Parietal dysfunction during number processing in children with fetal alcohol spectrum disorders.

Number processing deficits are frequently seen in children prenatally exposed to alcohol. Although the parietal lobe, which is known to mediate several key aspects of number processing, has been shown to be structurally impaired in fetal alcohol spectrum disorders (FASD), effects on functional activity in this region during number processing have not previously been investigated. This fMRI study of 49 children examined differences in activation associated with prenatal alcohol exposure in five key parietal regions involved in number processing, using tasks involving simple addition and magnitude comparison. Despite generally similar behavioral performance, in both tasks greater prenatal alcohol exposure was related to less activation in an anterior section of the right horizontal intraparietal sulcus known to mediate mental representation and manipulation of quantity. Children with fetal alcohol syndrome and partial fetal alcohol syndrome appeared to compensate for this deficit by increased activation of the angular gyrus during the magnitude comparison task.

A tensor-based morphometry analysis of regional differences in brain volume in relation to prenatal alcohol exposure.

Reductions in brain volumes represent a neurobiological signature of fetal alcohol spectrum disorders (FASD). Less clear is how regional brain tissue reductions differ after normalizing for brain size differences linked with FASD and whether these profiles can predict the degree of prenatal exposure to alcohol. To examine associations of regional brain tissue excesses/deficits with degree of prenatal alcohol exposure and diagnosis with and without correction for overall brain volume, tensor-based morphometry (TBM) methods were applied to structural imaging data from a well-characterized, demographically homogeneous sample of children diagnosed with FASD (n = 39, 9.6-11.0 years) and controls (n = 16, 9.5-11.0 years). Degree of prenatal alcohol exposure was significantly associated with regionally pervasive brain tissue reductions in: (1) the thalamus, midbrain, and ventromedial frontal lobe, (2) the superior cerebellum and inferior occipital lobe, (3) the dorsolateral frontal cortex, and (4) the precuneus and superior parietal lobule. When overall brain size was factored out of the analysis on a subject-by-subject basis, no regions showed significant associations with alcohol exposure. FASD diagnosis was associated with a similar deformation pattern, but few of the regions survived FDR correction. In data-driven independent component analyses (ICA) regional brain tissue deformations successfully distinguished individuals based on extent of prenatal alcohol exposure and to a lesser degree, diagnosis. The greater sensitivity of the continuous measure of alcohol exposure compared with the categorical diagnosis across diverse brain regions underscores the dose dependence of these effects. The ICA results illustrate that profiles of brain tissue alterations may be a useful indicator of prenatal alcohol exposure when reliable historical data are not available and facial features are not apparent.

Alteration of infant attention and activity by polychlorinated biphenyls: unravelling critical windows of susceptibility using physiologically based pharmacokinetic modeling.

Pre- and postnatal exposure to polychlorinated biphenyls (PCBs) can impair behavioural function in animal models at doses within the range at which humans are commonly exposed. Yet, epidemiologic studies conducted in the US and Europe are inconsistent with regard to the developmental effects of lactational exposure to these chemicals. This inconsistency may be due to limitations in the current methodological approaches for assessing postnatal exposure to PCBs. Our study used a physiologically based pharmacokinetic (PBPK) model to simulate blood PCB levels during specific pre- and postnatal periods and to evaluate the relation of those levels to infant behaviour. A previously validated PBPK model was used to simulate infant blood PCB-153 levels at delivery and on a month-by-month basis during the first year of life for Inuit infants enrolled in a longitudinal birth cohort. Infant behaviour was assessed using the Behaviour Rating Scales (BRS) of the Bayley Scales of Infant Development (BSID-II) at 11 months of age and video coding of inattention and activity measured during the administration of the mental development subscale of the BSID-II. The estimated pre- and postnatal PCB exposure measures predicted significant increases in inattention and activity at 11 months. Whereas inattention was related to prenatal exposure, activity level, measured by non-elicited activity, was best predicted by postnatal exposure, with the strongest association obtained for simulated PCB levels during the 4th month of life. These findings are consistent with previous reports indicating PCB-induced behavioural alteration in attention and activity level. Simulated infant toxicokinetic profiles for the first year of life revealed windows of susceptibility during which PCBs may impair infant attention and activity.

Behavioural correlates of the P3b event-related potential in school-age children.

The latency and amplitude of the P3b component of event-related potentials (ERPs) have been related to behavioural performance on several attention and memory tasks in adult populations. However, the extent to which these results apply to children is unknown. This study examined the neurobehavioral correlates of the P3b component in a longitudinal sample of school-age children from Arctic Québec. Children (N=110; mean age=11.3years) were assessed on an ERP auditory oddball paradigm and a neurobehavioral evaluation targeting several aspects of cognition, including the Stewart Extended Continuous Performance Test (E-CPT), California Verbal Learning Test (CVLT), Stroop Color-Word Interference Test, and five subtests from the Wechsler Intelligence Scale for Children-Fourth edition (WISC-IV). P3b latency was positively related to reaction time measures and negatively associated with performance on the WISC-IV Digit Span Forward subtest. Amplitude of the P3b was associated with shorter completion time on the Stroop test and better delayed recognition memory performance among children who did not use semantic strategies on the CVLT. Profile analyses revealed no difference in scalp distribution of the P3b according to performance on these tests. The results are consistent with previous studies with older participants and suggest that, despite age-related differences in waveform and scalp distribution, the P3b component relates to similar neurocognitive processes in children and adults.

Prenatal alcohol exposure alters the patterns of facial asymmetry.

Directional asymmetry, the systematic differences between the left and right body sides, is widespread in human populations. Changes in directional asymmetry are associated with various disorders that affect craniofacial development. Because facial dysmorphology is a key criterion for diagnosing fetal alcohol syndrome (FAS), the question arises whether in utero alcohol exposure alters directional asymmetry in the face. Data on the relative position of 17 morphologic landmarks were obtained from facial scans of children who were classified as either FAS or control. Shape data obtained from the landmarks were analyzed with the methods of geometric morphometrics. Our analyses showed significant directional asymmetry of facial shape, consisting primarily of a shift of midline landmarks to the right and a displacement of the landmarks around the eyes to the left. The asymmetry of FAS and control groups differed significantly and average directional asymmetry was increased in those individuals exposed to alcohol in utero. These results suggest that the developmental consequences of fetal alcohol exposure affect a wide range of craniofacial features in addition to those generally recognized and used for diagnosis of FAS.

Automated diagnosis of fetal alcohol syndrome using 3D facial image analysis.

OBJECTIVES: Use three-dimensional (3D) facial laser scanned images from children with fetal alcohol syndrome (FAS) and controls to develop an automated diagnosis technique that can reliably and accurately identify individuals prenatally exposed to alcohol. METHODS: A detailed dysmorphology evaluation, history of prenatal alcohol exposure, and 3D facial laser scans were obtained from 149 individuals (86 FAS; 63 Control) recruited from two study sites (Cape Town, South Africa and Helsinki, Finland). Computer graphics, machine learning, and pattern recognition techniques were used to automatically identify a set of facial features that best discriminated individuals with FAS from controls in each sample. RESULTS: An automated feature detection and analysis technique was developed and applied to the two study populations. A unique set of facial regions and features were identified for each population that accurately discriminated FAS and control faces without any human intervention. CONCLUSION: Our results demonstrate that computer algorithms can be used to automatically detect facial features that can discriminate FAS and control faces.

The relation of low-level prenatal lead exposure to behavioral indicators of attention in Inuit infants in Arctic Quebec.

The aim of this study was to investigate the association between prenatal exposure to lead (Pb) and several aspects of behavioral function during infancy through examiner ratings and behavioral coding of video recordings. The sample consisted of 169 11-month-old Inuit infants from Arctic Quebec. Umbilical cord and maternal blood samples were used to document prenatal exposure to Pb. Average blood Pb levels were 4.6 mug/dL and 5.9 mug/dL in cord and maternal samples respectively. The Behavior Rating Scales (BRS) from the Bayley Scales of Infant Development (BSID-II) were used to assess behavior. Attention was assessed through the BRS and behavioral coding of video recordings taken during the administration of the BSID-II. Whereas the examiner ratings of behaviors detected very few associations with prenatal Pb exposure, cord blood Pb concentrations were significantly related to the direct observational measures of infant attention, after adjustment for confounding variables. These data provide evidence that increasing the specificity and the precision of the behavioral assessment has considerable potential for improving our ability to detect low-to-moderate associations between neurotoxicants, such Pb and infant behavior.

Prenatal exposure of the northern Québec Inuit infants to environmental contaminants.

The Inuit population residing in Nunavik (northern Québec, Canada) relies on species from the marine food web for subsistence and is therefore exposed to high doses of environmental contaminants such as polychlorinated biphenyls and methylmercury and to a lesser extent lead. In view of the neurotoxic properties of these substances following developmental exposure, we initiated a study on infant development in this remote coastal population. Here we report the magnitude of prenatal exposure to these contaminants and to selective nutrients in Inuit mothers and their newborns who were recruited on the Hudson Bay coast. We conducted interviews during the women's pregnancies and at 1 and 11 months postpartum and collected biological samples for mercury, lead, polychlorinated biphenyls (PCBs), and chlorinated pesticides analyses as well as selenium and N-3 polyunsaturated fatty acids (n3-PUFA). Cord blood, maternal blood, and maternal hair mercury concentrations averaged 18.5 microg/L, 10.4 microg/L, and 3.7 microg/g, respectively, and are similar to those found in the Faroe Islands but lower than those documented in the Seychelles Islands and New Zealand cohorts. Concentrations of PCB congener 153 averaged 86.9, 105.3, and 131.6 microg/kg (lipids) in cord plasma, maternal plasma, and maternal milk, respectively; prenatal exposure to PCBs in the Nunavik cohort is similar to that reported in the Dutch but much lower than those in other Arctic cohorts. Levels of n3-PUFA in plasma phospholipids and selenium in blood are relatively high. The relatively low correlations observed between organochlorine and methylmercury concentrations may make it easier to identify the specific developmental deficits attributable to each toxicant. Similarly, the weak correlations noted between environmental contaminants and nutrients will facilitate the documentation of possible protective effects afforded by either n3-PUFA or selenium against neurotoxic contaminants.

Determinants of polychlorinated biphenyls and methylmercury exposure in inuit women of childbearing age.

The objectives of this study were to to identify maternal characteristics associated with traditional food consumption and to examine food items associated with polychlorinated biphenyls (PCBs) and mercury body burden in pregnant Inuit women from Northern Québec. We interviewed women from three communities at mid-pregnancy and at 1 and 11 months postpartum. We measured PCBs, Hg, and selenium in maternal blood; Hg was also measured in maternal hair. The women reported eating significant amounts of fish, beluga muktuk/fat, seal meat, and seal fat. Although consumption of fish and seal was associated with lower socioeconomic status, consumption of beluga whale was uniform across strata. Fish and seal meat consumption was associated with increased Hg concentrations in hair. Traditional food intake during pregnancy was unrelated to PCB body burden, which is more a function of lifetime consumption. This study corroborated previous findings relating marine mammal and fish consumption to increased Hg and selenium body burden. Despite widespread knowledge regarding the presence of these contaminants in traditional foods, a large proportion of Inuit women increased their consumption of these foods during pregnancy, primarily because of pregnancy-related changes in food preferences and the belief that these foods are beneficial during pregnancy.

The influence of maternal drinking and drug use on the quality of the home environment of school-aged children.

BACKGROUND: Although many studies have examined the development of children of male alcoholics, few studies have considered substance use by the female caregiver. This study evaluated the relationship between substance use by female caregivers and factors that affect the child-rearing environment. METHODS: A total of 480 inner-city African-American women were recruited during pregnancy for a longitudinal study of the effects of prenatal alcohol use and substance use by caregivers on the development of their children. All women were screened for alcohol consumption at their first prenatal visit to a large urban maternity hospital. Those who averaged seven or more drinks per week (0.5 oz absolute alcohol per day) at the time of conception were invited to participate in the study, as was a 5% random sample of lighter drinkers and abstainers. At the 7.5-year follow-up assessment, the quantity and frequency of alcohol consumption and drug use, as well as several measures of the child-rearing environment, were assessed for 231 of the caregivers. RESULTS: Current alcohol use was uncorrelated with standard demographic factors, such as socioeconomic status, but was related to poorer family functioning, lower quality of parental intellectual stimulation, and higher levels of domestic violence. There were independent effects of illicit drug use on family environment, domestic violence, and caregiver depression. History of drinking during pregnancy, however, was not related to the current child-rearing environment. Poorer parental functioning generally was found only among the caregivers who currently drank both heavily (six or more drinks/occasion) and frequently (three or more days/week). After controlling for lifetime alcohol problems, current drinking still predicted a less cohesive and organized family environment and higher levels of domestic violence. CONCLUSIONS: Current heavy, frequent drinking in this relatively homogenous, economically disadvantaged sample was unrelated to demographics and seemed to have an important negative impact on the quality of the child-rearing environment, whereas drinking during pregnancy was unrelated to the current child-rearing environment.

Neurobehavioral effects of prenatal alcohol exposure at 26 months.

Effects of prenatal alcohol exposure on the Bayley Scales of Infant Development were evaluated at 13 and 26 months and on three language measures at 26 months, in 92 economically disadvantaged, African American toddlers. After consideration of 17 potential confounders, a significant alcohol-related deficit in the Mental Development Index (MDI) was seen at 13 months as was a tendency for poorer Psychomotor Development Index (PDI) performance. The PDI deficit continued to be evident at 26 months. When the 26-month MDI was factor analyzed, four factors emerged: Linguistic Representation, Spatial Fine Motor, Other Fine Motor, and Relational Representation. As in a previous study of these children at 13 months of age, Spatial Fine Motor deficits were specifically associated with prenatal alcohol exposure. These findings appear consistent with reports relating prenatal alcohol exposure to poorer spatial visualization and spatial memory in adolescence. No effects of prenatal exposure were detected on language. Maternal postpartum drinking was associated with decreased language intelligibility.

Breastfeeding effects on intelligence quotient in 4- and 11-year-old children.

OBJECTIVE: A study of preterm children found an IQ advantage among those who were breastfed as infants after controlling for maternal social class and educational status. However, this advantage needs to be examined in light of other maternal characteristics, such as maternal IQ and parenting skills, which were not measured in that study and which have been found to be related to breastfeeding. METHODOLOGY: IQ was assessed in 323 children at 4 years of age on the McCarthy Scales of Children's Abilities and the Peabody Picture Vocabulary Test-Revised and in 280 children on the Wechsler Intelligence Test for Children-Revised at 11 years of age. RESULTS: Children who were breastfed in infancy had significantly higher scores on IQ tests at both ages, even after adjusting for social class and education, confirming the earlier findings and extending them to a predominantly full-term sample. However, the effect of breastfeeding was no longer significant after adjusting for maternal IQ assessed on the Peabody Picture Vocabulary Test-Revised and for parenting skills assessed on the Home Observation for Measurement of the Environment. Significant relations between breastfeeding and Woodcock Reading Achievement scores at 11 years were also reduced to nonsignificant levels after the inclusion of maternal IQ and the Home Observation for Measurement of the Environment. CONCLUSIONS: These findings suggest that the observed advantage of breastfeeding on IQ is related to genetic and socioenvironmental factors rather than to the nutritional benefits of breastfeeding on neurodevelopment. They should not be interpreted as detracting from the medical benefits associated with breastfeeding.

Assessment of long-chain polyunsaturated fatty acid nutritional supplementation on infant neurobehavioral development and visual acuity.

The aims of this paper are (i) to consider how best to examine effects of long-chain polyunsaturated fatty acid nutritional supplementation or deficiency on infant neurobehavioral development, after controlling for other factors that might influence outcome, including maternal demographic, intellectual, and personality characteristics, and (ii) to present new findings on the relation between visual acuity and processing speed and the effects of prenatal alcohol exposure and visual acuity on infant information processing. The following topics are also addressed: (i) breastfeeding and intelligence, (ii) criteria for the selection and control of potential confounding variables, and (iii) new infant information processing measures.

Drinking moderately and pregnancy. Effects on child development.

Children exposed to moderate levels of alcohol during pregnancy show growth deficits and intellectual and behavioral problems similar to, although less severe than, those found in children with fetal alcohol syndrome. Research has begun to examine the extent to which these problems affect the child's ability to function on a day-to-day basis at school and with peers. Findings indicate that "moderate" drinking has much more impact on child development when the mother consumes several drinks in a single day than when she drinks the same quantity in doses of one to two drinks per day over several days.

Effects of prenatal alcohol and cocaine exposure on infant cortisol levels.

Elevated corticosterone levels to stress have been found in adult rats exposed prenatally to alcohol, but little is known about the effects of prenatal alcohol exposure on the cortisol response in humans. To date, one study has found that crack/cocaine was related to depressed newborn cortisol levels following a heel prick. In the present study saliva samples were obtained before and after a blood draw from 83 inner-city African American 13-month-old infants exposed prenatally to alcohol, cocaine, and other illicit drugs. Post-blood draw cortisol levels did not differ from basal levels in many of the infants, confirming recent studies indicating adaptation of the adrenocortical response to this type of stress at this age. Maternal depression and emergence of teeth were positively related to cortisol levels. Alcohol exposure was related to elevated basal levels, cocaine to lower basal levels. As predicted from animal findings, heavy alcohol exposure was related to elevated poststress cortisol levels.

Specificity of neurobehavioral outcomes associated with prenatal alcohol exposure.

A current issue in alcohol research is whether a "neurobehavioral profile" can be identified for prenatal alcohol exposure, even when dysmorphic features are not present, or whether comparable neurobehavioral deficits are detected when damage is incurred by numerous neurotoxicants to which the fetus is exposed during a common developmental period. Failure to detect such differences may, in part, be an artifact of the global developmental tests used to assess outcome. Cognitive effects of prenatal exposure to three different teratogens [polychlorinated biphenyls (PCBs), alcohol, and cocaine] are examined to determine whether exposure to each substance results in a common or different pattern of impairment on the same set of newer, more narrow band infant tests. Comparison of findings from three independent cohorts indicate that PCB exposure was related to poorer recognition memory on the Fagan Test of Infant Intelligence (FTII) in Michigan infants exposed prenatally to PCB-contaminated fish, whereas prenatal alcohol exposure was unrelated to recognition memory but to slower processing speed on a new FTII measure and slower reaction time on Haith's Visual Expectancy Paradigm (VExP) in our Detroit alcohol-exposed infants. Preliminary findings from a new study of infants recently born to Taiwanese women accidentally contaminated with sizable amounts of PCBs indicate recognition memory deficits, confirming our Michigan findings, but no processing speed effects on the FTII. Recent findings from our Detroit cohort suggest that heavy prenatal cocaine exposure is related to poorer recognition memory on the FTII, but faster reaction times on the VExP, a pattern different from that seen for either PCBs or alcohol.

Relation of maternal age and pattern of pregnancy drinking to functionally significant cognitive deficit in infancy.

Prospective studies of the effects of prenatal alcohol exposure on development have focused primarily on the detection of subtle deficits. This study was designed to extend those findings by evaluating dose-response, functional significance, and pattern of drinking in greater detail. 480 African-American infants, recruited to overrepresent prenatal exposure at moderate-to-heavy levels, were assessed. For the five outcomes tested, nonparametric and hockey stick regression analyses both indicated essentially no relation between pregnancy drinking and developmental outcome below a median threshold of 0.5 oz absolute alcohol/day, with the impact of the exposure increasing gradually above threshold. Functional deficit was defined in terms of performance in the bottom 10th percentile of the distribution. For four of the five outcomes tested, there was no increased incidence of functionally significant deficit in infants born to moderate-to-heavy drinking mothers <30 years old, whereas those born to older drinking mothers were 2 to 5 times more likely to be functionally impaired. Among the infants exposed above threshold, functionally significant deficits were seen primarily in those whose mothers averaged at least 5 drinks/occasion on an average of at least once/week. By contrast, a history of alcohol abuse was not related to functional deficit. These data suggest that efforts to reduce the incidence of alcohol-related functional impairment should specifically target the older mother who engages in intermittent heavy drinking during pregnancy.