- Email: [email protected]
Cognitive development and low-level lead exposure in poly-drug exposed children
M. Stanton et al. / Neurotoxicology and Teratology 30 (2008) 243–259
evident at 300 and 1000 ppm, and augmentations in long-term potentiation were observed in the population spike measure at the highest dose. Dose-dependent deficits in hippocampal synaptic function were detectable with relatively minor perturbations of the thyroid axis indicative of an irreversible impairment in synaptic transmission in response to developmental exposure to perchlorate (does not reflect US EPA policy). doi:10.1016/j.ntt.2008.03.022
NBTS20 Behavioral lateralization and prenatal exposure to antiepileptic drugs: Evidence for increased non-right hand preference Kelly Marie McVearry a, Gholam Motamedi a, Kimford Meador b a Georgetown University Department of Neurology, United States b University of Florida McKnight Brain Institute, United States
Background. A fundamental issue in human neurodevelopment is the effect of teratogenic exposures on the organization of the cerebral cortex. Handedness is a prominent manifestation of behavioral lateralization in the human population, and aberrant distributions of handedness may be indicative of abnormal cerebral lateralization. The effects of prenatal exposure to antiepileptic drugs (AEDs) on behavioral lateralization are unknown. Objectives. We report hand preference observations from a prospective cohort study of children exposed in utero to AED monotherapy. Methods. Subjects (n = 43) are prospectivelyenrolled preschool children between 3.5 and 5 years of age (mean age = 4.17) from mother–child pairs who met stringent inclusion criteria in the NEAD Study, and are characterized by in utero exposure to carbamazepine, lamotrigine, phenytoin, or valproate monotherapy. Hand preference data (right hand, left hand, or ambiguous hand preference) were collected via three age-appropriate measures: (a) clinical observation of fine motor performance tasks, (b) clinical observation of gross motor performance task, and (c) parental report. Results. Across monotherapy groups, 30.9% children showed non-right hand preference, which is significantly different from the normal population average of 90% (p b 0.0001). Among AED monotherapy groups, non-right hand preference was greatest in valproate-exposed children (60.0%; n = 9), followed by carbamazepine-exposed children (42.9%; n = 16). Teratogenic risk. These results suggest altered neurodevelopment in children exposed to antiepileptic medication during gestation. doi:10.1016/j.ntt.2008.03.023
NBTS21 Fetal terbutaline exposure and child neurobehavioral outcome: A preliminary evaluation Jane Adams a, Stephanie Lagaert b, Patricia Janulewicz a, Kelly Kao b, Christina Chambers b, Kenneth Jones b a University of MA Boston, United States b UCSD School of Medicine, United States
Terbutaline (T; BrethineTM), a β2 adrenergic receptor agonist, approved for asthma treatment, has widespread off label use for the suppression of premature labor. Research indicates successful prolongation of pregnancy (Morrison et al., 2003; Mawaldi
249
et al., 2008) with very low serious adverse effects (Elliott et al., 2004), but child neurobehavioral outcome has received limited attention. Connors et al. (2005) reported that T may interact with a polymorphism relevant to signaling at β2 adrenergic receptors and increase concordance rates for autism among twins. Case reports of adverse outcomes have fueled a class action lawsuit. Thus, it is prudent to determine neurobehavioral risks associated with fetal exposure. From 24 prospectivelyascertained exposed registrants with the California Teratology Information Service, 19 with gestational exposure to Terbutaline have agreed to participate in further follow-up studies. None of the registrants had an infant with major malformations. Neurobehavioral evaluations of these and control (C) children are ongoing. Child performance on the Mullen Scale of Early Learning is being evaluated with maternal scores on the Wechsler Abbreviated Scale of Intelligence used as a covariate in uni- or multi-variate analyses of variance. Preliminary data (9 T and 8 C) suggest no significant group differences in the early learning composite scores of the children (T = 102.5; C = 94.9), and no significant differences in receptive or expressive language, visual processing, or fine motor ability, despite lower average scores in T-exposed children. Data on a larger sample analyzed to examine other relevant variables will be presented. doi:10.1016/j.ntt.2008.03.024
NBTS22 Cognitive development and low-level lead exposure in poly-drug exposed children Meeyoung Min a, Lynn Singer a, Sonia Minnes a, H. Lester Kirchner b, Suchitra Nelson a a Case Western Reserve University, United States b Geisinger Center for Health Research, United States
The impact of early postnatal lead exposure on children's IQ and academic achievement at 4, 9, and 11 years of age was examined in a sample of 278 innercity, primarily African American children who were prenatally polydrug exposed. As part of a longitudinal prospective study, blood lead levels were measured at 4 years of age (mean = 7.0 µg/dL (SD = 4.1), range 1.3–23.8). Regression analyses, using the restricted cubic spline function, indicated a linear effect of lead exposure on outcomes. Full Scale IQ point losses of 4.1–5.4 were estimated for each 10 μg/dL increase at 4, 9, and 11 years of age as a function of 4 year blood lead level after adjusting for prenatal tobacco, alcohol, marijuana and cocaine exposure, birth head circumference, iron-deficiency anemia, quality of the caregiving environment (HOME), and maternal characteristics. Specific cognitive domains were differentially affected at different ages. Nonverbal reasoning deficits were consistently associated with higher lead exposure throughout preschool– elementary school ages, while verbal deficits became apparent only at 11 years. Lower reading summary scores were associated with higher lead exposure at 9 and 11 years, while deficits in mathematics were shown only at 11 years. Subgroup analyses on children with blood lead level b 10 μg/dL (n = 226) showed detrimental lead effects even at the 5 μg/dL, providing additional evidence of adverse effects occurring at blood lead levels below the current 10 μg/dL public health blood lead action level. doi:10.1016/j.ntt.2008.03.025
evident at 300 and 1000 ppm, and augmentations in long-term potentiation were observed in the population spike measure at the highest dose. Dose-dependent deficits in hippocampal synaptic function were detectable with relatively minor perturbations of the thyroid axis indicative of an irreversible impairment in synaptic transmission in response to developmental exposure to perchlorate (does not reflect US EPA policy). doi:10.1016/j.ntt.2008.03.022
NBTS20 Behavioral lateralization and prenatal exposure to antiepileptic drugs: Evidence for increased non-right hand preference Kelly Marie McVearry a, Gholam Motamedi a, Kimford Meador b a Georgetown University Department of Neurology, United States b University of Florida McKnight Brain Institute, United States
Background. A fundamental issue in human neurodevelopment is the effect of teratogenic exposures on the organization of the cerebral cortex. Handedness is a prominent manifestation of behavioral lateralization in the human population, and aberrant distributions of handedness may be indicative of abnormal cerebral lateralization. The effects of prenatal exposure to antiepileptic drugs (AEDs) on behavioral lateralization are unknown. Objectives. We report hand preference observations from a prospective cohort study of children exposed in utero to AED monotherapy. Methods. Subjects (n = 43) are prospectivelyenrolled preschool children between 3.5 and 5 years of age (mean age = 4.17) from mother–child pairs who met stringent inclusion criteria in the NEAD Study, and are characterized by in utero exposure to carbamazepine, lamotrigine, phenytoin, or valproate monotherapy. Hand preference data (right hand, left hand, or ambiguous hand preference) were collected via three age-appropriate measures: (a) clinical observation of fine motor performance tasks, (b) clinical observation of gross motor performance task, and (c) parental report. Results. Across monotherapy groups, 30.9% children showed non-right hand preference, which is significantly different from the normal population average of 90% (p b 0.0001). Among AED monotherapy groups, non-right hand preference was greatest in valproate-exposed children (60.0%; n = 9), followed by carbamazepine-exposed children (42.9%; n = 16). Teratogenic risk. These results suggest altered neurodevelopment in children exposed to antiepileptic medication during gestation. doi:10.1016/j.ntt.2008.03.023
NBTS21 Fetal terbutaline exposure and child neurobehavioral outcome: A preliminary evaluation Jane Adams a, Stephanie Lagaert b, Patricia Janulewicz a, Kelly Kao b, Christina Chambers b, Kenneth Jones b a University of MA Boston, United States b UCSD School of Medicine, United States
Terbutaline (T; BrethineTM), a β2 adrenergic receptor agonist, approved for asthma treatment, has widespread off label use for the suppression of premature labor. Research indicates successful prolongation of pregnancy (Morrison et al., 2003; Mawaldi
249
et al., 2008) with very low serious adverse effects (Elliott et al., 2004), but child neurobehavioral outcome has received limited attention. Connors et al. (2005) reported that T may interact with a polymorphism relevant to signaling at β2 adrenergic receptors and increase concordance rates for autism among twins. Case reports of adverse outcomes have fueled a class action lawsuit. Thus, it is prudent to determine neurobehavioral risks associated with fetal exposure. From 24 prospectivelyascertained exposed registrants with the California Teratology Information Service, 19 with gestational exposure to Terbutaline have agreed to participate in further follow-up studies. None of the registrants had an infant with major malformations. Neurobehavioral evaluations of these and control (C) children are ongoing. Child performance on the Mullen Scale of Early Learning is being evaluated with maternal scores on the Wechsler Abbreviated Scale of Intelligence used as a covariate in uni- or multi-variate analyses of variance. Preliminary data (9 T and 8 C) suggest no significant group differences in the early learning composite scores of the children (T = 102.5; C = 94.9), and no significant differences in receptive or expressive language, visual processing, or fine motor ability, despite lower average scores in T-exposed children. Data on a larger sample analyzed to examine other relevant variables will be presented. doi:10.1016/j.ntt.2008.03.024
NBTS22 Cognitive development and low-level lead exposure in poly-drug exposed children Meeyoung Min a, Lynn Singer a, Sonia Minnes a, H. Lester Kirchner b, Suchitra Nelson a a Case Western Reserve University, United States b Geisinger Center for Health Research, United States
The impact of early postnatal lead exposure on children's IQ and academic achievement at 4, 9, and 11 years of age was examined in a sample of 278 innercity, primarily African American children who were prenatally polydrug exposed. As part of a longitudinal prospective study, blood lead levels were measured at 4 years of age (mean = 7.0 µg/dL (SD = 4.1), range 1.3–23.8). Regression analyses, using the restricted cubic spline function, indicated a linear effect of lead exposure on outcomes. Full Scale IQ point losses of 4.1–5.4 were estimated for each 10 μg/dL increase at 4, 9, and 11 years of age as a function of 4 year blood lead level after adjusting for prenatal tobacco, alcohol, marijuana and cocaine exposure, birth head circumference, iron-deficiency anemia, quality of the caregiving environment (HOME), and maternal characteristics. Specific cognitive domains were differentially affected at different ages. Nonverbal reasoning deficits were consistently associated with higher lead exposure throughout preschool– elementary school ages, while verbal deficits became apparent only at 11 years. Lower reading summary scores were associated with higher lead exposure at 9 and 11 years, while deficits in mathematics were shown only at 11 years. Subgroup analyses on children with blood lead level b 10 μg/dL (n = 226) showed detrimental lead effects even at the 5 μg/dL, providing additional evidence of adverse effects occurring at blood lead levels below the current 10 μg/dL public health blood lead action level. doi:10.1016/j.ntt.2008.03.025