A Fetal Alcohol Syndrome Screening Tool

The purpose of this study was to derive a multivariate, quantitative case definition of the fetal alcohol syndrome (FAS) facial phenotype from a dysmorphologist-derived gold standard and use it to develop an effective screening tool for identification of children at risk for FAS. The facial and physical features of a racially mixed group of children (0.2–10.0 years of age), evaluated by a single dysmorphologist in the University of Washington FAS Clinic, were used to determine which feature or set of features best differentiated between children with and without a diagnosis of FAS. The study population was divided into two groups balanced on gender, age at examination, race, diagnosis, and date of examination. Group 1 was used to identify the most differentiating feature(s), and group 2 was used to validate the differentiating capability of the feature(s). Group 1 included 97 children (20 with FAS and 77 without FAS). Group 2 included 97 children (19 with FAS and 78 without FAS). Discriminant analysis identified smooth philtrum, thin upper lip, and short palpebral fissures as the cluster of features that best differentiated children with and without FAS based on the discriminant function [D = 1.7953086 + 0.8116083 (thin upper lip) + 2.6411562 (smooth philtrum) - 3.4073780 (% predicted right palpebral fissure length)]. Patients with a D-score ± 1.5 were classified as at-risk for FAS (screen positive). Using this cut-off value for the D-score, children in group 1 were classified with 100% sensitivity (20 of 20 true positives) and 90.0% specificity (70 of 77 true negatives). The children in group 2 were classified with 100% sensitivity (19 of 19 true positives) and 87.3% specificity (68 of 78 true negatives). Across all 194 patients, sensitivity was 100% [95% confidence interval (97–100)] and specificity was 89% [95% confidence interval (85 to 93)]. Seventy-one percent (n= 12) of the 17 false-positives had a true classification of possible fetal alcohol effects. Sensitivity and specificity were unaffected by race, gender, and age through 10 years. This screening tool is effective at differentiating children with and without FAS as diagnosed by a single dysmorphologist (S.K.C.) at the University of Washington FAS Clinic. Assessment of diagnostic interrater agreement between trained dysmorphologists and testing in other clinic populations will be needed to assess the tool's external validity.     

Fetal Alcohol Effects in Alcoholic Veteran Patients

Fetal alcohol syndrome is often associated with severe physical and neuropsychiatric maldevelopment. On the other hand, some offspring of women who drank during pregnancy appear to be affected in minimal ways and function relatively well within society. We questioned whether this effect of prenatal alcohol in the adult is generally minimal. To bear on this, we determined whether we could distinguish alcohol-exposed from nonexposed individuals in a population of male veterans, selected because of both their accepted level of function within society (e.g., honorable discharge from the military) and their admission to an alcohol treatment unit (thus, a greater likelihood of parental alcoholism, because of its familial aggregation). Consecutively admitted alcoholics (cases; n= 77) with likely maternal alcohol ingestion during their pregnancy or the first 10 years of life were matched with alcoholics with no maternal alcohol exposure during these periods (controls; n= 161). Each subject completed questionnaires regarding personal birthweight, alcohol, drug, educational and work histories, and family (including parental) alcohol and drug histories. We measured height, weight, and head circumference; checked for facial and hand anomalies; and took a frontal facial photograph, from which measurements of features were made. Data were analyzed by univariate statistics and stepwise logistic regression. No case had bona fide fetal alcohol syndrome. With univariate statistical analyses, the cases differed from the controls in 10 variables, including duration of drinking, width of alae nasae, being hyperactive or having a short attention span, and being small at birth. By stepwise logistic regression, the variables marital status, small size at birth, duration of drinking, and the presence of a smooth philtrum were marginally (the first two) or definitely (the last two) significant predictors of case status. Analysis of only the 37 cases in whom maternal prenatal drinking was the most likely yielded a marginal association for small size at birth (odds ratio = 3.1, p= 0.08) and a significant association for the presence of a smooth philtrum (odds ratio = 11.9, p= 0.005). Predictability was poor in all regression models. Based on the presence of this single physical finding (smooth philtrum), we estimate that the prevalence of manifestations of fetal alcohol exposure (fetal alcohol effects) is 6 to 13% in adult male veteran children (not necessarily nonveteran offspring) of women who drank alcohol during pregnancy. Thus, in our study of adult veterans, most individuals who were born to women who drank during pregnancy could not be differentiated from normal individuals, and those who were affected were distinguished by a single, nonspecific physical finding.     

Alcohol consumption during pregnancy in nonindigenous west Australian women

BACKGROUND: High alcohol intake in pregnancy has been linked to abnormal fetal development. There are limited published data in Australia on standard drinks of alcohol consumed on a typical occasion during the periconceptional period or pregnancy. METHODS: During 1995 to 1997, a 10% random sample of all nonindigenous women giving birth in Western Australia was surveyed 12 weeks after delivery (N=4,839). Women were asked questions about alcohol consumption in each of the 4 time periods: the 3 months before pregnancy and each trimester of pregnancy. Questions were framed to measure volume, frequency, and type of alcoholic beverage. RESULTS: 46.7% of the women had not planned their pregnancy. Most women (79.8%) reported drinking alcohol in the 3 months before pregnancy, with 58.7% drinking alcohol in at least 1 trimester of pregnancy. The proportion of women consuming 1 to 2 drinks on a typical occasion did not change much during pregnancy, but the number of occasions declined. Although the proportion of women consuming more than 2 standard drinks on a typical occasion declined after the first trimester, 19.0% of women consumed this amount in at least 1 trimester of pregnancy and 4.3% of women consumed 5 or more standard drinks on a typical occasion in at least 1 trimester of pregnancy. In the first trimester of pregnancy, 14.8% of women drank outside the current Australian guideline for alcohol consumption in pregnancy, decreasing to 10% in the second and third trimesters. CONCLUSIONS: Women generally reduced their average alcohol consumption and the number of standard drinks on a typical occasion as their pregnancy progressed, although 10 to 14% were drinking outside current guidelines for pregnancy. It is important that all women of child-bearing age are aware, well before they consider pregnancy, of the risks of drinking alcohol during pregnancy so they can make informed decisions about their alcohol consumption in pregnancy.     

Prenatal alcohol exposure predicts continued deficits in offspring size at 14 years of age

BACKGROUND: Growth deficits are among the cardinal features for the diagnosis of fetal alcohol syndrome. Growth deficits have also been noted among those who were exposed to alcohol prenatally but who do not have fetal alcohol syndrome. Few studies have observed subjects past early and middle childhood, however, to evaluate the longer-term effects of prenatal alcohol exposure on growth in adolescence. This is a report of the effects of alcohol exposure during gestation on the size of the offspring at 14 years of age. METHODS: Women were recruited in their fourth prenatal month. These women were interviewed in the fourth and seventh months of pregnancy and at delivery. The women and their children were seen when the offspring were 14 years of age. RESULTS: Growth deficits associated with prenatal alcohol exposure were identified among the offspring at 14 years of age. Weight, height, head circumference, and skinfold thickness continued to be significantly affected by prenatal alcohol exposure after controlling for other significant predictors of size. These effects exhibited a dose-response pattern, and significant effects were found at levels below one drink per day. For example, first trimester alcohol exposure predicted weights of 152 lbs for the offspring of abstainers, 149 lbs for the offspring of light drinkers (>0 and <0.2 drinks per day), 143 lbs for the offspring of moderate drinkers (>0.2 and <0.89 drinks per day), and 136 lbs for the offspring of heavy drinkers (>0.89 drinks per day). CONCLUSIONS: Prenatal alcohol exposure continues to affect size at age 14 years in this cohort of children followed since their fourth month of gestation.     

Maternal Drinking During Pregnancy: Attention and Short-Term Memory in 14-Year-Old Offspring—A Longitudinal Prospective Study

A large and compelling experimental literature has documented the adverse impact of prenatal alcohol exposure on the developing brain of the offspring. This is the first report of adolescent attention/ memory performance and its relationship with prenatal alcohol exposure in a population-based, longitudinal, prospective study ( n = 462) involving substantial covariate control and "blind" examiners. Prenatal alcohol exposure was significantly related to attention/memory deficits in a dose-dependent fashion. A latent variable reflecting 13 measures of maternal drinking was correlated 0.26 with a latent variable representing 52 scores from 6 tests measuring various components of attention and short-term memory performance. The number of drinks/occasion was the strongest alcohol predictor. Fluctuating attentional states, problems with response inhibition, and spatial learning showed the strongest association with prenatal alcohol exposure. A latent variable reflecting the pattern of attention/memory deficits observed at 14 years correlated 0.67 with a composite pattern of deficits previously detected on neurobehavioral tests administered during the first 7 years of life. The 14-year attention/memory deficits observed in the present study appear to be the adolescent sequelae of deficits observed earlier in development. As is usual in such studies, not all exposed offspring showed deficits.     

An Event‐Related Potential Study of Response Inhibition in ADHD With and Without Prenatal Alcohol Exposure

Background: The attention and cognitive problems seen in individuals with a history of prenatal alcohol exposure often resemble those associated with attention deficit hyperactivity disorder (ADHD), but few studies have directly assessed the unique influence of each on neurobehavioral outcomes. Methods: We recorded event‐related potentials (ERPs) during a Go/No‐go response inhibition task in young adults with prospectively obtained histories of prenatal alcohol exposure and childhood ADHD. Results: Regardless of prenatal alcohol exposure, participants with childhood ADHD were less accurate at inhibiting responses. However, only the ADHD group without prenatal alcohol exposure showed a markedly diminished P3 difference between No‐go and Go, which may reflect a more effortful strategy related to inhibitory control at the neural processing level. Conclusion: This finding supports a growing body of evidence suggesting that the manifestation of idiopathic ADHD symptoms may stem from a neurophysiologic process that is different from the ADHD symptomatology associated with prenatal alcohol exposure. Individuals who have been prenatally exposed to alcohol and present with ADHD symptomatology may represent a unique endophenotype of the disorder, which may require different treatment approaches from those found to be effective with idiopathic ADHD.     

Verbal and Nonverbal Memory in Adults Prenatally Exposed to Alcohol

Background: Neurocognitive effects of prenatal alcohol exposure in adulthood are not well documented. Questions persist regarding the extent to which there are specific, measurable effects beyond those associated with global ability deficits, whether individuals without the full fetal alcohol syndrome (FAS) demonstrate alcohol‐related cognitive impairments, and whether observed memory effects are specific to a particular modality, i.e., verbal vs. visual/spatial domains. Methods: In this study, verbal and nonverbal selective reminding paradigms were used to assess memory function in 234 young adults (M age: 22.78, SD: 1.79). Alcohol exposure was quantified prenatally. Alcohol groups included: Individuals with physical effects of alcohol exposure (Dysmorphic group, n = 47); Exposed individuals without such effects (n = 74). Contrast groups included: Controls (n = 59) matched for ethnicity, socioeconomic status, and hospital of birth; Special Education contrast group (n = 54) included to control for disability status. Memory outcomes entailed total recall, delayed recall, and measures of encoding and retrieval, and learning over trials as indexed by slope. Results: Results indicated that Dysmorphic individuals were significantly less efficient in memory performance than Controls on all of the outcomes measured, but they did not differ from those in the Special Education contrast group. The nondysmorphic, alcohol‐exposed group was intermediate in their performance, suggesting a continuum of effects of prenatal exposure. Evaluation of the encoding and retrieval aspects of memory performance indicated that learning rather than forgetting accounted for the deficits associated with prenatal alcohol exposure. Finally, no interaction was found between modality of presentation (verbal and nonverbal) and effects of alcohol exposure on memory performance. Conclusion: These findings indicate that prenatal alcohol exposure is associated with persistent and specific effects on memory performance, and these problems result from less efficient encoding of information across both verbal and nonverbal modalities. Education and training efforts with this clinical group should take these characteristics into account.     

All three trimester binge alcohol exposure causes fetal cerebellar purkinje cell loss in the presence of maternal hypercapnea, acidemia, and normoxemia: ovine model

BACKGROUND: The third trimester equivalent has been identified, both in rat and sheep models, as a period of cerebellar vulnerability to alcohol-mediated injury. We wished to determine whether alcohol exposure throughout gestation results in greater injury compared with exposure limited to the third trimester equivalent. While this question has previously been addressed in the rat model, where the third trimester equivalent occurs postnatally, it has not yet been addressed in an animal model where all 3 trimester equivalents occur prenatally, as in the ovine. We also wished to correlate cerebellar Purkinje cell loss to alcohol-mediated alterations in maternal arterial pH and blood gases as these responses might be important mechanistically in mediating the damage. METHODS: Three groups of pregnant sheep were used: an untreated normal control group, a saline control group, and an alcohol group (1.75 g/kg of the body weight). The alcohol exposure regimen was designed to mimic a human binge pattern; alcohol was administered intravenously on 3 consecutive days, followed by 4 days without alcohol, beginning day 4 of gestation, continuing to the end of the third trimester equivalent of human brain growth, day 132 of gestation. RESULTS: All 3 trimester alcohol-exposed fetal brains exhibited significant deficits in cerebellar volume and Purkinje cell number compared with those of control subjects. We did not detect a difference in the reduction of Purkinje cell number when comparing between all 3 trimester and third trimester alcohol exposure studies. The neuronal loss was accompanied by maternal hypercapnea, acidemia, and normoxemia. CONCLUSIONS: These findings demonstrate in an ovine model where all 3 trimester equivalent of brain growth occur in utero that the fetal cerebellar Purkinje cells are more sensitive to the timing of alcohol exposure and less so to the duration of exposure. Decreases in maternal P(a)O(2) were not detected, suggesting that maternal hypoxia does not play a role in fetal Purkinje cell loss. And finally, we conclude that alcohol-induced changes in maternal arterial pH may play a role in alcohol-mediated developmental brain injury.     

Epidemiology of FASD in a province in Italy: Prevalence and characteristics of children in a random sample of schools

BACKGROUND: Accurate estimates of the prevalence and characteristics of fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders (FASD) in a Western European population are lacking and are of particular interest in settings where the usual pattern of alcohol consumption is thought to be daily drinking with meals. To address these issues, an epidemiology study of FAS and other FASD was undertaken in Italian schools. METHODS: Primary schools (n = 25) in 2 health districts of the Lazio region were randomly selected and recruited for the study. Five hundred forty-three children, 50% of those enrolled in first-grade classes, received parental permission to participate in a 2-tiered, active case ascertainment screening process. Detailed evaluation of children selected in a preliminary screening phase was carried out on those who were small for height, weight, and head circumference and/or referred by teachers for suspected learning and behavioral problems. Detailed evaluation was carried out on each child's: (1) physical growth and dysmorphology, (2) psychological development and behavior, and (3) prenatal exposure to alcohol and other risk factors for FASD via maternal interviews. A group of 67 randomly selected children without FASD from the same classes was utilized as a comparison group. RESULTS: Using 2 denominators for prevalence estimation, a conservative one and a strict sample-based estimate, the prevalence of FAS in this province of Italy was 3.7 to 7.4 per 1,000 children. When cases of partial FAS (PFAS) and a case of alcohol-related neurodevelopmental deficits (ARND) were added to FAS cases, the rate of FASD was 20.3 to 40.5 per 1,000 and estimated at 35 per 1,000 overall or between 2.3 and 4.1% of all children. This exceeds previously published estimates of both FAS and FASD for the western world. Detailed data are presented that demonstrate the utility of the guidelines of the revised Institute of Medicine diagnostic criteria for FASD. Children with FASD are significantly more impaired/affected (p < 0.05) than randomly selected comparison children on all measures of growth deficiency, key facial features of FASD, overall dysmorphology scores, language comprehension, nonverbal IQ, and behavior. Maternal reports of current drinking were significantly higher for mothers of FASD children than comparison mothers, but reported rates of overall drinking during pregnancy were not significantly different. In contrast to expectations, daily drinking among mothers of the comparison group was not common. However, dysmorphology scores of the children were significantly correlated with drinking in the second and third trimesters, drinks per current drinking day, and current drinks per month. Finally, children with the physical features of FASD had lower IQs; nonverbal IQ was significantly correlated with head circumference and negatively correlated with overall dysmorphology score, smooth philtrum, and several other facial and physical anomalies characteristic of FAS. CONCLUSIONS: Using careful measures of ascertainment in a primary school setting, these results provide relatively high estimates of the prevalence of FASD and raise the question of whether FASD is more common in the western world than previously estimated.     

Drinking During Pregnancy Decreases Word Attack and Arithmetic Scores on Standardized Tests: Adolescent Data From a Population-Based Prospective Study

Women (1529) were interviewed in midpregnancy, and a cohort of their children has been examined at various ages. The two standardized tests presented herein are part of a large battery of tests administered when the children were 14 years old. "Word Attack" ( n =462) measures phonological processing on a task involving the reading of pseudowords in nontimed performance. "Arithmetic" ( n =191) measures auditorily processed mental computations in timed performance. Scores on both tests were associated with prenatal alcohol exposure in a dose-dependent fashion. These effects were robust when considered in relation to a wide variety of potentially confounding variables, such as prenatal exposure to tobacco and other drugs, sociodemographic characteristics, and traumatic postnatal events. A variety of alcohol scores were related to these two performance measures, but those involving a massing of drinks on a given occasion had the strongest association. The higher the average number of drinks/occasion, the poorer the offspring performance on tasks thought to underlie numerical problem solving and reading proficiency. Earlier reports of prenatal, alcohol-related neurobehavioral deficits in childhood have now been extended into adolescence.     

Prenatal Alcohol Use Among Teenagers: Effects on Neonatal Outcomes

BACKGROUND: This longitudinal study examines the effects of alcohol use during pregnancy on the growth and gestational age at birth of 413 offspring of adolescents. METHODS: Data were collected during 1990 to 1994. The adolescents were from a prenatal clinic in Pittsburgh, PA. They were interviewed at mid-pregnancy and at delivery to obtain information on alcohol and other substance use before and during pregnancy. Infants were examined 24 to 36 hr after birth. RESULTS: The average maternal age was 16.3 (12-18) years; 68% were African American. Prenatal exposure to alcohol during the second trimester was significantly related to decreases in head circumference, birthweight, and chest circumference. There was also a significant relationship between alcohol exposure in each trimester and lower Apgar scores. All of the analyses controlled for other prenatal substance use and covariates of drinking during pregnancy. CONCLUSION: Prenatal alcohol exposure is associated with decreases in fetal growth and in APGAR scores in the offspring of adolescents.     

Number processing in adolescents with prenatal alcohol exposure and ADHD: differences in the neurobehavioral phenotype

Background: Poor arithmetic performance is among the most sensitive outcomes associated with prenatal alcohol exposure and is also common in individuals with attention‐deficit hyperactivity disorder (ADHD). We hypothesized that prenatal alcohol exposure would be associated with deficits in the most fundamental aspects of number processing, representation of quantity and distance, whereas ADHD would be associated with deficits in calculation, the form of number processing most dependent on attention and memory. Methods: Two hundred and sixty‐two inner‐city, African American adolescents, who had been evaluated prospectively for prenatal alcohol exposure and ADHD, were assessed on a number‐processing test comprised of 7 subtests. Results: More heavily alcohol‐exposed adolescents were 4 times more likely to meet diagnostic criteria for ADHD than those whose mothers abstained from alcohol use during pregnancy. Two dimensions of number processing were identified in a factor analysis—magnitude comparison and calculation. As hypothesized, prenatal alcohol exposure was more strongly related to the former and ADHD to the latter. Moreover, the relation of prenatal alcohol to calculation was fully mediated by magnitude comparison, whereas the relation of ADHD to calculation was mediated by IQ but not by magnitude comparison. Conclusion: These data confirm findings from previous studies identifying arithmetic as a particularly sensitive developmental endpoint for prenatal alcohol exposure. Whereas difficulties with arithmetic in ADHD are mediated by domain‐general deficits in overall cognitive ability, fetal alcohol‐related arithmetic difficulties are mediated primarily by a specific deficit in the core quantity system involving the ability to mentally represent and manipulate number. These data suggest that different interventions are likely to be effective for remediating arithmetic problems in children with prenatal alcohol exposure than in non‐exposed children with ADHD.     

Temporal vulnerability of fetal cerebellar Purkinje cells to chronic binge alcohol exposure: ovine model

BACKGROUND: Human magnetic resonance imaging (MRI) and autopsy studies reveal abnormal cerebellar development in children who had been exposed to alcohol prenatally, independent of the exposure period. Animal studies conducted utilizing the rat model similarly demonstrate a broad period of vulnerability, albeit the third trimester-equivalent of human brain development is reported to be the most vulnerable period, and the first trimester-equivalent exposure produces cerebellar Purkinje cell loss only at high doses of alcohol. However, in the rat model, all 3 trimester-equivalents do not occur prenatally, requiring the assumption that intrauterine environment, placenta, maternal interactions, and parturition do not play an important role in mediating the damage. In this study, we utilized the ovine model, where all 3 trimester-equivalents occur in utero, to determine the critical window of vulnerability of fetal cerebellar Purkinje cells. METHODS: Four groups of pregnant sheep were used: first trimester-equivalent pair-fed saline control group, first trimester-equivalent alcohol group (1.75 g/kg), third trimester-equivalent pair-fed saline control group, and third trimester-equivalent alcohol group (1.75 g/kg). The alcohol exposure regimen was designed to mimic a human binge pattern. Alcohol was administered intravenously on 3 consecutive days beginning on day 4 and day 109 of gestation in the first and third trimester-equivalent groups, respectively, and the alcohol treatment was followed by a 4-day inter-treatment interval when the animals were not exposed to alcohol. Such treatment episodes were replicated until gestational day 41 and 132 in the first and third trimester-equivalent groups, respectively. All fetal brains were harvested on day 133 and processed for stereological cerebellar Purkinje cell counting. RESULTS: Significant deficits were found in the fetal cerebellar Purkinje cell number and density in the first and third trimester-equivalent alcohol exposed fetuses compared with those in the saline controls. However, there was no difference between the first and third trimester-equivalent alcohol administered groups. When comparing the present findings to those from a previous study where the duration of alcohol exposure was all 3 trimester-equivalents of gestation, we did not detect a difference in fetal cerebellar Purkinje cell number. CONCLUSIONS: We conclude that the fetal cerebellar Purkinje cells are sensitive to alcohol exposure at any time during gestation and that women who engage in binge drinking during the first trimester are at a high risk of giving birth to children with cerebellar damage even if drinking ceases after the first trimester. Our findings also support the hypothesis that only a certain population of Purkinje cells are vulnerable to alcohol-induced depletion irrespective of the timing or duration of alcohol exposure.     

Alcohol, Marijuana, and Tobacco: Effects of Prenatal Exposure on Offspring Growth and Morphology at Age Six

Little is known about the long-term effects of prenatal exposure to alcohol. There are even fewer reports on the longitudinal effects of exposure to either marijuana or tobacco during pregnancy. This study is on the 6-year follow-up of 668 children enrolled in the Maternal Health Practices and Child Development Project. Mothers were interviewed at the 4th and 7th months of pregnancy, and mothers and children were evaluated at delivery, 8, and 18 months, and 3 and 6 years postpartum. At 6 years of age, children who were exposed to alcohol prenatally were significantly smaller in weight, height, head circumference, and palpebral fissure width. These effects on size were mediated by the effect of prenatal alcohol exposure on the offspring at 8 months. Prenatal alcohol exposure was also significantly associated with maternal reports of the child's appetite at 6 years. There were no effects of prenatal marijuana or tobacco exposure on growth when the children were age 6. There were also no significant relationships between prenatal exposure to alcohol, marijuana, or tobacco and the rate of morphologic anomalies, including the features of the fetal alcohol syndrome.     

A Review of the Neuroanatomical Findings in Children with Fetal Alcohol Syndrome or Prenatal Exposure to Alcohol

Human and animal studies have clearly demonstrated that alcohol is both a physical and behavioral teratogen and that heavy prenatal alcohol exposure can lead to a distinct pattern of birth defects termed the fetal alcohol syndrome. Underlying the behavioral and cognitive anomalies seen in fetal alcohol syndrome are alterations in brain structure and/or function. This paper reviews the literature examining brain anomalies attributable to prenatal alcohol exposure, beginning with a survey of autopsy studies and leading up to current findings using magnetic resonance imaging and positron emission tomography studies. Autopsy reports clearly illustrate the wide and devastating influence alcohol has on the developing brain, although for the most part no specific pattern of brain malformation has been identified. More recent magnetic resonance imaging studies, particularly when combined with quantitative analysis, have indicated that specific brain areas–such as the basal ganglia, the corpus callo-sum, and parts of the cerebellum–might be especially susceptible to alcohol's teratogenic effects. Further studies using functional brain imaging techniques may provide even more information about the unique effects prenatal alcohol exposure has on the developing brain. Discovering specific areas of the brain that are affected by alcohol may allow clinicians and researchers to look for patterns of vulnerable regions in the brain, thereby helping in the future detection of children who are prenatally exposed to alcohol.     

Fetal alcohol spectrum disorders in children residing in Russian orphanages: a phenotypic survey

BACKGROUND: Alcohol use in Russia is among the highest in the world. Over 600,000 children reside in institutional care in Russia, most of them in baby homes and orphanages. The actual prevalence of fetal alcohol spectrum disorders (FASD) among these children is unknown. Therefore, we performed a systematic survey of phenotypic features associated with prenatal alcohol exposure among institutionalized Russian children and related these findings to their growth, development, medical, and social histories. METHODS: Phenotypic screening was conducted of all 234 baby home residents in the Murmansk region of Russia (mean age 21+12.6 months). Phenotypic expression scores were devised based on facial dysmorphology and other readily observable physical findings. Growth measurements from birth, time of placement in the baby home, and at present were analyzed. In addition, the charts of 64% of the children were randomly selected for retrospective review. Information collected included maternal, medical, developmental, and social histories. RESULTS: Thirteen percent of children had facial phenotype scores highly compatible with prenatal alcohol exposure and 45% had intermediate facial phenotype scores. These scores correlated with maternal gravidity and age. At least 40% of mothers in whom history was available ingested alcohol during pregnancy; some also used illicit drugs and tobacco. Z scores for growth measurements corresponded to phenotypic score, as did the degree of developmental delay. Children with no or mild delay had significantly lower phenotypic scores than those with moderate or severe delay (p = 0.04); more than 70% of children with high phenotypic scores were moderately or severely delayed. CONCLUSIONS: More than half of residents of the baby homes in Murmansk, Russia, have intermediate (45%) or high (13%) phenotypic expression scores suggesting prenatal exposure to alcohol. Despite good physical care, stable daily routine, availability of well-trained specialists, and access to medical care, these vulnerable children show significant growth and developmental delays compared with their institutionalized peers.     

Fetal alcohol exposure and temporal vulnerability: regional differences in cell loss as a function of the timing of binge-like alcohol exposure during brain development

This study was conducted to determine the temporal and regional vulnerability of the brain as a function of exposure to alcohol during brain development. Our goal was to manipulate the timing of alcohol exposure and assess the relative risk of cell loss in two different brain regions. Groups of timed pregnant Sprague-Dawley rats received binge-like alcohol exposure during either the first 10 days (first-trimester equivalent) or second 10 days of gestation (second-trimester equivalent), or the combination of first- and second-trimester equivalents for prenatal treatments. Offspring from some of the animals exposed to alcohol during the combined first- and second-trimester equivalent were reared artificially from postnatal days (P) 4 through 9 (part of the third-trimester equivalent) and also received binge-like alcohol during this period, producing animals that were exposed to alcohol during all three trimesters equivalent. Offspring from untreated dams were also reared artificially and received alcohol from only P4-9, thus creating animals that were exposed to alcohol only during part of the third-trimester equivalent. All pups were perfused on P10. Appropriate controls (nutritional and normally reared) were matched to every alcohol treatment combination. Peak blood alcohol concentrations were not different among the treatment groups for a given sampling time. Total cell numbers in the cerebellum (Purkinje and granule cells) and the olfactory bulb (mitral and granule cells) were estimated by the unbiased stereological technique, the optical disector. In terms of temporal vulnerability, alcohol exposure during the equivalent of all three trimesters resulted in a greater reduction in cerebellar Purkinje cell numbers compared with exposure to alcohol during the third-trimester equivalent, whereas both groups had a significant reduction in cell number compared with all other timing groups. Cerebellar granule cell number was reduced after alcohol exposure during all three trimesters equivalent, compared with all other timing groups. Alcohol exposure during the third-trimester equivalent resulted in a decrement in the number of olfactory bulb mitral cell numbers compared with all other groups, but there were no differences among the timing groups in numbers of olfactory bulb granule cells. When the cell loss in the two regions was compared within each alcohol treatment group to determine the relative regional vulnerability, the primary salient finding was that cerebellar Purkinje cells were more vulnerable to alcohol-induced loss subsequent to exposure during all three trimesters equivalent. No other regional differences were detected. These results extend earlier findings by showing that alcohol exposure during different periods of brain development results in regional differences in cell loss as a function of the timing of alcohol exposure during brain development and illustrate the variability of alcohol-induced neuronal loss.     

Verbal and visuospatial learning and memory function in children with moderate prenatal alcohol exposure

BACKGROUND: This study investigated the effects of moderate prenatal alcohol exposure on learning and memory in 14-year-old adolescents. The Children's Memory Scale was used to assess learning and memory function in the verbal/auditory and visual/spatial domains. In addition, both short- and long-term memory function were assessed. METHODS: Data were collected as part of the Maternal Health Practices and Child Development Project, a longitudinal study including 580 children and their mothers. Women were assessed during each trimester of pregnancy and with their children from birth to 16 years of age. At age 14, memory function was evaluated using the Children's Memory Scale, an assessment tool that measures learning and immediate and delayed memory function in the verbal and visual-spatial domains. RESULTS: Prenatal alcohol exposure during the first trimester predicted deficits in learning, short-term memory, and long-term memory, specifically in the verbal domain. Deficits in performance were specific to learning and memory of word-pairs. In addition, deficits in memory were mediated by learning performance. CONCLUSIONS: Results demonstrated that prenatal alcohol exposure lead to deficits in encoding processes as indicated by deficits in verbal learning. Initial deficits in acquisition were responsible for deficits in immediate and delayed recall of verbal information in children who were exposed to alcohol during pregnancy but did not have fetal alcohol syndrome.     

An Update on Fetal Alcohol Syndrome—Pathogenesis,Risks, and Treatment

Alcohol is a well‐established teratogen that can cause variable physical and behavioral effects on the fetus. The most severe condition in this spectrum of diseases is known as fetal alcohol syndrome (FAS). The differences in maternal and fetal enzymes, in terms of abundance and efficiency, in addition to reduced elimination, allow for alcohol to have a prolonged effect on the fetus. This can act as a teratogen through numerous methods including reactive oxygen species (generated as by products of CYP2E1), decreased endogenous antioxidant levels, mitochondrial damage, lipid peroxidation, disrupted neuronal cell–cell adhesion, placental vasoconstriction, and inhibition of cofactors required for fetal growth and development. More recently, alcohol has also been shown to have epigenetic effects. Increased fetal exposure to alcohol and sustained alcohol intake during any trimester of pregnancy is associated with an increased risk of FAS. Other risk factors include genetic influences, maternal characteristics, for example, lower socioeconomic statuses and smoking, and paternal chronic alcohol use. The treatment options for FAS have recently started to be explored although none are currently approved clinically. These include prenatal antioxidant administration food supplements, folic acid, choline, neuroactive peptides, and neurotrophic growth factors. Tackling the wider impacts of FAS, such as comorbidities, and the family system have been shown to improve the quality of life of FAS patients. This review aimed to focus on the pathogenesis, especially mechanisms of alcohol teratogenicity, and risks of developing FAS. Recent developments in potential management strategies, including prenatal interventions, are discussed.     

Prenatal Alcohol Exposure and Preschool Physical Growth: A Longitudinal Analysis

This report examines the effects of fetal alcohol exposure on size and growth in an urban cohort followed prospectively through early childhood. Indices of prenatal drinking were related to measurements of weight, stature (length), and head circumference obtained at birth and during five subsequent in-home assessments. Small but statistically significant relationships were detected between short-term recall estimates of drinking during pregnancy and weight and length at birth. The strength of these relationships diminished during the preschool assessments. However, estimates of catch-up growth associated with alcohol exposure were not statistically significant. With the exception of a single case with a profile of signs characteristic of fetal alcohol syndrome, an adverse effect of prenatal alcohol exposure on head circumference was not indicated.