Sandra W. Jacobson

Intellectual Impairment in Children Exposed to Polychlorinated Biphenyls in Utero

BACKGROUND In utero exposure to polychlorinated biphenyls, a ubiquitous environmental contaminant, has been linked to adverse effects on neurologic and intellectual function in infants and young children. We assessed whether these effects persist through school age and examined their importance in the acquisition of reading and arithmetic skills. METHODS We tested 212 children, recruited as newborns to overrepresent infants born to women who had eaten Lake Michigan fish contaminated with polychlorinated biphenyls. A battery of IQ and achievement tests was administered when the children were 11 years of age. Concentrations of polychlorinated biphenyls in maternal serum and milk at delivery were slightly higher than in the general population. A composite measure of prenatal exposure was derived from concentrations in umbilical-cord serum and maternal serum and milk. RESULTS Prenatal exposure to polychlorinated biphenyls was associated with lower full-scale and verbal IQ scores after control for potential confounding variables such as socioeconomic status (P = 0.02). The strongest effects related to memory and attention. The most highly exposed children were three times as likely to have low average IQ scores (P <0.001) and twice as likely to be at least two years behind in reading comprehension (P = 0.03). Although larger quantities of polychlorinated biphenyls are transferred by breast-feeding than in utero, there were deficits only in associated with transplacental exposure, suggesting that the developing fetal brain is particularly sensitive to these compounds. CONCLUSIONS In utero exposure to polychlorinated biphenyls in concentrations slightly higher than those in the general population can have a long-term impact on intellectual function.

Effects of in utero exposure to polychlorinated biphenyls and related contaminants on cognitive functioning in young children

Because prenatal exposure to polychlorinated biphenyls (PCBs) and related contaminants has been associated with reduced birth weight, neonatal behavioral anomalies, and poorer recognition memory in infants born to women who have consumed Lake Michigan sports fish, 236 children, previously evaluated for PCB-related deficits in infancy, were assessed at 4 years of age. Prenatal exposure (indicated by umbilical cord serum PCB level) predicted poorer short-term memory function on both verbal and quantitative tests in a dose-dependent fashion. These effects cannot be attributed to a broad range of potential confounding variables, the impact of which was evaluated statistically. Although much larger quantities of PCBs are transferred postnatally via lactation than prenatally across the placenta, exposure from nursing was unrelated to cognitive performance. The data demonstrate the continuation of a toxic impact received in utero and observed initially during infancy on a dimension of cognitive functioning fundamental to learning.

The Effect of Intrauterine PCB Exposure on Visual Recognition Memory.

Adverse neonatal outcomes have been associated with intrauterine exposure to polychlorinated biphenyls (PCBs). In a follow-up study of exposed and nonexposed infants, 123 infants tested at birth were administered Fagans test of visual recognition memory at 7 months. 2 measures of prenatal PCB exposure, cord serum PCB level and maternal report of contaminated fish consumption, both predicted less preference for a novel stimulus. Preference for novelty decreased in a dose-dependent fashion with increasing levels of prenatal PCB exposure. Postnatal exposure from nursing was not related to visual recognition memory. The relation between prenatal exposure and visual recognition was not mediated by the neonatal deficits, suggesting that intrauterine PCB exposure may have a delayed effect on central nervous system (CNS) functioning.

Effects of exposure to PCBs and related compounds on growth and activity in children

Two hundred thirty-six children from two established cohorts at risk for exposure to polychlorinated biphenyls (PCBs) and related contaminants were evaluated at age 4 years. Prenatal exposure (assessed by cord serum PCB level) was associated with lower weight, an effect consistent with reports of growth retardation in laboratory rats and in children exposed at high levels in Taiwan and at general population levels in Japan. The highest exposed children weighed 1.8 kg less on the average than the least exposed. Contemporary body burden (assessed by 4-year serum PCB level) was associated with reduced activity based on composite ratings provided by the childs mother and two independent examiners. This effect, attributable to lactation exposure, was strongest among the offspring of women with above average milk PCB levels who breast fed for at least 1 year. While the weight deficit is consistent with previous data linking developmental effects of low-dose human PCB exposures specifically to the prenatal period, activity is the first domain found to be affected by lactation at contemporary levels of exposure.

Functional aspects of developmental toxicity of polyhalogenated aromatic hydrocarbons in experimental animals and human infants

A scientific evaluation was made of functional aspects of developmental toxicity of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in experimental animals and in human infants. Persistent neurobehavioral, reproductive and endocrine alterations were observed in experimental animals, following in utero and lactational exposure to PCBs, PCDDs and PCDFs. The lowest observable adverse effect levels (LOAELs) for developmental neurobehavioral and reproduction endpoints, based on body burden of TCDD-toxic equivalents (TEQs) in animals, are within the range of current background human body burdens. Relatively subtle adverse effects on neurobehavioral development and thyroid hormone alterations have also been observed in infants and children exposed to background levels. Exclusive use of the toxic equivalency factor (TEF) approach may underestimate the risk of neurodevelopmental effects, because both Ah receptor dependent and independent mechanisms may be involved in these effects. The use of marker congeners and/or bioassays based on Ah receptor mediated mechanisms are rapid, low cost pre-screening alternatives for expensive and time consuming gas chromatographic-mass spectrometric analysis.

The transfer of polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs) across the human placenta and into maternal milk

Cord serum and maternal milk levels of polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs) were examined in relation to maternal serum levels. Maternal serum levels were significantly higher than cord serum levels for both types of compounds. Placental passage was indicated by significant maternal to cord serum correlations for both PCBs (r = .42) and PBBs (r = .81). Correlations between maternal serum and milk levels were similar. Higher PBB correlations were probably due to greater reliability in the measurement of PBB levels in serum and milk.

Impact of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls on human and environmental health, with special emphasis on application of the toxic equivalency factor concept

A scientific evaluation was made of the mechanisms of action of polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls. Distinction is made between the aryl-hydrocarbon (Ah) receptor-mediated and non-Ah receptor-mediated toxic responses. Special attention is paid to the applicability of the toxic equivalency factor (TEF) concept.

Prenatal exposure to polychlorinated biphenyls and attention at school age

Abstract Objective To examine the relation of prenatal polychlorinated biphenyl (PCB) exposure to child performance on neuropsychological tests of attention and information processing. Study design In this prospective, longitudinal study, assessment of prenatal PCB exposure was based on umbilical cord serum and maternal serum and milk concentrations. The children were tested in their homes at age 11 years. Multiple regression was used to examine the relation of this exposure to performance on 15 neuropsychological tests after controlling for a broad range of potential confounding variables. Results Adverse effects were seen primarily in children who had not been breast fed. Among these children, prenatal PCB exposure was associated with greater impulsivity, poorer concentration, and poorer verbal, pictorial, and auditory working memory. There was no evidence of visual-spatial deficit or increased hyperactivity. Conclusions These findings are consistent with earlier reports of greater vulnerability to prenatal PCB exposure in children who were not breast fed. It is not clear whether the protection offered by breast-feeding is caused by nutrients in breast milk or better quality of intellectual stimulation often provided by breast-feeding mothers.

Detecting risk drinking during pregnancy: a comparison of four screening questionnaires.

OBJECTIVES This study investigated the efficacy of screening for risk drinking during pregnancy with two brief questionnaires, TWEAK and T-ACE. Both include an assessment of tolerance based on the number of drinks women report they can hold. METHODS Subjects were disadvantaged African-American obstetric patients in Detroit, Mich. Traditional alcoholism screens (Michigan Alcohol Screening Test [MAST], CAGE) and the tolerance question were administered (n = 2717); TWEAK and T-ACE were constructed from tolerance and embedded MAST and CAGE items. In a separate sample (n = 1420), only the T-ACE was administered. Periconceptional risk drinking was the gold standard. Screen evaluations were based on receiver-operating characteristic analyses. RESULTS At the cutpoint of 2, sensitivity/specificity for embedded screens were 91/77 for TWEAK and 88/79 for T-ACE; comparable values for T-ACE alone were 67/86. TWEAK and T-ACE screened more effectively than CAGE or MAST. CONCLUSIONS Embedded versions of TWEAK and T-ACE were both highly sensitive to periconceptional risk drinking in this population. Administering T-ACE alone reduced its sensitivity; this suggests that MAST and CAGE administration improves its performance.

New evidence for neurobehavioral effects of in utero cocaine exposure

Most studies of prenatal cocaine exposure have found gestational age or intrauterine growth deficits but few, if any, cognitive effects. In a large, well-controlled study we detected cognitive deficits in relation to heavy cocaine exposure. These findings demonstrate that prenatal exposure to cocaine at sufficiently high doses early in pregnancy has the potential to produce cognitive changes in infants and that more focused, narrow-band tests may be necessary to detect these subtle neurobehavioral effects. A total of 464 inner-city, black infants whose mothers were recruited prenatally on the basis of pregnancy alcohol and cocaine use were tested at 6.5, 12, and 13 months of age. Standard analyses, based on presence or absence of cocaine use during pregnancy, confirmed effects on gestational age but failed to detect cognitive effects. A new approach to identifying heavy users found that heavy exposure early in pregnancy was related to faster responsiveness on an infant visual expectancy test but to poorer recognition memory and information processing, deficits consistent with prior human and animal findings. These persistent neurobehavioral effects of heavy prenatal cocaine exposure appear to be direct effects of exposure and independent of effects on gestational age.