For Fetal Alcohol Spectrum Disorders Research Articles

Maternal risk factors for fetal alcohol spectrum disorders: Distal variables.

A variety of maternal risk factors for fetal alcohol spectrum disorders (FASD) have been described in the literature. Here, we conducted a multivariate analysis of a large array of potential distal influences on FASD risk. Interviews were conducted with 2515 mothers of first-grade students whose children were evaluated to assess risk for FASD. Topics included: physical/medical status, childbearing history, demographics, mental health, domestic violence, and trauma. Regression modeling utilized usual level of alcohol consumption by trimester and six selected distal variables (maternal head circumference, body mass index, age at pregnancy, gravidity, marital status, and formal years of education) to differentiate children with FASD from control children. Despite individual variation in distal maternal risk factors among and within the mothers of children with each of the common diagnoses of FASD, patterns emerged that differentiated risk among mothers of children with FASD from mothers whose children were developing typically. Case-control comparisons indicate that mothers of children with FASD were significantly smaller physically, had higher gravidity and parity, and experienced more miscarriages and stillbirths, were less likely to be married, reported later pregnancy recognition, more depression, and lower formal educational achievement. They were also less engaged with a formal religion, were less happy, suffered more childhood trauma and interpersonal violence, were more likely to drink alone or with her partner, and drank to deal with anxiety, tension, and to be part of a group. Regression analysis showed that the predictor variables explain 57.5% of the variance in fetal alcohol syndrome (FAS) diagnoses, 30.1% of partial FAS (PFAS) diagnoses, and 46.4% of alcohol-related neurodevelopmental disorder (ARND) diagnoses in children with FASD compared to controls. While the proximal variables explained most of the diagnostic variance, six distal variables explained 16.7% (1 /6 ) of the variance in FAS diagnoses, 13.9% (1 /7 ) of PFAS, and 12.1% (1 /8 ) of ARND. Differences in distal FASD risks were identified. Complex models to quantify risk for FASD hold promise for guiding prevention/intervention.

Results of a screening tool for fetal alcohol spectrum disorders are associated with neuropsychological and behavioral measures.

This study assessed whether the outcome of a screening tool for fetal alcohol spectrum disorders (FASD), the FASD-Tree, was associated with neuropsychological and behavioral outcomes. Data for this study were collected as part of the fourth phase of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD-4). Participants (N = 175, 5 to 16 years) with or without histories of prenatal alcohol exposure were recruited from San Diego and Minneapolis. Each participant was screened using the FASD-Tree and administered a neuropsychological test battery; parents or guardians completed behavioral questionnaires. The FASD-Tree incorporates physical and behavioral measures and provides an outcome regarding the presence of FASD (FASD-Positive or FASD-Negative). Logistic regression was used to test whether the FASD-Tree outcome was associated with general cognitive ability, executive function, academic achievement, and behavior. Associations were tested in two groups: the whole sample and only correctly classified participants. Results of the FASD-Tree were associated with neuropsychological and behavioral measures. Participants classified as FASD-Positive were more likely than those classified as FASD-Negative to have a lower IQ score and exhibit poorer performance on measures of executive and academic functions. Behaviorally, participants classified as FASD-Positive were rated as having more behavior problems and adaptive difficulties. Similar relationships were found for all measures when including only participants correctly classified by the FASD-Tree screening tool. Results from the FASD-Tree screening tool were associated with neuropsychological and behavioral measures. Participants classified as FASD-Positive were more likely to have impairment in all domains tested. The results support the effectiveness of the FASD-Tree as a screening tool for use in clinical settings, providing an efficient and accurate way to identify patients in need of additional evaluation.

Prenatal alcohol exposure results in brain region- and sex-specific changes in circHomer1 expression in adult mouse brain.

Circular RNAs (circRNAs) are a novel category of covalently-closed non-coding RNAs mainly derived from the back-splicing of exons or introns of protein-coding genes. In addition to their inherent high overall stability, circRNAs, have been shown to have strong functional effects on gene expression via a multitude of transcriptional and post-transcriptional mechanisms. Furthermore, circRNAs, appear to be particularly enriched in the brain and able to influence both prenatal development and postnatal brain function. However, little is known about the potential involvement of circRNAs in the long term influence of prenatal alcohol exposure (PAE) in the brain and their relevance for Fetal Alcohol Spectrum Disorders (FASD). Using circRNA-specific quantification, we have found that circHomer1, an activity-dependent circRNA derived from Homer protein homolog 1 (Homer1) and enriched in postnatal brain, is significantly down-regulated in the male frontal cortex and hippocampus of mice subjected to modest PAE. Our data further suggest that the expression of H19, an imprinted embryonic brain-enriched long non-coding RNA (lncRNA), is significantly up-regulated in the frontal cortex of male PAE mice. Furthermore, we show opposing changes in the developmental- and brain region specific- expression of circHomer1 and H19. Lastly, we show that knockdown of H19 results in robust increases in circHomer1 but not linear HOMER1 mRNA expression in human glioblastoma cell lines. Taken together, our work uncovers notable sex- and brain region-specific alterations in circRNA and lncRNA expression following PAE and introduces novel mechanistic insights with potential relevance to FASD.

Effects of prenatal ethanol exposure on choline-induced long-term depression in the hippocampus.

Choline is an essential nutrient under evaluation as a cognitive enhancing treatment for fetal alcohol spectrum disorders (FASD) in clinical trials. As a result, there is increased pressure to identify therapeutic mechanism(s) of action. Choline is not only a precursor for several essential cell membrane components and signaling molecules but also has the potential to directly affect synaptic mechanisms that are believed important for cognitive processes. In the current work, we study how the direct application of choline can affect synaptic transmission in the dentate gyrus (DG) of hippocampal slices obtained from adolescent (postnatal days 21-28) Sprague-Dawley rats (Rattus norvegicus). The acute administration of choline chloride (2 mM) reliably induced a long-term depression (LTD) of field excitatory postsynaptic potentials (fEPSPs) in the DG in vitro. The depression required the involvement of M1 receptors, and the magnitude of the effect was similar in slices obtained from male and female animals. To further study the impact of choline in an animal model of FASD, we examined offspring from dams fed an ethanol-containing diet (35.5% ethanol-derived calories) throughout gestation. In slices from the adolescent animals that experienced prenatal ethanol exposure (PNEE), we found that the choline induced an LTD that uniquely involved the activation of N-methyl-d-aspartate (NMDA) and M1 receptors. This study provides a novel insight into how choline can modulate hippocampal transmission at the level of the synapse and that it can have unique effects following PNEE.NEW & NOTEWORTHY Choline supplementation is a nutraceutical therapy with significant potential for a variety of developmental disorders; however, the mechanisms involved in its therapeutic effects remain poorly understood. Our research shows that choline directly impacts synaptic communication in the brain, inducing a long-term depression of synaptic efficacy in brain slices. The depression is equivalent in male and female animals, involves M1 receptors in control animals, but uniquely involves NMDA receptors in a model of FASD.

Maternal adverse childhood experiences are associated with binge drinking during pregnancy in a dose-dependent pattern: Findings from the All Our Families cohort

BackgroundBinge drinking (BD) is a serious risk factor for fetal alcohol spectrum disorders (FASD) and associated with more severe forms of the disorder. Thus, special attention to specific risk factors for BD adjacent to and during pregnancy is warranted. Objectives(1) To examine the role that maternal adverse childhood experiences (ACEs) may play in BD in the 12 months before pregnancy and during pregnancy in a sample of women with moderate to high socioeconomic status; and (2) to examine the sociodemographic correlates of BD before and during pregnancy within this sample. Participants and settingThis secondary analysis (N = 1663) was derived from the All Our Families prospective cohort study collected in Alberta, Canada between 2008-2011. MethodsData were collected using three mailed surveys completed by women during and after pregnancy. An established scale examined maternal ACEs before 18 years. Adjusted logistic regression models tested associations between ACE score and BD before and during pregnancy. ResultsApproximately 5 in 10 (48.3 %) and 1 in 10 (10.0 %) women reported ≥1 BD episode before and during pregnancy; respectively. In adjusted models, a woman’s ACE score was associated with BD pre-pregnancy in a weak, nonmonotonic fashion; and during pregnancy in a moderate, dose-response fashion. Overall, ACEs resulted in two to three-fold increase in the odds of BD during pregnancy. ConclusionsMaternal ACEs were common in this middle to upper-middle income, well-educated sample and impacted the next generation through BD in pregnancy. These findings combine with others to speak to the public health significance of maternal ACEs on alcohol-related behaviour among expectant mothers across the socioeconomic spectrum, and the need for targeted evidence-based interventions for this population.

The best possible start: A qualitative study on the experiences of parents of young children with or at risk for fetal alcohol spectrum disorders

BackgroundThe developmental outcomes and life course trajectories of young children with or at-risk for fetal alcohol spectrum disorders (FASD) can be optimized when individual and family needs are identified early and met with family-centered early intervention (EI) services. However, little is known about access to and quality of EI services with this high-needs population. MethodTwenty-five biological or adoptive parents of children with or at high risk for FASD, living in the greater area of Seattle, Washington participated in this qualitative study. Three focus groups were conducted using a semi-structured interview guide. Participants described their experience with EI, as well as other supports and challenges faced in their child's first three years of life. Interviews were audio recorded, transcribed verbatim and coded using phenomenological methods. Themes that were consistent across participant groups emerged from the data, as well as themes that showed differences among participant experiences. ResultsCommon EI supports and needs between biological and adoptive parent groups were identified. In addition, perspectives and needs unique to each parent group were revealed. Themes were identified and organized into three categories: (1) child needs; (2) parent needs and priorities; and (3) EI capacity. When parents talked about their child's cognitive, physical, communication or adaptive development, they all discussed how EI was meeting those needs. In contrast, when parents expressed concern for their child's social-emotional development, a description of how EI was supporting these needs was missing from the conversation. Parents appreciated when EI providers were truthful, provided anticipatory guidance, and connected them with supports for their own social-emotional well-being. Yet there were unmet needs for respite care, and parents expressed that support for basic needs related to child or family survival was not consistently recognized as a top priority for families. This high-risk group of young children and their parents also encountered a multitude of transitions in their child's early years and later. Parents wanted more support navigating these transitions as they entered or moved through different systems of care. ConclusionsParents appreciated and endorsed the importance of EI with its provision of individualized, family-centered supports and resources. Examination of the gaps and unmet needs that are common and distinct underscore the importance of an FASD-informed approach to EI. Study findings provide insight into areas for which EI enhancements could be developed in order to tailor supports for the complex needs of this diverse population of children and parents.

Alcohol-Induced Molecular Dysregulation in Human Embryonic Stem Cell-Derived Neural Precursor Cells.

Adverse effect of alcohol on neural function has been well documented. Especially, the teratogenic effect of alcohol on neurodevelopment during embryogenesis has been demonstrated in various models, which could be a pathologic basis for fetal alcohol spectrum disorders (FASDs). While the developmental defects from alcohol abuse during gestation have been described, the specific mechanisms by which alcohol mediates these injuries have yet to be determined. Recent studies have shown that alcohol has significant effect on molecular and cellular regulatory mechanisms in embryonic stem cell (ESC) differentiation including genes involved in neural development. To test our hypothesis that alcohol induces molecular alterations during neural differentiation we have derived neural precursor cells from pluripotent human ESCs in the presence or absence of ethanol treatment. Genome-wide transcriptomic profiling identified molecular alterations induced by ethanol exposure during neural differentiation of hESCs into neural rosettes and neural precursor cell populations. The Database for Annotation, Visualization and Integrated Discovery (DAVID) functional analysis on significantly altered genes showed potential ethanol’s effect on JAK-STAT signaling pathway, neuroactive ligand-receptor interaction, Toll-like receptor (TLR) signaling pathway, cytokine-cytokine receptor interaction and regulation of autophagy. We have further quantitatively verified ethanol-induced alterations of selected candidate genes. Among verified genes we further examined the expression of P2RX3, which is associated with nociception, a peripheral pain response. We found ethanol significantly reduced the level of P2RX3 in undifferentiated hESCs, but induced the level of P2RX3 mRNA and protein in hESC-derived NPCs. Our result suggests ethanol-induced dysregulation of P2RX3 along with alterations in molecules involved in neural activity such as neuroactive ligand-receptor interaction may be a molecular event associated with alcohol-related peripheral neuropathy of an enhanced nociceptive response.

Maternal risk factors for fetal alcohol spectrum disorders in a province in Italy

BackgroundMaternal risk factors for fetal alcohol spectrum disorders (FASD) in Italy and Mediterranean cultures need clarification, as there are few studies and most are plagued by inaccurate reporting of antenatal alcohol use. MethodsMaternal interviews (n=905) were carried out in a population-based study of the prevalence and characteristics of FASD in the Lazio region of Italy which provided data for multivariate case control comparisons and multiple correlation models. ResultsCase control findings from interviews seven years post-partum indicate that mothers of children with FASD are significantly more likely than randomly-selected controls or community mothers to: be shorter; have higher body mass indexes (BMI); be married to a man with legal problems; report more drinking three months pre-pregnancy; engage in more current drinking and drinking alone; and have alcohol problems in her family. Logistic regression analysis of multiple candidate predictors of a FASD diagnosis indicates that alcohol problems in the child's family is the most significant risk factor, making a diagnosis within the continuum of FASD 9 times more likely (95%C.I.=1.6 to 50.7). Sequential multiple regression analysis of the child's neuropsychological performance also identifies alcohol problems in the child's family as the only significant maternal risk variable (p<.001) when controlling for other potential risk factors. ConclusionsUnderreporting of prenatal alcohol use has been demonstrated among Italian and other Mediterranean antenatal samples, and it was suspected in this sample. Nevertheless, several significant maternal risk factors for FASD have been identified.

Prevalence of Fetal Alcohol Spectrum Disorders in Child Care Settings: A Meta-analysis

Children often enter a child-care system (eg, orphanage, foster care, child welfare system) because of unfavorable circumstances (eg, maternal alcohol and/or drug problems, child abuse/neglect). Such circumstances increase the odds of prenatal alcohol exposure, and thus this population can be regarded as high risk for fetal alcohol spectrum disorders (FASD). The primary objective was to estimate a pooled prevalence for fetal alcohol syndrome (FAS) and FASD in various child-care systems based on data from existing studies that used an active case ascertainment method. A systematic literature review, using multiple electronic bibliographic databases, and meta-analysis of internationally published and unpublished studies that reported the prevalence of FAS and/or FASD in all types of child-care systems were conducted. The pooled prevalence estimates and 95% confidence intervals (CIs) were calculated by using the Mantel-Haenszel method, assuming a random effects model. Sensitivity analyses were performed for studies that used either passive surveillance or mixed methods. On the basis of studies that used active case ascertainment, the overall pooled prevalence of FAS and FASD among children and youth in the care of a child-care system was calculated to be 6.0% (60 per 1000; 95% CI: 38 to 85 per 1000) and 16.9% (169 per 1000; 95% CI: 109 to 238 per 1000), respectively. The results confirm that children and youth housed in or under the guardianship of the wide range of child-care systems constitute a population that is high-risk for FASD. It is imperative that screening be implemented in these at-risk populations.

Choline supplementation in children with fetal alcohol spectrum disorders has high feasibility and tolerability

There are no biological treatments for fetal alcohol spectrum disorders (FASDs), lifelong conditions associated with physical anomalies, brain damage, and neurocognitive abnormalities. In preclinical studies, choline partially ameliorates memory and learning deficits from prenatal alcohol exposure. This phase I pilot study evaluated the feasibility, tolerability, and potential adverse effects of choline supplementation in children with FASD. We hypothesized that choline would be well tolerated with minimal adverse events. The study design was a double-blind, randomized, placebo-controlled trial. Participants included 20 children aged 2.5 to 4.9 years with prenatal alcohol exposure and FASD diagnoses. Participants were randomly assigned to 500 mg choline or placebo daily for 9 months (10 active, 10 placebo). Primary outcome measures included feasibility, tolerability, adverse effects, and serum choline levels. Seventeen participants completed the study. Compliance was 82% to 87%, as evidenced by parent-completed log sheets and dose counts. Periodic 24-hour dietary recalls showed no evidence of dietary confounding. Adverse events were minimal and were equivalent in the active and placebo arms with the exception of fishy body odor, which occurred only in the active group. There were no serious adverse events to research participants. This phase I pilot study demonstrates that choline supplementation at 500 mg/d for 9 months in children aged 2 to 5 years is feasible and has high tolerability. Further examination of the efficacy of choline supplementation in FASD is currently underway.

Involving consumers and the community in the development of a diagnostic instrument for fetal alcohol spectrum disorders in Australia

BackgroundAustralia’s commitment to consumer and community participation in health and medical research has grown over the past decade. Participatory research models of engagement are the most empowering for consumers.MethodsAs part of a project to develop a diagnostic instrument for fetal alcohol spectrum disorders (FASD) in Australia (FASD Project), the Australian FASD Collaboration (Collaboration), including a consumer advocate and two consumer representatives, was established. On completion of the FASD Project an on-line survey of Collaboration members was conducted to assess their views on consumer involvement. Women in the community were also invited to participate in Community Conversations to discuss real life situations regarding communications with health professionals about alcohol and pregnancy. Community Conversation feedback was analysed qualitatively and attendees were surveyed about their views of the Community Conversation process.ResultsThe on-line survey was completed by 12 members of the Collaboration (71%). Consumer and community participation was considered important and essential, worked well, and was integral to the success of the project. The 32 women attending the Community Conversations generated 500 statements that made reference to prevention, how information and messages are delivered, and appropriate support for women. Nearly all the attendees at the Community Conversations (93%) believed that they had an opportunity to put forward their ideas and 96% viewed the Community Conversations as a positive experience.ConclusionsThe successful involvement of consumers and the community in the FASD Project can be attributed to active consumer and community participation, which included continued involvement throughout the project, funding of participation activities, and an understanding of the various contributions by the Collaboration members.

Consensus diagnostic criteria for fetal alcohol spectrum disorders in Australia: a modified Delphi study

ObjectiveTo evaluate health professionals' agreement with components of published diagnostic criteria for fetal alcohol spectrum disorders (FASD) in order to guide the development of standard diagnostic guidelines for Australia.DesignA modified...

Anxiety- and depression-like behaviors are accompanied by an increase in oxidative stress in a rat model of fetal alcohol spectrum disorders: Protective effects of voluntary physical exercise

Prenatal ethanol exposure can damage the developing nervous system, producing long-lasting impairments in both brain structure and function. In this study we analyzed how exposure to this teratogen during the period of brain development affects the intracellular redox state in the brain as well as the development of anxiety- and depressive-like phenotypes. Furthermore, we also tested whether aerobic exercise might have therapeutic potential for fetal alcohol spectrum disorders (FASD) by increasing neuronal antioxidant capacity and/or by alleviating ethanol-induced behavioral deficits. Sprague-Dawley rats were administered ethanol across all three-trimester equivalents (i.e., throughout gestation and during the first 10 days of postnatal life). Ethanol-exposed and control animals were assigned to either sedentary or running groups at postnatal day (PND) 48. Runners had free access to a running wheel for 12 days and at PND 60 anxiety- and depressive-like behaviors were assessed. Perinatal ethanol exposure resulted in the occurrence of depressive and anxiety-like behaviors in adult rats without affecting their locomotor activity. Voluntary wheel running reversed the depressive-like behaviors in ethanol-exposed males, but not in ethanol-exposed females. Levels of lipid peroxidation and protein oxidation were significantly increased in the hippocampus and cerebellum of ethanol-exposed rats, and there was a concomitant reduction in the levels of the endogenous antioxidant glutathione. Voluntary exercise was able to reverse the deficits in glutathione both in ethanol-exposed males and females. Thus, while voluntary physical exercise increased glutathione levels in both sexes, its effects at the behavioral level were sex dependent, with only ethanol-exposed male runners showing a decrease in depressive-like behaviors.

Psychological distress among Plains Indian mothers with children referred to screening for Fetal Alcohol Spectrum Disorders

BackgroundPsychological distress (PD) includes symptoms of depression and anxiety and is associated with considerable emotional suffering, social dysfunction and, often, with problematic alcohol use. The rate of current PD among American Indian women is approximately 2.5 times higher than that of U.S. women in general. Our study aims to fill the current knowledge gap about the prevalence and characteristics of PD and its association with self-reported current drinking problems among American Indian mothers whose children were referred to screening for fetal alcohol spectrum disorders (FASD).MethodsSecondary analysis of cross-sectional data was conducted from maternal interviews of referred American Indian mothers (n = 152) and a comparison group of mothers (n = 33) from the same Plains culture tribes who participated in an NIAAA-funded epidemiology study of FASD. Referred women were from one of six Plains Indian reservation communities and one urban area who bore children suspected of having an FASD. A 6-item PD scale (PD-6, Cronbach's alpha = .86) was constructed with a summed score range of 0-12 and a cut-point of 7 indicating serious PD. Multiple statistical tests were used to examine the characteristics of PD and its association with self-reported current drinking problems.ResultsReferred and comparison mothers had an average age of 31.3 years but differed (respectively) on: education (<high school: 47.4%, 9.1%), PD-6 mean scores (3.57, 1.48), current prevalence of serious PD (19.1%, 0.0%), and a current drinking problem (31.6%, 12.1%). Among referred mothers, those with a current drinking problem had a significantly higher mean PD-6 score. Having PD, serious PD, and 2 specific scale items significantly increased the odds that a referred mother would have a current drinking problem.ConclusionsPsychological distress among referred mothers is significantly associated with having a self-reported drinking problem. FASD prevention requires multi-level prevention efforts that provide real opportunities for educational attainment and screening and monitoring of PD and alcohol use during the childbearing years. Mixed methods studies are needed to illuminate the social and cultural determinants at the base of the experience of PD and to identify the strengths and protective factors of unaffected peers who reside within the same communities.

The impact of maternal age on the effects of prenatal alcohol exposure on attention.

Prenatal exposure to alcohol has a variety of morphologic and neurobehavioral consequences, yet more than 10% of women continue to drink during pregnancy, placing their offspring at risk for fetal alcohol spectrum disorders (FASD). Identification of at-risk pregnancies has been difficult, in part, because the presence and severity of FASD are influenced by factors beyond the pattern of alcohol consumption. Establishing maternal characteristics, such as maternal age, that increase the risk of FASD is critical for targeted pregnancy intervention. We examined the moderating effect of maternal age on measures of attention in 462 children from a longitudinal cohort born to women with known alcohol consumption levels (absolute ounces of alcohol per day at conception) who were recruited during pregnancy. Analyses examined the impact of binge drinking, as average ounces of absolute alcohol per drinking day. Smoking and use of cocaine, marijuana, and opiates were also assessed. At 7 years of age, the children completed the Continuous Performance Test, and their teachers completed the Achenbach Teacher Report Form. After controlling for covariates, stepwise multiple regression analyses revealed a negative relation between levels of prenatal binge drinking and several measures of attention. The interaction between alcohol consumption and maternal age was also significant, indicating that the impact of maternal binge drinking during pregnancy on attention was greater among children born to older drinking mothers. These findings are consistent with previous findings that children born to older alcohol-using women have more deleterious effects of prenatal alcohol exposure on other neurobehavioral outcomes.

The plausibility of maternal nutritional status being a contributing factor to the risk for fetal alcohol spectrum disorders: The potential influence of zinc status as an example

There is increasing evidence that human pregnancy outcome can be significantly compromised by suboptimal maternal nutritional status. Poor diet results in a maternal-fetal environment in which the teratogenicity of other insults such as alcohol might be amplified. As an example, there is evidence that zinc (Zn) can interact with maternal alcohol exposure to influence the risk for fetal alcohol spectrum disorders (FASD). Studies with experimental animals have shown that the teratogenicity of alcohol is increased under conditions of Zn deficiency, whereas its teratogenicity is lessened when animals are given Zn-supplemented diets or Zn injections before the alcohol exposure. Alcohol can precipitate an acute-phase response, resulting in a subsequent increase in maternal liver metallothionein, which can sequester Zn and lead to decreased Zn transfer to the fetus. Importantly, the teratogenicity of acute alcohol exposure is reduced in metallothionein knockout mice, which can have improved Zn transfer to the conceptus relative to wild-type mice. Consistent with the above, Zn status has been reported to be low in alcoholic women at delivery. Preliminary data from two basic science and clinical nutritional studies that are ongoing as part of the international Collaborative Initiative on Fetal Alcohol Spectrum Disorders support the potential role of Zn, among other nutritional factors, relative to risk for FASD. Importantly, the nutrient levels being examined in these studies are relevant to general clinical populations and represent suboptimal levels rather than severe deficiencies. These data suggest that moderate deficiencies in single nutrients can act as permissive factors for FASD, and that adequate nutritional status or intervention through supplementation may provide protection from some of the adverse effects of prenatal alcohol exposure.

A 14-year retrospective maternal report of alcohol consumption in pregnancy predicts pregnancy and teen outcomes

Detecting patterns of maternal drinking that place fetuses at risk for fetal alcohol spectrum disorders (FASDs) is critical to diagnosis, treatment, and prevention but is challenging because information on antenatal drinking collected during pregnancy is often insufficient or lacking. Although retrospective assessments have been considered less favored by many researchers due to presumed poor reliability, this perception may be inaccurate because of reduced maternal denial and/or distortion. The present study hypothesized that fetal alcohol exposure, as assessed retrospectively during child adolescence, would be related significantly to prior measures of maternal drinking and would predict alcohol-related behavioral problems in teens better than antenatal measures of maternal alcohol consumption. Drinking was assessed during pregnancy, and retrospectively about the same pregnancy, at a 14-year follow-up in 288 African-American women using well-validated semistructured interviews. Regression analysis examined the predictive validity of both drinking assessments on pregnancy outcomes and on teacher-reported teen behavior outcomes. Retrospective maternal self-reported drinking assessed 14 years postpartum was significantly higher than antenatal reports of consumption. Retrospective report identified 10.8 times more women as risk drinkers (≥ one drink per day) than the antenatal report. Antenatal and retrospective reports were moderately correlated and both were correlated with the Michigan Alcoholism Screening Test. Self-reported alcohol consumption during pregnancy based on retrospective report identified significantly more teens exposed prenatally to at-risk alcohol levels than antenatal, in-pregnancy reports. Retrospective report predicted more teen behavior problems (e.g., attention problems and externalizing behaviors) than the antenatal report. Antenatal report predicted younger gestational age at birth and retrospective report predicted smaller birth size; neither predicted teen IQ. These results suggest that if only antenatal, in-pregnancy maternal report is used, then a substantial proportion of children exposed prenatally to risk levels of alcohol might be misclassified. The validity of retrospective assessment of prior drinking during pregnancy as a more effective indicator of prenatal exposure was established by predicting more behavioral problems in teens than antenatal report. Retrospective report can provide valid information about drinking during a prior pregnancy and may facilitate diagnosis and subsequent interventions by educators, social service personnel, and health-care providers, thereby reducing the life-long impact of FASDs.

Genetic polymorphisms: Impact on the risk of fetal alcohol spectrum disorders

Clinical reports on monozygotic and dizygotic twins provided the initial evidence for the involvement of genetic factors in risk vulnerability for fetal alcohol spectrum disorders (FASD) including fetal alcohol syndrome (FAS). Research with selectively bred and inbred rodents, genetic crosses of these lines and strains, and embryo culture studies have further clarified the role of both maternal and fetal genetics in the development of FASD. Research to identify specific polymorphisms contributing to FASD is still at an early stage. To date, polymorphisms of only one of the genes for the alcohol dehydrogenase enzyme family, the ADH1B, have been demonstrated to contribute to FASD vulnerability. In comparison with ADH1B*1, both maternal and fetal ADH1B*2 have been shown to reduce risk for FAS in a mixed ancestry South African population. ADH1B*3 appears to afford protection for FASD outcomes in African-American populations. Other candidate genes should be examined with respect to FASD risk, including those for the enzymes of serotonin metabolism, in particular the serotonin transporter. By its very nature, alcohol teratogenesis is the expression of the interaction of genes with environment. The study of genetic factors in FASD falls within the new field of ecogenetics. Understanding of the array of genetic factors in FASD will be enhanced by future genetic investigations, including case-control, family association, and linkage studies.