Claire D. Coles

Effects of prenatal alcohol exposure at school age. I. Physical and cognitive development

Alcohol is a potent teratogen associated with dysmorphology, growth retardation, and neurological damage in children with the full fetal alcohol syndrome (FAS); alcohol is also associated with growth retardation and behavioral alterations in neonates prenatally exposed to various dosages. Questions remain about the long-term consequences of prenatal alcohol exposure. This study reports on the follow-up of a subsample of 68 children, the majority of whom were low income and black (mean age: 5 years, 10 months) who were first evaluated as neonates. Physical and cognitive outcomes of 25 children of women who drank throughout pregnancy [absolute alcohol (AA)/week: mean = 11.80 oz), even after receiving an educational intervention to stop drinking, were compared with outcomes of children in two contrast groups: a) women (n = 22) who stopped drinking (AA/week: mean = 11.46 oz) in the second trimester after an educational intervention but resumed postpartum; and b) women who did not drink during pregnancy and who drank little postnatally (n = 21). Children were compared for alcohol-related birth defects (ARBDs), growth (height, weight, and head circumference), and cognitive, academic, and adaptive measures. Neonatal and current physical measures were correlated to determine predictability of neonatal status. When the effects of age and gender were controlled, children in the continued-to-drink group showed significantly more ARBDs and had smaller head circumferences than those in the other two groups. When current drinking reported by caretakers was controlled, the children who were exposed throughout pregnancy also showed significant and consistent deficits in several areas of intellectual functioning including sequential processing (short-term memory and encoding) and overall mental processing. Alcohol-exposed children displayed significant deficits in preacademic skills when compared with children of nondrinkers, with both alcohol groups deficient in premath and reading skills. There were no differences in adaptive behavior at follow-up. These data suggest that alcohol exposure throughout pregnancy is correlated with persistent physical differences as well as identifiable deficits in sequential memory processes and specific academic skills. However, even when alcohol use is limited to the first part of pregnancy, significant deficits in academic skills and growth parameters are measurable.

Effects of cocaine and alcohol use in pregnancy on neonatal growth and neurobehavioral status.

Effects on fetal growth and neonatal behavior of cocaine and alcohol use in pregnancy were investigated in infants born to women in a low-income, predominantly black population. Despite the increased use of cocaine by pregnant women and the accompanying public concern, behavioral studies of exposed neonates are limited in number and scope. In most studies, confounding factors (e.g., polydrug abuse, prematurity, infant health status) have not been controlled so the actual effects of cocaine and other drug exposure are not clear. Accordingly, this study investigated effects of prenatal drug exposure although controlling experimentally for other factors known to be associated with poor outcomes in infants: prematurity, other illicit drug use, associated diseases (e.g., sexually transmitted diseases [STDs]), and duration of drug use. In addition, other factors statistically controlled were: experimenter effects, timing of assessment, and effects of duration, amount, and frequency of cocaine, alcohol, marijuana, and nicotine exposure. One hundred and seven full-term infants were assessed at 2, 14, and 28 days using the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) by testers blind to infant status. Growth factors (i.e., birthweight, length, head circumference) were also assessed.

Effects of prenatal alcohol exposure at school age. II. Attention and behavior

Alcohol, a potent teratogen, has been suggested as an etiologic agent in attention deficit disorder with hyperactivity (ADHD), which is often diagnosed in children with fetal alcohol syndrome (FAS) and in children of alcoholics. We studied attentional and behavioral factors associated with diagnosis of this disorder in children selected from a predominantly low-income, black population who were tested as part of a longitudinal follow-up of children with prenatal alcohol exposure. Sixty-eight children with a mean age of 5 years 10 months, born to three groups of mothers, were assessed. These groups consisted of: a) women who reported not drinking during pregnancy (n = 21), b) women who reported drinking throughout pregnancy (n = 25), and c) women who reported drinking an equivalent amount but who stopped drinking after educational intervention during the second trimester (n = 22). Dimensions assessed included factors related to attention on a computerized task, impulsivity, and the presence of psychiatrically significant internalizing and externalizing behaviors. In addition, free play and mother-child interactions were video-taped, and evidence of overactive and noncompliant behaviors were noted. Hyperactivity and impulsive behavior were not evident. Results indicated that children exposed throughout pregnancy showed deficits in the ability to sustain attention and were more often described by teachers, although not by their mothers, as showing attentional and behavioral problems. Problems in both internalizing and externalizing behaviors also were noted by teachers. However, when current drinking was controlled, only externalizing behaviors remained different by group.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of Corpus Callosum Anisotropy in Young Adults With Fetal Alcohol Syndrome According to Diffusion Tensor Imaging

BACKGROUND Fetal alcohol syndrome (FAS) and associated disorders resulting from maternal alcohol use during gestation are among the most common developmental disorders. However, they are rarely diagnosed and not fully understood in terms of their behavioral and neurocognitive phenotype. Prenatal exposure leads to alterations in facial morphology, growth, and neurocognition. The nature and extent of teratogenic effects on the brain and the relationship between such effects and observed behaviors remain in debate because there are no established markers for the neurological effects of exposure. In this study, we examined the impact of prenatal alcohol exposure on white-matter integrity in the corpus callosum by using diffusion tensor imaging (DTI) and herein describe the relationship between such effects and observed physical and behavioral outcomes. METHODS DTI was used to evaluate diffusion anisotropy in the genu and splenium of corpus callosum in 16 low-income, primarily African-American volunteers. Volunteers were recruited from a cohort of young adults who had received neuropsychological evaluations during adolescence. Nine had been prenatally exposed to alcohol and had characteristics of FAS, and seven were nonexposed controls. RESULTS Significant difference in the means for diffusion fractional anisotropy (t = 2.26, df = 9, p <0.002) and apparent diffusion coefficient (t = 2.14, df = 14, p < 0.008) were observed in the corpus callosum of alcohol-exposed youth compared with nonexposed youth. No significant differences were found in intracranial volume between these groups. CONCLUSIONS Our results illustrate that DTI can be used in evaluating the integrity of corpus callosum in alcohol-exposed individuals. If future studies support these findings, diffusion anisotropy, represented by fractional anisotropy, has the potential to be used as a clinical marker in the diagnosis of FAS.

Further Development of a Neurobehavioral Profile of Fetal Alcohol Spectrum Disorders

BACKGROUND Heavy prenatal alcohol exposure (AE) results in a broad array of neurobehavioral deficits. Recent research has focused on identification of a neurobehavioral profile or profiles that will improve the identification of children affected by AE. This study aimed to build on our preliminary neurobehavioral profile to improve classification accuracy and test the specificity of the resulting profile in an alternate clinical group. METHODS A standardized neuropsychological test battery was administered to 3 groups of children: subjects with AE (n = 209), typically developing controls (CON, n = 185), and subjects with attention-deficit/hyperactivity disorder (ADHD, n = 74). We assessed a large sample from 6 sites in the United States and South Africa, using standardized methodology. Data were analyzed using 3 latent profile analyses including (i) subjects with fetal alcohol syndrome (FAS) and controls, (ii) subjects with AE without FAS and controls, and (iii) subjects with AE (with or without FAS) and subjects with ADHD. RESULTS Classification accuracy was moderate but significant across the 3 analyses. In analysis 1, overall classification accuracy was 76.1% (77.2% FAS, 75.7% CON). In the second analysis, overall classification accuracy was 71.5% (70.1% AE/non-FAS, 72.4% CON). In the third analysis, overall classification accuracy was 73.9% (59.8% AE, 75.7% ADHD). Subjects that were misclassified were examined for systematic differences from those that were correctly classified. CONCLUSIONS The results of this study indicate that the neuropsychological effects of AE are clinically meaningful and can be used to accurately distinguish alcohol-affected children from both typically developing children and children with ADHD. Further, in combination with other recent studies, these data suggest that approximately 70% of children with heavy prenatal alcohol exposure are neurobehaviorally affected, while the remaining 30% are spared these often-devastating consequences, at least those in the domains under study. Refining the neurobehavioral profile will allow improved identification and treatment development for children affected by prenatal alcohol exposure.

Neurobehavioral consequences of prenatal alcohol exposure: an international perspective.

This article represents the proceedings of a symposium at the 2002 Research Society on Alcoholism/International Society for Biomedical Research on Alcoholism meeting in San Francisco, CA. The organizers were Edward P. Riley and Sarah N. Mattson, and the chairperson was Edward P. Riley. The presentations were (1) Neurobehavioral deficits in alcohol-exposed South African infants: preliminary findings, by Sandra W. Jacobson, Christopher D. Molteno, Denis Viljoen, and Joseph L. Jacobson; (2) A pilot study of classroom intervention for learners with fetal alcohol syndrome in South Africa, by Colleen Adnams, M. W. Rossouw, M. D. Perold, P. W. Kodituwakku, and W. Kalberg; (3) Differential effects of prenatal alcohol exposure on fluid versus crystallized intelligence, by P. W. Kodituwakku, W. Kalberg, L. Robinson, and P. A. May; (4) Neurobehavioral outcomes of prenatal alcohol exposure: early identification of alcohol effects, by Claire D. Coles; (5) Fetal alcohol syndrome in Moscow, Russia: neuropsychology test performance, by Sarah N. Mattson, E. P. Riley, A. Matveeva, and G. Marintcheva; and (6) Long-term follow-up of Finnish children exposed to alcohol in utero in various durations, by Marit I. Korkman and I. Autti-Rämö. The discussant was Ting-Kai Li.

Updated clinical guidelines for diagnosing fetal alcohol spectrum disorders

The adverse effects of prenatal alcohol exposure constitute a continuum of disabilities (fetal alcohol spectrum disorders [FASD]). In 1996, the Institute of Medicine established diagnostic categories delineating the spectrum but not specifying clinical criteria by which diagnoses could be assigned. In 2005, the authors published practical guidelines operationalizing the Institute of Medicine categories, allowing for standardization of FASD diagnoses in clinical settings. The purpose of the current report is to present updated diagnostic guidelines based on a thorough review of the literature and the authors’ combined expertise based on the evaluation of >10 000 children for potential FASD in clinical settings and in epidemiologic studies in conjunction with National Institute on Alcohol Abuse and Alcoholism–funded studies, the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, and the Collaboration on FASD Prevalence. The guidelines were formulated through conference calls and meetings held at National Institute on Alcohol Abuse and Alcoholism offices in Rockville, MD. Specific areas addressed include the following: precise definition of documented prenatal alcohol exposure; neurobehavioral criteria for diagnosis of fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder; revised diagnostic criteria for alcohol-related birth defects; an updated comprehensive research dysmorphology scoring system; and a new lip/philtrum guide for the white population, incorporating a 45-degree view. The guidelines reflect consensus among a large and experienced cadre of FASD investigators in the fields of dysmorphology, epidemiology, neurology, psychology, developmental/behavioral pediatrics, and educational diagnostics. Their improved clarity and specificity will guide clinicians in accurate diagnosis of infants and children prenatally exposed to alcohol.

Maternal drug use during pregnancy: Are preterm and full-term infants affected differently?

This study examined whether preterm infants are more vulnerable to the effects of prenatal drug exposure than are full-term infants. The sample of 235 low-income African American mothers and their infants included 119 cocaine-polydrug users, 19 alcohol-only users, and 97 nonusers; 148 infants were full term and 87 were preterm. Direct effects of exposure on birth weight, birth length, ponderal index, and irritability were moderated by length of gestation: Fetal growth deficits were more extreme in later-born infants, whereas increases in irritability were more extreme in earlier born infants. Effects of exposure on cardiorespiratory reactivity to a neonatal exam were not moderated by length of gestation. In general, effects of exposure occurred for both cocaine-polydrug and alcohol only users and so could not be unambiguously attributed to either of these drugs alone.

Voxelwise and skeleton‐based region of interest analysis of fetal alcohol syndrome and fetal alcohol spectrum disorders in young adults

Though fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders are among the most common developmental disorders, their understanding is incomplete. Diffusion tensor imaging (DTI), which is sensitive to microstructural organization in white matter, may provide a relevant measure in this population demonstrating incompletely characterized white matter pathology. In this study, tract‐based spatial statistics (TBSS) routine and a skeleton‐based region of interest analyses were employed to detect differences in DTI‐derived metrics between young adults who were alcohol exposed and an unexposed control group. Participants include 28 with dysmorphic features associated with FAS, 29 who were prenatally exposed but do not show physical effects, and 25 with the same low socioeconomic status but unexposed. The TBSS analysis revealed a statistically significant decrease in fractional anisotropy at the isthmus of the corpus callosum and its connected callosal fibers in dysmorphic individuals relative to controls (clusterwise PFWE < 0.05). This finding was consistent with that of the follow‐up skeleton‐based region of interest analysis (F(2,79) = 3.256, p = 0.044). In addition, the patterns in axial and radial diffusivity changes suggest that demyelination may be associated with the degraded white matter integrity observed in the dysmorphic group. Hum Brain Mapp, 2009.

Collaborative initiative on fetal alcohol spectrum disorders: methodology of clinical projects

The Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD) was created in 2003 to further understanding of fetal alcohol spectrum disorders. Clinical and basic science projects collect data across multiple sites using standardized methodology. This article describes the methodology being used by the clinical projects that pertain to assessment of children and adolescents. Domains being addressed are dysmorphology, neurobehavior, 3-D facial imaging, and brain imaging.