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Biomedical subjects

H M Barr

Publications and source records attributed to H M Barr.

36 records · Page 2Linked to original sources

Facial effects of fetal alcohol exposure: assessment by photographs and morphometric analysis.

This study was designed to assess the limits of alcohol-related facial dysmorphogenesis. Standard full face and lateral facial photographs were obtained on 21 7-year-old children who had been exposed gestationally to known, heavy quantities of ethanol. Only two of these children had been previously considered to have definite fetal alcohol syndrome (FAS). Similar photographs of 21 other 7-year-old children with negligible gestational ethanol exposure were obtained for control purposes. Copies of the 42 photographs were given to each of seven expert clinicians who were asked to select any child with an FAS-related facial appearance. Six of seven judges were accurate in identifying children with high levels of alcohol exposure as having a fetal alcohol-affected face. A set of homologous points on the photographs were then digitized and analyzed by newly developed morphometric methods to determine the facial shape characteristics that distinguish the selected photographs of highly exposed children. The analysis confirmed that the judges specifically identified children with facial changes consistent with those previously published as defining the face of the FAS: short palpebral fissures, a relatively long and flat midface, and a retrusive mandible. This methodology may be useful in more accurately delineating the facial phenotype in other conditions diagnosed primarily on the basis of subjective clinical criteria.

Anthropometry↗

Aspirin and acetaminophen use by pregnant women and subsequent child IQ and attention decrements.

In a longitudinal prospective study of 1,529 women pregnant in 1974-1975, aspirin and acetaminophen were the two medications most frequently taken during the first half of pregnancy (46 and 41%, respectively). In a selected cohort of 421 offspring of these women, examined at 4 years of age, maternal aspirin use during the first half of pregnancy was significantly related to IQ and attention decrements in the exposed children. Multiple regression analyses were used to statistically adjust for a variety of potentially confounding factors including demographic characteristics, child characteristics, other exposures, and lifestyle/environmental variables. Continuous dose-response and step-function parameterizations of aspirin exposure were both statistically significant and not clearly distinguishable from each other. The estimated aspirin effect is significantly greater for girls than boys. Aspirin effects on offspring function were found in the absence of effects on physical size both at birth and at 4 years. Maternal acetaminophen use was not significantly related to child IQ or attention. As this exploratory research originated from observations of a data set gathered for other purposes, it would be desirable to have these findings replicated in other studies. Further follow-up of the children at a later age is planned.

Acetaminophen↗

Studying alcohol teratogenesis from the perspective of the fetal alcohol syndrome: methodological and statistical issues.

Alcohol is a teratogenic drug and the effects appear to be grossly dose related. The severest effects are observable clinically as the fetal alcohol syndrome and are associated with heavy prenatal alcohol exposure and a history of chronic maternal abuse of alcohol. Hypotheses for subtler behavioral effects associated with lower levels of exposure can be generated from observation of the behavioral effects in FAS. Behavioral effects associated with various levels of prenatal alcohol exposure in humans include poor sucking and poor habituation in the newborn, poorer mental and motor development in infancy, and attentional and reaction time effects at four and seven years of age. Human behavioral teratology studies are necessarily complex due to the large number of covariates that affect behavior, modify the effects of teratogens, and influence interpretation. Challenging problems exist in assessing exposure, outcomes, and covariates. Common to assessment of all these classes of variables are the multiplicity of measurement and the indirect nature of the measurement. Answering specific questions about timing and dose effects demands careful statistical modeling procedures and large, complex data bases. Large data bases and indirect measurement problems suggest factor analytic extensions of current regression methodology, which we have proposed in this paper.

Child, Preschool↗

Alcohol exposure in utero and functional deficits in children during the first four years of life.

The behavioural effects of varying amounts of alcohol exposure in utero were studied using a longitudinal prospective design. An unselected sample of 1529 pregnant women was interviewed in the fifth month of pregnancy regarding beverage consumption, diet, drug use, and socioeconomic background; a cohort of approximately 500 infants was selected at delivery for follow-up. Lengthy individual behavioural and anthropometric examinations were made of the children between birth and four years of age. Alcohol-related behavioural effects are still statistically significant at four years, as they were at birth and eight months, even after adjustment for variables such as maternal smoking, drug use and diet, education, birth order and family stress. Habituation, sucking pressure and latency to suck are some of the behaviours most affected on days 1 and 2, while reaction time, attention and response latency are most affected at four years. Thus alcohol exposure in utero appears to affect the speed and accuracy of information-processing in the offspring. The findings support a dose-response rather than a threshold effect on most of these behavioural outcomes. However, increased risk of a clinically suspect or abnormal child occurs only at the heavier drinking levels. Examination of the cohort of 500 children at seven years of age is under way.

Child Behavior Disorders↗

Infant size at 8 months of age: relationship to maternal use of alcohol, nicotine, and caffeine during pregnancy.

To examine the relationship of maternal alcohol consumption, caffeine use, and smoking to infant size at 8 months of age, a follow-up cohort of 453 infants was examined at birth and again at their 8-month birthday. Even after adjustment for other relevant variables, maternal alcohol use during early pregnancy (average ounces of absolute alcohol by self-report) was significantly related to infant weight and length at 8 months of age but not as strongly related to head circumference. Maternal smoking and caffeine use during pregnancy were not significantly related to infant size at 8 months, although nicotine use had been highly related to the birth size in this sample. Maternal use of marijuana was significantly and negatively related to infant length at 8 months of age, but not to weight or head circumference. The magnitude of the growth retardation is smaller at 8 months than at birth in this sample of infants whose mothers are primarily white, married, and well-educated, and who report a variety of alcohol use patterns. Significance was tested using multiple regression analyses that adjusted for the effects of nicotine use, caffeine use, birth order, maternal height, and gestational age as well as sex and age of infant at examination.

Alcohol Drinking↗

Comparison of drinking and smoking patterns during pregnancy over a six-year interval.

Changes in the drinking and smoking habits of pregnant women in Seattle, Washington, were examined in the 6-year period that followed the first American announcement of the fetal alcohol syndrome. Between 1974/1975 and 1980/1981, the number of women who reported any alcohol use around the time of the first prenatal visit dropped from 81% to 42%, whereas the number of smokers dropped from 25% to 22%; binge and heavier drinking also declined. However, among drinkers, there was no decrease in the proportion of women who reported heavier drinking. Although the proportion of women who drink during pregnancy has decreased in the past 6 years, the relative constancy in the proportion of "heavier" drinkers and binge drinkers, particularly around the time of conception, suggests the need for more attention to this important period of gestation in advice to women who are planning a pregnancy. Possible reasons for such changes in this particular community are discussed.

Adolescent↗

Alcohol use and iron status in pregnant women.

Iron status, assessed by ferritin (ng/ml), transferrin saturation (%), and hemoglobin (g/100 ml), was examined in a sample of 1398 women from blood samples drawn at their first prenatal visit and in 712 of these women later at their 32-week prenatal visit. Self-reported alcohol use (average ounces of absolute alcohol consumed per day around the time of conception) was not systematically related to iron status. Furthermore, the proportion of iron-depleted or anemic women did not vary according to different levels of alcohol use. An exception is noted in a small group of nine very heavy drinkers, reporting eight or more drinks per day, who, at 32 weeks gestation, had a higher proportion of iron depletion but not anemia. It was concluded that at least in a sample of primarily middle class women receiving good prenatal care, iron depletion and/or anemia probably do not explain the alcohol-related adverse pregnancy outcomes that have been reported previously. Nevertheless, results from several very heavy drinkers suggest that the iron status of pregnant alcoholic women should be investigated further.

Adolescent↗

Maternal alcohol use and neonatal habituation assessed with the Brazelton scale.

Newborn behavioral effects of intrauterine alcohol exposure were examined in 417 infants given the Brazelton Neonatal Assessment Scale. In this longitudinal prospective study, maternal alcohol use was obtained by self-report during the fifth month of pregnancy. Factor analysis of the Brazelton scale yielded 6 factors that were entered into a multiple regression analysis as dependent variables. Maternal alcohol use in mid-pregnancy was significantly related to poorer habituation and increased low arousal in newborn infants, even after adjusting for smoking and caffeine use by mothers, maternal age and nutrition during pregnancy, sex and age of the infant, and obstetric medication. This study lends further support to recognition of maternal alcohol use during pregnancy as a risk factor for alterations in newborn behavior.

Adult↗

Offspring effects and pregnancy complications related to self-reported maternal alcohol use.

The purpose of this research was to study the relationship between alcohol use (assessed by self-report) and status of the newborn (assessed from medical records). Sample size was 1,439 and the mothers were primarily white, married, and of middle socioeconomic class. Maternal alcohol use during pregnancy was related to low Apgar scores, bradycardia, variable deceleration, and respiratory distress. These results were not accounted for by other factors that were also examined such as maternal smoking, use of caffeine, "street' drugs, prenatal care or weight gain during pregnancy. While this study cannot evaluate the possible discrepancy between self-reported and actual alcohol consumption, these data suggest an increased risk for neonatal distress among infants of mothers who report alcohol use patterns that are often considered within the realm of social drinking.

Abnormalities, Drug-Induced↗

The Seattle longitudinal prospective study on alcohol and pregnancy.

An unselected sample of 1529 women (predominantly white, married, and middle-class) were interviewed during pregnancy regarding their use of alcohol, nicotine, caffeine, drugs, and other variables. Subsets of offspring were examined to assess the relationship of self-reported maternal alcohol use to infant health and development. Multiple regression statistical tests were utilized to permit adjustment for other possibly confounding factors. The following are among those outcomes significantly related to increase maternal alcohol use after adjusting for smoking and other variables: smaller infant size (birth weight, length and head circumference); lower Apgar scores; poorer neonatal habituation; decreased sucking pressure; increased tremulousness and head-turns-to-left; decreased vigorous activity; and a higher frequency of minor dysmorphic characteristics combined with low birth weight and microcephaly. A drinking by smoking interaction was related to poorer newborn conditioning in two separate studies. Significantly lower mental and motor development and lower length and weight were found on follow-up of 468 infants at age 8 months. Follow-up studies continue.

Alcohol Drinking↗

Decreased birth weight in infants of alcoholic women who abstained during pregnancy.

Fifty infants born to women who reported total abstinence during pregnancy, but who had a history of alcoholism prior to conception, were compared to 50 infants born to alcoholic women who reported drinking heavily during pregnancy, and to 50 infants of nonalcoholic controls. Mean birth weight of infants born to the abstinent alcoholics was 258 gm less than mean birth weight of the control infants. Infants of drinking alcoholics weighed 493 gm less than the control infants. These differences in offspring birth weight were statistically significant after adjusting for maternal smoking, height, age, and parity, as well as gestational age and sex of child. This finding suggests that a history of maternal alcoholism may pose a risk to fetal growth independent of alcohol use during the pregnancy.

Adult↗

Effects of maternal alcohol, nicotine, and caffeine use during pregnancy on infant mental and motor development at eight months.

Infant mental and motor development at 8 mo of age is significantly related to maternal alcohol use during early pregnancy. Data on 462 infants were analyzed with multiple regression techniques, adjusting for effects of nicotine, caffeine, gestational age, parity, and maternal education. Other possible intervening variables were evaluated and not found to explain the results. This study presents further evidence that maternal alcohol use during pregnancy at levels of about four drinks per day and above has an adverse effect on offspring, even in a sample that is basically low risk.

Adolescent↗

Neurobehavioral effects of prenatal alcohol: Part I. Research strategy.

This paper, Part I of a three-part series, reviews the literature on the neurobehavioral effects of prenatal alcohol exposure and describes a large group of tests assembled to assess neurobehavioral outcomes of alcohol teratogenesis in 7-year-old children. This paper presents the distribution of these test scores for our sample and discusses their relationships with an alcohol binge score and with full-scale IQ. This group of tests is suitable for children with a wide range of abilities and provides a broad assessment of neurobehavioral deficits. Part II of this series describes a new method of statistical analysis, Partial Least Squares (PLS), which is particularly well suited to complex multivariate data sets such as these, and with its aid, examines the effects of prenatal alcohol exposure on IQ, achievement, vigilance and classroom behavior, a total of 43 outcome scores. Part III examines prenatal alcohol effects on outcomes from the broad group of 164 scores deriving from 17 neuropsychologic tests, using the Partial Least Squares methodology, and summarizes the implications of our findings for the behavioral teratology of alcohol.

Child↗

Neurobehavioral effects of prenatal alcohol: Part II. Partial least squares analysis.

This paper, the second in a series of three, introduces Partial Least Squares (PLS) methods for assessing the effects of moderate levels of prenatal alcohol exposure on performance and behavior in young school-age children. Studies of human behavioral teratology pose statistical problems for which standard multiple regression methods are inadequate. Prenatal alcohol exposure, the teratogenic "dose," can be assessed only indirectly through a variety of measures of alcohol consumption. Similarly, the behavioral outcomes we examine--IQ, achievement, classroom behavior, and vigilance--are each measured indirectly in terms of multiple items or indicators. We find that a single latent variable, estimated as a linear combination of the measures of alcohol consumption, provides an appropriate measure of "dose" for summarizing the relationships between alcohol exposure and each of the four blocks of outcome variables. A pattern of alcohol consumption emphasizing binge behavior (i.e., reporting average consumption of multiple drinks per drinking occasion, or at least five drinks on any single occasion) in the period prior to recognition of pregnancy is significantly correlated with latent variables computed from each of the four outcome blocks: IQ, academic achievement, classroom behavior and attention/vigilance.

Arousal↗

Neurobehavioral effects of prenatal alcohol: Part III. PLS analyses of neuropsychologic tests.

This paper is the third in a three-part series describing an investigation of the effects of prenatal alcohol exposure on the neurobehavioral functioning of 384 children about 7 1/2 years old. Here we describe the use of Partial Least Squares for data reduction and analysis of 158 neurobehavioral measures as they relate to 13 aspects of prenatal alcohol exposure. A general alcohol latent variable, emphasizing both binge and regular drinking patterns in the period prior to pregnancy recognition as well as during pregnancy, predicts a pattern of neurobehavioral deficit that includes attentional and memory deficits across both verbal and visual modalities; a variety of "process" variables reflecting poor integration and quality of responses; behavior patterns involving distractibility and poor organization; and an inflexible approach to problem-solving. The prominence of poorer spatial organization and arithmetic as primary outcomes of alcohol teratogenesis suggests a possible "nonverbal learning disability" pattern of deficit associated with prenatal alcohol exposure at the level of social drinking.

Behavior↗

Caffeine use during pregnancy and child outcome: a 7-year prospective study.

Caffeine (from coffee, tea, cola, and/or chocolate) was the most frequently ingested drug among 1529 pregnant women interviewed in 1974-75. Linear and threshold effects of prenatal caffeine on pregnancy outcome and offspring development were examined in a cohort of approximately 500 offspring. After appropriate statistical adjustment for relevant covariates (cigarette smoking, alcohol, maternal size, demographics, etc.) prenatal caffeine exposure was not related to most newborn and infant outcome measures, including height, weight or head circumference, or to individually administered IQ and attention tests at 7 years of age. Only one isolated dependent variable of the many was significantly associated with prenatal caffeine exposure: namely breech presentation. However, since this report involved a secondary analysis of data gathered for other purposes, specifically designed studies would be required to determine the validity of the observed association for any particular variable. The general conclusion is that the long-term consequences of prenatal caffeine in this cohort are null.

Adolescent↗

Neonatal neurobehavioral outcome following prenatal exposure to cocaine.

This substudy of a longitudinal prospective study was designed to assess neurodevelopmental and neurobehavioral performance in newborn infants who were maternally exposed to cocaine and other drugs of abuse or the other drugs without cocaine. Sample selection procedures were designed to permit statistical control for marijuana, alcohol, and tobacco. Cocaine was assessed with both self-report and radioimmunoassay of hair. One hundred ninety-one newborns with a mean age of 43 h were assessed for 35 to 40 min on tests of reflexes, activity level, head-turning preference, tremors, nonnutritive sucking, habituation, and state. The testers were blinded to the baby's drug exposure. Cocaine-exposed newborns were developmentally at risk on the tests administered compared to infants exposed to the other three drugs alone or in some combination. A dose-response effect was found: higher amounts of cocaine were associated with higher neurobehavioral risk scores.

Adolescent↗

Attention, distraction and reaction time at age 7 years and prenatal alcohol exposure.

This report is one phase of a longitudinal prospective study on the behavioral teratology of alcohol. The present study evaluated the effect of early prenatal alcohol exposure (assessed during pregnancy) on reaction time, attention and distraction in 475 young school-age children who took a computerized CPT vigilance task. Multiple regression analyses were adjusted for a variety of co-variates including other exposures, postnatal conditions and demographics. Prenatal alcohol exposure was most significantly related to CPT errors of commission, reaction time, and the vigilance errors summary score. Error scores on the vigilance task were also significantly correlated with independent behavior ratings of endurance, persistence, organization, distractibility and impulsivity. This study supports and extends earlier reports of alcohol-related attentional deficits observable in the neonatal period and in the preschool years.

Attention↗