Maternal depression, alcohol use, and transient effects of perinatal paraprofessional home visiting in South Africa: Eight-year follow-up of a cluster randomized controlled trial.

BACKGROUND: South African mothers confront synergistic challenges from depression, alcohol use, and HIV/AIDS. The importance of maternal functioning for child development motivates interventions, yet long-term outcomes seldom are tracked. Furthermore, little is known about trajectories and the role of social-cultural factors in maternal depression and alcohol use across parenthood in low- and middle-income countries. METHODS: We examined maternal outcomes at 5- and 8-years' post-birth, from the Philani Intervention Program (PIP), a randomized controlled trial of a prenatally-initiated home visiting intervention lasting through 6 months' post-birth which yielded some benefits for children and mothers through 3 years. Longitudinal Bayesian mixed-effects models assessed intervention effects for maternal depression and alcohol use from pre-birth through 8 years post-birth. We plotted trajectories of depression and alcohol use and analyzed their relationship over time. RESULTS: Maternal benefits appeared limited and intervention outcomes differed at 5 and 8 years. Reduced depression in PIP versus standard care (SC) mothers at 3 years disappeared by 5 and 8 years. Depression prevalence declined from 35.1% prenatally to 5.5% at 8 years, independent of intervention or alcohol use. Alcohol use in both groups rebounded from a post-birth nadir; fewer PIP than SC mothers drank alcohol and reported problematic use at 5 but not 8 years. HIV+ prevalence did not differ by condition and increased from 26% to 45% over the reported period. CONCLUSIONS: Dissipation of early child benefits from home visiting by age 8 years likely reflects lack of durable change in maternal behaviors compounded by social-cultural factors and cumulative effects of community deprivation. High prenatal rates warrant screening and treatment for depression in standard antenatal care. Low-and-middle income countries may need sustained interventions, including alcohol use reduction, to capitalize on initial gains from targeted interventions and address community social-cultural factors. HIV/AIDS continues to spread in this population.

Combining neuroimaging and behavior to discriminate children with attention deficit-hyperactivity disorder with and without prenatal alcohol exposure.

In many patients, ostensible idiopathic attention deficit-hyperactivity disorder (ADHD) may actually stem from covert prenatal alcohol exposure (PAE), a treatment-relevant distinction. This study attempted a receiver-operator characteristic (ROC) classification of children with ADHD into those with PAE (ADHD+PAE) and those without (ADHD-PAE) using neurobehavioral instruments alongside magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) of supraventricular brain white matter. Neurobehavioral, MRS, and DTI endpoints had been suggested by prior findings. Participants included children aged 8-13 years, 23 with ADHD+PAE, 19 with familial ADHD-PAE, and 28 typically developing (TD) controls. With area-under-the-curve (AUC) >0.90, the Conners 3 Parent Rating Scale Inattention (CIn) and Hyperactivity/Impulsivity (CHp) scores and the Behavioral Regulation Index (BRI) of the Behavior Rating Inventory of Executive Function (BRIEF2) excellently distinguished the clinical groups from TD, but not from each other (AUC < 0.70). Combinations of MRS glutamate (Glu) and N-acetyl-compounds (NAA) and DTI mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) yielded "good" (AUC > 0.80) discrimination. Neuroimaging combined with CIn and BRI achieved AUC 0.72 and AUC 0.84, respectively. But neuroimaging combined with CHp yielded 14 excellent combinations with AUC ≥ 0.90 (all p < 0.0005), the best being Glu·AD·RD·CHp/(NAA·FA) (AUC 0.92, sensitivity 1.00, specificity 0.82, p < 0.0005). Using Cho in lieu of Glu yielded AUC 0.83. White-matter microstructure and metabolism may assist efforts to discriminate ADHD etiologies and to detect PAE, beyond the ability of commonly used neurobehavioral measures alone.

Impact of prenatal alcohol exposure on intracortical myelination and deep white matter in children with attention deficit hyperactivity disorder.

White matter alterations have been reported in children with prenatal alcohol exposure (PAE) and in children with attention deficit hyperactivity disorder (ADHD); however, as children with PAE often present with ADHD, covert PAE may have contributed to previous ADHD findings. Additionally, data regarding intracortical myelination in ADHD are lacking. Therefore, we evaluated intracortical myelination (assessed as the T1w/T2w ratio at 4 cortical ribbon levels) and myelin-related deep white matter features in children (aged 8-13 years) with ADHD with PAE (ADHD + PAE), children with familial ADHD without PAE (ADHD-PAE), and typically developing (TD) children. In widespread tracts, ADHD + PAE children showed higher mean and radial diffusivity than TD and ADHD-PAE children and lower fractional anisotropy than ADHD-PAE children; ADHD-PAE and TD children did not differ significantly. Compared to TD children, ADHD + PAE children had lower intracortical myelination only at the deepest cortical level (mainly in right insula and cingulate cortices), while ADHD-PAE children had lower intracortical myelination at multiple cortical levels (mainly in right insula, sensorimotor, and cingulate cortices); ADHD + PAE and ADHD-PAE children did not differ significantly in intracortical myelination. Considering the two ADHD groups jointly (via non-parametric combination) revealed common reductions in intracortical myelination, but no common deep white matter abnormalities. These results suggest the importance of considering PAE in ADHD studies of white matter pathology. ADHD + PAE may be associated with deeper, white matter abnormalities, while familial ADHD without PAE may be associated with more superficial, cortical abnormalities. This may be relevant to the different treatment response observed in these two ADHD etiologies.

Cortical gyrification in children with attention deficit-hyperactivity disorder and prenatal alcohol exposure.

BACKGROUND: An improved understanding of the neurodevelopmental differences between attention deficit hyperactivity disorder with and without prenatal alcohol exposure (ADHD + PAE and ADHD-PAE, respectively) is needed. Herein, we evaluated gyrification (cortical folding) in children with ADHD + PAE compared to that in children with familial ADHD-PAE and typically developing (TD) children. METHODS: ADHD + PAE (n = 37), ADHD-PAE (n = 25), and TD children (n = 27), aged 8-13 years, were compared on facial morphological, neurobehavioral, and neuroimaging assessments. Local gyrification index (LGI) maps were compared between groups using general linear modelling. Relationships between LGI and clincobehavioral parameters in children with ADHD ± PAE were evaluated using multivariate partial least squares. RESULTS: ADHD + PAE and ADHD-PAE groups showed significantly lower LGI (relative to TD) in numerous regions, overlapping in medial prefrontal, parietal, and temporo-occipital cortices (p < 0.001). However, LGI in left mid-dorsolateral prefrontal cortex was uniquely lower in the ADHD + PAE group (p < 0.001). Partial least squares analysis identified one significant latent variable (accounting for 59.3 % of the crossblock correlation, p < 0.001), reflecting a significant relationship between a profile of lower LGI in prefrontal (including left mid-dorsolateral), insular, cingulate, temporal, and parietal cortices and a clinicobehavioral profile of PAE, including a flat philtrum and upper vermillion border, lower IQ, poorer behavioral regulation scores, and greater hyperactivity/impulsivity. CONCLUSIONS: Children with ADHD + PAE uniquely demonstrate lower mid-dorsolateral LGI, with widespread lower LGI related to more severe facial dysmorphia and neurobehavioral impairments. These findings add insight into the brain bases of PAE symptoms, potentially informing more targeted ADHD treatments based on an objective differential diagnosis of ADHD + PAE vs. ADHD-PAE.

Neuroimaging of Supraventricular Frontal White Matter in Children with Familial Attention-Deficit Hyperactivity Disorder and Attention-Deficit Hyperactivity Disorder Due to Prenatal Alcohol Exposure.

Attention-deficit hyperactivity disorder (ADHD) is common in patients with (ADHD+PAE) and without (ADHD-PAE) prenatal alcohol exposure (PAE). Many patients diagnosed with idiopathic ADHD actually have covert PAE, a treatment-relevant distinction. To improve differential diagnosis, we sought to identify brain differences between ADHD+PAE and ADHD-PAE using neurobehavioral, magnetic resonance spectroscopy, and diffusion tensor imaging metrics that had shown promise in past research. Children 8-13 were recruited in three groups: 23 ADHD+PAE, 19 familial ADHD-PAE, and 28 typically developing controls (TD). Neurobehavioral instruments included the Conners 3 Parent Behavior Rating Scale and the Delis-Kaplan Executive Function System (D-KEFS). Two dimensional magnetic resonance spectroscopic imaging was acquired from supraventricular white matter to measure N-acetylaspartate compounds, glutamate, creatine + phosphocreatine (creatine), and choline-compounds (choline). Whole brain diffusion tensor imaging was acquired and used to to calculate fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity from the same superventricular white matter regions that produced magnetic resonance spectroscopy data. The Conners 3 Parent Hyperactivity/Impulsivity Score, glutamate, mean diffusivity, axial diffusivity, and radial diffusivity were all higher in ADHD+PAE than ADHD-PAE. Glutamate was lower in ADHD-PAE than TD. Within ADHD+PAE, inferior performance on the D-KEFS Tower Test correlated with higher neurometabolite levels. These findings suggest white matter differences between the PAE and familial etiologies of ADHD. Abnormalities detected by magnetic resonance spectroscopy and diffusion tensor imaging co-localize in supraventricular white matter and are relevant to executive function symptoms of ADHD.

South African mothers' immediate and 5-year retrospective reports of drinking alcohol during pregnancy.

Prenatal alcohol-drinking is often measured with self-report, but it is unclear whether mothers give more accurate answers when asked while pregnant or some time after their pregnancy. There is also the question of whether to measure drinking in a dichotomous or continuous fashion. We sought to examine how the timing and scale of self-reports affected the content of reports. From a sample of 576 black mothers around Cape Town, South Africa, we compared prenatal reports of prenatal drinking with 5-year retrospective reports, and dichotomous metrics (drinking or abstinent) with continuous metrics (fluid ounces of absolute alcohol drunk per day). Amounts increased over the 5-year period, whereas dichotomous measures found mothers less likely to report drinking later. All four measures were weakly associated with birth weight, birth height, child head circumference soon after birth, and child intelligence at age 5. Furthermore, neither reporting time nor the scale of measurement were consistently related to the strengths of these associations. Our results point to problems with self-report, particularly with this population, but we recommend post-birth continuous measures as the best of the group for their flexibility and their consistency with previous research.

Differential neuroimaging indices in prefrontal white matter in prenatal alcohol-associated ADHD versus idiopathic ADHD.

BACKGROUND: Attention deficit-hyperactivity disorder (ADHD) is common in fetal alcohol spectrum disorders (FASD) but also in patients without prenatal alcohol exposure (PAE). Many patients diagnosed with idiopathic ADHD may actually have ADHD and covert PAE, a treatment-relevant distinction. METHODS: We compared proton magnetic resonance spectroscopic imaging (MRSI; N = 44) and diffusion tensor imaging (DTI; N = 46) of the anterior corona radiata (ACR)-a key fiber tract in models of ADHD-at 1.5 T in children with ADHD with PAE (ADHD+PAE), children with ADHD without PAE (ADHD-PAE), children without ADHD with PAE (non-ADHD+PAE), and children with neither ADHD nor PAE (non-ADHD-PAE, i.e., typically developing controls). Levels of choline-compounds (Cho) were the main MRSI endpoint, given interest in dietary choline for FASD; the main DTI endpoint was fractional anisotropy (FA), as ACR FA may reflect ADHD-relevant executive control functions. RESULTS: For ACR Cho, there was an ADHD-by-PAE interaction (p = 0.038) whereby ACR Cho was 26.7% lower in ADHD+PAE than in ADHD-PAE children (p < 0.0005), but there was no significant ACR Cho difference between non-ADHD+PAE and non-ADHD-PAE children. Voxelwise false-discovery rate (FDR)-corrected analysis of DTI revealed significantly (q ≤ 0.0101-0.05) lower FA in ACR for subjects with PAE (ADHD+PAE or non-ADHD+PAE) than for subjects without PAE (ADHD-PAE or non-ADHD-PAE). There was no significant effect of ADHD on FA. Thus, in overlapping samples, effects of PAE on Cho and FA were observed in the same white-matter tract. CONCLUSIONS: These findings point to tract focal, white-matter pathology possibly specific for ADHD+PAE subjects. Low Cho may derive from abnormal choline metabolism; low FA suggests suboptimal white-matter integrity in PAE. More advanced MRSI and DTI-and neurocognitive assessments-may better distinguish ADHD+PAE from ADHD-PAE, helping identify covert cases of FASD.

Suicide risk in adolescents with fetal alcohol spectrum disorders.

BACKGROUND: The teratogenic effects of prenatal alcohol exposure (PAE) have been extensively documented over the course of 45 years of research and psychiatric problems are pervasive in this population. In adults with PAE, suicidal risk is high but less is known about the suicidal risk in adolescents with fetal alcohol spectrum disorders (FASD). This study describes the prevalence of suicidal ideation and serious suicide attempts in a sample of 54 adolescents between the ages of 13 and 18 years with FASD. METHODS: Adolescents were diagnosed with FASD using the Updated Clinical Guidelines for Diagnosing Fetal Alcohol Spectrum Disorders. The Children's Interview for Psychiatric Syndromes was used to identify those adolescents who experienced suicidal ideation and/or who had made a serious suicide attempt in the last 12 months. RESULTS: The prevalence of suicidal behaviors in this sample was high with 35.2% of teens reporting incidences of suicidal ideation and 13.0% reporting at least one serious suicide attempt in the past year. This finding is in contrast to the 17.2% and 2.4% for ideation and serious attempts, respectively, reported in the general U.S. adolescent population. Alarmingly, 29.2% of males with FASD reported a serious suicide attempt which was 19½ times higher than national norms for males. No females reported attempts. Number of home placements and the presence of a depressive disorder contributed to study outcomes. CONCLUSIONS: Findings demonstrate the significant risk for suicidality in this population, particularly adolescent males, and the need to assess and treat this life threatening behavior.

Alcohol Intervention for Adolescents with Fetal Alcohol Spectrum Disorders: Project Step Up, a Treatment Development Study.

BACKGROUND: Project Step Up proposed to reduce alcohol consumption and alcohol-related negative outcomes in adolescents with fetal alcohol spectrum disorders (FASD). METHODS: The 54 participants (30 females, 24 males) were assigned to either Project Step Up Intervention (SUI) or Control conditions and were assessed prior to intervention, immediately following intervention, and at 3-month follow-up. Adolescents in the SUI condition participated in a 6-week, 60-minute group intervention that provided alcohol education and promoted adaptive responses to alcohol-related social pressures. Caregivers attended concurrent but separate sessions on the effects of prenatal alcohol exposure on the brain and how to handle parenting challenges associated with alcohol use in teens with FASD. RESULTS: Thirty-three percent (n = 18) of adolescents were classified as light/moderate drinkers, and 67% (n = 36) were abstinent/infrequent drinkers based on their lifetime drinking histories. Results revealed a significant decrease in self-reported alcohol risk and in alcohol-related negative behaviors (Cohen's d = 1.08 and 0.99) in light/moderate drinkers in the SUI compared to the Control group. These results were partially sustained at 3-month follow-up. Furthermore, adolescents in the abstinent/infrequent group exhibited no increase in alcohol-related outcomes suggesting that the group intervention used in this study was not iatrogenic. CONCLUSIONS: The success of this treatment development study provides preliminary support for effective treatment of adolescents with FASD to prevent or reduce alcohol use and its negative consequences in this high risk population.

Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE): Proposed DSM-5 Diagnosis.

Over the past 40 years, a significant body of animal and human research has documented the teratogenic effects of prenatal alcohol exposure (PAE). Neurobehavioral Disorder associated with PAE is proposed as a new clarifying term, intended to encompass the neurodevelopmental and mental health symptoms associated with PAE. Defining this disorder is a necessary step to adequately characterize these symptoms and allow clinical assessment not possible using existing physically-based diagnostic schemes. Without appropriate diagnostic guidelines, affected individuals are frequently misdiagnosed and treated inappropriately (often to their considerable detriment) by mental health, educational, and criminal justice systems. Three core areas of deficits identified from the available research, including neurocognitive, self-regulation, and adaptive functioning impairments, are discussed and information regarding associated features and disorders, prevalence, course, familial patterns, differential diagnosis, and treatment of the proposed disorder are also provided.

A cluster randomised controlled effectiveness trial evaluating perinatal home visiting among South African mothers/infants.

BACKGROUND: Interventions are needed to reduce poor perinatal health. We trained community health workers (CHWs) as home visitors to address maternal/infant risks. METHODS: In a cluster randomised controlled trial in Cape Town townships, neighbourhoods were randomised within matched pairs to 1) the control, healthcare at clinics (n = 12 neighbourhoods; n = 594 women), or 2) a home visiting intervention by CBW trained in cognitive-behavioural strategies to address health risks (by the Philani Maternal, Child Health and Nutrition Programme), in addition to clinic care (n = 12 neighbourhoods; n = 644 women). Participants were assessed during pregnancy (2% refusal) and 92% were reassessed at two weeks post-birth, 88% at six months and 84% at 18 months later. We analysed 32 measures of maternal/infant well-being over the 18 month follow-up period using longitudinal random effects regressions. A binomial test for correlated outcomes evaluated overall effectiveness over time. The 18 month post-birth assessment outcomes also were examined alone and as a function of the number of home visits received. RESULTS: Benefits were found on 7 of 32 measures of outcomes, resulting in significant overall benefits for the intervention compared to the control when using the binomial test (p = 0.008); nevertheless, no effects were observed when only the 18 month outcomes were analyzed. Benefits on individual outcomes were related to the number of home visits received. Among women living with HIV, intervention mothers were more likely to implement the PMTCT regimens, use condoms during all sexual episodes (OR = 1.25; p = 0.014), have infants with healthy weight-for-age measurements (OR = 1.42; p = 0.045), height-for-age measurements (OR = 1.13, p<0.001), breastfeed exclusively for six months (OR = 3.59; p<0.001), and breastfeed longer (OR = 3.08; p<0.001). Number of visits was positively associated with infant birth weight ≥2500 grams (OR = 1.07; p = 0.012), healthy head-circumference-for-age measurements at 6 months (OR = 1.09, p = 0.017), and improved cognitive development at 18 months (OR = 1.02, p = 0.048). CONCLUSIONS: Home visits to neighbourhood mothers by CHWs may be a feasible strategy for enhancing maternal/child outcomes. However, visits likely must extend over several years for persistent benefits. TRIAL REGISTRATION: ClinicalTrials.gov NCT00996528.

Multiple risk factors during pregnancy in South Africa: the need for a horizontal approach to perinatal care.

South African children's long-term health and well-being is jeopardized during their mothers' pregnancies by the intersecting epidemics of HIV, alcohol use, low birth weight (LBW; <2,500 g) related to poor nutrition, and depressed mood. This research examines these overlapping risk factors among 1,145 pregnant Xhosa women living in 24 township neighborhoods in Cape Town, South Africa. Results revealed that 66 % of pregnant women experienced at least one risk factor. In descending order of prevalence, 37 % reported depressed mood, 29 % were HIV+, 25 % used alcohol prior to knowing that they were pregnant, and 15 % had a previous childbirth with a LBW infant. Approximately 27 % of women had more than one risk factor: depressed mood was significantly associated with alcohol use and LBW, with a trend to significance with HIV+. In addition, alcohol use was significantly related to HIV+. These results suggest the importance of intervening across multiple risks to maternal and child health, and particularly with depression and alcohol use, to positively impact multiple maternal and infant outcomes.

Screening for fetal alcohol spectrum disorders by nonmedical community workers.

BACKGROUND: South Africa has the highest prevalence of Fetal Alcohol Spectrum Disorders (FASD) in the world yet many women have no access to clinic care or to physicians in their communities. The shortage of physicians trained in the diagnosis of FASD is even more severe. Thus there is a need to train community workers to assist in the delivery of health care. OBJECTIVES: This study reports on the effectiveness of training community workers to screen for a possible diagnosis of a FASD. METHODS: Community workers in Cape Town, South Africa were trained to screen for FASD in 139, 18-month-old toddlers with prenatal alcohol exposure (PAE). Children were assessed according to the salient characteristics of individuals with PAE using height, weight, head circumference (OFC), philtrum, and lip measurements according to criteria set forth by the Institute of Medicine. Screen-positive children were referred for diagnostic assessment to a pediatrician reliably trained in the diagnosis of FASD. RESULTS: Of the screen-positive children, 93% received an FASD diagnosis suggesting that the screening procedure was highly sensitive. Diagnoses included 15% with fetal alcohol syndrome (FAS), 23% with Partial FAS, and 62% with Alcohol Related Neurodevelopmental Disorder (ARND, provisional). CONCLUSION: The use of community workers to screen for FASD represents a promising approach to effective diagnosis of children affected by PAE in areas lacking adequate medical resources.

Outcomes of home visits for pregnant mothers and their infants: a cluster randomized controlled trial.

OBJECTIVE: To evaluate the effect of home visits by community health workers (CHWs) on maternal and infant well being from pregnancy through the first 6 months of life for women living with HIV (WLH) and all neighborhood mothers. DESIGN AND METHODS: In a cluster randomized controlled trial in Cape Town townships, neighborhoods were randomized within matched pairs to either standard care, comprehensive healthcare at clinics (n=12 neighborhoods; n=169 WLH; n=594 total mothers); or Philani Intervention Program, home visits by CHWs in addition to standard care (PIP; n=12 neighborhoods; n=185 WLH; n=644 total mothers). Participants were assessed during pregnancy (2% refusal) and reassessed at 1 week (92%) and 6 months (88%) postbirth. We analyzed PIP's effect on 28 measures of maternal and infant well being among WLH and among all mothers using random effects regression models. For each group, PIP's overall effectiveness was evaluated using a binomial test for correlated outcomes. RESULTS: Significant overall benefits were found in PIP compared to standard care among WLH and among all participants. Secondarily, compared to standard care, PIP WLH were more likely to complete tasks to prevent vertical transmission, use one feeding method for 6 months, avoid birth-related medical complications, and have infants with healthy height-for-age measurements. Among all mothers, compared to standard care, PIP mothers were more likely to use condoms consistently, breastfeed exclusively for 6 months, and have infants with healthy height-for-age measurements. CONCLUSION: PIP is a model for countries facing significant reductions in HIV funding whose families face multiple health risks.

Higher functioning children with prenatal alcohol exposure: is there a specific neurocognitive profile?

Recent attempts to identify a neurocognitive profile of children with prenatal alcohol exposure (PAE) have led to an emerging "generalized deficit" conceptualization marked by diffuse information processing and integration difficulties as opposed to a specific profile. This study examines whether this conceptualization can be extended to higher functioning children with PAE who are without intellectual disability and addresses several limitations of previous research. One hundred twenty-five children aged 6-12 years with social skills deficits, 97 of whom met diagnostic criteria for a Fetal Alcohol Spectrum Disorder (FASD), underwent a comprehensive, multi-informant assessment of neurocognitive, emotional, social, behavioral, and adaptive functioning. Multivariate analyses of variance examined differences in functioning between the PAE group and a nonexposed comparison group with and without controlling for child IQ. Results indicated that the PAE group returned significantly poorer scores than the nonexposed group on every construct assessed, including executive functioning, attention, working/visuospatial memory, linguistic abstraction, adaptive behavior, emotional/behavioral functioning, and social cognition. These differences largely maintained after controlling for IQ and were similar regardless of informant, although teachers reported somewhat fewer group differences. Within the PAE group, no differences were found across FASD subtypes. These results provide evidence extending the emerging generalized deficit conceptualization of children with PAE to those higher functioning individuals without global intellectual disability.

White matter microstructural alterations in children with prenatal methamphetamine/polydrug exposure.

Little is known about the effects of prenatal methamphetamine exposure on white matter microstructure, and the impact of concomitant alcohol exposure. Diffusion tensor imaging and neurocognitive testing were performed on 21 children with prenatal methamphetamine exposure (age 9.8±1.8 years; 17 also exposed to alcohol), 19 children with prenatal alcohol but not methamphetamine exposure (age 10.8±2.3 years) and 27 typically developing children (age 10.3±3.3 years). Whole-brain maps of fractional anisotropy (FA) were evaluated using tract-based spatial statistics. Relative to unexposed controls, children with prenatal methamphetamine exposure demonstrated higher FA mainly in left-sided regions, including the left anterior corona radiata (LCR) and corticospinal tract Post-hoc analyses of these FA differences showed they likely result more from lower radial diffusivity (RD) than higher axial diffusivity (AD). Relative to the methamphetamine-exposed group, children with prenatal alcohol exposure showed lower FA in frontotemporal regions-particularly, the right external capsule. We failed to find any group-performance interaction (on tests of executive functioning and visuomotor integration) in predicting FA; however, FA in the right external capsule was significantly associated with performance on a test of visuomotor integration across groups. This report demonstrates unique diffusion abnormalities in children with prenatal methamphetamine/polydrug exposure that are distinct from those associated with alcohol exposure alone, and illustrates that these abnormalities in brain microstructure are persistent into childhood and adolescence--long after the polydrug exposure in utero.

A longitudinal study of the long-term consequences of drinking during pregnancy: heavy in utero alcohol exposure disrupts the normal processes of brain development.

Exposure to alcohol in utero can cause birth defects, including face and brain abnormalities, and is the most common preventable cause of intellectual disabilities. Here we use structural magnetic resonance imaging to measure cortical volume change longitudinally in a cohort of human children and youth with prenatal alcohol exposure (PAE) and a group of unexposed control subjects, demonstrating that the normal processes of brain maturation are disrupted in individuals whose mothers drank heavily during pregnancy. Trajectories of cortical volume change within children and youth with PAE differed from those of unexposed control subjects in posterior brain regions, particularly in the parietal cortex. In these areas, control children appear to show a particularly plastic cortex with a prolonged pattern of cortical volume increases followed by equally vigorous volume loss during adolescence, while the alcohol-exposed participants showed primarily volume loss, demonstrating decreased plasticity. Furthermore, smaller volume changes between scans were associated with lower intelligence and worse facial morphology in both groups, and were related to the amount of PAE during each trimester of pregnancy in the exposed group. This demonstrates that measures of IQ and facial dysmorphology predict, to some degree, the structural brain development that occurs in subsequent years. These results are encouraging in that interventions aimed at altering "experience" over time may improve brain trajectories in individuals with heavy PAE and possibly other neurodevelopmental disorders.

Frontostriatal connectivity in children during working memory and the effects of prenatal methamphetamine, alcohol, and polydrug exposure.

Various abnormalities in frontal and striatal regions have been reported in children with prenatal alcohol and/or methamphetamine exposure. In a recent fMRI study, we observed a correlation between accuracy on a working-memory task and functional activation in the putamen in children with prenatal methamphetamine and polydrug exposure. Because the putamen is part of the corticostriatal motor loop whereas the caudate is involved in the executive loop, we hypothesized that a loss of segregation between distinct corticostriatal networks may occur in these participants. The current study was designed to test this hypothesis using functional connectivity MRI. We examined 50 children ranging in age from 7 to 15, including 19 with prenatal methamphetamine exposure (15 of whom had concomitant prenatal alcohol exposure), 13 with prenatal exposure to alcohol but not methamphetamine, and 18 unexposed controls. We measured the coupling between blood oxygenation level dependent (BOLD) fluctuations during a working-memory task in four striatal seed regions and those in the rest of the brain. We found that the putamen seeds showed increased connectivity with frontal brain regions involved in executive functions while the caudate seeds showed decreased connectivity with some of these regions in both groups of exposed subjects compared to controls. These findings suggest that localized brain abnormalities resulting from prenatal exposure to alcohol and/or methamphetamine lead to a partial rewiring of corticostriatal networks. These results represent important progress in the field, and could have substantial clinical significance in helping devise more targeted treatments and remediation strategies designed to better serve the needs of this population.

Regional brain volume reductions relate to facial dysmorphology and neurocognitive function in fetal alcohol spectrum disorders.

Individuals with heavy prenatal alcohol exposure can experience significant deficits in cognitive and psychosocial functioning and alterations in brain structure that persist into adulthood. In this report, data from 99 participants collected across three sites (Los Angeles and San Diego, California, and Cape Town, South Africa) were analyzed to examine relationships between brain structure, neurocognitive function, facial morphology, and maternal reports of quantities of alcohol consumption during the first trimester. Across study sites, we found highly significant volume reductions in the FASD group for all of the brain regions evaluated. After correcting for scan location, age, and total brain volume, these differences remained significant in some regions of the basal ganglia and diencephalon. In alcohol-exposed subjects, we found that smaller palpebral fissures were significantly associated with reduced volumes in the ventral diencephalon bilaterally, that greater dysmorphology of the philtrum predicted smaller volumes in basal ganglia and diencephalic structures, and that lower IQ scores were associated with both smaller basal ganglia volumes and greater facial dysmorphology. In subjects from South Africa, we found a significant negative correlation between intracranial volume and total number of drinks per week in the first trimester. These results corroborate previous reports that prenatal alcohol exposure is particularly toxic to basal ganglia and diencephalic structures. We extend previous findings by illustrating relationships between specific measures of facial dysmorphology and the volumes of particular subcortical structures, and for the first time show that continuous measures of maternal alcohol consumption during the first trimester relates to overall brain volume reduction.

Translation of an evidence-based social skills intervention for children with prenatal alcohol exposure in a community mental health setting.

BACKGROUND: Children with prenatal alcohol exposure (PAE) have significant social skills deficits and are often treated in community mental health settings. However, it remains unclear whether these children can be effectively treated using manualized, evidence-based interventions that have been designed for more general mental health populations. METHODS: To shed light on this issue, the effectiveness of Children's Friendship Training (CFT) versus Standard of Care (SOC) was assessed for 85 children ages 6 to 12 years with and without PAE in a community mental health center. RESULTS: Children participating in CFT showed significantly improved knowledge of appropriate social skills, improved self-concept, and improvements in parent-reported social skills compared to children in the SOC condition. Moreover, results revealed that within the CFT condition, children with PAE performed as well as children without PAE. Findings indicated that CFT, an evidence-based social skills intervention, yielded greater gains than a community SOC social skills intervention and was equally effective for children with PAE as for those without PAE. CONCLUSIONS: Results suggest that children with PAE can benefit from treatments initiated in community settings in which therapists are trained to understand their unique developmental needs, and that they can be successfully integrated into treatment protocols that include children without PAE.