A Validation Study of the Alcohol Related Neurodevelopmental Disorders Behavioral Checklist.

BACKGROUND: The initial confirmatory factor analysis of the Alcohol Related Neurodevelopmental Disorder Behavioral Checklist (ABC) utilized a population of 203 children. The analysis identified 10 independent measures (executive functioning, attention and concentration, cognition, memory, confabulation, gullibility, communication skills, academic skills, living/social skills, and juvenile justice). The 10 measures differentiated children with FASD from non-FASD controls. In this study, we present a validity study of the ABC using a different population of children with FASD and non-FASD controls. METHODS: A chart review identified 224 children with ABC checklist scores who had been evaluated for FASD. From this sample, we implemented a case-control study of 76 children diagnosed with FASD and 76 non-FASD controls who were matched by gender and closest age in years (mean age was 8.5 years). RESULTS: The averages of the total score and individual domain scores were compared between the 2 data sets and then between children with FASD and non-FASD controls. Children with FASD had significantly higher scores on all 10 measures than the non-FASD controls. There were very high sensitivity and specificity scores for the total score cutoff and for all 10 of the individual measures. CONCLUSIONS: In an independent sample, we found minimal differences between the previous data and the current validation study on measures of average total score cutoffs, scores for the 10 measures and correlations. Combining the 2 samples yielded robust differences in scores between children with FASD and non-FASD controls. The sensitivity, specificity and accuracy estimates were also very high. The ABC Screen appears to have acceptable epidemiologic performance data to support its use as a screening tool and as an initial step in differentiating children with FASD from those who do not have FASD.

Association of adverse childhood experiences and neurodevelopmental disorders in people with fetal alcohol spectrum disorders (FASD) and non-FASD controls.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is a highly prevalent lifelong disorder with high rates of comorbid neurodevelopmental disorders. Individuals with FASD are often exposed to abuse, neglect and foster home placements which have uncertain effects on the lifelong course of FASD. In this study we compare the prevalence of adverse childhood events (ACEs) and neurodevelopmental disorders in subjects with fetal alcohol spectrum disorders (FASD) and non-FASD controls. METHODS: A cross-sectional chart review of patients referred to a regional developmental center was used to identify people with FASD and non-FASD controls. We recorded the number of ACEs and neurodevelopmental disorders in each patient's chart. The most common diagnoses were attention deficit hyperactivity disorder, comprehension deficits, sleep disorders, and cognitive impairments. T-tests and a regression equation were utilized to determine significant differences between the groups. RESULTS: The review identified 203 subjects, 98 with FASD and 105 non-FASD controls. Group mean age was 8.6 years and 64.5% were male. People with FASD were more likely to have any ACEs (mean 5.3) with ACE scores 3.7 points higher than non-FASD controls (mean 1.69) (t = 11.29; p < .001). Increased ACEs were associated with increased rates of neurodevelopmental disorders for people with FASD (R = .179, p = .026) but not for non-FASD controls (R = .130, p = .094). CONCLUSIONS: Both FASD and subsequent exposure to ACEs are associated with increased risk for development of comorbid neurodevelopmental disorders. Prevention of ACEs during childhood may decrease risk for development of comorbid neurodevelopmental disorders.

Cardiorespiratory physiology in the safe passage study: protocol, methods and normative values in unexposed infants.

AIM: The Safe Passage Study, conducted by the Prenatal Alcohol in SIDS and Stillbirth Network, is investigating contributions of prenatal alcohol exposure to foetal and infant demise. This current report presents physiological data from full-term infants with no prenatal exposure to alcohol or maternal smoking. METHODS: Data are from 666 infants from the Northern Plains (North and South Dakota) and South Africa. A standardised protocol assessed cardiorespiratory function during baseline and head-up tilts shortly after birth and at one month of age. RESULTS: Analyses revealed significant increases in heart rate and decreases in BP from the newborn to one-month time period as well as diminished heart rate responses to head-up tilt in one-month-old infants. CONCLUSION: The Safe Passage Study was successful in characterising physiology in a large number of infants at sites known to have elevated risks for SIDS. Results demonstrate that even with low prenatal adverse exposures, there are significant changes in cardiorespiratory function as infants enter the window of increased risk for SIDS.

FASD and ADHD: Are they related and How?

In this issue of the journal, consensus criteria for the diagnosis and management of attention deficit hyperactivity disorder (ADHD) in people who have fetal alcohol spectrum disorders (FASD) are presented. In the absence of an adequate body of research on diagnosis and intervention, this expert consensus opinion is a welcome advance and should provide some guidance for clinicians managing people with FASD who have a comorbid ADHD.

The Economic Burden of Fetal Alcohol Spectrum Disorder in Canada in 2013.

AIM: To estimate the economic burden and cost attributable to Fetal Alcohol Spectrum Disorder (FASD) in Canada in 2013. METHODS: This cost-of-illness study examined the impact of FASD on the material welfare of the Canadian society in 2013 by analyzing the direct costs of resources expended on health care, law enforcement, children and youth in care, special education, supportive housing, long-term care, prevention and research, as well as the indirect costs of productivity losses of individuals with FASD due to their increased morbidity and premature mortality. RESULTS: The costs totaled approximately $1.8 billion (from about $1.3 billion as the lower estimate up to $2.3 billion as the upper estimate). The highest contributor to the overall FASD-attributable cost was the cost of productivity losses due to morbidity and premature mortality, which accounted for 41% ($532 million-$1.2 billion) of the overall cost. The second highest contributor to the total cost was the cost of corrections, accounting for 29% ($378.3 million). The third highest contributor was the cost of health care at 10% ($128.5-$226.3 million). CONCLUSIONS: FASD is a significant public health and social problem that consumes resources, both economic and societal, in Canada. Many of the costs could be reduced with the implementation of effective social policies and intervention programs.

Clinical sensitivity and specificity of meconium fatty acid ethyl ester, ethyl glucuronide, and ethyl sulfate for detecting maternal drinking during pregnancy.

BACKGROUND: We investigated agreement between self-reported prenatal alcohol exposure (PAE) and objective meconium alcohol markers to determine the optimal meconium marker and threshold for identifying PAE. METHODS: Meconium fatty acid ethyl esters (FAEE), ethyl glucuronide (EtG), and ethyl sulfate (EtS) were quantified by LC-MS/MS in 0.1 g meconium from infants of Safe Passage Study participants. Detailed PAE information was collected from women with a validated timeline follow-back interview. Because meconium formation begins during weeks 12-20, maternal self-reported drinking at or beyond 19 weeks was our exposure variable. RESULTS: Of 107 women, 33 reported no alcohol consumption in pregnancy, 16 stopped drinking by week 19, and 58 drank beyond 19 weeks (including 45 third-trimester drinkers). There was moderate to substantial agreement between self-reported PAE at ≥19 weeks and meconium EtG ≥30 ng/g (κ = 0.57, 95% CI 0.41-0.73). This biomarker and associated cutoff was superior to a 7 FAEE sum ≥2 nmol/g and all other individual and combination marker cutoffs. With meconium EtG ≥30 ng/g as the gold standard condition and maternal self-report at ≥19 weeks' gestation as the test condition, 82% clinical sensitivity (95% CI 71.6-92.0) and 75% specificity (95% CI 63.2-86.8) were observed. A significant dose-concentration relationship between self-reported drinks per drinking day and meconium EtG ≥30 ng/g also was observed (all P < 0.01). CONCLUSIONS: Maternal alcohol consumption at ≥19 weeks was better represented by meconium EtG ≥30 ng/g than currently used FAEE cutoffs.

Review of ethanol dispersion, distribution, and elimination from the fetal compartment.

BACKGROUND: This study is a review of alcohol dispersion into and elimination from the fetal compartment. METHODS: PubMed searches were conducted for all years and all languages for relevant papers. We also hand searched the reference list of papers and text books for additional references. RESULTS: Alcohol concentration is determined by body water (49% for women), grams of ethanol consumed, and duration of drinking. The fetus has very limited metabolic capacity and transfer from the fetal compartment to maternal circulation is the major pathway to reduce fetal exposure. Vasoconstriction of the placenta-umbilical unit from alcohol and smoking decreases rates of alcohol elimination from the fetal compartment. By 20 weeks of gestation, keratinization of fetal skin reduces the permeability of fetal skin to very low levels, increasing the duration of fetal exposure and complicating alcohol elimination from the fetal compartment. Two reabsorption pathways, the intramembranous pathway and fetal swallowing, create a recycling system where much of the ethanol the fetus excretes will be reabsorbed back into its circulatory system. Fetal re-excretion of ethanol into the amniotic fluid occurs by means of fetal urine, breathing movements, and nasal excretions. Amniotic fluid then functions as a reservoir for ethanol, prolonging fetal exposure. CONCLUSION: While the fetus has the ability to metabolize some ethanol, removal from the fetal-maternal unit relies primarily on maternal metabolic capacity. The alcohol elimination rate from the fetal compartment is approximately 3% to 4% of the maternal rate. We conclude with examples of the clinical relevance of information from this review. .

Fetal alcohol syndrome surveillance: age of syndrome manifestation in case ascertainment.

BACKGROUND: Fetal alcohol syndrome (FAS) is a leading cause of developmental disability (Abel & Sokol, ). Active public health surveillance through medical record abstraction has been used to estimate FAS prevalence rates, typically based on birth cohorts. There is an extended time for FAS characteristics to become apparent in infants and young children, and there are often delays in syndrome recognition and documentation. This methodological study analyzes the age at case ascertainment in a large surveillance program. METHODS: The Fetal Alcohol Syndrome Surveillance (FASSLink) Project, funded by the Centers for Disease Control and Prevention, sought to estimate FAS prevalence rates in eight U.S. states. FASSLink used linked abstractions from multiple health care records of suspected cases of FAS. The present study analyzed data from this effort to determine the child's age in months at confirming abstraction. RESULTS: The average age at abstraction for confirmed/probable FAS cases (n = 422) was 48.3 (±19.5) months with a range of 0 to 94 months. Age of ascertainment varied by state and decreased with each birth year; the number of cases ascertained also decreased in a steep stepwise gradient over the 6 birth years in the study. CONCLUSION: FAS surveillance efforts should screen records of children who are much older than is typical in birth defects surveillance. To best establish rates of FAS using medical records abstraction, surveillance efforts should focus on 1-year birth cohorts followed for a fixed number of years or, if using multi-year cohorts, should implement staggered end dates allowing all births to be followed for up to 8 years of age.

Fetal alcohol spectrum disorders and childhood cancer: a concise review of case reports and future research considerations.

We reviewed the published literature on the relationship between childhood cancer and fetal alcohol spectrum disorders (FASD). A Pub Med search identified 12 subjects with the co-occurrence of FASD and cancer. We included an additional case from the author's institution. Neuroblastomas comprised 6 of the 13 (46%) case reports, yet neuroblastomas comprise only about 10% of childhood cancers (z = 4.1; P < 0.001). Other than rhabdomyosarcoma, no other cancer was reported more than once. Few cases of childhood cancer associated with FASD were identified likely due to under ascertainment of FASD.

The safe passage study: design, methods, recruitment, and follow-up approach.

BACKGROUND: The Safe Passage Study is a large, prospective, multidisciplinary study designed to (1) investigate the association between prenatal alcohol exposure, sudden infant death syndrome (SIDS), and stillbirth, and (2) determine the biological basis of the spectrum of phenotypic outcomes from exposure, as modified by environmental and genetic factors that increase the risk of stillbirth, SIDS, and in surviving children, fetal alcohol spectrum disorders. METHODS: The results provided are based on an interim assessment of 6004 women enrolled, out of the 12,000 projected, from the Northern Plains, US, and Cape Town, South Africa, areas known to be of high risk for maternal drinking during pregnancy. Research objectives, study design, and descriptive statistics, including consent, recruitment, and retention information, are provided. RESULTS: Overall visit compliance is 87%, and includes prenatal, delivery/newborn, and postnatal contacts through 1 year post-delivery. Pregnancy outcome ascertainment is 98% prior to medical chart review; less than 2% of women withdraw. Consent for the use of DNA and placental tissue exceed 94%, and consent to participate in the autopsy portion of the study is 71%. CONCLUSIONS: The Safe Passage Study is the first multi-site study of SIDS and stillbirth to integrate prospectively collected exposure information with multidisciplinary biological information in the same maternal and fetal/infant dyad using a common protocol. Essential components of the study design and its success are close ties to the community and rigorous systems and processes to ensure compliance with the study protocol and procedures.

Fetal alcohol spectrum disorder diagnostic clinic capacity in Canadian Provinces and territories.

This study investigated the diagnostic capacity for Fetal Alcohol Spectrum Disorder (FASD) in multidisciplinary clinics across several provincial and one territorial jurisdictions of Canada: Alberta, British Columbia, Manitoba, Ontario and Northwest Territories. The data were collected directly from clinics capable of providing diagnoses of FASD and examined annual capacity for the assessment and diagnosis of FASD per year from 2015 to 2019. In total, 58 FASD diagnostic clinics were identified and 33 clinics participated in this survey. The study identified inadequate FASD diagnostic capacity in all participating jurisdictions. Based on the findings and the current population sizes, it is estimated that 98% of individuals with FASD are undiagnosed or misdiagnosed in Canada. Wait times for FASD diagnosis ranged from 1 month to 4.5 years across participating jurisdictions. The annual FASD diagnostic capacity in the select provinces and territories require at least a 67-fold increase per year.

Prenatal alcohol exposure in the Republic of the Congo: prevalence and screening strategies.

OBJECTIVE: To determine prevalence of prenatal alcohol use in Brazzaville, Congo and to evaluate a prenatal screening tool for use in this population. METHODS: A prospective population screening program of 3099 women at 10 prenatal care clinics in Brazzaville, Congo using the 1-Question screen. To validate the 1-Question screen in this population we screened 764 of these women again using the T-ACE as a gold standard for comparison study. The study outcomes were as follows: prevalence of self-reported prenatal alcohol use in Brazzaville using the 1-Question screen, estimation of number of drinking days, drinks per drinking day, most drinks on any one occasion. We also estimated the epidemiologic performance criteria for the 1-Question screen. RESULTS: The 3099 women screened were classified as follows: no risk 77% (n=2,384); at risk 3.7% (n=115); and as high risk 19.3% (n=600). Of the women reporting drinking during pregnancy, 87.4% reported drinking 4 or more drinks on any occasion. The agreement for detection of alcohol use during pregnancy by the 1-Question Screen and a positive T-ACE score was 94.7%. CONCLUSIONS: 23.3% of women attending prenatal care in Brazzaville reported alcohol use during pregnancy and 83% of them continued to drink after recognition of pregnancy. Prenatal alcohol exposure should be the focus of efforts to improve identification of alcohol use prior to and during pregnancy to improve maternal and child health. Birth Defects Research (Part A) 97:489-496, 2013. © 2013 Wiley Periodicals, Inc.

Cost of specialized addiction treatment of clients with fetal alcohol spectrum disorder in Canada.

BACKGROUND: Individuals with Fetal Alcohol Spectrum Disorder (FASD) constitute a special population that may be at particularly high risk for substance use. The purpose of the current study was to estimate the utilization of specialized addiction treatment services (SATS) and the associated cost, as a part of the total cost of health care associated with FASD in Canada. METHODS: The current study was a modeling study. Data on SATS by lifetime mental disorder status were obtained from the Drug and Alcohol Treatment Information System (DATIS) in Ontario, Canada for 2010/11. The number of clients with FASD who received SATS in Ontario in 2010/11 was estimated, assuming that approximately 37% (confidence interval: 21.6%-54.5%) of individuals with FASD abuse or are addicted to alcohol and/or drugs and that their utilization rate of SATS is the same as those for people with a lifetime mental disorder. The data from DATIS was then extrapolated to the total Canadian population. RESULTS: The cost of SATS for clients with FASD in Canada in 2010/11 ranged from $1.65 million Canadian dollars (CND) to $3.59 million CND, based on 5,526 outpatient visits and 9,529 resident days. When the sensitivity analysis was performed the cost of SATS ranged from $979 thousand CND to $5.34 million CND. CONCLUSIONS: Special attention must be paid to at-risk groups of individuals such as those with FASD, in order to reduce the likelihood of the development of co-morbid substance abuse problems, and thus, reducing the overall burden on Canadian society.

Common developmental trajectories and clinical identification of children with fetal alcohol spectrum disorders: A synthesis of the literature.

At an estimated prevalence of up to five percent in the general population, fetal alcohol spectrum disorders (FASD) are the most common neurodevelopmental disorder, at least if not more prevalent than autism (2.3%). Despite this prevalence in the general population, pediatricians and other developmental specialists have thus far failed to diagnose this disability, leaving most children and adults without the supports provided for most other disabilities. This paper will provide a review of clinically relevant literature that describes the developmental challenges of children with fetal alcohol spectrum disorders and addresses similarities to and differences of FASD from other neurodevelopmental disorders such as autism and attention deficit hyperactivity disorder. A subsequent discussion will describe how a diagnosis of an FASD can establish a basis for understanding the developmental and behavioral challenges of children with an FASD, and how specific interventions can help support child development and maximize adult independence.

Screening for Alcohol Use in Pregnancy: a Review of Current Practices and Perspectives.

Global trends of increasing alcohol consumption among women of childbearing age, social acceptability of women's alcohol use, as well as recent changes in alcohol use patterns due to the COVID-19 pandemic may put many pregnancies at higher risk for prenatal alcohol exposure (PAE), which can cause fetal alcohol spectrum disorder (FASD). Therefore, screening of pregnant women for alcohol use has become more important than ever and should be a public health priority. This narrative review presents the state of the science on various existing prenatal alcohol use screening strategies, including the clinical utility of validated alcohol use screening instruments. It also discusses barriers for alcohol use screening in pregnancy, such as practitioner constraints, unplanned pregnancies, delayed access to prenatal care, and stigma associated with substance use in pregnancy, providing recommendations to address these barriers. By implementing consistent alcohol use screening, prenatal care providers have the opportunity to facilitate access to counseling and brief interventions and thus, to prevent new cases of FASD and improve maternal and child health.

Screening for fetal alcohol spectrum disorder in infants and young children.

Introduction: With an estimated prevalence of up to five percent in the general population, fetal alcohol spectrum disorders (FASD) are the most common neurodevelopmental disorder and more prevalent than autism. Early identification and subsequent early intervention have the potential to improve developmental trajectory of children with FASD. In addition, new research suggests supplementation with choline may ameliorate the developmental impairments associated with prenatal alcohol exposure. Availability of a screening tool with acceptable epidemiologic performance criteria may be clinical useful in identification of young children at increased risk for FASD. In this paper we describe the Early Fetal Alcohol Spectrum Disorder Screening Test (E-FAST) to identify young children at increased risk for an FASD. Methods: We developed the E-FAST dataset from previously published studies, comprised of 281 children under 5 years of age, 180 (64.1%) were diagnosed with FASD and 101 (35.9%) were non-FASD. Analysis: The analysis identified seven useful variables (prenatal alcohol exposure, ADHD (Attention Deficit Hyperactivity Disorder), foster care or adopted, small OFC (occipital frontal circumference), communication impairments, impaired social skills, and cognitive deficits. All variables were categorized as yes/no for ease of use in a screening tool. Risk ratios for each of the seven indicators were estimated using two-way table analyses. Weights for each variable were estimated based on the relative strength of their odds ratios. Results: The average age was 2.7 years of age (S.D. 1.29) and ranged from infant (6.4%) to 4 years old (35.9%). Maternal alcohol use alone had a sensitivity of 0.97, specificity 0.65, and accuracy 0.86. For the combined seven variables, sensitivity was 0.94, specificity 0.74, and accuracy 0.87. Thus, the seven-item E-FAST screen had acceptable epidemiologic screening characteristics. Discussion: In the United States, up to 547 infants with FASD are born each day which far exceeds the capacity of multidisciplinary diagnostic clinics. During routine clinical management of infants and young children the use of an evidence-based screening tool provides a time efficient means to exclude large numbers of young children from further follow-up for FASD. Conversely, a positive screen identifies a smaller number of children at increased risk for FASD requiring more intensive evaluation and follow-up.

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.