Prenatal alcohol exposure, blood alcohol concentrations and alcohol elimination rates for the mother, fetus and newborn.

Fetal alcohol spectrum disorders (FASDs) are a common cause of intellectual impairment and birth defects. More recently, prenatal alcohol exposure (PAE) has been found to be a risk factor for fetal mortality, stillbirth and infant and child mortality. This has led to increased concern about detection and management of PAE. One to 2 h after maternal ingestion, fetal blood alcohol concentrations (BACs) reach levels nearly equivalent to maternal levels. Ethanol elimination by the fetus is impaired because of reduced metabolic capacity. Fetal exposure time is prolonged owing to the reuptake of amniotic-fluid containing ethanol by the fetus. Alcohol elimination from the fetus relies on the mother's metabolic capacity. Metabolic capacity among pregnant women varies eightfold (from 0.0025 to 0.02 g dl(-1) h(-1)), which may help explain how similar amounts of ethanol consumption during pregnancy results in widely varying phenotypic presentations of FASD. At birth physiological changes alter the neonate's metabolic capacity and it rapidly rises to a mean value of 83.5% of the mother's capacity. FASDs are highly recurrent and younger siblings have increased risk. Detection of prenatal alcohol use offers an important opportunity for office-based interventions to decrease exposure for the remainder of pregnancy and identification of women who need substance abuse treatment. Mothers of children with FAS have been found to drink faster, get drunk quicker and to have higher BACs. A modest increase in the prevalence of a polymorphism of alcohol dehydrogenase, which increases susceptibility to adverse outcomes from PAE has been reported. Lastly, detection of alcohol use and appropriate management would decrease risk from PAE for subsequent pregnancies.

Control of hepatitis A through routine vaccination of children.

CONTEXT: The impact of routine hepatitis A vaccination of children living in large communities with elevated disease rates has not been evaluated. OBJECTIVE: To determine the effect of routine vaccination of children on disease incidence in a community with recurrent hepatitis A epidemics. DESIGN, SETTING, AND PARTICIPANTS: Community-based demonstration project conducted from January 12, 1995, through December 31, 2000, in Butte County, California, among children aged 2 to 17 years. INTERVENTION: In 1995, vaccination was offered to children aged 2 to 12 years during vaccination clinics conducted on 2 occasions 6 to 12 months apart at most schools in the county. In 1996-2000, vaccine was distributed to community health care clinicians, who vaccinated eligible children without charge. Vaccine was also available at health department clinics, selected child care centers, and other sites. MAIN OUTCOME MEASURES: Hepatitis A vaccination coverage, hepatitis A incidence, and vaccine effectiveness. RESULTS: During the study period, 29 789 (66.2%) of an estimated 44 982 eligible children received at least 1 vaccine dose; 17 681 (39.3%) received a second dose. The number of hepatitis A cases among the entire county population declined 93.5% during the study period, from 57 cases in 1995 to 4 in 2000, the lowest number of cases reported in the county since hepatitis A surveillance began in 1966. The 2000 incidence rate of 1.9 per 100 000 population was the lowest of any county in the state. Of the 245 cases reported during the 6-year period, 40 (16.3%) occurred among children 17 years of age or younger, of which 16 (40%) occurred in 1995 and only 1 in 2000. One of the 27 case patients eligible for vaccination had been vaccinated, having received the first dose 3 days before symptom onset. The estimated protective vaccine efficacy was 98% (95% confidence interval, 86%-100%). CONCLUSIONS: In this population, hepatitis A vaccine was highly effective in preventing disease among recipients. Childhood vaccination appears to have decreased hepatitis A incidence among children and adults and controlled the disease in a community with recurrent epidemics.

Neuropsychiatric genetics: misclassification in linkage studies of phenotype-genotype research.

Research on neuropsychiatric disorders has produced a number of very important findings in the last few decades. However, several problems continue to hinder research in this area. One problem area has been the appropriate classification of disease status for probands and extended family members in linkage studies. In this article, we examine rates of misclassification in a 12-year follow-up study of children previously diagnosed with Tourette syndrome. At the 12-year follow-up, we found a 5 to 12% rate of misclassification of previously diagnosed cases. We present a model of a linkage study with three classification steps. The model demonstrates that an error rate of 5% would result in misclassification of 20% of true cases by step three. Adding additional steps to improve diagnostic accuracy may increase rather than decrease classification error.

Long-term follow-up of an epidemiologically defined cohort of patients with Tourette syndrome.

The goal of this study was to collect prospective longitudinal information on the development of an epidemiologically defined cohort of patients with Tourette syndrome. These data may improve prognostic understanding of the condition. This information will also be important for specification of an adult phenotype for genetic marker studies. A prospective longitudinal cohort study was conducted. Fifty-four of 73 patients from our 1986 prevalence study of Tourette syndrome in North Dakota school-aged children were eligible for inclusion. The subjects were diagnosed in 1984 and 1985. We were able to interview 39 of 54 eligible patients for 507 person-years of follow-up. For the cohort, tic severity declined by 59%, global assessment of functioning improved by 50%, and the average number of comorbidities decreased by 42%. Forty-four percent of patients were essentially symptom free at follow-up. Only 22% were on medication as adults. Tourette syndrome is a developmental neuropsychiatric disorder with a long-term course that is favorable for most patients. Males demonstrated substantially more variability in improvement but overall demonstrated more improvement than females.

A 15-year follow-up of a boy with pyridoxine (vitamin B6)-dependent seizures with autism, breath holding, and severe mental retardation.

Pyridoxine (vitamin B6) (2q31) dependency is a rare autosomal-recessive disorder that causes a severe seizure disorder of prenatal or neonatal onset. The abnormality appears to inhibit the binding of vitamin B6 to the enzyme glutamic acid decarboxylase-1, which is needed for the biosynthesis of gamma-aminobutyric acid (GABA). Most patients with pyridoxine-dependent seizures require lifelong treatment with pyridoxine. The full range of associated symptomatology is unknown since fewer than 100 cases have been reported. A majority of cases are mentally retarded. We report a 15-year-old boy with pyridoxine-dependent seizures, nonpyridoxine-dependent seizures, severe mental retardation, autistic disorder, aerophagia, breath holding, and self-injury. This complex outcome should alert clinicians to the wide range of neuropsychiatric outcomes associated with this disorder.

Asperger's syndrome, X-linked mental retardation (MRX23), and chronic vocal tic disorder.

Pervasive developmental disorders are severe disorders of development with no consistent neurobiologic etiology and most often an idiopathic etiology. We report a 12-year-old male who met criteria for a pervasive developmental disorder (Asperger's syndrome) and a chronic tic disorder. The child also has an X-linked cognitive impairment (MRX23). The presence of tic symptomatology, pervasive developmental disorder, and fragile X syndrome has previously been reported. Since no singular etiology for Asperger's syndrome has been found, the possibility of other cases of Asperger's syndrome occurring with concurrent abnormalities on the X chromosome should be considered by clinicians, especially if tic symptomatology is present.

An international perspective on Tourette syndrome: selected findings from 3,500 individuals in 22 countries.

We have established a multisite, international database of 3,500 individuals diagnosed with Tourette syndrome (TS). The male:female ratio is 4.3:1 for the total sample, with wide variation among sites; the male excess occurs at every site. Anger control problems, sleep difficulties, coprolalia, and self-injurious behavior only reach impressive levels in individuals with comorbidity. Anger control problems are strongly correlated with comorbidity, regardless of site, region, or whether assessed by neurologists or psychiatrists. The mean age at onset of tics is 6.4 years. At all ages, about 12% of individuals with TS have no reported comorbidity. The most common reported comorbidity is attention-deficit-hyperactivity disorder. Males are more likely to have comorbid disorders than females. The earlier the age at onset, the greater the likelihood of a positive family history of tics. An understanding of the factors producing these and other variations might assist in better subtyping of TS. Because behavioral problems are associated with comorbidity, their presence should dictate a high index of suspicion of the latter, whose treatment may be at least as important as tic reduction. The established database can be used as the entry point for further research when large samples are studied and generalizability of results is important.

Prevalence of SIDS risk factors: before and after the "Back to Sleep" campaign in North Dakota Caucasian and American Indian infants.

The objective of this study was to compare rates of infant sleeping position and other risk factors for sudden infant death syndrome from 1991 before the "Back to Sleep" campaign to rates in 1998 after the campaign. We used a cross-sectional risk factor prevalence study of risk factors for the years 1991 and 1998. In North Dakota the prevalence rates of prone sleeping declined 72% for American Indian infants and 62% for Caucasian infants. We were unable to identify a corresponding decline in SIDS in North Dakota for this time period. The relationship between sleeping position and SIDS may be more complex in rural and frontier settings and in American Indian populations than in urban and majority populations. The generalizability of this study is limited by the rural setting and small sample size. Longer term surveillance and additional reports from sites with pre "Back to Sleep" data as a baseline for both SIDS rates and sleeping position will be important to clarify the rate of prone sleeping position and SIDS.

A prevalence methodology for mental illness and developmental disorders in rural and frontier settings.

A prevalence study methodology developed for use in rural and frontier settings is described. The general method was developed over a 15 year period and has been successfully adapted and used in studies of 14 different childhood onset developmental disorders. Subjects were the 168,000 school aged children from North Dakota who were first surveyed for cases of autism--pervasive developmental disorders in 1985 and 1986. The results of the prevalence study were compared with the results of a 12-year ongoing surveillance of the cohort. The 12-year ongoing surveillance identified one case missed by the original prevalence study. Thus the original prevalence study methodology identified 98% of the cases of autism-pervasive developmental disorder in the population. This methodology may also be useful for studies of other developmental disorders in rural and frontier settings.

Comorbid Down's syndrome, Tourette syndrome and intellectual disability: registry prevalence and developmental course.

The co-occurrence of Tourette syndrome (TS) and Down's syndrome (DS) has been previously reported in the literature. In the present study, a retrospective record review was conducted using the North Dakota TS registry in order to ascertain the number of cases of TS and DS, and to develop case descriptions. We identified five cases from North Dakota. Two of these patients were simply comorbid for TS and DS. One was additionally comorbid for bipolar disorder, another for childhood disintegrative disorder and a third had a D/G group translocation. The association between DS and TS occured in 2% of TS patients. Contrary to the situation in patients with pervasive developmental disorders, the presence of TS in DS may be a negative prognostic indicator.

Peek-a-boo fragile site at 16d associated with Tourette syndrome, bipolar disorder, autistic disorder, and mental retardation.

Five patients with a fragile site at 16q22-23 and neuropsychiatric disorders are reported. Three of five had Tourette disorder, three had mental retardation, two had bipolar disorder, and one had autistic disorder. During our attempts to study the fragile sites in more detail we were unable to reproduce the fragile sites found several years earlier. The potential relationship between the fragile sites and the neuropsychiatric disorders in these patients is discussed. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:69-73, 2000.

Screening for fetal alcohol syndrome: is it feasible and necessary?

The potential to utilize screening strategies to improve the identification and outcome of persons with fetal alcohol syndrome (FAS) is reviewed. FAS is a condition where screening and surveillance activities would be appropriate. Development of FAS screening and surveillance programs is encouraged because the disorder is expensive. People with FAS have poor outcomes as adults with less than 10% living independently. Several useful tools and models are available. Screening would improve ascertainment and prevalence estimates. Early identification could improve access to services and long term outcome, secondary disabilities and, by extension, excess disability in affected children could be decreased. Lastly, mothers who are at the highest risk to have additional children with FAS could be identified and offered treatment. While both screening and surveillance activities are discussed, the principle focus of this article is a review of the screening process. Two screening tools and several screening methodologies for FAS are available. Since no test will be appropriate in all settings, screening tests need to be selected depending on the setting and population of interest. Screening for FAS should be conducted in a variety of settings and in populations of both high and moderate risk. The results would also provide important data to influence public policy development and resource allocation. Appropriate evaluation of the efficacy, efficiency and effectiveness of FAS screening tools and methodologies would be important before utilization in screening programs.

Prenatal and perinatal risk factors for Tourette disorder.

AIMS: To identify pre- and perinatal risk factors for Tourette disorder. METHODS: Case control study. We matched names of patients who met DSM criteria for Tourette disorder with their birth certificates. For each case five controls were selected. The controls were matched by sex, year and month of birth. RESULTS: Univariate analysis of the 92 cases and the 460 matched controls identified 4 risk factors; one categorical variable--trimester prenatal care begun and 3 continuous variables--apgar score at 5 minutes, month prenatal began and number of prenatal visits. Logistic modeling to control for confounding produced a three variable model (apgar score at 5 minutes (OR = 1.31), number of prenatal visits (OR = .904) and fathers age (OR = .909). The model parameters were: chi 2 = 19.76; df = 3; p < .001. CONCLUSIONS: This is an inexpensive methodology to identify potential risk factors of patients with Tourette disorder and other mental illness.

Recognition and management of Tourette's syndrome and tic disorders.

Tic disorders and Tourette's syndrome are conditions that primary care physicians are likely to encounter. Up to 20 percent of children have at least a transient tic disorder at some point. Once believed to be rare, Tourette's syndrome is now known to be a more common disorder that represents the most complex and severe manifestation of the spectrum of tic disorders. Tourette's syndrome is a chronic familial disorder with a fluctuating course; the long-term outcome is generally favorable. Although the exact underlying pathology has yet to be determined, evidence indicates a disorder localized to the frontal-subcortical neural pathways. Tourette's syndrome is commonly associated with attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, behavior problems and learning disabilities. These comorbid conditions make the management of Tourette's syndrome more challenging. Management of Tourette's syndrome should include timely and accurate diagnosis, education, and behavior or pharmacologic interventions. Use of neuroleptic medications and dopamine D2 antagonist drugs can be effective but may be associated with significant side effects.

Prenatal and perinatal risk factors for autism.

AIM: To identify pre- and perinatal risk factors for autism. METHOD: Case control study. We matched names of patients from North Dakota who met DSM criteria for autism, a pervasive developmental disorder, and autistic disorder with their birth certificates. Five matched controls were selected for each case. RESULTS: Univariate analysis of the 78 cases and 390 controls identified seven risk factors. Logistic modeling to control for confounding produced a five variable model. The model parameters were chi 2 = 36.6 and p < 0.001. The five variables in the model were decreased birth weight, low maternal education, later start of prenatal care, and having a previous termination of pregnancy. Increasing father's age was associated with increased risk of autism. CONCLUSION: This methodology may provide an inexpensive method for clinics and public health providers to identify risk factors and to identify maternal characteristics of patients with mental illness and developmental disorders.

The FAS Screen: a rapid screening tool for fetal alcohol syndrome.

Fetal alcohol syndrome (FAS) is an important cause of mental retardation and developmental disabilities. A population based screening tool would allow for early diagnosis and entry into intervention programs. The aim of the study was to develop a brief screening tool for use in population-based settings to improve the identification of children with FAS. The FAS Screen was developed and tested in six sites. These were sites that served children and all were located in North Dakota. Screening was completed on 1013 children, 65 were found to have a positive screening score and were referred for further investigation. Forty were seen for evaluation by a medical geneticist and six were diagnosed with FAS. The estimated values for the screening tool were: specificity 94.1%, sensitivity 100%, positive predictive value 9.1% and negative predictive value 100%. The cost of screening was $13.00 per child and the cost per case identified was $4,100. The FAS Screen is a brief screening test with acceptable performance characteristics and is cost effective.

Two males with childhood disintegrative disorder: a prospective 14-year outcome study.

A prospective 14-year outcome study of two children meeting DSM-IV criteria for childhood disintegrative disorder is presented. Their ages at first evaluation were 4 years 7 months and 6 years 3 months. Both are now adults and continue to have a severe pervasive developmental disorder, mental retardation, seizure disorder, and are non-verbal. Both require residential care.

Fetal alcohol syndrome: maternal and neonatal characteristics.

UNLABELLED: Alcohol is the most common identifiable teratogenic cause of mental retardation in North America. Fetal Alcohol Syndrome (FAS) is a major public health problem, which is frequently under diagnosed by physicians. OBJECTIVE: To identify and quantify the maternal risk factors and neonatal characteristics of children with FAS. DESIGN: A retrospective case-control study using birth certificate data of North Dakota children diagnosed with FAS. Five controls were selected for each patient. Controls were selected from the computerized birth registry and matched by gender, year and month of birth. SUBJECTS AND SETTING: A list of all the children diagnosed with FAS from the North Dakota FAS Registry was sent to the State Health Department. We were able to locate the birth certificates for 132 (56%) of the 228 cases on the registry. RESULTS: Of the 132 FAS cases, 106 (80.3%) were Native Americans and 24 (18.2%) were Caucasians. In this sample 51 (38.6%) of the cases were male and 81 (61.4%) were female. Statistically significant maternal characteristics at p < 0.01 were: older mother's age, lower education level, fewer months of prenatal care, fewer prenatal visits, lower gestational age at time of delivery and less prenatal weight gain. Significant neonatal differences at p < 0.01 were lower birth weight and Apgar scores and higher incidence of congenital malformations. CONCLUSION: FAS is a completely preventable developmental disability. Consumption of alcohol during pregnancy can result in lifelong physical and mental impairments on the fetus. All pregnant women should be screened for alcohol use during prenatal visits. Women with positive screens or at high risk should be identified early by the primary care physician and referred for treatment and counseling.

Reductions in self-injury produced by transcutaneous electrical nerve stimulation.

Transcutaneous electrical nerve stimulation is used to reduce pain but also may be useful for self-injurious behavior (SIB). In the current investigation, a microcurrent electromedical device, classified as a transcutaneous electrical nerve stimulator (TENS), was applied with a man with Down syndrome who displayed SIB that persisted in the absence of social contingencies. Although clinically significant results were not maintained, a clear difference in the rates of SIB during active and inactive TENS was observed.