Levels Of Prenatal Alcohol Exposure Research Articles

Guidelines for pregnancy: What's an acceptable risk, and how is the evidence (finally) shaping up?

The lack of consensus about whether low to moderate levels of prenatal alcohol exposure are a risk factor for fetal development has generated considerable debate about what advice policies and guidelines should provide. This paper reviews the evidence from systematic reviews and meta-analyses examining the risk from low and moderate levels of prenatal alcohol exposure, along with the results of articles published 2009-2010, after the reviews. The reported significant effects from low levels of prenatal alcohol exposure are likely due to methodological issues such as confounding and/or misclassification of exposure or outcome and there is no strong research evidence of fetal effects from low levels of alcohol exposure. However, harm is well-documented with heavy exposure and moderate levels of exposure, 30-40 g per occasion and no more than 70 g per week, have been demonstrated to increase the risk of child behaviour problems. With such a small margin before there is increased risk to the fetus, it would be morally and ethically unacceptable for policies and guidelines to condone consumption of alcohol during pregnancy. Not all women will follow this advice and some women will inadvertently consume alcohol prior to pregnancy awareness requiring non-judgmental counselling and the provision of rational advice about the likelihood of risk to the fetus. The policy advice that 'the safest choice for pregnant women is to abstain from alcohol during pregnancy' should be maintained. However, the abstinence message needs to be presented in a balanced and rational manner to prevent unintended negative consequences.

Prenatal alcohol exposure and cortisol activity in 19-month-old toddlers: an investigation of the moderating effects of sex and testosterone

Early exposure to stress and teratogenic substances have an impact on brain structures involved in cognition and mental health. While moderate-to-high levels of prenatal alcohol exposure (PAE) have repeatedly been associated with long-term neurodevelopmental deficits, no consensus has yet been reached on the detrimental effects of low-to-moderate PAE on the children's functioning, including the limbic-hypothalamic-pituitary-adrenal axis. The study aims to examine the association between low PAE and cortisol response to unfamiliar situations in 19-month-old children and to determine whether this association was moderated by sex and testosterone levels. Information regarding PAE, cortisol response to unfamiliar situations, and testosterone activity was available in a total of 130 children participating to the Québec Newborn Twin Study (Montréal, QC, Canada). Mother alcohol consumption during pregnancy was assessed via a semistructured interview conducted when the children were 6 months of age. The contribution of prenatal and postnatal confounds were examined. Disrupted patterns of cortisol activity were observed only in PAE males. Testosterone tended to be negatively associated with the cortisol response, but not for PAE males, suggesting an altered sensitivity to the inhibitory effects of testosterone in these participants. Low levels of PAE were associated with disrupted cortisol activity, and males may be at higher risk. These findings challenge the existence of a "safe level" of alcohol consumption during pregnancy and have public health implications.

Magnetic Resonance Imaging Outcomes From a Comprehensive Magnetic Resonance Study of Children With Fetal Alcohol Spectrum Disorders

Magnetic resonance (MR) technology offers noninvasive methods for in vivo assessment of neuroabnormalities. A comprehensive neuropsychological/psychiatric battery, coupled with MR imaging, (MRI), MR spectroscopy (MRS), and functional MRI (fMRI) assessments, were administered to children with fetal alcohol spectrum disorders (FASD) to determine if global and/or focal abnormalities could be identified, and distinguish diagnostic subclassifications across the spectrum. The 4 study groups included: (i) fetal alcohol syndrome (FAS)/partial FAS (PFAS); (ii) static encephalopathy/alcohol exposed (SE/AE); (iii) neurobehavioral disorder/alcohol exposed (ND/AE) as diagnosed with the FASD 4-Digit Code; and (iv) healthy peers with no prenatal alcohol exposure. Presented here are the MRI assessments that were used to compare the sizes of brain regions between the 4 groups. The neuropsychological/behavioral, MRS, and fMRI outcomes are reported separately. Progressing across the 4 study groups from Controls to ND/AE to SE/AE to FAS/PFAS, the mean absolute size of the total brain, frontal lobe, caudate, putamen, hippocampus, cerebellar vermis, and corpus callosum length decreased incrementally and significantly. The FAS/PFAS group (the only group with the 4-Digit FAS facial phenotype) had disproportionately smaller frontal lobes relative to all other groups. The FAS/PFAS and SE/AE groups [the 2 groups with the most severe central nervous system (CNS) dysfunction] had disproportionately smaller caudate regions relative to the ND/AE and Control groups. The prevalence of subjects in the FAS/PFAS, SE/AE, and ND/AE groups that had 1 or more brain regions, 2 or more SDs below the mean size observed in the Control group was 78, 58, and 43%, respectively. Significant correlations were observed between size of brain regions and level of prenatal alcohol exposure, magnitude of FAS facial phenotype, and level of CNS dysfunction. Magnetic resonance imaging provided further validation that ND/AE, SE/AE, and FAS/PFAS as defined by the FASD 4-Digit Code are 3 clinically distinct and increasingly more affected diagnostic subclassifications under the umbrella of FASD. Neurostructural abnormalities are present across the spectrum. MRI could importantly augment diagnosis of conditions under the umbrella of FASD, once population-based norms for structural development of the human brain are established.

Prenatal Alcohol Exposure and Language Delay in 2-Year-Old Children: The Importance of Dose and Timing on Risk

The aim of this study was to investigate the association of dose and timing of prenatal alcohol exposure with early language acquisition. We examined language delay in a randomly selected, population-based sample of Western Australian children born in 1995-1996 whose mothers had agreed to participate in a longitudinal study on health-related behaviors and who had completed the 2-year questionnaire (N = 1739). Information on alcohol consumption was collected at 3 months after birth for four periods; the three months pre-pregnancy and for each trimester separately. Prenatal alcohol exposure was grouped into none, low, moderate-heavy and binge (>5) based on the total quantity consumed per week, quantity consumed per occasion, and frequency of consumption. The communication scale from the Ages & Stages Questionnaire was used to evaluate language delay. Logistic regression analysis was used to generate odds ratios and 95% confidence intervals, adjusted for confounding factors. There was no association between low levels of alcohol consumption and language delay at any time period, although there was a nonsignificant 30% increase in risk when moderate-to-heavy levels of alcohol were consumed in the third trimester. Children exposed to a binge pattern of maternal alcohol consumption in the second trimester had nonsignificant, three-fold increased odds of language delay, with a similar estimate following third trimester alcohol exposure after controlling for covariates. This study did not detect an association between low levels of prenatal alcohol exposure and language delay when compared with women who abstained from alcohol during pregnancy. A nonsignificant threefold increase in the likelihood of language delay was seen in children whose mothers binged during late pregnancy. However, the small numbers of women with a binge-drinking pattern in late pregnancy limited the power of this study; studies analyzing larger numbers of children exposed to binge drinking in late pregnancy are needed.

The effect of maternal alcohol consumption on fetal growth and preterm birth

To investigate the relationship between prenatal alcohol exposure and fetal growth and preterm birth and to estimate the effect of dose and timing of alcohol exposure in pregnancy. A population-based cohort study linked to birth information on the Western Australian Midwives Notification System. Western Australia. A 10% random sample of births restricted to nonindigenous women who had delivered a singleton infant (n= 4719) in 1995-1997. The impact of alcohol consumption in pregnancy on fetal growth (small-for-gestational-age [SGA] and large-for-gestational-age infants [LGA]) and preterm birth (<37 weeks of gestation) was assessed using multivariate logistic regression analysis and adjusting for confounding factors. Odds ratios and 95% CI, attributable risk, and population attributable risk were calculated. The percentage of SGA infants and preterm birth increased with higher levels of prenatal alcohol exposure; however, the association between alcohol intake and SGA infants was attenuated after adjustment for maternal smoking. Low levels of prenatal alcohol were not associated with preterm birth; however, binge drinking resulted in a nonsignificant increase in odds. Preterm birth was associated with moderate and higher levels of prenatal alcohol consumption for the group of women who ceased drinking before the second trimester. This group of women was significantly more likely to deliver a preterm infant than women who abstained from alcohol (adjusted OR 1.73 [95% CI 1.01-3.14]). Alcohol intake at higher levels, particularly heavy and binge drinking patterns, is associated with increased risk of preterm birth even when drinking is ceased before the second trimester. This finding, however, is based on small numbers and needs further investigation. Dose and timing of prenatal alcohol exposure appears to affect preterm delivery and should be considered in future research and health education.

Low levels of prenatal alcohol exposure can cause fetal damage

Sir, In BJOG 114:3, Henderson et al. review studies on the effects of low to moderate prenatal alcohol exposure.1 Their stated goal was to review human studies tallying the following outcomes: ‘miscarriage, stillbirth, intrauterine growth restriction, prematurity, birthweight, small for gestational age at birth and birth defects including fetal alcohol syndrome’. The authors drew the conclusion that there is ‘no convincing evidence of adverse effects of prenatal alcohol exposure at low to moderate levels of exposure’. This broad conclusion is, in our opinion, misleading. First, Henderson et al.1 did not include studies examining cognitive or neurological effects of prenatal alcohol exposure, sequelae believed to be more common than the full fetal alcohol syndrome.2 Second, animal studies have shown that even transient, low levels of alcohol exposure can cause negative neurological effects.3 The only conclusion justified by the current scientific evidence is that pregnant women should be advised against drinking during pregnancy, a position supported by the Health Council of the Netherlands after weighing all the evidence, including animal studies.4 j

Authors response to: Low levels of prenatal alcohol exposure can cause fetal damage

Authors response to: Low levels of prenatal alcohol exposure can cause fetal damage

Letter and Category Fluency in Children With Fetal Alcohol Syndrome From a Community in South Africa

This study investigated whether there were differential effects of substantial prenatal alcohol exposure on letter and category fluency in children. Given that children with prenatal alcohol exposure are often impaired in executive functioning and that letter fluency taxes executive processes more than category fluency, it was expected that children with fetal alcohol syndrome (FAS) would be more impaired in letter than in category fluency. A second objective of the study was to examine the developmental trends in the two types of fluency in children with prenatal alcohol exposure. It was hypothesized that between the ages of 6 and 9 years, these FAS children would show age-related changes in category fluency but not in letter fluency. As part of a neuropsychological test battery designed for an international collaborative study of FAS in South Africa, tests of letter and category fluency were administered in Afrikaans. The participants were 62 children with FAS and 61 controls matched with respect to age, gender (58 boys and 65 girls), ethnicity, and socioeconomic status. Results showed that the FAS group had relatively greater difficulty with letter fluency than with category fluency and that the FAS group generated fewer words in both fluency conditions. Contrary to the expectation, however, alcohol-affected children demonstrated age-related linear trends in both letter and category fluency. This is the first study of verbal fluency involving a large sample of well-diagnosed children with FAS conducted in a nonwestern environment. The results are nonetheless consistent with those obtained in western countries in studies of children with various levels of prenatal alcohol exposure and various levels of fetal alcohol spectrum disorder. This study suggests that at least some aspects of the cognitive profile associated with prenatal alcohol exposure may be generalizable across cultural and ethnic boundaries.

Low level prenatal alcohol exposure was associated with adverse behavioural outcomes in children at 6 to 7 years of age

(2001) Pediatrics 108, e34. Sood B, Delaney-Black V, Covington, et al. . Prenatal alcohol exposure and childhood behavior at age 6 to 7 years: I. Dose-response effect. . Aug; ....

Prenatal alcohol exposure and childhood behavior at age 6 to 7 years: I. dose-response effect.

Moderate to heavy levels of prenatal alcohol exposure have been associated with alterations in child behavior, but limited data are available on adverse effects after low levels of exposure. The objective of this study was to evaluate the dose-response effect of prenatal alcohol exposure for adverse child behavior outcomes at 6 to 7 years of age. Beginning in 1986, women attending the urban university-based maternity clinic were routinely screened at their first prenatal visit for alcohol and drug use by trained research assistants from the Fetal Alcohol Research Center. All women reporting alcohol consumption at conception of at least 0.5 oz absolute alcohol/day and a 5% random sample of lower level drinkers and abstainers were invited to participate to be able to identify the associations between alcohol intake and child development. Maternal alcohol, cigarette, and illicit drug use were prospectively assessed during pregnancy and postnatally. The independent variable in this study, prenatal alcohol exposure, was computed as the average absolute alcohol intake (oz) per day across pregnancy. At each prenatal visit, mothers were interviewed about alcohol use during the previous 2 weeks. Quantities and types of alcohol consumed were converted to fluid ounces of absolute alcohol and averaged across visits to generate a summary measure of alcohol exposure throughout pregnancy. Alcohol was initially used as a dichotomous variable comparing children with no prenatal alcohol exposure to children with any exposure. To evaluate the effects of different levels of exposure, the average absolute alcohol intake was relatively arbitrarily categorized into no, low (>0 but <0.3 fl oz of absolute alcohol/day), and moderate/heavy (>/=0.3 fl oz of absolute alcohol/day) for the purpose of this study. Six years later, 665 families were contacted. Ninety-four percent agreed to testing. Exclusions included children who missed multiple test appointments, had major congenital malformations (other than fetal alcohol syndrome), possessed an IQ >2 standard deviations from the sample mean, or had incomplete data. The Achenbach Child Behavior Checklist (CBCL) was used to assess child behavior. The CBCL is a parent questionnaire applicable to children ages 4 to 16 years. It is widely used in the clinical assessment of children's behavior problems and has been extensively used in research. Eight syndrome scales are further grouped into Externalizing or undercontrolled (Aggressive and Delinquent) behavior and Internalizing or overcontrolled (Anxious/Depressed, Somatic Complaints, and Withdrawn) behaviors. Three syndromes (Social, Thought, and Attention Problems) fit neither group. Higher scores are associated with more problem behaviors. Research assistants who were trained and blinded to exposure status independently interviewed the child and caretaker. Data were collected on a broad range of control variables known to influence childhood behavior and/or to be associated with prenatal alcohol exposure. These included perinatal factors of maternal age, education, cigarette, cocaine, and other substances of abuse and the gestational age of the baby. Postnatal factors studied included maternal psychopathology, continuing alcohol and drug use, family structure, socioeconomic status, children's whole blood lead level, and exposure to violence. Data were collected only from black women as there was inadequate representation of other racial groups. Statistical analyses were performed using the SPSS statistical package. Frequency distribution, cross-tabulation, odds ratio, and chi(2) tests were used for analyzing categorical data. Continuous data were analyzed using t tests, analyses of variance (ANOVAs) with posthoc tests, and regression analysis. Testing was available for 501 parent-children dyads. Almost one fourth of the women denied alcohol use during pregnancy. Low levels of alcohol use were reported in 63.8% and moderate/heavy use in 13% of pregnancies. Increasing prenatal alcohol exposure was associated with lower birth weight and gestational age, higher lead levels, higher maternal age, and lower education level, prenatal exposure to cocaine and smoking, custody changes, lower socioeconomic status, and paternal drinking and drug use at the time of pregnancy. Children with any prenatal alcohol exposure were more likely to have higher CBCL scores on Externalizing (Aggressive and Delinquent) and Internalizing (Anxious/Depressed and Withdrawn) syndrome scales and the Total Problem Score. The odds ratio of scoring in the clinical range for Delinquent behavior was 3.2 (1.3-7.6) in children with any prenatal exposure to alcohol compared with nonexposed controls. The threshold dose was evaluated with the 3 prenatal alcohol exposure groups. One-way ANOVA revealed a significant between group difference for Externalizing (Aggressive and Delinquent) and the Total Problem Score. (ABSTRACT TRUNCATED)

Prenatal alcohol exposure and infant negative affect as precursors of depressive features in children

AbstractThis study examined the continuity of negative temperamental variations from infancy to early childhood. Also examined was the association of prenatal alcohol exposure with negative affect in infancy and with depressive features in early childhood. Participants were 41 6‐year‐old children who were followed longitudinally from 1 year of age. Infant negative affect was observed and behaviorally assessed at 1 year, and child depressive symptoms were measured at 6 years using a self‐report questionnaire. Results revealed continuity between infant negative affect and early childhood depressive symptoms. In addition, prenatal alcohol exposure appeared to be a significant risk factor in the development of depressive features through both its direct association with child outcome and its indirect effect on infant negative affect. Children with higher levels of prenatal alcohol exposure, who exhibited higher levels of negative affect at 1 year, reported more depressive symptoms at 6 years. This effect was observed primarily in girls. Results suggest one mechanism by which children exposed to alcohol in utero might be predisposed to display higher levels of negative emotionality in infancy placing them at greater risk for depression in early childhood. Continuity of negative affect and depressive symptoms in prenatally exposed youngsters suggests that interventions could begin in infancy and could be targeted specifically at negative child behaviors. © 2001 Michigan Association for Infant Mental Health.

Prenatal Alcohol Exposure and Depressive Features in Children

This study examined the association between prenatal alcohol exposure and self-report of depressive symptoms in 5- to 6-year-old children. Higher levels of prenatal alcohol exposure were hypothesized to be associated with endorsement of a greater number of depressive symptoms in children. It was also hypothesized that maternal depression, although associated with drinking behavior, would contribute independently to outcome. Finally, the mother's behavior toward the child, as well as current drinking practices, were postulated to mediate the relationship between prenatal alcohol exposure and child depressive symptoms. Participants were 41 mother-child dyads who had been followed longitudinally since the children were 1 year of age. Self-report questionnaires for maternal and child depression were used. Results revealed that prenatal alcohol exposure, maternal depression, and child gender seemed to be highly associated with child depressive symptoms. Girls who had higher levels of prenatal alcohol exposure and whose mothers acknowledged higher levels of depression endorsed the highest number of depressive symptoms. Neither the mother's behavior in interaction with the child nor her current level of alcohol consumption mediated the relationship. The importance of considering prenatal alcohol exposure as a risk variable in the prediction of childhood-onset depression and the possible neurological mechanisms underlying depression in children with alcohol exposure in utero are discussed.

Heavy prenatal alcohol exposure with or without physical features of fetal alcohol syndrome leads to IQ deficits

Objective: To assess general intellectual functioning in children with histories of heavy prenatal alcohol exposure, with or without the facial features and growth deficiencies characteristic of fetal alcohol syndrome (FAS).Design: Forty-seven alcohol-exposed children were recruited on evaluation at a dysmorphology clinic and evaluated as part of a university research project using standard tests of IQ. Thirty-four of the alcohol-exposed patients met the traditional diagnostic criteria for FAS. The other 13 alcohol-exposed children lacked both the pattern of facial features and prenatal or postnatal growth deficiency characteristic of the diagnosis.Results: Compared with normal control subjects matched for age, sex, and ethnicity, both groups of alcohol-exposed children displayed significant deficits in overall IQ measures and deficits on most of the subtest scores. Although those in the nondysmorphic group usually obtained marginally higher IQ scores than those in the FAS group, few significant differences were found between the two alcohol-exposed groups.Conclusions: These results indicate that high levels of prenatal alcohol exposure are related to an increased risk for deficits in intellectual functioning and that these can occur in children without all of the physical features required for a diagnosis of FAS. They also emphasize the need for conducting a thorough history of prenatal alcohol exposure in children with intellectual deficits. (J Pediatr 1997;131:718-21)

Association of Prenatal Alcohol Exposure With Behavioral and Learning Problems in Early Adolescence

To examine the association of moderate levels of prenatal alcohol exposure with learning and behavior in early adolescence. A population-based cohort of 464 children were followed longitudinally from birth to age 14 years. Alcohol exposure was assessed via in-depth maternal self-report in the fifth month of pregnancy. At age 14, learning and behavior were assessed with multiple measures, tapping parent, teenager, and psychologist viewpoints, drawn from adolescent laboratory examination and parent phone interview. The underlying pattern of association between prenatal alcohol and adolescent outcome was detected using partial least-squares statistical techniques; confounding factors were dealt with by regression methods. Analyses revealed a statistically significant, subtle relationship between greater prenatal alcohol use and increased behavior/learning difficulties during adolescence, even after accounting for other developmental influences. "Binge" maternal drinking and exposure early in pregnancy were associated with a profile of adolescent antisocial behavior, school problems, and self-perceived learning difficulties. Fetal alcohol exposure (even at "social drinking" levels) is associated with developmental difficulties in adolescence that are consistent with problems seen earlier in life. Clinicians should understand the potential role prenatal alcohol exposure plays in behavioral and cognitive problems.

Prenatal exposure to alcohol, caffeine, tobacco, and aspirin: Effects on fine and gross motor performance in 4-year-old children.

Multiple regression analyses of data from 449 children indicated statistically significant relationships between moderate levels of prenatal alcohol exposure and increased errors,increased latency,and increased total time on the Wisconsin Fine Motor Steadiness Battery and poorer balance on the Gross Motor Scale.

Measuring “dose” and “response” with multtvariate data using partial least squares techniques

Existing statistical methodology is weak in exploiting the multiplicity of measurement in complex uncontrolled human teratology studies of “dose” and “response”. We describe a study of the neurobehavioral effects of moderate levels of prenatal alcohol exposure which examines 13 alternate measures of alcohol exposure (reflecting timing and variability of maternal alcohol consumption) with respect to hundreds of outcome measures over seven years of elapsed time. We demonstrate how one fundamental statistical tactic, the modeling of crosscorrelation matrices by Partial Least Squares, has permitted us to address the problem of jointly studying dose and response in terms of the salience of alcohol exposure for the outcome measures and of the outcome deficits for estimation of dose. Using this technique we summarize the apparently distinct mechanisms of alcohol exposure (in regard to timing and variability of dose) with respect to 474 outcomes organized in 15 blocks of variables at 5 ages.

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.

Birth Defects Linked With Specific Level of Maternal Alcohol Use, but Abstinence Still Is the Best Policy

FOR THE CHILD-TO-BE, how much of mother's drinking is too much? New data from an ongoing study indicate that the level of prenatal alcohol exposure associated with increased risk for anatomic congenital anomalies is more than four drinks per day. This cutoff off point put 2% of more than 8300 mothers in this study in the high-risk group, according to Robert J. Sokol, MD, who spoke at the American College of Obstetricians and Gynecologists meeting in Las Vegas. The idea that there is a threshold level for alcohol-related effects remains controversial, according to Boris Tabakoff, MD, scientific director of intramural programs at the National Institute on Alcohol Abuse and Alcoholism (NIAAA). It is hard to talk about a threshold effect when the question is 'What effect? ' Tabakoff said in a telephone interview. He points out that alcohol can exert numerous effects, some obvious—such as anatomic defects—others more subtle, such as

Studying Alcohol Teratogenesis from the Perspective of the Fetal Alcohol Syndrome: Methodological and Statistical Issuesa

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.