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CORK Bibliography: Fetal Alcohol Syndrome/Fetal Alcohol Effects

71 citations. January 2006 to present

Prepared: September 2008

Adnams CM; Sorour P; Kalberg WO; Kodituwakku P; Perold MD; Kotze A et al. Language and literacy outcomes from a pilot intervention study for children with fetal alcohol spectrum disorders in South Africa. Alcohol 41(6): 403-414, 2007. (44 refs.)

This pilot study investigated the efficacy of a classroom language and literacy intervention in children with fetal alcohol spectrum disorders (FASD) in the Western Cape Province of South Africa. The study forms part of a larger, ongoing study that includes metacognitive and family support interventions in addition to language and literacy training (LLT). For the LLT study, 65 nine-year-old children identified as either FASD or not prenatally exposed to alcohol, were recruited. Forty children with FASD were randomly assigned to either a LLT intervention group or FASD control group (FASD-C). Twenty-five nonalcohol-exposed children were randomly selected as nonexposed controls (NONEXP-C). Prior to intervention and after nine school-term months of treatment, general scholastic tests, teacher and parent questionnaires, classroom observations and specific language and literacy tests were administered to the participants. The nine months assessment reflects the midpoint and the first assessment stage of the overall study. At initial diagnosis and prior to commencement of the interventions, participants with FASD were significantly weaker than NONEXP-C children in reading, spelling, addition, subtraction, phonological awareness, and other tests of early literacy. Teachers rated a range of adaptive behaviors of children with FASD as significantly worse than NONEXP-C. Mean scholastic and language and literacy scores for all groups showed improvement over baseline scores after 9 months of intervention. The mean test scores of children with FASD remained lower than those of NONEXP-C. Comparison of mean baseline to postintervention score changes between the LLT, FASD-C, and NONEXP-C groups revealed that although there were no significant gains by the LLT intervention group over control groups on the general scholastic assessment battery, significantly greater improvements occurred in the LLT intervention group compared to the FASD-C group in specific categories of language and early literacy. These categories were syllable manipulation, letter sound knowledge, written letters, word reading and nonword reading, and spelling. In spite of cognitive and classroom behavioral difficulties, children with FASD from a vulnerable environment demonstrated significant cognitive improvements in specific areas targeted by classroom interventions. To our knowledge, this is the first report of a systematic classroom intervention and resultant cognitive response in children with FASD.

Balachova TN; Bonner BL; Isurina GL; Tsvetkova LA. Use of focus groups in developing FAS/FASD prevention in Russia. Substance Use & Misuse 42(5): 881-894, 2007. (21 refs.)

Fetal alcohol syndrome is a severe outcome of alcohol use during pregnancy, and the rates may be higher in countries with greater use of alcohol. To obtain information from Russian physicians (N = 23), women (N = 23), and male partners (N = 5), focus groups were conducted with 51 participants in St. Petersburg, Russia. The main objective was to determine the participants' knowledge, attitudes, and behavior related to drinking during pregnancy. Data were analyzed using ATLAS-ti 5.0. The results will be used to develop a survey of Russian professionals and women leading to FAS prevention programming.

Baldwin MR. Fetal alcohol spectrum disorders and suicidality in a healthcare setting. International Association of Circumpolar Health Supplement 1: 54-60, 2007. (18 refs.)

Objectives. To present a clinical case report and provide a review of the available literature on fetal alcohol syndrome and the fetal alcohol spectrum disorders and suicidality to highlight important implications for providers. Study design. A case report and literature review. Results. Almost 6% of adolescents evaluated by the fetal alcohol spectrum disorders diagnostic clinic at the Alaska Native Medical Center had been seen for self-harm related consultation. Conclusions. Persons with the fetal alcohol syndrome and the fetal alcohol spectrum disorders, as a result of their disability, demonstrate characteristics or features that are commonly thought to be risk factors for suicide -- such as mental illness, alcohol and other drug abuse, impulsivity, history of trauma or abuse, and employment and relationship/social difficulties. These persons may experience mental health problems, including suicidal ideation and attempts, over the course of their life times.

Barr HM; Bookstein FL; O'Malley KD; Connor PD; Huggins JE; Streissguth AP. Binge drinking during pregnancy as a predictor of psychiatric disorders on the Structured Clinical Interview for DSM-IV in young adult offspring. American Journal of Psychiatry 163(6): 1061-1065, 2006. (28 refs.)

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.

Bonthius DJ; Olson HC; Thomas JD. Proceedings of the 2006 annual meeting of the Fetal Alcohol Spectrum Disorders Study Group. (review). Alcohol 40(1): 61-65, 2006. (0 refs.)

This article describes the proceedings of the 2006 Annual Meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG), which was held in Baltimore, Maryland on June 24, 2006. The meeting was held in conjunction with the annual meeting of the Research Society on Alcoholism and was supported by a grant from the National Institute on Alcohol Abuse and Alcoholism. The 2005-2006 FASDSG officers, Daniel J. Bonthius (President), Heather Carmichael Olson (Vice-President), and Jennifer Thomas (Secretary-Treasurer), organized the meeting. Nationally prominent speakers delivered plenary lectures on topics of newborn screening, ethics, and neuroscience. Selected members of the FASDSG provided brief scientific data (FASt) reports, describing new research findings. Representatives from national agencies involved in fetal alcohol syndrome (FAS) research, treatment, and prevention provided updates regarding priorities, funding, and agency activities. Presentations were also made by the 2006 Student Merit Award recipient and by the 2006 Rosett Award recipient. The meeting served as a forum for clinicians, neuroscientists, psychologists, social scientists, and other professionals to discuss recent advances in FAS research and to identify the most important gaps in the understanding of alcohol-induced teratology.

Boulter LT. The effectiveness of peer-led FAS/FAE prevention presentations in middle and high schools. Journal of Alcohol and Drug Education 51(3): 7-26, 2007. (17 refs.)

Pregnant women and women who might become pregnant, including middle school- and high school-age adolescents, continue to consume alcohol, placing themselves at risk of having a child with the effects of prenatal alcohol exposure. However, most prevention programs that attempt to increase public awareness and knowledge of FAS and related disorders have had limited success and are inappropriate for 11 through 17-year-old youth. This study assessed the effectiveness of a pilot multimedia presentation that was implemented by peers and slightly older college students and incorporated into the middle school and high school health education programs. Posttests and follow-up assessments were compared to pretest scores to measure change in knowledge related to the effects of prenatal alcohol exposure and understanding of the overall purpose of the program. In general, students' overall knowledge of presentation content increased from pretest to posttest. Overall follow-up scores showed that students' retention of the presentation information had increased since the posttest. The findings suggest that FAS/FAE presentations led by peers and utilizing a multimedia/discussion format effectively increase middle school and high school students "knowledge of the effects of alcohol consumption during pregnancy.

Caprara DL; Nash K; Greenbaum R; Rovet J; Koren G. Novel approaches to the diagnosis of fetal alcohol spectrum disorder. (review). Neuroscience and Biobehavioral Reviews 31(2): 254-260, 2007. (47 refs.)

The diagnosis of fetal alcohol spectrum disorder is a difficult task, especially in cases where clear, physical markers of in utero alcohol exposure are not apparent. Reviewed in the following paper are some older tools for screening alcohol use in pregnancy and present novel approaches to the diagnosis of FASD, including ethanol biomarker development to behavioural phenotyping. Improving current FASD diagnostic methodology through more novel approaches may provide the possibility of earlier and wider diagnosis, allowing intervention and treatment at stages where the advanced effects of alcohol can still be mitigated.

Carter RC; Jacobson SW; Molteno CD; Jacobson JL. Fetal alcohol exposure, iron-deficiency anemia, and infant growth. Pediatrics 120(3): 559-567, 2007. (29 refs.)

OBJECTIVES. Our goals were to determine whether prenatal alcohol exposure is associated with an increased incidence of iron-deficiency anemia in infancy and to compare effects of fetal alcohol exposure and iron-deficiency anemia on infant growth. We also tested whether effects of fetal alcohol exposure on growth are mediated or moderated by iron-deficiency anemia. METHODS. A total of 96 infants born to mothers from the Coloured (mixed ancestry) community in Cape Town, South Africa, were recruited prenatally; 42 mothers drank heavily during pregnancy, and 54 abstained or drank small amounts of alcohol. Growth was assessed at birth and 6.5 and 12 months, and iron-deficiency anemia was assessed at 6.5 or 12 months. RESULTS. Infants whose mothers binge drank during pregnancy (>= 4 drinks per occasion) were 3.6 times more likely to be diagnosed with iron-deficiency anemia at 12 months than were infants whose mothers did not binge drink. Prenatal alcohol exposure was associated with reduced weight at birth, 6.5 months, and 12 months and with shorter length at 6.5 and 12 months. Iron-deficiency anemia was related to reduced 12-month weight and head circumference and to slower growth velocity between 6 and 12 months. The effects of prenatal alcohol on weight were not mediated by iron-deficiency anemia; however, they were seen primarily in infants with iron-deficiency anemia. CONCLUSIONS. The association of maternal binge drinking with an increased incidence of iron-deficiency anemia may reflect disruption of accumulation of fetal iron stores or postnatal deficiencies in iron uptake, absorption, or intake. Moreover, iron deficiency seems to exacerbate the prenatal alcohol effects on growth.

Chang G; McNamara TK; Orav EJ; Wilkins-Haug L. Brief intervention for prenatal alcohol use: The role of drinking goal selection. Journal of Substance Abuse Treatment 31(4): 419-424, 2006. (25 refs.)

The behavioral problems and cognitive deficits resulting from even small amounts of prenatal alcohol exposure can be significant and enduring but completely preventable. The purpose of this study was to examine the impact of a prenatal drinking goal selected during a brief intervention for 115 pregnant women and their partners on subsequent consumption. Higher proportions of women having their first pregnancy chose abstinence as a goal over drinking reduction. Goal selection was highly predictive of subsequent drinking behavior. Interestingly, the participants who were abstinent at enrollment and who chose to remain abstinent had the highest rates of abstinence. In contrast, the women who chose cutting down on drinking were the least likely to drink less subsequently, despite recognizing more situations putting them at risk for drinking and identifying more alternatives to consumption. We conclude that goal choice in behavioral self-management of alcohol use by pregnant women is critical.

Chang G; McNamara T; Wilkins-Haug L; Orav EJ. Stages of change and prenatal alcohol use. Journal of Substance Abuse Treatment 32(1): 105-109, 2007. (34 refs.)

This study evaluated stage of change as a predictor of alcohol use in a sample of 301 pregnant women who were either in the precontemplation (62%) or in the action (38%) stage of change in their first trimester. Stage of change distinguished between different patterns of alcohol consumption before and after pregnancy. Those in the precontemplation stage drank more per episode and more often before pregnancy than those in the action stage. The precontemplation group also had a significantly greater quantity of alcohol after pregnancy. However, stage of change did not directly predict subsequent prenatal alcohol use. Previous alcohol use, age, and education were the most significant predictors of prenatal drinks per drinking day. Temptation to drink alcohol was the best predictor of prenatal drinking frequency after study enrollment. Women in both stages of change reduced the quantity and the frequency of their alcohol consumption while pregnant and achieved comparable rates of abstinence.

Chapman K; Tarter RE; Kirisci L; Cornelius MD. Childhood neurobehavior disinhibition amplifies the risk of substance use disorder: Interaction of parental history and prenatal alcohol exposure. Journal of Developmental and Behavioral Pediatrics 28(3): 219-224, 2007. (41 refs.)

Objective: This investigation examined the influence of parental substance use disorder (SUD) and mother's alcohol consumption during pregnancy on neurobehavior disinhibition (ND) measured in 10- to 12-year-old children. The extent to which ND predicted SUD outcome 7 to 9 years later was also determined. Methods: SUD was documented in each parent and as the outcome variable in their 19-year-old sons. Average daily alcohol consumption during the mother's pregnancy was recorded using a structured interview. ND was assessed using indicators of behavior undercontrol, affect modulation and executive cognitive functions. Results: Paternal SUD and the interaction between maternal SUD and alcohol consumption during pregnancy predicted child's ND score. ND at 10 to 12 years of age was a significant predictor of SUD at age 19. Conclusions: The disinhibitory disturbance associated with risk of SUD has both transmissible and teratogenic causes. The ramifications of this finding for pediatric practice are discussed.

Christopher S; Dunnagan T; Haynes G; Stiff L. Determining client need in a multi-state fetal alcohol syndrome consortium: from training to practice. Behavioral and Brain Functions 3: article 10, 2007. (25 refs.)

Background: A multi-state consortium was developed in the US to conduct baseline data collection and intervention research on fetal alcohol syndrome. Each state employed support specialists whose job it was to reduce or eliminate alcohol consumption in women who were at high risk for drinking alcohol during their pregnancy. The purpose of this paper is to report how support specialists in three primarily rural/frontier states were trained to assess client need and how client need was actually assessed in the field. Methods: A qualitative process evaluation was conducted using semi-structured interviews. Interviews were conducted with state staff involved in support specialist training and consortium activities and the support specialists themselves. Inductive analyses were conducted with interview data. Results: Need determination varied by state and for one state within the state. How support specialists were trained to assess need and how need was assessed in the field was mostly congruent. Conclusion: Process evaluation is an effective method for providing practical and useful answers to questions that cannot be answered by outcome evaluation alone.

Connolly-Ahern C; Broadway SC. "To booze or not to booze?" Newspaper coverage of fetal alcohol spectrum disorders. Science Communication 29(3): 362-385, 2008. (62 refs.)

This article reports the results of a qualitative framing analysis of the coverage of fetal alcohol spectrum disorders (FASD). The findings indicate that media discourse about FASD is characterized by differing story types and competing frames. The study also documents the recent emergence of a new frame in opposition to the prevailing abstinence frame in health coverage. This frame has shown physicians to be conflicted in their advice about drinking during pregnancy.

Cronk C; Weiss M. Diagnosis, surveillance and screening for fetal alcohol syndrome spectrum disorders: Methods and dilemmas. (review). International Journal on Disability and Human Development 6(4): 343-359, 2007. (82 refs.)

Fetal Alcohol Spectrum Disorder (FASD) is a prevalent preventable disorder with a significant societal burden related to the cognitive and behavioral disabilities associated with this disorder. This paper reviews the published work on FASD diagnosis, surveillance, and screening programs. Challenges inherent to FASD diagnosis remain and complicate attempts to estimate FAS prevalence. In addition, the drive toward diagnostic accuracy has led to the formulation of screening children at school ages after many disabilities associated with FASD are established. We present the design and selected findings from a regional multi-stage screening project piloted in Wisconsin. Small for gestational age (SGA) newborns with birth head circumference less than 10(th) percentile were selected in the first screening stages. Those meeting these criteria were evaluated for growth, development and FAS facial features at about 2 years of age. Of newborns meeting the initial screening criteria, 30% demonstrated growth deficits and developmental delays at about 2 years of age. Children with any FAS facial feature (of 177 children assessed, n=13 with 2 or 3 facial findings, n=77 with one facial finding) showed greater deficits in growth and a greater proportion were developmentally delayed. The findings demonstrate the potential value of embedding screening for FAS within a multistage screening method to identify infants at risk for any developmental delay. Because this model would be a part of larger population screening for developmental delay, cost efficiencies could be achieved. Problems relating to protection and confidentiality that inevitably accompany screening to identify FASD would also be reduced.

Cruz RP. The greatest source of wealth: Washington State's response to prenatal substance abuse. Gonzaga Law Review 41: 1-27, 2006. (248 legal refs.)

It has been over thirty years since President Nixon declared war on drugs, naming drug abuse "public enemy number one in the United States." This paper discusses the medical and economic impact of prenatal substance abuse. It will present the various policies a number of states have adopted to address the problem, and most importantly, will discuss Washington's current policy, critique the proposed revision to this policy, and argue the need for earlier intervention. Part II of this paper identifies the damaging health effects of in utero drug exposure to a fetus. An overwhelming amount of medical research demonstrates that exposing a fetus to chemical substances could have irreparable and, in some cases, deadly health consequences. Part III examines the various state responses to the problem. More specifically, it discusses state initiatives that have taken a more punitive approach, including criminal and civil commitment statutes, along with child welfare laws recognizing a newborn's positive toxicology result as evidence of parental neglect. Part IV will detail both Washington's current policy and its proposal to take a minimal involvement approach to prenatal substance abuse. It will critique both degrees of state initiatives, discussing the economic and social impact of both a punitive approach and a minimal involvement approach. In Part V, the author discusses the importance of early intervention - the necessity of offering prenatal care and drug treatment services on a voluntary basis at the earliest possible time when an expectant mother is suspected of abusing substances.

Elliott AJ; Hanson JD. Fetal alcohol syndrome in South Dakota. South Dakota Medicine 59(8): 341-342, 2006

Elliott EJ; Payne J; Haan E; Bower C. Diagnosis of foetal alcohol syndrome and alcohol use in pregnancy: A survey of paediatricians' knowledge, attitudes and practice. Journal of Paediatrics and Child Health 42(11): 698-703, 2006. (29 refs.)

Aim: To measure paediatricians' knowledge, attitudes and practices regarding foetal alcohol syndrome (FAS) and alcohol use during pregnancy. Methods: Postal survey of paediatricians in Western Australia in 2004. Of 179 eligible paediatricians, 132 (73.7%) responded (90 consultant paediatricians and 42 paediatric trainees). Results: Of the 132 respondents, 18.9% identified all four essential diagnostic features for FAS. Only 49.2% had previously diagnosed FAS (range 1-30 cases) but 91.7% had seen children diagnosed by others; 76.5% had suspected but not diagnosed FAS; 12.1% had been convinced of but not recorded the diagnosis; and 31.8% had referred children for diagnostic confirmation. Although 79.6% agreed early diagnosis might be advantageous, 69.6% said diagnosis might be stigmatising and 36.4% thought parents might resist referral for assessment and treatment. Although 78.2% agreed avoiding binge drinking may reduce FAS, only 43.9% believed women should abstain from using alcohol in pregnancy. Only 4.5% felt very prepared to deal with a patient with FAS: most wanted educational materials for themselves (69.7%) and child carers (71.2%). Only 23.3% routinely ask about alcohol use when taking a pregnancy history and 4.2% routinely provide information on the consequences of alcohol use. Only 11.4% had read the current Australian National Health Guideline regarding alcohol consumption in pregnancy and 9.1% provided advice consistent with the guideline. Conclusion: Paediatricians identified the need for educational materials about FAS and alcohol use in pregnancy for themselves and their clients. Lack of knowledge about FAS diagnosis and management will limit opportunities for diagnosis, prevention and early intervention.

Floyd RL; O'Connor MJ; Bertrand J; Sokol R. Reducing adverse outcomes from prenatal alcohol exposure: A clinical plan of action. Alcoholism: Clinical and Experimental Research 30(8): 1271-1275, 2006. (51 refs.)

Fetal alcohol spectrum disorders (FASDs) are among the leading preventable causes of developmental disorders in the United States; however, recognition and prevention of these conditions cannot be achieved without informed and educated health providers. This commentary addresses the importance of recognition and prevention of FASDs through the use of well-established standardized practices of diagnosis, screening, and brief alcohol reduction counseling. It is hoped that more knowledge on currently available procedures will encourage their use in the provision of routine health care to all women of childbearing age.

Fryer SL; Tapert SF; Mattson SN; Paulus MP; Spadoni AD; Riley EP. Prenatal alcohol exposure affects frontal-striatal BOLD response during inhibitory control. Alcoholism: Clinical and Experimental Research 31(8): 1415-1424, 2007. (61 refs.)

Background: Prenatal alcohol exposure can lead to widespread cognitive impairment and behavioral dysregulation, including deficits in attention and response inhibition. This study characterized the neural substrates underlying the disinhibited behavioral profile of individuals with fetal alcohol spectrum disorders (FASD). Methods: Children and adolescents (ages 8-18) with (n=13) and without (n=9) histories of heavy prenatal alcohol exposure underwent functional magnetic resonance imaging while performing a response inhibition (go/no-go) task. Results: Despite similar task performance (mean response latency, performance accuracy, and signal detection), blood oxygen level-dependent (BOLD) response patterns differed by group. Region-of-interest analyses revealed that during portions of the behavioral task that required response inhibition, alcohol-exposed participants showed greater BOLD response across prefrontal cortical regions (including the left medial and right middle frontal gyri), while they showed less right caudate nucleus activation, compared with control participants. Conclusions: These data provide an account of response inhibition-related brain functioning in youth with FASD. Furthermore, results suggest that the frontal-striatal circuitry thought to mediate inhibitory control is sensitive to alcohol teratogenesis.

Gahagan S; Sharpe TT; Brimacombe M; Fry-Johnson Y; Levine R; Mengel M et al. Pediatricians' knowledge, training, and experience in the care of children with fetal alcohol syndrome. Pediatrics 118(3): E657-E668, 2006. (47 refs.)

OBJECTIVES. Prenatal exposure to alcohol interferes with fetal development and is the leading preventable cause of birth defects and developmental disabilities. The purpose of this study was to identify current knowledge, diagnosis, prevention, and intervention practices related to fetal alcohol syndrome and related conditions by members of the American Academy of Pediatrics. METHODS. This study was developed collaboratively by the American Academy of Pediatrics and the Centers for Disease Control and Prevention. Questionnaires were mailed to a 3% random sample (n = 1600) of American Academy of Pediatrics members in the United States. General pediatricians, pediatric subspecialists, and pediatric residents were included. RESULTS. Participation rate was 55% (n = 879). Respondents almost universally knew the teratology and clinical presentation of fetal alcohol spectrum disorders. However, they were less likely to report comfort with routine pediatric care of these children. Whereas 62% felt prepared to identify and 50% felt prepared to diagnose, only 34% felt prepared to manage and coordinate the treatment of children with fetal alcohol spectrum disorders. Even fewer (n = 114 [13%]) reported that they routinely counsel adolescent patients about the risks of drinking and pregnancy. CONCLUSIONS. The survey confirms that pediatricians are knowledgeable about fetal alcohol syndrome but do not feel adequately trained to integrate the management of this diagnosis or prevention efforts into everyday practice. Furthermore, the respondents were not active in routine anticipatory guidance with adolescents for prevention of alcohol-affected pregnancies. The development, dissemination, and implementation of best practice tools for prevention, diagnosis, and referral of fetal alcohol syndrome that are specific for general and subspecialist pediatricians are recommended.

Garcia-Algar O; Kulaga V; Gareri J; Koren G; Vall O; Zuccaro P et al. Alarming prevalence of fetal alcohol exposure in a Mediterranean city. Therapeutic Drug Monitoring 30(2): 249-254, 2008. (19 refs.)

The prevalence of gestational ethanol exposure and subsequent fetal exposure has been assessed in a cohort of mother-infant dyads in a Mediterranean city (Barcelona, Spain) by mcconium analysis of fatty acid ethyl esters (FAEEs) after showing in this population a high prevalence of meconium opiates (8.7%), cocaine (4.4%), and cannabis (5.3%). Of the 353 mcconium samples analyzed for FAEEs, 159 (45%) contained a total amount of seven FAEEs equal or above 2 nmol/g meconium, the cutoff internationally accepted to differentiate heavy maternal alcohol consumption during pregnancy from occasional use or no use at all. No parental sociodemographic differences or maternal features differentiated exposed from unexposed newborns. The prevalence of gestational consumption of ethanol was similar between women using and not using drugs of abuse during pregnancy (45.7% and 44.7% of samples with total FAEEs equal or higher than 2 nmol/g meconium, respectively). Meconium samples from newborns exposed in utero to ethanol, and positive for at least one illicit drug (cocaine, opiates, or cannabis), had total FAEEs and five of nine individual FAEEs statistically higher than the meconium samples that were negative for the most frequently used illicit drugs of abuse. Among the most prevalent FAEEs, oleic acid ethyl ester showed the best correlation to total FAEE concentration followed by palmitoleic acid ethyl ester. This study, which highlights a 45% ethanol consumption during pregnancy in a low socioeconomic status cohort, may serve as an eye opener for Europeans that gestational alcohol exposure is not endemic only in areas outside of Europe.

Gareri J; Klein J; Koren G. Drugs of abuse testing in meconium. (review). Clinica Chimica Acta 366(1-2): 101-111, 2006. (84 refs.)

Prenatal substance abuse is an ongoing concern with significant impact on neonatal health and development across socioeconomic lilies. Meconium, passed by neonates during their first post-natal bowel movements, is a matrix unique to the developing fetus and contains a long history of prenatal metabolism. Over the last two decades, the use of meconium as a matrix for assessing prenatal exposure to drugs of abuse has yielded methods exhibiting higher sensitivity, easier collection, and a larger window of detection than traditional matrices. Recently, a method has been developed for the analysis of fatty acid ethyl esters in meconium as a biomarker of fetal alcohol exposure, potentially facilitating the future diagnosis of Fetal Alcohol Spectrum Disorder in situations where gestational alcohol consumption history is unknown. Screening for prenatal exposure to illicit and abused licit drugs in meconium is possible by use of a variety of immunoassay methods with conformational analysis usually occurring by GCMS or LCMS. In spite of increased sample preparation time relative to blood and urine, the long metabolic history, coupled with the case and wide window of collection of meconium make it the ideal matrix for determining fetal drug exposure.

Gareri J; Lynn H; Handley M; Rao C; Koren G. Prevalence of fetal ethanol exposure in a regional population-based sample by meconium analysis of fatty acid, ethyl esters. Therapeutic Drug Monitoring 30(2): 239-245, 2008. (39 refs.)

Challenges in identifying children exposed prenatally to ethanol necessitate the development of a biomarker for neonates at risk for fetal alcohol spectrum disorder. Meconium fatty acid ethyl esters (FAEE), products of nonoxidative ethanol metabolism, have been established as a novel biomarker of fetal ethanol exposure. We present the first application of this biomarker to a population-based sample in Canada. Six-hundred eighty-two meconium specimens were anonymously collected in the region of Grey Bruce, Ontario, Canada. Meconium FAEE were extracted by liquid-liquid and solid-phase extraction and analyzed by gas chromatography with flame-ionization detection confirmed by gas chromatography with mass spectrometry. We measured ethyl palmitate (E16:0), ethyl palmitoleate (E16:1), ethyl stearate (E18:0), ethyl oleate (E18:1), ethyl linoleate (E18:2), ethyl linolenate (E18:3), and ethyl arachidonate (E20:4). Seventeen of 682 meconium samples tested positive for significant prenatal ethanol exposure (> 2.0 nmol/g). FAEE analysis detected fivefold more ethanol-exposed pregnancies than standard postpartum questionnaires in this population (2.5% versus 0.5%) (P < 0.001). The prevalence of ethanol-exposed pregnancies was consistent with Centers for Disease Control and Prevention estimates of "frequent" prenatal drinking and previously published estimates of fetal alcohol spectrum disorder disease prevalence in the general North American population. The FAEE concentrations of negative (95% confidence interval, 0.38-0.49 nmol/g) versus positive (95% confidence interval, 7.74-151.28 nmol/g) samples were distinct, further demonstrating the specificity of this.biomarker in determining significant prenatal ethanol exposure. Meconium FAEE analysis demonstrates a fivefold increase in sensitivity over currently used methods of self-report-based screening in Ontario for the detection of ethanol-exposed pregnancies in a clinical setting.

Gemma S; Vichi S; Testai E. Metabolic and genetic factors contributing to alcohol induced effects and fetal alcohol syndrome. (review). Neuroscience and Biobehavioral Reviews 31(2): 221-229, 2007. (53 refs.)

Alcohol-related damages on newborns and infants include a wide variety of complications from facial anomalies to neurodevelopmental delay, known as fetal alcohol syndrome (FAS). However, only less than 10% of women drinking alcohol during pregnancy have children with FAS. Understanding the risk factors increasing the probability for newborn exposed in utero to alcohol to develop FAS is therefore a key issue. The involvement of genetics as a one risk factor in FAS has been suggested by animal models and by molecular epidemiological studies on different populations, bearing allelic variants for those enzymes, such as ADH e CYP2E1, involved in ethanol metabolism. Indeed, one of the major factors determining the peak blood alcohol exposure to the fetus is the metabolic activity of the mother, in addition to placental and fetal metabolism, explaining, at least partially, the risk of FAS. The different rates of ethanol metabolism may be the result of genetic polymorphisms, the most relevant of which have been described in the paper.

Gohlke JM; Hiller-Sturmhofel S; Faustman EM. A systems-based computational model of alcohol's toxic effects on brain development. Alcohol Research & Health 31(1): 76-83, 2008. (37 refs.)

Important stages during neurodevelopment include the generation of new nerve cells (i.e., neurogenesis), differentiation and migration of these cells to their final location in the brain, formation of connections with neighboring cells (i.e., synaptogenesis), and cell death of neurons that fail to form the appropriate connections. Research found that alcohol exposure during fetal development can interfere with all of these processes. A systems biology approach using computational models of brain development in different species has been used to determine the relative contributions of alcohol-induced impairment of neurogenesis and synaptogenesis to alcohol-related neurodevelopmental deficits in mice, rats, rhesus monkeys, and humans. The results obtained with these models suggest that alcohol's impact on cell division during neurogenesis results in greater deficits in neuron numbers in the adult than the alcohol-induced increase in cell death during synaptogenesis. In primates, the accelerated development of susceptible brain regions may convey increased sensitivity to alcohol-induced neurodevelopmental deficits. Systems-based approaches, such as the computational models described here, can help to translate research findings obtained at a molecular or cellular level in different species into assessment of risk associated with alcohol exposure during human development.

Public Domain

Haley DW; Handmaker NS; Lowe J. Infant stress reactivity and prenatal alcohol exposure. Alcoholism: Clinical and Experimental Research 30(12): 2055-2064, 2006. (81 refs.)

Background: Animal studies have shown that prenatal alcohol exposure (PAE) is linked to alterations in the stress response systems. To date, little is known about the impact of PAE on stress systems in human infants. The current study examined PAE effects on the stress response, as evidenced by the activation of the limbic-hypothalamic-pituitary-adrenal (L-HPA) axis and autonomic system and changes in negative affect during a social-emotional challenge in human infants. We also examined whether the effects of PAE on infant responsiveness differed in boys and girls. Methods: Measures of cortisol, heart rate, and negative affect were obtained during a modified version of Tronick's still-face procedure, a standardized developmental paradigm used to study emotion and stress regulation. Our sample included fifty-five 5- to 7-month-old infants whose mothers were enrolled in an alcohol intervention study. Measures of maternal alcohol consumption during pregnancy and after delivery were obtained using Timeline Followback interviewing methods. Relationships between prenatal alcohol consumption and infant outcomes were examined. In addition, mothers were divided into high and low-frequency drinkers, based on the mean percent of prenatal drinking days (PDD) to facilitate between-group comparisons of infant stress measures. Results: Mothers enrolled in our study reported significant reductions in alcohol consumption after learning of their pregnancies. Nevertheless, PDD from conception to pregnancy recognition was related to increases in cortisol reactivity, elevated heart rate, and negative affect in their infants. The effects of PAE on infant responsiveness were significant after controlling for the effects of maternal depression and annual income. In addition, the effects of PAE on cortisol reactivity differed for boys and girls. Conclusions: Greater PAE was related to greater activation of stress response systems. Our findings suggest that PAE affects the development of infant stress systems and that these effects differ in boys and girls. This work supports the possibility that PAE is related to alterations in infant stress systems, which could underlie problems in cognitive and social-emotional functioning that are common among persons exposed prenatally to alcohol.

Handmaker NS; Rayburn WF; Meng C; Bell JB; Rayburn BB; Rappaport VJ. Impact of alcohol exposure after pregnancy recognition on ultrasonographic fetal growth measures. Alcoholism: Clinical and Experimental Research 30(5): 892-898, 2006. (34 refs.)

Background: More than 3 decades after Jones and Smith (1973) reported on the devastation caused by alcohol exposure on fetal development, the rates of heavy drinking during pregnancy remain relatively unchanged. Early identification of fetal alcohol exposure and maternal abstinence led to better infant Outcomes. This study examined the utility of biometry for detecting alcohol-related fetal growth impairment. Methods: We obtained fetal ultrasound measures from routine ultrasound examinations for 167 pregnant hazardous drinkers who were enrolled in a brier alcohol intervention study. The fetal measures for women who quit after learning of their pregnancies were compared with measures for women who continued some drinking throughout the course of their pregnancies. Because intensity of alcohol consumption is associated with poorer fetal outcomes, separate analyses were conducted for the heavy (average of >= 5 drinks per drinking day) alcohol consumers. Fetal measures from the heavy-exposed fetuses were also compared with measures from a nondrinking group that was representative of normal, uncomplicated pregnancies from Our clinics. Analyses of covariance were used to determine whether there were differences between groups after controlling for influences of gestational age and drug abuse. Results: Nearly half of the pregnant drinkers abstained after learning of their pregnancies. When women reportedly quit drinking early in their pregnancies, fetal growth measures were not significantly different from a non-alcohol-exposed group, regardless of prior drinking patterns. Any alcohol consumption postpregnancy recognition among the heavy drinkers resulted in reduced cerebellar growth as well as decreased cranial to body growth in comparison with women who either quit drinking or who were nondrinkers. Amphetamine abuse was predictive of larger cranial to body growth ratios. Conclusions: Alterations in fetal biometric measurements were observed among the heavy drinkers only when they continued drinking after becoming aware of their pregnancies. Although the reliance on self-reported drinking, is a limitation in this study, these findings support the benefits of early abstinence and the potential for ultrasound examinations in the detection of fetal alcohol effects.

Hopkins RB; Paradis J; Roshankar T; Bowen J; Tarride JE; Blackhouse G et al. Universal or targeted screening for fetal alcohol exposure: A cost-effectiveness analysis. Journal of Studies on Alcohol and Drugs 69(4): 510-519, 2008. (38 refs.)

Objective: In this article, we compared the costs of testing meconium for alcohol exposure in newborns with the lifetime benefits of early detection and intervention. Method: A decision analytic model was developed to assess the cost-effectiveness of testing meconium for two scenarios: (1) all infants in the Canadian province of Ontario and (2) infants who have an older sibling diagnosed with fetal alcohol spectrum disorder (FASD). The model incorporated the costs of early screening, early intervention, and the lifetime societal benefits of early intervention. Results: The cost of the meconium test is Can. $150. The lifetime societal cost of the disease is Can. $1.3 million per incident case. The benefit of early intervention is an improvement in literacy, which improves the quality of life parameter by 0.17 and increases adult lifetime earnings by $26,400 per year. The ratio of the incremental cost to the incremental benefits results in an incremental cost-effectiveness ratio for mandating a universal screen of all newborns in Ontario of $65,874 per quality-adjusted life years. When considering targeted screening, there is a cost savings for society and improvements in quality of life. Conclusions: Depending on society's willingness-to-pay threshold for improving infants' lives in a setting of considerable equity concerns, universal screening and targeted screening of infants who have an older sibling diagnosed with FASD both represent policies that are good value for the money.

Jacobson SW; Stanton ME; Molteno CD; Burden MJ; Fuller DS; Hoyme HE et al. Impaired eyeblink conditioning in children with fetal alcohol syndrome. Alcoholism: Clinical and Experimental Research 32(2): 365-372, 2008. (43 refs.)

Background: Eyeblink conditioning (EBC) is a Pavlovian paradigm that involves contingent temporal pairing of a conditioned stimulus (e.g., tone) with an unconditioned stimulus (e.g., air puff). Animal studies have shown that binge consumption of alcohol during pregnancy impairs EBC and that this impairment is likely mediated by a loss of neurons in the inferior olive and the cerebellar cortex and deep nuclei, as well as by a reduction in neural plasticity in the cerebellar deep nuclei. Methods: Short delay EBC was examined in 98 5-year-old children born to women from the Coloured (mixed ancestry) community in Cape Town, South Africa, who were recruited prenatally and are participating in the first prospective longitudinal study of children with fetal alcohol syndrome (FAS). FAS status was assessed at 5 years by expert dysmorphologists. Two sessions of 50 trials each were administered to the children; a third session was administered the following day to those children who did not meet criterion of 40% conditioned responses in session 2. Results: Not a single child with FAS met criterion for conditioning as contrasted with 75.0% of the controls. Whereas 86.7% of the controls who were conditioned met criterion by the end of Session 2, a large proportion of the relatively few alcohol-exposed nonsyndromal children who conditioned did not do so until Session 3. These alcohol effects on EBC persisted after controlling for IQ. Three of 4 microcephalic children who were not exposed to alcohol were successfully conditioned. Conclusions: This is the first prospective study to demonstrate impaired EBC in children diagnosed with FAS. Successful EBC in a microcephalic group supports the inference that the EBC deficit is specific to prenatal alcohol exposure and a potential biomarker for diagnosis of exposed children lacking the distinctive FAS dysmorphology. Delay EBC has a high sensitivity for identifying individuals with a diagnosis of probable FAS.

Jaddoe VWV; Bakker R; Hofman A; Mackenbach JP; Moll HA; Steegers EAP; Witteman JCM. Moderate alcohol consumption during pregnancy and the risk of low birth weight and preterm birth. The generation R study. Annals of Epidemiology 17(10): 834-840, 2007. (24 refs.)

PURPOSE: To examine the associations of alcohol consumption in different periods of pregnancy with the risks of low birth weight and preterm birth. METHODS: This study was based on 7141 subjects participating in a population-based prospective cohort study from early pregnancy. Alcohol consumption was assessed in early, mid, and late pregnancy. Birth outcomes were birth weight in grams, low birth weight (< 2500 g), small size for gestational age at birth (< -2 standard deviation scores) and preterm birth (gestational age < 3 7 weeks). RESULTS: Overall, alcohol consumption during pregnancy was not associated with adverse birth outcomes. However, dose-response analyses showed tendencies toward adverse effects of average consumption of 1 or more alcoholic drinks per day in early pregnancy on birth weight (difference -129 g [95% confidence interval (CI): -271, 12]), low birth weight (adjusted odds ratio [aOR] 4.81 [95% CI: 1.10, 21.08]), small size for gestational age at birth (aOR 1.45 [95% CI: 0.33, 6.44]) and preterm birth (aOR 2.51 [95% CI: 0.92, 6.81]). Similar effects were found in late pregnancy. CONCLUSION: Average consumption of one or more but not less than one alcoholic drink per day in early or late pregnancy seems to be associated with adverse birth outcomes in the offspring.

Jones KL; Robinson LK; Bakhireva LN; Marintcheva G; Storojev V; Strahova A et al. Accuracy of the diagnosis of physical features of fetal alcohol syndrome by pediatricians after specialized training. Pediatrics 118(6): e1734-e1738, 2006. (18 refs.)

OBJECTIVES. Accurate and early diagnosis of the fetal alcohol syndrome is important for secondary prevention, intervention, and treatment, yet many pediatricians lack expertise in recognition of the characteristic features of this disorder. After a structured training program for pediatricians, we examined the ability to accurately diagnose fetal alcohol syndrome. METHODS. Two dysmorphologists conducted a 2-day training program in the diagnosis of the physical features of fetal alcohol syndrome for 4 pediatricians in Moscow. Dysmorphologists and pediatricians worked in teams to examine children, demonstrate techniques, and validate that pediatricians could identify physical features of this disorder under direct observation. Subsequently, pediatricians independently evaluated children in 41 boarding schools and orphanages. Those children diagnosed with fetal alcohol syndrome or deferred (possible fetal alcohol syndrome) by the pediatricians were then evaluated by the dysmorphologists. Accuracy of the diagnosis of fetal alcohol syndrome or deferred was assessed, as well as the interrater agreement for specific selected features of the disorder. RESULTS. A total of 110 children were examined by both the pediatricians and the dysmorphologists. Of these, 79 were identified with fetal alcohol syndrome by the pediatricians; in 66 (83.5%) of these children, the diagnosis was confirmed by the dysmorphologists. Among 31 children who were classified as deferred by the pediatricians, 21 (67.7%) were confirmed with either fetal alcohol syndrome or deferred by the dysmorphologists. With respect to selected structural features characteristic of fetal alcohol syndrome, good interrater agreement was noted for height and head circumference <= 10th centile, whereas moderate-to-fair agreement was noted for smooth philtrum, long philtrum, presence of "hockey-stick" palmar crease, and palpebral fissure length <= 10th centile. Poor agreement was noted for thin upper lip. CONCLUSIONS. After a relatively short training session, pediatricians were reasonably accurate in diagnosing fetal alcohol syndrome on the basis of physical features and in recognizing most of the selected specific features associated with the disorder.

Kable JA; Coles CD; Taddeo E. Socio-cognitive habilitation using the math interactive learning experience program for alcohol-affected children. Alcoholism: Clinical and Experimental Research 31(8): 1425-1434, 2007. (90 refs.)

Background: Fetal alcohol syndrome (FAS) has been recognized as a disabling condition with a significant impact on the neurobehavioral functioning of affected individuals, including cognition, behavior, and academic functioning, but little research has been performed on targeted interventions for these children. Methods: A socio-cognitive habilitative program focused on improving behavior and math functioning in children 3 to 10 years of age (n=61) was developed and evaluated. The intervention provided parental instruction on FAS, advocacy, and behavioral regulation via workshops and interactive math tutoring with children. All families received parental instruction and were then randomly assigned to either the math instruction or standard psychoeducational care groups. Results: Satisfaction with workshops was very high, with over 90% agreeing that trainers were knowledgeable and materials easy to understand and helpful. Significant gains in knowledge were found for information provided in the instructional groups. At posttesting, caregivers reported fewer problem behaviors on the Achenbach Child Behavior Checklist, Internalizing Problem Behavior, Externalizing Problem Behavior, and Total Problem Behavior summary scales. After 5 months, both groups of children demonstrated gains in math knowledge but significantly higher gains were found in the group receiving direct math instruction. The math treatment group was also more likely to demonstrate a gain of over 1 standard deviation on any of the 4 math outcome measures used. Conclusions: These findings suggest that parents of children with fetal alcohol spectrum disorders (FAS(D)) benefit from instruction in understanding their child's alcohol-related neurological damage and strategies to provide positive behavioral supports and that targeted psychoeducational programs may be able to remediate some of the math deficits associated with prenatal alcohol exposure.

Kalberg WO; Buckley D. FASD: What types of intervention and rehabilitation are useful? (review). Neuroscience and Biobehavioral Reviews 31(2): 278-285, 2007. (27 refs.)

Fetal alcohol spectrum disorders (FASD) occurs worldwide when children are prenatally exposed to alcohol. This paper discusses recent findings regarding the neuropsychological and behavioral effects of prenatal alcohol exposure and how it impacts the developmental and functional abilities of children with FASD. Specifically, recent research focus has concentrated on studies to elucidate a neurobehavioral phenotype for the alcohol-exposed population. As a result, the FASD field has learned what types of neurobehavioral issues occur most frequently with these children. This paper discusses how that information can be used to inform school assessment, intervention planning, and support. Strategies for functional assessment, individualized planning, structured teaching, and developments in cognitive-behavioral methods are described.

Kodituwakku PW. Defining the behavioral phenotype in children with fetal alcohol spectrum disorders: A review. Neuroscience and Biobehavioral Reviews 31(2): 192-201, 2007. (82 refs.)

While there exists a large body of literature on cognitive functions in children with prenatal alcohol exposure, it remains undetermined if these children exhibit a unique profile of cognitive-behavioral functioning or a behavioral phenotype. Researchers have consistently found that intellectual functioning, as assessed by IQ tests, of children with prenatal alcohol exposure is deficient. There is increasing evidence that prenatal alcohol exposure is associated with slow information processing and attentional problems, in particular inattentiveness. Studies examining specific cognitive abilities such as language, visual perception, and memory in alcohol-affected children have shown performance decrements associated with increased task complexity. Children with prenatal alcohol exposure have also been found to exhibit significant deficits in daily functional skills or adaptive behavior, with deficits in socialization becoming pronounced during adolescence. The above findings point to the conclusion that a generalized deficit in complex information processing constitutes the central cognitive-behavioral characteristic of children with prenatal alcohol exposure. Researchers have consistently documented that specific brain regions are more affected by alcohol than other regions. The problem of mapping focal anomalies of the brain with a generalized pattern of deficits can be solved by taking developmental processes into consideration.

Kodituwakku P; Coriale G; Fiorentino D; Aragon AS; Kalberg WO; Buckley D et al. Neurobehavioral characteristics of children with fetal alcohol spectrum disorders in communities from Italy: Preliminary results. Alcoholism: Clinical and Experimental Research 30(9): 1551-1561, 2006. (60 refs.)

Background: There has been considerable effort expended on defining neurobehavioral characteristics of children with fetal alcohol spectrum disorders (FASD). Children with FASD display a range of cognitive deficits and behavioral problems. In this article, we report on the neurobehavioral characteristics of children with FASD in selected communities in Italy. It was expected that both inattentive and hyperactive/impulsive characteristics would discriminate children with FASD from controls and that the groups would also differ on intellectual functioning, language comprehension, and academic skills. Methods: Eighty-two children, 22 diagnosed with FASD and 60 control children, participated in this study. The children were administered tests of nonverbal reasoning, language comprehension, academic achievement, and behavior. Results: On tests of nonverbal reasoning and language comprehension, the FASD group earned lower scores than did controls. Moreover, on a test of academic achievement the FASD group scored lower. When comparing these 2 groups on disruptive behavioral symptomatology, similar results were obtained, the FASD group showing greater attentional difficulties and hyperactivity/impulsivity behaviors and more overall behavioral problems. Stepwise logistic regression analysis showed that a model containing inattention and error scores on the language comprehension task correctly classified 85% of the participants. Compared with the control group, a significantly greater proportion of children with FASD met the Diagnostic and Statistical Manual of Mental Disorders-fourth edition (DSM-IV) criteria of ADD, inattentive type, as reported by teachers. In contrast, hyperactive symptoms among children with FASD were comparable with the control group. Teachers rated children with FASD as having more inattentive behaviors and as performing lower in academic skills than controls. The association between reported hyperactivity symptoms and achievement scores was nonsignificant for both language and math scores, suggesting that it is not the hyperactivity causing problems, but the child's inattention. Conclusions: This research indicates that a nonclinic-referred sample of Italian children with FASD display a profile of neurobehavioral functioning consistent with that reported by other researchers. Furthermore, the neurobehavioral characteristic most identified with children diagnosed with FASD was inattention followed by hyperactivity.

Krasemann T; Klingebiel S. Influence of chronic intrauterine exposure to alcohol on structurally normal hearts. Cardiology in the Young 17(2): 185-188, 2007. (12 refs.)

Abuse of alcohol during pregnancy is known to cause alcoholic embryopathy and congenital cardiac disease. We sought to establish if there were any cardiac abnormalities to be found in patients known to have alcoholic embryopathy, but with structurally normal hearts. We reviewed the electrocardiograms and echocardiographic data of 347 such patients without congenital cardiac disease. A shortened QT interval was found in half of the cases. The left ventricular diameter was small in one quarter of all patients, independent from age, gender, and the degree of alcoholic embryopathy. We conclude that intrauterine exposure to alcohol as a primary toxin can lead to minor cardiac abnormalities, even in the absence of structural congenital cardiac disease.

Kvigne VL; Leondardson GR; Welty TK. Characteristics of fathers who have children with fetal alcohol syndrome or incomplete fetal alcohol syndrome. South Dakota Medicine 59(8): 337-340, 2006

OBJECTIVES: Determine alcohol use, referrals to treatment, receiving treatment, and medical problems related to alcohol among fathers who have children with FAS or incomplete FAS. METHODS: Fathers who had American Indian children with FAS (Study 1) or incomplete FAS (Study 2) were compared with fathers whose children did not have FAS. RESULTS: About half of case and control fathers had alcohol use and alcohol-related medical problems documented in their medical records. Case fathers were more likely to receive alcohol treatment and have injuries related to alcohol abuse. CONCLUSION: Significantly more fathers of children with FAS were referred for alcohol treatment, received alcohol treatment, experienced injuries, and had delirium tremens than control fathers. Fathers of children with incomplete FAS were significantly more likely to drink alcohol, to have received alcohol treatment, and to have alcohol-related medical problems and injuries than control fathers.

Mancinelli R; Ceccanti M; Laviola G. Fetal alcohol spectrum disorders (FASD): From experimental biology to the search for treatment. (editorial). Neuroscience and Biobehavioral Reviews 31(2): 165-167, 2007. (11 refs.)

Manning MA; Hoyme HE. Fetal alcohol spectrum disorders: A practical clinical approach to diagnosis. Neuroscience and Biobehavioral Reviews 31(2): 230-238, 2007. (39 refs.)

In utero exposure to alcohol can have numerous adverse effects on a developing fetus. These effects represent a spectrum of structural anomalies and neurocognitive and behavioral disabilities that have recently been termed fetal alcohol spectrum disorders (FASD). Children at the most severe end of this spectrum and displaying the complete phenotype of characteristic facial anomalies, growth retardation and developmental abnormalities of the central nervous system are defined as having fetal alcohol syndrome (FAS). While FAS is the most readily clinically recognized form of FASD, other categories within the continuum of adverse effects due to prenatal alcohol exposure are becoming better defined. These include partial fetal alcohol syndrome (PFAS), alcohol-related birth defects (ARBD) and alcohol-related neurodevelopmental disorder (ARND). As more is learned regarding the exact manifestations of alcohol on brain development, these classifications may be expanded and/or refined. Because FASD represents a major public health concern, early recognition of at-risk children is important for initiating interventional strategies. Thus, the purpose of this report is to educate practicing physicians about the recognizable phenotypes of FASD in order to accurately identify these children and implement the most appropriate management plans.

May PA; Fiorentino D; Gossage JP; Kalberg WO; Hoyme HE; Robinson LK et al. Epidemiology of FASD in a province in Italy: Prevalence and characteristics of children in a random sample of schools. Alcoholism: Clinical and Experimental Research 30(9): 1562-1575, 2006. (55 refs.)

Background: Accurate estimates of the prevalence and characteristics of fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders (FASD) in a Western European population are lacking and are of particular interest in settings where the usual pattern of alcohol consumption is thought to be daily drinking with meals. To address these issues, an epidemiology study of FAS and other FASD was undertaken in Italian schools. Methods: Primary schools (n=25) in 2 health districts of the Lazio region were randomly selected and recruited for the study. Five hundred forty-three children, 50% of those enrolled in first-grade classes, received parental permission to participate in a 2-tiered, active case ascertainment screening process. Detailed evaluation of children selected in a preliminary screening phase was carried out on those who were small for height, weight, and head circumference and/or referred by teachers for suspected learning and behavioral problems. Detailed evaluation was carried out on each child's: (1) physical growth and dysmorphology, (2) psychological development and behavior, and (3) prenatal exposure to alcohol and other risk factors for FASD via maternal interviews. A group of 67 randomly selected children without FASD from the same classes was utilized as a comparison group. Results: Using 2 denominators for prevalence estimation, a conservative one and a strict sample-based estimate, the prevalence of FAS in this province of Italy was 3.7 to 7.4 per 1,000 children. When cases of partial FAS (PFAS) and a case of alcohol-related neurodevelopmental deficits (ARND) were added to FAS cases, the rate of FASD was 20.3 to 40.5 per 1,000 and estimated at 35 per 1,000 overall or between 2.3 and 4.1% of all children. This exceeds previously published estimates of both FAS and FASD for the western world. Detailed data are presented that demonstrate the utility of the guidelines of the revised Institute of Medicine diagnostic criteria for FASD. Children with FASD are significantly more impaired/affected (p < 0.05) than randomly selected comparison children on all measures of growth deficiency, key facial features of FASD, overall dysmorphology scores, language comprehension, nonverbal IQ, and behavior. Maternal reports of current drinking were significantly higher for mothers of FASD children than comparison mothers, but reported rates of overall drinking during pregnancy were not significantly different. In contrast to expectations, daily drinking among mothers of the comparison group was not common. However, dysmorphology scores of the children were significantly correlated with drinking in the second and third trimesters, drinks per current drinking day, and current drinks per month. Finally, children with the physical features of FASD had lower IQs; nonverbal IQ was significantly correlated with head circumference and negatively correlated with overall dysmorphology score, smooth philtrum, and several other facial and physical anomalies characteristic of FAS. Conclusions: Using careful measures of ascertainment in a primary school setting, these results provide relatively high estimates of the prevalence of FASD and raise the question of whether FASD is more common in the western world than previously estimated.

May PA; Gossage JP; Marais AS; Hendricks LS; Snell CL; Tabachnick BG et al. Maternal risk factors for fetal alcohol syndrome and partial fetal alcohol syndrome in South Africa: A third study. (review). Alcoholism: Clinical and Experimental Research 32(5): 738-753, 2008. (104 refs.)

Objectives: This is a third exploration of risk factors for the two most severe forms of fetal alcohol spectrum disorders (FASD), fetal alcohol syndrome (FAS) and Partial FAS (PFAS), in a South African community with the highest reported prevalence of FAS in the world. Methods: In a case control design, interview and collateral data concerning mothers of 72 first grade children with FAS or PFAS are compared with 134 randomly selected maternal controls of children from the same schools. Results: Significant differences were found between the mothers of FASD children and controls in socio-economic status, educational attainment, and a higher prevalence of FASD among rural residents. The birth order of the index children, gravidity, and still birth were significantly higher among mothers of FASD children. Mothers of children with a FASD are less likely to be married and more likely to have a male partner who drank during the index pregnancy. Current and gestational alcohol use by mothers of FASD children is bingeing on weekends, with no reduction in drinking reported in any trimester in 75 to 90% of the pregnancies that resulted in an FAS child or during 50 to 87% of PFAS-producing pregnancies. There was significantly less drinking among the controls in the second and third trimesters (11 to 14%). Estimated peak blood alcohol concentrations (BAC)s of the mothers of PFAS children range from 0.155 in the first trimester to 0.102 in the third, and for mothers of FAS children the range is from 0.197 to 0.200 to 0.191 in the first, second, and third. Smoking percentage during pregnancy was significantly higher for mothers of FASD children (82 to 84%) than controls (35%); but average quantity smoked is low in the 3 groups at 30 to 41 cigarettes per week. A relatively young average age of the mother at the time of FAS and PFAS births (28.8 and 24.8 years respectively) is not explained by early onset of regular drinking (mean = 20.3 to 20.5 years of age). But the mean years of alcohol consumption is different between groups, 16.3, 10.7, and 12.1 years respectively for mothers of FAS, FASD, and drinking controls. Mothers of FAS and PFAS children were significantly smaller in height and weight than controls at time of interview. The child's total dysmorphology score correlates significantly with mother's weight (-0.46) and BMI (-0.39). Bivariate correlations are significant between the child's dysmorphology and known independent demographic and behavioral maternal risk factors for FASD: higher gravidity and parity; lower education and income; rural residence; drinks consumed daily, weekly, and bingeing during pregnancy; drinking in all trimesters; partner's alcohol consumption during pregnancy; and use of tobacco during pregnancy. Similar significant correlations were also found for most of the above independent maternal risk variables and the child's verbal IQ, non-verbal IQ and behavioral problems. Conclusions: Maternal data in this population are generally consistent with a spectrum of effects exhibited in the children. Variation within the spectrum links greater alcohol doses with a greater severity of effects among children of older and smaller mothers of lower socio-economic status in their later pregnancies. Prevention is needed to address known maternal risk factors for FASD in this population.

May PA; Gossage JP; Marais AS; Adnams CM; Hoyme HE; Jones KL et al. The epidemiology of fetal alcohol syndrome and partial FAS in a South African community. Drug and Alcohol Dependence 88(2/3): 259-271, 2007. (65 refs.)

Objectives: The prevalence and characteristics of fetal alcohol syndrome (FAS) and partial fetal alcohol syndrome (PFAS) were determined in a third primary school cohort in a community in South Africa (SA). Methods: An active case ascertainment, two-tier screening methodology, and the revised Institute of Medicine diagnostic criteria were employed among 818 first grade pupils. Characteristics of children with FAS and PEAS are contrasted with a randomly selected control group. Data were collected and analyzed for children in the study regarding: (1) physical growth and development, including dysmorphology, (2) intelligence and behavioral characteristics, and (3) their mother's social, behavioral, and physical characteristics. Results: The rate of FAS and PFAS in this area continues as the highest reported in any overall community and is much higher than rates elsewhere. In this cohort it is 68.0-89.2 per 1000. Severe episodic drinking on weekends among mothers of children with FAS and PEAS accounts for 96% of all alcohol consumed. Various measures of maternal drinking are significantly correlated with negative outcomes of children in the areas of non-verbal intelligence (-0.26), verbal intelligence (-0.28), problem behavior (0.31), and overall dysmorphology score (0.59). Significantly more FAS and PFAS exists among children of rural residents (OR = 3.79). Conclusions: A high rate of FAS and PFAS was again documented in this community, and it has increased. Given population similarities, we suspect that other communities in the Western Cape Province of South Africa also have high rates. Programs for prevention are needed.

Mcgee CL; Fryer SL; Bjorkquist OA; Mattson SN; Riley EP. Deficits in social problem solving in adolescents with prenatal exposure to alcohol. American Journal of Drug and Alcohol Abuse 34(4): 423-431, 2008. (18 refs.)

This study evaluated the social problem solving skills of adolescents with histories of prenatal alcohol exposure. Adolescents (28 alcohol-exposed, 15 controls) completed a standardized questionnaire of social problem solving, and caregivers completed a parent-report measure of executive functioning. Both questionnaires were mailed to families, and caregivers were asked to recruit a non-exposed control. Results suggest that alcohol-exposed adolescents have substantial impairments in their abilities to solve problems in their everyday life, even in the absence of mental retardation. Such impairments are likely to have a significant impact on social and academic functioning and reflect their need for critical services otherwise unavailable to them.

Mcgee CL; Riley EP. Social and behavioral functioning in individuals with prenatal alcohol exposure. International Journal on Disability and Human Development 6(4): 369-382, 2007. (67 refs.)

Prenatal exposure to alcohol can lead to long-term impairments in cognition and behavior and represents a major public health concern. This paper reviews studies examining the social and behavioral functioning of individuals with prenatal alcohol exposure. Social and behavioral functioning are important domains for study because deficits in these areas can lead to problems in everyday functioning and to maladjustment in later life. Most research with individuals with prenatal alcohol exposure has used caregiver or self-report questionnaires or semi-structured interviews to sample behavior. The vast majority of studies indicate significant difficulties with interpersonal functioning, internalizing and externalizing behavior problems, and high rates of psychopathology. Recent intervention studies conducted with individuals with prenatal alcohol exposure have shown promising results in improving the social skills and behavioral functioning in this population. Finally, this paper concludes with recommendations for future studies in this area.

Mengel MB; Searight HR; Cook K. Preventing alcohol-exposed pregnancies. (review). Journal of the American Board of Family Medicine 19(5): 494-505, 2006. (103 refs.)

Fetal alcohol exposure affects approximately 1% to 3% of live births in the United States. Family physicians are in a unique position to reduce the incidence of alcohol-exposed pregnancy. Fetal alcohol exposure can be minimized through 2 general approaches: reducing alcohol consumption or increasing effective contraception among childbearing-aged women who engage in "at-risk" drinking and encouraging pregnant women to abstain from alcohol. Although no safe level of alcohol consumption during pregnancy is established, women who binge drink are more likely to deliver infants with physical and cognitive-developmental anomalies. Screening tools, such as quantity/frequency questions, the TWEAK and the T-ACE, developed specifically for prenatal care, are more useful with women than the CAGE and Michigan Alcohol Screening Test (MAST). Screening alone seems to reduce alcohol use among pregnant women. Brief interventions, including education about alcohol's effects on the developing fetus, are effective among women not responding to screening. Unfortunately, many barriers exist to effective implementation of alcohol-exposed pregnancy (AEP) prevention in the clinical setting. Designing effective office base systems so the entire burden of implementing AEP prevention activities doesn't fall solely on the family physician is critical.

Miller LC; Chan W; Litvinova A; Rubin A; Comfort K; Tirella L; Boston Murmansk Orphanage Research Team. Fetal alcohol spectrum disorders in children residing in Russian orphanages: A phenotypic survey. Alcoholism: Clinical and Experimental Research 30(3): 531-538, 2006. (46 refs.)

Background: Alcohol use in Russia is among the highest in the world. Over 600,000 children reside in institutional care in Russia, most of them in baby homes and orphanages. The actual prevalence of fetal alcohol spectrum disorders (FASD) among these children is unknown. Therefore, we performed a systematic survey of phenotypic features associated with prenatal alcohol exposure among institutionalized Russian children and related these findings to their growth, development, medical, and social histories. Methods: Phenotypic screening was conducted of all 234 baby home residents in the Murmansk region of Russia (mean age 21 + 12.6 months). Phenotypic expression scores were devised based on facial dysmorphology and other readily observable physical findings. Growth measurements from birth, time of placement in the baby home, and at present were analyzed. In addition, the charts of 64% of the children were randomly selected for retrospective review. Information collected included maternal, medical, developmental, and social histories. Results: Thirteen percent of children had facial phenotype scores highly compatible with prenatal alcohol exposure and 45% had intermediate facial phenotype scores. These scores correlated with maternal gravidity and age. At least 40% of mothers in whom history was available ingested alcohol during pregnancy; some also used illicit drugs and tobacco. Z scores for growth measurements corresponded to phenotypic score, as did the degree of developmental delay. Children with no or mild delay had significantly lower phenotypic scores than those with moderate or severe delay (p = 0.04); more than 70% of children with high phenotypic scores were moderately or severely delayed. Conclusions: More than half of residents of the baby homes in Murmansk, Russia, have intermediate (45%) or high (13%) phenotypic expression scores suggesting prenatal exposure to alcohol. Despite good physical care, stable daily routine, availability of well-trained specialists, and access to medical care, these vulnerable children show significant growth and developmental delays compared with their institutionalized peers.

Moore ES; Ward RE; Wetherill LF; Rogers JL; Autti-Ramo I; Fagerlund A et al. Unique facial features distinguish fetal alcohol syndrome patients and controls in diverse ethnic populations. Alcoholism: Clinical and Experimental Research 31(10): 1707-1713, 2007. (33 refs.)

Effective management of fetal alcohol spectrum disorders (FASD) is dependent on the timely and reliable diagnosis of affected individuals. There are significant diagnostic difficulties because of the reduced prominence of facial features as children age to adulthood as well as potential population or ethnic differences in the most characteristic alcohol-related facial features. A total of 276 subjects were recruited from 4 sites (Cape Town, South Africa; Helsinki, Finland; Buffalo, New York; and San Diego, California) and completed a detailed dysmorphology evaluation to classify subjects as either fetal alcohol syndrome (FAS; 43%) or control (57%). Computerized anthropometry was employed to identify facial features that could distinguish FAS patients from controls across a wide age range and across ethnically disparate study populations. Subjects were placed into 1 of 4 populations based on their ancestry (Cape Coloured, Finnish Caucasian, African American, or North American Caucasian). Analyses performed in each of the 4 study populations were able to identify a unique set of variables which provided excellent discrimination between the 2 groups (FAS, control). In each study group, at least one ocular-related measurement, shortened palpebral fissure, reduced outer canthal width, or reduced inner canthal width, was included in the final classification model. We found measurements that reflected reduced size of the eye orbit to be a consistent feature discriminating FAS and controls across each study population. However, each population had a unique, though often overlapping, set of variables which discriminated the 2 groups, suggesting important ethnic differences in the presentation of FAS. It is possible that these differences were accentuated by the wide age distribution of the study subjects.

Mukherjee RAS; Hollins S; Turk J. Fetal alcohol spectrum disorder: An overview (review). Journal of the Royal Society of Medicine 99(6): 298-302, 2006. (23 refs.)

There has been an increase in awareness of fetal alcohol spectrum disorders in both the lay and academic press of late. However, evidence from national, regional and local conferences as well as a pilot survey of awareness (unpublished data) suggests they remain a set of conditions that are poorly understood in the UK both by the general public and health practitioners. This is despite the conditions being relevant to specialties as diverse as obstetrics, paediatrics, general practice, neurology, public health and psychiatry. This article provides an overview to inform medical practitioners of important aspects related to their practice. Fetal alcohol spectrum disorder is an umbrella term for a set of disorders caused by the consumption of alcohol by a mother whilst pregnant. These conditions range in diversity. On a spectrum, there is the full presentation of fetal alcohol syndrome, involving a characteristic set of facial features (facial pattern of short palpebral fissures 10 percentile, thin upper lip vermillion, smooth philtrum), plus evidence of pre/postnatal growth retardation, and evidence of neurocognitive deficits) and a range of other conditions affecting the neurobehavioural components of the condition without all these features. There is a review of pathology, neurocognitive deficits, and secondary disabilities. In respect to the latter, 90% have some form of diagnosable mental disorder. These can be as diverse as ADHD, social and community impairments, personality disorders, addiction and depression. Fifty percent have some sexually inappropriate behaviour. Much of this can be related to their inability to control and maintain their behaviour attributable to damage caused to their executive function abilities combined with difficulties in receptive language and inability to consolidate memories because of temporal/hippocampal damage. Mangement is also reviewed, as well as prevention efforts and early detection, such as the routine use of the TQEAK (screening test), hair sampling, or meconium testing. There is also a table outlining the management approaches through life cycle.

O'Callaghan FV; O'Callaghan M; Najman JM; Williams GM; Bor W. Prenatal alcohol exposure and attention, learning and intellectual ability at 14 years: A prospective longitudinal study. Early Human Development 83(2): 115-123, 2007. (49 refs.)

Background: A range of adverse birth outcomes is associated with heavy prenatal alcohol exposure. Aim: To examine the effects of moderate levels of alcohol consumption during pregnancy on children's intellectual ability, learning and attention at 14 years of age. Study design and subjects: The Mater-University of Queensland Study of Pregnancy involves a prospective birth cohort of 7223 singletons whose mothers were enrolled at the first antenatat visit. At 14 years, 5139 mothers and adolescents completed attentional and learning questionnaires, and 3731 adolescents completed psychometric assessments. Outcome measures: For adolescents, the Wide Range Achievement Test - Revised (WRAT-R) and Raven's Standard Progressive Matrices Test (Raven's) were administered. Mothers completed the Child Behaviour Checklist (CBCL) and adolescents completed the Youth Self Report (YSR). Learning was assessed by a series of questions in the mother and adolescent questionnaires. Maternal measures included the quantity and frequency of alcohol consumption, and the extent of binge drinking. Conclusions: Although a number of study limitations need to be considered, the results suggest that consumption at the level of < 1 drink/day does not lead to adverse outcomes in relation to attention, learning and cognitive abilities, as measured in the current research.

O'Connor MJ; Paley B. The relationship of prenatal alcohol exposure and the postnatal environment to child depressive symptoms. Journal of Pediatric Psychology 31(1): 50-64, 2006. (80 refs.)

OBJECTIVE: This study examined the association between prenatal alcohol exposure and child depressive symptoms, and the mediating effects of maternal and child characteristics. METHODS: Participants were 42 children aged 4-5 years and their biological mothers. Prenatal alcohol consumption was assessed by self-report of maximum drinks per drinking occasion. The Pictorial Depression Scale (PDS) measured child depressive symptoms. Mother-child interactions were assessed using the family interaction puzzle task. RESULTS: Structural equation modeling indicated that prenatal alcohol exposure was associated with more negative child affect. In turn, mothers of more negative children were less emotionally connected to their children, and those children had higher levels of depressive symptomatology. Results could not be explained by current maternal drinking patterns or maternal depression. CONCLUSIONS: Study findings highlight the importance of examining prenatal alcohol exposure as a risk factor in the prediction of childhood-onset depression and the environmental mechanisms that may mediate that relationship.

Ostrea EM; Hernandez JD; Bielawski DM; Kan JM; Leonardo GM; Abela MB et al. Fatty acid ethyl esters in meconium: Are they biomarkers of fetal alcohol exposure and effect? Alcoholism: Clinical and Experimental Research 30(7): 1152-1159, 2006. (58 refs.)

Background: Biomarkers of fetal exposure to alcohol are important to establish so that early detection and intervention can be made on these infants to prevent undesirable outcomes. The aim of this study was to analyze long-chain fatty acid ethyl esters (FAEEs) in meconium as potential biomarkers of fetal alcohol exposure and effect. Methods: Fatty acid ethyl esters were analyzed in the meconium of 124 singleton infants by positive chemical ionization gas chromatography/mass spectrometry (GC/MS) and correlated to maternal ethanol use. Results: A total of 124 mother/infant dyads were enrolled in the study: 31 were in the control group and 93 were in the alcohol-exposed group. The incidence (28% vs 9.7%, p=0.037) of ethyl linoleate detected in meconium was significantly higher in the alcohol-exposed groups than the control groups. Similarly, when the concentrations of ethyl linoleate in meconium were grouped (trichotomized), there was a significant linear by linear association between alcohol exposure and group concentrations of ethyl linoleate (p=0.013). Furthermore, only alcohol-exposed infants were found in the group with the highest ethyl linoleate concentration. The sensitivity of ethyl linoleate in detecting prenatal alcohol exposure was only 26.9%, and its specificity and positive predictive value were 96.8 and 96.2%, respectively. There was no significant correlation between the concentration of ethyl linoleate in meconium and absolute alcohol consumed (oz) per drinking day across pregnancy, although a trend toward a positive correlation is seen at lower amounts of alcohol consumed. Among the polyunsaturated, long-chain FAEEs, there was weak evidence that the incidence (21.5% vs 6.5%, p=0.057) and concentration (p=0.064) of ethyl arachidonate (AA) were significantly higher in the alcohol-exposed groups than the control groups. Ethyl linolenate and ethyl docosahexanoate (DHA) in meconium were found only in the alcohol group, although not at statistically significant levels. Highly significant correlations were found among the concentrations of ethyl linoleate, ethyl linolenate, ethyl AA, and ethyl DHA in meconium (correlations ranged between r(s)=0.203, p=0.024; and r(s)=0.594, p < 0.001). Conclusion: We conclude that FAEEs in meconium, particularly ethyl linoleate and ethyl AA, are biomarkers of high specificity for prenatal exposure to alcohol in newborn infants. We also propose that ethyl AA and DHA could be potential biomarkers of fetal alcohol effects on the developing fetal brain and should be investigated further.

Paley B; O'Connor MJ. Neurocognitive and neurobehavioral impairments in individuals with fetal alcohol spectrum disorders: Recognition and assessment. International Journal on Disability and Human Development 6(2): 127-142, 2007. (146 refs.)

Fetal Alcohol Spectrum Disorders (FASDs) represent a continuum of development disabilities associated with maternal consumption of alcohol during pregnancy. This spectrum of disorders, which includes the Fetal Alcohol Syndrome (FAS), is characterized by a wide range of physical, cognitive, and behavioral impairments. Estimates of the number of live births in the United States meeting criteria for a diagnosis of FAS range from .5 to 2 infants per 1,000, with the prevalence of the entire continuum of FASDs estimated to be I in 100. This paper discusses some of the complexities involved in diagnosing individuals affected by prenatal alcohol exposure, provides a review of the neurocognitive and neurobehavioral deficits commonly seen in this population, and examines how such deficits may manifest during different developmental periods across the life span. Additionally, strategies for assessing these deficits are described, and specific measures that are appropriate for alcohol-exposed individuals are presented. The challenges of working with this under-identified and underserved population are highlighted, as well as the importance of early diagnosis and intervention.

Rasmussen C; Wyper K. Decision making, executive functioning, and risky behaviors in adolescents with prenatal alcohol exposure. (review). International Journal on Disability and Human Development 6(4): 405-416, 2007. (87 refs.)

Prenatal alcohol exposure can result in life-long primary and secondary disabilities in affected individuals. Adolescents with fetal alcohol spectrum disorder (FASD) and/or prenatal alcohol exposure display high rates of many risky behaviors. In this paper, we review the risky behaviors common in adolescents with FASD, including trouble with the law, delinquency, substance abuse, disrupted school experience and dropping out of school, inappropriate sexual behavior, suicidality, psychopathology, and maladaptive behavior. Next, we review factors that are related to high risk behaviors in individuals with FASD, which include executive functioning deficits, impaired decision making, and abnormalities of the prefrontal cortex. Finally, we discuss why adolescence is a period of increased risk taking and poor decision making, and how individuals with FASD are particularly vulnerable during adolescence.

Rassool GH; Villar-Luis M. Reproductive risks of alcohol and illicit drugs: An overview. Journal of Addictions Nursing 17(4): 211-213, 2006. (16 refs.)

Some studies suggest that alcohol and illicit substance abuse has an adverse effect on behavior, sexual performance, and reproduction. The aim of the paper is to present an overview of the effects of substance abuse and its risks for reproduction. Alcohol abuse is associated with high-risk behaviors and individuals who abuse alcohol are at risk for sexually transmitted infections and unwanted pregnancy. The primary concern of alcohol misuse in pregnancy is its teratogenic potential result that can in fetal alcohol syndrome and potential miscarriage. Cocaine is associated with perinatal complications and spontaneous abortion following maternal abuse during pregnancy and other risky behaviors. Cannabis also is associated with perinatal complications such as miscarriage, intrauterine growth restrictions, abruptio placentae, pre-term delivery, and neurobehavioral abnormalities. A preventative approach needs to be implemented in order to reduce the risks associated with substance abuse and to provide minimal interventions at primary and community care settings.

Ribeiro IM; Vale PJ; Tenedorio PA; Rodrigues PA; Bilhoto MA; Pereira HC. Ocular manifestations in fetal alcohol syndrome. European Journal of Ophthalmology 17(1): 104-109, 2007. (10 refs.)

PURPOSE. To report the prevalence of ocular abnormalities in a group of Portuguese children with a complete fetal alcohol syndrome (FAS). METHODS. Complete ophthalmologic examination in a sample of consecutive children with FAS. Ocular fundus photography was carried out on the cooperative FAS children and on 25 reference Children. Ocular fundus anomalies were recorded by the observation of ocular fundus photography. The ratio between the distance of the center of the disc to the fovea and optic disc diameter (DM/DD) was determined. Small optic disc was defined as a DM/DD ratio above mean control group +1 SD. RESULTS. The authors studied 32 children with FAS (mean age: 9 5 years; 72% boys). The mean corrected visual acuity (VA) was 0.8 +/- 0.2. Refraction ranged from -23.00 to +6.50 spherical equivalent. Ocular findings included short horizontal palpebral fissure (81% of children), strabismus (28% of children), epicanthus (27% of eyes), blepharoptosis (16% of eyes), telecanthus (13% of children), nystagmus (1 child), and cataract (1 eye). Ocular fundus photography analysis showed retinal vessel tortuosity in 30% of the eyes and optic disc hypoplasia in 25%. The mean DM/DD for the control and FAS groups was 2.72 +/- 0.20 and 2.89 +/- 0.25 (p=0.001). Forty percent of the eyes of FAS children had small optic discs. CONCLUSIONS. The most common ocular findings were anomalies of retinal fundus and minor changes in the outer region of the eyes. The authors noted better VA and less severity of disease than others, which might be due to a different selection of patients, different Pattern of alcohol consumption, or genetic differences.

Robbins JM; Bird TM; Tilford JM; Reading JA; Cleves MA; Aitken ME et al. Reduction in newborns with discharge coding of in utero alcohol effects in the United States, 1993 to 2002. Archives of Pediatrics & Adolescent Medicine 160(12): 1224-1231, 2006. (48 refs.)

Objective: To determine whether use of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for fetal alcohol effects has declined during the past 10 years among hospitalized newborns in the United States. Design: Trends in use of the ICD-9-CM code 760.71, "alcohol affecting the fetus," among newborns from 1993 through 2002 were compared with trends in self-reported drinking during pregnancy and maternal diagnoses of alcohol abuse during childbirth. Setting: Sampled short-term, nonfederal general and specialty hospitals. Participants: Infants born from 1993 to 2002 in the United States who were included in the Healthcare Cost and Utilization Project databases. Main Outcome Measures: Documentation of ICD-9-CM code 760.71 among newborns, self-reported drinking during pregnancy, and diagnoses of maternal alcohol abuse during childbirth from 1993 through 2002. Results: The prevalence of the ICD-9-CM code 760.71 for alcohol affecting the fetus, as documented in the discharge record of newborns, declined from 0.73 (95% confidence interval, 0.56-0.92) per 1000 live births in 1993 to 0.17 (95% confidence interval, 0.13-0.20) per 1000 live births in 2002. Rates declined concurrently with those of self-reported alcohol consumption during pregnancy and diagnoses of maternal alcohol abuse during childbirth. Conclusions: Use of the ICD-9-CM code for alcohol affecting the fetus among newborns declined 75% throughout 10 years. Results may be due to decreases in drinking during pregnancy, decreases in disclosure of alcohol use by the mother, or more selective use of the discharge code. National hospital discharge databases may allow cost-effective monitoring of public health interventions that address rare conditions of the fetus and newborn.

Rogers-Adkinson DL; Stuart SK. Collaborative services: Children experiencing neglect and the side effects of prenatal alcohol exposure. Language, Speech and Hearing Services in Schools 38(2): 149-156, 2007. (62 refs.)

Purpose: The purpose of this article is to provide critical knowledge regarding children who are served by the child welfare system and how these children's specialized needs affect speech-language services. Specifically, the structure of social services system models is presented, with an emphasis on the cultural and systemic interactions between services providers and families. In addition, the role of special education for children who have experienced abuse, neglect, and prenatal drug or alcohol exposure is presented, with an emphasis on social services and special education legal issues. Method: This article provides a critical analysis of the research literature to date regarding effective tools for providing collaborative intervention to children who are experiencing fetal alcohol syndrome disorder or abuse and/or neglect. Clinical implications: This article provides suggestions about the collaborative roles that speech-language pathologists should integrate into treatment milieu when delivering therapy to children with histories of abuse, neglect, and prenatal drug or alcohol exposure.

Rojas EY; Gretton HM. Background, offence characteristics, and criminal outcomes of aboriginal youth who sexually offend: A closer look at aboriginal youth intervention needs. Sexual Abuse 19(3): 257-283, 2007. (51 refs.)

Canada's Aboriginal peoples face a number of social and health issues. Research shows that Aboriginal youths are over-represented in the criminal justice system and youth forensic psychiatric programmes. Within the literature on sex offending youth, there appears to be no published data available to inform clinicians working with adjudicated Aboriginal youth. Therefore, the present study examines the background, offence characteristics, and criminal outcomes of Aboriginal (n = 102) and non-Aboriginal (n = 257) youths who engaged in sexual offending behaviour and were ordered to attend a sexual offender treatment programme in British Columbia between 1985 and 2004. Overall, Aboriginal youths were more likely than non-Aboriginal youths to have background histories of fetal alcohol spectrum disorders (FASD), substance abuse, childhood victimization, academic difficulties, and instability in the living environment. Both Aboriginal and non-Aboriginal youths had a tendency to target children under 12-years-old, females, and non-strangers. Aboriginal youths were more likely than non-Aboriginal youths to use substances at the time of their sexual index offence. Outcome data revealed that Aboriginal youths were more likely than their non-Aboriginal counterparts to recidivate sexually, violently, and non-violently during the 10-year follow-up period. Furthermore, the time between discharge and commission of all types of re-offences was significantly shorter for Aboriginal youths than for non-Aboriginal youths. Implications of these findings are discussed with regards to the needs of Aboriginal youth and intervention.

Romitti PA; Sun LX; Honein MA; Reefhuis J; Correa A; Rasmussen SA. Maternal periconceptional alcohol consumption and risk of orofacial clefts. American Journal of Epidemiology 166(7): 775-785, 2007. (55 refs.)

Using data from the National Birth Defects Prevention Study, the authors investigated the association between maternal reports of periconceptional alcohol consumption and clefting. Cases with a cleft lip, cleft palate, or both and unaffected controls delivered from 1997 through 2002 were ascertained. Interview reports of alcohol consumption were obtained from 1,749 (75.1%) case and 4,094 (68.2%) control mothers. Adjusted odds ratios and 95% confidence intervals were calculated to assess associations. Compared with odds ratios for mothers with no reported consumption, those for mothers who consumed alcohol tended to be near to (cleft lip, cleft lip with cleft palate) or to exceed (cleft palate) unity. The odds ratios associated with binge drinking were elevated but did not demonstrate significantly increased risk for any phenotype; however, the odds ratios differed by the type of alcohol consumed, particularly for cleft palate (distilled spirits > wine > beer). These odds ratios were further increased among mothers with no reported folic acid intake. Although these findings suggest that the association between alcohol consumption and clefting might be most influenced by the type of beverage consumed and folic acid intake, they are preliminary and might reflect chance associations. Such findings need exploration in additional, large studies.

Ryan DM; Bonnett DM; Gass CB. Sobering thoughts: Town hall meetings on fetal alcohol spectrum disorders. (editorial). AIDS Education and Prevention 96(12): 2098-2101, 2006. (7 refs.)

Prenatal exposure to alcohol is one of the leading causes of preventable birth defects and developmental disabilities. During the past 30 years, fetal alcohol spectrum disorders (FASD), including fetal alcohol syndrome, have gradually begun to attract attention. However, awareness and understanding of the disorders remain low, and people who are affected are seriously underserved. The FASD Center for Excellence held a series of town hall meetings in 2002 and 2003 to gauge the issues surrounding FASD nationwide. On the basis of its findings, the center proposed a series of recommendations to begin to remedy some of the deficiencies that were identified.

Schneider M; Norman R; Parry C; Bradshaw D; Pluddemann A. Estimating the burden of disease attributable to alcohol use in South Africa in 2000. South African Medical Journal 97(8, Part 2): 664-672, 2007. (49 refs.)

Objectives. To make quantitative estimates of the burden of disease attributable to alcohol use by sex and age group in South Africa in 2000. Design. The analysis follows the World Health Organization comparative risk assessment (CRA) methodology. Population-attributable fractions (PAFs) calculated from modelled prevalence estimates and relative risks based on the global review were applied to the burden of disease estimates from the revised South African National Burden of Disease study for 2000. The alcohol-attributable fractions for injuries were directly determined from blood alcohol concentrations (BAC > 0.05 g/100 ml) at the time of injury. Monte Carlo simulation-modelling techniques were used to quantify uncertainty in the estimates. Setting. South Africa. Subjects. Adults >= 15 years. Outcome measures. Deaths and disability-adjusted life years (DALYs) from ischaemic heart disease, stroke, hypertensive disease, diabetes, certain cancers, liver cirrhosis, epilepsy, alcohol use disorder, depression and intentional and unintentional injuries as well as burden from fetal alcohol syndrome (FAS) and low birth weight. Results. Alcohol harm accounted for an estimated 7.1% (95% uncertainty interval 6.6 - 7.5%) of all deaths and 7.0% (95% uncertainty interval 6.6 - 7.4%) of total DALYs in 2000. Injuries and cardiovascular incidents ranked first and second in terms of attributable deaths. Top rankings for overall attributable burden were interpersonal violence (39.0%), neuropsychiatric conditions (18.4%) and road traffic injuries (14.3%). Interpersonal violence accounted for 42.8% of the injury DALYs attributed to alcohol in males and 25.9% in females. In terms of alcohol-attributable disability, alcohol use disorders ranked first (44.6%), interpersonal violence second (23.2%), and FAS third (18.1%). Conclusions. Particular attention needs to be given to preventing and reducing the burden of alcohol-related homicide and violence, alcohol-related road traffic accidents, alcohol use disorders, and FAS. Multilevel interventions are required to target high-risk drinkers, in addition to creating awareness in the general population of the problems associated with alcohol abuse.

Spadoni AD; McGee CL; Fryer SL; Riley EP. Neuroimaging and fetal alcohol spectrum disorders. Neuroscience and Biobehavioral Reviews 31(2): 239-245, 2007. (52 refs.)

Heavy prenatal alcohol exposure causes permanent structural alterations to the brain and can lead to numerous cognitive and behavioral outcomes. Consistent with many of the neuropsychological and behavioral deficits that have been reported, neuroimaging studies reveal a pattern of structural abnormalities associated with prenatal alcohol exposure. This chapter systematically reviews structural anomalies by brain region, identifying cognitive and behavioral correlates when relevant. The consensus shows that in addition to the overall reduction of brain size, prominent brain shape abnormalities have been observed, with narrowing in the parietal region and reduced brain growth in portions of the frontal lobe. Commensurating with these anomalies, volumetric and tissue density findings cite disproportionate reductions in the parietal lobe, cerebellar vermis, corpus callosum, and the caudate nucleus, suggesting that certain areas of the brain may be especially vulnerable to prenatal alcohol exposure. In sum, neuroimaging techniques have greatly advanced our understanding of brain-behavior relationships in fetal alcohol spectrum disorders (FASD), and hopefully will lead to improved diagnosis and treatment options for those affected by prenatal exposure to alcohol.

Spohr HL; Willms J; Steinhausen HC. Fetal alcohol spectrum disorders in young adulthood. Journal of Pediatrics 150(2): 175-179, 2007. (26 refs.)

Objective: To test the hypothesis that fetal alcohol syndrome (FAS), with the full phenotype, and fetal alcohol effect (FAE), with some but not all of the features, can be combined under the umbrella term fetal alcohol spectrum disorders (FASD). Study design: We investigated the long-term sequelae of intrauterine alcohol exposure rising physical examination, psychosocial interviews, and a behavioral cheeklist in a 20-year follow-up study of 37 patients with FASD originally diagnosed as having FAS or FAE in infancy and childhood. Results: Although the characteristic craniofacial malformations of FAS/FAE diminish over time, microcephaly, a poorly developed philtrum and a thin upper lip, and, to a lesser degree, short stature and underweight (in boys) persist. In females, adult body weight increases. Persistent mental handicaps, including intellectual disability, limited occupational options, and dependent living, are the major sequelae, and the scores for various behavioral problems are significantly increased. Conclusions: The devastating effects of intrauterine exposure to alcohol persist into early adulthood and severely limit careers and independent living.

Streissguth A. Offspring effects of prenatal alcohol exposure from birth to 25 years: The Seattle prospective longitudinal study. Journal of Clinical Psychology in Medical Settings 14(2): 81-101, 2007. (72 refs.)

Before alcohol was generally known to cause birth defects, National Institute on Alcohol Abuse and Alcoholism in 1974 began funding a population-based Seattle study on alcohol use and pregnancy outcome. Women receiving prenatal care by mid-pregnancy were recruited (N = 1,529) and interviewed at home. Approximately 500 offspring exposed to a range of alcohol levels were examined on 11 occasions between day 1 and 25 years. Neuropsychological and neurobehavioral performance measures are correlated with prenatal alcohol dose, without substantial confounding by socio-demographic or rearing conditions, smoking, nutrition, or other drugs. Deficits in attention, arithmetic skill, spatial-visual memory, and IQ, as well as increased alcohol problems and psychiatric disorders are among offspring outcomes correlated at several ages with maternal drinking during and before pregnancy recognition. Findings are not confined to women who believed they had alcohol problems. Not all exposed offspring appear affected.

Tough S; Clarke M; Cook J. Fetal alcohol spectrum disorder prevention approaches among Canadian physicians by proportion of Native/Aboriginal patients: Practices during the preconception and prenatal periods. Maternal and Child Health Journal 11(4): 385-393, 2007. (45 refs.)

Objective: To examine if physician knowledge and practices related to fetal alcohol spectrum disorders (FASD) and its prevention vary based on the proportion of Native/Aboriginal patients served. Methods: A questionnaire was mailed to a national random sample of Canadian physicians between October 2001 and May 2002. The main outcome measure was responses regarding knowledge about and prevention of FASD. Bivariate analysis was used to compare practice patterns and knowledge between those who cared for a higher proportion (>= 10%) and a lower proportion (< 10%) of Native/Aboriginal patients. Results: The overall response rate was 39.4% (1,700/4,313), and 21.4% of physicians reported that >= 10% of their clinical practice was comprised of Native/Aboriginal patients. Those caring for a greater proportion of Native/Aboriginal patients were significantly (p < 0.05) more likely to discuss sexual and emotional abuse (approximately 20% vs. 10%) and a history of addictions (52% vs. 44%) with women of childbearing age. In prenatal interviews, they were also significantly (p < 0.05) more likely to routinely include a history of addictions treatment (70% vs. 62%) and drinking prior to pregnancy awareness (91% vs. 85%), as well as more likely to ask about evidence of alcohol related defects in other children (50% vs. 37%), and discuss the drinking pattern of the patient-s partner (25% vs. 18%). Conclusions: Physicians who had a higher proportion of Native/Aboriginal patients appeared to be more attuned to the issues of FASD and to assess risk in a more comprehensive manner. However, support for improved identification of women at risk and referral opportunities is warranted.

Toutain S; Lejeune C. Family management of infants with fetal alcohol syndrome or fetal alcohol spectrum disorders. Journal of Developmental and Physical Disabilities 20(5): 425-436, 2008. (26 refs.)

We studied the effects on family life of medical, social, and/or judiciary decisions taken when 28 infants born between 1995 and 2003 to alcohol-abusing mothers and diagnosed with fetal alcohol syndrome (FAS) or fetal alcohol spectrum disorders (FASD) were discharged from a neonatology hospital unit near Paris. Medical files of these infants and their mothers' obstetrical files (when available) were retrieved from the hospital database; data was then collected and analyzed retrospectively. Post-discharge familial settings were established using questionnaires or telephone interviews with their doctors or the staff of the institutions where they were fostered. The 28 mothers of these FAS/FASD children all came from underprivileged backgrounds, had chronic health problems and/or lived with alcohol abusers. The neonatology team has to decide, at discharge, whether the families can provide a 'good environment' for their babies, if not, they refer them to the courts. In any case, the mother/parents must obey certain rules (such as respecting follow-up appointments for example). These FAS/FASD infants usually came from dysfunctional families, and at hospital discharge, 18% of them were put in care, while the mothers could be given court-approved visiting rights. When the infants lived with their biological families, the mothers' marital situation usually deteriorated within 2 years. The mothers/parents often proved unable to look after their babies properly; this was reported to the courts, and their children put in care. Based on our results, we recommend that the current management of families with FAS/FASD children should be reviewed.

Traves C; College O; Cararach V; Gual A; De Tejada BM; Lopez-Tejero MD. Clinical approach to intestinal maturation in neonates prenatally exposed to alcohol. Alcohol and Alcoholism 42(5): 407-412, 2007. (54 refs.)

Aim: The need for a non-invasive diagnosis of the effects of ethanol in utero on the development of the intestine in humans led us to look for a serum marker of the structural integrity of the intestine. We propose apolipoprotein A-IV (apoA-IV) as a possible candidate. In humans this protein is synthesized only by intestinal mucosa, it is expressed in the enterocyte of the foetus from 20 weeks of gestation, and it is released to the blood stream after synthesis. Methods: We measured the levels of apoA-IV in the umbilical cord serum of neonates whose mothers had consumed alcohol during pregnancy and neonates born to women who had not (controls).The gestational age at delivery of the cases studied ranged from 36 to 42 weeks. ELISA and Western blot analysis were used. Results: There was no difference in the mean body weight of neonates from either group. Nevertheless, exposure to ethanol in utero significantly reduced (by about 30%) the apoA-IV levels in serum at birth, regardless of body weight. Conclusion: Our findings suggest that circulating apoA-IV levels could be used as a clinical marker of the prenatal effects of ethanol on the structural integrity of the intestine. Neonatal diagnosis of these intestinal effects could improve post-natal outcome.

Vangipuram SD; Grever WE; Parker GC; Lyman WD. Ethanol increases fetal human neurosphere size and alters adhesion molecule gene expression. Alcoholism: Clinical and Experimental Research 32(2): 339-347, 2008. (67 refs.)

Background: Ethanol (ETOH) consumption by pregnant women can result in Fetal Alcohol Spectrum Disorder (FASD). To date, the cellular targets and mechanisms responsible for FASD are not fully characterized. Our aim was to determine if ETOH can affect fetal human brain-derived neural progenitor cells (NPC). Methods: Neural progenitor cells were isolated by positive selection from normal second trimester fetal human brains (n = 4) and cultured, for up to 72 hours, in mitogenic media containing 0, 1, 10, or 100 mM ETOH. From 48 to 72 hours in culture, neurospheres generated in these conditions were filmed using time-lapse video microscopy. At the end of 72 hours, neurosphere diameter and roundness were measured using videographic software. Mitotic phase analysis of cell-cycle activity and apoptotic cell count were also performed at this time, by flow cytometry using propidium iodide (PI) staining. Real-time PCR was used to estimate expression of genes associated with cell adhesion pathways. Results: Neurosphere diameter correlated positively (r = 0.87) with increasing ETOH concentrations. There was no significant difference in cell-cycle activity and no significant increase in apoptosis with increasing ETOH concentrations. Time-lapse video microscopy showed that ETOH (100 mM) reduced the time for neurosphere coalescence. Real-time PCR analysis showed that ETOH significantly altered the expression of genes involved in cell adhesion. There was an increase in the expression of alpha and beta Laminins 1, beta Integrins 3 and 5, Secreted phosphoprotein1 and Sarcoglycan epsilon. No change in the expression of beta Actin was observed while the expression of beta Integrin 2 was significantly suppressed. Conclusions: ETOH had no effect on NPC apoptosis but, resulted in more rapid coalescence and increased volume of neurospheres. Additionally, the expression of genes associated with cell adhesion was significantly altered. ETOH induced changes in NPC surface adhesion interactions may underlie aspects of neurodevelopmental abnormalities in FASD.

Verma T; Adams J; White M. Portrayal of health-related behaviours in popular UK television soap operas. Journal of Epidemiology and Community Health 61(7): 575-577, 2007. (15 refs.)

Background: Evidence suggests that health-related story lines in popular television programmes may lead to increased viewer knowledge or behaviour change. However, little is currently known about the portrayal of common health-related behaviours on UK television soap operas. Methods: The portrayal of 11 key health-related behaviours on the 4 most popular soap operas set and broadcast in the UK over 4 weeks in spring 2005 was assessed. Results: Seven of the 11 behaviours of interest were recorded a total of 959 times during 32 h of programming ( or 30 behaviours per programming hour). The behaviour most frequently recorded was alcohol-related behaviours, recorded 619 times (19.3 per programming hour). No instances of four behaviours of interest were observed: driving soon after drinking, drinking during pregnancy, smoking during pregnancy or smoking around children. Conclusions: Popular television serials offer the chance to portray "healthy'' behaviours as normal, and so help change attitudes and shape behavioural norms among the viewing public. Engaging the makers of these programmes in a health promotion agenda may be a fruitful method of promoting healthy behaviours.

Weinberg J; Sliwowska JH; Lan N; Hellemans KGC. Prenatal alcohol exposure: Foetal programming, the hypothalamic-pituitary-adrenal axis and sex differences in outcome. Journal of Neuroendocrinology {Dartmouth e-journal} 20(4): 470-488, 2008. (221 refs.)

Prenatal exposure to alcohol has adverse effects on offspring neuroendocrine and behavioural functions. Alcohol readily crosses the placenta, thus directly affecting developing foetal endocrine organs. In addition, alcohol-induced changes in maternal endocrine function can disrupt the normal hormonal interactions between the pregnant female and foetal systems, altering the normal hormone balance and, indirectly, affecting the development of foetal metabolic, physiological and endocrine functions. The present review focuses on the adverse effects of prenatal alcohol exposure on offspring neuroendocrine function, with particular emphasis on the hypothalamic-pituitary-adrenal (HPA) axis, a key player in the stress response. The HPA axis is highly susceptible to programming during foetal and neonatal development. Here, we review data demonstrating that alcohol exposure in utero programmes the foetal HPA axis such that HPA tone is increased throughout life. Importantly, we show that, although alterations in HPA responsiveness and regulation are robust phenomena, occurring in both male and female offspring, sexually dimorphic effects of alcohol are frequently observed. We present updated findings on possible mechanisms underlying differential effects of alcohol on male and female offspring, with special emphasis on effects at different levels of the HPA axis, and on modulatory influences of the hypothalamic-pituitary-gonadal hormones and serotonin. Finally, possible mechanisms underlying foetal programming of the HPA axis, and the long-term implications of increased exposure to endogenous glucocorticoids for offspring vulnerability to illnesses or disorders later in life are discussed.

Willford JA; Leech SL; Day NL. Moderate prenatal alcohol exposure and cognitive status of children at age 10. Alcoholism: Clinical and Experimental Research 30(6): 1051-1059, 2006. (49 refs.)

The effects of prenatal alcohol exposure (PAE) on measures of intelligence have been well documented in children with fetal alcohol syndrome. However, deficits in general intellectual ability in children with low to moderate PAE are less well understood. The objective of this study was to assess the association between moderate PAE and cognitive ability in children at age 10 controlling for other prenatal and birth factors, maternal and child psychosocial factors, and environmental characteristics. Data were collected as part of the Maternal Health Practices and Child Development Project, a prospective study of prenatal substance use with 636 mother-child pairs. Women were assessed during each trimester of pregnancy and with their children at birth; 8 and 18 months; and 3, 6, and 10 years. Each phase included an evaluation of growth, development, cognitive, and psychological functioning. At age 10, cognitive ability was assessed using the composite score and verbal, abstract/visual, quantitative, and short-term memory area scores of the Stanford-Binet Intelligence Test, fourth edition. Maternal intellectual ability, maternal prenatal and current drug use, maternal and child psychosocial characteristics, demographics, and home environment were included in the analysis. A significant relation was found between alcohol exposure during the first and second trimesters and the composite score of the Stanford-Binet for African American children at age 10. Significant relations were also found for the verbal, abstract/visual, and quantitative subscales. Additional predictors of IQ at age 10 included mother's IQ, home environment, and child's report of depression. There is a significant association between PAE and cognitive ability at age 10 among African American offspring. There was no relation between PAE and scores on the Stanford-Binet scales among the Caucasian offspring.