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CORK Bibliography: Child Development after Prenatal Drug Exposure

43 citations. January 2008 to present

Prepared: September 2009

Aragon AS; Coriale G; Fiorentino D; Kalberg WO; Buckley D; Gossage JP et al. Neuropsychological characteristics of Italian children with fetal alcohol spectrum disorders. Alcoholism: Clinical and Experimental Research 32(11): 1909-1919, 2008. (67 refs.)

Background: Children with fetal alcohol spectrum disorders (FASD) display many problems ranging from deficits in intelligence to behavioral difficulties. Thus, many studies have aimed at defining the neuropsychological characteristics of children with FASD. The current article describes the neuropsychological characteristics of Italian children with severe diagnosis within FASD and compares them with controls. It was expected that intellectual functioning, language comprehension, academic skills, and inattention/hyperactivity would discriminate children with FASD from randomly selected peers without FASD. Methods: This article presents data from a second cohort of children examined in 2005 as part of an in-school epidemiological study of FASD in Italy. Of 80 children, 23 diagnosed with a FASD, and 57 randomly selected control children from the same first-grade classes, participated. After screening for FASD via growth and dysmorphology, the children were administered a test of general intelligence (WISC-R) as well as tests of nonverbal reasoning (Raven Colored Progressive Matrices), language comprehension (Rustioni), academic achievement (IPDA), and problem behavior (Disruptive Behavior Disorder Rating Scale). Results: Children diagnosed with a FASD achieved lower scores than control children on Verbal, Performance, and Full Scale IQ. Profile analysis of the WISC-R indicates overall differences between the groups. However, some intact functioning within the FASD group was found, as the Similarities and Vocabulary subtests were similar to the controls. After an alpha adjustment to 0.004, the Block Design, Object Assembly, and Mazes subtests were significantly different from controls. On tests of nonverbal reasoning, language comprehension, and academic achievement, the children with a FASD scored significantly lower. Moreover, teachers rated children with a severe diagnosis within FASD as showing more inattentive symptoms than controls, while hyperactive/impulsive characteristics among children with a FASD were comparable with the control children. Significant correlations between head circumference, child dysmorphology, WISC-R, and Raven CPM scores are also reported. Conclusions: This study indicates that a sample of Italian children with a FASD, when compared with control children, display poorer functioning on measures of general intelligence, nonverbal reasoning, academic achievement, and teacher-rated problem behaviors. The findings also contribute to the formulation of a neuropsychological profile of children diagnosed with a FASD.

Bennett DS; Bendersky M; Lewis M. Children's cognitive ability from 4 to 9 years old as a function of prenatal cocaine exposure, environmental risk, and maternal verbal intelligence. Developmental Psychology 44(4): 919-928, 2008. (81 refs.)

This study examined the effects of prenatal cocaine exposure, environmental risk, and maternal verbal intelligence on children's cognitive ability. Gender and age were examined as moderators of potential cocaine exposure effects. The Stanford-Binet IV intelligence test was administered to 23 1 children (91 cocaine exposed, 140 unexposed) at ages 4, 6, and 9 years. Neonatal medical risk and other prenatal exposures (alcohol, cigarettes, and marijuana) were also examined for their unique effects on child IQ. Mixed models analysis indicated that prenatal cocaine exposure interacted with gender, as cocaine-exposed boys had lower composite IQ scores. Age at assessment did not moderate this relation, indicating that cocaine-exposed boys had lower IQs across this age period. A stimulating home environment and high maternal verbal IQ also predicted higher composite IQ scores. Cocaine-exposed boys had lower scores on the Abstract[Visual Reasoning subscale, with trends for lower scores on the Short-Term Memory and Verbal Reasoning subscales, as exposure effects were observed across domains. The findings indicate that cocaine exposure continues to place children at risk for mild cognitive deficits into preadolescence. Possible mechanisms for the Exposure X Gender interaction are discussed.

Burns L; Mattick RP; Wallace C. Smoking patterns and outcomes in a population of pregnant women with other substance use disorders. Nicotine & Tobacco Research 10(6): 969-974, 2008. (38 refs.)

Using a retrospective cross-sectional study design, we examined smoking patterns and associated neonatal outcomes in infants born to women with a diagnosis of a substance use disorder in pregnancy. Antenatal and birth admissions were linked to midwives data on pregnancy care, services, and outcomes over a 5-year period (1998-2002). Birth admissions were flagged as positive for drug use where a birth admission or any pregnancy admission for that birth involved a cannabis-, opioid-, stimulant-, or alcohol-related ICD-10AM code. There were 4,346 live births to women with a substance-related diagnosis in pregnancy. Women with a substance-related diagnosis (the drug group) had an adjusted odds ratio for smoking during pregnancy of 10.8 (95% CI=9.9-11.7) relative to women without a substance-related diagnosis (the non-drug group). Women in the drug group also were heavier smokers; 26% smoked 1-10 cigarettes/day and 56% smoked more than 10 cigarettes/day compared with 8% in both groups in the non-drug group. Relative to the drug group, the adjusted odds ratio for quitting smoking during pregnancy in the non-drug group was 3.1 (95% CI=2.3-4.3). Among women in the drug group, any smoking significantly increased the risk of poor fetal growth, prematurity, and admission to the special care nursery. In conclusion, innovative and effective strategies for tobacco cessation should target pregnant women as a high priority. Further research should identify the models of tobacco cessation most suited to women who also use other substances during pregnancy.

Buschgens CJM; Swinkels SHN; van Aken MAG; Ormel J; Verhulst FC; Buitelaar JK. Externalizing behaviors in preadolescents: Familial risk to externalizing behaviors, prenatal and perinatal risks, and their interactions. European Child and Adolescent Psychiatry 18(2): 65-74, 2009. (53 refs.)

Background: Accumulating evidence indicates that there is a rich and varied interplay between persons and their environments, which strongly suggests that this involves gene-environment correlations and interactions. We investigated whether familial risk (FR) to externalizing behaviors and prenatal and perinatal risk factors, separately or in interaction with each other, predicted externalizing behaviors. Methods: The subjects were 10- to 12-year-old preadolescents who were taking part in TRAILS, a large prospective population-based cohort study (N=2,230). Regression analyses were used to determine the relative contribution of FR and prenatal and perinatal risks to parent and teacher ratings of inattention, hyperactivity/impulsivity aggression, and delinquency. Results: Regression models explained between 6 and 11% of the variance of externalizing behaviors. We found main effects of FR (vs. no FR), macrosomia (birth weight >4,500 g), maternal prenatal smoking ( MPS), pregnancy and delivery complications (PDCs), and gender that were rather consistent across rater and outcome measures. For some outcome measures, the effect of MPS and PDCs depended on the presence of FR. These included both positive and negative interaction effects. Correlations between FR and prenatal and perinatal risks were significant but rather low. Conclusions: Both main effects and interaction effects of FR and prenatal and perinatal risks contributed to externalizing behaviors in preadolescents, but all effects were of small size. Further research including use of candidate gene polymorphisms is necessary to identify the underlying neurobiological mechanisms of these main and interaction effects.

Chae SM; Covington CY. Biobehavioral outcomes in adolescents and young adults prenatally exposed to cocaine: Evidence from animal models. Biological Research for Nursing 10(4): 318-330, 2009. (83 refs.)

Cocaine has been a popular illicit drug among drugusing pregnant women over the last three decades. Prenatal cocaine exposure (PCE) has significant effects on children's development throughout early childhood. Very few human studies, however, report the effects of PCE on adolescent or early-adult development. As knowledge about early childhood effects in human children was informed by animal studies, this review considers the effects of PCE on behavioral outcomes in adolescent and young adult animals and provides potential guidance for research in human children. Animal models prenatally exposed to cocaine manifest play deficits, decreased social interaction, and increased aggression during competition in adolescence and young adulthood. Altered behavioral adaptation after stress exposure, including hormonal response change, is also evident. Attention deficits are reported in adult offspring with PCE, not only in a novel environment, but also in a final task session, indicating effects of PCE on transition and maintenance of attention. Animal studies support that PCE effects may extend beyond early childhood and continue to adolescence and adulthood. Additionally, some studies highlight that behavioral changes in offspring with PCE born without teratogenesis remain latent and reveal themselves during adulthood when animals are under stress conditions. Based on the evidence from animal models, well-designed human studies are needed to elucidate the effects of PCE on older human children. Research models that combine behavioral measures with stressful challenges may hold potential in discerning a longer term influence 4 PCE.

Chiodo LM; Janisse J; Delaney-Black V; Sokol RJ; Hannigan JH. A metric of maternal prenatal risk drinking predicts neurobehavioral outcomes in preschool children. Alcoholism: Clinical and Experimental Research 33(4): 634-644, 2009. (98 refs.)

Fetal Alcohol Spectrum Disorders (FASDs), including Fetal Alcohol Syndrome, continue to be high-incidence developmental disorders. Detection of patterns of maternal drinking that place fetuses at risk for these disorders is critical to diagnosis, treatment, and prevention, but is challenging and often insufficient during pregnancy. Various screens and measures have been used to identify maternal risk drinking but their ability to predict child outcome has been inconsistent. This study hypothesized that a metric of fetal "at-risk" alcohol exposure (ARAE) derived from several indicators of maternal self-reported drinking would predict alcohol-related neurobehavioral dysfunctions in children better than individual measures of maternal alcohol consumption alone. Self-reported peri-conceptional and repeated maternal drinking during pregnancy were assessed with semi-structured interviews and standard screens, i.e., the CAGE, T-ACE, and MAST, in a prospective sample of 75 African-American mothers. Drinking volumes per beverage type were converted to standard quantity and frequency measures. From these individual measures and screening instruments, a simple dichotomous index of prenatal ARAE was defined and used to predict neurobehavioral outcomes in the 4- to 5-year-old offspring of these women. Study outcomes included IQ, attention, memory, visual-motor integration, fine motor skill, and behavior. Statistical analyses controlled for demographic and other potential confounders. The current "at-risk" drinking metric identified over 62% of the mothers as drinking at risk levels-23% more than the selection criterion identified-and outperformed all individual quantity and frequency consumption measures, including averages of weekly alcohol use and "binge" alcohol exposures (assessed as intake per drinking occasion), as well as an estimate of the Maternal Substance Abuse Checklist (Coles et al., 2000), in predicting prenatal alcohol-related cognitive and behavioral dysfunction in 4- to 5-year-old children. A metric reflecting multiple indices of "at-risk" maternal alcohol drinking in pregnancy had greater utility in predicting various prenatal alcohol-related neurobehavioral dysfunction and deficits in children compared to individual measures of maternal self-reported alcohol consumption or a previous maternal substance abuse index. Assessing fetal risk drinking in pregnant women was improved by including multiple indicators of both alcohol consumption and alcohol-related consequences and, if appropriate practical applications are devised, may facilitate intervention by health care workers during pregnancy and potentially reduce the incidence or severity of FASDs.

Chiriboga CA; Starr D; Kuhn L; Wasserman GA. Prenatal cocaine exposure and prolonged focus attention. Developmental Neuroscience 31(1/2): 149-158, 2009. (66 refs.)

In experimental models, prenatal cocaine exposure has been found to perturb monoaminergic development of systems implicated in modulating attention. To determine whether prenatal cocaine exposure affects infant attention, we assessed visual recognition memory and focused attention during free play. We enrolled at birth 380 infants, 113 cocaine exposed, using multiple biomarkers to assess drug exposure. Behavior was videotaped and coded off-line for sustained looking time (i.e. focused attention), banging and intrusion. Prenatal cocaine exposure was not associated with visual recognition memory, but was significantly associated with longer sustained looking times (average focused attention) at ages 6 months (p = 0.02) and 12 months (p = 0.04) in analyses that adjusted for variables, including maternal intelligence, education, depressive scores and other exposures (alcohol, tobacco and marijuana). Cocaine-exposed infants at age 12 months also spent significantly less time in banging activity (p = 0.02) after adjusting for confounding variables. This finding was not explained through cocaine effects on motor development, neurological findings or time spent in focused attention. Prenatal cocaine exposure was significantly associated with longer periods of sustained looking or focused attention in infancy, a finding that could interpreted as a measure of poor processing efficiency, or alternatively as precocious maturation of attentional systems. Either interpretation has implications for later cognitive development. Lower banging activity among cocaine exposed was not explained through cocaine effects on motor development or neurological findings, suggesting that activity level itself is diminished in these infants. Whether focused attention findings impact long term development awaits further study.

Cornelius MD; Day NL. Developmental consequences of prenatal tobacco exposure. Current Opinion in Neurology 22(2): 121-125, 2009. (34 refs.)

Purpose of review: This paper reviews results from published, in press, and conference proceedings from 2007 and 2008 that link in-utero tobacco exposure to neurodevelopmental outcomes in exposed offspring. Recent findings: Prenatal tobacco exposure (PTE) affected speech processing, levels of irritability and hypertonicity, attention levels, ability to self-regulate, need to be handled, and response to novelty preference in infants. In early childhood, PTE effects were mostly behavioral outcomes including activity and inattention and externalizing behaviors, including conduct disorder and antisocial behavior. In adolescents, PTE predicted increased attention deficit hyperactivity disorder, modulation of the cerebral cortex and white matter structure, and nicotine addiction. Several studies found moderating effects with PTE and genetic susceptibilities including dopamine transporter, serotonergic synaptic function, and monomine oxidase pathways. Other studies suggested that environmental and genetic factors might be more important than the direct teratological effects of PTE. Summary: The majority of studies reviewed were prospective and tobacco exposure was quantified biologically. Most demonstrated a direct association between PTE and neurodevelopmental outcomes. More work is needed to examine multifactorial influences. Effects of PTE on the offspring appear to be moderated by genetic variability, neurobehavioral disinhibition, and sex.

D'Onofrio BM; Van Hulle CA; Waldman ID; Rodgers JL; Harden KP; Rathouz PJ et al. Smoking during pregnancy and offspring externalizing problems: An exploration of genetic and environmental confounds. Development and Psychopathology 20(1): 139-164, 2008. (80 refs.)

Previous studies have documented that smoking during pregnancy (SDP) is associated with offspring externalizing problems, even when measured covariates were used to control for possible confounds. However, the association may be because of nonmeasured environmental and genetic factors that increase risk for offspring externalizing problems. The current project used the National Longitudinal Survey of Youth and their children, ages 4-10 years, to explore the relations between SDP and offspring conduct problems (CPs), oppositional defiant problems (ODPs), and attention-deficit/hyperactivity problems (ADHPs) using methodological and statistical controls for confounds. When offspring were compared to their own siblings who differed in their exposure to prenatal nicotine, there was no effect of SDP on offspring CP and ODP. This suggests that SDP does not have a causal effect on offspring CP and ODP. There was a small association between SDP and ADHP, consistent with a causal effect of SDP, but the magnitude of the association was greatly reduced by methodological and statistical controls. Genetically informed analyses suggest that unmeasured environmental variables influencing both SDP and offspring externalizing behaviors account for the previously observed associations. That is, the current analyses imply that important unidentified environmental factors account for the association between SDP and offspring externalizing problems, not teratogenic effects of SDP.

Ghetau E; Bloor R; Firth AY. Identification of strabismus in children born to mothers misusing substances during pregnancy: A clinical and research challenge. Drugs: Education, Prevention and Policy 16(1): 88-93, 2009. (17 refs.)

Purpose: To increase awareness of the causal relationship between illicit drug use in pregnancy and the occurrence of strabismus in children amongst the relevant professionals and encourage the use of local arrangements for referral, assessment and treatment of this population at risk. Method: A review of the literature regarding the occurrence of strabismus in children of mothers misusing substances and an outline the consequences of strabismus. Results: Children prenatally exposed to the effects of psychoactive substances are at increased risk of neurodevelopmental and neurobehavioural abnormalities; ocular defects are frequently mentioned as some of them. Strabismus, the consequences of which are treatable, is amongst these. Conclusion: Research in this area is challenging, but while more evidence is awaited, current evidence indicates the increased risk of strabismus in this group and recommendations regarding the early detection of, and referral for, this condition are made.

Guerri C; Bazinet A; Riley EP. Foetal alcohol spectrum disorders and alterations in brain and behaviour. (review). Alcohol and Alcoholism 44(2): 108-114, 2009. (116 refs.)

The term 'Foetal Alcohol Spectrum Disorders (FASD)' refers to the range of disabilities that may result from prenatal alcohol exposure. This article reviews the effects of ethanol on the developing brain and its long-term structural and neurobehavioural consequences. Brain imaging, neurobehavioural and experimental studies demonstrate the devastating consequences of prenatal alcohol exposure on the developing central nervous system (CNS), identifying specific brain regions affected, the range of severity of effects and mechanisms involved. In particular, neuroimaging studies have demonstrated overall and regional volumetric and surface area reductions, abnormalities in the shape of particular brain regions, and reduced and increased densities for white and grey matter, respectively. Neurobehaviourally, FASD consists of a continuum of long-lasting deficits affecting multiple aspects of cognition and behaviour. Experimental studies have also provided evidence of the vulnerability of the CNS to the teratogenic effects of ethanol and have provided new insight on the influence of risk factors in the type and severity of observed brain abnormalities. Finally, the potential molecular mechanisms that underlie the neuroteratological effects of alcohol are discussed, with particular emphasis on the role of glial cells in long-term neurodevelopmental liabilities.

Herrmann M; King K; Weitzman M. Prenatal tobacco smoke and postnatal secondhand smoke exposure and child neurodevelopment. (review). Current Opinion in Pediatrics 20(2): 184-190, 2008. (112 refs.)

Purpose To review the recent scientific literature examining the association of prenatal tobacco and postnatal secondhand smoke exposure and child neurodevelopment. Recent findings Low birth weight and decreased in-utero brain growth are two of multiple potential etiologic pathways proposed as mediating the effects of prenatal tobacco smoke exposure on child neurodevelopment. These negative effects of prenatal exposure have been consistently demonstrated in animal models, and in humans have been found as early as the newborn period. The literature on both prenatal and postnatal exposure is remarkably consistent in showing associations with increased rates of behavior problems, including irritability, oppositional defiant behavior, conduct disorders and attention deficit hyperactivity disorder. A more rudimentary literature also suggests deficits in intelligence quotient. Recent studies have focused on elucidating the complex interaction among tobacco exposure, genetics and environmental factors. Questions still remain about the relative roles of prenatal vs. postnatal exposure and the potential role of genetic and social confounders, limiting the ability to infer a causal nature to these associations at this time. The consistency of findings across studies is, however, highly suggestive of a causal relationship between environmental tobacco exposure and adverse behavioral and cognitive outcomes in children. Summary Prenatal tobacco and postnatal secondhand smoke exposure is consistently associated with problems in multiple domains of children's neurodevelopment and behavior.

Huijbregts SCJ; Warren AJ; de Sonneville LMJ; Swaab-Barneveld H. Hot and cool forms of inhibitory control and externalizing behavior in children of mothers who smoked during pregnancy: An exploratory study. Journal of Abnormal Child Psychology 36(3): 323-333, 2008. (73 refs.)

This study examined whether children exposed to prenatal smoking show deficits in "hot" and/or "cool" executive functioning (EF). Hot EF is involved in regulation of affect and motivation, whereas cool EF is involved in handling abstract, decontextualized problems. Forty 7 to 9-year-old children (15 exposed to prenatal smoking, 25 non-exposed) performed two computerized tasks. The Sustained Attention Dots (SA-Dots) Task (as a measure of "cool" inhibitory control) requires 400 non-dominant hand and 200 dominant hand responses. Inhibitory control of the prepotent response is required for dominant hand responses. The Delay Frustration Task (DeFT) (as a measure of "hot" inhibitory control) consists of 55 simple maths exercises. On a number of trials delays are introduced before the next question appears on the screen. The extent of response-button pressing during delays indicates frustration-induced inhibitory control. Prenatally exposed children showed poorer inhibitory control in the DeFT than non-exposed children. A dose-response relationship was also observed. In addition, prenatally exposed children had significantly higher (dose-dependent) conduct problem- and hyperactivity-inattention scores. There were no significant group differences in inhibitory control scores from the SA-Dots. These results indicate that children exposed to prenatal smoking are at higher risk of hot but not cool executive function deficits.

Kable JA; Coles CD; Lynch ME; Platzman K. Physiological responses to social and cognitive challenges in 8-year olds with a history of prenatal cocaine exposure. Developmental Psychobiology 50(3): 251-265, 2008. (76 refs.)

Cocaine-exposed infants have been found to have altered arousal responses but little is known about such responses in later childhood. Physiological responses to stressors were used to assess the arousal modulation of school-aged, cocaine-exposed children (n = 73) and two contrast groups, socioeconomically-matched controls (n = 58) and children with behavioral disturbance (n = 35). The behaviorally disturbed group had the highest heart rate across conditions but demonstrated a pattern of hyporesponsiveness to the stressors. They had the smallest decrement in skin conductance response at baseline and the least recovery of skin conductance response following exposure to stressors. Cocaine-exposed children demonstrated greater acceleratory responses to the stressors as indexed by their skin conductance level and were intermediate between the socioeconomically-matched controls and children with behavioral disturbance in recovery of skin conductance response following stressors. Altered arousal responses associated with prenatal cocaine exposure persisted into middle childhood but were different from those found in behaviorally disturbed children.

Kelly Y; Sacker A; Gray R; Kelly J; Wolke D et al. Light drinking in pregnancy, a risk for behavioural problems and cognitive deficits at 3 years of age? International Journal of Epidemiology 38(1): 129-140, 2009. (50 refs.)

Background The objective of this study was to determine whether there was an association between mothers' light drinking during pregnancy and risk of behavioural problems, and cognitive deficits in their children at age 3 years. Methods Data from the first two sweeps of the nationally representative prospective UK Millennium Cohort study were used. Drinking patterns during pregnancy and behavioural and cognitive outcomes were assessed during interviews and home visits. Behavioural problems were indicated by scores falling above defined clinically relevant cut-offs on the parent-report version of the Strengths and Difficulties Questionnaire (SDQ). Cognitive ability was assessed using the naming vocabulary subscale from the British Ability Scale (BAS) and the Bracken School Readiness Assessment (BSRA). Results There was a J-shaped relationship between mothers drinking during pregnancy and the likelihood of high scores (above the cut-off) on the total difficulties scale of the SDQ and the conduct problems, hyperactivity and emotional symptom SDQ subscales. Children born to light drinkers were less likely to score above the cut-offs compared with children of abstinent mothers. Children born to heavy drinkers were more likely to score above the cut-offs compared with children of abstinent mothers. Boys born to mothers who had up to 1-2 drinks per week or per occasion were less likely to have conduct problems (OR 0.59, 95% CI 0.45-0.77) and hyperactivity (OR 0.71, 95% CI 0.54-0.94). These effects remained in fully adjusted models. Girls were less likely to have emotional symptoms (OR 0.72, 95% CI 0.51-1.01) and peer problems (OR 0.68, 95% CI 0.52-0.92) compared with those born to abstainers. These effects were attenuated in fully adjusted models. Boys born to light drinkers had higher cognitive ability test scores [standard deviations, (95% CI)] BAS 0.15 (0.08-0.23) BSRA 0.24 (0.16-0.32) compared with boys born to abstainers. The difference for BAS was attenuated on adjustment for socio-economic factors, whilst the difference for BSRA remained statistically significant. Conclusions Children born to mothers who drank up to 1-2 drinks per week or per occasion during pregnancy were not at increased risk of clinically relevant behavioural difficulties or cognitive deficits compared with children of abstinent mothers. Heavy drinking during pregnancy appears to be associated with behavioural problems and cognitive deficits in offspring at age 3 years whereas light drinking does not.

Knopik VS. Maternal smoking during pregnancy and child outcomes: Real or spurious effect? (review). Developmental Neuropsychology 34(1): 1-36, 2009. (155 refs.)

Maternal smoking during pregnancy (MSDP) is a major public health concern with clearly established consequences to both mother and newborn (e.g., low birth weight, altered cardiorespiratory responses). MSDP has also been associated with higher rates of a variety of poor cognitive and behavioral outcomes in children, including attention deficit hyperactivity disorder (ADHD), conduct disorder, impaired learning and memory, and cognitive dysfunction. However, the evidence suggesting causal effects of MSDP for these outcomes is muddied in the existing literature due to the frequent inability to separate prenatal exposure effects from other confounding environmental and genetic factors. Carefully designed studies using genetically sensitive strategies can build on current evidence and begin to elucidate the likely complex factors contributing to associations between MSDP and child outcomes.

Kurtz PF; Chin MD; Rush KS; Dixon DR. Treatment of challenging behavior exhibited by children with prenatal drug exposure. Research in Developmental Disabilities 29(6): 582-594, 2008. (41 refs.)

A large body of literature exists describing the harmful effects of prenatal drug exposure on infant and child development. However, there is a paucity of research examining strategies to ameliorate sequelae such as externalizing behavior problems. In the present study, functional analysis procedures were used to assess challenging behavior exhibited by two children who were prenatally exposed to drugs of abuse. Results for both children indicated that challenging behavior was maintained by access to positive reinforcement (adult attention and tangible items). For one child, challenging behavior was also maintained by negative reinforcement (escape from activities of daily living). Function-based interventions were effective in reducing challenging behavior for both children. Implications for utilizing methods of applied behavior analysis in research with children with prenatal drug exposure are discussed.

Lester BM; Padbury JF. Third pathophysiology of prenatal cocaine exposure. (review). Developmental Neuroscience 31(2): 23-25, 2009. (237 refs.)

The pathophysiology of the effects of cocaine on fetal development has been described along 2 major pathways: neurochemical effects and vasoconstrictive effects. Following a summary of these effects, we suggest a 'third pathophysiology' in which altered fetal programming affects the acute and long-term adverse effects of in utero cocaine exposure. We describe how cocaine as a stressor alters the expression of key candidate genes, increasing exposure to catecholamines and fetal cortisol-altering neuroendocrine (hypothalamic-pituitary-adrenal axis) activity, leading to infant behavioral dysregulation, poor behavioral control and emotion regulation during childhood and phenotypes that confer vulnerability to substance use in adolescence. This model is discussed in relation to follow-up studies of the effects of in utero cocaine exposure and maturational changes in brain development.

MacArthur AC; McBride ML; Spinelli JJ; Tamaro S; Gallagher RP; Theriault G et al. Risk of childhood leukemia associated with parental smoking and alcohol consumption prior to conception and during pregnancy: the cross-Canada childhood leukemia study. Cancer Causes and Control 19(3): 283-295, 2008. (45 refs.)

Objective As part of a larger case-control study, the authors evaluated risk of childhood leukemia relative to parental self-reported smoking and alcohol consumption. Methods Children 0-14 years of age diagnosed with leukemia between 1990 and 1994 were ascertained through population-based sources at the time of diagnosis. For each participating case, an age, gender, and area-matched control was randomly selected from provincial government health insurance rolls. Risk factor information was obtained through personal interviews with each child's parents. Conditional logistic regression models were used to examine risk of leukemia associated with parental smoking and drinking. Results Maternal alcohol consumption prior to conception (OR = 1.37, 95% CI, 0.99-1.90) and during pregnancy (OR = 1.39, 95% CI, 1.01-1.93) was associated with an excess risk of childhood leukemia, with a positive dose-response trend for increasing weekly consumption (p< 0.05). Similar results were observed for children diagnosed with acute lymphoblastic leukemia (ALL). Odds ratios for maternal cigarette smoking before and during pregnancy were consistently elevated above one, but not statistically significant. No relationship was observed with paternal drinking or smoking in the perinatal period. Conclusion Our study suggests that maternal alcohol drinking before or during pregnancy may contribute to an increased risk of childhood leukemia.

Martin RP; Dombrowski SC. Prenatal Exposures: Psychological and Educational Consequences for Children. New York: Springer, 2008

This book addresses the psychological and educational problems that can accompany prenatal drug exposure, not only to drugs of abuse, but also other toxic substances. Individual chapters address prenatal central nervous system development; low birth weight and prematurity and their impact on developmental; pre- perinatal anoxia and hypoxia; prenatal infections; maternal chronic illness; inadequate nutrition; maternal stress; nicotine; alcohol; other illicit drugs; air and water pollution; and heavy metals and household chemicals.

McGee CL; Bjorkquist OA; Riley EP; Mattson SN. Impaired language performance in young children with heavy prenatal alcohol exposure. Neurotoxicology and Teratology 31(2): 71-75, 2009. (31 refs.)

The aims of this study were to evaluate the language abilities of young children with heavy prenatal alcohol exposure and to determine if these abilities represent a relative strength or weakness for this population. Two matched groups of children (ages 3 to 5) completed the Clinical Evaluation of Language Fundamentals, Preschool version: 25 children with heavy prenatal alcohol exposure (ALC) and 26 non-exposed controls (CON). Consistent with previous research, the CON group had significantly higher full scale IQ (FSIQ) scores than the ALC group. Receptive and expressive language skills of the two groups were compared. The ALC group had significantly poorer language skills than the CON group and both groups had better receptive than expressive abilities. Language performance did not significantly deviate from what would be predicted by FSIQ for either group. These results indicate that receptive and expressive language abilities are impaired in children with heavy prenatal alcohol exposure but not more so than general intellectual functioning. However, these deficits are likely to impact the social interactions and behavioral adjustment of children with prenatal alcohol exposure.

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.

Mongraw-Chaffin ML; Cohn BA; Anglemyer AT; Cohen RD; Christianson RE. Maternal smoking, alcohol, and coffee use during pregnancy and son's risk of testicular cancer. Alcohol 43(3): 241-245, 2009. (38 refs.)

It has been suggested that increased risk for testicular cancer occurring worldwide may be due to exposures during fetal development. Lifestyle or environmental exposures may be the most important predictors of risk. However, few studies have directly examined these exposures prospectively. The Child Health and Development Studies is a 40-year follow-up of 20,530 pregnancies occurring between 1959 and 1967. There were 20 cases of testicular cancer diagnosed through 2003 among sons with a maternal interview in early pregnancy. Cases were matched to three controls on birth year and race. Odds ratios and 95% confidence intervals were calculated with exact conditional logistic regression. Compared to controls, mothers of testicular cancer cases were more likely to drink alcohol (unadjusted odds ratio, 3.2; 95% confidence interval, 0.83-15.48 for above vs. below the median for controls) and less likely to drink coffee (unadjusted odds ratio, 0.19; 95% confidence interval, 0.02-1.02 for above vs. below the median). Case mothers were neither more nor less likely to smoke. Although low power may limit interpretation of negative results, the prospective design minimizes bias. In this cohort, maternal serum testosterone in pregnancy was previously reported to be lower in women who drank alcohol. Because populations with high testicular cancer risk also have lower maternal testosterone, we suggest that testosterone could play a role in explaining the higher risk of son's testicular cancer among mothers who drank alcohol during pregnancy.

Montgomery SM; Bahmanyar S; Hillert J; Ekbom A; Olsson T. Maternal smoking during pregnancy and multiple sclerosis amongst offspring. European Journal of Neurology 15(12): 1395-1399, 2008. (34 refs.)

An association between parental smoking and multiple sclerosis (MS) in offspring has been reported. This study examined whether maternal smoking during pregnancy is associated with MS in offspring. Swedish general population registers provided prospectively recorded information on maternal smoking during pregnancy. The study identified 143 cases with MS diagnosed by 2006 and 1730 matched controls. Subjects were born since 1982 and individually matched by year of birth, age, sex and region of residence. Conditional logistic regression assessed the association of maternal smoking with MS in offspring with adjustment for socioeconomic index. Maternal smoking during pregnancy was not associated with MS in offspring, with an odds ratio (and 95% confidence interval) of 0.96 (0.65-1.44). When stratified by paediatric or later MS onset there was no association with maternal smoking in either stratum. It is unlikely that smoking during pregnancy represents a risk for early-onset MS amongst offspring.

Nestler EJ. Drug abuse, addiction and the developing brain. (foreword). Developmental Neuroscience 31(1/2): 6-6, 2009. (0 refs.)

Oddsberg J; Jia C; Nilsson E; Ye WM; Lagergren J. Maternal tobacco smoking, obesity, and low socioeconomic status during early pregnancy in the etiology of esophageal atresia. Journal of Pediatric Surgery 43(10): 1791-1795, 2008. (18 refs.)

Background: The etiology of the congenital malformation esophageal atresia (EA) is essentially unknown. We hypothesized that maternal tobacco smoking, obesity, and low socioeconomic status (SES) during early pregnancy might increase the risk of the fetus developing EA. Methods: A nationwide, population-based, case-control study was nested in a cohort of children born in Sweden in 1982 to 2004. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression. Matching, stratification, and multivariable regression were used to control for confounding. Results: Among 2,305,858 newborn children constituting the study cohort, 722 cases of EA and 36 10 controls were included. For women smoking 10 cigarettes or more daily, the adjusted OR was 0.88 (95% Cl, 0.62-1.25) compared to nonsmokers. For obese women (body mass index, >30), OR was 0.99 (95% Cl, 0.64-1.55) compared to lean women (body mass index, <20). Women with more than 12 years of formal education, representing SES, had an OR of 0.94 (95% CI, 0.69-1.29) compared to those with less than 10 years of education. The lack of association remained in stratified analyses of isolated EA and EA accompanied by associated malformations. Conclusion: This study provides evidence refuting the hypotheses of an increased risk of EA among children of women who smoke, are obese, or have a low SES during early pregnancy.

Paus T; Nawazkhan I; Leonard G; Perron M; Pike GB; Pitiot A et al. Corpus callosum in adolescent offspring exposed prenatally to maternal cigarette smoking. Neuroimage 40(2): 435-441, 2008. (60 refs.)

Teratogens, such as alcohol or anti-epileptic drugs, affect the size of the corpus callosum. Here we report findings obtained in a case-control study that investigated possible effects of teratogens contained in cigarette smoke on the size and structural properties of this structure. We recruited and scanned with magnetic resonance imaging a total of 408 adolescents (12 to 18 years of age); a subsample of 300 adolescents is considered in this report. Cases (n=146) were exposed to maternal cigarette smoking during pregnancy; non-exposed controls (n=154) were matched to cases by maternal education. We measured the size of corpus callosum (CC) and its sections (corrected for brain size), as well as mean values of magnetization-transfer ratio (MTR) in each CC section. Corpus callosum, and especially its posterior part, was smaller in the exposed vs. non-exposed female adolescents; no significant effects were found in males. Exposed and non-exposed subjects did not differ in the MTR-based index of myelination in either gender in any CC section. Given the lack of exposure effect on the myelination index, this finding might reflect a lower number of inter-hemispheric connections in female offspring of mothers who smoked during pregnancy.

Pulsifer MB; Butz AM; Foran MO; Belcher HME. Prenatal drug exposure: Effects on cognitive functioning at 5 years of age. Clinical Pediatrics 47(1): 58-65, 2008. (37 refs.)

The goal of this cross-sectional study was to compare cognitive functioning at age 5 years in prenatal drug-exposed children with nondrug-exposed children from a comparable inner-city environment. Children with prenatal drug exposure scored significantly lower on measures of language, school readiness skills, impulse control, and visual attention span/sequencing than controls matched for age and socioeconomic status. Intelligence, visual-motor, manual dexterity, and sustained attention scores were not significantly different between groups. The total sample scored significantly below the normative mean on standardized measures of intelligence, language, school readiness, visual-motor skills, impulse control, and sustained attention, with 40% scoring at least I standard deviation below the mean (IQ < 85) on a measure of intelligence. Findings suggest that children with prenatal drug exposure are at increased risk for learning and attention problems and are in need of close developmental surveillance and possible intervention to support school success and improve behavioral outcome.

Robinson M; Oddy WH; Li JH; Kendall GE; de Klerk NH; Silburn SR. Pre- and postnatal influences on preschool mental health: A large-scale cohort study. Journal of Child Psychology and Psychiatry 49(10): 1118-1128, 2008. (50 refs.)

Background: Methodological challenges such as confounding have made the study of the early determinants of mental health morbidity problematic. This study aims to address these challenges in investigating antenatal, perinatal and postnatal risk factors for the development of mental health problems in pre-school children in a cohort of Western Australian children. Methods: The Raine Study is a prospective cohort study of 2,868 live born children involving 2,979 pregnant women recruited at 18 weeks gestation. Children were followed up at age two and five years. The Child Behaviour Checklist (CBCL) was used to measure child mental health with clinical cut-points, including internalising (withdrawn/depressed) and externalising (aggressive/destructive) behaviours (n = 1707). Results: Multinomial logistic regression analysis showed that the significant risk factors for behaviour problems at age two were the maternal experience of multiple stress events in pregnancy (OR = 1.20, 95% CI = 1.06, 1.37), smoking during pregnancy (OR = 1.30, 95% CI = 1.06, 1.59) and maternal ethnicity (OR = 3.34, 95% CI = 1.61, 6.96). At age five the experience of multiple stress events (OR = 1.17, 95% CI = 1.08, 1.27), cigarette smoking (OR = 1.19, 95% CI = 1.03, 1.37), male gender (OR = 1.43, 95% CI = 1.02, 2.00), breastfeeding for a shorter time (OR = .97, 95% CI = .94, .99) and multiple baby blues symptoms (OR = 1.08, 95% CI = 1.02, 1.14) were significant predictors of mental health problems. Conclusions: Early childhood mental health is significantly affected by prenatal events in addition to the child's later environment. Interventions targeting adverse prenatal, perinatal and postnatal influences can be expected to improve mental health outcomes for children in the early years.

Rodriguez A; Miettunen J; Henriksen TB; Olsen J; Obel C; Taanila A et al. Maternal adiposity prior to pregnancy is associated with ADHD symptoms in offspring: Evidence from three prospective pregnancy cohorts. International Journal of Obesity 32(3): 550-557, 2008. (44 refs.)

Objectives: We examine whether pregnancy weight (pre-pregnancy body mass index (BMI) and/or weight gain) is related to core symptoms of attention deficit hyperactivity disorder (ADHD) in school-age offspring. Design: Follow-up of prospective pregnancy cohorts from Sweden, Denmark and Finland within the Nordic Network on ADHD. Methods: Maternal pregnancy and delivery data were collected prospectively. Teachers rated inattention and hyperactivity symptoms in offspring. High scores were defined as at least one core symptom rated as 'severe' and two as 'present' (approximately 10% of children scored in this range). Logistic regression and latent class analyses were used to examine maternal pregnancy weight in relation to children's ADHD core symptoms. Results: Teacher rated 12 556 school-aged children. Gestational weight gain outside of the Institute of Medicine guidelines was not related to ADHD symptoms (below recommendations: odds ratio (OR): 0.96; 95% confidence interval (CI): 0.81, 1.14; above recommendations: OR: 0.98; 95% CI: 0.82, 1.16). To examine various patterns of pre-pregnancy BMI and weight gain, we used latent class analysis and found significant associations between classes that included pre-pregnancy overweight or obesity and a high ADHD symptom score in offspring, ORs ranged between 1.37 (95% CI: 1.07, 1.75) and 1.89 (95% CI: 1.13, 3.15) adjusted for gestational age, birth weight, weight gain, pregnancy smoking, maternal age, maternal education, child gender, family structure and cohort country of origin. Children of women who were both overweight and gained a large amount of weight during gestation had a 2-fold risk of ADHD symptoms (OR: 2.10, 95% CI: 1.19, 3.72) compared to normal-weight women. Conclusions: We show for the first time that pre-pregnancy BMI is associated with ADHD symptoms in children. Our results are of public health significance if the associations are causal and will then add ADHD symptoms in offspring to the list of deleterious outcomes related to overweight and obesity in the prenatal period.

Rose-Jacobs R; Waber D; Beeghly M; Cabral H; Appugleise D; Heeren T et al. Intrauterine cocaine exposure and executive functioning in middle childhood. Neurotoxicology and Teratology 31(3): 159-168, 2009. (89 refs.)

This longitudinal study evaluated whether the level of intrauterine cocaine exposure (IUCE) or the interaction between IUCE and contextual variables was related during middle childhood to executive functioning, as assessed with the Stroop Color-Word and Rey Osterrieth Complex Figure tests. The Stroop Interference score measures verbal inhibitory control while the Rey Osterrieth Organizational score evaluates skills such as planning, Organization and perception. Masked examiners assessed 143 children at 9.5 and I I years of age (74 with IUCE and 69 demographically similar children without IUCE). Level of IUCE (Unexposed; Lighter. and Heavier) was documented by positive postpartum maternal reports and infant meconium assays. In covariate-controlled regressions, level of IUCE was not significantly associated with Stroop Interference or Rey Osterrieth Organization scores. However, in covariate controlled post-hoc tests comparing the Heavier exposed group to the combined Lighter/Unexposed group, children in the Heavier group had significantly Poorer Stroop Interference scores, but there was no significant group difference for Rey Osterrieth Organizational scores. Children's average Organization scores in Unexposed, Lighter, and Heavier exposed groups were well below the test norm means. Results of this study indicate that heavier IUCE may be associated with mild compromise on school-aged children's ability to inhibit prepotent verbal responses.

Sheinkopf SJ; Lester BM; Sanes JN; Eliassen JC; Hutchison ER; Seifer R et al. Functional MRI and response inhibition in children exposed to cocaine in utero. Psychiatric Services 31(1/2): 159-166, 2009. (43 refs.)

This study investigated the potential long-term effects of cocaine exposure on brain functioning using fMRI in school-aged children. The sample included 12 children with prenatal cocaine exposure and 12 non-exposed children (8-9 years old). Groups did not differ on IQ, socioeconomic status, or perinatal risk factors. A response inhibition task was administered during an fMRI scan using a 1.5-T MRI system. Task performance did not differentiate groups, but groups were differentiated by patterns of task-related brain activity. Cocaine-exposed children showed greater activation in the right inferior frontal cortex and caudate during response inhibition, whereas non-exposed children showed greater activations in temporal and occipital regions. These preliminary findings suggest that prenatal cocaine may affect the development of brain systems involved in the regulation of attention and response inhibition.

Simmons RW; Levy SS; Riley EP; Madra NM; Mattson SN. Central and peripheral timing variability in children with heavy prenatal alcohol exposure. Alcoholism: Clinical and Experimental Research 33(3): 400-407, 2009. (53 refs.)

The study examined whether prenatal alcohol exposure is associated with increased motor timing variability when the timing response is partitioned into central clock variability, which indexes information processing at the central nervous system (CNS) level and motor delay variability, which reflects timing processes at the level of the peripheral nervous system. Eighteen children with histories of prenatal alcohol exposure and 22 control children were assigned to young (7 to 11 years) or older (12 to 17 years) groups. Children tapped a single response key with the index finger in synchrony with a series of externally generated tones (the paced phase). At the conclusion of these tones, children continued tapping (the continuation phase) while attempting to maintain the same rate of tapping imposed by the paced phase. Two blocks of tapping were completed with inter-tone-intervals set at either 400 or 900 milliseconds. Inter-response interval, central clock variability, and motor delay variability produced during the continuation phase were the dependent variables. Mean inter-response interval for the 4 groups did not differ for either time interval. Central clock variability produced by the young alcohol-exposed group was significantly greater than the two older groups for the 400 millisecond interval and all other groups for the 900 millisecond interval. Motor delay variability produced by the young alcohol-exposed group was significantly greater than the other three groups for both time intervals. Central and motor delay variability in children with and without alcohol exposure was directly related to the duration of the interval to be reproduced. Central and peripheral timing variability was significantly greater for the young alcohol-exposed children. This atypical timing may be related to the teratogenic effects of alcohol, although the negative effects are limited to younger alcohol-exposed children since there were no differences in central and peripheral timing variability between the older alcohol-exposed children and controls.

Sobrian SK; Johnston M; Wright J; Kuhn D; Ameis K. Prenatal nicotine and/or cocaine differentially alters nicotine-induced sensitization in aging offspring. Annals of the the New York Academy of Sciences. Drug Addiction: Research Frontiers and and Treatment Advances 1139: 466-477, 2008. (67 refs.)

Repeated exposure to psychostimulant drugs can result in behavioral sensitization, an amplified response in locomotor activity and stereotypy, which is used to model aspects of drug addiction. The expression of behavioral sensitization, induced by i.p. injections of nicotine once daily for 5 days, was examined in 450-day-old male rats exposed prenatally on GD 8-20 to one of the following conditions: (1) low nicotine: 2.5 mg/kg/day nicotine [LN]; (2) high nicotine: 5.0 mg/kg/day nicotine [HN]; (3) low nicotine/high cocaine: 2.5 mg/kg/day nicotine plus 40 mg/kg/day cocaine [LN/HC]; (4) high nicotine/low cocaine: 5.0 mg/kg/day nicotine plus 20 mg/kg/day cocaine [HN/LC]; (5) pair-fed controls: food intake yoked to HC dams [PF]; and (6) saline controls: daily injections of 0.9% NaCl solution[SAL]. Initial injection of nicotine did not alter activity or stereotypy in comparison to saline injections, with offspring in all prenatal treatment groups showing a desensitization to nicotine. Five consecutive daily nicotine injections resulted in behavioral sensitization in HN and HN/LC prenatal drug groups. Offspring exhibited an increase in horizontal activity that was evident on day 3, and still present after a 1.0 mg/kg i.p. nicotine challenge 72 hours after the last injection (day 8). SAL offspring exhibited attenuated sensitization. In contrast, nicotine sensitization was not seen in the LN, HC/LN, and the PF offspring; activity remained at the level seen after the initial injection of nicotine. Moreover, nicotine significantly reduced total activity in the LN and PF groups in comparison with their saline-injected counterparts. These data suggest that gestational exposure to high-dose nicotine, either alone or in combination with cocaine, may carry a greater risk than low-dose nicotine exposure or stimulant abuse in later life.

Somm E; Schwitzgebel VM; Vauthay DM; Camm EJ; Chen CY; Giacobino JP et al. Prenatal nicotine exposure alters early pancreatic islet and adipose tissue development with consequences on the control of body weight and glucose metabolism later in life. Endocrinology 149(12): 6289-6299, 2008. (38 refs.)

Despite medical advice, 20-30% of female smokers continue to smoke during pregnancy. Epidemiological studies have associated maternal smoking with increased risk of obesity and type-2 diabetes in the offspring. In the present study, we investigated the impact of prenatal nicotine exposure ( 3 mg/kg in Sprague Dawley rats via osmotic Alzet minipumps) on the early endocrine pancreas and adipose tissue development in rat pups before weaning. Body weight, fat deposition, food intake and food efficiency, cold tolerance, spontaneous physical activity, glucose utilization, and insulin sensitivity were also examined at adulthood. Prenatal nicotine exposure led to a decrease in endocrine pancreatic islet size and number at 7 d of life ( postnatal d 7), which corroborates with a decrease in gene expression of specific transcription factors such as pancreatic and duodenal homeobox 1, Pax-6, Nkx6.1, and of hormones such as insulin and glucagon. The prenatal nicotine exposure also led to an increase in epididymal white adipose tissue weight at weaning ( postnatal d 21), and marked hypertrophy of adipocytes, with increased gene expression of proadipogenic transcription factors such as CAAT-enhancer-binding protein-alpha, peroxisome proliferator activated receptor-gamma, and sterol regulatory element binding protein-1C. These early tissue alterations led to significant metabolic consequences, as shown by increased body weight and fat deposition, increased food efficiency on high-fat diet, cold intolerance, reduced physical activity, and glucose intolerance combined with insulin resistance observed at adulthood. These results prove a direct association between fetal nicotine exposure and offspring metabolic syndrome with early signs of dysregulations of adipose tissue and pancreatic development.

Sun YL; Strandberg-Larsen K; Vestergaard M; Christensen J; Andersen AMN; Gronbaek M et al. Binge drinking during pregnancy and risk of seizures in childhood: A study based on the Danish National Birth Cohort. American Journal of Epidemiology 169(3): 313-322, 2009. (41 refs.)

Seizures are often found in children with fetal alcohol syndrome, but it is not known whether binge drinking during pregnancy by nonalcoholic women is associated with an increased risk of seizure disorders in children. The authors conducted a population-based cohort study of 80,526 liveborn singletons in the Danish National Birth Cohort (1996-2002). Information on maternal binge drinking (intake of >= 5 drinks on a single occasion) was collected in 2 computer-assisted telephone interviews during pregnancy. Children were followed for up to 8 years. Information on neonatal seizures, epilepsy, and febrile seizures was retrieved from the Danish National Hospitalital Register. Results showed that exposure to binge drinking episodes during pregnancy was not associated with an increased risk of seizure disorders in children, except for those exposed at 11-16 gestational weeks. These children had a 3.15-fold increased risk of neonatal seizures (95% confidence interval: 1.37, 7.25) and a 1.81-fold increased risk of epilepsy (95% confidence interval: 1.13, 2.90). These findings suggest that maternal binge drinking during a specific time period of pregnancy may be associated with an increased risk of specific seizure disorders in the offspring. The results are exploratory, however, and need to be replicated.

Topley J; Windsor D; Williams R. Behavioural, developmental and child protection outcomes following exposure to Class A drugs in pregnancy. Child Care, Health and Development 34(1): 71-76, 2008. (11 refs.)

Background: The long-term consequences of intrauterine exposure to Class A drugs are still relatively undocumented, and much of the literature relates to the North American experience, where cocaine use predominates. In Britain, heroin and amphetamine use is more common and, within Britain, patterns of drug use vary. Clearly the long-term educational and welfare needs of these children will be enhanced if the behavioural, developmental and child-care outcomes are known. This study attempts to explore some of these issues. Methods The developmental, behavioural and child protection outcomes in a group of 62 children exposed to Class A drugs in utero were investigated when the children were in full-time schooling. Results: Seventy-four per cent (46/62) of the children at the time of the study had no educational or behavioural problems, and 11 (17.7%) were receiving extra support in school. No child had a statement of special educational need. Twelve (19.3%) were reported to have behaviour and concentration problems, and in four cases, this was attributed to poor-quality parenting at the time of the study. Three of the 12 children had fetal alcohol syndrome. Twenty-six (42%) children were placed on the Child Protection Register, and care orders or residence orders were granted for 22 (35.5%) of those who were placed on the register. All of the 22 children went into substitute care at some stage. Of these children, nine were adopted and 10 were placed permanently with other family members. Ten of the 62 (16.1%) children at the time of the study were of concern to professionals for child protection reasons, and four of them were on the Child Protection Register. Conclusions: This study suggests we can be reasonably optimistic about the developmental and behavioural outcomes for children exposed to Class A drugs in utero. Over 50% required an intervention by social services, and 31% were in substitute care at the time of the study. There were continuing child protection concerns in 16% at school entry.

Troese M; Fukumizu M; Sallinen BJ; Gilles AA; Wellman JD; Paul JA et al. Sleep fragmentation and evidence for sleep debt in alcohol-exposed infants. Early Human Development 84(9): 577-585, 2008. (68 refs.)

Background: Infants exposed prenatally to alcohol are at increased risk for poor neurodevelopmental outcome including Sudden Infant Death Syndrome. Aim: To examine the relationship between prenatal alcohol exposure, sleep, arousal and sleep-related spontaneous motor movements in early infancy. Study design: Low-income women (N = 13) were interviewed regarding pre- and pregnancy rates of alcohol, cigarette smoking and other substance use in the perinatal period. Infants were examined in a laboratory nap study using EEG, videography and actigraphy at 6-8 weeks of age. Estimates of maternal pre- and pregnancy alcohol use were used to divide infants into high vs. tow maternal alcohol use groups. Subjects: Mother-infant dyads recruited from a family practice clinic. Outcome measures' Sleep-related spontaneous movements, behavioral state, and maternal assessments of infant alertness and irritability. Results: Pre-pregnancy rates of alcohol consumption including binge drinking correlated with maternal report of poor infant alertness, and increased irritability. High maternal exposure groups showed increased sleep fragmentation, e.g. frequency and duration of wakefulness following sleep onset and decreased active sleep. Bout analysis of the temporal structure of sleep-related spontaneous movements showed significantly reduced bout duration associated with high maternal alcohol use. Conclusion: These results present evidence that prenatal alcohol exposure disrupts postnatal sleep organization and suppresses spontaneous movements during sleep, and increased sleep fragmentation promotes sleep deprivation. Results: are consistent with the SIDS model of chronic sleep debt and suggest that attenuated sleep-related movements should be examined as an important modulator of cardiorespiratory functions during sleep in high-risk groups.

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.

Wiebe SA; Espy KA; Stopp C; Respass J; Stewart P; Jameson TR et al. Gene-environment interactions across development: Exploring DRD2 genotype and prenatal smoking effects on self-regulation. (review). Developmental Psychology 45(1): 31-44, 2009. (116 refs.)

Genetic factors dynamically interact with both pre- and postnatal environmental influences to shape development. Considerable attention has been devoted to gene-environment interactions (G X E) on important outcomes (A. Caspi & T. E. Moffitt, 2006). It is also important to consider the possibility that these G X E effects may vary across development, particularly for constructs like self-regulation that emerge slowly, depend on brain regions that change qualitatively in different developmental periods, and thus may be manifested differently. To illustrate one approach to exploring such developmental patterns, the relation between variation in the TaqIA polymorphism, related to D-2 dopamine receptor expression and availability, and prenatal exposure to tobacco was examined in two exploratory studies. First, in 4-week-old neonates, genotype-exposure interactions were observed for attention and irritable reactivity, but not for stress dysregulation. Second, in preschool children, genotype was related to Preschool Trail Making Test (K. A. Espy and M. F. Cwik, 2004) task performance on conditions requiring executive control; children with both the Al+ genotype and a history of prenatal tobacco exposure displayed disproportionately poor performance. Despite study limitations, these results illustrate the importance of examining the interplay between genetic and prenatal environmental factors across development.

Windham GC; Zhang LX; Longnecker MP; Klebanoff M. Maternal smoking, demographic and lifestyle factors in relation to daughter's age at menarche. Paediatric and Perinatal Epidemiology 22(6): 551-561, 2008. (60 refs.)

A previous study suggested a younger age at menarche (AAM) among daughters of heavy prenatal smokers, especially among non-Whites. The present study was designed to evaluate that association in another population and to examine other factors that may be related to AAM. We analysed data from the Collaborative Perinatal Project, a nationwide longitudinal study of pregnant women and their children conducted in 1959-66. At three sites, with a predominance of Black participants (80%), AAM was ascertained in the offspring when they were young adults. We included data on 1556 daughters who had a mean AAM of 12.7 years (standard deviation 1.8). Amount smoked by the mothers was obtained from a baseline interview and subsequent prenatal visits. Regression models were run including maternal smoking and other covariates, for only the prenatal period, as well as in models with some childhood characteristics. In the prenatal factor model, younger mean AAM in daughters was found with maternal characteristics of earlier AAM, being married, and of lower parity. Examining childhood variables, earlier AAM was found among girls with few or no siblings or with higher socio-economic status. Unlike our previous findings, mean AAM was later in daughters of heavy smokers (20+ cigarettes/day), with a delay of 0.31 years [95% confidence interval (CI) 0.008, 0.61], or about 3.7 months in the prenatal model, and 0.34 years [95% CI -0.02, 0.66] in the model with childhood variables included. The pattern was consistent by race. A number of prenatal and childhood factors related to AAM were identified that should be considered when examining exogenous exposures in relation to pubertal onset.

Yilmaz G; Hizli S; Karacan C; Yurdakok K; Coskun T; Dilmen U. Effect of passive smoking on growth and infection rates of breast-fed and non-breast-fed infants. Pediatric International 51(3): 352-358, 2009. (32 refs.)

The aim of the present study was to determine the effect of passive tobacco smoking on growth and infection rate of infants, and to evaluate whether breast-feeding might be protective against harmful effects of cigarette smoke. A cross-sectional study on 254 6-7-month-old infants was carried out. A questionnaire was given to mothers; and infants' head circumference, bodyweight, height, and urinary cotinine levels were measured. Multivariate analysis of factors influencing lower respiratory tract infections showed that smoking mothers increased the rate by 9.1-fold; breast-feeding decreased it by 3.3-fold; formula feeding at birth increased it by a factor of 15.2; another smoker at home increased it by a factor of 40.1. Multivariate analysis of factors influencing upper respiratory tract infections showed that smoking mothers increased the rate by a factor of 23; early formula feeding increased it by a factor of 62; breast-feeding decreased it by a factor of 5; smoking fathers increased it by a factor of 15. Multivariate analysis of factors influencing otitis media found that smoking mothers and fathers increased it by a factor of 9.4 and 6.15, respectively, and breast-feeding decreased it by a factor of 5.4. Tobacco smoke exposure of infants has negative consequences on growth, otitis media, and upper and lower respiratory tract infections. Breast-feeding promoted the growth of infants who were passively exposed to tobacco smoke and protected them against infections. Smoking should not be permitted in households with infants. When this is impossible, breast-feeding should be promoted to protect the infants against the health hazards of passive smoking.

Zagar RJ; Isbell SA; Busch KG; Hughes JR. An empirical theory of the development of homicide within individuals. (review). Psychological Reports 104(1, Special Issue): 199-245, 2009. (151 refs.)

There have been many attempts to explain violent behavior, identify its causes, and predict its occurrence among youth and adults. Research and theoretical constructions have dealt with such far-ranging aspects as childhood health, peer and parental interactions, neuropsychological function, school and community support, and substance use and dependency. Theories have tended to focus on one or a few of these aspects, but there is an effort by many researchers to converge on an integrated approach, By demonstrating unique risk patterns in random samples of later-homicidal abused infants, children, and youth, violent and homicidal delinquents, and homicidal adults, five studies by Zagar and colleagues provide the best current empirical evidence for a view of the development of delinquency as a process of accumulating risks. These risks begin with prenatal substance exposure and continue with abusive or neglectful parenting, academic failure, court contacts, compromised executive function and resultant poor social functioning. Analysis by sex shows that males' and females' risks are virtually identical. Various theories are evaluated with respect to these empirical risk patterns for development of violence and homicide. A proposal for the necessary elements of a successful, overarching explanatory theory is offered.