developmental and behavioural repertoire of the offspring were studied. Exposure occurred during days 11-14 plus ...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/0892-0362(93)90056-t
更新日期:1993-11-01 00:00:00
abstract::Prenatal exposure to cocaine in rats has previously been shown to alter the behavioral and hormonal responses to acute stressors, although no work has yet examined stress adaptation in these animals in adulthood, a possibility examined in this experiment. Male and female offspring of Sprague-Dawley rat dams given 40 m...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/s0892-0362(00)00104-5
更新日期:2000-11-01 00:00:00
abstract:OBJECTIVE:To examine the association between prenatal exposure to nicotine from tobacco smoke and infant neurobehavior using tobacco biomarkers and a sensitive and comprehensive measure of infant neurobehavior. STUDY DESIGN:Participants were 318 infants (206 White, 95 Black, 17 Other) and their mothers. Prenatal tobac...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2009.07.004
更新日期:2009-11-01 00:00:00
abstract::Ultrasonic calls are emitted by many species of rodents in a variety of situations. In particular, infants commonly emit such calls when removed from the nest; the rate and intensity of calling are related to the degree of development of homoiothermy. The relevant biological significance of these signals is documented...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/0892-0362(87)90093-6
更新日期:1987-03-01 00:00:00
abstract::We have studied the reactive responses of both astrocytes and microglia to dopaminergic denervation of the striatum by MPTP. Following MPTP treatment, increased GFAP immunoreactivity reached a peak at 2 days and persisted for at least 6 weeks. Immunoreactivity to vimentin was also markedly increased in astrocytes 48 h...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/0892-0362(94)00048-i
更新日期:1995-01-01 00:00:00
abstract::Volatile organic solvent (inhalant) abuse continues to be a major health concern throughout the world. Of particular concern is the abuse of inhalants by adolescents because of its toxicity and link to illicit drug use. Toluene, which is found in many products such as glues and household cleaners, is among the most co...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2007.08.001
更新日期:2007-11-01 00:00:00
abstract::Sulfites, which are commonly used as preservatives, are continuously formed in the body during metabolism of sulfur-containing amino acids. Sulfite is oxidized to sulfate ion by sulfite oxidase (SOX, EC. 1.8.3.1). The aim of this study was to investigate the possible toxic effects of sulfite on neurons by measuring ac...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2004.10.002
更新日期:2005-01-01 00:00:00
abstract::Pregnant rats received daily injections of saline, cocaine (20 mg/kg), morphine (2 mg/kg), or the combination of both drugs, on days 13-20 of gestation. Cyclin-dependent kinase 5 (Cdk5) activity was then measured in the resulting pups on postnatal days 1, 7, 14 and 28. Cocaine resulted in a time dependent increase in ...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2006.06.006
更新日期:2006-09-01 00:00:00
abstract::Visuoperceptual performance was examined in 146 9- to 12-year old children for whom prenatal exposure to marihuana and cigarettes had been ascertained. The subjects, participants in an ongoing longitudinal study, were from a low-risk, predominantly middle class sample. The tasks ranged in complexity from those that re...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/s0892-0362(99)00046-x
更新日期:2000-01-01 00:00:00
abstract::The developmental neurotoxicity of organophosphates such as chlorpyrifos (CPF) involves multiple mechanisms that ultimately compromise the function of specific neurotransmitter systems, notably acetylcholine (ACh) and serotonin (5-hydroxytryptamine, 5HT). Studies in mammalian models incorporate both direct effects on ...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2008.02.005
更新日期:2008-09-01 00:00:00
abstract::The present study was aimed at investigating the long-term effects of prenatal exposure to lamivudine (3TC), an antiretroviral drug used in clinical practice alone or in combination with zidovudine (AZT) to prevent mother-to-child transmission of the HIV virus. Pregnant CD-1 mice were given per os twice daily either 3...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/s0892-0362(00)00063-5
更新日期:2000-05-01 00:00:00
abstract::This is the first in a series of studies investigating the developmental stage-specific neurobehavioral effects of all-trans retinoic acid (RA) exposure. Because high doses of this compound are known to be lethal to the developing organism, we first conducted a dose-response study to identify RA doses that produce low...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/s0892-0362(97)00039-1
更新日期:1997-09-01 00:00:00
abstract::Previous work showed that rats develop tolerance to the acute behavioral effects of trichloroethylene (TCE) on signal detection if they inhale TCE while performing the task and that this tolerance depends more upon learning than upon changes in metabolism of TCE. The present study sought to characterize this tolerance...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/s0892-0362(01)00182-9
更新日期:2001-11-01 00:00:00
abstract::Methylphenidate (MPH) is a psychostimulant commonly used for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD). Since the long-term effects of this drug on the central nervous system (CNS) are not well understood, we conducted microPET/CT scans on young adult male rhesus monkeys (n=4/group) to gather in...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2016.06.005
更新日期:2016-07-01 00:00:00
abstract::1-beta-D-Arabinofuranosylcytosine (Ara-C), a cytidine analogue cytotoxic to proliferating cells, has a teratogenic effect in the brain of experimental animals and causes neural cell apoptosis in vitro and in vivo. In the present study, pregnant rats were injected with Ara-C on Day 13 of gestation and the fetal brain w...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2004.03.010
更新日期:2004-07-01 00:00:00
abstract::Cortical thickness abnormalities have been identified in youth using both alcohol and marijuana. However, limited studies have followed individuals pre- and post initiation of alcohol and marijuana use to help identify to what extent discrepancies in structural brain integrity are pre-existing or substance-related. Ad...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章,评审
doi:10.1016/j.ntt.2016.09.005
更新日期:2016-01-01 00:00:00
abstract::To identify the frequency range most sensitive to toluene-induced auditory damage, the auditory function of adult Long-Evans rats exposed to 1750 ppm of toluene (6 h/day, 5 days/week, 4 weeks), was tested by recording auditory-evoked potentials directly from the round window of the cochlea. The present electrocochleog...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/s0892-0362(98)00057-9
更新日期:1999-05-01 00:00:00
abstract:BACKGROUND:Prenatal tobacco exposure is a risk factor for the development of externalizing behaviors and is associated with several adverse health outcomes. Because pregnancy smoking is a complex behavior with both daily fluctuations and changes over the course of pregnancy, quantifying tobacco exposure is a significan...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2010.08.003
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Epidemiological studies examining the effects of prenatal toxic heavy metals exposure on neonatal development at the population-based level are limited. OBJECTIVE:To explore prenatal exposure levels to toxic heavy metals and examine whether exposure is associated with neonatal development. METHODS:A strati...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2011.05.010
更新日期:2011-07-01 00:00:00
abstract::Dysmorphologic and anthropometric assessments were performed on 154 6-year-old children prenatally exposed to cocaine (PCE) and 131 high-risk controls (NCE) of similar race and social class. Adjusted mean height z scores demonstrated a dose-response with metahydroxybenzoylecgonine above a threshold of 100 ng/g of meco...
journal_title:Neurotoxicology and teratology
pub_type: 杂志文章
doi:10.1016/j.ntt.2005.09.003
更新日期:2006-01-01 00:00:00