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.     

The alcoholism generator

Alcohol exposure largely affects 3 populations: fetuses, adolescents, and adults. These 3 developmental stages are inextricably intertwined such that elevated alcohol exposure at any time increases the probability of exposure at the others. This circular interdependency is called the alcoholism generator. Furthermore, exposure to large amounts of alcohol at these 3 times can cause cognitive dysfunction, largely through mechanisms of alcohol-induced perturbations in neurogenesis and synaptogenesis. Breaking this cycle is key to reducing problem alcohol drinking and the associated sequelae.     

Maternal risk factors for fetal alcohol syndrome and partial fetal alcohol syndrome in South Africa: a third study

Objectives: This is a third exploration of risk factors for the two most severe forms of fetal alcohol spectrum disorders (FASD), fetal alcohol syndrome (FAS) and Partial FAS (PFAS), in a South African community with the highest reported prevalence of FAS in the world. Methods: In a case control design, interview and collateral data concerning mothers of 72 first grade children with FAS or PFAS are compared with 134 randomly selected maternal controls of children from the same schools. Results: Significant differences were found between the mothers of FASD children and controls in socio‐economic status, educational attainment, and a higher prevalence of FASD among rural residents. The birth order of the index children, gravidity, and still birth were significantly higher among mothers of FASD children. Mothers of children with a FASD are less likely to be married and more likely to have a male partner who drank during the index pregnancy. Current and gestational alcohol use by mothers of FASD children is bingeing on weekends, with no reduction in drinking reported in any trimester in 75 to 90% of the pregnancies that resulted in an FAS child or during 50 to 87% of PFAS‐producing pregnancies. There was significantly less drinking among the controls in the second and third trimesters (11 to 14%). Estimated peak blood alcohol concentrations (BAC)s of the mothers of PFAS children range from 0.155 in the first trimester to 0.102 in the third, and for mothers of FAS children the range is from 0.197 to 0.200 to 0.191 in the first, second, and third. Smoking percentage during pregnancy was significantly higher for mothers of FASD children (82 to 84%) than controls (35%); but average quantity smoked is low in the 3 groups at 30 to 41 cigarettes per week. A relatively young average age of the mother at the time of FAS and PFAS births (28.8 and 24.8 years respectively) is not explained by early onset of regular drinking (mean = 20.3 to 20.5 years of age). But the mean years of alcohol consumption is different between groups, 16.3, 10.7, and 12.1 years respectively for mothers of FAS, FASD, and drinking controls. Mothers of FAS and PFAS children were significantly smaller in height and weight than controls at time of interview. The child’s total dysmorphology score correlates significantly with mother’s weight (?0.46) and BMI (?0.39). Bivariate correlations are significant between the child’s dysmorphology and known independent demographic and behavioral maternal risk factors for FASD: higher gravidity and parity; lower education and income; rural residence; drinks consumed daily, weekly, and bingeing during pregnancy; drinking in all trimesters; partner's alcohol consumption during pregnancy; and use of tobacco during pregnancy. Similar significant correlations were also found for most of the above independent maternal risk variables and the child’s verbal IQ, non‐verbal IQ and behavioral problems. Conclusions: Maternal data in this population are generally consistent with a spectrum of effects exhibited in the children. Variation within the spectrum links greater alcohol doses with a greater severity of effects among children of older and smaller mothers of lower socio economic status in their later pregnancies. Prevention is needed to address known maternal risk factors for FASD in this population.     

Phosphatidylethanol as Blood Biomarker of Alcohol Consumption in Early Pregnancy: An Observational Study in 4,067 Pregnant Women

Background

The teratogenic effects of alcohol are well documented, but there is a lack of screening methods to detect alcohol use during pregnancy. Phosphatidylethanol 16:0/18:1 (PEth) is a specific and sensitive biomarker reflecting alcohol intake up to several weeks after consumption. The aim of this study was to investigate the prevalence of positive PEth values as an indicator of early prenatal alcohol exposure in a general population of pregnant women.

Methods

Rhesus typing is routinely performed in Norway in all pregnancies around gestational week 12. Rhesus-negative women have an additional test taken around week 24. Blood samples submitted to St. Olav University Hospital in Trøndelag, Norway, for Rhesus typing during the period September 2017 to October 2018 were collected. A total of 4,533 whole blood samples from 4,067 women were analyzed for PEth (limit of quantification of 0.003 µM).

Results

Fifty-eight women had a positive PEth sample. Of these, 50 women were positive around gestational week 12, 3 women were positive around week 24, and in 5 cases, the timing was unknown. There were no significant differences in proportions of women with positive PEth values related to age, or rural versus urban residency.

Conclusion

In an unselected pregnant population in Norway, 1.4% had a positive PEth sample around gestational week 12, whereas 0.4% had a positive sample around week 24. The use of PEth as an alcohol biomarker should be further investigated as a diagnostic tool in the antenatal setting.

     

A Metric of Maternal Prenatal Risk Drinking Predicts Neurobehavioral Outcomes in Preschool Children

Background: Fetal Alcohol Spectrum Disorders (FASDs), including Fetal Alcohol Syndrome, continue to be high‐incidence developmental disorders. Detection of patterns of maternal drinking that place fetuses at risk for these disorders is critical to diagnosis, treatment, and prevention, but is challenging and often insufficient during pregnancy. Various screens and measures have been used to identify maternal risk drinking but their ability to predict child outcome has been inconsistent. This study hypothesized that a metric of fetal “at‐risk” alcohol exposure (ARAE) derived from several indicators of maternal self‐reported drinking would predict alcohol‐related neurobehavioral dysfunctions in children better than individual measures of maternal alcohol consumption alone. Methods: Self‐reported peri‐conceptional and repeated maternal drinking during pregnancy were assessed with semi‐structured interviews and standard screens, i.e., the CAGE, T‐ACE, and MAST, in a prospective sample of 75 African‐American mothers. Drinking volumes per beverage type were converted to standard quantity and frequency measures. From these individual measures and screening instruments, a simple dichotomous index of prenatal ARAE was defined and used to predict neurobehavioral outcomes in the 4‐ to 5‐year‐old offspring of these women. Study outcomes included IQ, attention, memory, visual‐motor integration, fine motor skill, and behavior. Statistical analyses controlled for demographic and other potential confounders. Results: The current “at‐risk” drinking metric identified over 62% of the mothers as drinking at risk levels—23% more than the selection criterion identified—and outperformed all individual quantity and frequency consumption measures, including averages of weekly alcohol use and “binge” alcohol exposures (assessed as intake per drinking occasion), as well as an estimate of the Maternal Substance Abuse Checklist ( Coles et al., 2000 ), in predicting prenatal alcohol‐related cognitive and behavioral dysfunction in 4‐ to 5‐year‐old children. Conclusions: A metric reflecting multiple indices of “at‐risk” maternal alcohol drinking in pregnancy had greater utility in predicting various prenatal alcohol‐related neurobehavioral dysfunction and deficits in children compared to individual measures of maternal self‐reported alcohol consumption or a previous maternal substance abuse index. Assessing fetal risk drinking in pregnant women was improved by including multiple indicators of both alcohol consumption and alcohol‐related consequences and, if appropriate practical applications are devised, may facilitate intervention by health care workers during pregnancy and potentially reduce the incidence or severity of FASDs.     

Applying a Developmental Framework to the Self‐Regulatory Difficulties of Young Children with Prenatal Alcohol Exposure: A Review

Prenatal alcohol exposure (PAE) can be associated with significant difficulties in self‐regulatory abilities. As such, interventions have been developed that focus on improving varying aspects of self‐regulation for this population. The application of a multilevel theoretical framework that describes the development of self‐regulation during early childhood could further advance the field. First, this framework could assist in elucidating mechanisms in the trajectories of early adjustment problems in this population and, second, informing the development of more precise assessment and interventions for those affected by PAE. The aims of the current review were to provide an overview of the self‐regulatory framework proposed by Calkins and colleagues (e.g., Calkins, 2007; Calkins and Fox, 2002); examine the self‐regulatory difficulties that are commonly experienced during infancy (i.e., 0 to 2 years) and early childhood (i.e., 3 to 8 years) in children with PAE in the context of the developmental framework; and describe how the framework can inform the development of future assessment and intervention provision for young children with PAE. The application of a developmental framework, such as proposed by Calkins and colleagues, allows for a systematic and theoretically driven approach to assessment and intervention programs for young children with PAE.     

Effect of Choline Supplementation on Neurological,Cognitive, and Behavioral Outcomes in Offspring Arising from Alcohol Exposure During Development: A Quantitative Systematic Review of Clinical and Preclinical Studies

Prenatal alcohol exposure results in cognitive, behavioral, and neurological deficits in offspring. There is an urgent need for safe and effective treatments to overcome these effects. Maternal choline supplementation has been identified as a potential intervention. Our objective was to review preclinical and clinical studies using choline supplementation in known cases of fetal alcohol exposure to determine its effectiveness in ameliorating deficits in offspring. A systematic search of 6 electronic databases was conducted and studies selected by reviewing titles/abstracts against specific inclusion/exclusion criteria. Study characteristics, population demographics, alcohol exposure, and intervention methods were tabulated, and quality of reporting was assessed. Data on cognitive, behavioral, and neurological outcomes were extracted and tabulated. Quantitative analysis was performed to determine treatment effects for individual study outcomes. A total of 189 studies were retrieved following duplicate removal. Of these, 22 studies (2 randomized controlled trials, 2 prospective cohort studies, and 18 preclinical studies) met the full inclusion/exclusion criteria. Choline interventions were administered at different times relative to alcohol exposure, impacting on their success to prevent deficits for specific outcomes. Only 1 clinical study showed significant improvements in information processing in 6‐month‐old infants from mothers treated with choline during pregnancy. Preclinical studies showed significant amelioration of deficits due to prenatal alcohol exposure across a wide variety of outcomes, including epigenetic/molecular changes, gross motor, memory, and executive function. This review suggests that choline supplementation has the potential to ameliorate specific behavioral, neurological, and cognitive deficits in offspring caused by fetal alcohol exposure, at least in preclinical studies. As only 1 clinical study has shown benefit, we recommend more clinical trials be undertaken to assess the effectiveness of choline in preventing deficits across a wider range of cognitive domains in children.     

Prenatal Alcohol Use and Offspring Size at 10 Years of Age

The Maternal Health Practices and Child Development Project is a longitudinal study of the effects of prenatal exposure to alcohol and other substances. Women were selected from a prenatal clinic and interviewed at the 4th and 7th months of pregnancy. Their offspring were examined at delivery, at 8 and 18 months, and at 3, 6, and 10 years. This report examined 610 offspring, at age 10, who were exposed prenatally to alcohol. Most alcohol use in this low-income cohort was light to moderate, although the entire spectrum of alcohol use is represented. The weight, length, head circumference, and skinfold thickness of the offspring were measured. At each assessment phase, we found a significant association between size and prenatal exposure to alcohol. At age 10, the children who were prenatally exposed to alcohol continued to be significantly smaller in weight, height, head circumference, and skinfold thickness. These results indicate that prenatal alcohol exposure has a long-term impact on offspring growth.     

Alcohol consumption among low-income pregnant Latinas

BACKGROUND: Due to changing cultural norms, Latinas of childbearing age residing in the U.S. may be at increasing risk of drinking harmful levels of alcohol during pregnancy, and may also be unaware of the risks for Fetal Alcohol Spectrum Disorders associated with this behavior. We assessed the prevalence of alcohol consumption in a sample of low-income pregnant Latinas and examined risk factors for alcohol use in the periconceptional period. METHODS: As part of a larger intervention trial, a cross-sectional in-home interview study was conducted among a sample of 100 pregnant low-income Latinas receiving services from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in San Diego County, California. RESULTS: Fifty-seven percent of respondents indicated they were either life-time abstainers or had not consumed any alcohol in the periconceptional period. Forty-three percent reported some alcohol use in the three months prior to recognition of the current pregnancy, and 20% reported at least one binge episode of four or more standard drinks during that time frame. Five percent reported drinking seven or more drinks per week, and 8% continued drinking alcohol after recognition of pregnancy. Significant predictors of any alcohol use in the periconceptional period included English language/higher level of acculturation, younger maternal age, lower parity, higher level of education, younger age at first drink, and having ever smoked. Women who were aware of alcohol warning messages and /or had more knowledge of the Fetal Alcohol Syndrome (FAS) were significantly more likely to have consumed alcohol in the periconceptional period. Frequency of periconceptional use of alcohol did not differ between women who planned or did not plan the pregnancy. CONCLUSION: The prevalence and pattern of early pregnancy alcohol consumption in this sample of Latinas is similar to patterns noted in other race/ethnic groups in the U.S. Level of knowledge about FAS and awareness of warning messages was not protective for early pregnancy alcohol consumption, suggesting that specific knowledge was insufficient to prevent exposure or that other factors reinforce maintenance of alcohol consumption in early pregnancy. Selective interventions in low-income Latinas are warranted, and should be focused on women of reproductive age who are binge or frequent drinkers and who are at risk of becoming pregnant.     

Prenatal alcohol exposure patterns and alcohol-related birth defects and growth deficiencies: a prospective study

Background: The physical features of fetal alcohol syndrome include smooth philtrum, thin vermillion border, short palpebral fissures, microcephaly, and growth deficiencies on weight and height. However, little is known about the specific quantities of alcohol exposure, pattern of drinking, timing of exposure, and magnitude of risk for each of these features. Methods: Using data on 992 subjects collected prospectively in California between 1978 and 2005, we examined the patterns and timing of alcohol exposure in relation to these features. Structural features were assessed by a dysmorphologist who performed a blinded physical examination of all infants. Patterns of drinking were evaluated by drinks per day, number of binge episodes, and maximum number of drinks. Timing of exposure was evaluated 0 to 6 weeks postconception, 6 to 12 weeks postconception, first trimester, second trimester, and third trimester. Results: Higher prenatal alcohol exposure in every pattern was significantly associated with the incidence of smooth philtrum but not with short palpebral fissures. The strongest associations were with timing of exposure in the second half of the first trimester (RR 1.25, 95% CI 1.14 to 1.36 for average number of drinks per day; RR 1.17, 95% CI 1.09 to 1.26 for maximum number of drinks in 1 episode). Similarly, thin vermillion border was most strongly associated with exposure in the second half of the first trimester. Findings with respect to timing of exposure were similar for microcephaly and reduced birth weight. However, reduced birth length was increased with exposure in any trimester. These associations were linear, and there was no evidence of a threshold. Conclusions: Reduced birth length and weight, microcephaly, smooth philtrum, and thin vermillion border are associated with specific gestational timing of prenatal alcohol exposure and are dose‐related without evidence of a threshold. Women should continue to be advised to abstain from alcohol consumption from conception throughout pregnancy.     

Neuropsychological characteristics of Italian children with fetal alcohol spectrum disorders

Background: Children with fetal alcohol spectrum disorders (FASD) display many problems ranging from deficits in intelligence to behavioral difficulties. Thus, many studies have aimed at defining the neuropsychological characteristics of children with FASD. The current article describes the neuropsychological characteristics of Italian children with severe diagnosis within FASD and compares them with controls. It was expected that intellectual functioning, language comprehension, academic skills, and inattention/hyperactivity would discriminate children with FASD from randomly selected peers without FASD. Methods: This article presents data from a second cohort of children examined in 2005 as part of an in‐school epidemiological study of FASD in Italy. Of 80 children, 23 diagnosed with a FASD, and 57 randomly selected control children from the same first‐grade classes, participated. After screening for FASD via growth and dysmorphology, the children were administered a test of general intelligence (WISC‐R) as well as tests of nonverbal reasoning (Raven Colored Progressive Matrices), language comprehension (Rustioni), academic achievement (IPDA), and problem behavior (Disruptive Behavior Disorder Rating Scale). Results: Children diagnosed with a FASD achieved lower scores than control children on Verbal, Performance, and Full Scale IQ. Profile analysis of the WISC‐R indicates overall differences between the groups. However, some intact functioning within the FASD group was found, as the Similarities and Vocabulary subtests were similar to the controls. After an alpha adjustment to 0.004, the Block Design, Object Assembly, and Mazes subtests were significantly different from controls. On tests of nonverbal reasoning, language comprehension, and academic achievement, the children with a FASD scored significantly lower. Moreover, teachers rated children with a severe diagnosis within FASD as showing more inattentive symptoms than controls, while hyperactive/impulsive characteristics among children with a FASD were comparable with the control children. Significant correlations between head circumference, child dysmorphology, WISC‐R, and Raven CPM scores are also reported. Conclusions: This study indicates that a sample of Italian children with a FASD, when compared with control children, display poorer functioning on measures of general intelligence, nonverbal reasoning, academic achievement, and teacher‐rated problem behaviors. The findings also contribute to the formulation of a neuropsychological profile of children diagnosed with a FASD.     

Reducing adverse outcomes from prenatal alcohol exposure: a clinical plan of action

Fetal alcohol spectrum disorders (FASDs) are among the leading preventable causes of developmental disorders in the United States; however, recognition and prevention of these conditions cannot be achieved without informed and educated health providers. This commentary addresses the importance of recognition and prevention of FASDs through the use of well-established standardized practices of diagnosis, screening, and brief alcohol reduction counseling. It is hoped that more knowledge on currently available procedures will encourage their use in the provision of routine health care to all women of childbearing age.     

Prenatal alcohol exposure affects frontal-striatal BOLD response during inhibitory control

BACKGROUND: Prenatal alcohol exposure can lead to widespread cognitive impairment and behavioral dysregulation, including deficits in attention and response inhibition. This study characterized the neural substrates underlying the disinhibited behavioral profile of individuals with fetal alcohol spectrum disorders (FASD). METHODS: Children and adolescents (ages 8-18) with (n=13) and without (n=9) histories of heavy prenatal alcohol exposure underwent functional magnetic resonance imaging while performing a response inhibition (go/no-go) task. RESULTS: Despite similar task performance (mean response latency, performance accuracy, and signal detection), blood oxygen level-dependent (BOLD) response patterns differed by group. Region-of-interest analyses revealed that during portions of the behavioral task that required response inhibition, alcohol-exposed participants showed greater BOLD response across prefrontal cortical regions (including the left medial and right middle frontal gyri), while they showed less right caudate nucleus activation, compared with control participants. CONCLUSIONS: These data provide an account of response inhibition-related brain functioning in youth with FASD. Furthermore, results suggest that the frontal-striatal circuitry thought to mediate inhibitory control is sensitive to alcohol teratogenesis.