Philip A. May

A Practical Clinical Approach to Diagnosis of Fetal Alcohol Spectrum Disorders: Clarification of the 1996 Institute of Medicine Criteria

Background. The adverse effects of alcohol on the developing human represent a spectrum of structural anomalies and behavioral and neurocognitive disabilities, most accurately termed fetal alcohol spectrum disorders (FASD). The first descriptions in the modern medical literature of a distinctly recognizable pattern of malformations associated with maternal alcohol abuse were reported in 1968 and 1973. Since that time, substantial progress has been made in developing specific criteria for defining and diagnosing this condition. Two sets of diagnostic criteria are now used most widely for evaluation of children with potential diagnoses in the FASD continuum, ie, the 1996 Institute of Medicine (IOM) criteria and the Washington criteria. Although both approaches have improved the clinical delineation of FASD, both suffer from significant drawbacks in their practical application in pediatric practice. Objective. The purpose of this report is to present specific clarifications of the 1996 IOM criteria for the diagnosis of FASD, to facilitate their practical application in clinical pediatric practice. Methods. A large cohort of children who were prenatally exposed to alcohol were identified, through active case-ascertainment methods, in 6 Native American communities in the United States and 1 community in the Western Cape Province of South Africa. The children and their families underwent standardized multidisciplinary evaluations, including a dysmorphology examination, developmental and neuropsychologic testing, and a structured maternal interview, which gathered data about prenatal drinking practices and other demographic and family information. Data for these subjects were analyzed, and revisions and clarifications of the existing IOM FASD diagnostic categories were formulated on the basis of the results. Results. The revised IOM method defined accurately and completely the spectrum of disabilities among the children in our study. On the basis of this experience, we propose specific diagnostic criteria for fetal alcohol syndrome and partial fetal alcohol syndrome. We also define alcohol-related birth defects and alcohol-related neurodevelopmental disorder from a practical standpoint. Conclusions. The 1996 IOM criteria remain the most appropriate diagnostic approach for children prenatally exposed to alcohol. The proposed revisions presented here make these criteria applicable in clinical pediatric practice.

PREVALENCE AND EPIDEMIOLOGIC CHARACTERISTICS OF FASD FROM VARIOUS RESEARCH METHODS WITH AN EMPHASIS ON RECENT IN-SCHOOL STUDIES

Researching the epidemiology and estimating the prevalence of fetal alcohol syndrome (FAS) and other fetal alcohol spectrum disorders (FASD) for mainstream populations anywhere in the world has presented a challenge to researchers. Three major approaches have been used in the past: surveillance and record review systems, clinic-based studies, and active case ascertainment methods. The literature on each of these methods is reviewed citing the strengths, weaknesses, prevalence results, and other practical considerations for each method. Previous conclusions about the prevalence of FAS and total FASD in the United States (US) population are summarized. Active approaches which provide clinical outreach, recruitment, and diagnostic services in specific populations have been demonstrated to produce the highest prevalence estimates. We then describe and review studies utilizing in-school screening and diagnosis, a special type of active case ascertainment. Selected results from a number of in-school studies in South Africa, Italy, and the US are highlighted. The particular focus of the review is on the nature of the data produced from in-school methods and the specific prevalence rates of FAS and total FASD which have emanated from them. We conclude that FAS and other FASD are more prevalent in school populations, and therefore the general population, than previously estimated. We believe that the prevalence of FAS in typical, mixed-racial, and mixed-socioeconomic populations of the US is at least 2 to 7 per 1,000. Regarding all levels of FASD, we estimate that the current prevalence of FASD in populations of younger school children may be as high as 2-5% in the US and some Western European countries.

Epidemiology of fetal alcohol syndrome in a South African community in the Western Cape Province.

OBJECTIVES This study determined the characteristics of fetal alcohol syndrome in a South African community, and methodology was designed for the multidisciplinary study of fetal alcohol syndrome in developing societies. METHODS An active case ascertainment, 2-tier methodology was used among 992 first-grade pupils. A case-control design, using measures of growth, development, dysmorphology, and maternal risk, delineated characteristics of children with fetal alcohol syndrome. RESULTS A high rate of fetal alcohol syndrome was found in the schools--40.5 to 46.4 per 1000 children aged 5 to 9 years--and age-specific community rates (ages 6-7) were 39.2 to 42.9. These rates are 18 to 141 times greater than in the United States. Rural residents had significantly more fetal alcohol syndrome. After control for ethnic variation, children with fetal alcohol syndrome had traits similar to those elsewhere: poor growth and development, congruent dysmorphology, and lower intellectual functioning. CONCLUSIONS This study documented the highest fetal alcohol syndrome rate to date in an overall community population. Fetal alcohol syndrome initiatives that incorporate innovative sampling and active case ascertainment methods can be used to obtain timely and accurate data among developing populations.

Prevalence and Characteristics of Fetal Alcohol Spectrum Disorders

OBJECTIVES: To determine the prevalence and characteristics of fetal alcohol spectrum disorders (FASD) among first grade students (6- to 7-year-olds) in a representative Midwestern US community. METHODS: From a consented sample of 70.5% of all first graders enrolled in public and private schools, an oversample of small children (≤25th percentile on height, weight, and head circumference) and randomly selected control candidates were examined for physical growth, development, dysmorphology, cognition, and behavior. The children’s mothers were interviewed for maternal risk. RESULTS: Total dysmorphology scores differentiate significantly fetal alcohol syndrome (FAS) and partial FAS (PFAS) from one another and from unexposed controls. Alcohol-related neurodevelopmental disorder (ARND) is not as clearly differentiated from controls. Children who had FASD performed, on average, significantly worse on 7 cognitive and behavioral tests and measures. The most predictive maternal risk variables in this community are late recognition of pregnancy, quantity of alcoholic drinks consumed 3 months before pregnancy, and quantity of drinking reported for the index child’s father. From the final multidisciplinary case findings, 3 techniques were used to estimate prevalence. FAS in this community likely ranges from 6 to 9 per 1000 children (midpoint, 7.5), PFAS from 11 to 17 per 1000 children (midpoint, 14), and the total rate of FASD is estimated at 24 to 48 per 1000 children, or 2.4% to 4.8% (midpoint, 3.6%). CONCLUSIONS: Children who have FASD are more prevalent among first graders in this Midwestern city than predicted by previous, popular estimates.

Maternal risk factors for fetal alcohol syndrome in the Western cape province of South Africa: a population-based study.

OBJECTIVES We defined risk factors for fetal alcohol syndrome (FAS) in a region with the highest documented prevalence of FAS in the world. METHODS We compared mothers of 53 first-grade students with FAS (cases) with 116 randomly selected mothers of first-grade students without FAS (controls). RESULTS Differences between case and control mothers in our study population existed regarding socioeconomic status, religiosity, education, gravidity, parity, and marital status. Mothers of children with FAS came from alcohol-abusing families in which heavy drinking was almost universal; control mothers drank little to no alcohol. Current and past alcohol use by case mothers was characterized by heavy binge drinking on weekends, with no reduction of use during pregnancy in 87% of the mothers. Twenty percent of control mothers drank during pregnancy, a rate that declined to 12.7% by the third trimester. The percentage who smoked during pregnancy was higher for case mothers than for control mothers (75.5% vs 30.3%), but the number of cigarettes smoked was low among case mothers. The incidence of FAS in offspring of relatively young women (28 years) was not explained by early drinking onset or years of drinking (mean, 7.6 years among case mothers). In addition to traditional FAS risk factors, case mothers were smaller in height, weight, head circumference, and body mass index, all anthropomorphic measures that indicate poor nutrition and second-generation fetal alcohol exposure. CONCLUSIONS Preventive interventions are needed to address maternal risk factors for FAS.

Maternal Risk Factors for Fetal Alcohol Syndrome and Partial Fetal Alcohol Syndrome in South Africa: A Third Study

OBJECTIVES This is a third exploration of risk factors for the two most severe forms of fetal alcohol spectrum disorders (FASD), fetal alcohol syndrome (FAS) and Partial FAS (PFAS), in a South African community with the highest reported prevalence of FAS in the world. METHODS In a case control design, interview and collateral data concerning mothers of 72 first grade children with FAS or PFAS are compared with 134 randomly selected maternal controls of children from the same schools. RESULTS Significant differences were found between the mothers of FASD children and controls in socio-economic status, educational attainment, and a higher prevalence of FASD among rural residents. The birth order of the index children, gravidity, and still birth were significantly higher among mothers of FASD children. Mothers of children with a FASD are less likely to be married and more likely to have a male partner who drank during the index pregnancy. Current and gestational alcohol use by mothers of FASD children is bingeing on weekends, with no reduction in drinking reported in any trimester in 75 to 90% of the pregnancies that resulted in an FAS child or during 50 to 87% of PFAS-producing pregnancies. There was significantly less drinking among the controls in the second and third trimesters (11 to 14%). Estimated peak blood alcohol concentrations (BAC)s of the mothers of PFAS children range from 0.155 in the first trimester to 0.102 in the third, and for mothers of FAS children the range is from 0.197 to 0.200 to 0.191 in the first, second, and third. Smoking percentage during pregnancy was significantly higher for mothers of FASD children (82 to 84%) than controls (35%); but average quantity smoked is low in the 3 groups at 30 to 41 cigarettes per week. A relatively young average age of the mother at the time of FAS and PFAS births (28.8 and 24.8 years respectively) is not explained by early onset of regular drinking (mean = 20.3 to 20.5 years of age). But the mean years of alcohol consumption is different between groups, 16.3, 10.7, and 12.1 years respectively for mothers of FAS, FASD, and drinking controls. Mothers of FAS and PFAS children were significantly smaller in height and weight than controls at time of interview. The childs total dysmorphology score correlates significantly with mothers weight (-0.46) and BMI (-0.39). Bivariate correlations are significant between the childs dysmorphology and known independent demographic and behavioral maternal risk factors for FASD: higher gravidity and parity; lower education and income; rural residence; drinks consumed daily, weekly, and bingeing during pregnancy; drinking in all trimesters; partners alcohol consumption during pregnancy; and use of tobacco during pregnancy. Similar significant correlations were also found for most of the above independent maternal risk variables and the childs verbal IQ, non-verbal IQ and behavioral problems. CONCLUSIONS Maternal data in this population are generally consistent with a spectrum of effects exhibited in the children. Variation within the spectrum links greater alcohol doses with a greater severity of effects among children of older and smaller mothers of lower socio economic status in their later pregnancies. Prevention is needed to address known maternal risk factors for FASD in this population.

Substance Abuse and American Indians: Prevalence and Susceptibility

The use of alcohol and other substances by American Indians has received considerable popular attention over the years. Empirical studies of prevalence for all types of substance abuse, however, have generally been few and limited in scope. In this paper prevalence studies among Indians are reviewed and analyzed by comparison with each other and national studies. In addition, issues important to the research of Indian alcohol and drug abuse are discussed. Finally a specific scheme of susceptibility is proposed which may explain the patterns of variation in both tribal and individual substance abuse.

Epidemiology of fetal alcohol syndrome among American Indians of the southwest

Abstract The epidemiological features of Fetal Alcohol Syndrome (FAS) were examined among American Indians in the southwestern United States. All FAS suspects were screened in specific populations of Navajo, Pueblo, and Plains culture tribes. A total of 115 alcohol‐affected children were identified. The incidence of FAS was found to be highly variable from one cultural group to the next, ranging from 1.3 per 1,000 births (1/749) for the Navajo to 10.3 (1/97) for the Plains. The pattern of age‐specific prevalence indicates an increase over the past fifteen years. The overall rate of mothers who have produced fetal alcohol children was 6.1 per 1,000 women of childbearing age with a range of 4 to 33 per 1,000. These maternal prevalence rates were important for the accurate prediction of public health risk because 25 per cent of all mothers who had produced one affected child had also produced others. The average per mother was 1.3 alcohol‐affected children. Other findings indicate that the mothers of these c...

APPROACHING THE PREVALENCE OF THE FULL SPECTRUM OF FETAL ALCOHOL SPECTRUM DISORDERS IN A SOUTH AFRICAN POPULATION-BASED STUDY

BACKGROUND The prevalence and characteristics of fetal alcohol spectrum disorders (FASD) were determined in this fourth study of first-grade children in a South African community. METHODS Active case ascertainment methods were employed among 747 first-grade pupils. The detailed characteristics of children within the continuum of FASD are contrasted with randomly selected, normal controls on (i) physical growth and dysmorphology; (ii) cognitive/behavioral characteristics; and (iii) maternal risk factors. RESULTS The rates of specific diagnoses within the FASD spectrum continue to be among the highest reported in any community in the world. The prevalence (per 1,000) is as follows: fetal alcohol syndrome (FAS)-59.3 to 91.0; partial fetal alcohol syndrome (PFAS)-45.3 to 69.6; and alcohol-related neurodevelopmental disorder (ARND)-30.5 to 46.8. The overall rate of FASD is therefore 135.1 to 207.5 per 1,000 (or 13.6 to 20.9%). Clinical profiles of the physical and cognitive/behavioral traits of children with a specific FASD diagnosis and controls are provided for understanding the full spectrum of FASD in a community. The spectral effect is evident in the characteristics of the diagnostic groups and summarized by the total (mean) dysmorphology scores of the children: FAS = 18.9; PFAS = 14.3; ARND = 12.2; and normal controls, alcohol exposed = 8.2 and unexposed = 7.1. Documented drinking during pregnancy is significantly correlated with verbal (r = -0.253) and nonverbal ability (r = -0.265), negative behaviors (r = 0.203), and total dysmorphology score (r = 0.431). Other measures of drinking during pregnancy are significantly associated with FASD, including binge drinking as low as 3 drinks per episode on 2 days of the week. CONCLUSIONS High rates of specific diagnoses within FASD were well documented in this new cohort of children. FASD persists in this community. The data reflect an increased ability to provide accurate and discriminating diagnoses throughout the continuum of FASD.

Alcohol consumption and other maternal risk factors for fetal alcohol syndrome among three distinct samples of women before, during, and after pregnancy: The risk is relative

Data were obtained from three samples of women of childbearing age. One sample of women is from prenatal clinics serving Plains Indian women. The second sample is of women from the Plains whose children were referred to special diagnostic developmental clinics, as their children were believed to have developmental issues consistent with prenatal alcohol consumption. The third sample is of women from South Africa, each of whom has given birth to a child diagnosed with full fetal alcohol syndrome (FAS). Data across samples conform to expected trends on many variables. For example, the maternal age at time of pregnancy, a major risk factor for FAS, ranged from a mean of 23.5 years for the prenatal clinic sample, to 23.8 years for the developmental clinic sample, to 27.6 for the sample of women who have delivered children with FAS. Other variables of maternal risk for FAS expected from the extant literature, such as high gravidity and parity, binge drinking, heavy intergenerational drinking in the mothers extended family and immediate social network, and length of drinking career, were compared across the three samples with variable results. However, normative measures of drinking problems are unreliable when reported across cultures. An unexpected finding from this three‐sample comparison was the differential risk found when comparing U.S. women to South African women. Women in the U.S. Plains Indian samples report a high consumption of alcohol in a binge pattern of drinking, yet there is less detectable damage to the fetus than among the South African women. Body mass index (BMI) and lifelong and current nutrition may have a substantial impact, along with the above factors, in relative risk for an FAS birth. The level of risk for producing a child with FAS is influenced by environmental and behavioral conditions that vary between populations and among individual women. Also, because many syndromes are genetically based, there is a need for full behavioral and genetic histories of the mother, family, and child being studied. Collecting extensive behavioral information as well as genetic histories will provide the requisite information for making an accurate diagnosis of FAS.