Implementation of a shared data repository and common data dictionary for fetal alcohol spectrum disorders research.

Many previous attempts by fetal alcohol spectrum disorders researchers to compare data across multiple prospective and retrospective human studies have failed because of both structural differences in the collected data and difficulty in coming to agreement on the precise meaning of the terminology used to describe the collected data. Although some groups of researchers have an established track record of successfully integrating data, attempts to integrate data more broadly among different groups of researchers have generally faltered. Lack of tools to help researchers share and integrate data has also hampered data analysis. This situation has delayed improving diagnosis, intervention, and treatment before and after birth. We worked with various researchers and research programs in the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CI-FASD) to develop a set of common data dictionaries to describe the data to be collected, including definitions of terms and specification of allowable values. The resulting data dictionaries were the basis for creating a central data repository (CI-FASD Central Repository) and software tools to input and query data. Data entry restrictions ensure that only data that conform to the data dictionaries reach the CI-FASD Central Repository. The result is an effective system for centralized and unified management of the data collected and analyzed by the initiative, including a secure, long-term data repository. CI-FASD researchers are able to integrate and analyze data of different types, using multiple methods, and collected from multiple populations, and data are retained for future reuse in a secure, robust repository.

Alcohol use before and during pregnancy in western Washington, 1989-2004: implications for the prevention of fetal alcohol spectrum disorders.

OBJECTIVE: We examined trends in rates of self-reported pregnancy alcohol use among women in western Washington. STUDY DESIGN: Between 1989 and 2004, we conducted 3 studies in western Washington State on problems that are associated with maternal prenatal alcohol or drug abuse (n = 12,526). To determine study eligibility, we screened hospitalized postpartum women for alcohol and drug use in the month before and during pregnancy. We examined trends in alcohol use rates and identified characteristics that were associated with any drinking and binge drinking (> or = 5 drinks on any occasion). RESULTS: We found a substantial decrease in pregnancy alcohol use between 1989 and 2004 (from 30-12%) across almost all demographic categories. Binge drinking in the month before pregnancy increased significantly among all race categories, except Native American. CONCLUSION: Increased prepregnancy binge drinking rates may estimate alcohol use during very early gestation and warrant clinical attention because of the potential for fetal alcohol spectrum disorders.

Many infants prenatally exposed to high levels of alcohol show one particular anomaly of the corpus callosum.

INTRODUCTION: Effects of prenatal alcohol exposure on the brain are seen at every age. The earlier they can be quantified, the better the prognosis for the affected child. Here we show measurable alcohol effects at birth on a structure currently used for nosology only much later in life. METHODS: Midline shape of the corpus callosum was imaged in infants via averaged unwarped transfontanelle ultrasound. We compared measures of these shapes among 23 infants prenatally exposed to high levels of alcohol and 21 infants unexposed to alcohol or only lightly exposed. RESULTS: A particular feature of the corpus callosum, the appearance of a "hook" (obtuse angle) between the splenium and the long diameter of the arch in this plane, is strongly associated with prenatal alcohol exposure. In half of the high-exposed infants, the splenium angle is larger than in any of the unexposed brains. Simply characterizing this angle as less than or greater than 90 degrees detects 12 of the 23 exposed infants as anomalous with only 1 false positive among the unexposed. This apparently direct effect of prenatal ethanol exposure on the details of the callosum in about half the at-risk subjects cannot be attributed to any of several plausible competing exposures or other confounding factors applying during or after gestation. CONCLUSION: An average of the images for the unexposed subjects has the geometry of textbook images of normal babies; but the average for the subgroup of high-angle subjects may serve as a template or guide to this regional damage parallel to the familiar photographic exemplars that help to assess facial signs.

Damage to the human cerebellum from prenatal alcohol exposure: the anatomy of a simple biometrical explanation.

Since 1973, it has become clear that exposure of otherwise normal human fetuses to high levels of alcohol damages a substantial number of the exposed brains in a wide variety of ways nowadays referred to collectively as the fetal alcohol spectrum disorders (FASDs). Averages of images and measurements of brains with these disorders are quantitatively different from normal, and the cerebellum is one of the structures at which differences are typically noted. The present article extends these techniques to a simple, practical, and enlightening detection rule for fetal alcohol damage in adolescents and adults known to have been heavily exposed. The data arise from 180 clinical MR brain images (half of adolescents, half of adults; half male, half female; one-third each fetal alcohol syndrome, fetal alcohol effects, and unexposed). The 180 cerebellums were represented by 328-semilandmark triangulations covering most of the cerebellar surface. Statistical analysis exploited the now-conventional methods of Procrustes analysis in three dimensions, along with a recent extension to incorporate size information explicitly. If we reduce the data complexity even further, to just 23 points along the silhouette of the cerebellum as viewed from above along the aqueductal axis, the analysis becomes more precise. Now a single multivariate summary score, very strongly correlated with size, supports a discrimination (diagnosed vs. unexposed) with about 75% accuracy. About one-quarter of our FASD sample overlaps with the central range of the unexposed in the distribution of this size-based score, with the other three-quarters distinctly showing cerebellar damage. The finding, which corresponds quite closely to the fundamental finding of cerebellar hypoplasia in animal experiments, bears implications for fetal alcohol epidemiology, for geometric morphometrics, and for the geometric complexity of useful data structures derived from clinical brain imaging.

Binge drinking during pregnancy as a predictor of psychiatric disorders on the Structured Clinical Interview for DSM-IV in young adult offspring.

OBJECTIVE: This study explored the extent to which the high frequency of psychiatric problems reported in clinical groups with fetal alcohol spectrum disorders might also be observed in a nonclinical group of young adults and the psychiatric conditions that are related to prenatal alcohol exposure in this group. METHOD: From a longitudinal prospective study beginning with interviews of 1,529 pregnant women, a birth cohort of about 500 newborns was chosen to include all of the most heavily alcohol exposed plus a sampling of the continuum of alcohol exposures from total abstinence through heavy drinking. At an average age of 25.7 years, 400 members of this birth cohort were administered valid Structured Clinical Interviews for DSM-IV (SCID), including both the SCID for axis I disorders and the SCID for axis II personality disorders. RESULTS: The odds of the appearance of six psychiatric disorders and traits were more than double in adults exposed to one or more binge alcohol episodes in utero. Three of these six odds ratios were uniformly stable against confounding: axis I substance dependence or abuse disorders and axis II passive-aggressive and antisocial personality disorders or traits. CONCLUSIONS: Prenatal exposure to alcohol may be a risk factor for specific psychiatric disorders and traits in early adulthood, even in a nonclinical group.

Effects of prenatal alcohol exposure on fine motor coordination and balance: A study of two adult samples.

Motor coordination was assessed in two samples of adult subjects: one sample (n = 90) included adults previously diagnosed with one of a number of Fetal Alcohol Spectrum Disorders (FASD) and comparison peers, the second was a prospective longitudinal study of adults who were exposed to varying levels of alcohol as fetuses (n = 402). This comparative analysis sought to determine whether motor effects seen in both clinical and nonclinical children persist into adulthood, whether any individual motor tasks show significant effects of prenatal alcohol exposure across the age range, and whether motor assessments of adults have any role in diagnostic strategies for adults suspected of FASD. Motor tests included balance and unilateral, bilateral, finger, hand and foot coordination. Three-quarters of the subjects with FASD demonstrated deficits in motor function outside the range of comparison subjects. Adults with FASD performed more poorly, on average, on all individual tests including balance and fine motor control. In the prospective longitudinal sample, only subjects who had been previously identified in childhood as having a possible diagnosis on the Fetal Alcohol Spectrum were still in deficit as adults on motor tasks, relative to comparison subjects. Thus, the dose-dependent motor coordination effects of alcohol previously found in children do not appear to persist into adulthood, except in those most highly exposed children who also have other accompanying neuropsychological effects in childhood.

Preliminary evidence that prenatal alcohol damage may be visible in averaged ultrasound images of the neonatal human corpus callosum.

Brain damage consequent to prenatal alcohol exposure can be detected by measurements of the corpus callosum in the midline magnetic resonance (MR) brain image in adolescents and adults. The present article extends this finding into the neonatal period, when the power of detection to ameliorate the quality of the child's future life is greatest. The midline corpus callosum of the very young infant can be located reliably in multiple frames of clinical transfontanelle ultrasound. We studied a sample of 18 children aged 17 weeks or less, 7 of whom were exposed to high levels of alcohol prenatally and 11 of whom were not exposed or only minimally exposed. The midline callosum of each child was imaged up to 50 times by a standard clinical device, and coplanar subsets of these series were averaged with reference to fiducial image structures. On each average image four semilandmark points were set and their configuration quantified by standard landmark methods. The angle between the terminal bulb of splenium and the long axis of the callosal outline classifies four of the seven exposed infants as different from all 11 of the unexposed infants. This simple angle measurement upon averaged ultrasound images of the human neonatal midline corpus callosum, perhaps a version of the long-sought "biomarker of prenatal alcohol damage," may be able to discriminate baby brains affected by prenatal alcohol exposure from those that were unaffected.

Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects.

Clinical descriptions of patients with Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) suggest major problems with adaptive behavior. Five operationally defined adverse outcomes and 18 associated risk/protective factors were examined using a Life History Interview with knowledgeable informants of 415 patients with FAS or FAE (median age 14 years, range 6-51; median IQ 86, range 29-126). Eighty percent of these patients were not raised by their biological mothers. For adolescents and adults, the life span prevalence was 61% for Disrupted School Experiences, 60% for Trouble with the Law, 50% for Confinement (in detention, jail, prison, or a psychiatric or alcohol/drug inpatient setting), 49% for Inappropriate Sexual Behaviors on repeated occasions, and 35% for Alcohol/Drug Problems. The odds of escaping these adverse life outcomes are increased 2- to 4-fold by receiving the diagnosis of FAS or FAE at an earlier age and by being reared in good stable environments.

A 21-year longitudinal analysis of the effects of prenatal alcohol exposure on young adult drinking.

BACKGROUND: Prenatal alcohol exposure may be a risk factor for the development of alcohol problems in humans. METHODS: We use data beginning with interviews of women in prenatal care at midpregnancy to predict alcohol use and alcohol-related problems in their offspring now aged 21 years. Maternal drinking during pregnancy was assessed from November 4, 1974, through October 2, 1975, along with measures of maternal smoking, use of caffeine and other drugs, and demographic factors. Family history of alcohol problems was assessed from interviews with parents when offspring were 14 years of age and updated when offspring were 21 years of age. Measures of parental use of alcohol and other drugs and many aspects of the family environment were assessed at 7 different ages, prenatally through 21 years. Young adult offspring (age, 21 years [N = 433]) provided self-reports of drinking quantity and frequency and completed the Alcohol Dependence Scale as a measure of alcohol-related problems and dependence. RESULTS: Univariate, partial least squares, and regression analyses indicate that prenatal alcohol exposure is significantly associated with alcohol problems at 21 years of age. The relationship persists independent of the effects of family history of alcohol problems, nicotine exposure, other prenatal exposures, and postnatal environmental factors including parental use of other drugs. Prenatal nicotine exposure was not associated with alcohol problems by offspring at 21 years of age. CONCLUSIONS: Prenatal alcohol exposure is a risk factor for the development of drinking problems in humans. Potential mechanisms for the role of fetal exposure and the development of alcohol problems deserve study.

Midline corpus callosum is a neuroanatomical focus of fetal alcohol damage.

Prenatal exposure to high levels of alcohol often induces birth defects that combine morphological stigmata with neurological or neuropsychological deficits. But it has proved problematic to diagnose these syndromes in adolescents and adults, in whom the morphological signs are absent or attenuated, the behavioral deficits nonspecific, and the exposure history often difficult to reconstruct. Localizing the associated brain abnormalities might circumvent most of these difficulties. To this end, three-dimensional (3D) locations were recorded for 67 homologous points on or near the corpus callosum in magnetic resonance (MR) brain images from 60 adolescents and adults who were normal, 60 diagnosed with fetal alcohol syndrome, and 60 diagnosed with fetal alcohol effects. We combined the standard statistical approach to this type of geometric data, Procrustes analysis, with a multivariate strategy focusing on differences in variability. In this data set, the shape of the corpus callosum and its vicinity proves systematically much more variable in the alcohol-affected brains than in those of the normal subjects. From this excess variability follows a promising classification rule, having both high sensitivity (100 out of 117) and high specificity (49 out of 60) in this sample. The discrimination uses four landmark points and two summary scores of callosal outline shape. The information from the corpus callosum and vicinity, as viewed in MR brain images of full-grown subjects, may serve as a permanent record of the prenatal effects of alcohol, even in patients who are first suspected of these syndromes relatively late in life or who lack the facial signs of prenatal alcohol damage. The statistical pattern underlying the callosal diagnosis also leads to speculations on mechanisms of the prenatal damage.

Corpus callosum shape and neuropsychological deficits in adult males with heavy fetal alcohol exposure.

Persons with brain damage consequent to prenatal alcohol exposure have typically been diagnosed with either fetal alcohol syndrome (FAS) or fetal alcohol effects (FAE), depending on facial features. There is great variability of behavioral deficits within these groups. We sought to combine neuroanatomical measures with neurocognitive and neuromotor measures in criteria of greater sensitivity over the variety of consequences of alcohol exposure. To this end, midline curves of the corpus callosum were carefully digitized in three dimensions from T1-weighted MR scans of 15 adult males diagnosed with FAS, 15 with FAE, and 15 who were unexposed and clinically normal. From 5 h of neuropsychological testing we extracted 260 scores and ratings pertaining to attention, memory, executive function, fine and gross motor performance, and intelligence. Callosal midline shape was analyzed by new morphometric methods, and the relation of shape to behavior by partial least squares. The FAS and FAE subgroups have strikingly more variability of callosal shape than our normal subjects. With the excess shape variation are associated two different profiles of behavioral deficit unrelated to full-scale IQ or to the FAS/FAE distinction within the exposed subgroup. A relatively thick callosum is associated with a pattern of deficit in executive function; one that is relatively thin, with a deficit in motor function. The two combine in a very promising bipolar discrimination of the exposed from the unexposed in this sample. Thus there is considerable information in callosal form for prognosis of neuropsychological deficits in this frequently encountered birth defect.

Three-year developmental outcomes in children with prenatal alcohol and drug exposure.

PURPOSE: The purpose of this study was to describe the performance of children whose mothers abused alcohol and drugs heavily during pregnancy, using the Bayley Scales of Infant Development Second Edition (BSID-II) at three years, and to examine the effects of study group, prenatal binge alcohol exposure, and prematurity on developmental outcome. METHODS: Children were born to mothers recruited from two large hospitals or through community referral. Hospital recruits were randomly assigned to either a three-year paraprofessional home visitation intervention program (n = 30) or a control group (n = 31). Community recruits were enrolled in the intervention program (n = 35). RESULTS: Among all children the mean BSID-II Mental Developmental Index (MDI) was 84.4 (SD = 14.4) and mean Psychomotor Developmental Index (PDI) was 84.1 (SD = 16.9). Box plots of the MDI and PDI scores by study group, maternal prenatal binge alcohol status, and a binary indicator of prematurity suggested an effect of maternal binge drinking on MDI and PDI scores: children of mothers with a history of binge alcohol consumption have, on average, slightly lower scores. We saw no evidence of a systematic effect of the maternal intervention. CONCLUSIONS: Developmental performance of preschool children exposed to alcohol and drugs prenatally was, on average, substantially lower than expected for age regardless of study group. Although this home visitation intervention has been shown to be effective in helping mothers address a wide spectrum of needs, it is unlikely sufficient to overcome complex developmental risks of children exposed to alcohol and drugs prenatally. The effect of more comprehensive, multidimensional services specifically designed for the children should be investigated within this context.

Effects of Prenatal Exposure to Alcohol Across the Life Span.

Prenatal exposure to alcohol can have many detrimental effects throughout the life span. Of primary concern are changes in the brain that lead to deficiencies in cognitive functioning, including memory and learning problems, attention deficits, poor motor coordination, and difficulties with problem-solving. These cognitive deficiencies create long-standing problems in many spheres of life, including disturbances in work, school, and social functioning. Treatment strategies that have been used with other cognitively impaired populations may be adapted to assist patients who display the various cognitive symptoms associated with prenatal alcohol exposure.

A Long-Term Perspective of FAS.

Few people in their adolescent or adult years are diagnosed as having FAS. Studies have shown that most FAS patients outgrow the characteristic FAS facies after puberty. However, they may still suffer from mental handicaps and have poor age-appropriate life skills. Further research is needed to understand these patients' unique needs and to develop the most effective intervention strategies.