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While benchmark dose (BMD) methodology is well‐established for settings with a single exposure, these methods cannot easily handle multidimensional exposures with nonlinear effects. We propose a framework for BMD analysis to characterize the joint effect of a two‐dimensional exposure on a continuous outcome using a generalized additive model while adjusting for potential confounders via propensity scores. This leads to a dose–response surface which can be summarized in two dimensions by a contour plot in which combinations of exposures leading to the same expected effect are identified. In our motivating study of prenatal alcohol exposure, cognitive deficits in children are found to be associated with both the frequency of drinking as well as the amount of alcohol consumed on each drinking day during pregnancy. The general methodological framework is useful for a broad range of settings, including combinations of environmental stressors, such as chemical mixtures, and in explorations of the impact of dose rate rather than simply cumulative exposure on adverse outcomes. [ABSTRACT FROM AUTHOR]

Fetal Alcohol Spectrum Disorders affect up to 5% of the population, with additional children affected by prenatal drug exposures. The majority of these children display symptoms of ADHD and poor emotional dysregulation, a common reason for seeking psychiatric care. However, high prevalence of comorbid look-alike symptoms and limited availability of evidence-based treatments complicates psychiatric decision making in this population. The goal of the current study is to report on the effectiveness of psychotropic medications in a case series of 16 individuals with prenatal alcohol/drug exposure and propose a model for psychiatric care for this population. In addition to traditional subjective reports, an objective continuous performance test (T.O.V.A.®) was used to aid with guiding treatment. We found that T.O.V.A.®-scores improved on average from − 6.5 to − 2.9 with our psychiatric approach (p = 0.03). T.O.V.A.®-measurements were helpful in differentiating ADHD symptoms from comorbid symptoms and to guide decision-making on starting and changing medications. [ABSTRACT FROM AUTHOR]

Background: Most studies of the effects of prenatal alcohol exposure (PAE) on cognitive function have assumed that the dose-response curve is linear. However, data from a few animal and human studies suggest that there may be an inflection point in the dose-response curve above which PAE effects are markedly stronger and that there may be differences associated with pattern of exposure, assessed in terms of alcohol dose per drinking occasion and drinking frequency. Methods: We performed second-order confirmatory factor analysis on data obtained at school age, adolescence, and early adulthood from 2227 participants in six US longitudinal cohorts to derive a composite measure of cognitive function. Regression models were constructed to examine effects of PAE on cognitive function, adjusted for propensity scores. Analyses based on a single predictor (absolute alcohol (AA)/day) were compared with analyses based on two predictors (dose/occasion and drinking frequency), using (1) linear models and (2) nonparametric general additive models (GAM) that allow for both linear and nonlinear effects. Results: The single-predictor GAM model showed virtually no nonlinearity in the effect of AA/day on cognitive function. However, the two-predictor GAM model revealed differential effects of maternal drinking pattern. Among offspring of infrequent drinkers, PAE effects on cognitive function were markedly stronger in those whose mothers drank more than ~3 drinks/occasion, and the effect of dose/occasion was strongest among the very frequent drinkers. Frequency of drinking did not appear to alter the PAE effect on cognitive function among participants born to mothers who limited their drinking to ~1 drink/occasion or less. Conclusions: These findings suggest that linear models based on total AA/day are appropriate for assessing whether PAE affects a given cognitive outcome. However, examination of alcohol dose/occasion and drinking frequency is needed to fully characterize the impact of different levels of alcohol intake on cognitive impairment. [ABSTRACT FROM AUTHOR]

The proposed symptoms for Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE) were evaluated in children who participated in the Collaboration on Fetal Alcohol Spectrum Disorders Prevalence study. Children "at-risk" for ND-PAE (n = 204) were contrasted to children with no prenatal alcohol exposure, alcohol-related dysmorphia or growth deficits (n = 908). Symptoms were defined based on neuropsychological testing using two diagnostic threshold levels (1.0 and 1.5 STD). Individuals at risk for ND-PAE had higher endorsement rates of the self-regulation and adaptive impairments at the 1.0 threshold and of the neurocognitive and self-regulation impairments at the 1.5 threshold. Endorsement of the disorder significantly differed at the 1.0 threshold. Receiver operating characteristic curve analysis indicated that having an IQ below 70 was not predictive of the diagnosis but modifications of the IQ criterion improved predictive validity. Discrimination validity was poor without documentation of PAE which continues to be a necessity for a diagnosis of ND-PAE. [ABSTRACT FROM AUTHOR]

Background: The neurobehavioral health impairments associated with prenatal alcohol exposure are now known to persist through adulthood. However, little is known about how these impairments affect individuals' parenting abilities and the neurobehavioral health of their offspring. This study compares parents with fetal alcohol spectrum disorder (FASD) with socioeconomically matched, nonexposed parents on measures of parenting and family support and assesses the neurobehavioral health of the children in both groups. Methods: Forty‐nine parent–child dyads were recruited from a longitudinal cohort of low socioeconomic status. Measures included the Parenting Styles and Dimensions Questionnaire, Family Support Scale, an in‐depth psychosocial history, the Pediatric Symptom Checklist (PSC; parent and child reports), the Achenbach Child Behavior Checklist (CBCL), a screening psychiatric evaluation of the child, the NIH Toolbox Cognition Battery for Children, The Vineland Adaptive Behavior Scales‐Third Edition caregiver rating form, and the Traumatic Events Screening Inventory (parent and child reports). Results: Cognitive functioning was impaired for both offspring of parents with FASD (x¯ = 81.1, SD = 13.0) and control parents (x¯ = 79.9, SD = 16.1), but despite similar impairments, children of parents with FASD were less likely to have an Individualized Education Plan than controls. Adaptive functioning was adequate for both groups (x¯ = 92.1, SD = 15.4 in exposed vs. x¯ = 94.3, SD = 12.3 in controls) and CBCL and PSC scores in both groups were within normal limits. Parents in both groups showed a predominantly authoritative parenting style. Despite a similar frequency of adverse childhood experiences in both groups, parents with FASD were less likely to recognize their child's adverse experiences. Conclusion: Parents with FASD display notable strengths including a predominantly authoritative parenting style. However, parents with FASD underrecognize child trauma and underutilize developmental services compared to socioeconomically matched controls, despite similar neurocognitive impairments. Impairments in adaptive functioning in parents with FASD may translate into difficulties with child–parent communication and limit both insight into neurobehavioral problems and advocacy skills. There is a need to identify and support parents with FASD to optimize their parenting abilities in the context of their individual strengths and difficulties. [ABSTRACT FROM AUTHOR]

Summary: High levels of prenatal alcohol exposure (PAE) result in significant cognitive deficits in children, but the exact nature of the dose‐response relationship is less well understood. To investigate this relationship, data were assembled from six longitudinal birth cohort studies examining the effects of PAE on cognitive outcomes from early school age through adolescence. Structural equation models (SEMs) are a natural approach to consider, because of the way they conceptualise multiple observed outcomes as relating to an underlying latent variable of interest, which can then be modelled as a function of exposure and other predictors of interest. However, conventional SEMs could not be fitted in this context because slightly different outcome measures were used in the six studies. In this paper we propose a multi‐group Bayesian SEM that maps the unobserved cognition variable to a broad range of observed outcomes. The relation between these variables and PAE is then examined while controlling for potential confounders via propensity score adjustment. By examining different possible dose‐response functions, the proposed framework is used to investigate whether there is a threshold PAE level that results in minimal cognitive deficit. [ABSTRACT FROM AUTHOR]

Background: It is estimated that 1%–5% of children in the United States are affected by prenatal alcohol exposure while only a small percentage are so identified in clinical practice. One explanation for this discrepancy may be the way in which diagnostic criteria are operationalized. Methods: To evaluate the extent to which three commonly used systems for the diagnosis of Fetal Alcohol Spectrum Disorder (FASD) consistently identified children in a community sample, data from the Collaboration on Fetal Alcohol Spectrum Disorders Prevalence (COFASP) study were re‐analyzed. In the data set, there were 2325 children with variables necessary to allow diagnosis by three systems commonly used in North America. These systems were (1) that used by COFASP, which is a revised modification of the Institute of Medicine's recommendations, (2) the 4‐Digit Code, and (3) the most recent Canadian Guidelines. To determine the degree of association among these classifications, the Fleiss Multirater Kappa measure of agreement was applied. Results: Among these three systems, 408 children were classified as FASD, 208 by the CoFASP system, 319 by the 4‐Digit Code, and 28 by the Canadian Guidelines. Agreement among the findings from the three systems varied from slight to fair. Conclusions: These results indicate a lack of consistency in these approaches to FASD diagnosis. Discrepancies result from differences in specifying the criteria used to define the diagnosis, including growth, physical features, neurobehavior, and alcohol‐use thresholds. The question of their relative accuracy cannot be resolved without reference to a measure of validity that does not currently exist, and this suggests the need for a more empirically based diagnostic schema. [ABSTRACT FROM AUTHOR]

Background: The vascular system may be particularly vulnerable to prenatal alcohol exposure (PAE). Alterations in angiogenesis and epigenetic changes to vascular development have been implicated as a probable mechanism for this vulnerability. Methods: We assessed the long‐term impact of prenatal alcohol exposure (PAE) on adult vascular health using a prospective cohort first identified while in utero. Participants with no PAE (n = 37, mean age = 36.7 [SD = 1.6] years) were compared to participants with PAE (n = 51, mean age = 36.3 [SD = 1.7] years). Their vascular health was assessed by arterial blood pressure (BP) and peripheral arterial tonometry, which yields an index of endothelial function (reactive hyperemia index) and a measure of arterial stiffness (augmentation index). Blood samples were collected to assess cholesterol levels and insulin resistance (glucose, hemoglobin A1C, and insulin). Path analysis was used to examine the direct and indirect effects of PAE on vascular health after adjusting for other known physical outcomes. Results: Participants with a history of PAE weighed less, trended towards being shorter, had smaller body mass, and had more alcohol‐related dysmorphic features than those without PAE. Path analysis suggested that the impact of PAE on BP was through its indirect relationships with height, body mass index, and dysmorphic features and resulted in protective effects relative to the Contrast group who were disproportionately overweight. PAE was also found to have a direct negative effect on endothelial function. An index of total alcohol‐related dysmorphic features was negatively had both a direct effect on arterial stiffness and an indirect effect on endothelial function. Conclusions: Prenatal alcohol exposures' impact on vascular function is not independent of other common physical and environmental factors but endothelial function and arterial stiffness seemed most compromised after controlling for these other factors. Level of alcohol‐related dysmorphic features seems to be predictive of more adverse effects than endothelial function and vascular stiffness. [ABSTRACT FROM AUTHOR]

Evidence from animal models and epidemiological studies has linked prenatal alcohol exposure (PAE) to a broad range of long-term cognitive and behavioural deficits. However, there is a paucity of evidence regarding the nature and levels of PAE associated with increased risk of clinically significant cognitive deficits. To derive robust and efficient estimates of the effects of PAE on cognitive function, we have developed a hierarchical meta-analysis approach to synthesize information regarding the effects of PAE on cognition, integrating data on multiple outcomes from six U.S. longitudinal cohort studies. A key assumption of standard methods of meta-analysis, effect sizes are independent, is violated when multiple intercorrelated outcomes are synthesized across studies. Our approach involves estimating the dose–response coefficients for each outcome and then pooling these correlated dose–response coefficients to obtain an estimated “global” effect of exposure on cognition. In the first stage, we use individual participant data to derive estimates of the effects of PAE by fitting regression models that adjust for potential confounding variables using propensity scores. The correlation matrix characterizing the dependence between the outcome-specific dose–response coefficients estimated within each cohort is then run, while accommodating incomplete information on some outcome. We also compare inferences based on the proposed approach to inferences based on a full multivariate analysis. [ABSTRACT FROM AUTHOR]

Background: Fetal alcohol spectrum disorders (FASD) are developmental disabilities that are estimated to occur in 2–5% of elementary school children and that negatively impact a child's ability to function without support. Timely diagnosis‐informed interventions are crucial to optimizing the developmental trajectory of children with FASD. The true prevalence of FASD among children receiving services for developmental disabilities is unknown. Methods: An FASD prevalence study was carried out between 2011 and 2014 among a sample of 5‐ to 7‐year‐old children who were receiving services provided by the California State Regional Center for Developmental Disabilities in San Diego County. Children whose parent or caregiver consented were evaluated using the Collaboration on Fetal Alcohol Spectrum Disorders Prevalence study assessment protocol and classification criteria. Results: Among 216 eligible caregiver‐child dyads, 44 completed assessments that were sufficient to obtain a classification for FASD, including fetal alcohol syndrome (FAS), partial FAS, alcohol‐related neurodevelopmental disorder, or no fetal alcohol spectrum disorder. Fifteen children were classified as meeting the criteria for an FASD. A minimum FASD prevalence rate of 69.4 per 1000 (6.9%) among all eligible children was estimated. None of the children classified as FASD were receiving services because of an FASD diagnosis, and none had previously been diagnosed with FASD. Autism was the most common qualifying diagnosis for which children classified as FASD were receiving services. Conclusions: The 6.9% prevalence estimate among Regional Center clients was higher than the prevalence estimate of 2.3% in the same community among 5‐ to 7‐year‐old children in the general population, though the estimate was based on only 20% of eligible dyads. All children in the sample were receiving Regional Center services for another diagnosis. Barriers to eligibility for services for children with FASD may lead to less than optimum care for these children. Study findings support the facilitation of access to developmental services for children with FASD. An FASD prevalence study was carried out among a sample of 5‐7‐year old children receiving services provided by the California State Regional Center for Developmental Disabilities in San Diego County. Among 216 eligible children, 44 completed assessments, and fifteen met criteria for an FASD. A minimum FASD prevalence rate of 69.4 per 1,000 (6.9%) was estimated. None of the children identified had previously been diagnosed with FASD. Study findings support facilitation of access to developmental services for children with FASD. [ABSTRACT FROM AUTHOR]

Psychiatric symptoms in children with Fetal Alcohol Spectrum Disorders (FASD) present with high prevalence and morbidity, often across symptom domains, e.g. ADHD-like symptoms, emotional dysregulation and sleep problems. Polypharmacy is often used, but no empirically-based guidelines exist regarding optimal treatment for these children. Moreover, stimulant use in these children is controversial as their responsiveness may be different due to altered neural circuitry associated with prenatal alcohol exposure. The objective of this review is to give an overview of existing data on pharmacological treatments of neurobehavioral symptoms in FASD. Our literature review yielded limited and conflicting clinical data on the effectiveness of pharmacological treatments for psychiatric symptoms in children with FASD, with some symptom domains lacking data altogether. We emphasize the need for clinical trials to guide pharmacological treatments in this complex population. [ABSTRACT FROM AUTHOR]

Background: Although the effects of prenatal alcohol exposure (PAE) have been studied extensively, there is relatively little information available on adult mental health functioning among exposed individuals. The current study compares the self‐reported midlife mental health status of individuals who were prenatally exposed to alcohol and diagnosed in childhood with the effects of this exposure with that of unexposed individuals. Methods: Participants (N = 292) were recruited from two longitudinal cohorts in Atlanta and Seattle and asked to complete an Adult Health Questionnaire that surveyed their current health and mental health status. The questionnaire was completed either in‐person or remotely and included questions about current symptoms of depression and anxiety and mental health disorder diagnoses. The analysis compared a Nonexposed Contrast group to those in two exposure groups: (1) Alcohol Exposed with Fetal Alcohol Effect but not meeting criteria for Fetal Alcohol Syndrome (FAS) and (2) Alcohol Affected and meeting criteria for FAS. Results: Both alcohol‐exposed groups reported higher levels of current depressive symptoms and a higher prevalence of diagnoses of depression, anxiety, bipolar disorder, and/or attention deficit/hyperactivity disorder. No differences were noted for psychotic disorders. PAE was also associated with greater environmental stressors, including higher levels of adverse childhood events and lower current socioeconomic status. Path analyses suggested that PAE was indirectly related to mood disorders with its effects being mediated by other environmental factors. Conclusions: PAE is associated with greater rates of mental health disorders in middle adulthood. These outcomes appear to result from multiple stressors that affect individuals made vulnerable by their early alcohol exposure. Clinical outcomes could be improved by prevention efforts directed at preventing prenatal alcohol use and reducing environmental stressors later in life, and by the early identification of PAE and its effects. [ABSTRACT FROM AUTHOR]

Background: This study aimed to develop an efficient and easily calculable risk score that can be used to identify an individual's risk of having been exposed to alcohol prenatally. Methods: Data for this study were collected as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, Phases 2 and 3. Two cohorts (ages 5 to 17 years) completed a comprehensive neurobehavioral battery and a standard dysmorphology exam: a development cohort (DC; n = 325) and a comparative cohort (CC; n = 523). Both cohorts included two groups: those with histories of heavy prenatal alcohol exposure (AE‐DC, n = 121; AE‐CC, n = 177) and a control group that included subjects with minimal or no prenatal alcohol exposure (CON‐DC, n = 204; CON‐CC, n = 346). Behavioral assessments and physical exam data were combined using regression techniques to derive a risk score indicating the likelihood of prenatal alcohol exposure. Subjects were then divided into two subgroups: (1) low risk and (2) high risk. Chi‐square (χ2) determined classification accuracy and ROC curves were produced to assess the predictive accuracy. Correlations between risk scores and intelligence quotient and executive function scores were calculated. Results: Subjects were accurately classified in the DC (χ2 = 78.61, p < 0.001) and CC (χ2 = 86.63, p < 0.001). The classification model also performed well in the DC (ROC = 0.835 [SE = 0.024, p < 0.001]) and CC (ROC = 0.786 [SE = 0.021, p < 0.001]). In the AE‐CC and CON‐CC, there were modest but significant associations between the risk score and executive function (AE‐CC: r = −0.20, p = 0.034; CON‐CC: r = −0.28, p < 0.001) and intelligence quotient (AE‐CC: r = −0.20, p = 0.034; CON‐CC: r = −0.28, p < 0.001). Conclusion(s): The risk score significantly distinguished alcohol‐exposed from control subjects and correlated with important cognitive outcomes. It has significant clinical potential and could be easily deployed in clinical settings. [ABSTRACT FROM AUTHOR]

Effects of prenatal alcohol exposure (PAE) are rarely measured in preschool children due to relative insensitivity of assessment methods at this age. To examine the potential of a nonverbal battery in early identification of cognitive problems in alcohol-exposed children, 291 prospectively identified Ukrainian children were evaluated using a test battery focusing on early executive functioning (EF) and visuospatial skills, areas of cognitive development particularly sensitive to PAE in older children. Tests included the Differential Ability Scales, 2nd Edition (DAS-2) and several NEPSY/NEPSY-II subtests, standardized in the United States. Others were adapted from commonly used non-standardized neuropsychological measures of EF (Preschool Spatial Span, Imitation Hand Game, A not B, Delayed Attention, Subject Ordered Pointing). Children in two sites in Ukraine, Rivne and Khmelnitsky, were tested at 3 ½-4 ½ years to identify effects of PAE. Although most children performed within the average range, Alcohol-Exposed preschoolers had lower scores on DAS-II Summary Scores as well as on specific subtests. To evaluate the effects of alcohol dose during the pre-pregnancy recognition period and during mid-gestation of pregnancy, generalized linear regression models were used controlling for demographic and individual variables. In addition to DAS-II variables, measures reflecting sustained attention, working memory and ability to shift cognitive set were impacted by alcohol dose. Early executive function appears to subsume these performance differences. In conclusion, findings indicate that the effects of PAE can be identified in the preschool period and reliably measured using tests assessing nonverbal and spatial skills supported by executive functioning. [ABSTRACT FROM AUTHOR]

Background: Cognitive and behavioral sequelae of prenatal alcohol exposure (PAE) continue to be prevalent in the United States and worldwide. Because these sequelae are also common in other neurodevelopmental disorders, researchers have attempted to identify a distinct neurobehavioral profile to facilitate the differential diagnosis of fetal alcohol spectrum disorders (FASD). We used an innovative, individual participant meta‐analytic technique to combine data from six large U.S. longitudinal cohorts to provide a more comprehensive and reliable characterization of the neurobehavioral deficits seen in FASD than can be obtained from smaller samples. Methods: Meta‐analyses were performed on data from 2236 participants to examine effects of PAE (measured as oz absolute alcohol/day (AA/day)) on IQ, four domains of cognition function (learning and memory, executive function, reading achievement, and math achievement), sustained attention, and behavior problems, after adjusting for potential confounders using propensity scores. Results: The effect sizes for IQ and the four domains of cognitive function were strikingly similar to one another and did not differ at school age, adolescence, or young adulthood. Effect sizes were smaller in the more middle‐class Seattle cohort and larger in the three cohorts that obtained more detailed and comprehensive assessments of AA/day. PAE effect sizes were somewhat weaker for parent‐ and teacher‐reported behavior problems and not significant for sustained attention. In a meta‐analysis of five aspects of executive function, the strongest effect was on set‐shifting. Conclusions: The similarity in the effect sizes for the four domains of cognitive function suggests that PAE affects an underlying component or components of cognition involving learning and memory and executive function that are reflected in IQ and academic achievement scores. The weaker effects in the more middle‐class cohort may reflect a more cognitively stimulating environment, a different maternal drinking pattern (lower alcohol dose/occasion), and/or better maternal prenatal nutrition. These findings identify two domains of cognition—learning/memory and set‐shifting—that are particularly affected by PAE, and one, sustained attention, which is apparently spared. [ABSTRACT FROM AUTHOR]

Background: Few studies have investigated the partner's influence on risk factors such as alcohol consumption and depression during pregnancy. Partner substance use and lower relationship satisfaction predict higher maternal alcohol use and depressive symptoms. Because prenatal alcohol use and maternal depression affect infant outcomes, it is imperative to examine how the partner affects these maternal risk factors. The current study examined the effect of a latent construct of partner influence on maternal alcohol use and depressive symptoms, and the effects on infant development of these maternal factors. Methods: Participants were 246 pregnant women from 2 sites in Western Ukraine from whom longitudinal data were collected as part of a multisite study. In the first trimester, mothers reported on relationship satisfaction, partner substance use, and socioeconomic status (SES). In the third trimester, they reported on alcohol use and depressive symptoms. Infants were assessed using the Bayley Scale of Infant Development (average age = 6.93 months). A latent construct titled partner influence was formed using partner substance use and measures of relationship satisfaction, including the frequency of quarreling, happiness in the relationship, and the ease of talking with the partner. Using structural equation modeling, a model was specified in which partner influence and SES predicted maternal alcohol use and depressive symptoms, which in turn predicted infant neurodevelopmental outcomes. Results: Higher partner influence significantly predicted lower prenatal alcohol use and lower depressive symptoms, controlling for the effect of SES. Higher maternal prenatal alcohol use significantly predicted lower infant mental and psychomotor development. Maternal depressive symptoms did not predict infant development over and above the effect of alcohol use. Conclusions: Partner influence is an important contributor to prenatal alcohol use and maternal depressive symptoms, over and above the effect of SES. The significant paths from prenatal alcohol exposure to infant neurodevelopmental outcomes underscore the importance of partner influence during pregnancy. [ABSTRACT FROM AUTHOR]

Objective: Evidence suggests that prenatal alcohol exposure (PAE) may adversely impact insulin production and signaling but there is limited information on the range of these effects and their future health consequences. Method: A prospective cohort of predominantly African‐American individuals identified while in utero and followed into adulthood were used to evaluate differences in various indicators of diabetes, including fasting plasma glucose, hemoglobin A1c (HbA1c), and insulin levels. The homeostatic model assessment of insulin resistance (HOMA‐IR) was also computed. Body mass index (BMI) was calculated and normal defined as < 25 kg/m2. Participants were categorized as having PAE (n = 39) if their mothers drank at least 1 ounce of absolute alcohol per week or more during the 1st trimester of pregnancy and as Controls (n = 22) if their mothers reported abstaining from alcohol consumption during pregnancy. Results: Mean age of the sample was 36.0 ± 1.5 years. Indices of glucose metabolism, including fasting plasma glucose and hemoglobin A1c levels, did not vary by group status but insulin levels and HOMA‐IR values varied by group status and BMI level. PAE individuals with a normal BMI had lower insulin levels than Controls. However, in PAE subjects, there was a steeper increase in insulin levels relative to their BMI than in Control subjects. A cluster of 5 PAE cases had low levels of insulin and 4 of the 5 had severe cognitive impairment. Conclusions: The bidirectional effects on insulin level and insulin resistance associated with PAE may indicate differential rates of diabetes disease impact or differential PAE impact in the brain and peripheral areas involved in insulin production and signaling. These alterations may contribute to the metabolic disease risk associated with PAE. [ABSTRACT FROM AUTHOR]

Background: Rating scales are designed to complement traditional performance‐based measures, and both can provide useful information about the functioning of youth with histories of prenatal alcohol exposure. Few studies, however, have compared ratings from multiple informants or the relationship between these subjective rating scale scores and the objective results from laboratory performance‐based scales. Methods: The current study addressed both of these questions in 3 study groups: children with histories of prenatal alcohol exposure (n = 47), attention‐deficit/hyperactivity disorder (ADHD; n = 41), and typically developing controls (CON; n = 73). All subjects completed a standardized neuropsychological test battery, including laboratory measures of executive functioning and a self‐report measure of executive function behaviors. Parents and teachers completed corresponding rating scales of executive function behaviors for each subject. This study assessed the relationship between these behavior rating scales and corresponding neuropsychological tests, and interrater agreement among the multiple informants. Results: Weak correlations were found between the rating scales and laboratory measures, indicating poor convergent validity for the behavior rating scale. Interrater reliability was found but it differed by group. Agreement was found between parent and teacher ratings for children with prenatal alcohol exposure, whereas teacher–child agreement was found for those with ADHD. Conclusions: Findings from this study indicate that behavior ratings can be used to supplement laboratory measures but may not be measuring cognitive abilities regardless of whether a clinical diagnosis is present. A multimethod approach should be used when measuring skills in this domain. This was one of the first studies to examine cross‐informant agreement in a sample of children with prenatal alcohol exposure. Further research is necessary to understand why interrater agreement differed for children with prenatal alcohol exposure and those with ADHD. [ABSTRACT FROM AUTHOR]

Background: Prenatal alcohol exposure (PAE) has been identified as one of the leading preventable causes of developmental disabilities, but early identification of those impacted has been challenging. This study evaluated the use of infant cardiac orienting responses (CORs), which assess neurophysiological encoding of environmental events and are sensitive to the impact of PAE, to predict later fetal alcohol spectrum disorder (FASD) status. Methods: Mother–infant dyads from Ukraine were recruited during pregnancy based on the mother's use of alcohol. Participants (n = 120) were then seen at 6 and 12 months when CORs were collected and in the preschool period when they were categorized as having (i) fetal alcohol syndrome (FAS), (ii) partial FAS (pFAS), (iii) alcohol‐related neurodevelopmental disorder (ARND), (iv) PAE and no diagnosis, or (v) no PAE and no diagnosis. To assess CORs, stimuli (auditory tones and pictures) were presented using a fixed‐trial habituation/dishabituation paradigm. Heart rate (HR) responses were aggregated across the first 3 habituation and dishabituation trials and converted to z‐scores relative to the sample's mean response at each second by stimuli. Z‐scores greater than 1 were then counted by condition (habituation or dishabituation) to compute a total risk index. Results: Significant group differences were found on total deviation scores of the CORs elicited from visual but not auditory stimuli. Those categorized as pFAS/FAS had significantly higher total deviation scores than did those categorized as ARND or as having no alcohol‐related diagnosis with or without a history of PAE. Receiver operating characteristic curve analysis of the visual response yielded an area under the curve value of 0.765 for predicting to pFAS/FAS status. Conclusions: A score reflecting total deviation from typical HR during CORs elicited using visual stimuli in infancy may be useful in identifying individuals who need early intervention as a result of their PAE. [ABSTRACT FROM AUTHOR]

Background: In children with prenatal alcohol exposure, spatial working memory is affected and brain regions important for spatial working memory performance exhibit atypical neurodevelopment. We therefore hypothesized that children with prenatal alcohol exposure may also have atypical development of spatial working memory ability. Methods: We examined the relation between spatial working memory and age using a cross‐sectional developmental trajectory approach in youth with and without histories of heavy prenatal alcohol exposure. The Cambridge Neuropsychological Test Automated Battery Spatial Working Memory subtest was administered to children 5.0 to 16.9 years old. Results: While the controls and children with prenatal alcohol exposure showed similar performance at younger ages, larger group differences were observed in older children. This effect was replicated in a separate sample. Conclusions: The atypical brain development that has previously been reported in children with heavy prenatal alcohol exposure may have clinically relevant implications for cognitive development; however, longitudinal cognitive analyses are needed. [ABSTRACT FROM AUTHOR]

Background: The effects of prenatal alcohol exposure (PAE) are conceptualized as fetal alcohol spectrum disorder, with fetal alcohol syndrome (FAS) as the most severe. Many find it more difficult to characterize behavioral and cognitive effects of exposure on the central nervous system when physical signs are not present. In the current study, an operational definition of alcohol‐related neurodevelopmental disorder (ARND) was examined to determine its usefulness in discrimination of children classified as ARND based on behavior (ARND/B) and cognition (ARND/C) from children in 4 contrast groups: (i) children exposed to study‐defined "risky drinking"; (ii) children with any reported PAE; (iii) children classified as "Higher Risk" for developmental problems; and (iv) children classified as "Lower Risk." Methods: A total of 1,842 children seen as part of a surveillance study (J Am Med Assoc, 319, 2018, 474) were evaluated for alcohol exposure and physical characteristics of FAS, and completed neurodevelopmental testing. Ninety‐one were identified as either ARND/B or ARND/C and contrasted with other groups to further identify distinguishing patterns. Multinomial logistic regression (MLR) was used to examine the accuracy of classification and to identify factors contributing to such classification. Results: Children described as ARND/C were distinct from other groups based on cognition and behavior as well as demographic factors (e.g., age, race, SES), child characteristics (e.g., gestational age; sex), and other drug exposures, while those described as ARND/B differed only on behavior and other drug exposures. MLR models successfully discriminated ARND groups from children in other groups with accuracy ranging from 79% (Higher Risk) to 86.7% (Low Risk). Conclusions: ARND has been a subject of debate. This analysis suggests the effects of alcohol on behavior and cognition even in the absence of the characteristic facial features and growth deficiency that can be identified. The results also indicate that it may be possible to distinguish such children from those in other high‐risk groups. [ABSTRACT FROM AUTHOR]

The positive relationship between socioeconomic status (SES) and cognitive performance is mediated, in part, by differences in brain structure in typically developing youth. Associations between brain regions that relate to SES overlap with brain regions known to be sensitive to prenatal alcohol exposure (PAE). Animal models demonstrate that PAE attenuates neural and cognitive benefits of early life enrichment. However, whether or not environmental factors related to SES are associated with brain development in youth affected by PAE remains unknown in humans. Methods: T1-weighted magnetic resonance imaging (MRI) scans were obtained in participants with PAE and compared to age- and sex- matched Controls (n = 197, 48% with PAE, 44% girls, 6.5–17.7 years old). General linear modeling was utilized to examine associations between SES and subcortical brain volumes for youth with PAE compared to Controls. Results: Group by SES interactions were observed within the hippocampus (HPC), nucleus accumbens (NAc) and ventral diencephalon (vDC) (corrected p values <0.05), where positive associations (e.g., higher SES related to larger subcortical volumes) were observed within Controls, but not youth with PAE. Post hoc analyses examined associations between SES and brain volumes within each group independently, and revealed widespread positive associations among Controls (Amyg, HPC, NAc, Pallidum, Putamen, vDC), but not youth with PAE. Across both groups, larger subcortical volumes were related to higher cognitive performance. Conclusion: Typically developing youth exhibit increased subcortical volumes with increased SES, and surprisingly, this relationship is absent in adolescents with PAE. Findings suggest that subcortical brain volumes are neurocognitively relevant in both groups. The present results expand our understanding of the impact of PAE on the developing human brain within varying environmental contexts, and may inform novel environmental interventions that aim to improve, in part, on-going disruptions in brain development among youth with PAE. Our study highlights novel complexities in the pursuit to understand SES-brain associations, as we provide evidence that SES matters for brain outcomes among typically developing youth, and possibly not as much on an already altered brain as a result of PAE. [ABSTRACT FROM AUTHOR]

Objective: Polyunsaturated fatty acids are vital for optimal fetal neuronal development. The relationship between maternal alcohol consumption and smoking with third trimester plasma fatty acids were examined and their association with Fetal Alcohol Spectrum Disorders (FASD).Methods: Moderate to heavy alcohol-using and low/unexposed comparison women were recruited during mid-pregnancy from two prenatal clinics in Ukraine. The participants' infants underwent physical and neurobehavioral exams prior to one-year of age and classified as having FASD by maternal alcohol consumption and neurobehavioral scores. A subset of mother-child pairs was selected representing three groups of cases and controls: Alcohol-Exposed with FASD (AE-FASD, n = 30), Alcohol-Exposed Normally Developing (AE-ND, n = 33), or Controls (n = 46). Third trimester maternal plasma samples were analyzed for fatty acids and levels were compared across groups.Results: The percent of C18:0 (p < 0.001), arachidonic acid (AA, C20:4n-6, p = 0.017) and C22:5n-6 (p = 0.001) were significantly higher in AE-FASD women than controls or AE-ND women. Alcohol-exposed women who smoked had lower C22:5n-3 (p = 0.029) and docosahexaenoic acid (DHA, C22:6n-3, p = 0.005) and higher C22:5n-6 (p = 0.013) than women consuming alcohol alone or abstainers.Conclusion: Alterations in fatty acid profiles were observed in moderate to heavy alcohol-consuming mothers with infants classified with FASD compared to alcohol-exposed normally developing infants or controls. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests that cytokine imbalances may be at the root of deficits that occur in numerous neurodevelopmental disorders, including schizophrenia and autism spectrum disorder. Notably, while clinical studies have demonstrated maternal cytokine imbalances with alcohol consumption during pregnancy-and data from animal models have identified immune disturbances in alcohol-exposed offspring-to date, immune alterations in alcohol-exposed children have not been explored. Thus, here we hypothesized that perturbations in the immune environment as a result of prenatal alcohol exposure will program the developing immune system, and result in immune dysfunction into childhood. Due to the important role of cytokines in brain development/function, we further hypothesized that child immune profiles might be associated with their neurodevelopmental status.Methods: As part of a longitudinal study in Ukraine, children of mothers reporting low/no alcohol consumption or moderate-to-heavy alcohol consumption during pregnancy were enrolled in the study and received neurodevelopmental assessments. Group stratification was based on maternal alcohol consumption and child neurodevelopmental status resulting in the following groups: A/TD, alcohol-consuming mother, typically developing child; A/ND, alcohol-consuming mother, neurodevelopmental delay in the child; C/TD, control mother (low/no alcohol consumption), typically development child; and C/ND, control mother, neurodevelopmental delay in the child. Forty cytokines/chemokines were measured in plasma and data were analyzed using regression and constrained principle component analysis.Results: Analyses revealed differential cytokine network activity associated with both prenatal alcohol exposure and neurodevelopmental status. Specifically, alcohol-exposed children showed activation of a cytokine network including eotaxin-3, eotaxin, and bFGF, irrespective of neurodevelopmental status. However, another cytokine network was differentially activated based on neurodevelopmental outcome: A/TD showed activation of MIP-1β, MDC, and MCP-4, and inhibition of CRP and PlGF, with opposing pattern of activation/inhibition detected in the A/ND group. By contrast, in the absence of alcohol-exposure, activation of a network including IL-2, TNF-β, IL-10, and IL-15 was associated with neurodevelopmental delay.Conclusions: Taken together, this comprehensive assessment of immune markers allowed for the identification of unique immune milieus that are associated with alcohol exposure as well as both alcohol-related and alcohol-independent neurodevelopmental delay. These findings are a critical step towards establishing unique immune biomarkers for alcohol-related and alcohol-independent neurodevelopmental delay. [ABSTRACT FROM AUTHOR]

Relationships between neurodevelopmental functioning and hemodynamic changes in the prefrontal cortex (PFC) were contrasted between children with prenatal alcohol exposure (PAE) and children who differed relative to their history of PAE and the presence of other neurodevelopmental impairment. For all groups, deoxygenated hemoglobin (HBR) levels in the medial PFC area were negatively related to externalizing problems and levels in the medial and right lateral PFC were positively related to errors on a cognitive inhibition task. Hemodynamic changes in the medial and right lateral PFC of children with PAE demonstrated stronger relationships to aspects of executive functioning relative to contrast groups. [ABSTRACT FROM AUTHOR]

Background: This study examined the relationship between prenatal exposure to alcohol, manifested through fetal alcohol syndrome (FAS) and pFAS, and hypertension in children and adolescents. Methods: This study was designed to analyze the association between fetal alcohol spectrum disorders (FASD) Status and hypertension status. FAS/pFAS‐diagnosed respondents (n = 125) were collected from a FASD Clinical database in Atlanta, Georgia. Non‐FAS/pFAS respondents (n = 500) were taken from the National Health and Nutrition Examination Survey (NHANES). Chi‐square analyses were used to examine the extent to which FASD status, sex, race/ethnicity, medication use, and obesity status each related to hypertension status. A logistic regression was performed analyzing the relationship between FASD status (y/n: independent) and hypertension status (y/n: dependent) while controlling for age, sex, race/ethnicity, medication use, and obesity status. Results: Univariate relationships between hypertension status and FASD status (OR = 8.46, p < 0.001), medication use (OR = 3.25, p < 0.001), and obesity status (OR = 3.03, p = 0.02) proved to be statistically significant (p < 0.05). FASD status significantly predicted hypertension status (β = 2.31, OR = 10.06, p < 0.001) after accounting for age, sex, race/ethnicity, medication use, and obesity status. Conclusions: The major findings of this study suggest a significant relationship between FASD and hypertension in youth. Race/ethnicity and obesity also proved important in predicting hypertensive blood pressure readings independent of FASD diagnosis. Further research is needed to isolate prenatal alcohol exposure (PAE) as a factor promoting increased hypertension and to assess the risk for hypertension in alcohol‐affected adults. The relationship between FASD and hypertension in clinically‐referred children and adolescents was investigated. Logistic regression indicated a significant predictive relationship between FASD and elevations in both systolic and diastolic blood pressure after controlling for age, sex, race/ethnicity, medication use, and obesity status. Race/ethnicity and obesity also proved significant in predicting hypertension independently of FASD diagnosis. Further research is needed to isolate prenatal alcohol exposure as a factor in youth hypertension and to assess the risk for hypertension in alcohol‐affected adults. [ABSTRACT FROM AUTHOR]

Background: Adaptive function and general intellectual function are two important and often correlated domains. While youth with prenatal alcohol exposure frequently demonstrate impairments in both domains, it is not clear whether the relation between these domains is consistent across levels of ability or whether, for example, adaptive function is less affected by intellectual function at higher ability levels. The aim of the current study was to test this relation in youth with and without prenatal alcohol exposure. Methods: As part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, Phase II, subjects with heavy prenatal alcohol exposure (AE) and nonexposed subjects with and without other clinical conditions or concerns (CON) completed a comprehensive neurobehavioral battery. Multiple regression analyses tested the relation between full scale IQ (FSIQ) and overall adaptive function. Interaction terms between Group and each variable were created to formally test for group differences. Three subsequent regression analyses tested which adaptive function domains (Communication, Daily Living Skills, Socialization) significantly contributed to results. Follow‐up analyses examined correlations based on IQ range (low IQ <85; high IQ ≥85). Results: The interaction between FSIQ and Group on overall adaptive function was significant; the relationship between FSIQ and adaptive function was weaker in the AE group than in the CON group. Regarding specific adaptive function domains, the interaction between FSIQ and Group was significant only in the Communication domain. Follow‐up analyses showed, within the low IQ range, the correlation between FSIQ and Communication was stronger in the CON group than the AE group. Within the high IQ range, the correlation between FSIQ and Communication was significant only in the CON group. Conclusions: Although higher intellectual functioning was associated with better adaptive function ability among controls, this was not found among the alcohol‐exposed youth where a general dampening of adaptive ability was noted. Further, the differential relationship between IQ and adaptive function between groups appears to be driven by communication abilities. These findings suggest that level of intellectual functioning of children with prenatal alcohol exposure does not fully account for caregiver‐reported communication and overall adaptive function deficits particularly at higher levels of functioning. [ABSTRACT FROM AUTHOR]

Background: Of the many negative outcomes associated with gestational alcohol use, one that has received relatively little attention is preterm birth and its possible contribution to effects of prenatal alcohol exposure (PAE) on development. To examine the increased risk for premature delivery associated with PAE and the joint influence of preterm birth and alcohol on child outcomes, analysis was carried out in a longitudinal cohort recruited in Western Ukraine. Methods: Alcohol‐using women and low or nondrinking controls were identified prenatally for a clinical trial of multivitamins and minerals (MVM) in ameliorating effects of PAE. Women were interviewed to provide information about medical and social status and other drug use. At delivery, information was collected about infant (N = 686) status including gestational age (GA) in weeks. Finally, 441 infants were followed to 6 months of age and cognitive (Mental Developmental Index [MDI]) and motor development (Psychomotor Developmental Index [PDI]) (measured using the Bayley Scales of Infant Development, second Ed (BSID‐II). Results: Seven percent infants were born at <37 weeks GA. The odds ratio for preterm delivery for Alcohol Exposed versus Low/No Alcohol was 2.6 (95% Confidence Interval 1.37, 4.94) (p < .003); MVM supplements were associated with a lower rate of preterm delivery overall, but the relative proportion of preterm births did not vary by MVM supplement status between alcohol exposure groups. In mediation models of 6 month cognitive and motor development with reference to Barron and Kenney in 1986, GA significantly mediated alcohol effects (MDI: Z = −2.64, p < .008; PDI: Z = −2.35, p < .02) although PAE independently affected both outcomes (MDI: t = −5.6, p < .000; PDI: t = −3.19, p < .002). Conclusion: Results suggest that PAE is associated with higher rates of preterm birth and that alcohol's effect on development in infancy may be both direct and mediated by shortened length of gestation. [ABSTRACT FROM AUTHOR]

Background: Youth with heavy prenatal alcohol exposure have high rates of behavioral concerns and psychopathology, including increased oppositional and conduct behaviors. The relation between those concerns and executive function (EF) deficits is unknown. We investigated the association of oppositional and conduct behavior and EF in adolescents to inform targeted intervention. Methods: Subjects (N = 267) ages 10 to 17 years comprised 3 groups: alcohol‐exposed with oppositional/conduct behaviors (AE+), alcohol‐exposed without oppositional/conduct behaviors (AE−), and controls (CON). Group differences on direct neuropsychological (Delis‐Kaplan Executive Function System [D‐KEFS]) and indirect parent‐report (Behavior Rating Inventory of Executive Function [BRIEF]) EF measures were tested with multivariate analysis of covariances, followed by univariate analysis of variances and pairwise comparisons. The contribution of attention‐deficit/hyperactivity disorder (ADHD) within the AE groups was assessed in secondary analyses. Results: On the D‐KEFS, there was an omnibus main effect of group, with significant main effects on 3 of 6 variables (CON>AE+, AE−). Within the AE groups, ADHD did not alter the results. On the BRIEF, there was an omnibus significant main effect of group, with significant main effects on all scales (CON

Oxygenated (HBO) and deoxygenated hemoglobin (HBR) levels in the prefrontal cortex (PFC) were measured using functional near-infrared spectroscopy (fNIRS) to determine if PFC activity during a cognitive inhibition task distinguishes children with prenatal alcohol exposure (PAE, n = 26) from both typically developing controls (n = 19) and a contrast group of children with other neurobehavioral problems (n = 14). Despite showing evidence of increased PFC activity in the non-inhibitory condition relative to controls, children in the PAE group displayed reduced PFC HBO and increased HBR relative to both other groups in the inhibitory condition, suggesting reduced PFC activity but increased oxygen consumption without sufficient oxygen replacement. [ABSTRACT FROM AUTHOR]

Objectives: Caregivers of youth with heavy prenatal alcohol exposure report impaired communication, which can significantly impact quality of life. Using data collected as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD), we examined whether cognitive variables predict communication ability of youth with histories of heavy prenatal alcohol exposure. Methods: Subjects (ages 10–16 years) comprised two groups: adolescents with heavy prenatal alcohol exposure (AE) and non-exposed controls (CON). Selected measures of executive function (NEPSY, Delis-Kaplan Executive Function System), working memory (CANTAB), and language were tested in the child, while parents completed communication ratings (Vineland Adaptive Behavior Scales – Second Edition). Separate multiple regression analyses determined which cognitive domains predicted communication ability. A final, global model of communication comprised the three cognitive models. Results: Spatial Working Memory and Inhibition significantly contributed to communication ability across groups. Twenty Questions performance related to communication ability in the CON group only while Word Generation performance related to communication ability in the AE group only. Effects remained significant in the global model, with the exception of Spatial Working Memory. Conclusions: Both groups displayed a relation between communication and Spatial Working Memory and Inhibition. Stronger communication ability related to stronger verbal fluency in the AE group and Twenty Questions performance in the CON group. These findings suggest that alcohol-exposed adolescents may rely more heavily on learned verbal storage or fluency for daily communication while non-exposed adolescents may rely more heavily on abstract thinking and verbal efficiency. Interventions aimed at aspects of executive function may be most effective at improving communication ability of these individuals. (JINS , 2018, 24 , 1026–1037) [ABSTRACT FROM AUTHOR]

Objective: This brief report describes the GoFAR intervention designed to improve attention, behavior, and adaptive functioning in children with FASD, ages 5 to 10 years. Methods: Thirty children were randomized to one of three conditions: GoFAR; FACELAND, and CONTROL; 25 completed the interventions. Over 10 sessions children and caregivers learned a metacognitive strategy (FAR) designed to improve cognitive control of behavior and adaptive functioning and practiced it during behavior analog therapy. Attention, behavior problems, and adaptive skills were measured pre- and post-intervention. Results: From pre- to post-testing the GoFAR intervention group improved on the Test of Variables of Attention (TOVA). Both intervention groups improved in Daily Living Skills. Conclusion: This pilot study demonstrated that children with FASD and their caregivers benefit from a focused intervention designed to improve effortful control of behavior. The study suggests the need for a larger clinical trial to evaluate the intervention’s effectiveness. [ABSTRACT FROM AUTHOR]

Prenatal alcohol exposure can impact both brain development and neurobehavioral function, including verbal learning and recall, although the relation between verbal recall and brain structure in this population has not been examined fully. We aimed to determine the structural neural correlates of verbal learning and recall in youth with histories of heavy prenatal alcohol exposure using a region of interest (ROI) approach. As part of an ongoing multisite project, subjects (age 10-16 years) with prenatal alcohol exposure (AE, n = 81) and controls (CON, n = 81) were tested using the CVLT-C and measures of cortical volume, surface area, and thickness as well as hippocampal volume were derived from MRI. Group differences in brain and memory indices were tested with ANOVA. Multiple regression analyses tested whether brain ROIs significantly predicted memory performance. The AE group had lower scores than the CON group on all CVLT-C variables (ps ≤ .001) and volume and surface area (ps < .025), although results varied by ROI. No group differences in cortical thickness were found. The relations between cortical structure and memory performance differed between group among some ROIs, particularly those in the frontal cortex, generally with smaller surface area and/or thinner cortex predicting better performance in CON but worse performance in AE. Cortical surface area appears to be the most sensitive index to the effects of prenatal alcohol exposure, while cortical thickness appears to be the least sensitive. These findings also indicate that the neural correlates of verbal memory are altered in youth with heavy prenatal alcohol exposure compared to controls. [ABSTRACT FROM AUTHOR]

The internal validity of the proposed Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE) was evaluated in children diagnosed with either Fetal Alcohol Syndrome (FAS) or partial FAS who were 3-10 years of age and had enrolled in a math intervention study. Symptoms were coded as present or absent using assessments conducted in the study, including standardized measures of neurocognitive and behavioral functioning, parent interview, and direct observations of the child. The number of endorsed ND-PAE symptoms was not related to environmental factors but was moderately related to the child's age. ND-PAE symptoms were highly consistent and this did not vary by age. Evidence suggested the ND-PAE adaptive symptoms may be too restrictive and only one symptom from this domain may be sufficient. Impulsiveness was not related to an endorsement of the ND-PAE disorder but research is needed with other clinical groups to establish the discriminative validity of this symptom. [ABSTRACT FROM AUTHOR]

Consistent with well-documented structural and microstructural abnormalities in prenatal alcohol exposure (PAE), recent studies suggest that functional connectivity (FC) may also be disrupted. We evaluated whole-brain FC in a large multi-site sample, examined its cognitive correlates, and explored its potential to objectively identify neurodevelopmental abnormality in individuals without definitive dysmorphic features. Included were 75 children with PAE and 68 controls from four sites. All participants had documented heavy prenatal alcohol exposure. All underwent a formal evaluation of physical anomalies and dysmorphic facial features. MRI data were collected using modified matched protocols on three platforms (Siemens, GE, and Philips). Resting-state FC was examined using whole-brain graph theory metrics to characterize each individual's connectivity. Although whole-brain FC metrics did not discriminate prenatally-exposed from unexposed overall, atypical FC (> 1 standard deviation from the grand mean) was significantly more common (2.7 times) in the PAE group vs.Controls: In a subset of 55 individuals (PAE and controls) whose dysmorphology examination could not definitively characterize them as either Fetal Alcohol Syndrome (FAS) or non-FAS, atypical FC was seen in 27 % of the PAE group, but 0 % of controls. Across participants, a 1 % difference in local network efficiency was associated with a 36 point difference in global cognitive functioning. Whole-brain FC metrics have potential to identify individuals with objective neurodevelopmental abnormalities from prenatal alcohol exposure. When applied to individuals unable to be classified as FAS or non-FAS from dysmorphology alone, these measures separate prenatally-exposed from non-exposed with high specificity. [ABSTRACT FROM AUTHOR]

Background Considered the leading cause of developmental disabilities worldwide, fetal alcohol spectrum disorders ( FASD) are a global health problem. To take advantage of neural plasticity, early identification of affected infants is critical. The cardiac orienting response ( COR) has been shown to be sensitive to the effects of prenatal alcohol exposure and is an inexpensive, easy to administer assessment tool. The purpose of this study was to evaluate the COR effectiveness in assessing individual risk of developmental delay. Methods As part of an ongoing longitudinal cohort study in Ukraine, live-born infants of women with some to heavy amounts of alcohol consumption in pregnancy were recruited and compared to infants of women who consumed low or no alcohol. At 6 and 12 months, infants were evaluated with the Bayley Scales of Infant Development- II. CORs were also collected during a habituation/dishabituation learning paradigm. Using a supervised logistic regression classifier, we compared the predictive utility of the COR indices to that of the 6-month Bayley scores for identification of developmental delay based on 12-month Bayley scores. Heart rate collected at each second (Standard COR) was compared to key features (Key COR) extracted from the response. Results Negative predictive values ( NPV) were 85% for Standard COR, 82% for Key COR, and 77% for the Bayley, and positive predictive values ( PPV) were 66% for Standard COR, 62% for Key COR, and 43% for the Bayley. Conclusions Predictive analysis based on the COR resulted in better NPV and PPV than the 6-month Bayley score. As the resources required to obtain a Bayley score are substantially more than in a COR-based paradigm, the findings are suggestive of its utility as an early scalable screening tool based on the COR. Further work is needed to test its long-term predictive accuracy. [ABSTRACT FROM AUTHOR]

Background Prenatal alcohol exposure ( PAE) has been found to impact neurophysiological encoding of environmental events negatively in the first year of life but has not been evaluated in older infants or toddlers. Cardiac orienting responses ( ORs) collected during a habituation/dishabituation learning paradigm were obtained from 12- to 18-month-olds to assess the impact of PAE beyond the first year of life. Methods Participants included women and their toddlers who differed in PAE histories and enrolled in a randomized clinical trial of multivitamin/mineral usage during pregnancy. Those who were randomly assigned to the no intervention group were used for this analysis. The habituation/dishabituation paradigm consisted of 10 habituation and 5 dishabituation trials. Baseline heart rate ( HR) was collected for 30 seconds prior to stimulus onset, and responses to the stimuli were assessed by sampling HR for 12 seconds poststimulus onset. Results The speed of the OR in response to auditory stimuli in the dishabituation condition was found to be altered as a function of maternal alcohol use around conception. For visual stimuli, positive histories of PAE were predictive of the magnitude but not the speed of the response on habituation and dishabituation trials. A history of binge drinking was associated with reduced magnitude of the OR response on visual encoding trials, and level of alcohol exposure at the time of conception was predictive of the magnitude of the response on visual dishabituation trials. Conclusions Cardiac ORs collected in the toddler period were sensitive to the effects of PAE. The magnitude of the OR was more sensitive to the impact of PAE than in previous research with younger infants, and this may be a function of brain maturation. Additional research assessing the predictive utility of using ORs in making decisions about individual risk was recommended. [ABSTRACT FROM AUTHOR]

The article discusses a student project undertaken to study the high mortality rate of children below 5 years in Lusaka City in Zambia as a result of being exposed to unsanitary conditions including contamination of drinking water and puts threats to child health in Africa in perspective.

The article talks about social determinants of health and the difference between health inequalities and health inequity stating health inequalities may be unavoidable but health inequity can be avoidable.

Background Neurobehavioral consequences of heavy prenatal alcohol exposure are well documented; however, the role of age or sex in these effects has not been studied. The current study examined the effects of prenatal alcohol exposure, sex, and age on neurobehavioral functioning in children. Methods Subjects were 407 youth with prenatal alcohol exposure ( n = 192) and controls ( n = 215). Two age groups (child [5 to 7 years] or adolescent [10 to 16 years]) and both sexes were included. All subjects completed standardized neuropsychological testing, and caregivers completed parent-report measures of psychopathology and adaptive behavior. Neuropsychological functioning, psychopathology, and adaptive behavior were analyzed with separate 2 (exposure history) × 2 (sex) × 2 (age) multivariate analyses of variance (MANOVAs). Significant effects were followed by univariate analyses. Results No 3-way or 2-way interactions were significant. The main effect of group was significant in all 3 MANOVAs, with the control group performing better than the alcohol-exposed group on all measures. The main effect of age was significant for neuropsychological performance and adaptive functioning across exposure groups with younger children performing better than older children on 3 measures (language, communication, socialization). Older children performed better than younger children on a different language measure. The main effect of sex was significant for neuropsychological performance and psychopathology; across exposure groups, males had stronger language and visual spatial scores and fewer somatic complaints than females. Conclusions Prenatal alcohol exposure resulted in impaired neuropsychological and behavioral functioning. Although adolescents with prenatal alcohol exposure may perform more poorly than younger exposed children, the same was true for nonexposed children. Thus, these cross-sectional data indicate that the developmental trajectory for neuropsychological and behavioral performance is not altered by prenatal alcohol exposure, but rather, deficits are consistent across the 2 age groups tested. Similarly, observed sex differences on specific measures were consistent across the groups and do not support sexually dimorphic effects in these domains. [ABSTRACT FROM AUTHOR]