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Verbal and Visuospatial Learning and Memory Function in Children With Moderate Prenatal Alcohol Exposure
Abstract
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.
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.
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.
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.
... Among the many possible adverse outcomes of such heavy prenatal alcohol exposure (PAE), damage of the developing brain and resulting neurobehavioral deficits are the most devastating (Mattson and Riley, 1998;Riley and McGee, 2005;Fryer et al., 2007b;Coles, 2011;Mattson et al., 2011). Problems with impulsivity, response inhibition, attention, activity, learning, and memory are widespread among FASD individuals (Streissguth et al., 1994;Uecker and Nadel, 1996;1998;Coles et al., 1997;Kaemingk et al., 2000;O'Malley and Nanson, 2002;Burden et al., 2005;Willford et al., 2004;Bhatara et al., 2006;Kodituwakku et al., 2006;Manji et al., 2009;Graham et al., 2013;Glass et al., 2014). Many of these deficits have been duplicated in experimental animals exposed prenatally to high doses of ethanol (Driscoll et al., 1990;Becker et al., 1996;Berman and Hannigan, 2000). ...
... A C C E P T E D M A N U S C R I P T 5 including childhood mental health problems, adolescent antisocial behavior, and conduct disorders resulting in problems in school (Coles et al., 1997;Sayal et al., 2007;Larkby et al., 2011), as well as self-perceived learning problems (Olson et al., 1997), deficits in verbal and visuospatial learning, and short-term and long-term memory (Willford et al., 2004;2006). ...
... Rats with lesions or functional inactivation of the dorsolateral striatum (posterior lateral putamen of humans) show distinct deficits in habit learning/long-term reference memory (Packard and White, 1990;Packard and McGaugh, 1996;Yin et al., 2004;Jacobson et al., 2012;Ferbinteanu, 2016). In children with FASD, deficits in learning and memory are worse in spatial memory (place learning) than in other learning categories (Willford et al., 2004;2006;Uecker and Nadel, 1996;1998; Kaemingk et al., 2000;Hamilton et al., 2003;Manji et al., 2009;Rasmussen et al., 2011;Malisza et al., 2012), and structural MRI studies document that the basal ganglia, including the striatum, are among the brain areas significantly reduced in size (reviewed by Moore et al., 2014). Studies have shown that acute high dose PAE during gastrulation causes diminution of the progenitor cell population in the anterior neural plate, resulting in hypoplasia of the lateral ganglionic eminences from which the dorsal striatum derives, as well as the medial ganglionic eminences from which part of the globus pallidus forms, along with subsequent reduction in cholinergic and GABAergic neurons in these locations (Sulik et al., 1984;Schambra et al., 1990;Ashwell and Zhang, 1996;Godin et al., 2010;2011;O'Leary-Moore et al., 2011;Lipinski et al., 2012). ...
Debate continues on the merits of strictly limiting alcohol consumption during all of pregnancy, and whether “safe” consumption levels and/or times exist. Only a relatively few experimental studies have been conducted that limit the timing of exposure to specific events during development and the exposure level to one that might model sporadic, incidental drinking during pregnancy. In the present study, the effects of two acute gavage exposures to low and moderate levels of ethanol (peak blood ethanol concentrations (BEC) of 104 and 177 mg/dl, respectively) either during gastrulation on gestational day (GD) 7 (at GD7:0 h and GD7:4 h) or during neurulation on GD8 (at GD8:6 h and GD8:10 h) on the spatial learning and memory abilities of adult mice in the radial arm maze (RAM) were examined. Mice were selected from a prenatal ethanol exposure (PAE) cohort that had been tested as neonates for their sensorimotor development (Schambra et al., 2015) and as juveniles and young adults for open field activity levels and emotionality (Schambra et al., 2016). Mice exposed on either of the two gestational days to acute, low or moderate levels of ethanol were deficient in overall performance in the RAM in adulthood. Importantly, mice in ethanol exposed groups took longer to reach criterion in the RAM, and many mice in these groups failed to do so after 48 trials when testing was terminated. Exposure to a low level of ethanol on either GD7 or GD8, or a moderate level on GD7, resulted in significant impairment in spatial reference (long-term) memory, while only mice exposed on GD7 to the low level of ethanol were significantly impaired in spatial working (short-term) memory. Mice exposed to the low ethanol level on either day had significantly shorter response latencies, which may reflect impairment of processes related to response inhibition or executive attention in these mice. For all measures, distributions of individual scores revealed a relatively small subset of mice in each PAE group who scored well outside the range of the control group, which skewed the population distributions to varying degrees in the direction of worse performance for the PAE groups. Overall the data suggest that after acute, low level ethanol exposure early in gestation, the likelihood that an individual mouse embryo experienced measureable ill-effects due to the exposure was rather low, but in a few of the embryos, damage occurred that resulted in significant deficits in later performance. The overall characteristics of our cohort of PAE mice, including delayed sensorimotor development, mild hypoactivity and increased emotionality, as shown in previous studies, together with deficits in spatial learning and memory as shown here, resemble those in a subset of human Fetal Alcohol Spectrum Disorder (FASD) diagnoses, specifically ADHD-Inattentive type (ADHD-I) and/or Sluggish Cognitive Tempo (SCT). Although possible correspondences between mechanisms underlying PAE-induced deficits in mice and those operating in humans remain undefined, further study with this mouse PAE model may ultimately help advance understanding of the causes of these conditions in affected children. This study highlights the possibility of risk associated with low to moderate sporadic alcohol consumption during the first month of human pregnancy.
... Some of these studies have reported that, in comparison to typically developing controls, PAE children display poorer learning of the wordlist (Fryer et al., 2012;Sowell et al., 2008), whereas others have also reported impairments in recalling and/or recognizing the words Lewis et al., 2015;Mattson, Riley, Delis, Stern, & Jones, 1996;Mattson et al., 1998;Mattson & Roebuck, 2002;Roebuck-Spencer & Mattson, 2004;Willoughby, Sheard, Nash, & Rovet, 2008). Impairments on other wordlist tasks have been echoed in both PAE adult and children samples (Coles et al., 2010;Kaemingk et al., 2003;Pei et al., 2008;Willford et al., 2004). ...
... However, studies have reported that, in comparison to normally developing controls, PAE children show impairments in story recall at immediate and delayed time points (Willoughby et al., 2008). PAE has also been shown to predict story recall on the Wide Range Assessment of Memory and Learning (WRAML) in 10-year olds (Richardson, Ryan, Willford, Day, & Goldschmidt, 2002), but not in the same longitudinal cohort at 14 years of age using the story subtest of the Children's Memory Scale (CMS) (Willford et al., 2004). These inconsistent findings could possibly be attributed to either differences in memory task demands or that impairments may resolve with age through improved memory strategy. ...
... Interestingly, studies that have utilized the same scale to measure verbal and visual-spatial memory have reported somewhat inconsistent results. For instance, both Pei et al. (2008) and Willford et al. (2004), who utilized the CMS, reported that PAE was associated with a verbal but not a visual-spatial memory impairment, whereas Rasmussen et al. (2006) reported the reverse pattern using the same battery. However, none of these studies compared the performance of the PAE children to a control group (Other studies that have utilized the CMS have reported that PAE children display impaired performance on both the stories and word pairs subtests (Willoughby et al., 2008) and faces subtest (Wheeler et al., 2012) when compared to control participants.). ...
Objective
The aim of this paper was to provide a systematic review and update on the available longitudinal studies on the impact of prenatal alcohol exposure (PAE) on language, speech and communication development, as well as associated potential environmental confounders during the preschool period.
Methods
A literature search was restricted to English, full‐text, peer‐reviewed, longitudinal studies in from 1970 until present: PUBMed, Scopus, Web of Science {C-e Collection, Biological Abstracts, KCI-Kean Journal Database, Russian Science Citation Index, SciELO Citation Index, Zoological Rec-d}, Academic Search Premier (Africa-Wide Information, CINAHL, MEDLINE, PsycINFO. Keywords included: prenatal alcohol exposure (PAE); speech or language or communication outcomes; neurocognitive or neurodevelopment or neurobehavioral or neurobehavioural; infant or baby or toddler or preschooler; longitudinal or follow-up. The inclusion criteria included (i) longitudinal cohorts with at least 2 time-points; (ii) association of light, moderate or heavy PAE on language, speech or communication delay, development or disorder; (iii) environmental confounders; (iv) infants up to preschool age.
Results
Six studies satisfied the threshold for inclusion. Three studies reported that PAE was significantly associated with receptive or expressive delay. These studies demonstrated lower scores on either receptive or expressive communication in the alcohol group in comparison to the non-alcohol group, even after controlling for environmental factors up to 36 months.
Conclusion
Evidence from the longitudinal studies reviewed suggest that PAE influenced delays in receptive and expressive communication up to 36 months. Contextual risk factors played a significant role in language development over time and especially as children approached school age.
... Recent research has begun to suggest that abnormal brain development in childhood may be the "norm" in FASD (Fagerlund, Autti-Ramo, Hoyme, Mattson, & Korkman, 2011;O'Connor, Kogan, & Findlay, 2002), suggesting that postnatal as well as prenatal brain development abnormalities may be responsible for the learning problems, mental illness, social problems, and coping difficulties that seem to increase with age in this population (Howell, Lynch, Platzman, Smith, & Coles, 2006;Streissguth et al.,1996). It is well understood in the FASD literature that children exposed to alcohol prenatally have considerable difficulty with academic learning, with higher rates of learning disabilities than non-exposed children (Coles, 2011;Crocker, Vaurio, Riley, & Mattson, 2011;Howell et al., 2006;Kaemingk, Mulvaney, & Halverson, 2003;Mattson et al., 1996a;Olson, Streissguth, & Sampson, 1997;Sowell et al., 2007;Willford, Richardson, Leech, & Day, 2004). Although FASD and PAE are associated with a wide range of impairments across a number of neuropsychological domains (Coles, Platzman, Lynch, & Freides, 2002;Kodituwakku, 2007Kodituwakku, , 2009Rasmussen, 2005), it is clear that executive dysfunction has a profoundly debilitating impact on the verbal and nonverbal learning and memory problems in this population (Mattson et al., 1996a;Roebuck-Spencer & Mattson, 2004). ...
... For example, in a verbal learning study that compared children with heavy PAE, nonexposed children with ADHD, and nonexposed controls matched on age, sex, race, ethnicity, handedness, and socioeconomic status , performance on the Children's Version of the California Verbal Learning Test (CVLT-C) led to led to a conclusion that children with heavy PAE had difficulty encoding information while ADHD children had difficulty retrieving learned material. Results of this study replicated findings in earlier studies Willford et al., 2004). In a similar study that investigated sensory processing differences between children with FASD/PAE and ADHD (Carr, Agnihotri, & Keightley, 2010), results indicated greater deficits in children who met FASD diagnostic criteria than in exposed but undiagnosed children. ...
... A wide range of basic executive impairments is consistently found in FASD, including self-regulation of activity level so as to support attention (Kopera-Frye, Carmichael- Nanson & Hiscock, 1990;Oesterheld & Wilson, 1997;Streissguth et al., 1986Streissguth et al., , 1994Streissguth, Bookstein, Sampson, & Barr, 1995;Streissguth, Martin, Barr, & Sandman, 1984), response inhibition (Green, Munoz, Nikkel, & Reynolds, 2007;Kaemingk & Paquette, 1999;Mattson, Goodman, Caine, Delis, & Riley, 1999;Noland, Singer, Arendt, Minnes, Short, & Bearer, 2003;Rasmussen & Bisanz, 2009), focusing and sustaining attention (Carmichael- Olson, Feldman, & Streissguth, 1992;Coles et al., 1997Coles et al., , 2002Kodituwakku et al., 1995;Nanson & Hiscock, 1990;Steinhausen, Nestler, & Huth, 1982;Streissguth et al., 1984Streissguth et al., , 1986Streissguth et al., , 1994Streissguth et al., , 1995, short-term auditory attention and memory (Carmichael-Olson et al., 1998), encoding new information (Coles et al., 1997;Willford et al., 2004), complex attention (i.e., ability to flexibly control selection by either switching or dividing attention between two or more things) (Kerns, Don, Mateer, & Streissguth, 1997), verbal memory (Coles, Lynch, Kable, Johnson, & Goldstein, 2010;Crocker et al., 2011;Kerns et al., 1997;Mattson et al., 1996a;Vaurio et al., 2011;Willford et al., 2004), visualspatial memory (Chiodo, Janisse, Delaney-Black, Sokol, & Hannigan, 2009;Hamilton et al., 2003;Kaemingk & Halverson, 2000;Kaemingk et al., 2003;Kaemingk & Paquette, 1999), declarative memory (Carmichael- Olson et al., 1998), and logical memory (Aragon, 2008). With respect to auditory attention in particular, task difficulty appears to matter. ...
Executive functioning, essential for effective learning, is a central and pervasive impairment in children with fetal alcohol spectrum disorders (FASD). This chapter describes how prenatal alcohol exposure (PAE) affects executive functioning in FASD and, by extension, capacity to learn from life experiences. Neuroimaging findings are reviewed in the context of earlier research, providing a rich understanding of how PAE damages the central nervous system before birth, how that damage also alters brain development after birth, and how this ongoing trauma impairs executive control over cognitive processes essential for social as well as academic learning. The chapter ends on a positive note with research regarding evidence-based interventions that show promise in improving learning capacity in this population.
... Some of these studies have reported that, in comparison to typically developing controls, PAE children display poorer learning of the wordlist (Fryer et al., 2012;Sowell et al., 2008), whereas others have also reported impairments in recalling and/or recognizing the words Lewis et al., 2015;Mattson, Riley, Delis, Stern, & Jones, 1996;Mattson et al., 1998;Mattson & Roebuck, 2002;Roebuck-Spencer & Mattson, 2004;Willoughby, Sheard, Nash, & Rovet, 2008). Impairments on other wordlist tasks have been echoed in both PAE adult and children samples (Coles et al., 2010;Kaemingk et al., 2003;Pei et al., 2008;Willford et al., 2004). ...
... However, studies have reported that, in comparison to normally developing controls, PAE children show impairments in story recall at immediate and delayed time points (Willoughby et al., 2008). PAE has also been shown to predict story recall on the Wide Range Assessment of Memory and Learning (WRAML) in 10-year olds (Richardson, Ryan, Willford, Day, & Goldschmidt, 2002), but not in the same longitudinal cohort at 14 years of age using the story subtest of the Children's Memory Scale (CMS) (Willford et al., 2004). These inconsistent findings could possibly be attributed to either differences in memory task demands or that impairments may resolve with age through improved memory strategy. ...
... Interestingly, studies that have utilized the same scale to measure verbal and visual-spatial memory have reported somewhat inconsistent results. For instance, both Pei et al. (2008) and Willford et al. (2004), who utilized the CMS, reported that PAE was associated with a verbal but not a visual-spatial memory impairment, whereas Rasmussen et al. (2006) reported the reverse pattern using the same battery. However, none of these studies compared the performance of the PAE children to a control group (Other studies that have utilized the CMS have reported that PAE children display impaired performance on both the stories and word pairs subtests (Willoughby et al., 2008) and faces subtest (Wheeler et al., 2012) when compared to control participants.). ...
Objective
This paper systematically reviews the literature on the effects of prenatal alcohol exposure (PAE) on episodic memory. Specifically, the review focuses on recurring questions of whether memory deficits are consistent across memory domains, whether the impairments are consistent across the stages of episodic memory, and whether the impairments are primary episodic memory impairments or secondary to a global performance deficit or a higher order deficit.
Method
In total, 33 relevant studies were identified through searches on electronic databases. Journal articles were limited to those that included human subjects and that were published in English-language journals.
Results
The vast majority of reviewed studies examined memory in school-aged children and adolescents. Twenty-three studies examined verbal memory and 19 studies examined visual-spatial memory. Although all of the reviewed studies examined encoding of new material, only 10 studies examined retention of the learned material over time. Ten studies controlled for IQ, either statistically or with matched controls, when analyzing memory task performance.
Conclusion
In general, studies show that PAE results in impaired verbal and visual-spatial episodic memory performance in affected individuals and these impairments are unlikely to be secondary to a global impairment. However, impairments on some memory tests are specific to the encoding stage, whereas retention is relatively spared; suggesting that the episodic memory deficit might be influenced, at least in part, by higher order cognitive processes.
... À ce même test, Lewis et al. (2015) ont confirmé que ces patients présentent d'importantes difficultés pour élaborer des stratégies impliquant en l'occurrence des catégories sémantiques. De fait, d'autres travaux suggèrent que l'absence de stratégies d'apprentissage durant l'encodage des informations est responsable du déficit mnésique (Mattson et Roebuck, 2002;Willford, Richardson, Leech et Day, 2004). Willford et al. (2004) ont proposé à des patients deux épreuves de mémoire : une épreuve de rappel de paires de mots et une autre de rappel d'une histoire. ...
... De fait, d'autres travaux suggèrent que l'absence de stratégies d'apprentissage durant l'encodage des informations est responsable du déficit mnésique (Mattson et Roebuck, 2002;Willford, Richardson, Leech et Day, 2004). Willford et al. (2004) ont proposé à des patients deux épreuves de mémoire : une épreuve de rappel de paires de mots et une autre de rappel d'une histoire. Les résultats ont montré d'importantes difficultés dans le rappel des paires de mots, tandis que le rappel de l'histoire était préservé. ...
... Indeed, evidence has been provided for a consistent pattern of long-term impairments in learning and memory functions in offspring exposed to light and moderate levels of alcohol during the first trimester of pregnancy. 15 Moreover, the question on the effect of small amounts of alcohol consumed occasionally during pregnancy on the child's development is also relevant when referred to beverages designated as alcohol-free drinks. Such beverages often contain 0.5% alcohol and the question can be posed if this amount of alcohol is safe for the foetus. ...
... 18 Symptoms of attention deficits, hyperactivity, impulsiveness, delayed learning, poor memory, primarily for working memory, poor coordination, impaired executive functioning and impaired social ability have repeatedly been reported, even in children whose mother's alcohol consumption during pregnancy was moderate. 15,[19][20][21][22] Recently, Day et al. 23 demonstrated a dose-response effect of prenatal alcohol exposure, for each of the three trimesters separately, on self-reported behaviour problems in 22-year-old offsprings, after controlling for race, sex, maternal depression, hostility during pregnancy, prenatal marijuana exposure, prenatal tobacco exposure and the young adult's own substance use. Another recent study reported causal inference between moderate alcohol drinking (up to 6 units per week without binge drinking) in pregnancy and an increased risk for children's early-onset-persistent conduct problems. ...
Several explanations for the diverse results in research on Foetal Alcohol Spectrum Disorders (FASD) or Alcohol-Related Neuro-developmental Disorder (ARND) might be at hand: timing, amount and patterns of alcohol exposure, as well as complex epigenetic responses. The genetic background of the offspring and its interaction with other prenatal and postnatal environmental cues are likely also of importance. In the present report, key findings about the possible effects of low and moderate doses of maternal alcohol intake on the neuropsychological development of the offspring are reviewed and plausible mechanisms discussed. Special focus is put on the serotonergic system within developmental and gene-environment frameworks. The review also suggests guidelines for future studies, as well as summarises some of to be-answered questions of relevance to clinical practice. Contradictory findings and paucity of studies on the effects of exposure to low alcohol levels during foetal life for the offspring's neuropsychological development call for large prospective studies, as well as for studies including neuroimaging and multi-omics analyses to dissect the neurobiological underpinnings of alcohol exposure-related phenotypes and to identify biomarkers. Finally, it remains to be investigated whether any safe threshold of alcohol drinking during pregnancy can be identified. This article is protected by copyright. All rights reserved.
... Periodic reliability checks were conducted among examiners. Only the auditory scales were used to assess memory at this phase due to time constraints and our previous findings at 14 years (Willford et al., 2004). The Auditory Immediate Index, composed of the Logical Memory (LM) I and Verbal Paired Associates (VPA) I subtests, is an indication of short-term memory in the verbal auditory domain. ...
... Notably, this study did not show a significant association between maternal smoking or alcohol and memory function. The MHPCD has previously reported the effects of prenatal tobacco exposure on verbal learning and design memory in children at age 10 (Cornelius et al., 2001) and the effects of prenatal alcohol on verbal learning and memory in adolescents at age 14 (Willford et al., 2004). The lack of effect of prenatal tobacco or alcohol on young adult memory in the MHPCD could be explained, in part, by one or more of the following: there is no effect of prenatal tobacco or alcohol exposure on memory function in young adults; an inability to detect subtle changes in memory due to elements of study design or characteristics of the MHPCD cohorts; or "catch up" in the development of cognitive functions in which deficits related to prenatal tobacco or alcohol exposure were reported at younger ages. ...
More Americans are using marijuana than in previous decades but there are concerns over its long-term impact on cognitive functioning, especially memory. The literature on marijuana use and cognitive functioning is mixed, with some studies showing recovery of functioning upon abstinence from the drug and others showing long-term effects that persist. The latter seems especially true for individuals who initiate marijuana at a younger age and engage in more chronic patterns of use. The goal of the current study is to use prospectively collected data on young adults from a prenatal cohort to determine if there is an effect of early and/or current marijuana use on young adult memory, controlling for prenatal exposure to marijuana use, childhood memory deficits, and other significant covariates of memory functioning. At the 22-year follow-up phase of the Maternal Health Practices and Child Development (MHPCD) study, 524 young adults (58% Black, 42% White, 52% female) completed the Wechsler Memory Scale-III. Multiple regression analyses and structural equation modeling were used to determine the effect of marijuana exposure during gestation, early adolescence, and young adulthood on young adult memory function. Results indicated that initiating marijuana use before age 15 placed young adults at greater risk of memory deficits, even after controlling for childhood memory and current marijuana use. First trimester marijuana exposure also indirectly predicted young adult memory function via childhood memory deficits and early initiation of marijuana. These findings highlight the risk of prenatal marijuana exposure and early initiation of marijuana for long-term memory function in adulthood.
... The effects of prenatal alcohol exposure (PAE) on offspring development have been identified in both the human and animal literature (Day and Richardson, 1991a;Jacobson and Jacobson, 2003;Riley, 1990). Effects have been found on offspring growth (Cornelius et al., 2002;Day et al., 1994), cognitive deficits (Richardson et al., 1995;Willford et al., 2004;, and higher levels of activity and attention deficits (Leech et al., 1999). Individuals with PAE are more likely to have both internalizing and externalizing behavior problems (Day et al., 2013;Sood et al., 2001). ...
Purpose. A longitudinal cohort of adolescents who initiated drinking before age 15 were studied to determine which factors distinguished between early initiators who continued to drink (persisters) from those who stopped drinking (desisters). There were 308 early initiators in the total sample (n = 917); 247 were persisters, and 61 were desisters. Method. A stepwise discriminant analysis identified differences between the two groups. Considered risk/protective factors were parenting practices, peer drinking, child and maternal depression, child behavior, prenatal alcohol exposure, home environment, and demographic factors. Results. Desistence was significantly related to African American race and more parental strictness. Exposure to ≥1 drink/day during pregnancy and high levels of autonomy from parents were significant predictors of persistent drinking. Conclusions. Early initiation places adolescents at risk for continued and heavier drinking. Identifying characteristics of those who start early but do or do not continue drinking can inform education programs to better target the most appropriate adolescents.
... Deficits exist across aspects of executive function including planning, set-shifting, cognitive flexibility, response inhibition, and working memory. Alcohol-exposed children also struggle with poor performance in learning new material, both in visual and verbal domains, with stronger support for the latter Pei et al. 2008;Willford et al. 2004;Willoughby et al. 2008). Learning deficits are also apparent in the presence of decreased academic performance across domains, with particular weaknesses seen in areas of mathematical functioning (Glass et al. 2015;Goldschmidt et al. 1996;Howell et al. 2006). ...
This grand rounds manuscript reviews important considerations in developing case conceptualizations for individuals with a history of prenatal alcohol exposure. This case study provides an introduction to fetal alcohol spectrum disorders, diagnostic issues, a detailed description of the individual’s history, presenting symptoms, neuropsychological test results, and an integrated summary. We describe a 9-year-old girl diagnosed with a fetal alcohol spectrum disorder (FASD): Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE). This patient is a composite of a prototypical child who participated as part of a research project at the Center for Behavioral Teratology who was subsequently seen at an outpatient child psychiatry facility.
... Alcohol use in pregnancy has been shown to predict a host of adverse outcomes for children. These have ranged from pervasive developmental damage as manifested in fetal alcohol syndrome resultant from heavy alcohol use in pregnancy (e.g., Larkby & Day, 1997;Mattson & Riley, 1998) to less drastic but nevertheless damaging effects of moderate alcohol exposure (Jacobson & Jacobson, 2002;Willford, Richardson, Leech, & Day, 2004), although results from some studies have been mixed (for review, see e.g., Testa, Quigley, & Eiden, 2003). ...
This study examined whether parental alcohol use in adolescence, adulthood, and for mothers, during pregnancy, was related to their young children's functioning in terms of their on-time development as indicated by the number of developmental areas in which children experienced delay. Observed parenting practices and family socioeconomic status were tested as potential explanatory mechanisms of these links. Data came from the surveys and videotaped observations of a community sample of 123 biological parents and their 1- to 5-year-old children followed longitudinally. Results suggest that the negative association between parental alcohol use and children's development operates primarily through fathers' alcohol use. Additionally, father's adolescent regular alcohol use predicted the family's low socioeconomic status, which in turn predicted less skilled maternal parenting practices and children's developmental delay. This study examined whether parental alcohol use in adolescence, adulthood, and, for moms, during pregnancy was related to their young childrens' functioning in terms of their developmental functioning. Observed parenting practices and family socioeconomic status were tested as potential explanatory mechanisms of these links. There was a negative association between parental alcohol use, and children's development operates primarily through fathers = 92 alcohol use. Additionally, father's adolescent regular alcohol use predicted the family's low SES, which in turn predicted less skilled maternal parenting practices and children's developmental delay. Findings highlight the importance of prevention and intervention efforts aimed at reducing alcohol misuse both in adolescence, even before the young people have children, and in young adulthood. Furthermore, prevention and treatment programs providing support and education in parenting skills to families with a history of alcohol misuse could show benefits across generations.
... Learning and memory in young adolescents (14 years) has been found to be impaired after low to moderate alcohol intake during pregnancy. 92 Socialisation skill deficits became more apparent with age in another study, where an arrest of social development at age six was suggested to be associated with prenatal alcohol exposure. 84 However, maternal intellectual ability significantly influenced all child learning and memory parameters 92 93 and maternal verbal IQ (Peabody picture vocabulary test) was a significant covariate in the association between prenatal alcohol exposure and child verbal IQ and delinquent behaviour in a sample of black Grade 1 students. ...
... Extensive research has also been conducted in adolescence, attesting altered frontal activation, and a broad range of difficulties in higher-order activities consequent to alcohol exposure (Olson et al., 1998;Willford et al., 2001Willford et al., , 2004Mattson and Roebuck, 2002). Executive function deficits are common in drug exposed adolescent offspring (Rasmussen, 2005;Rose-Jacobs et al., 2011;Grant et al., 2013), but it is worth mentioning that some studies report inconsistent results and the specific effects of prenatal exposure remain unclear (Minnes et al., 2014). ...
Parental substance use is a major risk factor for child development, heightening the risk of drug problems in adolescence and young adulthood, and exposing offspring to several types of traumatic events. First, prenatal drug exposure can be considered a form of trauma itself, with subtle but long-lasting sequelae at the neuro-behavioral level. Second, parents' addiction often entails a childrearing environment characterized by poor parenting skills, disadvantaged contexts and adverse childhood experiences (ACEs), leading to dysfunctional outcomes. Young adults born from/raised by parents with drug problems and diagnosed with a Substance Used Disorder (SUD) themselves might display a particularly severe condition in terms of cognitive deficits and impaired personality function. This preliminary study aims to investigate the role of early exposure to drugs as a traumatic event, capable of affecting the psychological status of young drug addicts. In particular, it intends to examine the neuropsychological functioning and personality profile of young adults with severe SUDs who were exposed to drugs early in their family context. The research involved three groups, each consisting of 15 young adults (aged 18–24): a group of inpatients diagnosed with SUDs and exposed to drugs early, a comparison group of non-exposed inpatients and a group of non-exposed youth without SUDs. A neuropsychological battery (Esame Neuropsicologico Breve-2), an assessment procedure for personality disorders (Shedler-Westen Assessment Procedure-200) and the Symptom CheckList-90-Revised were administered. According to present preliminary results, young drug addicts exposed to drugs during their developmental age were characterized by elevated rates of neuropsychological impairments, especially at the expense of attentive and executive functions (EF); personality disorders were also common but did not differentiate them from non-exposed youth with SUDs. Alternative multi-focused prevention and intervention programs are needed for children of drug-misusing parents, addressing EF and adopting a trauma-focused approach.
... We administered the Children's Memory Scale (CMS; Cohen, 1997), as well as an Episodic Memory task developed to test young children Riggins & Rollins, 2015). The CMS is a standardized and well-known measure of episodic memory (e.g., Willford, Richardson, Leech, & Day, 2004;Jack, MacDonald, Reese, & Hayne, 2009), which provides a "gross" measure of episodic memory. The Episodic memory task is a labbased task designed to specifically probe context details surrounding an event, tapping memory for what happened and where it happened. ...
Episodic memory undergoes dramatic improvement in early childhood; the reason for
this is poorly understood. In adults, episodic memory relies on a distributed neural network.
Key brain regions that supporting these processes include the hippocampus, portions of the
parietal cortex, and portions of prefrontal cortex, each of which shows different developmental
profiles. Here we asked whether developmental differences in the axonal pathways connecting
these regions may account for the robust gains in episodic memory in young children. Using
diffusion weighted imaging, we examined whether white matter connectivity between brain
regions implicated in episodic memory differed with age, and were associated with memory
performance differences in 4- and 6-year-old children. Results revealed that white matter
connecting the hippocampus to the inferior parietal lobule significantly predicted children’s
performance on episodic memory tasks. In contrast, variation in the white matter connecting
the hippocampus to the medial prefrontal cortex did not relate to memory performance. These
findings suggest that structural connectivity between the hippocampus and lateral parietal
regions is relevant to the development of episodic memory.
... The effects of prenatal alcohol exposure on offspring development have been identified in both the human and animal literature (Jacobson & Jacobson, 2003;Riley, 1990). Reported effects of prenatal alcohol exposure include growth reduction (Cornelius et al., 2002;Day et al., 1994), cognitive deficits (Richardson et al., 1995;Willford et al., 2004;, and increased rates of activity and attention deficits (Leech et al., 1999). Adolescents with prenatal alcohol exposure have higher rates of psychological symptoms and psychiatric diagnoses 2011) and more behavior problems in young adulthood (Day et al., 2013).Two studies reported a significant association between maternal drinking during pregnancy and increased risk of drinking in their adolescent daughters (Griesler & Kandel, 1998;Pfinder et al., 2014). ...
Adverse conditions, including exposures to drugs and other environmental influences during early development, may affect behaviors later in life. This study examined the role of environmental influences from the gestation and childhood on adolescent drinking behavior. 917 mother/offspring dyads were followed prospectively from pregnancy to a 16-year follow-up assessment. Interim assessments occurred at delivery, 6, 10, and 14 years. Prenatal exposures to alcohol, tobacco, and marijuana were measured during gestation. Data were collected at each phase on childhood environment, including parenting practices, quality of the home environment, maternal depression and hostility, and lifetime exposure to child maltreatment and community violence. Alcohol outcomes were offspring age of drinking initiation and level of drinking at age 16 years. Cox Proportional Hazards ratios were used to model offspring age of drinking initiation. Logistic regression analyses were used to evaluate significant predictors of drinking level. Childhood environment, including less parental strictness, greater exposure to violence and childhood maltreatment, significantly predicted earlier age of alcohol initiation. Level of drinking among the adolescent offspring was significantly predicted by prenatal exposure to alcohol, less parental strictness, and exposures to maltreatment and violence during childhood. Whites and offspring with older mothers were more likely to initiate alcohol use early and drink at higher levels. Early and heavier alcohol use was associated with early exposures to adversity such as prenatal alcohol exposure, and child exposures to maltreatment and violence. These results highlight the importance of environmental adversity and less effective parenting practices on the development of adolescent drinking behavior.
... The effects of prenatal alcohol exposure (PAE) on offspring development have been identified in both the human and animal literature (Day and Richardson, 1991a;Jacobson and Jacobson, 2003;Riley, 1990). Effects have been found on offspring growth (Cornelius et al., 2002;Day et al., 1994), cognitive deficits (Richardson et al., 1995;Willford et al., 2004;, and higher levels of activity and attention deficits (Leech et al., 1999). Individuals with PAE are more likely to have both internalizing and externalizing behavior problems (Day et al., 2013;Sood et al., 2001). ...
... Differences in gender, ethnicity, history and genetics434445 – to name a few – have all been shown to contribute to alcohol's effects, as has the timing, frequency and quantity of alcohol consumption. Although dose per occasion is likely more important than drinking frequency [46], binge drinking does occur in all types of prenatal alcohol consuming women – low/light, moderate and heavy [47]. As most of the published data related to drinking alcohol during pregnancy is collected from mothers either prospectively or retrospectively, it may be inherently flawed, as studies have shown that women tend to under-report (or not report) their alcohol consumption during pregnancy484950. ...
... Hippocampus-Clinical investigations have established a distinct association between gestational ethanol consumption and learning and memory deficits in exposed offspring (Willford et al., 2004). Owing to this vulnerability even moderate levels of ethanol exposure during development are sufficient to reduce hippocampal CA1 and CA3 pyramidal cell number, and alter dendritic morphology. ...
Background:
In utero alcohol, or ethanol (EtOH), exposure produces developmental abnormalities in the brain of the fetus, which can result in lifelong behavioral abnormalities. Fetal alcohol spectrum disorders (FASD) is a term used to describe a range of adverse developmental conditions caused by EtOH exposure during gestation. Children diagnosed with FASD potentially exhibit a host of phenotypes including growth retardation, facial dysmorphology, central nervous system anomalies, abnormal behavior, and cognitive deficits. Previous research suggests that abnormal gene expression and circuitry in the neocortex may underlie reported disabilities of learning, memory, and behavior resulting from early exposure to alcohol (J Neurosci, 33, 2013, 18893).
Methods:
Here, we utilize a mouse model of FASD to examine effects of prenatal EtOH exposure (PrEE), on brain anatomy in newborn (postnatal day [P]0), weanling (P20), and early adult (P50) mice. We correlate abnormal cortical and subcortical anatomy with atypical behavior in adult P50 PrEE mice. In this model, experimental dams self-administered a 25% EtOH solution throughout gestation (gestational days 0 to 19, day of birth), generating the exposure to the offspring.
Results:
Results from these experiments reveal long-term alterations to cortical anatomy, including atypical developmental cortical thinning, and abnormal subcortical development as a result of in utero EtOH exposure. Furthermore, offspring exposed to EtOH during the prenatal period performed poorly on behavioral tasks measuring sensorimotor integration and anxiety.
Conclusions:
Insight from this study will help provide new information on developmental trajectories of PrEE and the biological etiologies of abnormal behavior in people diagnosed with FASD.
... These deficits were present in both children with and without the dysmorphic features of FAS [12,36]. Some studies have suggested that the long-term retention of verbal information is intact in alcohol-exposed children but that the initial encoding processes may be impaired [36,38]. In addition to non-verbal memory difficulties, children with FASD showed visuospatial processing deficits [35], suggesting damage and abnormalities in the frontal-subcortical pathway. ...
One of the unique features of prenatal alcohol exposure in humans is impaired cognitive and behavioral function resulting from damage to the central nervous system (CNS), which leads to a spectrum of impairments referred to as fetal alcohol spectrum disorder (FASD). Human FASD phenotypes can be reproduced in the rodent CNS following prenatal ethanol exposure. Several mechanisms are expected to contribute to the detrimental effects of prenatal alcohol exposure on the developing fetus, particularly in the developing CNS. These mechanisms may act simultaneously or consecutively and differ among a variety of cell types at specific developmental stages in particular brain regions. Studies have identified numerous potential mechanisms through which alcohol can act on the fetus. Among these mechanisms are increased oxidative stress, mitochondrial damage, interference with the activity of growth factors, glia cells, cell adhesion molecules, gene expression during CNS development and impaired function of signaling molecules involved in neuronal communication and circuit formation. These alcohol-induced deficits result in long-lasting abnormalities in neuronal plasticity and learning and memory and can explain many of the neurobehavioral abnormalities found in FASD. In this review, the author discusses the mechanisms that are associated with FASD and provides a current status on the endocannabinoid system in the development of FASD.
... A longitudinal study of low (<3 drinks/week) to moderate (up to 1 drink/day) prenatal exposure levels did not detect verbal learning and memory deficits at younger (through ages 5 and 6 years) ages (Fried and Watkinson, 1990;Fried et al., 1992); however, these impairments became apparent later (ages 10 and 14 years) with FASD (Richardson et al., 2002;Willford et al., 2004). In typically developing children, there is often improvement on executive functioning across adolescent development, possibly related to maturation of the frontal-lobe structures and accompanying organizational strategies that occur during this time period (Anderson, 2002;Blakemore and Choudhury, 2006). ...
... Despite the widely described dose-dependent teratogenic effect of alcohol (Kodituwakku, 2007;Ornoy and Ergaz, 2010), approximately 10% of women aged between 15 and 44 years consume alcohol during pregnancy, with 3% exhibiting a bingedrinking pattern (SAMHSA, 2011). Irrespective of the amount and pattern of consumption, a wealth of clinical evidence describes that prenatal alcohol exposure markedly impairs cognitive, behavioral, and motor functions of offspring (Mattson et al., 1998;Coles et al., 2002;Richardson et al., 2002;Willford et al., 2004;Riley and McGee, 2005;Howell et al., 2006). Maternal moderate to heavy drinking produces a group of pathological conditions termed fetal alcohol spectrum disorder (FASD). ...
The perinatal temporal window is a highly vulnerable time in which environmental factors, such as nutrients, drugs, infections, chemicals, and stress, experienced by the mother can be communicated to the offspring and produce lasting consequences on the new-born brain, thus contributing the evolutionary origin of non-communicable neuropsychiatric diseases. Most of these disorders are preventable, since they are due to modifiable risk factors such as lifestyle and the environment.
... Dysfunctions associated with prenatal exposition to ethanol are collectively termed FASD and are characterized by a range of developmental, cognitive, and neurobehavioral abnormalities (Jones and Smith, 1973;Clarren and Smith, 1978). Moderate maternal drinking (1-2 drinks per day) does not typically cause full-blown FAS; however, it is associated with cognitive and behavioral alterations in the offspring, probably expressed during demanding situations (Streissguth et al., 1990(Streissguth et al., , 1994Willford et al., 2004). ...
Ethanol exposure increases oxidative stress in developing organs, including the brain. Antioxidant treatment during maternal ethanol ingestion improves behavioral deficits in rodent models of fetal alcohol spectrum disorder (FASD). However, the impact of general antioxidant treatment in their adult offspring and the Specific Reactive Species (ROS)-dependent mechanism, are not fully understood. We hypothesized that pre and early postnatal ethanol exposure (PEE) modifies redox homeostasis, in particular NOX2 function during reward signaling in the mesocorticolimbic pathway, which reinforces the effects of alcohol. We developed a FASD rat model which was evaluated during adolescence (P21) and adulthood (P70). We first studied whether redox homeostasis is affected in PEE animals, by analyzing mRNA expression of SOD1, CAT, and Gpx1. We found that PEE reduced the mRNA levels of these three anti-oxidant enzymes in PFC and HIPP at P21 and in the VTA at P70. We also analyzed basal mRNA and protein expression of NOX2 subunits such as gp91phox, p22 phox, and p47 phox, in mesocorticolimbic brain areas of PEE rat brains. At P21, gp91 phox, and p47 phox levels in the VTA were decreased. At P70, gp91 phox mRNA levels was decreased in HIPP and both mRNA and protein levels were decreased in PFC. Since NOX2 is regulated by the N-methyl-D-aspartate Receptor (NMDAR), we analyzed NMDAR mRNA expression and found differential expression of NMDAR subunits (NR1 and NR2B) in the PFC that was age dependent, with levels decreased at P21 and increased at P70. The analysis also revealed decreased NR2B mRNA expression in HIPP and VTA at P70. Offspring from maternal ethanol users consumed 25% more ethanol in a free choice alcohol consumption test than control rats, and showed place preference for an alcohol-paired compartment. In vivo inhibition of NOX2 using apocynin in drinking water, or infusion of blocked peptide gp91 phox ds in the VTA normalized alcohol place preference, suggesting that NOX2 plays an important role in addictive like behavior. Taken together, PEE significantly affects the expression of antioxidant enzymes, NOX2, NMDAR in an age, and brain region dependent manner. Moreover, we demonstrate that NOX2 regulates alcohol seeking behavior.
... In contrast, ARND accounting for most FASD cases has only neurobehavioral manifestations and no discernible physical characteristics [11]. Across subtypes, children with FASD display reduced IQ [12][13][14], poor academic achievement [15][16][17] especially in math [18], and significant disabilities in language, memory, visuospatial, attention, and executive functioning areas [19][20][21][22][23][24][25][26][27]. Within the executive function domain, their impairments reflect poor planning and decision-making and difficulties in working memory and inhibitory control [27][28][29][30][31][32][33]. ...
Children with fetal alcohol spectrum disorder (FASD) exhibit behavioral dysregulation, executive dysfunction, and atypical function in associated brain regions. Previous research shows early intervention mitigates these outcomes but corresponding brain changes were not studied. Given the Alert® Program for Self-Regulation improves behavioral regulation and executive function in children with FASD, we asked if this therapy also improves their neural functioning in associated regions. Twenty-one children with FASD aged 8–12 years were randomized to the Alert®-treatment (TXT; n = 10) or waitlist-control (WL; n = 11) conditions. They were assessed with a Go-NoGo functional magnetic resonance imaging (fMRI) paradigm before and after training or the wait-out period. Groups initially performed equivalently and showed no fMRI differences. At post-test, TXT outperformed WL on NoGo trials while fMRI in uncorrected results with a small-volume correction showed less activation in prefrontal, temporal, and cingulate regions. Groups also demonstrated different patterns of change over time reflecting reduced signal at post-test in selective prefrontal and parietal regions in TXT and increased in WL. In light of previous evidence indicating TXT at post-test perform similar to non-exposed children on the Go-NoGo fMRI paradigm, our findings suggest Alert® does improve functional integrity in the neural circuitry for behavioral regulation in children with FASD.
... Troubles de planification, d'organisation des tâches à 4 ans (Fried et al., 2001). Troubles de la flexibilité et de la planification encore présents à 14 ans (Willford et al., 2004). ...
Introduction : Les études internationales déjà réalisées montrent que la consommation d’alcool, de tabac et de cannabis pendant la grossesse peut entraîner des conséquences graves sur la grossesse, le nouveau-né et à plus long terme, sur l’enfant. Les chiffres de prévalence de ces consommations sont souvent sous évalués en France comme dans le monde. Cette étude est la première étude de prévalence en France où on a réalisé un couplage entre les données déclaratives par la mère et les dosages toxicologiques dans le méconium du nouveau-né. Objectifs de l’étude : (1) Établir la prévalence de la consommation de tabac, d’alcool et de cannabis chez la femme enceinte en couplant des dosages biologiques (cotinine, marqueur du tabac ; 11-nor- Δ9-carboxy-tétrahydrocannabinol (THC-COOH), marqueur du cannabis et Ethyl Glucuronide (EtG), marqueur de l’alcool) chez le nouveau-né (méconium) avec les données de l'interrogatoire chez la mère réalisé notamment avec l'Addiction Severity Index (ASI, questionnaire validé), (2) réaliser les concordances entre résultats biologiques et questionnaires chez la mère, (3) évaluer les facteurs de risques de consommation d’alcool, de tabac et de cannabis, (4) évaluer le profil des femmes qui poursuivent la consommation de tabac après la découverte de la grossesse. Matériel et méthodes : L’étude s’est déroulée sur 2 périodes consécutives en 2010 et en 2011 dans les trois maternités de Rouen (Centre Hospitalier Universitaire de Rouen, hôpital public ; Le Belvédère, clinique privée ; Mathilde, clinique privée). Des enquêteurs ont été chargés de faire passer des questionnaires dont l’ASI à toutes les jeunes accouchées. Les analyses toxicologiques ont été réalisées dans les laboratoires de Lille et de Limoges. Résultats : 993 accouchements ont eu lieu pendant la période d’inclusion. 724 mères ont été incluses et 645 méconium ont été collectés ; 94% des femmes ont accepté de participer à l’étude. La prévalence de la consommation de tabac est rapportée par 21.2% des femmes pendant la grossesse versus 30.1% avant la grossesse, l’alcool par 15.4% pendant la grossesse versus 57.2% avant la grossesse et le cannabis par 1.0% pendant la grossesse versus 2.9% avant la grossesse. La détection de la cotinine est fortement corrélée à la consommation déclarée de tabac pendant le troisième trimestre (valeur Kappa : 0,79). En outre, la détection dans le méconium semble plus précise dans la prédiction des conséquences néonatales de l'exposition prénatale au tabac comparativement à la déclaration de la mère (au niveau de la taille et du périmètre crânien notamment). En revanche, nous avons trouvé une concordance plus faible entre les interviews de la mère pendant le troisième trimestre et les résultats toxicologiques dans le méconium pour l’EtG et le THC-COOH (valeur Kappa : 0.025 et 0.33 respectivement). En ce qui concerne les analyses multivariées : le fait d'avoir fait des études supérieures diminue le risque de consommer du tabac pendant la grossesse. Le risque est également diminué lorsque la grossesse est désirée. Le risque est augmenté lorsque le conjoint consomme du tabac et lorsque la femme dit avoir eu des antécédents dépressifs. De la même façon, la femme a plus de risque de poursuivre le tabac pendant la grossesse si son conjoint fume et il est diminué si elle a fait des études supérieures. Le fait d'avoir eu des périodes importantes pendant lesquelles il y a eu des conflits avec le partenaire de vie ou avec un parent proche augmente le risque de consommer de l'alcool pendant la grossesse. Ce risque est également augmenté lorsque la femme a été traitée avant la grossesse pour des problèmes psychologiques ou émotionnels. Nous n’avons pas trouvé de facteurs protecteurs pour la consommation d’alcool. L’analyse multivariée n’a pas pu être réalisée pour le cannabis au vu du manque de puissance. (...)
... Alcohol induces the cognitive impairment, and cause dysfunctions in behavioural process in children during maternity 21,22 . Low or moderate alcohol exposure cause neurological defects in children during gestation [23][24][25][26] . Prenatal alcohol exposure has been implicated in the delayed development and behavioural problems. ...
Environmental Toxicants have been implicated in the pathogenesis of many neurological disorders. It causes learning and memory disorders. Hippocampus and dentate gyrus are two main brain regions which are mostly affected by neurotoxicants. Reactive oxygen species has been also played a detrimental role in neurodegenerative diseases. Exposure of toxicants alters the antioxidant level and increase the lipid peroxidation level. Neurotoxicants disrupt the blood brain barrier and they also played damaging role in blood related disorders. Neurotoxicants are responsible for mood alteration and neuronal dysfunction. This review will focus on the current epidemiological evidence of neuro developmental toxicity in children and adults, with emphasis on memory and cognitive dysfunction. In this study we report that brain development process is considered to be a critical target of environmental neurotoxicants and provide an overview of recent findings of role of neurotoxicants on developmental neurotoxicity and highlight chemicals of concern, beyond traditionally defined neurotoxicants. Finally, we discuss some useful strategies to encounter the toxic effect including the use of rehabilitation, counselling and medications.
KGMU Journal of Physiology (ISSN 2320-2777)
... It can cause a range of developmental, cognitive, and behavioral problems, which together is known as fetal alcohol spectrum disorder (FASD). FASD is identified through pervasive neuropsychological manifestations , including the disturbance of hippocampus (HP) and neocortex (NC) functions (Mattson et al., 1996b;Clark et al., 2000;Bookstein et al., 2001), which cause learning and memory abnormalities (Mattson et al., 1996a(Mattson et al., , 1999Jacobson and Jacobson, 1999;Clark et al., 2000;Kaemingk and Halverson, 2000;Willford et al., 2004;Rasmussen et al., 2006). Rodents are the most frequently used animal model for FASD research, and a major component of neurodevelopment in this species takes place after birth (Tran et al., 2000;Cronise et al., 2001). ...
Alcohol exposure can affect brain development, leading to long-lasting behavioral problems, including cognitive impairment, which together is defined as fetal alcohol spectrum disorder (FASD). However, the fundamental mechanisms through which this occurs are largely unknown. In this study, we report that the exposure of postnatal day 7 (P7) mice to ethanol activates caspase-3 via cannabinoid receptor type-1 (CB1R) in neonatal mice and causes a reduction in methylated DNA binding protein (MeCP2) levels. The developmental expression of MeCP2 in mice is closely correlated with synaptogenesis and neuronal maturation. It was shown that ethanol treatment of P7 mice enhanced Mecp2 mRNA levels but reduced protein levels. The genetic deletion of CB1R prevented, and administration of a CB1R antagonist before ethanol treatment of P7 mice inhibited caspase-3 activation. Additionally, it reversed the loss of MeCP2 protein, cAMP response element binding protein (CREB) activation, and activity-regulated cytoskeleton-associated protein (Arc) expression. The inhibition of caspase-3 activity prior to ethanol administration prevented ethanol-induced loss of MeCP2, CREB activation, epigenetic regulation of Arc expression, long-term potentiation (LTP), spatial memory deficits and activity-dependent impairment of several signaling molecules, including MeCP2, in adult mice. Collectively, these results reveal that the ethanol-induced CB1R-mediated activation of caspase-3 degrades the MeCP2 protein in the P7 mouse brain and causes long-lasting neurobehavioral deficits in adult mice. This CB1R-mediated instability of MeCP2 during active synaptic maturation may disrupt synaptic circuit maturation and lead to neurobehavioral abnormalities, as observed in this animal model of FASD.
... In general, the research focuses on children with a FASD diagnosis, combined groups of children and adolescents with FASD or PAE, and adolescents with PAE that was assessed for part of the pregnancy, rather than for all three trimesters in pregnancy. Weak verbal memory skills are seen in children with FASD and adolescents with PAE (Becker et al. 1990, Olson et al. 1998, Willford et al. 2004. Hearing loss is also common among children with FASD (McLaughlin et al. 2019). ...
Background
Prenatal alcohol exposure (PAE) is associated with growth deficits and neurodevelopmental impairment including foetal alcohol spectrum disorder (FASD). Difficulties with oral and written communication skills are common among children with PAE; however, less is known about how communication skills of adolescents who have PAE compare with those who do not. Adolescence is a critical time for development, supporting the transition into adulthood, but it is considered a high-risk period for those with FASD.
Aims
We conducted a systematic review to synthesize evidence regarding oral and written communication skills of adolescents with PAE or FASD and how they compare with those with no PAE.
Methods & Procedures
A comprehensive search strategy used seven databases: Cochrane Library, Cinahl, Embase, Medline, PsycInfo, Eric and Web of Science. Included studies reported on at least one outcome related to oral and written communication for a PAE (or FASD) group as well as a no/low PAE group, both with age ranges of 10–24 years. Quality assessment was undertaken.
Main Contribution
Communication skills most often assessed in the seven studies included in this review were semantic knowledge, semantic processing, and verbal learning and memory. These communication skills, in addition to reading and spelling, were commonly weaker among adolescents with PAE compared with those with no/low PAE. However, the findings were inconsistent across studies, and studies differed in their methodologies.
Conclusions & Implications
Our results emphasize that for adolescents with PAE, communication skills in both oral and written modalities should be comprehensively understood in assessment and when planning interventions. A key limitation of the existing literature is that comparison groups often include some participants with a low level of PAE, and that PAE definitions used to allocate participants to groups differ across studies.
What this paper adds
What is already known on the subject
• PAE and FASD are associated with deficits in oral and written communication skills. Studies to date have mostly focused on children with a FASD diagnosis as well as combined groups of children and adolescents with FASD or PAE. There is a gap in what is known about oral and written communication skills of adolescents, specifically, who have PAE or FASD. This has implications for the provision of assessment and supports during a period of increased social and academic demands.
What this study adds to existing knowledge
• This review provides systematic identification, assessment and synthesis of the current literature related to oral and written communication skills of adolescents with PAE compared with those with no/low PAE. The review revealed a small knowledge base with inconsistent methodologies and findings across studies. However, the findings overall highlight that adolescents with PAE have weaker skills in oral and written language than those with no/low PAE. Results are discussed in relation to education, social and emotional well-being, and forensic contexts.
What are the potential or actual clinical implications of this work?
• Findings emphasize that for adolescents with PAE, comprehensive assessment of both oral and written communication skills, through both standardized and functional tasks, should be undertaken. Speech–language pathologists have a key role in assessment with individuals who have PAE.
... In a prospective human cohort, Chen and colleagues (2011) found that alterations in placental expression of COPGIT2 and DHCR24 were associated with 2 infant neurodevelopmental outcomes: reduced infant movement quality and increased signs of physiologic stress (Green et al., 2015;Marsit et al., 2012). IGF2 and NNAT have been shown in animal studies to be important in the development and function of the hippocampus, a brain structure that plays a prominent role in the extensively documented FASD deficits in learning and memory (Coles et al., 2011;Lewis et al., 2015;Mattson and Roebuck, 2002;Willford et al., 2004) and eyeblink conditioning Jacobson et al., 2008Jacobson et al., , 2011b. IGF2 is involved in hippocampal-mediated encoding and retrieval Cordova-Palomera et al., 2014). ...
Background
A growing body of evidence in animal models has implicated alcohol‐induced alterations in epigenetic programming as an important mechanism in fetal alcohol spectrum disorders (FASD). Imprinted genes, a subset of epigenetically‐regulated genes that are sensitive to the prenatal environment, are chiefly involved in growth and neurobehavior. We tested the hypothesis that alterations in placental imprinted gene expression mediate fetal alcohol growth restriction.
Methods
Placental expression of 109 genes previously shown to be imprinted and expressed in the placenta was assessed using the NanoStringTM nCounter Analysis System in flash‐frozen samples from 34 heavy drinkers and 31 control women in Cape Town, South Africa, from whom prospective pregnancy alcohol consumption data had been obtained. Length/height, weight, and head circumference were measured at 6.5 and 12 months and at an FASD diagnostic clinic (at ages 1.1‐4.6 yr) that we organized. Imprinted gene expression between exposed and control placentas was compared using the limma R package. The relation of alcohol exposure to WHO length‐for‐age z‐scores was examined before and after inclusion of expression for each alcohol‐related imprinted gene, using hierarchical mixed regression models with repeated measures.
Results
Heavy drinkers averaged 8 standard drinks on 2‐3 days/week (vs. 0 for controls). Prenatal alcohol exposure was associated with smaller length/height and weight during the postnatal period. Heavy exposure was related to alterations in expression of 11 of 93 expressed imprinted genes, including increased expression of 5 genes found to be negatively associated with growth and decreased expression 3 genes positively associated with growth. Alcohol‐related alterations in expression of 5 genes statistically mediated the effect of prenatal alcohol exposure on length.
Conclusions
These findings identify alcohol‐related alterations in placental imprinted gene expression as potential biomarkers of adverse effect in FASD and suggest that these alterations may play a mechanistic role in fetal alcohol growth restriction. Future studies are needed to determine whether alterations in imprinted gene expression also mediate FASD neurobehavioral deficits and whether such alterations are amenable to intervention.
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... These findings are consistent with past work showing poorer memory function in the pediatric FASD population compared to healthy controls. 6,7,[63][64][65][66] Moreover, deficits in memory observed in this population may be a result of prenatal alcohol related abnormalities in brain region development, including the hippocampus, a region critical for learning and memory and highly susceptible to the damaging effects of alcohol exposure. 33,34,67 The results also fit with previous research demonstrating everyday memory difficulties in children and adults with a variety of clinical disorders that share some similarity in neurocognitive profile to individuals with FASD. ...
Purpose: To investigate whether significant differences exist in everyday memory between youth with Fetal Alcohol Spectrum (FASD) compared with a nonexposed (NE) control group, while controlling for socioeconomic status and other comorbidities.
Methods: Caregiver ratings using the Everyday Memory Questionnaire were obtained for 105 youth (9–17 years of age). Scores were compared between youth with a FASD diagnosis (N = 41; 56% male) and the NE group (N = 64; 53% male) using multivariate analysis of variance.
Results: Significantly poorer scores were found across all domains of everyday memory in youth with FASD (p<0.01 for all comparisons). Findings maintained significance after controlling for group differences in socioeconomic status, presence of learning, and attention disorders, as well as exposure to other teratogens.
Conclusions: This study provides important insights regarding the memory issues that underlie daily functional challenges faced by youth with FASD and the need for future intervention research.
... Despite the widely described dose-dependent teratogenic effect of alcohol (Kodituwakku, 2007;Ornoy and Ergaz, 2010), approximately 10% of women aged between 15 and 44 years consume alcohol during pregnancy, with 3% exhibiting a bingedrinking pattern (SAMHSA, 2011). Irrespective of the amount and pattern of consumption, a wealth of clinical evidence describes that prenatal alcohol exposure markedly impairs cognitive, behavioral, and motor functions of offspring (Mattson et al., 1998;Coles et al., 2002;Richardson et al., 2002;Willford et al., 2004;Riley and McGee, 2005;Howell et al., 2006). Maternal moderate to heavy drinking produces a group of pathological conditions termed fetal alcohol spectrum disorder (FASD). ...
Despite great efforts to warn pregnant women that drugs of abuse impact development of the embryo and the fetus, the use of legal and illegal drugs by childbearing women is still a major public health concern. In parallel with well-established teratogenic effects elicited by some drugs of abuse, epidemiological studies show that certain psychoactive substances do not induce birth defects but lead to subtle neurobehavioral alterations in the offspring that manifest as early as during infancy. Although gender differences in offspring susceptibility have not been fully investigated, a number of longitudinal studies indicate that male and female progeny exposed in utero to drugs of abuse show different vulnerabilities to deleterious effects of these substances in cognitive, executive, and behavioral domains. Here, we briefly review the existing literature focusing on gender differences in the neurobehavioral consequences of maternal exposure to drugs of abuse. Overall, the data strongly indicate that male exposed progeny are more susceptible than female to dysfunctions in cognitive processing and emotional regulation. However, insights into the mechanisms determining this natural phenomenon are not currently available. Our analysis prompts future investigations to implement clinical studies including the influence of gender/sex as a biological variable in the outcome of offspring prenatally exposed to drugs of abuse.
... variety of neurocognitive impairments, such as impaired executive function, working memory, sustained attention, learning and memory, and processing speed (Brown et al., 1991;Burden et al., 2005;Connor et al., 2000;Jacobson et al., 1993;Richardson et al., 2002;Willford et al., 2004). Neurocognitive impairments and externalizing behavior, in turn, might make it more likely for adolescents to seek out alcohol-promoting environments or associate with alcoholpromoting or deviant peer groups (see Sher et al., 2005). ...
Background
Prenatal alcohol exposure has been linked to a host of negative outcomes, although it remains largely unknown whether prenatal exposure leads to earlier age of alcohol use initiation and/or exacerbates early alcohol initiation. The current study examined whether adolescents exposed to heavy drinking during gestation began drinking earlier than their non‐exposed peers and whether earlier age of alcohol re‐exposure in adolescence exacerbated associations with alcohol outcomes.
Methods
Adolescents (17 years of age; 57% female; 96% White) from a longitudinal, population‐based cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC), reported on their age at first whole drink and alcohol behaviors. Adolescents’ mothers also reported on their own heavy drinking during pregnancy (i.e., any consumption of 4+ U.K. units in a drinking day at either 18‐ or 32‐weeks gestation).
Results
Survival analyses indicated that prenatal heavy drinking exposure was not associated with earlier initiation of alcohol use after controlling for potential demographic and parental mental health and substance use confounds. Generalized negative binomial models demonstrated that prenatal heavy drinking exposure moderated associations of alcohol initiation age with alcohol quantity and heavy drinking frequency (but not alcohol frequency or Alcohol Use Disorders Identification Test score), after controlling for the same demographic and parental confounds. Specifically, earlier alcohol initiation was associated with more adverse alcohol outcomes regardless of prenatal exposure. However, the protective associations of delayed alcohol initiation diminished among adolescents exposed to prenatal heavy drinking.
Conclusions
This study provides evidence for interplay between prenatal and postnatal alcohol exposures. Importantly, even when adolescent re‐exposure was delayed, prenatally exposed adolescents appeared to be less protected by such later alcohol initiation.
One of the most tragic outcomes of a woman's addiction to or abuse of alcohol is the effects on the unborn child. Fetal Alcohol Spectrum Disorder (FASD) is common and preventable. Western estimates suggest that FASD affects 1% of the population, and in some communities, the frequency is much higher. FASD is caused by a mother's use of alcohol with or without other substances of abuse that can result in permanent physical and neurodevelopmental impairments to her unborn child. In addition to the primary effects of FASD, affected children are at risk of developing secondary disabilities, including drug and alcohol addictions. It is uncertain what factors, genetic and/or environmental, lead to this addiction. The individual, social, and financial costs are enormous. Multidisciplinary teams have been developed to improve ascertainment of, and standardized approaches to, FASD diagnosis. Strategies and mentorship programs have been developed to better recognize and support women at risk for having FASD children. We discuss issues specific to the treatment and management of FASD adolescents and adults who are struggling with addiction to alcohol and other substances. © 2012 Springer Science+Business Media, LLC. All rights reserved.
This chapter describes a practical and forensically tested approach to conducting adaptive behavior assessments, also known as functional behavior evaluations (FBAs), in the FASD context. From stand-alone FBAs in contexts such as disabilities determination, where mental health evaluators conduct neuropsychological testing as well as adaptive assessments, to “gold standard” multidisciplinary assessments in high-stakes criminal matters involving multiple mental health and medical experts, the ultimate role of the FBA expert is to synthesize and analyze data from multiple sources and methods across the lifespan, integrating neurocognitive/adaptive assessment data with behavioral data to explain brain–behavior connections. The chapter highlights empirically based patterns expected in psychometric testing and adaptive assessment of those with FASD as well as behaviors that typically stem from such patterns, linking that information with neurobehavioral disorder associated with fetal alcohol exposure (ND-PAE), the DSM-5 diagnosis for the central nervous system (CNS) impairment in FASD medical conditions. The chapter concludes with suggestions for mental health professionals on how to present relevant data in reports or testimony in order to describe how the behavior at issue is consistent with developmental trajectory.
Background: Previous studies using Mendelian randomization have found that fetal alcohol exposure may be associated with lower IQ and test scores in childhood.
Objectives: We aim to replicate and extend these findings in Generation R Study, a birth cohort based
in Rotterdam, the Netherlands.
Methods: We used data from Generation R which recruited pregnant women between 2002 and 2006. Alcohol use was assessed via questionnaire during each trimester. IQ was measured in the children between ages 5 and 8 using the Snijders-Oomen Non-Verbal Intelligence Test. Scores from a national standardized test administered around age 12 were used as a measure of cognition. We estimated the associations between ten genetic variants in the mothers previously found to be related to alcohol consumption and metabolism and each of the outcomes. In the children, we also estimated the association between the same genetic variants as well as two polygenic scores for alcohol consumption and the outcomes.
Results: Maternal genetic variants were not found to be related to either outcome but wide confidence intervals did not preclude important effects. A few genetic variants in the children were suggestive of a decrease in IQ. Likewise, one genetic variant and the genetic score had estimates and confidence intervals consistent with increases in standardized test scores.
Conclusions: Our results provide slight support for associations between genetic variants in children related to maternal prenatal alcohol consumption and IQ and cognition outcomes. These findings are in line with two previous studies on this topic.
Since Fetal Alcohol Spectrum Disorder (FASD): Canadian Guidelines for Diagnosis was published as a supplement to the Canadian Medical Association Journal in 2005, new evidence and recommendations have emerged necessitating an update and revision. A survey was sent to all diagnostic centres in Canada (between 2013-2014) to identify the strengths and weaknesses of the 2005 guidelines, and to highlight areas needing revision. The survey was developed and customized by the steering committee to ensure that the necessary information was collected to address the key questions identified for this project. Data supported the addition of sections pertaining to the approach for diagnosis in infants and young children, and adults, as well as improvements to the clarity, validity and implementation of both standardized anthropometric measures and neurodevelopmental assessment domains across the lifespan. A steering committee was tasked to review, analyze and integrate current approaches to diagnosis in an effort to achieve agreement on standard recommendations for best practices in FASD diagnoses using the AGREE II (Appraisal of Guidelines, Research and Evaluation) instrument. The purpose of this paper is to present the updated set of diagnostic guidelines for FASD with recommendations on their application for individuals at risk for alcohol-related effects across the lifespan. The evidence-based guidelines and recommendations are based on widespread consultation with expert practitioners as well as research and community partners in the field and were developed using the Grading or Recommendations, Assessment, Development and Evaluation (GRADE) system to describe both the strength of recommendations and quality of evidence. There was unanimous agreement that the diagnostic process should continue to involve a comprehensive, multidisciplinary approach that includes a history, physical examination, and neurodevelopmental assessment.
This chapter enables the clinicians to hypothesize potential causes of low WISC-IV Integrated scores and recommend skills to be measured. It is organized by cognitive domain: language, executive functioning, memory and learning, and academic achievement. Specific tests that measure these skills are discussed and the relationship between executive functioning and intellectual test scores are presented for some measures. It provides reliabilities, standard errors of measurement, scaled score to standard score conversion, confidence intervals, and directional base rates for VCI versus Recognition. A method for integrating the assessment of intellectual functioning and specific cognitive indicators of reading problems in the early reading success indicator is proposed. The inclusion of test measuring skills suggested to affect WISC-IV and WISC-IV Integrated findings is discussed. The association between the WISC-IV Integrated and other tests is demonstrated by concurrent validity data and the impact of specific cognitive weaknesses on WISC-IV Integrated scores is illustrated by clinical data. The similarities between multiple choice and picture vocabulary subtests have the lowest correlation with current language functioning among the WISC-IV Integrated subtests. The potential deficits of clinical groups in executive functioning are also analyzed with the help of various statistical examples.
Despite several decades of research and prevention efforts, fetal alcohol spectrum disorders (FASD) remain the most common preventable cause of neurodevelopmental disabilities worldwide. Animal and human studies have implicated fetal alcohol-induced alterations in epigenetic programming as a chief mechanism in FASD. Several studies have demonstrated fetal alcohol-related alterations in methylation and expression of imprinted genes in placental, brain, and embryonic tissue. Imprinted genes are epigenetically regulated in a parent-of-origin-specific manner, in which only the maternal or paternal allele is expressed, and the other allele is silenced. The chief functions of imprinted genes are in placental development, somatic growth, and neurobehavior—three domains characteristically affected in FASD. In this review, we summarize the growing body of literature characterizing these changes and discuss potential mechanistic roles for alterations in imprinted gene methylation and/or expression in the teratogenic effects of prenatal alcohol exposure. Future research is needed to examine potential physiologic mechanisms by which alterations in imprinted genes disrupt development in FASD, which may, in turn, elucidate novel targets for intervention. Furthermore, mechanistic alterations in imprinted gene expression and/or methylation in FASD may inform screening assays that identify individuals with FASD neurobehavioral deficits who may benefit from early interventions.
Objective
To characterize patterns of prenatal alcohol exposure (PAE), and determine whether PAE trajectories were associated with behavior from a community-based sample of first-grade children.
Methods
Using data collected as part of the Collaboration of Fetal Alcohol Spectrum Disorders Prevalence study (n=1,663), we performed longitudinal cluster analysis on prenatal alcohol use reported for four time points around conception and pregnancy. From the sample, 638 respondents reported any alcohol use in pregnancy and were included in trajectories for average daily and maximum drinks per drinking day (max DDD). We then estimated the association with behavioral problems measured by the Child Behavior Checklist (CBCL) and Teacher Report Form (TRF) with multivariable linear regression. The reference group had 1,025 children with no reported PAE.
Results
Five trajectories were selected to describe max DDD patterns: very low/discontinuing (n=186), low/discontinuing (n=111), very low/continuing (n=47), med/high (n=245), and high (n=49). Six trajectories best described average daily alcohol use: very low/discontinuing (n=378), very low/continuing (n=98), low/continuing (n=56), low/discontinuing (n=37), medium/high (n=35), and high (n=31). When assessing max DDD trajectories for both the CBCL and TRF, individuals with PAE in the two highest trajectories and the very low/continuing trajectory had more behavioral problems relative to children with no PAE, although confidence intervals for most estimates included the null. PAE modeled as average drinks per day did not predict behavior in any consistent pattern.
Conclusions
In this community-based sample, select PAE trajectories were associated with behavior, even at relatively low levels of PAE that continued later in gestation.
Alcohol dehydrogenase is a critical enzyme in the metabolism of alcohol. Expression of three alleles at the ADH1B locus results in enzymes that differ in turnover rate and affinity for alcohol. ADH1B?2, which is primarily found in Asian and Jewish populations, and ADH1B?3, which is primarily observed in those of African descent, are associated with faster alcohol metabolism. Individuals who carry at least one of these two alleles appear to drink less and have a reduced risk for developing alcohol use disorders. This chapter reviews evidence showing that these alcohol dehydrogenase alleles also protect against alcohol-related neuropathology, particularly in regard to fetal alcohol spectrum disorders. Children and adolescents born to alcohol-drinking mothers who carry at least one of these alleles are less likely to exhibit the effects of prenatal alcohol exposure, including reduced growth, cognitive deficits, and behavioral abnormalities.
Background
Attention deficits caused by prenatal ethanol exposure (PE) are a prevalent condition in fetal alcohol spectrum disorders (FASD). Importantly, the deficits are observed in individuals with FASD who have normal IQs and show no dysmorphic facial features caused by heavy PE. These observations suggest that even moderate PE could lead to attention deficits. This possibility was investigated using a rat model in the present study.
Methods
Pregnant Sprague Dawley rats were administered with ethanol (3 g/kg/day) or vehicle via intragastric gavage on gestational days 8 – 20. The blood ethanol concentration (BEC) in ethanol‐treated rats was 87.7 ± 1.2 mg/dL (1 h after the gavage), similar to the BEC levels reported in other moderate PE studies in rodents. Moderate PE did not produce teratogenic effects on birth weight or litter size. The adult offspring underwent a 2‐choice reaction time task.
Results
Moderate PE led to augmented action impulsivity in both sexes, indicated by more rapid response initiation and increased premature responses. More marked deficits were observed in males than in females. No increases in lapse of attention, assessed by incorrect or relatively slow responses, were observed in rats of either sex with moderate PE. In addition, no deficits in learning or motor function were detected after moderate PE. Interestingly, rats with moderate PE completed more trials than controls.
Conclusions
Our results confirm that moderate PE indeed leads to attention deficits in both sexes, which is demonstrated by greater action impulsivity, but not increased lapses of attention. This effect is different from that of heavy PE observed in our previous study, which is manifested as impaired action impulsivity and lapses of attention in both sexes.
Prenatal alcohol exposure is the leading preventable cause of developmental disorders and intellectual disability. Such exposure can cause lifelong impairments resulting in significant personal and societal costs and thus represents a major public health concern. Individuals with histories of alcohol exposure are often under-identified and underserved due to a variety of factors that hinder diagnostic clarification. The effects of alcohol exposure occur along a spectrum, and therefore the clinical presentation of affected individuals is quite heterogeneous. The neurobehavioral effects associated with prenatal alcohol exposure include impairments in intellectual abilities, academic achievement, neuropsychological performance, and behavioral outcomes. This chapter provides an overview of the neurobehavioral effects of prenatal alcohol exposure and discusses bourgeoning and clinically significant areas of research. These topics include definitional issues, diagnostic outcomes, special education eligibility, considerations for prevention, intervention, school accommodations, prognosis, and moderating factors. This discussion focuses primarily on research conducted on heavy prenatal alcohol exposure, though literature on lower levels of exposure is included when appropriate. Supporting neuroimaging findings are also discussed.
Maternal alcohol consumption during pregnancy is known to produce a spectrum of morphological and neurocognitive outcomes in the offspring. The most severely affected on the spectrum exhibit a cluster of birth defects called fetal alcohol syndrome, which is characterized by a unique pattern of anomalies on the face, prenatal and/or postnatal growth deficiency, and evidence of central nervous system (CNS) dysfunction (Jones et al, Lancet 1:1267–1271, 1973). The characteristic pattern of malformations on the face includes a smooth philtrum, thin upper lip, and short palpebral fissures (see Fig. 1). Children with FASD are usually small in stature, with their height and weight falling below the 10th percentile. The deleterious effects of alcohol on the central nervous system are evidenced by microcephaly and cognitive and behavioral deficits. Children with prenatal alcohol exposure have also been observed to exhibit birth defects involving other systems such as cardiac (e.g., atrial and ventricular septal defects), skeletal (e.g., clinodactyly and camptodactyly), ocular (e.g., strabismus), and auditory (e.g., conductive hearing loss). However, the majority of children on the spectrum display only some or none of the above physical features but exhibit evidence of CNS dysfunction. The term, “alcohol-related neurodevelopmental disorder” (ARND), is used to label neurodevelopmental difficulties in those alcohol-exposed children without clinically discernable physical anomalies (Stratton et al (eds) Fetal alcohol syndrome: diagnosis, epidemiology, prevention, and treatment. National Academy Press, Washington, DC, 1996). Although not a diagnostic label, the term “fetal alcohol spectrum disorders” (FASDs) has been introduced to denote the full spectrum of morphological and neurocognitive outcomes resulting from prenatal alcohol exposure. While estimated prevalence rates of FAS range from .5 to 2 cases per 1,000 live births, the rate of FASD is estimated at 1 per 100 (Sampson et al, Teratology 56:317–326, 1997)
In utero alcohol exposure can disrupt the development of the fetal brain and result in a wide‐range of neurobehavioral outcomes collectively known as fetal alcohol spectrum disorders (FASD). This paper provides a comprehensive review of the cognitive and behavioral outcomes of prenatal alcohol exposure, including domains of general intelligence, executive functioning, language development, learning and memory, adaptive functioning, academic performance, and concurrent psychopathology. In addition, the current status of the neurobehavioral profile of FASD and its potential as a diagnostic tool will be discussed. This article is protected by copyright. All rights reserved.
Blootstelling aan alcohol tijdens de ontwikkeling van de foetus kan in het meest extreme geval leiden tot het Foetaal Alcohol Syndroom (FAS). De diagnosecriteria voor FAS zijn: groeiachterstand, afwijkende gelaatskenmerken en neurologische afwijkingen. Minder duidelijke vormen van deze aandoening zijn de Alcohol-Related Neurodevelopmental Disorder (ARND) en de Alcohol-Related Birth Defects (ARBD), waarbij ARND staat voor de gedrags- en/of cognitieve stoornissen en ARBD voor de lichamelijke afwijkingen zoals hart-, bot- en/of orgaanproblemen. Bovendien zijn er kinderen die schade oplopen die niet ernstig genoeg is om van een syndroom of een afwijking te spreken. Ze komen relatief normaal over, maar kunnen toch leer - en gedragsstoornissen vertonen.
Memory impairments, including spatial and object processing, are often observed in individuals with Fetal Alcohol Spectrum Disorders. The neurobiological basis of memory deficits after prenatal alcohol exposure (PAE) is often linked to structural and functional alterations in the medial temporal lobe, including the hippocampus. Recent evidence suggests that the medial temporal lobe plays a critical role in processing high-order sensory stimuli such as complex objects and their associated locations in space.
Methods
In the first experiment, we tested male rat offspring with moderate PAE in a medial temporal-dependent object-place paired-associate (OPPA) task. The OPPA task requires a conditional discrimination between an identical pair of objects presented at two spatial locations 180° opposite arms of a radial arm maze. Food reinforcement is contingent upon selecting the correct object of the pair for a given spatial location. Adult rats were given a total of 10 trials per day over 14 consecutive days of training. PAE male rats made significantly more errors than male saccharin (SACC) control rats during acquisition of the OPPA task. In Experiment 2, rats performed an object-discrimination task in which a pair of objects were presented in a single arm of the maze. Moderate PAE and SACC control rats exhibited comparable performance. The results suggest that moderate PAE rats can learn to discriminate objects, but are impaired when required to discriminate between objects on the basis of spatial location in the environment.
Objective:
Fetal Alcohol Spectrum Disorder (FASD) is a preventable disorder caused by maternal alcohol consumption and marked by a range of physical and mental disabilities. Although recognized by the scientific and medical community as a clinical disorder, no internationally standardized diagnostic tool yet exists for FASD.
Methods and results:
This review seeks to analyse the discrepancies in existing diagnostic tools for FASD, and the repercussions these differences have on research, public health, and government policy.
Conclusions:
Disagreement on the adoption of a standardised tool is reflective of existing gaps in research on the conditions and factors that influence fetal vulnerability to damage from exposure. This discordance has led to variability in research findings, inconsistencies in government messaging, and misdiagnoses or missed diagnoses. The objective measurement of the timing and level of prenatal alcohol exposure is key to bridging these gaps; however, there is conflicting or limited evidence to support the use of existing measures.
Fetal Alcohol Spectrum Disorders (FASD) represent a large unmet medical need. Exposure of the developing human embryo to alcohol can lead to life-long suffering. Despite the well documented deleterious effects of alcohol on the developing fetus, pregnant women continue to drink alcohol, and FASD remains the leading cause of preventable mental retardation and other behavioral abnormalities. Particularly prevalent are the milder forms of the disease cluster, representing children who do not show obvious physical signs and who may be undiagnosed or misdiagnosed. To develop treatment and diagnostic tools, researchers have turned to animal models. The zebrafish is becoming one of the leading biomedical research organisms that may facilitate discovery of the biological mechanisms underlying this disease and the identification of biomarkers that may be used for diagnosis. Here we review the latest advances of this field, mostly focussing on the discoveries made in our own laboratory and others with zebrafish employed to analyze the effects of moderate to low level of exposure to alcohol. We argue that the zebrafish represents unique advantages, and adding information obtained with this species to the mix of other animal models will significantly increase translational relevance of animal biomedical research for the analysis of human FASD.
An embryo’s in-utero exposure to ethanol due to a mother’s alcohol drinking results in a range of deficits in the child that are collectively termed fetal alcohol spectrum disorders (FASDs). Prenatal ethanol exposure is one of the leading causes of preventable intellectual disability. Its neurobehavioral underpinnings warrant systematic research. We investigated the immediate effects on embryos of acute prenatal ethanol exposure during gestational days (GDs) and the influence of such exposure on persistent neurobehavioral deficits in adult offspring. We administered pregnant C57BL/6J mice with ethanol (1.75 g/kg) (GDE) or saline (GDS) intraperitoneally (i.p.) at 0 h and again at 2 h intervals on GD 8 and GD 12. Subsequently, we assessed apoptosis, differentiation, and signaling events in embryo forebrains (E13.5; GD13.5). Long-lasting effects of GDE were evaluated via a behavioral test battery. We also determined the long-term potentiation and synaptic plasticity-related protein expression in adult hippocampal tissue. GDE caused apoptosis, inhibited differentiation, and reduced pERK and pCREB signaling and the expression of transcription factors Pax6 and Lhx2. GDE caused persistent spatial and social investigation memory deficits compared with saline controls, regardless of sex. Interestingly, GDE adult mice exhibited enhanced repetitive and anxiety-like behavior, irrespective of sex. GDE reduced synaptic plasticity-related protein expression and caused hippocampal synaptic plasticity (LTP and LTD) deficits in adult offspring. These findings demonstrate that binge-like ethanol exposure at the GD8 and GD12 developmental stages causes defects in pERK–pCREB signaling and reduces the expression of Pax6 and Lhx2, leading to impaired cellular differentiation during the embryonic stage. In the adult stage, binge-like ethanol exposure caused persistent synaptic and behavioral abnormalities in adult mice. Furthermore, the findings suggest that combining ethanol exposure at two sensitive stages (GD8 and GD12) causes deficits in synaptic plasticity-associated proteins (Arc, Egr1, Fgf1, GluR1, and GluN1), leading to persistent FASD-like neurobehavioral deficits in mice.
The investigation of memory function using functional magnetic resonance imaging (fMRI) is an expanding field of research. The aim of this study was to demonstrate brain-activity patterns related to a word-pair association task employing a whole-brain EPI sequence. Six right-handed, healthy male volunteers (mean age: 27.5 years) took part in the study. fMRI was performed at a field strength of 1. 5 Tesla with 26-32 slices parallel to the AC-PC line, depending on individual brain size. Distributed brain regions were activated in episodic encoding and retrieval with similarities, but also (distinct) differences in activation patterns. Bilateral prefrontal cortical areas were involved when comparing encoding as well as retrieval to the reference condition (nonsense words). Furthermore, activation was observed in cerebellar areas during encoding, and activation in bilateral parietal areas (precuneus and inferior parietal cortex) was differentially more pronounced during retrieval. The activation of left dorsomedial thalamus during retrieval of high imagery-content word-pair associates may point to the role of this structure in episodic retrieval. The direct cognitive subtraction of encoding minus retrieval yielded a differentially larger left prefrontal activation. There was a differentially higher right prefrontal activation during retrieval than during encoding, underlining the proposed right/left asymmetry for episodic memory processes.
This study examined the relationship of volume of alcohol consumed to the occurrence of alcohol-related problems among male and female college students to develop a gender-specific measure of heavy episodic or binge drinking by college students for public health research. A self-administered survey was mailed to a national representative sample of students at 140 4-year colleges in 40 states and the District of Columbia. A total of 17,592 college students completed the survey. Women who typically drink four drinks in a row were found to have roughly the same likelihood of experiencing drinking-related problems as men who typically drink five drinks in a row. Use of the same standard for both sexes underestimates binge drinking and the negative health risks for women.
The relationship between social and community ties and mortality was assessed using the 1965 Human Population Laboratory survey of a random sample of 6928 adults in Alameda County, California and a subsequent nine-year mortality follow-up. The findings show that people who lacked social and community ties were more likely to die in the follow-up period than those with more extensive contacts. The age-adjusted relative risks for those most Isolated when compared to those with the most social contacts were 2.3 for men and 2.8 for women. The association between social ties and mortality was found to be independent of self-reported physical health status at the time of the 1965 survey, year of death, socioeconomic status, and health practices such as smoking, alcoholic beverage consumption, obesity, physical activity, and utilization of preventive health services as well as a cumulative index of health practices.
Background: Memory deficits are reported commonly in children with fetal alcohol syndrome. However, little is known about nonverbal memory performance in this population.
Methods: The current study examined learning and memory abilities in alcohol-exposed children and nonexposed controls. Multiple verbal and nonverbal measures were used that incorporated repeated learning trials and delayed recall trials. The alcohol-exposed group included children with heavy prenatal alcohol exposure with and without fetal alcohol syndrome. Children ranged in age from 8 to 16 years, and groups were matched on age, sex, ethnicity, and socioeconomic status.
Results: Children with heavy prenatal alcohol exposure displayed deficits in learning and recall of verbal and nonverbal information across all measures. On learning trials, they recalled fewer words and displayed a lower rate of acquisition. However, when we analyzed delayed verbal recall data after controlling for initial verbal learning, group differences were not apparent. The same pattern did not occur for nonverbal information; children with prenatal alcohol exposure recalled less on delayed recall even when we accounted for initial learning.
Conclusions: These data are consistent with previous studies that indicate immediate memory deficits but suggest that, at least for verbal information, delayed recall deficits in this population are better accounted for by deficits in initial learning. Importantly, a different pattern of results was demonstrated for verbal versus nonverbal information, which suggests the need for additional research in this area.
The 1956 adaptation for children of Taylor's Manifest Anxiety Scale, the Children's Manifest Anxiety Scale, was revised to meet current psychometric standards. A 73-item revision draft was administered to 329 school children from grades 1 to 12. Based on item-analysis criteria for rbis greater than or equal to .4 and .30 less than or equal to p less than or equal to .70, 28 anxiety items were retained along with 9 of the original 11 Lie scale items. A cross-validation sample of 167 children from grades 2, 5, 9, 10, and 11 produced a KR20 reliability estimate of .85. Anxiety scores did not differ across grade or race. Females scored significantly higher than males. For the Lie scale, significant differences appeared by grade and race. No sex differences were obtained on the Lie scale. The resulting scale appears useful for children in grades 1 to 12 and may aid in future studies of anxiety as well as assisting the clinician in the understanding of individual children.
The present study compared the recognition memory deficit in different groups of amnesics using scores from a standard test. The data, taken from a literature search, came from 33 studies reporting the performance of amnesic subjects on the recognition memory test (RMT) [77]. A total of 112 amnesic subjects were grouped according to their pathology. In addition, the analysis included subjects with schizophrenia, amygdala damage, or frontal lobe damage. Of these three nonamnesic groups, only the frontal lobe subjects were impaired on both RMT subtests, while the schizophrenics showed a disproportionate impairment for the recognition of faces. The amygdala subjects were also poor at face recognition. Among the amnesic groups, those subjects likely to have multiple sites of pathology (e.g. Korsakoff amnesics, post-encephalitics) were found to be the most impaired on the RMT. In contrast, those amnesics with more focal, limbic lesions in the hippocampus, fornix, or mamillary body region showed much milder deficits on the RMT task, some performing at normal levels. Despite their apparent sparing of recognition, the overall severity of amnesia in those subjects with limbic lesions appeared comparable to that in the remaining amnesics. These findings indicate that deficits on both subtests of the RMT are a frequent but not inevitable component of anterograde amnesia. They also point to a distinct subgroup of amnesias associated with selective damage in the hippocampus or its diencephalic targets, in which there is a relative sparing of recognition under certain test conditions.
Recent neuroimaging studies have provided a wealth of information about areas within prefrontal cortex involved in long-term memory. These studies prompted a proposal by Tulving and colleagues (Tulving, Kapur, Craik, Habib, & Houle, 1994) that prefrontal contributions to memory function are related to laterality differences (the hemispheric encoding/retrieval asymmetry model). This review goes beyond a general characterization of prefrontal lobes to a more specific analysis of distinct areas within the prefrontal cortex. Separate prefrontal areas, sometimes within the same hemisphere, are discussed in terms of selective contributions that they might make to memory retrieval. In the end, it is concluded that a framework which tries to understand prefrontal function in terms of specific areas is a useful complement to models, like HERA, which attempt to find unifying principles across multiple areas.
The CES-D scale is a short self-report scale designed to measure depressive symptomatology in the general population. The items of the scale are symptoms associated with depression which have been used in previously validated longer scales. The new scale was tested in household interview surveys and in psychiatric settings. It was found to have very high internal consistency and adequate test- retest repeatability. Validity was established by pat terns of correlations with other self-report measures, by correlations with clinical ratings of depression, and by relationships with other variables which support its construct validity. Reliability, validity, and factor structure were similar across a wide variety of demographic characteristics in the general population samples tested. The scale should be a useful tool for epidemiologic studies of de pression.
This study considers 2 pathways for the effects of prenatal alcohol on executive function: a direct effect and an indirect effect through prenatal alcohol's effect on IQ. The authors compared 30 men who had been diagnosed with Fetal Alcohol Syndrome (FAS) or Effect (FAE) with 419 young adults participating in a longitudinal prospective study and 15 control participants. Participants were evaluated on 9 tests (including 58 scores) of executive function. For some but not all of the tests in this executive function battery, the decrement in the alcohol exposure group is greater than would be predicted from their IQ scores. The authors found that 3 of 6 Stroop scores, 2 of 4 Trails scores, 9 of 16 Wisconsin Card Sorting scores, 1 of 2 Ruff's Figural Fluency scores, and 2 of 4 Consonant Trigrams scores appear to be particularly sensitive to the direct effects of prenatal alcohol damage for patients with FAS and FAE. The findings suggest that these executive function tests would be particularly useful in clinical evaluations of persons suspected of fetal alcohol damage because they would not simply reflect deficits in IQ or facial stigmata. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Provides 3 tables for clinicians to use to obtain Full Scale IQ estimates in the use of short forms of the Wechsler Adult Intelligence Scale—Revised (WAIS—R). These tables are based on a method presented by J. J. Cyr and B. H. Brooker (see record
1985-02886-001) that jointly considers the validity and reliability of each subtest. None of the IQ equivalents will be in error by more than 1 point. (7 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The population-based Seattle Longitudinal Prospective Study on Alcohol and Pregnancy unites the fields of developmental psychopathology and behavioral teratology. Examining prenatal biological influences on childhood learning problems, this report is the first to extend earlier findings of alcohol-related deficits into late childhood. This follow-up study of 458 singletons assesses the degree to which children's classroom behavior and achievement difficulties at age 11 are predicted by prenatal alcohol exposure across the full spectrum of maternal use. Partial least squares statistical techniques are used to summarize complex multiple measures of exposure and outcome as latent variables. Accounting for many factors potentially important in development, analyses reveal a significant and subtle dose-response relationship between prenatal alcohol exposure and children's school performance a decade later. Maternal binge drinking (five or more drinks per occasion) and drinking during very early pregnancy are particularly salient for children's poorer school performance. A wide variety of problematic classroom behaviors, including attentional, activity, information-processing, and academic difficulties, are salient for prenatal alcohol exposure. Considered within the body of data on alcohol teratogenesis, these findings suggest that prenatal alcohol exposure has an enduring and predictable relationship with developmental difficulties through late childhood. Clinical, research, and public health implications are discussed.
Magnetic resonance imaging was conducted on six children and adolescents with fetal alcohol syndrome and seven matched normal controls. Detailed volumetric analyses demonstrated significant reductions in the cerebral vault, basal ganglia, and diencephalon in the children with fetal alcohol syndrome, compared with control children. In addition, the volume of the cerebellar vault was smaller than controls in 4 of the 6 children with fetal alcohol syndrome, although the group difference did not reach significance. When the basal ganglia were divided into the caudate and lenticular nuclei, both of these regions were significantly reduced in the children with fetal alcohol syndrome. Finally, when the overall reduction in brain size was controlled, the proportional volume of the basal ganglia and, more specificatly, the caudate nucleus was reduced in the children with fetal alcohol syndrome. These results may relate to behavioral findings in both humans and animals exposed to alcohol prenatally.
: Children with heavy prenatal alcohol exposure have well documented deficits in overall cognitive ability. Recently, attention has turned to the executive function (EF) domain in this population. Until recently, comprehensive measures of EF have not been available within one test battery. This study used a battery of tests to assess four domains of EF in alcohol-exposed children.
: The Delis-Kaplan Executive Function Scale was used to evaluate EF in 18 children with heavy prenatal alcohol exposure, with and without a diagnosis of fetal alcohol syndrome (FAS), and 10 nonexposed controls. Children ranged in age from 8 to 15 years. Measures from four domains of executive functioning were analyzed: planning ability, cognitive flexibility, selective inhibition, and concept formation and reasoning. Tasks consisted of primary EF measures as well as measures of secondary component skills.
: Alcohol-exposed children were deficient on EF measures compared with nonexposed controls. Furthermore, in most cases, children with and without the FAS diagnosis did not differ from one another. These deficits were not entirely explainable by concomitant deficits on component skills. Specific impairments were identified within the domains of planning and response inhibition, with additional deficits in abstract thinking and flexibility.
: Deficits in executive functioning were observed in alcohol-exposed children with or without the diagnosis of FAS and in the absence of mental retardation. Performance on these EF tasks provides insight into the cognitive processes driving overall performance and has implications for adaptive and daily functions. These results arc consistent with anecdotal and empirical reports of deficits in behavioral control and with neuroanatomical evidence of volumetric reductions in structures within the frontal-subcortical system in children with heavy prenatal alcohol exposure.
Our previous studies revealed abnormalities on structural MRI (sMRI) in small groups of children exposed to alcohol prenatally. Microcephaly, disproportionately reduced basal ganglia volume, and abnormalities of the cerebellar vermis and corpus callosum were demonstrated. The present study used sMRI to examine in detail the regional pattern of brain hypoplasia resulting from prenatal exposure to alcohol using a higher resolution imaging protocol and larger sample sizes than reported previously. Fourteen participants (mean 11.4 years; eight females, six males) with fetal alcohol syndrome (FAS) and 12 participants (mean 14.8 years; four females, eight males) with prenatal exposure to alcohol (PEA) but without the facial features of FAS were compared to a group of 41 control participants (mean 12.8 years, 20 females, 21 males). Findings of significant microcephaly and disproportionately reduced basal ganglia volumes in the FAS group were confirmed. Novel findings were that in FAS participants, white matter volumes were more affected than gray matter volumes in the cerebrum, and parietal lobes were more affected than temporal and occipital lobes. Among subcortical structures, in contrast to the disproportionate effects on caudate nucleus, the hippocampus was relatively preserved in FAS participants. Differences between the PEA group and controls were generally non-significant; however, among a few of the structures most affected in FAS participants, there was some evidence for volume reduction in PEA participants as well, specifically in basal ganglia and the parietal lobe. There were no group differences in cerebral volume asymmetries. Severe prenatal alcohol exposure appears to produce a specific pattern of brain hypoplasia.
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.
This longitudinal, prospective, population-based study examined the long-term effects of moderate prenatal alcohol exposure on 482 school aged children. Maternal reports of alcohol use obtained during pregnancy were significantly related to child IQ, achievement test scores, and classroom behaviors in second grade children, even after statistical adjustment for appropriate covariates. Consumption of two drinks per day or more on the average was related to a 7-point decrement in IQ in 7-year-old children even after statistically adjusting for appropriate covariates. Low paternal education and more children in the household were identified as environmental factors exacerbating the effect of prenatal alcohol exposure on child IQ. Learning problems were associated with the alcohol “BINGE” pattern of five or more drinks on at least one occasion. This study shows that alcohol use patterns within the social drinking range can have long lasting effects on IQ and learning problems in young school aged children. These patterns should not be interpreted as biologic thresholds. It should also be noted that these are group effects of prenatal alcohol exposure, not necessarily predictable in the individual child, and that for the most part these children were functioning within the normal range of intelligence.
The purpose of this study was to determine whether developmental alcohol exposure could induce permanent neuronal deficits, whether the peak blood alcohol concentration (BAC) influences the severity of the effects, and whether the effects are gender related. Rat pups were reared artifically over postnatal days (PD) 4 through 11 (a period of rapid brain growth, comparable to part of the human third trimester). Alcohol treatments were administered on PD 4 through 9. Patterns of alcohol exposure that produce different peak BACs have been shown to affect differentially the amount of brain weight deficits and neuron loss shortly after the exposure period, so this study investigated whether the pattern of alcohol exposure was also effective in producing permanent deficits. Two groups received a daily alcohol dose of 4.5 g/kg, condensed into either four or two feedings. A third group received a higher daily alcohol dose of 6.6 g/kg administered in 12 uniformly spaced daily feedings. Pups were fostered back to dams on PD 11 and perfused on PD 90. Brain weights were measured, and Purkinje cells and granule cells were counted in each of the 10 lobules of the cerebellar vermis. In the hippocampal formation, cell counts were made of the pyramidal cells of fields CA1 and CA2/3, the multiple cell types of CA4 and the granule cells of the dentate gyrus. The groups receiving the lower daily dose (4.5 g/kg) condensed into either four or two feedings were exposed to higher peak BACs and suffered significant permanent brain weight deficits and neuronal losses, relative to controls. The group receiving the higher daily dose (6.6 g/kg) in continuous fractions had no significant brain weight reductions or neuronal loss. Vulnerability to alcohol-induced neuronal loss varied among regions and cell populations and as a function of peak BAC. In the hippocampus, only the CA1 pyramidal cells were significantly reduced in number and only in group receiving the most condensed alcohol treatment. In the cerebellum, the severity of Purkinje cell and granule cell losses varied among lobules, and Purkinje cell vulnerability appeared to depend on the maturational state of the neuron at the time of the alcohol exposure, with the more mature Purkinje cells being the more vulnerable.
This report summarizes findings from a prospective longitudinal study of the effects of prenatal alcohol exposure on a birth cohort of 500 offspring selected from 1529 consecutive pregnant women in prenatal care by mid-pregnancy at two representative community hospitals. Effects of prenatal alcohol observable on size measures at birth were insignificant after 8 months. Morphometric analysis of facial features identified effects only at the very highest alcohol exposure levels. By contrast, dose-dependent effects on neurobehavioral function from birth to 14 years have been established using partial least squares (PLS) methods jointly analysing multiple measures of both alcohol dose and outcome. Particularly salient effects included problems with attention, speed of information processing, and learning problems, especially arithmetic.
This paper, the second in a series of three, introduces Partial Least Squares (PLS) methods for assessing the effects of moderate levels of prenatal alcohol exposure on performance and behavior in young school-age children. Studies of human behavioral teratology pose statistical problems for which standard multiple regression methods are inadequate. Prenatal alcohol exposure, the teratogenic “dose,” can be assessed only indirectly through a variety of measures of alcohol consumption. Similarly, the behavioral outcomes we examine—IQ, achievement, classroom behavior, and vigilance—are each measured indirectly in terms of multiple items or indicators. We find that a single latent variable, estimated as a linear combination of the measures of alcohol consumption, provides an appropriate measure of “dose” for summarizing the relationships between alcohol exposure and each of the four blocks of outcome variables. A pattern of alcohol consumption emphasizing binge behavior (i.e., reporting average consumption of multiple drinks per drinking occasion, or at least five drinks on any single occasion) in the period prior to recognition of pregnancy is significantly correlated with latent variables computed from each of the four outcome blocks: IQ, academic achievement, classroom behavior and attention/vigilance.
This paper, Part I of a three-part series, reviews the literature on the neurobehavioral effects of prenatal alcohol exposure and describes a large group of tests assembled to assess neurobehavioral outcomes of alcohol teratogenesis in 7-year-old children. This paper presents the distribution of these test scores for our sample and discusses their relationships with an alcohol binge score and with full-scale IQ. This group of tests is suitable for children with a wide range of abilities and provides a broad assessment of neurobehavioral deficits. Part II of this series describes a new method of statistical analysis, Partial Least Squares (PLS), which is particularly well suited to complex multivariate data sets such as these, and with its aid, examines the effects of prenatal alcohol exposure on IQ, achievement, vigilance and classroom behavior, a total of 43 outcome scores. Part III examines prenatal alcohol effects on outcomes from the broad group of 164 scores deriving from 17 neuropsychologic tests, using the Partial Least Squares methodology, and summarizes the implications of our findings for the behavioral teratology of alcohol.
This paper is the third in a three-part series describing an investigation of the effects of prenatal alcohol exposure on the neurobehavioral functioning of 384 children about years old. Here we describe the use of Partial Least Squares for data reduction and analysis of 158 neurobehavioral measures as they relate to 13 aspects of prenatal alcohol exposure. A general alcohol latent variable, emphasizing both binge and regular drinking patterns in the period prior to pregnancy recognition as well as during pregnancy, predicts a pattern of neurobehavioral deficit that includes attentional and memory deficits across both verbal and visual modalities; a variety of “process” variables reflecting poor integration and quality of responses; behavior patterns involving distractibility and poor organization; and an inflexible approach to problem-solving. The prominence of poorer spatial organization and arithmetic as primary outcomes of alcohol teratogenesis suggests a possible “nonverbal learning disability” pattern of deficit associated with prenatal alcohol exposure at the level of social drinking.
The relationship between social and community ties and mortality was assessed using the 1965 Human Population Laboratory survey of a random sample of 6928 adults in Alameda County, California and a subsequent nine-year mortality follow-up. The findings show that people who lacked social and community ties were more likely to die in the follow-up period than those with more extensive contacts. The age-adjusted relative risks for those most isolated when compared to those with the most social contacts were 2.3 for men and 2.8 for women. The association between social ties and mortality was found to be independent of self-reported physical health status at the time of the 1965 survey, year of death, socioeconomic status, and health practices such as smoking, alcoholic beverage consumption, obesity, physical activity, and utilization of preventive health services as well as a cumulative index of health practices.
This paper challenges several arguments for rejecting the rationale of Holmes' and Rahe's Social Readjustment Rating Scale and proposes procedural improvements for three aspects of life-event scale construction: construction of a life-event list, selection of judges, and tests of whether judges agree on their ratings. The proposed procedures are illustrated with the Psychiatric Epidemiology Research Interview (PERI) Life Events Scale. This list of 102 events was developed on the basis of surveys of events actually experienced in various populations. Ratings of the amount of change entailed in these events were collected from a community probability sample. Analysis of these ratings suggests that there are group differences, with more of these differences being due to ethnic background than to sex or social class.
Neuropsychological, neuroanatomical, and electrophysiological data are presented on two subjects with fetal alcohol syndrome (FAS). Both boys had intelligence quotients in the mentally deficient range and were found to have several other severe, specific deficits. Magnetic resonance imaging showed abnormalities of the corpus callosum, and reductions in the size of the basal ganglia and thalamic structures. No focal abnormalities were noted in the electroencephalogram records, although the electroencephalograms of both boys were moderately abnormal for their age group. A multidisciplinary approach to the study of FAS, hopefully will lead to a more unified concept of the disorder and perhaps indicate specific areas of vulnerability.
Cognitive and receptive language development were examined in 135 60-month-old and 137 72-month-old children for whom prenatal exposure to marijuana, cigarettes, and alcohol had been ascertained. Discriminant Function analysis revealed an association between prenatal cigarette exposure and lower cognitive and receptive language scores at 60 and 72 months. This paralleled and extended observations made with this sample at annual assessments at 12 to 48 months of age. Unlike observations made at 48 months, prenatal exposure to marijuana was not associated with the cognitive and verbal outcomes. Relatively low levels of maternal alcohol consumption did not have significant relationships with the outcome variables. The importance of assessing subtle components rather than global cognitive and language skills to detect potential behavioral teratogenic effects of the drugs being examined is discussed.
A rat model of third trimester fetal alcohol exposure was used to determine whether a smaller daily dose of alcohol can induce more severe microencephaly and neuronal loss than a larger dose, if the small dose is consumed in such a way that it produces higher blood alcohol concentrations (BACs). The possibility of regional differences within the developing brain to alcohol-induced neuronal loss was also investigated. Sprague-Dawley rat pups were reared artificially over postnatal Days 4-10 (a period of rapid brain growth similar to that of the human third trimester). Two groups received a daily alcohol dose of 4.5 g/kg, administered either as a 5.1% solution in four of the 12 daily feedings or as a 10.2% solution in two of the 12 feedings. A third group received a higher daily dose (6.6 g/kg) administered as a 2.5% solution in every feeding. Gastrostomy and suckle controls were also reared. On postnatal Day 10, the animals were perfused, and brain weights were obtained. In the hippocampal formation, cell counts were made of the pyramidal cells of fields CA1 and CA2/3, the multiple cell types of CA4 and the granule cells of the dentate gyrus. In the cerebellum, Purkinje cells and granule cells were counted in each of the ten lobules of the vermis. The lower daily dose (4.5 g/kg) condensed into two or four feedings produced high maximum BACs (means of 361.6 and 190.7 mg/dl, respectively) and significant microencephaly and cell loss, relative to controls. The higher daily dose (6.6 g/kg), administered continuously, resulted in low BACs (mean of 39.2 mg/dl) and induced no microencephaly or cell loss. Regional differences in neuronal vulnerability to alcohol were evident. In the hippocampus, CA1 neuronal number was significantly reduced only by the most condensed alcohol treatment, while CA3, CA4, and the dentate gyrus populations were not reduced with any alcohol treatment. In the cerebellum, some lobules suffered significantly greater Purkinje cell loss and granule cell loss than did others. The regions in which Purkinje cells were most mature at the time of the alcohol exposure were the most vulnerable to Purkinje cell loss.
Depressed juveniles show evidence of functional impairment in various cognitive and social domains. Actual school performance seems to be more consistently affected by depression than cognitive and intellectual abilities. In addition, depressed youth appear to be less socially adept than nondepressed peers, although depression does not consistently impair social-cognitive abilities. Indications that depressed youth show mild declines in tested verbal performance over time and that residual problems in social functioning persist after symptomatic recovery suggest that major depression may have negative effects on development in childhood.
Alcohol is a potent teratogen associated with dysmorphology, growth retardation, and neurological damage in children with the full fetal alcohol syndrome (FAS); alcohol is also associated with growth retardation and behavioral alterations in neonates prenatally exposed to various dosages. Questions remain about the long-term consequences of prenatal alcohol exposure. This study reports on the follow-up of a subsample of 68 children, the majority of whom were low income and black (mean age: 5 years, 10 months) who were first evaluated as neonates. Physical and cognitive outcomes of 25 children of women who drank throughout pregnancy [absolute alcohol (AA)/week: mean = 11.80 oz), even after receiving an educational intervention to stop drinking, were compared with outcomes of children in two contrast groups: a) women (n = 22) who stopped drinking (AA/week: mean = 11.46 oz) in the second trimester after an educational intervention but resumed postpartum; and b) women who did not drink during pregnancy and who drank little postnatally (n = 21). Children were compared for alcohol-related birth defects (ARBDs), growth (height, weight, and head circumference), and cognitive, academic, and adaptive measures. Neonatal and current physical measures were correlated to determine predictability of neonatal status. When the effects of age and gender were controlled, children in the continued-to-drink group showed significantly more ARBDs and had smaller head circumferences than those in the other two groups. When current drinking reported by caretakers was controlled, the children who were exposed throughout pregnancy also showed significant and consistent deficits in several areas of intellectual functioning including sequential processing (short-term memory and encoding) and overall mental processing. Alcohol-exposed children displayed significant deficits in preacademic skills when compared with children of nondrinkers, with both alcohol groups deficient in premath and reading skills. There were no differences in adaptive behavior at follow-up. These data suggest that alcohol exposure throughout pregnancy is correlated with persistent physical differences as well as identifiable deficits in sequential memory processes and specific academic skills. However, even when alcohol use is limited to the first part of pregnancy, significant deficits in academic skills and growth parameters are measurable.
This longitudinal, prospective, population-based study examined the long-term effects of moderate prenatal alcohol exposure on 482 school aged children. Maternal reports of alcohol use obtained during pregnancy were significantly related to child IQ, achievement test scores, and classroom behaviors in second grade children, even after statistical adjustment for appropriate covariates. Consumption of two drinks per day or more on the average was related to a 7-point decrement in IQ in 7-year-old children even after statistically adjusting for appropriate covariates. Low paternal education and more children in the household were identified as environmental factors exacerbating the effect of prenatal alcohol exposure on child IQ. Learning problems were associated with the alcohol "BINGE" pattern of five or more drinks on at least one occasion. This study shows that alcohol use patterns within the social drinking range can have long lasting effects on IQ and learning problems in young school aged children. These patterns should not be interpreted as biologic thresholds. It should also be noted that these are group effects of prenatal alcohol exposure, not necessarily predictable in the individual child, and that for the most part these children were functioning within the normal range of intelligence.