Validation of the ND-PAE Diagnosis in Children with Heavy Prenatal Alcohol Exposure.

This study evaluated criteria for Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE). Kable et al. (2022) assessed the validity of this diagnosis in a sample with low exposure to alcohol. The current study expanded this assessment to a sample with a wider age range and heavier alcohol exposure. Data were collected from participants (5-17y) with prenatal alcohol exposure (PAE) and typically developing controls at six Collaborative Initiative on Fetal Alcohol Spectrum Disorders sites using neuropsychological assessment and caregiver reports. Impairment was tested at 1SD, 1.5SD, and 2SD below the normative average and a modification of the adaptive functioning requirement was tested. Testing impairment at 1SD resulted in the highest endorsement rates in both groups. Our findings replicated the study by Kable et al. and show that current criteria captured a high rate of those with PAE and that requiring fewer adaptive functioning criteria resulted in higher sensitivity to PAE.

Continuous wound infusion catheter as part of a multimodal analgesia regimen for post-Caesarean delivery pain: a quality improvement impact study.

Background: The role of continuous wound infusion catheters as part of a multimodal analgesia strategy after Caesarean delivery is unclear. We introduced continuous wound infusion catheters to our multimodal analgesia regimen to evaluate the impact on analgesic outcomes after Caesarean delivery. Methods: After institutional review board (IRB) approval, a 4-month practice change was instituted as a quality improvement initiative. In addition to multimodal analgesia, continuous wound infusion catheters for up to 3 days were offered on alternate weeks for all women undergoing Caesarean deliveries. The primary outcome was postoperative in-hospital opioid consumption. Secondary outcomes were static and dynamic pain scores at 24 and 72 h, time until first analgesic request, opioid-related side-effects, length of stay, satisfaction (0-100%), and continuous wound infusion catheter-related complications. Results: All women scheduled for Caesarean delivery (n=139) in the 4-month period were included in the analysis, with 70 women receiving continuous wound infusion catheters, and 69 in the control group. Opioid consumption (continuous wound infusion catheter group 11.3 [7.5-61.9] mg morphine equivalents vs control group 30.0 [11.3-48.8] mg morphine equivalents), pain scores (except 24 h resting pain scores which were higher in the control group 2 [1-3] vs 1.5 [0-3] in the continous wound infusion catheters group; P=0.05), side-effects, length of stay, and complications were similar between groups. Satisfaction scores at 24 h were higher with continuous wound infusion catheters (100% [91-100%] vs 90% [86-100%]; P=0.003) with no differences at 72 h. One patient demonstrated symptoms of systemic local anaesthetic toxicity which resolved without significant harm. Conclusions: The addition of continuous wound infusion catheters to a multimodal analgesia regimen for post-Caesarean delivery pain management demonstrated minimal clinically significant analgesic benefits. Future studies are needed to explore the use of continuous wound infusion catheters in populations that may benefit most from this intervention.

Brain Volume in Fetal Alcohol Spectrum Disorders Over a 20-Year Span.

Importance: Anomalous brain development and mental health problems are prevalent in fetal alcohol spectrum disorders (FASD), but there is a paucity of longitudinal brain imaging research into adulthood. This study presents long-term follow-up of brain volumetrics in a cohort of participants with FASD. Objective: To test whether brain tissue declines faster with aging in individuals with FASD compared with control participants. Design, Setting, and Participants: This cohort study used magnetic resonance imaging (MRI) data collected from individuals with FASD and control individuals (age 13-37 years at first magnetic resonance imaging [MRI1] acquired 1997-2000) compared with data collected 20 years later (MRI2; 2018-2021). Participants were recruited for MRI1 through the University of Washington Fetal Alcohol Syndrome (FAS) Follow-Up Study. For MRI2, former participants were recruited by the University of Washington Fetal Alcohol and Drug Unit. Data were analyzed from October 2022 to August 2023. Main Outcomes and Measures: Intracranial volume (ICV) and regional cortical and cerebellar gray matter, white matter, and cerebrospinal fluid volumes were quantified automatically and analyzed, with group and sex as between-participant factors and age as a within-participant variable. Results: Of 174 individuals with MRI1 data, 48 refused participation, 36 were unavailable, and 24 could not be located. The remaining 66 individuals (37.9%) were rescanned for MRI2, including 26 controls, 18 individuals with nondysmorphic heavily exposed fetal alcohol effects (FAE; diagnosed prior to MRI1), and 22 individuals with FAS. Mean (SD) age was 22.9 (5.6) years at MRI1 and 44.7 (6.5) years at MRI2, and 35 participants (53%) were male. The FAE and FAS groups exhibited enduring stepped volume deficits at MRI1 and MRI2; volumes among control participants were greater than among participants with FAE, which were greater than volumes among participants with FAS (eg, mean [SD] ICV: control, 1462.3 [119.3] cc at MRI1 and 1465.4 [129.4] cc at MRI2; FAE, 1375.6 [134.1] cc at MRI1 and 1371.7 [120.3] cc at MRI2; FAS, 1297.3 [163.0] cc at MRI1 and 1292.7 [172.1] cc at MRI2), without diagnosis-by-age interactions. Despite these persistent volume deficits, the FAE participants and FAS participants showed patterns of neurodevelopment within reference ranges: increase in white matter and decrease in gray matter of the cortex and decrease in white matter and increase in gray matter of the cerebellum. Conclusions and Relevance: The findings of this cohort study support a nonaccelerating enduring, brain structural dysmorphic spectrum following prenatal alcohol exposure and a diagnostic distinction based on the degree of dysmorphia. FASD was not a progressive brain structural disorder by middle age, but whether accelerated decline occurs in later years remains to be determined.

Effect of an electronic medical record nudge to improve quality improvement program tracking of neuraxial catheter replacements in obstetric patients.

BACKGROUND: Monitoring complications associated with medical procedures requires reliable and accurate record keeping. Nudge reminders executed by way of electronic medical record (EMR) alerts influence clinician behaviour. We hypothesised that the introduction of an EMR nudge would improve documentation of replaced neuraxial blocks by obstetric anaesthesiologists at our institution. METHODS: We developed an EMR nudge that would alert the physician to a replaced neuraxial block if two or more neuraxial procedure notes in a single patient encounter were detected. The nudge encouraged physicians to document neuraxial block replacements in our institution's quality improvement database. We assessed the rate of physician adherence to replaced neuraxial block charting prior to the introduction of the nudge (January 2019-September 2019) and after the implementation (October 2019-December 2020). RESULTS: 494 encounters during the chart review period, January 2019-December 2020, required a neuraxial block replacement, representing an actual neuraxial replacement rate of 6.3% prior to the introduction of the nudge in October 2019. This rate was largely unchanged (6.2%) after the introduction of the nudge (0.1% difference, 95% CI: -0.0119 to 0.0099). Prior to the introduction of the nudge, the proportion of correctly charted failed/replaced blocks in our quality improvement database was 80.0%, and after nudge introduction, the rate was 96.2% (p value <0.00001, OR=6.32, 95% CI: 3.15 to 12.66). A p-chart of the monthly adherence rate demonstrated sustained improvement over time. CONCLUSIONS: EMR nudge technology significantly improved adherence with quality metric monitoring of neuraxial catheter replacement in obstetric patients. The results imply that data collection for quality metric databases of neuraxial block failures and replacements that rely on clinician memory without a nudge are likely under-reporting neuraxial block failures and replacements. This study supports widespread implementation of nudges in EMRs to improve quality metric reporting.

Results of a screening tool for fetal alcohol spectrum disorders are associated with neuropsychological and behavioral measures.

PURPOSE: This study assessed whether the outcome of a screening tool for fetal alcohol spectrum disorders (FASD), the FASD-Tree, was associated with neuropsychological and behavioral outcomes. METHODS: Data for this study were collected as part of the fourth phase of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD-4). Participants (N = 175, 5 to 16 years) with or without histories of prenatal alcohol exposure were recruited from San Diego and Minneapolis. Each participant was screened using the FASD-Tree and administered a neuropsychological test battery; parents or guardians completed behavioral questionnaires. The FASD-Tree incorporates physical and behavioral measures and provides an outcome regarding the presence of FASD (FASD-Positive or FASD-Negative). Logistic regression was used to test whether the FASD-Tree outcome was associated with general cognitive ability, executive function, academic achievement, and behavior. Associations were tested in two groups: the whole sample and only correctly classified participants. RESULTS: Results of the FASD-Tree were associated with neuropsychological and behavioral measures. Participants classified as FASD-Positive were more likely than those classified as FASD-Negative to have a lower IQ score and exhibit poorer performance on measures of executive and academic functions. Behaviorally, participants classified as FASD-Positive were rated as having more behavior problems and adaptive difficulties. Similar relationships were found for all measures when including only participants correctly classified by the FASD-Tree screening tool. CONCLUSION: Results from the FASD-Tree screening tool were associated with neuropsychological and behavioral measures. Participants classified as FASD-Positive were more likely to have impairment in all domains tested. The results support the effectiveness of the FASD-Tree as a screening tool for use in clinical settings, providing an efficient and accurate way to identify patients in need of additional evaluation.

Automated Alert System of Second-Line Uterotonic Drug Administration.

Multidisciplinary team management of postpartum hemorrhage (PPH) is needed to optimize care and improve outcomes. Lucile Packard Children's Hospital, Stanford, is a tertiary referral center with 4600 deliveries/y (>70% high-risk deliveries), and there have been times when the obstetric anesthesia team was alerted late or not at all for PPHs. Introduction of an automated alert process to the obstetric anesthesia team when a second-line uterotonic drug was administered has ensured prompt evaluation. Utilization of this automated drug alert system has improved communication and reduced failure to inform the obstetric anesthesiology team of PPH after vaginal and cesarean deliveries.

Atypical developmental trajectories of white matter microstructure in prenatal alcohol exposure: Preliminary evidence from neurite orientation dispersion and density imaging.

Introduction: Fetal alcohol spectrum disorder (FASD), a life-long condition resulting from prenatal alcohol exposure (PAE), is associated with structural brain anomalies and neurobehavioral differences. Evidence from longitudinal neuroimaging suggest trajectories of white matter microstructure maturation are atypical in PAE. We aimed to further characterize longitudinal trajectories of developmental white matter microstructure change in children and adolescents with PAE compared to typically-developing Controls using diffusion-weighted Neurite Orientation Dispersion and Density Imaging (NODDI). Materials and methods: Participants: Youth with PAE (n = 34) and typically-developing Controls (n = 31) ages 8-17 years at enrollment. Participants underwent formal evaluation of growth and facial dysmorphology. Participants also completed two study visits (17 months apart on average), both of which involved cognitive testing and an MRI scan (data collected on a Siemens Prisma 3 T scanner). Age-related changes in the orientation dispersion index (ODI) and the neurite density index (NDI) were examined across five corpus callosum (CC) regions defined by tractography. Results: While linear trajectories suggested similar overall microstructural integrity in PAE and Controls, analyses of symmetrized percent change (SPC) indicated group differences in the timing and magnitude of age-related increases in ODI (indexing the bending and fanning of axons) in the central region of the CC, with PAE participants demonstrating atypically steep increases in dispersion with age compared to Controls. Participants with PAE also demonstrated greater increases in ODI in the mid posterior CC (trend-level group difference). In addition, SPC in ODI and NDI was differentially correlated with executive function performance for PAE participants and Controls, suggesting an atypical relationship between white matter microstructure maturation and cognitive function in PAE. Discussion: Preliminary findings suggest subtle atypicality in the timing and magnitude of age-related white matter microstructure maturation in PAE compared to typically-developing Controls. These findings add to the existing literature on neurodevelopmental trajectories in PAE and suggest that advanced biophysical diffusion modeling (NODDI) may be sensitive to biologically-meaningful microstructural changes in the CC that are disrupted by PAE. Findings of atypical brain maturation-behavior relationships in PAE highlight the need for further study. Further longitudinal research aimed at characterizing white matter neurodevelopmental trajectories in PAE will be important.

Validation of the FASD-Tree as a screening tool for fetal alcohol spectrum disorders.

BACKGROUND: As many as 80% of individuals with fetal alcohol spectrum disorders (FASD) are misdiagnosed or not diagnosed. This study tests the accuracy and validity of a web-based screening tool (the FASD-Tree) for identifying children and adolescents with FASD. METHODS: Children with histories of prenatal alcohol exposure (PAE) and controls (N = 302, including 224 with PAE and 78 controls) were examined for physical signs of fetal alcohol syndrome (FAS), and parents completed behavioral questionnaires. Data were entered into the FASD-Tree, a web-based decision tree application. The FASD-Tree provided two outcomes: a dichotomous indicator (yes/no) and a numeric risk score (0 to 5), which have been shown separately to identify children with PAE and neurobehavioral impairment and to correlate with neurobehavioral outcomes. Overall accuracy (ACC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the decision tree, risk score, and their combination. Misclassified cases were examined for systematic bias. RESULTS: The FASD-Tree was successful in accurately identifying youth with histories of PAE and the subgroup of individuals with FASD, indicating its validity as an FASD screening tool. Overall accuracy rates for FASD-Tree components ranged from 75.0% to 84.1%, and both the decision tree outcome and risk score, and their combination, resulted in fair to good discrimination (area under the curve = 0.722 to 0.862) of youth with histories of PAE or FASD. While most participants were correctly classified, those who were misclassified differed in IQ and attention. Race, ethnicity, and sex did not affect the results. CONCLUSION: The FASD-Tree is not a biomarker of PAE and does not provide definitive evidence of prenatal alcohol exposure. Rather it is an accurate and valid screening tool for FASD and can be used by clinicians who suspect that a patient has a history of PAE, even if the exposure is unknown.

Fetal alcohol spectrum disorders.

Alcohol readily crosses the placenta and may disrupt fetal development. Harm from prenatal alcohol exposure (PAE) is determined by the dose, pattern, timing and duration of exposure, fetal and maternal genetics, maternal nutrition, concurrent substance use, and epigenetic responses. A safe dose of alcohol use during pregnancy has not been established. PAE can cause fetal alcohol spectrum disorders (FASD), which are characterized by neurodevelopmental impairment with or without facial dysmorphology, congenital anomalies and poor growth. FASD are a leading preventable cause of birth defects and developmental disability. The prevalence of FASD in 76 countries is >1% and is high in individuals living in out-of-home care or engaged in justice and mental health systems. The social and economic effects of FASD are profound, but the diagnosis is often missed or delayed and receives little public recognition. Future research should be informed by people living with FASD and be guided by cultural context, seek consensus on diagnostic criteria and evidence-based treatments, and describe the pathophysiology and lifelong effects of FASD. Imperatives include reducing stigma, equitable access to services, improved quality of life for people with FASD and FASD prevention in future generations.

Spiral drawing deficits in children with prenatal alcohol exposure.

AIMS: Empirical investigations reveal that, in comparison to their typically developing peers, children with histories of prenatal alcohol exposure experience deficits in writing but not drawing skills, both of which require fine motor control. This study examines drawing skills in this clinical group by assessing simple free-form spiral drawings with indices of spectral features and structural organization. METHODS: Children with (n = 15) and without (n = 24) prenatal alcohol exposure used their dominant and nondominant hands to draw a series of spirals using a wireless pen stylus that either provided concurrent visual feedback in the form of a black ink trace or left no visible ink trace of each drawing. Spirals were drawn on a sheet of paper placed on a digitizing table, which facilitated online data acquisition. The data were assessed by power spectral density function analysis and sample entropy analysis. RESULTS: In comparison to their typically developing peers, children with prenatal alcohol exposure produced spirals with a lower mean frequency and less spectral variability. Spirals in the prenatally exposed group were also lower in complexity and structural organization than in the control group. These results occurred independently of hand dominance or the availability of visual feedback. CONCLUSIONS: The drawing skills of children with prenatal alcohol exposure have inherent signal characteristics that differ significantly from those produced by typically developing peers. Simple tasks requiring fine motor control may be useful in identifying individuals with fetal alcohol spectrum disorders.

Obstetric Anesthesia Procedure-Based Workload and Facility Utilization of Society of Obstetric Anesthesia and Perinatology Centers of Excellence Designated Institutions.

BACKGROUND: Optimal workload and staffing for obstetric anesthesia services have yet to be determined. We surveyed Society of Obstetric Anesthesia and Perinatology (SOAP) Centers of Excellence (COE) for Obstetric Anesthesia Care institutions to evaluate procedure-based obstetric anesthesia workload and facility use. METHODS: After institutional review board (IRB) exemption, an online survey instrument (REDCap) was sent by email (1 initial and 2 reminders) to all SOAP COEs. Survey data included the number of deliveries, cesarean delivery rate, neuraxial labor analgesia rate, the number of labor and operating rooms, and the number of in-house and backup obstetric anesthesia providers. Obstetric anesthesia activity was estimated using a time-based workload ratio per provider (Stanford Work Index, 1.0 = clinically working every minute of every hour on duty) during weekday, weeknight, and weekend shifts. We compared workload between academic and nonacademic centers and correlated operating and labor rooms with cesarean and vaginal delivery volume. RESULTS: Fifty-one of 53 surveys were returned (96% response rate). Data from 33 academic and 14 nonacademic US institutions were analyzed. For academic centers, median Stanford Work Index for all staff (included trainees and Certified Registered Nurse Anesthetists) was 0.20 (weekday) and 0.19 (weeknight and weekends); nonacademic centers were 0.33 (weekday, P < .001 versus academic), 0.23 (weeknight, P = .009 versus academic), and 0.23 (weekends, P = .03 versus academic practices). Attending-only Stanford Work Indices were similar between academic and nonacademic centers. Total number of rooms on the obstetric suite (operating, labor, or triage room) was strongly correlated with delivery volume ( R2 = 0.55). CONCLUSIONS: The results outline staffing procedure-based workload ratios and facility utilization at SOAP COEs in the United States. These data can be used by other institutions that provide obstetric anesthesia services to guide their obstetric anesthesia staffing. The importance of considering the workload associated with different shifts and between academic and nonacademic centers is also highlighted. The results show that approximately one-third of an obstetric anesthesiologist's workload is spent on performing procedures. We did not, however, measure the other tasks anesthesiologists practice as peripartum physicians (eg, managing critically ill parturients, doing pre- and postprocedural evaluations, or performing emergent and unexpected procedures), and future studies are required to determine the time required to perform these tasks. Studies to determine the optimal staffing models to handle workload fluctuations and improve outcomes are also required.

Calcium chloride for the prevention of uterine atony during cesarean delivery: A pilot randomized controlled trial and pharmacokinetic study.

STUDY OBJECTIVE: To assess the feasibility, patient tolerance, pharmacokinetics, and potential effectiveness of a randomized controlled trial protocol investigating intravenous calcium chloride for the prevention of uterine atony during cesarean delivery. DESIGN: Double-blind, randomized controlled pilot trial with nested population pharmacokinetic analysis. SETTING: This study was performed at Lucile Packard Children's Hospital, from August 2018 to September 2019. PATIENTS: Forty patients with at least two risk factors for uterine atony at the time of cesarean delivery. INTERVENTIONS: One gram of intravenous calcium chloride (n = 20 patients) or a saline placebo control (n = 20 patients), in addition to standard care with oxytocin, upon umbilical cord clamping. MEASUREMENTS: The primary efficacy-related outcome was the presence of uterine atony defined as the use of a second-line uterotonic medication, surgical interventions for atony, or hemorrhage with blood loss >1000 mL. Blood loss, uterine tone numerical rating scores, serial venous blood calcium levels, hemodynamics, and potential side effects were also assessed. MAIN RESULTS: The study protocol proved feasible. The incidence of atony was 20% in parturients who received calcium compared to 50% in the placebo group (relative risk 0.38, P = 0.07, 95% CI 0.15-1.07, NNT 3.3). Calcium recipients tolerated the drug infusion well, with no adverse events and an equal incidence of potential side effects in the calcium and placebo groups. Ionized calcium concentration rose significantly in all patients who received calcium infusion, from baseline 1.18 mmol/L to peak levels 1.50-1.60 mmol/L. One-compartment population pharmacokinetics established clearance of 0.93 (95% CI 0.63-1.52) L/min and volume of distribution 76 (95% CI 49-94) L. CONCLUSIONS: In this pilot study, investigators found that intravenous calcium chloride was well-tolerated by the 20 patients assigned to receive the study drug and may be effective in prevention of uterine atony. A 1-g dose was sufficient to substantially increase calcium levels without any critically elevated lab values or concern for adverse side effects. These encouraging findings warrant further investigation of calcium as a novel agent to prevent uterine atony with an adequately powered clinical trial. Clinical trial registry NCT03867383 https://clinicaltrials.gov/ct2/show/NCT03867383.

Development and validation of a postnatal risk score that identifies children with prenatal alcohol exposure.

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.

Validity and Reliability of Executive Function Measures in Children With Heavy Prenatal Alcohol Exposure: Correspondence Between Multiple Raters and Laboratory Measures.

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.

Executive and Social Functioning Across Development in Children and Adolescents With Prenatal Alcohol Exposure.

BACKGROUND: Prenatal alcohol exposure (PAE) is linked to a variety of neurodevelopmental challenges, including social functioning (SF) and executive functioning (EF) deficits. These deficits present differently across developmental stages from preschool age to adolescence. METHODS: The post hoc analyses described here were conducted on data from 83 preschool-age children with PAE (early childhood group; ages 2.5 to 5.0) and 95 adolescents (49 with PAE, 46 controls; ages 8 to 16). Each child completed EF tasks as part of several prior studies. Parents completed social and communication inventories about their child's abilities. Thirty-three participants from the early childhood group returned for a 4-year follow-up and completed both SF and EF measures. RESULTS: Both the early childhood and adolescent groups with PAE showed deficits in SF and EF. There was a relationship between SF and EF within the adolescent PAE group that was not present in the adolescent control group or the early childhood PAE group. However, at the 4-year follow-up (Mage  = 8.45), participants originally in the early childhood PAE group also demonstrated this relationship. CONCLUSIONS: These findings support previous research on EF/SF deficits in adolescents with PAE while also addressing a gap in the literature concerning early childhood research on this topic. Additionally, these findings suggest that the relationship between EF and SF deficits may strengthen throughout development. This line of research highlights potential sensitive periods for SF and EF training in children with PAE and suggests that fetal alcohol spectrum disorders programs consider targeting EF training as a component of social skill interventions.

Cross-Sectional Analysis of Spatial Working Memory Development in Children with Histories of Heavy Prenatal Alcohol Exposure.

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.

Para-limbic Structural Abnormalities Are Associated With Internalizing Symptoms in Children With Prenatal Alcohol Exposure.

BACKGROUND: Prenatal alcohol exposure (PAE) is associated with a variety of structural abnormalities in the brain, including several within the para-limbic system. Children with PAE have higher rates of internalizing disorders, including depression and anxiety, which may be related to underlying limbic system anomalies. METHODS: Children aged 8 to 16 with PAE (n = 41) or without PAE (n = 36) underwent an magnetic resonance imaging of the brain and parents completed behavioral questionnaires about their children. Semi-automated procedures (FreeSurfer) were used to derive para-limbic volumes from T1-weighted anatomical images. RESULTS: There were significant group differences (PAE vs. nonexposed controls) in the caudate, hippocampus, and the putamen; children with PAE had smaller volumes in these regions even after controlling for total intracranial volume. A trend-level association was seen between caudate volume and internalizing symptoms in children with PAE; smaller caudate volumes (presumably reflecting less optimal neurodevelopment) were associated with higher levels of anxiety and depression symptoms in these children. CONCLUSIONS: Caudate structure may be disproportionately affected by PAE and may be associated with the later development of internalizing symptoms in those affected by PAE.