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Background: This study is the ninth cross-sectional community study of fetal alcohol spectrum disorders (FASD) conducted by the multidisciplinary Fetal Alcohol Syndrome Epidemiology Research team in the Western Cape Province of South Africa. It is the third comprehensive study of FASD in a rural, agricultural region of South Africa., Methods: Population-based, active case ascertainment methods were employed among a school-based cohort to assess child physical and neurobehavioral traits, and maternal risk factor interviews were conducted to identify all children with FASD to determine its prevalence., Results: Consent was obtained for 76.7% of 1158 children attending first grade in the region's public schools. Case-control results are presented for 95 with fetal alcohol syndrome (FAS), 64 with partial fetal alcohol syndrome (PFAS), 77 with alcohol-related neurodevelopmental disorder (ARND), 2 with alcohol-related birth defects (ARBD), and 213 randomly-selected controls. Four techniques estimating FASD prevalence from in-person examinations and testing yielded a range of total FASD prevalence of 206-366 per 1000. The final weighted, estimated prevalence of FAS was 104.5 per 1000, PFAS was 77.7 per 1000, ARND was 125.2 per 1000, and total FASD prevalence was 310 per 1000 (95% CI = 283.4-336.7). Expressed as a percentage, 31% had FASD. Although the rate of total FASD remained steady over 9 years, the proportion of children within the FASD group has changed significantly: FAS trended down and ARND trended up. A detailed evaluation is presented of the specific child physical and neurobehavioral traits integral to assessing the full continuum of FASD. The diagnosis of a child with FASD was significantly associated with maternal proximal risk factors such as: co-morbid prenatal use of alcohol and tobacco (OR = 19.1); maternal drinking of two (OR = 5.9), three (OR = 5.9), four (OR = 38.3), or more alcoholic drinks per drinking day; and drinking in the first trimester (OR = 8.4), first and second trimesters (OR = 17.7), or throughout pregnancy (OR = 18.6). Distal maternal risk factors included the following: slight or small physical status (height, weight, and head circumference), lower BMI, less formal education, late recognition of pregnancy, and higher gravidity, parity, and older age during the index pregnancy., Conclusion: The prevalence of FASD remained a significant problem in this region, but the severity of physical traits and anomalies within the continuum of FASD is trending downwards., (© 2022 Research Society on Alcoholism.)

Objective: To investigate gestational age and growth at birth as predictors of fetal alcohol spectrum disorders (FASD)., Methods: The sample analyzed here comprises 737 randomly selected children who were assessed for growth, dysmorphology, and neurobehavior at 7 years of age. Maternal interviews were conducted to ascertain prenatal alcohol exposure and other maternal risk factors. Birth data originated from clinic records and the data at 7 years of age originated from population-based, in-school studies. Binary linear regression assessed the relationship between preterm birth, small for gestational age (SGA), and their combination on the odds of a specific FASD diagnosis or any FASD., Results: Among children diagnosed with FASD at 7 years of age (n = 255), a review of birth records indicated that 18.4% were born preterm, 51.4% were SGA, and 5.9% were both preterm and SGA. When compared to non-FASD controls (n = 482), the birth percentages born preterm, SGA, and both preterm and SGA were respectively 12.0%, 27.7%, and 0.5%. Mothers of children with FASD reported more drinking during all trimesters, higher gravidity, lower educational attainment, and older age at pregnancy. After controlling for usual drinks per drinking day in the first trimester, number of trimesters of drinking, maternal education, tobacco use, and maternal age, the odds ratio of an FASD diagnosis by age 7 was significantly associated with SGA (OR = 2.16, 95% CI: 1.35 to 3.45). SGA was also significantly associated with each of the 3 most common specific diagnoses within the FASD continuum: fetal alcohol syndrome (FAS; OR = 3.1), partial FAS (OR = 2.1), and alcohol-related neurodevelopmental disorder (OR = 2.0)., Conclusion: SGA is a robust early indicator for FASD in this random sample of children assessed at 7 years of age., (© 2021 by the Research Society on Alcoholism.)

Background: This paper reports findings from the first longitudinal study on the evolution of the physical phenotypes of fetal alcohol syndrome (FAS) and partial FAS (PFAS) from early childhood through adolescence., Methods: The sample consisted of 155 children (78 males and 77 females) born to women recruited at an antenatal clinic serving a Cape Coloured (mixed ancestry) population in Cape Town, South Africa. Two expert FASD dysmorphologists, blind regarding prenatal alcohol exposure, independently evaluated each child's growth and dysmorphology at 4 clinics conducted over an 11-year period. Case conferences were held to reach consensus regarding which children had FAS or PFAS growth and physical features using the Revised Institute of Medicine (2005) guidelines., Results: The prevalence of the physical phenotype was stable across the 4 ages for about half of the children with FAS and about one-third of those with PFAS but more variable for the others. Test-retest reliability was substantial for the FAS phenotype, but poorer for PFAS. Two distinct patterns were seen: a "strong phenotype" that was consistently identified and a less consistent one in which dysmorphic features and/or anthropometric deficits fluctuated or diminished with age. The physical phenotype was most apparent during early childhood and least apparent during puberty, due to differences in timing of the growth spurt and the evolving adult face. Short palpebral features and small head circumference diminished with age, flat philtrum fluctuated, while thin vermilion and weight and height restriction were stable., Conclusions: Key facial features that characterize FASD in early childhood diminish or evolve in some individuals, making diagnostic examinations that rely on these characteristics most sensitive during early childhood and school age. Moreover, puberty poses classification problems due to variability in timing of the growth spurt. Given that several features and small head circumference diminished with age, many individuals would be misdiagnosed if only examined at a later age., (© 2020 by the Research Society on Alcoholism.)

Objective: To detail the characteristic traits of children with fetal alcohol spectrum disorders (FASDs) and maternal risk factors in a southeastern U.S. County., Methods: Independent samples were drawn from 2 different cohorts of first-grade students. All consented children (49.8%) were measured for height, weight, and head circumference, and those ≤ 25th centile entered the study along with a random sample drawn from all enrolled students. Study children were examined for physical growth, dysmorphology, and neurobehavior, and their mothers were interviewed., Results: Total dysmorphology scores discriminated well the physical traits of children across the FASD continuum: fetal alcohol syndrome (FAS) = 15.8, partial FAS (PFAS) = 10.8, alcohol-related neurobehavioral disorder (ARND) = 5.2, and typically developing controls = 4.4. Additionally, a neurobehavioral battery distinguished children with each FASD diagnosis from controls. Behavioral problems qualified more children for FASD diagnoses than cognitive traits. Significant proximal maternal risk variables were as follows: reports of prepregnancy drinking, drinking in any trimester, and comorbid use of other drugs in lifetime and during pregnancy, especially alcohol and marijuana (14.9% among mothers of children with FASD vs. 0.4% for controls). Distal maternal risks included reports of other health problems (e.g., depression), living unmarried with a partner during pregnancy, and a lower level of spirituality. Controlling for other drug use during pregnancy, having a child diagnosed with a FASD was 17.5 times greater for women who reported usual consumption of 3 drinks per drinking day prior to pregnancy than for nondrinking mothers (p < 0.001, 95% CI = 5.1 to 59.9). There was no significant difference in the prevalence of FASD by race, Hispanic ethnicity, or socioeconomic status. The prevalence of FASD was not lower than 17.3 per 1,000, and weighted estimated prevalence was 49.0 per 1,000 or 4.9%., Conclusion: This site had the second lowest rate in the CoFASP study, yet children with FASD are prevalent., (© 2020 by the Research Society on Alcoholism.)

Objective: To determine the characteristics of children with fetal alcohol spectrum disorders (FASD) and their mothers in a Midwestern city., Methods: Case-control samples were drawn from 2 separate first-grade cohorts (combined N = 4,047) in every city school using different methods. In Cohort Sample 1, all consented small children (≤25th centile on height, weight, and/or head circumference) entered the study along with a random sample from all enrolled students. Cohort Sample 2 was drawn totally at random. Child growth, dysmorphology, and neurobehavior were assessed using the Collaboration on FASD Prevalence (CoFASP) criteria, and mothers were interviewed., Results: For the samples combined, 891 children received dysmorphology examinations, and 692 were case-conferenced for final diagnosis. Forty-four children met criteria for FASD. Total dysmorphology scores differentiated diagnostic groups: fetal alcohol syndrome (FAS), 16.7; partial FAS, 11.8; alcohol-related neurodevelopmental disorder (ARND), 6.1; and typically developing controls, 4.2. Neurobehavioral tests distinguished children with FASD from controls, more for behavioral problems than cognitive delay. Children with ARND demonstrated the poorest neurobehavioral indicators. An adjusted regression model of usual prepregnancy drinking indicated that maternal reports of 3 drinks per drinking day (DDD) were significantly associated with a FASD diagnosis (p = 0.020, OR = 10.1, 95% CI = 1.44 to 70.54), as were 5 or more DDD (p < 0.001, OR = 26.47, 95% CI = 4.65 to 150.62). Other significant maternal risk factors included the following: self-reported drinking in any trimester; smoking and cocaine use during pregnancy; later pregnancy recognition and later and less prenatal care; lower maternal weight, body mass index (BMI), and head circumference; and unmarried status. There was no significant difference in FASD prevalence by race, Hispanic ethnicity, or socioeconomic status at this site, where the prevalence of FASD was 14.4 to 41.2 per 1,000 (1.4 to 4.1%)., Conclusion: This city displayed the lowest prevalence of FASD of the 4 CoFASP sites. Nevertheless, FASD were common, and affected children demonstrated a common, recognizable, and measurable array of traits., (© 2020 by the Research Society on Alcoholism.)

Objective: To document prevalence and traits of children with fetal alcohol spectrum disorders (FASD) and maternal risk factors in a Rocky Mountain city., Methods: Variations on active case ascertainment methods were used in 2 first-grade cohorts in all city schools. The consent rate was 59.2%. Children were assessed for physical growth, dysmorphology, and neurobehavior and their mothers interviewed., Results: Thirty-eight children were diagnosed with FASD and compared with 278 typically developing controls. Total dysmorphology scores summarized well the key physical indicators of FASD and defined specific diagnostic groups. On average, children with FASD performed significantly poorer than controls on intellectual, adaptive, learning, attention, and behavioral tasks. More mothers of children with FASD reported drinking prior to pregnancy and in the first and second trimesters, and had partners with drinking problems than mothers of controls; however, reports of comorbid alcohol use and 6 other drugs were similar for mothers of children with FASD and mothers of controls. Mothers of children with FASD were significantly younger at pregnancy, had lower average weight before pregnancy and less education, initiated prenatal clinic visits later, and reported more health problems (e.g., stomach ulcers and accidents). Children with FASD had significantly lower birth weight and more problems at birth, and were less likely to be living with biological mother and father. Controlling for other drug and tobacco use, a FASD diagnosis is 6.7 times (OR = 6.720, 95% CI = 1.6 to 28.0) more likely among children of women reporting prepregnancy drinking of 3 drinks per drinking day (DDD) and 7.6 times (OR = 7.590, 95% CI = 2.0 to 31.5) more likely at 5 DDD. Prevalence of FAS was 2.9-5.8 per 1,000 children, and total FASD was 34.9 to 82.5 per 1,000 children or 3.5 to 8.3% at this site., Conclusion: This site had the second highest prevalence of FASD of the 4 Collaboration on FASD Prevalence sites and clearly identifiable child and maternal risk traits., (© 2020 by the Research Society on Alcoholism.)

Background: We recently demonstrated the acceptability and feasibility of a randomized, double-blind choline supplementation intervention for heavy drinking women during pregnancy. In this study, we report our results relating to the efficacy of this intervention in mitigating adverse effects of prenatal alcohol exposure (PAE) on infant growth and cognitive function., Methods: Sixty-nine Cape Coloured (mixed ancestry) heavy drinkers in Cape Town, South Africa, recruited in mid-pregnancy, were randomly assigned to receive a daily oral dose of either 2 g of choline or placebo from time of enrollment until delivery. Each dose consisted of an individually wrapped packet of powder that, when mixed with water, produced a sweet tasting grape-flavored drink. The primary outcome, eyeblink conditioning (EBC), was assessed at 6.5 months. Somatic growth was measured at birth, 6.5, and 12 months, recognition memory and processing speed on the Fagan Test of Infant Intelligence, at 6.5 and 12 months., Results: Infants born to choline-treated mothers were more likely to meet criterion for conditioning on EBC than the placebo group. Moreover, within the choline arm, degree of maternal adherence to the supplementation protocol strongly predicted EBC performance. Both groups were small at birth, but choline-treated infants showed considerable catch-up growth in weight and head circumference at 6.5 and 12 months. At 12 months, the infants in the choline treatment arm had higher novelty preference scores, indicating better visual recognition memory., Conclusions: This exploratory study is the first to provide evidence that a high dose of choline administered early in pregnancy can mitigate adverse effects of heavy PAE on EBC, postnatal growth, and cognition in human infants. These findings are consistent with studies of alcohol-exposed animals that have demonstrated beneficial effects of choline supplementation on classical conditioning, learning, and memory., (Copyright © 2018 by the Research Society on Alcoholism.)

Background: Our objective is to help clinicians detect the facial effects of prenatal alcohol exposure by developing computer-based tools for screening facial form., Methods: All 415 individuals considered were evaluated by expert dysmorphologists and categorized as (i) healthy control (HC), (ii) fetal alcohol syndrome (FAS), or (iii) heavily prenatally alcohol exposed (HE) but not clinically diagnosable as FAS; 3D facial photographs were used to build models of facial form to support discrimination studies. Surface curvature-based delineations of facial form were introduced., Results: (i) Facial growth in FAS, HE, and control subgroups is similar in both cohorts. (ii) Cohort consistency of agreement between clinical diagnosis and HC-FAS facial form classification is lower for midline facial regions and higher for nonmidline regions. (iii) Specific HC-FAS differences within and between the cohorts include: for HC, a smoother philtrum in Cape Coloured individuals; for FAS, a smoother philtrum in Caucasians; for control-FAS philtrum difference, greater homogeneity in Caucasians; for control-FAS face difference, greater homogeneity in Cape Coloured individuals. (iv) Curvature changes in facial profile induced by prenatal alcohol exposure are more homogeneous and greater in Cape Coloureds than in Caucasians. (v) The Caucasian HE subset divides into clusters with control-like and FAS-like facial dysmorphism. The Cape Coloured HE subset is similarly divided for nonmidline facial regions but not clearly for midline structures. (vi) The Cape Coloured HE subset with control-like facial dysmorphism shows orbital hypertelorism., Conclusions: Facial curvature assists the recognition of the effects of prenatal alcohol exposure and helps explain why different facial regions result in inconsistent control-FAS discrimination rates in disparate ethnic groups. Heavy prenatal alcohol exposure can give rise to orbital hypertelorism, supporting a long-standing suggestion that prenatal alcohol exposure at a particular time causes increased separation of the brain hemispheres with a concomitant increase in orbital separation., (Copyright © 2017 by the Research Society on Alcoholism.)

Background: Magnetic resonance imaging (MRI) studies have consistently demonstrated disproportionately smaller corpus callosa in individuals with a history of prenatal alcohol exposure (PAE) but have not previously examined the feasibility of detecting this effect in infants. Tissue segmentation of the newborn brain is challenging because analysis techniques developed for the adult brain are not directly transferable, and segmentation for cerebral morphometry is difficult in neonates, due to the latter's incomplete myelination. This study is the first to use volumetric structural MRI to investigate PAE effects in newborns using manual tracing and to examine the cross-sectional area of the corpus callosum (CC)., Methods: Forty-three nonsedated infants born to 32 Cape Coloured heavy drinkers and 11 controls recruited prospectively during pregnancy were scanned using a custom-designed birdcage coil for infants, which increases signal-to-noise ratio almost 2-fold compared to the standard head coil. Alcohol use was ascertained prospectively during pregnancy, and fetal alcohol spectrum disorders diagnosis was conducted by expert dysmorphologists. Data were acquired using a multi-echo FLASH protocol adapted for newborns, and a knowledge-based procedure was used to hand-segment the neonatal brains., Results: CC was disproportionately smaller in alcohol-exposed neonates than controls after controlling for intracranial volume. By contrast, CC area was unrelated to infant sex, gestational age, age at scan, or maternal smoking, marijuana, or methamphetamine use during pregnancy., Conclusions: Given that midline craniofacial anomalies have been recognized as a hallmark of fetal alcohol syndrome in humans and animal models since this syndrome was first identified, the CC deficit identified here in newborns may support early identification of a range of midline structural impairments. Smaller CC during the newborn period may provide an early indicator of fetal alcohol-related cognitive deficits that have been linked to this critically important brain structure in childhood and adolescence., (Copyright © 2017 by the Research Society on Alcoholism.)

Background: The prevalence and characteristics of fetal alcohol spectrum disorders (FASD) were determined in this fourth study of first-grade children in a South African community., Methods: Active case ascertainment methods were employed among 747 first-grade pupils. The detailed characteristics of children within the continuum of FASD are contrasted with randomly selected, normal controls on (i) physical growth and dysmorphology; (ii) cognitive/behavioral characteristics; and (iii) maternal risk factors., Results: The rates of specific diagnoses within the FASD spectrum continue to be among the highest reported in any community in the world. The prevalence (per 1,000) is as follows: fetal alcohol syndrome (FAS)-59.3 to 91.0; partial fetal alcohol syndrome (PFAS)-45.3 to 69.6; and alcohol-related neurodevelopmental disorder (ARND)-30.5 to 46.8. The overall rate of FASD is therefore 135.1 to 207.5 per 1,000 (or 13.6 to 20.9%). Clinical profiles of the physical and cognitive/behavioral traits of children with a specific FASD diagnosis and controls are provided for understanding the full spectrum of FASD in a community. The spectral effect is evident in the characteristics of the diagnostic groups and summarized by the total (mean) dysmorphology scores of the children: FAS = 18.9; PFAS = 14.3; ARND = 12.2; and normal controls, alcohol exposed = 8.2 and unexposed = 7.1. Documented drinking during pregnancy is significantly correlated with verbal (r = -0.253) and nonverbal ability (r = -0.265), negative behaviors (r = 0.203), and total dysmorphology score (r = 0.431). Other measures of drinking during pregnancy are significantly associated with FASD, including binge drinking as low as 3 drinks per episode on 2 days of the week., Conclusions: High rates of specific diagnoses within FASD were well documented in this new cohort of children. FASD persists in this community. The data reflect an increased ability to provide accurate and discriminating diagnoses throughout the continuum of FASD., (Copyright © 2012 by the Research Society on Alcoholism.)

Background: The identification of individuals exposed prenatally to alcohol can be challenging, with only those having the characteristic pattern of facial features, central nervous system abnormality, and growth retardation receiving a clinical diagnosis of fetal alcohol syndrome (FAS)., Methods: Seventeen anthropometric measurements were obtained at 5 and 9 years from 125 Cape Town, South African children, studied since birth. The children were divided into 3 groups: FAS or partial FAS (PFAS), heavily exposed nonsyndromal (HE), and non-alcohol-exposed controls (C). Anthropometric measurements were evaluated for mean group differences. Logistic regression models were used to identify the subset of anthropometric measures that best predicted group membership. Anthropometric measurements were examined at the 2 ages in relation to prenatal alcohol exposure obtained prospectively from the mothers during pregnancy. Correlation of these facial measurements with key neurobehavioral outcomes including Wechsler Intelligence Scales for Children-IV IQ and eyeblink conditioning was used to assess their utility as indicators of alcohol-related central nervous system impairment., Results: Significant group differences were found for the majority of the anthropometric measures, with means of these measures smaller in the FAS/PFAS compared with HE or C. Upper facial widths, ear length, lower facial depth, and eye widths were consistent predictors distinguishing those exposed to alcohol from those who were not. Using longitudinal data, unique measures were identified that predicted facial anomalies at one age but not the other, suggesting the face changes as the individual matures. And 41% of the FAS/PFAS group met criteria for microtia at both ages. Three of the predictive anthropometric measures were negatively related to measures of prenatal alcohol consumption, and all were positively related to at least 1 neurobehavioral outcome., Conclusions: The analysis of longitudinal data identified a common set of predictors, as well as some that are unique at each age. Prenatal alcohol exposure appears to have its primary effect on brain growth, reflected by smaller forehead widths, and may suppress neural crest migration to the branchial arches, reflected by deficits in ear length and mandibular dimensions. These results may improve diagnostic resolution and enhance our understanding of the relation between the face and the neuropsychological deficits that occur., (Copyright © 2012 by the Research Society on Alcoholism.)

Background: Classical eyeblink conditioning (EBC) involves contingent temporal pairing of a conditioned stimulus (e.g., tone) with an unconditioned stimulus (e.g., air puff). Impairment of EBC has been demonstrated in studies of alcohol-exposed animals and in children exposed prenatally at heavy levels., Methods: Fetal alcohol syndrome (FAS) was diagnosed by expert dysmorphologists in a large sample of Cape Coloured, South African children. Delay EBC was examined in a new sample of 63 children at 11.3 years, and trace conditioning in 32 of the same children at 12.8 years. At each age, 2 sessions of 50 trials each were administered on the same day; 2 more sessions the next day, for children not meeting criterion for conditioning., Results: Six of 34 (17.6%) children born to heavy drinkers were diagnosed with FAS, 28 were heavily exposed nonsyndromal (HE), and 29 were nonexposed controls. Only 33.3% with FAS and 42.9% of HE met criterion for delay conditioning, compared with 79.3% of controls. The more difficult trace conditioning task was also highly sensitive to fetal alcohol exposure. Only 16.7% of the FAS and 21.4% of HE met criterion for trace conditioning, compared with 66.7% of controls. The magnitude of the effect of diagnostic group on trace conditioning was not greater than the effect on short delay conditioning, findings consistent with recent rat studies. Longer latency to onset and peak eyeblink CR in exposed children indicated poor timing and failure to blink in anticipation of the puff. Extended training resulted in some but not all of the children reaching criterion., Conclusions: These data showing alcohol-related delay and trace conditioning deficits extend our earlier findings of impaired EBC in 5-year-olds to school-age. Alcohol-related impairment in the cerebellar circuitry required for both forms of conditioning may be sufficient to account for the deficit in both tasks. Extended training was beneficial for some exposed children. EBC provides a well-characterized model system for assessment of degree of cerebellar-related learning and memory dysfunction in fetal alcohol exposed children., (Copyright © 2010 by the Research Society on Alcoholism.)

Background: Number processing deficits are frequently seen in children exposed to alcohol in utero., Methods: Functional magnetic resonance imaging was used to examine the neural correlates of number processing in 15 right-handed, 8- to 12-year-old children diagnosed with fetal alcohol syndrome (FAS) or partial FAS (PFAS) and 18 right-handed, age- and gender-matched controls from the Cape Coloured (mixed ancestry) community in Cape Town, South Africa, using Proximity Judgment and Exact Addition tasks., Results: Control children activated the expected fronto-parietal network during both tasks, including the anterior horizontal intraparietal sulcus (HIPS), left posterior HIPS, left precentral sulcus, and posterior medial frontal cortex. By contrast, on the Proximity Judgment task, the exposed children recruited additional parietal pathways involving the right and left angular gyrus and posterior cingulate/precuneus, which may entail verbally mediated recitation of numbers and/or subtraction to assess relative numerical distances. During Exact Addition, the exposed children exhibited more diffuse and widespread activations, including the cerebellar vermis and cortex, which have been found to be activated in adults engaged in particularly challenging number processing problems., Conclusions: The data suggest that, whereas control children rely primarily on the fronto-parietal network identified in previous studies to mediate number processing, children with FAS/PFAS recruit a broader range of brain regions to perform these relatively simple number processing tasks. Our results are consistent with structural neuroimaging findings indicating that the parietal lobe is relatively more affected by prenatal alcohol exposure and provide the first evidence for brain activation abnormalities during number processing in children with FAS/PFAS, effects that persist even after controlling statistically for group differences in total intracranial volume and IQ.

Background: Both executive function deficits and slower processing speed are characteristic of children with fetal alcohol exposure, but the temporal dynamics of neural activity underlying cognitive processing deficits in fetal alcohol spectrum disorder have rarely been studied. To this end, event-related potentials (ERPs) were used to examine the nature of alcohol-related effects on response inhibition by identifying differences in neural activation during task performance., Methods: We recorded ERPs during a Go/No-go response inhibition task in 2 groups of children in Cape Town, South Africa (M age = 11.7 years; range = 10 to 13)-one diagnosed with fetal alcohol syndrome (FAS) or partial FAS (FAS/PFAS; n = 7); the other, a control group whose mothers abstained or drank only minimally during pregnancy (n = 6). Children were instructed to press a "Go" response button to all letter stimuli presented except for the letter "X," the "No-go" stimulus, which occurred relatively infrequently., Results: Task performance accuracy and reaction time did not differ between groups, but differences emerged for 3 ERP components-P2, N2, and P3. The FAS/PFAS group showed a slower latency to peak P2, suggesting less efficient processing of visual information at a relatively early stage ( approximately 200 ms after stimulus onset). Moreover, controls showed a larger P2 amplitude to Go versus No-go, indicating an early discrimination between conditions that was not seen in the FAS/PFAS group. Consistent with previous literature on tasks related to cognitive control, the control group showed a well-defined, larger N2 to No-go versus Go, which was not evident in the FAS/PFAS group. Both groups showed the expected larger P3 amplitude to No-go versus Go, but this condition difference persisted in a late slow wave for the FAS/PFAS group, suggesting increased cognitive effort., Conclusions: The timing and amplitude differences in the ERP measures suggest that slower, less efficient processing characterizes the FAS/PFAS group during initial stimulus identification. Moreover, the exposed children showed less sharply defined components throughout the stimulus and response evaluation processes involved in successful response inhibition. Although both groups were able to inhibit their responses equally well, the level of neural activation in the children with FAS/PFAS was greater, suggesting more cognitive effort. The specific deficits in response inhibition processing at discrete stages of neural activation may have implications for understanding the nature of alcohol-related deficits in other cognitive domains as well.

Background: Eyeblink conditioning (EBC) is a Pavlovian paradigm that involves contingent temporal pairing of a conditioned stimulus (e.g., tone) with an unconditioned stimulus (e.g., air puff). Animal studies have shown that binge consumption of alcohol during pregnancy impairs EBC and that this impairment is likely mediated by a loss of neurons in the inferior olive and the cerebellar cortex and deep nuclei, as well as by a reduction in neural plasticity in the cerebellar deep nuclei., Methods: Short delay EBC was examined in 98 5-year-old children born to women from the Coloured (mixed ancestry) community in Cape Town, South Africa, who were recruited prenatally and are participating in the first prospective longitudinal study of children with fetal alcohol syndrome (FAS). FAS status was assessed at 5 years by expert dysmorphologists. Two sessions of 50 trials each were administered to the children; a third session was administered the following day to those children who did not meet criterion of 40% conditioned responses in session 2., Results: Not a single child with FAS met criterion for conditioning as contrasted with 75.0% of the controls. Whereas 86.7% of the controls who were conditioned met criterion by the end of Session 2, a large proportion of the relatively few alcohol-exposed nonsyndromal children who conditioned did not do so until Session 3. These alcohol effects on EBC persisted after controlling for IQ. Three of 4 microcephalic children who were not exposed to alcohol were successfully conditioned., Conclusions: This is the first prospective study to demonstrate impaired EBC in children diagnosed with FAS. Successful EBC in a microcephalic group supports the inference that the EBC deficit is specific to prenatal alcohol exposure and a potential biomarker for diagnosis of exposed children lacking the distinctive FAS dysmorphology. Delay EBC has a high sensitivity for identifying individuals with a diagnosis of probable FAS.

Background: Effective management of fetal alcohol spectrum disorders (FASD) is dependent on the timely and reliable diagnosis of affected individuals. There are significant diagnostic difficulties because of the reduced prominence of facial features as children age to adulthood as well as potential population or ethnic differences in the most characteristic alcohol-related facial features., Methods: A total of 276 subjects were recruited from 4 sites (Cape Town, South Africa; Helsinki, Finland; Buffalo, New York; and San Diego, California) and completed a detailed dysmorphology evaluation to classify subjects as either fetal alcohol syndrome (FAS; 43%) or control (57%). Computerized anthropometry was employed to identify facial features that could distinguish FAS patients from controls across a wide age range and across ethnically disparate study populations., Results: Subjects were placed into 1 of 4 populations based on their ancestry (Cape Coloured, Finnish Caucasian, African American, or North American Caucasian). Analyses performed in each of the 4 study populations were able to identify a unique set of variables which provided excellent discrimination between the 2 groups (FAS, control). In each study group, at least one ocular-related measurement, shortened palpebral fissure, reduced outer canthal width, or reduced inner canthal width, was included in the final classification model., Conclusions: We found measurements that reflected reduced size of the eye orbit to be a consistent feature discriminating FAS and controls across each study population. However, each population had a unique, though often overlapping, set of variables which discriminated the 2 groups, suggesting important ethnic differences in the presentation of FAS. It is possible that these differences were accentuated by the wide age distribution of the study subjects.