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CORK Bibliography: Child Development after Prenatal Drug Exposure

88 citations. January 2009 to present

Prepared: September 2011

Anderko L; Braun J; Auinger P. Contribution of tobacco smoke exposure to learning disabilities. Journal of Obstetric, Gynecologic and Neonatal Nursing 39(1): 111-117, 2010. (34 refs.)

Objective: To investigate the contribution of exposure to prenatal tobacco smoke (PTS) and environmental tobacco smoke (ETS) to parent-reported learning disabilities. Design: A nationally representative, cross-sectional survey conducted in the United States, the National Health and Nutrition Examination Survey (NHANES) 1999 to 2002, was used to explore the association between reported learning disability and exposure to PTS and ETS. Participants: Data were analyzed from 5,420 children ages 4 to 15 years old. Methods: Secondary data analysis was conducted using logistic regression controlling for a number of potential confounders and covariates. Results: Overall, 10.6% of children had a parent-reported learning disability (LD), exceeding previous estimates. Exposure to PTS (odds ratio [OR] = 1.6) and ETS (OR = 1.6) were significantly associated with increased odds for LD in children, with a greater odds noted (OR = 2.6) when exposed to PTS and ETS. Conclusion: Exposure to tobacco smoke significantly increases the odds for children to have a learning disability. Overall, results indicate that if tobacco exposure is causally associated to LD, eliminating exposures could prevent an estimated 750,000 of parent-reported learning disabilities in the United States. Results underscore the need for diligence in the promotion of smoking prevention and cessation efforts.

Accornero VH; Anthony JC; Morrow CE; Xue L; Mansoor E; Johnson AL et al. Estimated effect of prenatal cocaine exposure on examiner-rated behavior at age 7 years. Neurotoxicology and Teratology 33(3): 370-378, 2011. (69 refs.)

Prenatal cocaine exposure has been linked to increased child behavior difficulties in some studies but not others. Objective: The primary aim was to estimate the relationship between in utero cocaine exposure and child behavioral functioning at age 7 years with ratings made by blinded examiners during a structured testing session. A second aim was to examine whether caregiver drug use and psychological problems might mediate suspected relationships between prenatal cocaine exposure and aspects of examiner-rated behavior. Methods: 407 children (212 cocaine-exposed, 195 non-exposed) participating in the longitudinal Miami Prenatal Cocaine Study (MPCS) were rated with regard to their behavior during a neuropsychological assessment conducted at age 7 years. Raters were trained research psychometricians blinded to drug exposure status. Individual behavioral items were summarized and the cocaine-behavior relationship was estimated within the context of latent variable modeling, using Mplus software. Results: Two latent variables, Behavioral Regulation and Sociability, were derived via exploratory latent structure analysis with promax rotation. Prenatal cocaine exposure, statistically controlling for child sex, test age, and prenatal exposure to alcohol, tobacco, and marijuana, was associated with Behavioral Regulation (estimated slope beta = -0.25; 95% CI = -0.48. -0.02; p = 0.04) but not Sociability (estimated slope beta = 0.03; 95% Cl = -0.26, 0.20; p = 0.79). Neither postnatal drug use by caregivers nor the severity of their psychological problems at age 5 follow-up predicted levels of child Behavioral Regulation or Sociability at age 7 years (p>0.10). Conclusions: Examiner ratings of child behavior at age 7 revealed less optimal behavioral regulation for prenatally cocaine-exposed compared to non-exposed children, in contrast with what had been previously found from parent-report data. This evidence highlights the potential value of trained observers in assessing behavioral outcomes of children exposed in utero to drugs and other toxicants.

Anderko L; Braun J; Auinger P. Contribution of tobacco smoke exposure to learning disabilities. Journal of Obstetric, Gynecologic and Neonatal Nursing 39(1): 111-117, 2010. (34 refs.)

Aros S; Mills JL; Iniguez G; Avila A; Conley MR; Troendle J et al. Effects of prenatal ethanol exposure on postnatal growth and the insulin-like growth factor axis. Hormone Research in Paediatrics 75(3): 166-173, 2011. (42 refs.)

Aims:To study the effect of in-utero alcohol exposure on the insulin-like growth factor axis (IGF) and leptin during infancy and childhood, considering that exposed children may exhibit pre- and postnatal growth retardation. Methods: We prospectively identified heavily drinking pregnant women who consumed on average 4 or more drinks of ethanol per day (>= 48 g/day) and assessed growth in 69 of their offspring and an unexposed control group of 83 children, measuring serum IGF-I (radioimmunoassay), IGF-II (immunoradiometric assay, IRMA), insulin-like growth factor-binding protein 3 (IGFBP-3) (IRMA) and leptin (IRMA) at 1 month and 1, 2, 3, 4, and 5 years of age. Results: IGF-II levels increased with age in both groups, but the rate of increase was significantly higher in exposed children, and levels were significantly higher in ethanol-exposed children at 3, 4, and 5 years of age. In exposed children, IGF-I levels were higher at 3 and 4 years and leptin levels were significantly lower at 1 and 2 years. Exposed subjects showed a much lower correlation between IGF-I and growth parameters than unexposed subjects. Conclusion: Exposure to ethanol during pregnancy increases IGF-I and IGF-II and decreases leptin during early childhood. The increase in serum IGF-II concentrations in ethanol-exposed children suggests that this hormone should be explored as a potential marker for prenatal alcohol exposure.

Bay B; Kesmodel US. Prenatal alcohol exposure: A systematic review of the effects on child motor function. (review). Acta Obstetricia et Gynecologica Scandinavica 90(3): 210-226, 2011. (55 refs.)

Objective. To systematically review the available evidence on the effects of prenatal alcohol exposure on motor function in humans. Design. Systematic review. Population. Pregnant women and their offspring. Methods. The search strategy included Medline, Embase, The Cochrane Library and Scopus. The authors read titles and abstracts, and the articles that met the predefined criteria for inclusion were obtained and the full text read. The articles were assessed for quality using the Newcastle-Ottawa Quality Assessment Scale. Main outcome measures. Motor function measured on standardized or validated tests. Results. The search resulted in 311 titles and abstracts, of which 39 were found relevant for inclusion. The findings of this review suggest a negative effect when the maternal consumption exceeded a certain level. Of all studies reporting a maternal intake of more than four drinks/day, only one study showed no effect on motor function, and of all studies reporting intake levels of less than 10 drinks/week, only one study showed deficit on the children's motor function. Conclusions. While it appears consistent that high daily alcohol intake is associated with deficits in gross and fine motor function, and low weekly intake is not associated with such deficits, the issue of binge drinking is unsettled.

Bjerg A; Hedman L; Perzanowski M; Lundback B; Ronmark E. A strong synergism of low birth weight and prenatal smoking on asthma in schoolchildren. Pediatrics 127(4): E905-E912, 2011. (34 refs.)

BACKGROUND: Prenatal smoke exposure is associated with airway inflammation and asthma in children. It also increases the risk of low birth weight (LBW). LBW is associated with decreased lung function independently of smoking. OBJECTIVE: To study the independent and joint effects of prenatal smoking and LBW on childhood asthma. METHODS: In 1996, all children aged 7 to 8 years in 3 cities in northern Sweden were invited to an International Study of Asthma and Allergy in Childhood questionnaire survey. This study focused on the follow-up of children aged 11 to 12 years, in which 3389 children (96%) participated. A subset of 2121 children underwent skin-prick testing. Self-reported physician-diagnosed asthma has been clinically validated. RESULTS: Mean birth weight was 3360 g in children exposed to prenatal smoking and 3571 g in nonexposed children (P < .001). The association of prenatal smoking with physician-diagnosed asthma was stronger in LBW children (risk ratio: 8.8 [95% confidence interval: 2.1-38]) than in normal birth weight children (risk ratio: 1.3 [95% confidence interval: 1.0-1.8]). LBW alone was not an independent predictor of asthma. These associations were similar in multivariate analysis, and the interaction term LBW x smoking was highly statistically significant. CONCLUSIONS: There was a strong interaction of LBW and prenatal-smoking on the risk of physician-diagnosed asthma, which has not been demonstrated previously. This was consistently seen with adjustment for known risk factors, including allergic sensitization. Plausibly, airway inflammation from prenatal smoke exposure induces obstructive symptoms more easily in the underdeveloped airways of LBW children.

Blood-Siegfried J; Rende EK. The long-term effects of prenatal nicotine exposure on neurologic development. Journal of Midwifery & Women's Health 55(2): 143-152, 2010. (81 refs.)

A large body of documented evidence has found that smoking during pregnancy is harmful to both the mother and the fetus. Prenatal exposure to nicotine in various forms alters neurologic development in experimental animals and may increase the risk for neurologic conditions in humans. There is a positive association between maternal smoking and sudden infant death syndrome (SIDS); however, the connection between nicotine addiction, depression, attention disorders, and learning and behavior problems in humans is not straightforward. Nicotine's action on the production and function of neurotransmitters makes it a prime suspect in the pathology of these diseases. Nicotine accentuates neurotransmitter function in adults but desensitizes these functions in prenatally exposed infants and children. This desensitization causes an abnormal response throughout the lifespan. Furthermore, nicotine use by adolescents and adults can alleviate some of the symptoms caused by these neurotransmitter problems while they increase the risk for nicotine addiction. Although nicotine replacement drugs are used by pregnant women, there is no clear indication that they improve outcomes during pregnancy, and they may add to the damage that occurs to the developing neurologic system in the fetus. Understanding the effects of nicotine exposure is important in providing safe care for pregnant women, children, and families and for developing appropriate smoking cessation programs during pregnancy.

Breton CV; Byun HM; Wenten M; Pan F; Yang A; Gilliland FD. Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation. American Journal of Respiratory and Critical Care Medicine 180(5): 462-467, 2009. (32 refs.)

Rationale: Prenatal exposure to tobacco smoke increases the risk for diseases later in the child's life that may be mediated through alterations in DNA methylation. Objectives: To demonstrate that differences in DNA methylation patterns occur in children exposed to tobacco smoke and that variation in detoxification genes may alter these associations. Methods: Methylation of DNA repetitive elements, LINE1 and AluYb8, was measured using bisulfite conversion and pyrosequencing in buccal cells of 348 children participating in the Children's Health Study. Gene-specific CpG methylation differences associated with smoke exposure were screened in 272 participants in the Children's Health Study children using an Illumina GoldenGate panel. CpG loci that demonstrated a statistically significant difference in methylation were validated by pyrosequencing. Estimates were standardized across loci using a Z score to enable cross-comparison of results. Measurements and Main Results: DNA methylation patterns were associated with in utero exposure to maternal smoking. Exposed children had significantly lower methylation of AluYb8 (beta, -0.31; P = 0.03). Differences in smoking-related effects on LINE1 methylation were observed in children with the common GSTM1 null genotype. Differential methylation of CpG loci in eight genes was identified through the screen. Two genes, AXL and PTPRO, were validated by pyrosequencing and showed significant increases in methylation of 0.37 (P = 0.005) and 0.34 (P = 0.02) in exposed children. The associations with maternal smoking varied by a common GSTP1 haplotype. Conclusions: Life-long effects of in utero exposures may be mediated through alterations in DNA methylation. Variants in detoxification genes may modulate the effects of in utero exposure through epigenetic mechanisms.

Brown CW; Olson HC; Croninger RG. Maternal alcohol consumption during pregnancy and infant social, mental, and motor development. Journal of Early Intervention 32(2): 110-126, 2010. (55 refs.)

Maternal alcohol consumption during pregnancy is a significant social problem associated with developmental difficulties in young children. Child developmental and behavioral characteristics were examined from the 9-month data point of the Early Childhood Longitudinal Studies-Birth Cohort, a prospective nationally representative study. Several findings indicate linear patterns between the amount of prenatal alcohol dosage and sensory regulation, mental, and motor development outcomes. Undesirable social engagement and child interaction were found to be statistically significant at the prenatal alcohol level of one to three drinks per week. Children exposed to four or more drinks per week showed statistically significant and clinically passive behavior on three sensory regulation variables.

Bruin JE; Gerstein HC; Holloway AC. Long-term consequences of fetal and neonatal nicotine exposure: A critical review. (review). Toxicological Sciences 116(2): 364-374, 2010. (167 refs.)

Cigarette smoking during pregnancy is associated with numerous obstetrical, fetal, and developmental complications, as well as an increased risk of adverse health consequences in the adult offspring. Nicotine replacement therapy (NRT) has been developed as a pharmacotherapy for smoking cessation and is considered to be a safer alternative for women to smoking during pregnancy. The safety of NRT use during pregnancy has been evaluated in a limited number of short-term human trials, but there is currently no information on the long-term effects of developmental nicotine exposure in humans. However, animal studies suggest that nicotine alone may be a key chemical responsible for many of the long-term effects associated with maternal cigarette smoking on the offspring, such as impaired fertility, type 2 diabetes, obesity, hypertension, neurobehavioral defects, and respiratory dysfunction. This review will examine the long-term effects of fetal and neonatal nicotine exposure on postnatal health.

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.

Chang L; Cloak C; Jiang CS; Farnham S; Tokeshi B; Buchthal S et al. Altered neurometabolites and motor integration in children exposed to methamphetamine in utero. Neuroimage 48(2): 391-397, 2009. (43 refs.)

Methamphetamine (METH) is a neurotoxic drug. This study aimed to evaluate brain metabolite levels and cognitive function in young children with prenatal METH exposure. 101 children ages 3-4 years were evaluated with neuropsychological tests and underwent proton magnetic resonance spectroscopy (H-1-MRS) without sedation. Complete datasets from 49 METH-exposed and 49 controls who completed the neuropsychological test battery, and 38 METH-exposed and 37 controls with high-quality MR spectra are reported here. Despite similar physical characteristics (including head circumference), global cognitive function (on Stanford-Binet), parental education, intelligence, mood, and socioeconomic status, METH-exposed children had higher total creatine (tCr: + 7%, p= 0.003), N-acetyl compounds (NA: + 4.3%, p= 0.004) and glutamate+glutamine (GLX: + 9.6%, p= 0.02) concentrations in the frontal white matter, but lower myoinositol (MI: -7%, p= 0.01) and MI/tCr (-7.5%, p= 0.03) in the thalamus, than control children. The higher frontal white matter NA in the METH-exposed children was due to the higher NA in the METH-exposed girls (+ 10.2%, p= 0.003), but not the boys (+ 0.8%) compared to sex-matched controls. Furthermore, the METH-exposed children had poorer performance on a visual motor integration (VMI) task, which correlated with lower MI in the thalamus (r-0.26, p-0.03). The higher NA, tCr and GLX concentrations suggest higher neuronal density or cellular compactness in the white matter, especially in the girls, whereas the lower MI suggests lower glial content in the thalamus of these METH-expose children. These findings combined with their poorer performance on VMI also suggest accelerated but aberrant neuronal and glial development in these brain regions.

Chiodo LM; da Costa DE; Hannigan JH; Covington CY; Sokol RJ; Janisse J et al. The impact of maternal age on the effects of prenatal alcohol exposure on attention. Alcoholism: Clinical and Experimental Research 34(10): 1813-1821, 2010. (76 refs.)

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

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.

Cohen RT; Raby BA; Van Steen K; Fuhlbrigge AL; Celedon JC; Rosner BA et al. In utero smoke exposure and impaired response to inhaled corticosteroids in children with asthma. Journal of Allergy and Clinical Immunology 126(3): 491-497, 2010. (38 refs.)

Background: Few studies have examined the effects of in utero smoke exposure (IUS) on lung function in children with asthma, and there are no published data on the impact of IUS on treatment outcomes in children with asthma. Objectives: To explore whether IUS exposure is associated with increased airway responsiveness among children with asthma and whether IUS modifies the response to treatment with inhaled corticosteroids (ICSs). Methods: To assess the impact of parent-reported IUS exposure on airway responsiveness in childhood asthma, we performed a repeated-measures analysis of methacholine PC20 data from the Childhood Asthma Management Program, a 4-year, multicenter, randomized, double-masked, placebo-controlled trial of 1041 children age 5 to 12 years comparing the long-term efficacy of ICS with mast cell stabilizing agents or placebo. Results: Although improvement was seen in both groups, children with asthma and IUS exposure had on average 26% less of an improvement in airway responsiveness over time compared with unexposed children (P = .01). Moreover, while children who were not exposed to IUS who received budesonide experienced substantial improvement in PC20 compared with untreated children (1.25-fold increase; 95% CI, 1.03-1.50; P = .02), the beneficial effects of budesonide were attenuated among children with a history of IUS exposure (1.04-fold increase, 95% CI, 0.65-1.68; P = .88). Conclusion: In utero smoke exposure reduces age-related improvements in airway responsiveness among children with asthma. Moreover, IUS appears to blunt the beneficial effects of ICS use on airways responsiveness. These results emphasize the importance of preventing this exposure through smoking cessation counseling efforts with pregnant women.

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.

Cutajar MC; Mullen PE; Ogloff JRP; Thomas SD; Wells DL; Spataro J. Psychopathology in a large cohort of sexually abused children followed up to 43 years. Child Abuse & Neglect 34(11): 813-822, 2010. (61 refs.)

Objective: To determine the rate and risk of clinical and personality disorders diagnosed in childhood and adulthood in those known to have been sexually abused during childhood. Methods: Forensic medical records of 2,759 sexually abused children assessed between 1964 and 1995 were linked with a public psychiatric database between 12 and 43 years later. Cases were compared to control subjects matched on gender and age groupings drawn from the general population through a random sample of the national electoral database. Results: A lifetime record of contact with public mental health services was found in 23.3% of cases compared to 7.7% of controls. The rate of contact among child sexual abuse victims was 3.65 times higher (95% Cl, 3.09-4.32, p < 0.001). It was estimated that child sexual abuse accounted for approximately 7.83% of mental health contact. Exposure to sexual abuse increased risks for the majority of outcomes including psychosis, affective, anxiety, substance abuse, and personality disorders. Rates of clinical disorders diagnosed in adulthood and childhood remained significantly higher among child sexual abuse cases. Older age at sexual abuse and those exposed to severe abuse involving penetration or multiple offenders were associated with greater risk for psychopathology. Conclusions: This study confirms that child sexual abuse is a substantial risk factor for a range of mental disorders in both childhood and adulthood. Practice implications: Those treating victims of sexual abuse must assess not only disorders commonly associated with trauma, but also low prevalence disorders such as psychosis.

Dahal GP; Johnson FA; Padmadas SS. Maternal smoking and acute respiratory infection symptoms among young children in Nepal: Multilevel analysis. Journal of Biosocial Science 41(6): 747-761, 2009. (23 refs.)

The association between maternal smoking and adverse child health outcomes has not been systematically explored In less developed countries, especially in Nepal where over a quarter of women of reproductive age smoke tobacco products. This study aims to quantify the effect of maternal smoking on acute respiratory infection (ARI) symptoms among children aged below five years, using the 2001 Nepal Demographic and Health Survey. It is hypothesized that children born to mothers who smoke frequently are at higher risk of developing ARI symptoms. Four-level random intercept logistic regression models were used to disentangle the independent effect of maternal smoking on children's ARI symptoms, controlling for potential biological, socioeconomic, seasonal and spatial variables. Maternal smoking status had a significant effect on children's ARI symptoms; the effects were significantly higher (adjusted OR 1.41; 95% CI 1.02-1.96) among those born to mothers who smoked more frequently than their counterparts. Furthermore, a strong spatial pattern was evident in the prevalence of ARI symptoms, after adjusting for maternal smoking and relevant control variables. The findings underscore the importance of designing exclusive public health intervention measures to prevent tobacco smoking within households, for example through awareness campaigns highlighting the adverse effect of maternal smoking on child health.

Dodge NC; Jacobson JL; Molteno CD; Meintjes EM; Bangalore S; Diwadkar V et al. Prenatal alcohol exposure and interhemispheric transfer of tactile information: Detroit and Cape Town findings. Alcoholism: Clinical and Experimental Research 33(9): 1628-1637, 2009. (55 refs.)

Background: Previous research has demonstrated that heavy prenatal alcohol exposure affects the size and shape of the corpus callosum (CC) and compromises interhemispheric transfer of information. The aim of this study was to confirm the previous reports of poorer performance on a finger localization test (FLT) of interhemispheric transfer in a cohort of heavily exposed children and to extend these findings to a cohort of moderately exposed young adults. Methods: In Study 1, the FLT was administered to 40 heavily exposed and 23 nonexposed children from the Cape Coloured community of Cape Town, South Africa, who were evaluated for fetal alcohol syndrome (FAS) dysmorphology and growth. Anatomical images of the CC were obtained using structural MRI on a subset of these children. In Study 2, the FLT was administered to a cohort of 85 moderate-to-heavily exposed young adults participating in a 19-year follow-up assessment of the Detroit Prenatal Alcohol Exposure cohort, whose alcohol exposure had been ascertained prospectively during gestation. Results: In Study 1, children with FAS showed more transfer-related errors than controls after adjustment for confounding, and increased transfer-related errors were associated with volume reductions in the isthmus and splenium of the CC. In Study 2, transfer-related errors were associated with quantity of alcohol consumed per occasion during pregnancy. More errors were made if the mother reported binge drinking (>= 5 standard drinks) during pregnancy than if she drank regularly (M >= 1 drink/day) without binge drinking. Conclusions: These findings confirm a previous report of impaired interhemispheric transfer of tactile information in children heavily exposed to alcohol in utero and extend these findings to show that these deficits are also seen in more moderately exposed individuals, particularly those exposed to binge-like pregnancy drinking.

D'Onofrio BM; Singh AL; Iliadou A; Lambe M; Hultman CM; Neiderhiser JM et al. A quasi-experimental study of maternal smoking during pregnancy and offspring academic achievement. Child Development 81(1): 80-100, 2010. (41 refs.)

The current study, based on all births in Sweden from 1983 to 1991 (N = 654,707), explored the processes underlying the association between smoking during pregnancy (SDP) and offspring school grades and mathematic proficiency at age 15. The analyses compared relatives who varied in their exposure to SDP and who varied in their genetic relatedness. Although SDP was statistically associated with academic achievement (AA) when comparing unrelated individuals, the results suggest that SDP does not cause poorer academic performance, as full siblings differentially exposed to SDP did not differ in their academic scores. The pattern of results suggests that genetic factors shared by parents and their offspring help explain why offspring exposed to SDP have lower levels of AA.

Eiden RD; Schuetze P; Colder CR; Veira Y. Maternal cocaine use and mother-toddler aggression. Neurotoxicology and Teratology 33(3): 360-369, 2011. (84 refs.)

This study examined the direct and indirect associations between maternal cocaine use during pregnancy and mother-toddler aggression in an interactive context at 2 years of child age. We hypothesized that in addition to direct effects of cocaine exposure on maternal and child aggression, the association between maternal cocaine use and mother-toddler aggression may be indirect via higher maternal psychiatric symptoms, negative affect, or poor infant autonomic regulation at 13 months. Participants consisted of 220 (119 cocaine exposed, 101 non-cocaine exposed) mother-toddler dyads participating in an ongoing longitudinal study of prenatal cocaine exposure. Results indicated that mothers who used cocaine during pregnancy displayed higher levels of aggression toward their toddlers compared to mothers in the control group. Results from model testing indicated significant indirect associations between maternal cocaine use and maternal aggression via higher maternal negative affect as well as lower infant autonomic regulation at 13 months. Although there were no direct associations between cocaine exposure and toddler aggression, there was a significant indirect effect via lower infant autonomic regulation at 13 months. Results highlight the importance of including maternal aggression in predictive models of prenatal cocaine exposure examining child aggression. Results also emphasize the important role of infant regulation as a mechanism partially explaining associations between cocaine exposure and mother-toddler aggression.

Eliasen M; Tolstrup JS; Andersen AMN; Gronbaek M; Olsen J; Strandberg-Larsen K. Prenatal alcohol exposure and autistic spectrum disorders: A population-based prospective study of 80,552 children and their mothers. International Journal of Epidemiology 39(4): 1074-1081, 2010. (42 refs.)

Methods: Participants were 80,552 children and their mothers enrolled in the Danish National Birth Cohort from 1996 to 2002. Alcohol consumption was obtained by self-report during pregnancy. Information on ASD was obtained from the Danish Central Psychiatry Register. Follow-up ended on February 2008. Data were analysed by means of Cox regression. Results In total, 401 children were diagnosed with ASD and 157 with infantile autism. No association was found between average alcohol consumption and ASD or infantile autism, respectively. For binge drinking, the adjusted hazard ratio (HR) for ASD was 0.72 [95% confidence interval (CI): 0.53-0.97] among women who binge drank once during pregnancy compared with women who did not binge drink. The corresponding HR for infantile autism was 0.61 (95% CI: 0.36-1.02). However, the HR for ASD was 0.84 (95% CI: 0.51-1.36) when restricting the analysis to first-time pregnancies conceived within 6 months of trying. No estimate was made for infantile autism due to low number of cases. No association was seen for more than one binge episode and for the timing of binge drinking. Conclusion: Our findings do not support that a low prenatal alcohol exposure increases the risk of ASD or infantile autism. The lower risk for women who binge drank once during pregnancy is most likely non-causal.

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.

Greenbaum RL; Stevens SA; Nash K; Koren G; Rovet J. Social cognitive and emotion processing abilities of children with fetal alcohol spectrum disorders: A comparison with attention deficit hyperactivity disorder. (review). Alcoholism: Clinical and Experimental Research 33(10): 1656-1670, 2009. (110 refs.)

Background: Although children with Fetal Alcohol Spectrum Disorders (FASDs) are at high risk of attention deficit hyperactivity disorder (ADHD), direct comparisons show distinct cognitive phenotypes in the 2 diagnoses. However, these groups have not been directly compared for social problems or social cognition, nor has social cognition been directly examined in FASDs. Objectives: To compare FASDs and ADHD groups on social cognition tasks and determine whether deficient social cognition and emotion processing predict behavioral problems and social skills. Methods: Studied were 33 children with FASDs, 30 with ADHD, and 34 normal controls (NC). All received tasks of social cognition and emotion processing. Parents and teachers rated children on measures of completed questionnaires assessing child's behavioral problems and social skills using the Child Behavior Checklist, Teacher Report Form, and Social Skills Rating Scale. Children received 3 subtests from the Saltzman-Benaiah and Lalonde (2007) Theory of Mind Task as a measure of social cognition and 4 subtests from the Minnesota Test of Affective Processing (Lai et al., 1991) to assess emotion processing. Results : Parents and teachers reported more behavior problems and poorer social skills in children in FASD and ADHD than NC groups. FASDs demonstrated significantly weaker social cognition and facial emotion processing ability than ADHD and NC groups. Regression analyses identified social cognition as a significant predictor of behavior problems and emotion processing as a significant predictor of social skills. Conclusions: Children with FASDs show a distinct behavioral profile from children with ADHD. Difficulties in social cognition and emotion processing in children with FASDs may contribute to their high incidence of social behavioral problems.

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.

Habek D; Kovacevic M. Adverse pregnancy outcomes and long-term morbidity after early fetal hypokinesia in maternal smoking pregnancies. Archives of Gynecology and Obstetrics 283(3): 491-495, 2011. (33 refs.)

The aim of this study is to evaluate perinatal outcome and subsequent morbidity and neurodevelopment in 10-year-old children with fetal hypokinesia intrauterinely verified by ultrasonography in early pregnancy as a pattern of abnormal fetal behavior due to maternal chronic smoking. This study revealed significant global fetal hypokinesia as well as head and arm hypokinesia in early pregnancy in mothers' chronic smokers (group 3-more than 20 cigarettes a day). This retrospective study was performed in mothers and their 10-year-old children included in the study of the effect of cigarette smoking on fetal movements in early pregnancy. Perinatal outcome was assessed according to maternal data, course, and outcome of pregnancy and delivery. Data on the long-term (10 years) development and morbidity from infancy during childhood until age 10 years were obtained from the children's medical histories and medical rehabilitation records, maternal, and paternal histories. The psycholinguistic development was estimated. In group 3, there was a poor overall perinatal outcome and high rate of the bronchoconstrictive syndrome and recurrent infections, while one case of the sudden infant death syndrome. Poor school performance was recorded in five children, attention-deficit/hyperactivity disorder in four, and autism, dystonia syndrome, social maladaptation, and minimally cerebral disfunction in one child each. Retarded psycholinguistic development was found in seven children, only three of them attending speech therapy (P < 0.05). Fetal hypokinesia in early pregnancy related with maternal smoking was found to correlate with poor perinatal outcome, subsequent morbidity, and developmental impairments in 10-year-old children born to mothers smoking more than 20 cigarettes a day.

Hamilton R; McGlone L; MacKinnon JR; Russell HC; Bradnam MS; Mactier H. Ophthalmic, clinical and visual electrophysiological findings in children born to mothers prescribed substitute methadone in pregnancy. British Journal of Ophthalmology 94(6): 696-700, 2010. (24 refs.)

Background and aims: There are growing concerns regarding visual outcome of infants exposed to opiates (including substitute methadone) and/or benzodiazepines in utero. We describe the combined ophthalmology and visual electrophysiology findings in 20 infants and children who had been exposed to substitute methadone and other drugs of misuse in utero. Methods: This was a descriptive case series of 20 patients, all of whom had been referred to a paediatric visual electrophysiology service because of concerns regarding visual function, and all of whom had been exposed to methadone in utero. All children underwent a full ophthalmic and orthoptic examination as well as visual electrophysiology testing deemed appropriate on an individual basis. A review was undertaken of paediatric case notes and of maternal antenatal urine toxicology. Results: Ophthalmic abnormalities included reduced acuity (95%), nystagmus (70%), delayed visual maturation (50%), strabismus (30%), refractive errors (30%), and cerebral visual impairment (25%). Visual electrophysiology was abnormal in 60%. A quarter of the children had associated neurodevelopmental abnormalities. The majority of children with nystagmus (79%) had been treated for neonatal abstinence syndrome (NAS). Conclusion: Infants born to drug-misusing mothers prescribed methadone in pregnancy are at risk of a range of visual problems, the underlying causes of which are not clear. Those infants with NAS severe enough to receive pharmaceutical treatment may be at particular risk of developing nystagmus. The inclusion of visual electrophysiology in comprehensive visual assessment of children exposed to substance misuse in utero may help clarify the underlying causes by differentiating abnormalities of retinal and cortical origin.

Hansen K; Mangrio E; Lindstrom M; Rosvall M. Early exposure to secondhand tobacco smoke and the development of allergic diseases in 4 year old children in Malmo, Sweden. BMC Pediatrics 10: article 61, 2010. (29 refs.)

Background: Earlier studies have shown an association between secondhand tobacco smoke and allergy development in children. Furthermore, there is an increased risk of developing an allergy if the parents have an allergy. However, there are only few studies investigating the potential synergistic effect of secondhand tobacco smoke and allergic heredity on the development of an allergy. Methods: The study was population-based cross-sectional with retrospective information on presence of secondhand tobacco smoke during early life. The study population consisted of children who visited the Child Health Care (CHC) centres in Malmo for their 4-year health checkup during 2006-2008 and whose parents answered a self-administered questionnaire (n = 4,278 children). The questionnaire was distributed to parents of children registered with the CHC and invited for the 4-year checkup during the study period. Results: There was a two to four times increased odds of the child having an allergy or having sought medical care due to allergic symptoms if at least one parent had an allergy, while there were rather small increased odds related to presence of secondhand smoke during the child's first month in life or at the age of 8 months. However, children with heredity for allergies and with presence of secondhand tobacco smoke during their first year in life had highly increased odds of developing an allergy and having sought medical care due to allergic symptoms at 4 years of age. Thus, there was a synergistic effect enhancing the independent effects of heredity and exposure to secondhand tobacco smoke on allergy development. Conclusions: Children with a family history of allergies and early exposure to secondhand tobacco smoke is a risk group that prevention and intervention should pay extra attention to. The tobacco smoke effect on children is an essential and urgent question considering it not being self chosen, possibly giving life lasting negative health effects and being possible to reduce.

Hayatbakhsh MR; Sadasivam S; Mamun AA; Najman JM; Williams GM; O'Callaghan MJ. Maternal smoking during and after pregnancy and lung function in early adulthood: A prospective study. Thorax 64(9): 810-814, 2009. (29 refs.)

Background and aims: There is a paucity of evidence about whether exposure to antenatal smoking impacts on offspring's lung function in early adulthood. This study aimed to examine whether (1) in utero exposure to maternal smoking is related to poorer respiratory functioning in early adulthood; (2) the impact of prenatal smoking is independent of postnatal maternal smoking; and (3) the link between prenatal smoking and a young adult's lung function is explained by the child's birth weight, smoking or history of asthma. Methods: Data were from a 21-year follow-up of mothers and their children recruited into the Mater University of Queensland Study of Pregnancy, a longitudinal prebirth cohort. The study is based on 2409 young adults (1185 males and 1224 females) who had prospective data available on respiratory function at 21 years and maternal smoking during and after pregnancy. A Spirobank G spirometer system was used to measure forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and forced expiratory flow between 25% and 75% of FVC (FEF25-75). Results: In utero exposure to maternal smoking was associated with a reduction in FEV1 and FEF25-75 in males (regression coefficient, -0.16; 95% CI, -0.30 to -0.02), after accounting for maternal smoking after pregnancy. At least part of the effect of in utero smoking on young adults' lung function was explained by the child's birth weight and subsequent asthma. Conclusions: Adverse effects of antenatal smoking on development of airway growth may persist into early adulthood. Gender differences noted in this longitudinal cohort need to be explored further.

Heinonen K; Raikkonen K; Pesonen AK; Andersson S; Kajantie E; Eriksson JG et al. Longitudinal study of smoking cessation before pregnancy and children's cognitive abilities at 56 months of age. Early Human Development 87(5): 353- 359, 2011. (57 refs.)

Background: An inverse relationship exists between the rates of maternal smoking during pregnancy and children's cognitive abilities. The effect of maternal cessation of smoking before pregnancy on child's cognitive development is less clear. Aims: To study whether maternal cessation of smoking before pregnancy is associated with children's cognitive abilities. Study design and subjects: The original cohort included all 1535 live-born infants admitted to the neonatal wards during 1 year and 658 randomly recruited non-admitted infants. The present study sample comprised 1019 (68.2%) children of the original sample born at term and free of any major impairment followed up to 56 months. Outcome measures: Child's general reasoning, visual-motor integration, verbal competence, and language comprehension at 56 months of age. Results: The results showed that children whose mothers smoked >10 cigarettes per day before pregnancy but none during pregnancy, fared 12.07 (95% confidence interval [CI]: 4.07 to 20.08) and 11.23 (95% Cl: 2.81 to 19.66) age-standardized points poorer in general reasoning and in language comprehension tests, respectively, than children of never-smokers. All results were adjusted for the sex, gestational age-adjusted birth weight, multiple/singleton pregnancy, birth order, preeclampsia, maternal diabetes, admission to neonatal ward, 5-minute Apgar score (<7), breastfeeding, parental level of education, maternal age, BMI at the end of pregnancy and single parenting. Conclusions: Heavy smoking before pregnancy is associated with children's lower cognitive abilities even if the mother has quit smoking before pregnancy. Identification and intervention of heavy smoking women of fertile age would potentially improve not only their odds to become pregnant but also benefit the offspring's cognitive functioning.

Hjerkinn B; Lindbaek M; Skogmo I; Rosvold EO. Neuropsychological screening of children of substance-abusing women attending a Special Child Welfare Clinic in Norway. Substance Abuse Treatment, Prevention and Policy 5(e-journal 17), 2010. (45 refs.)

Background: Exposure to alcohol and illicit substances during pregnancy can have an impact on the child for the rest of his/her life. A Special Child Welfare Clinic (SCWC) in Norway provides care for pregnant women with substance abuse problems. Treatment and support are provided without replacement therapy. Methods: We performed a neuropsychological screening of 40 children aged four to 11 years whose mothers had attended the SCWC during pregnancy, and of a comparison group of 80 children of women without substance abuse problems. The children were presented with tests chosen from Wechsler Intelligence Scale for Children, third version (WISC-III), Nepsy, Halstead-Reitan and Raven's Progressive Matrices, Coloured Version. The tests were grouped into five main domains; (1) learning and memory, (2) visual scanning, planning and attention, (3) executive function, (4) visuo-motor speed and dexterity and (5) general intellectual ability. Results: No children in the study had test results in the clinical range in any domain. Bivariate analyses revealed that children of short-term substance-abusing mothers (who stopped substance abuse within the first trimester) had significantly lower test scores than the comparison group in three out of five domains (domain 2,3,4). Children of long-term substance abusers (who maintained moderate substance abuse throughout pregnancy) had significantly lower test results than the comparison group in one domain of the test results (domain 1). All but one child in the long-term group were or had been in foster homes. Most children in the short-term group stayed with their mothers. Multivariate regression analyses revealed that foster care minimum 50% of life time was associated with better scores on domains (1) learning and memory, (2) visual scanning, planning and attention, and (3) executive functions, while no significant associations with test scores was found for substance abuse and birth before 38 weeks of gestation. Conclusion: Children raised by former substance abusing mothers scored worse on the neuropsychological screening than children who had substance abusing mothers and mostly were raised in foster homes. This indicates that it is important to focus on the environment in cases where help and support are provided to presently or formerly addicted women raising children.

Hjerkinn B; Rosvold EO; Lindbaek M. Neonatal findings among children of substance-abusing women attending a special child welfare clinic in Norway. Scandinavian Journal of Public Health 37(7): 751-757, 2009. (30 refs.)

Aims: A special child welfare clinic (SCWC) in Norway provides care for pregnant women with substance abuse problems to prevent the adverse effects of substances. The SCWC aims to give treatment without replacements. This article describes neonatal findings among children of substance-abusing women at the clinic. Methods: This was a retrospective cohort study including 62 children whose mothers had attended the SCWC during pregnancy. A comparison group with children of women with no substance abuse was included. Data were collected from medical records and by means of a questionnaire concerning neonatal data, health, and living conditions. SCWC mothers were divided into short-term users (substance use stopped within first trimester) and long-term users (continued moderate substance use throughout pregnancy). Results: Average birthweight and head circumference were significantly lower in the substance-abusing groups: 3084 g and 34.0 cm in the short-term group, 3048 g and 33.9 cm in the long-term group, and 3496 g and 34.8 cm in the comparison group. There was no difference in Apgar score. Substance abuse and psychiatric illness were associated with low birthweight. Long-term users were more likely than comparisons to experience premature birth and have low-birthweight children. This difference was not found among short-term users. We found no difference in Caesarean sections and vacuum extractions. Conclusions: Substance abusers who stop their drug use early in pregnancy tend to have birth outcomes that are similar to those of mothers with no substance abuse. The study indicates that attendance at a voluntary, low-threshold initiative for pregnant substance abusers, with a focus on prenatal care and substance abuse treatment without replacements, may reduce the harmful effect of the abuse on the newborn.

Huijbregts SCJ; van Berkel SR; Swaab-Barneveld H; van Goozen SHM. Neurobiological and behavioral stress reactivity in children prenatally exposed to tobacco. Psychoneuroendocrinology 36(6): 913-918, 2011. (23 refs.)

This study examined neurobiological and behavioral stress reactivity in children who had been prenatally exposed to tobacco. Neurobiological stress reactivity was measured using salivary cortisol and alpha-amylase levels at five different time points throughout a stressful neuropsychological test session, which involved a competition against a videotaped opponent. Participants (mean age: 10.6 years, SD 1.3) were 14 prenatally exposed (PE) children, 9 children with disruptive behavior problems (DBD), and 15 normal controls (NC). For cortisol responses, no significant differences between the three groups were observed. Normal controls, however, had significantly higher alpha-amylase levels than PE-children throughout the test session, and their alpha-amylase levels also increased throughout the session, whereas these remained low and stable for PE-children. Alpha-amylase levels and trajectory of PE-children were similar to those observed for DBD-children. PE-children also showed significantly increased behavioral stress reactivity compared to NC-children, and neurobiological and behavioral stress reactivity were inversely related in PE-children, again similar to what was observed for DBD-children. These results support the hypothesis that prenatal smoking may lead to long-lasting neurobiological and behavioral changes in exposed offspring.

Iliadou AN; Koupil I; Villamor E; Altman D; Hultman C; Langstrom N et al. Familial factors confound the association between maternal smoking during pregnancy and young adult offspring overweight. International Journal of Epidemiology 39(5): 1193-1202, 2010. (36 refs.)

Methods: In a population-based Swedish cohort comprising 124 203 singleton males born to Nordic mothers between 1983 and 1988, we examined the association between maternal smoking during pregnancy and the risk of overweight in the offspring at age similar to 18 years. We also investigated the association within siblings, controlling for common genes and shared environment. Results: In the cohort analyses, the risk of overweight was increased in sons of smoking mothers compared with sons of non-smokers: adjusted odds ratios 1.41, 95% confidence interval (CI) 1.34-1.49, and 1.56, 95% CI 1.46-1.66, for one to nine cigarettes per day, and > 10 cigarettes per day, respectively. Stratifying for maternal smoking habits across two subsequent male pregnancies, there was an increased risk of overweight for the second son only if the mother was smoking in both male pregnancies. The effect of smoking during pregnancy on the offspring's body mass index was not present when the association was evaluated within full and half sibling pairs. Conclusion: The association between maternal smoking during pregnancy and offspring's risk of overweight appears to be confounded by familial factors.

Ino T. Maternal smoking during pregnancy and offspring obesity: Meta-analysis. Pediatrics International 52(1): 94-99, 2010. (49 refs.)

Background: Recent reports have suggested that maternal smoking may increase the risk of development of obesity in the unborn child in later life, but relatively few cohort studies have been done on the relationship between maternal smoking during pregnancy and future development of metabolic syndrome. Methods: A systematic review and meta-analysis of observational studies reporting effect estimates and 95% confidence intervals (95%CI) was conducted on the association between maternal smoking during pregnancy and obesity of future offspring. Results: Seventeen papers were identified from 444 English-language papers (key word search: maternal smoking and obesity) in PubMed. All papers showed a positive association between maternal smoking during pregnancy and childhood obesity. The meta-analysis, using the DerSimonian-Laird method, found the association to be statistically significant. In association with maternal smoking during pregnancy and body mass index with more than 95%CI in the offspring aged 3-33 years, the pooled odds ratio calculated from 16 of these 17 studies was 1.64 (95%CI: 1.42-1.90). After adjustment for publication bias, the pooled adjusted odds ratio was 1.52 (95%CI: 1.36-1.70). In addition, confounders of maternal obesity, low social status, low birthweight and not being breast-fed seemed to be risk factors for offspring obesity. Conclusion: Maternal smoking during pregnancy may cause future obesity and metabolic syndrome.

Jansson LM; DiPietro JA; Elko A; Velez M. Infant autonomic functioning and neonatal abstinence syndrome. Drug and Alcohol Dependence 109(1-3): 198-204, 2010. (50 refs.)

Background: Neonatal abstinence syndrome (NAS) expression is widely variable among affected infants and the reasons for this variability are largely unknown; mechanisms that predispose infants to NAS expression are not understood. It has been postulated that the regulatory problems of prenatally drug exposed infants are manifested in dysfunctional vagal regulation of autonomic processes. The current study examines whether cardiac vagal tone, an indicator of parasympathetic neuroregulation, provides a marker for autonomic dysregulation subsequently expressed as NAS in prenatally opioid-exposed newborns. Methods: Heart period (HP) and cardiac vagal tone (V) were derived from electrocardiogram data collected from 64 methadone-exposed infants on postnatal days 1 and 3. The postpartum NAS course was assessed serially. Results: Infants with lower V on day 1 had significantly higher NAS symptomatology on day 3. Boys had more severe NAS symptoms than girls through the first 4 days of life and, among infants receiving pharmacologic treatment for NAS, boys required longer treatment course and hospitalizations. Greater poly-drug exposure, detected through toxicology screening throughout pregnancy, and cocaine use in particular, were associated with lower V and shorter HP (faster heart rate) in newborns. Multiple regression models accounted for 25-35% of the variance in NAS symptoms and duration of hospitalization in methadone-exposed infants. Significant predictors included infant sex, SSRI/SNRI use, and cigarette smoking. Conclusions: Results support the hypothesis of a biologic vulnerability of autonomic regulatory functioning in methadone-exposed infants and greater male infant vulnerability to maternal methadone use.

Keil V; Paley B; Frankel F; O'Connor MJ. Impact of a social skills intervention on the hostile attributions of children with prenatal alcohol exposure. Alcoholism: Clinical and Experimental Research 34(2): 231-241, 2010. (74 refs.)

Background: Prenatal alcohol exposure (PAE) has been linked to a wide array of developmental deficits, including significant impairments in social skills. Given the extensive body of evidence linking social information-processing patterns with social behavior, it is possible that social information-processing may represent one mechanism of behavioral change. The present investigation sought to answer the question of whether a well-established social skills intervention decreased the hostile attributions of children with PAE. Further, was there a differential impact of the intervention on hostile attributions in the context of peer provocation versus group entry scenarios? Methods: Participants consisted of 100 children (51% male) with PAE between the ages of 6 and 12 years. Participants were randomly assigned to either a social skills intervention, Children's Friendship Training (CFT), or to a Delayed Treatment Control (DTC) condition. Results: Analyses indicated that the social skills intervention resulted in a significantly lower proportion of hostile attributions in peer group entry, but not peer provocation, scenarios. This decrease was maintained over a 3-month follow-up period. Conclusions: Deficits in social information-processing among individuals with PAE can be improved through social skills intervention, and these changes may lead to more positive developmental outcomes.

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.

Kiechl-Kohlendorfer U; Ralser E; Peglow UP; Reiter G; Griesmaier E; Trawoger R. Smoking in pregnancy: A risk factor for adverse neurodevelopmental outcome in preterm infants? Acta Paediatrica 99(7): 1016-1019, 2010. (25 refs.)

Aim: To assess whether smoking in pregnancy influences neurodevelopmental outcome at 2-years of age in preterm infants with a gestational age <32 weeks. Methods: Between January 2003 and December 2005 we prospectively enrolled 181 infants born alive between 23 and 32 weeks of gestation; 142 infants (78.5%) completed the follow-up visit. The association between candidate risk factors and delayed motor or mental development (Bayley Scales of Infant Development II; psychomotor or mental developmental index <85) was analysed by means of logistic regression analysis. Results: Low maternal age, smoking in pregnancy, low gestational age, low birth weight, small for gestational age, chronic lung disease, intracerebral haemorrhage, periventricular leucomalacia, and retinopathy of prematurity (stages 3 and 4) all were associated with an increased risk for delayed development (p < 0.05, each). Smoking in pregnancy, small for gestational age and chronic lung disease maintained significance in a multivariable analysis. Conclusion: Smoking in pregnancy emerged as a risk predictor for adverse neurodevelopmental outcome in our study. Strategies to reduce smoking in pregnancy should be further endorsed.

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.

Koshy G; Delpisheh A; Brabin BJ. Dose response association of pregnancy cigarette smoke exposure, childhood stature, overweight and obesity. European Journal of Public Health 21(3): 286-291, 2011. (36 refs.)

Background: The combined dose response effects of pregnancy cigarette smoke exposure on childhood overweight, obesity and short stature have not been reported. Method: A community based cross-sectional survey of 3038 children aged 5-11 years from 15 primary schools in Merseyside, UK. Self-completed parental questionnaires were used for family characteristics, socio-economic status and parental smoking practices. Children were measured for height and weight and z-scores calculated for parental smoking categories. Results: Of 689 (34.0%) mothers who smoked during pregnancy 50.5% smoked ten or more cigarettes daily (heavy smokers). Children of maternal non-smokers had prevalence estimates for overweight, obesity and short stature of 25, 9.6 and 3.2%, respectively. Prevalence estimates were higher in children of mothers who were heavy smokers during pregnancy, 31.5% (P = 0.001), 15.6% (P < 0.001) and 5.5% (P = 0.001), respectively. Mean height for age z-scores was lower among heavy maternal (P < 0.001) and paternal smokers (P < 0.01) compared to non-smokers. Childhood overweight, obesity or short stature were all associated with heavy maternal smoking during pregnancy (all P < 0.001). Mean body mass index (BMI) z-scores were higher in boys of mothers who smoked (P = 0.043). The adjusted odds ratio for short stature in children of heavy maternal smokers was 2.76 (95% CI 1.21-6.33) and 4.28 (1.37-13.37) if both parents were heavy smokers. The adjusted OR for obesity in children of maternal smokers was 1.61(1.19-2.18). The population attributable risk for short stature was 8.8% (1.1-22.7) for heavy maternal smokers. Conclusion: A dose-response association was observed between pregnancy smoking exposure, short stature and obesity.

Kuja-Halkola R; D'Onofrio BM; Iliadou AN; Langstrom N; Lichtenstein P. Prenatal smoking exposure and offspring stress coping in late adolescence: No causal link. International Journal of Epidemiology 39(6): 1531-1540, 2010. (49 refs.)

Background: In utero exposure to tobacco smoking has been suggested to cause persistent alterations in cognitive functioning. We examined if mothers' smoking during pregnancy (SDP) is associated with long-term impairment in offspring stress coping and the causal mechanism behind a possible link. Methods: We used a large cohort (n = 187 106) of young males in Sweden (mean age = 18.2 years), who underwent a semi-structured psychological assessment in 1997-2006, including an evaluation of stress coping ability, as part of the compulsory military conscript examination. We compared differentially exposed siblings within nuclear families and cousins in extended families and used multilevel structural equation models to disentangle genetic from environmental contributions to the association between SDP and stress coping. Results: SDP and offspring stress coping was moderately strongly associated when comparing unrelated individuals [regression coefficient (b) = -0.38 on a nine-point scale; 95% confidence interval (CI) -0.40 to -0.36, P < 0.0001]. In contrast, it disappeared when siblings were compared (b = 0.11; 95% CI -0.01 to 0.23, P = 0.071). This familial confounding was entirely due to genetic influences. Conclusions: SDP is an established risk factor for pregnancy- and birth-related complications. However, we found no long-term effect of SDP on offspring stress coping. Rather, the observed association was due to familial confounding of genetic origin; women prone to SDP also transmit genes to their children that are associated with poorer coping with stress.

Kyu HH; Georgiades K; Boyle MH. Maternal smoking, biofuel smoke exposure and child height-for-age in seven developing countries. International Journal of Epidemiology 38(5): 1342-1350, 2009. (36 refs.)

Background: Children are at high risk of exposure to environmental tobacco smoke and biofuel smoke at home in developing countries. This study examines whether exposure to cigarette and biofuel smoke is associated with height-for-age of children (0-59 months) in seven developing countries. Methods: The data are from Demographic and Health Surveys conducted in Cambodia, Dominican Republic, Haiti, Jordan, Moldova, Namibia and Nepal between 2005 and 2007. The respondents were women (15-49 years) and their children in seven countries (n = 28 439), and men (15-59 years) from four countries. The outcome is a physical measurement of child height-for-age in standard deviation units. Results Multilevel regression analysis showed that the country of residence modified the association between maternal smoking and child height-for-age. Exposure to maternal smoking was associated negatively with child height-for-age in Cambodia, Namibia and Nepal, whereas it was not in other countries. Multilevel regression analysis revealed that biofuel smoke exposure was associated with a decrease in child height-for-age [b = -0.13, 95% confidence interval (CI) = -0.19 to -0.07, P < 0.001]. No interaction was found between country of residence and biofuel smoke exposure. Multinomial logistic regression results showed that biofuel smoke exposure was associated with both stunting [odds ratio (OR) = 1.25, 95% CI = 1.08-1.44, P = 0.002) and severe stunting (OR = 1.27, 95% CI = 1.02-1.59, P = 0.04), after controlling for covariates. Conclusion: The findings suggest that exposure to maternal smoking and biofuel smoke may contribute to growth deficiencies in young children. Programmes are needed to ensure smoke-free home environments for children.

Lau C; Rogers JM; Desai M; Ross MG. Fetal programming of adult disease: Implications for prenatal care. Obstetrics and Gynecology 117(4): 978-985, 2011. (80 refs.)

The obesity epidemic, including a marked increase in the prevalence of obesity among pregnant women, represents a critical public health problem in the United States and throughout the world. Over the past two decades, it has been increasingly recognized that the risk of adult health disorders, particularly metabolic syndrome, can be markedly influenced by prenatal and infant environmental exposures (ie, developmental programming). Low birth weight, together with infant catch-up growth, is associated with a significant risk of adult obesity and cardiovascular disease, as well as adverse effects on pulmonary, renal, and cerebral function. Conversely, exposure to maternal obesity or high birth weight also represents an increased risk for childhood and adult obesity. In addition, fetal exposure to select chemicals (eg, phytoestrogens) or environmental pollutants (eg, tobacco smoke) may affect the predisposition to adult disease. Animal models have confirmed human epidemiologic findings and provided insight into putative programming mechanisms, including altered organ development, cellular signaling responses, and epigenetic modifications (ie, control of gene expression without modification of DNA sequence). Prenatal care is transitioning to incorporate goals of optimizing maternal, fetal, and neonatal health to prevent or reduce adult-onset diseases. Guidelines regarding optimal pregnancy nutrition and weight gain, management of low-and high-fetal-weight pregnancies, use of maternal glucocorticoids, and newborn feeding strategies, among others, have yet to fully integrate long-term consequences on adult health.

Lee BE; Hong YC; Park H; Ha M; Kim JH; Chang N et al. Secondhand smoke exposure during pregnancy and infantile neurodevelopment. Environmental Research 111(4): 539- 544, 2011. (59 refs.)

During prenatal development, the nervous system may be more susceptible to environmental toxicants, such as secondhand smoke. The authors assessed the effects of prenatal and postnatal secondhand smoke exposure on the neurodevelopment of 6-month infants. The subjects were 414 mother and infant pairs with no medical problems, taken from the Mothers' and Children's Environmental Health study. Prenatal and postnatal exposures to secondhand smoke were determined using maternal self-reports. Examiners, unaware of exposure history, assessed the infants at 6 months of age using the Bayley Scales of Infant Development. Bayley scores were compared for secondhand smoke exposed and unexposed groups after adjusting for potential confounders. Multiple logistic regression analysis was carried out to estimate the risk of developmental delay posed by SHS exposure. The multivariate model included residential area, maternal age, pre-pregnancy body mass index, education, income, infant sex, parity, birth weight, and type of feeding. After adjusting for covariates, secondhand smoke exposure during pregnancy was found to be related to a decrease in mental developmental index score, but not to a decrease in psychomotor developmental index score. In addition, secondhand smoke exposure during pregnancy was found to increase the risk of developmental delay (mental developmental index score 5 85) at 6 months. This study suggests that the infants of non-smoking women exposed to secondhand smoke are at risk of neurodevelopmental delay.

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.

Mangrio E; Lindstrom M; Rosvall M. Early life factors and being overweight at 4 years of age among children in Malmo, Sweden. BMC Public Health 10: e-article 764, 2010. (43 refs.)

Background: Rising rates of obesity and overweight is an increasing public health problem all over the world. Recent research has shown the importance of early life factors in the development of child overweight. However, to the best of our knowledge there are no studies investigating the potential synergistic effect of early life factors and presence of parental overweight on the development of child overweight. Methods: The study was population-based and cross-sectional. The study population consisted of children who visited the Child Health Care (CHC) centers in Malmo for their 4-year health check during 2003-2008 and whose parents answered a self-administered questionnaire (n = 9009 children). Results: The results showed that having overweight/obese parents was strongly associated with the child being overweight or obese. Furthermore, there was an association between unfavorable early life factors (i.e., mother smoking during pregnancy, presence of secondhand tobacco smoke early in life, high birth weight) and the development of child overweight/obesity at four years of age, while breastfeeding seemed to have a protective role. For example, maternal smoking during pregnancy was associated with an odds ratio (OR) of 1.47 (95% CI: 1.22, 1.76) for overweight and 2.31 (95% CI: 1.68, 3.17) for obesity. The results further showed synergistic effects between parental overweight and exposure to unfavourable early life factors in the development of child overweight. Conclusions: The present study shows the importance of early life factors in the development of child overweight and obesity, and thus puts focus on the importance of early targeted interventions.

Maritz GS; Harding R. Life-long programming implications of exposure to tobacco smoking and nicotine before and soon after birth: Evidence for altered lung development. International Journal of Environmental Research and Public Health 8(3): 875-898, 2011. (134 refs.)

Tobacco smoking during pregnancy remains common, especially in indigenous communities, and likely contributes to respiratory illness in exposed offspring. It is now well established that components of tobacco smoke, notably nicotine, can affect multiple organs in the fetus and newborn, potentially with life-long consequences. Recent studies have shown that nicotine can permanently affect the developing lung such that its final structure and function are adversely affected; these changes can increase the risk of respiratory illness and accelerate the decline in lung function with age. In this review we discuss the impact of maternal smoking on the lungs and consider the evidence that smoking can have life-long, programming consequences for exposed offspring. Exposure to maternal tobacco smoking and nicotine intake during pregnancy and lactation changes the genetic program that controls the development and aging of the lungs of the offspring. Changes in the conducting airways and alveoli reduce lung function in exposed offspring, rendering the lungs more susceptible to obstructive lung disease and accelerating lung aging. Although it is generally accepted that prevention of maternal smoking during pregnancy and lactation is essential, current knowledge of the effects of nicotine on lung development does not support the use of nicotine replacement therapy in this group.

Matijasevich A; Brion MJ; Menezes AM; Barros AJD; Santos IS; Barros FC. Maternal smoking during pregnancy and offspring growth in childhood: 1993 and 2004 Pelotas cohort studies. Archives of Disease in Childhood 96(6): 519- 525, 2011. (32 refs.)

Objective To explore the effects of maternal smoking during pregnancy on offspring growth using three approaches: (1) multiple adjustments for socioeconomic and parental factors, (2) maternal-paternal comparisons as a test of putative intrauterine effects and (3) comparisons between two birth cohort studies. Methods Population-based birth cohort studies were carried out in Pelotas, Brazil, in 1993 and 2004. Cohort members were followed up at 3, 12, 24 and 48 months. Multiple linear regression analysis was used to examine the relationships between maternal and paternal prenatal smoking and offspring anthropometric indices. In the 2004 cohort, the association of smoking with trunk length, leg length and leg-to-sitting-height ratio at 48 months was also explored. Results: Maternal smoking during pregnancy was associated with reduced z scores of length/height-for-age at each follow-up in both cohorts and reduced leg length at 48 months in the 2004 cohort. Children older than 3 months born to smoking women showed a higher body mass index-for-age z score than children of nonsmoking women. Conclusions: The results of this study strongly support the hypothesis that maternal smoking during pregnancy impairs linear growth and promotes overweight in childhood.

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.

McGlone L; Mactier H; Weaver LT. Drug misuse in pregnancy: Losing sight of the baby? Archives of Disease In Childhood 94(9): 708-712, 2009. (66 refs.)

Maternal drug misuse can seriously affect the health of the fetus and newborn infant. The association of maternal drug misuse with prematurity, intrauterine growth restriction (IUGR) and neonatal abstinence syndrome (NAS) is well recognised, and there is growing concern about infant visual development and longer-term neuro-developmental outcome. Drug misuse is associated with changes in the visual system as measured by the visual evoked potential (VEP) in adults and animal models. A recent study has shown abnormal VEPs in newborn infants exposed to methadone in utero, consistent with reports of delayed visual development in this population. Since visual abnormalities and neurodevelopmental abnormalities can be predicted by abnormal VEPs in infancy, it is postulated that the VEP may be a valuable tool in the detection of the adverse effects of maternal drug misuse upon the infant. This review summarises the impact of maternal drug misuse upon the health of the fetus and newborn infant, addresses the specific effects of maternal drug misuse upon the developing visual system and discusses the potential role of the VEP in the assessment of these infants.

Minnes S; Singer LT; Kirchner HL; Short E; Lewis B; Satayathum S et al. The effects of prenatal cocaine exposure on problem behavior in children 4-10 years. Neurotoxicology and Teratology 32(4): 443-451, 2010. (58 refs.)

Background: Children prenatally exposed to cocaine may be at increased risk for behavioral problems due to disruptions of monaminergically regulated arousal systems and/or environmental conditions. Objective: To assess behavioral outcomes of cocaine (CE) and non-cocaine-exposed (NCE) children, 4 through 10 years old, controlling for other prenatal drug exposures and environmental factors. Methods: Low socioeconomic status (SES), primarily African American children (n=381 (193 (CE), 188 (NCE)) were recruited from birth. Generalized Estimating Equation (GEE) analyses were used to assess the predictive relationship of prenatal cocaine exposure to odds of caregiver reported clinically elevated behavioral problems at 4, 6, 9 and 10 years of age, controlling for confounders. Results: Prenatal cocaine exposure was associated with increased rates of caregiver reported delinquency (OR = 1.93, Cl: 1.09-3.42, p<0.02). A significant prenatal cocaine exposure by sex interaction was found for delinquency indicating that only females were affected (OR = 3.57, Cl: 1.67-7.60, p<0.001). There was no effect of cocaine on increased odds of other CBCL subscales. Higher prenatal tobacco exposure was associated with increased odds of externalizing symptoms at 4,9 and 10 years of age. For CE children, those in foster or adoptive care were rated as having more behavior problems than those in biologic mother or relative care. Greater caregiver psychological distress was associated with increased behavioral problems. There were no independent effects of elevated blood lead level on increased behavior problems after control for prenatal drug exposure and other environmental conditions. Conclusion: Prenatal cocaine and tobacco exposure were associated with greater externalizing behavior after control for multiple prenatal drug exposures, other environmental and caregiving factors and lead exposure from 4 through 10 years of age. Greater caregiver psychological distress negatively affected caregiver ratings of all CBCL domains. Since cocaine and tobacco use during pregnancy and maternal psychological distress have the potential to be altered through prenatal educational, drug treatment and mental health interventions, they warrant attention in efforts to reduce rates of problem behaviors in children.

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.

Mook-Kanamori DO; Steegers EAP; Eilers PH; Raat H; Hofman A; Jaddoe VWV. Risk factors and outcomes associated with first-trimester fetal growth restriction. Journal of the American Medical Association 303(6): 527-534, 2010. (32 refs.)

Context: Adverse environmental exposures lead to developmental adaptations in fetal life. The influences of maternal physical characteristics and lifestyle habits on first-trimester fetal adaptations and the postnatal consequences are not known. Objective: To determine the risk factors and outcomes associated with first-trimester growth restriction. Design, Setting, and Participants Prospective evaluation of the associations of maternal physical characteristics and lifestyle habits with first-trimester fetal crown to rump length in 1631 mothers with a known and reliable first day of their last menstrual period and a regular menstrual cycle. Subsequently, we assessed the associations of first-trimester fetal growth restriction with the risks of adverse birth outcomes and postnatal growth acceleration until the age of 2 years. The study was based in Rotterdam, the Netherlands. Mothers were enrolled between 2001 and 2005. Main Outcome Measures: First-trimester fetal growth was measured as fetal crown to rump length by ultrasound between the gestational age of 10 weeks 0 days and 13 weeks 6 days. Main birth outcomes were preterm birth (gestational age <37 weeks), low birth weight (<2500 g), and small size for gestational age (lowest fifth birth centile). Postnatal growth was measured until the age of 2 years. Results: In the multivariate analysis, maternal age was positively associated with first-trimester fetal crown to rump length (difference per maternal year of age, 0.79 mm; 95% confidence interval [CI], 0.41 to 1.18 per standard deviation score increase). Higher diastolic blood pressure and higher hematocrit levels were associated with a shorter crown to rump length (differences, -0.40 mm; 95% CI, -0.74 to -0.06 and -0.52 mm; 95% CI, -0.90 to -0.14 per standard deviation increase, respectively). Compared with mothers who were nonsmokers and optimal users of folic acid supplements, those who both smoked and did not use folic acid supplements had shorter fetal crown to rump lengths (difference, -3.84 mm; 95% CI, -5.71 to -1.98). Compared with normal first-trimester fetal growth, first-trimester growth restriction was associated with increased risks of preterm birth (4.0% vs 7.2%; adjusted odds ratio [OR], 2.12; 95% CI, 1.24 to 3.61), low birth weight (3.5% vs 7.5%; adjusted OR, 2.42; 95% CI, 1.41 to 4.16), and small size for gestational age at birth (4.0% vs 10.6%; adjusted OR, 2.64; 95% CI, 1.64 to 4.25). Each standard deviation decrease in first-trimester fetal crown to rump length was associated with a postnatal growth acceleration until the age of 2 years (standard deviation score increase, 0.139 per 2 years; 95% CI, 0.097 to 0.181). Conclusions Maternal physical characteristics and lifestyle habits were independently associated with early fetal growth. First-trimester fetal growth restriction was associated with an increased risk of adverse birth outcomes and growth acceleration in early childhood.

Morrow CE; Accornero VH; Xue LH; Manjunath S; Culbertson JL; Anthony JC et al. Estimated risk of developing selected DSM-IV disorders among 5-year-old children with prenatal cocaine exposure. Journal of Child and Family Studies 18(3): 356-364, 2009. (49 refs.)

We estimated childhood risk of developing selected DSM-IV Disorders, including Attention-Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), and Separation Anxiety Disorder (SAD), in children with prenatal cocaine exposure (PCE). Children were enrolled prospectively at birth (n = 476) with prenatal drug exposures documented by maternal interview, urine and meconium assays. Study participants included 400 African-American children from the birth cohort, 208 cocaine-exposed (CE) and 192 non-cocaine-exposed (NCE), who attended a 5-year follow-up assessment and whose caregiver completed the Computerized Diagnostic Interview Schedule for Children. Under a generalized linear model (logistic link), Fisher's exact methods were used to estimate the PCE-associated relative risk (RR) of these disorders. Our results indicated a modest but statistically robust elevation of ADHD risk associated with increasing levels of PCE (p < 0.05). Binary comparison of CE versus NCE children indicated no PCE-associated RR. Estimated cumulative incidence proportions among CE children were 2.9% for ADHD (vs 3.1% NCE); 1.4% for SAD (vs 1.6% NCE); and 4.3% for ODD (vs 6.8% NCE). Our findings suggest evidence of increased risk of ADHD (but not ODD or SAD) in relation to an increasing gradient of PCE during gestation.

Motlagh MG; Katsovich L; Thompson N; Lin HQ; Kim YS; Scahill L et al. Severe psychosocial stress and heavy cigarette smoking during pregnancy: An examination of the pre- and perinatal risk factors associated with ADHD and Tourette syndrome. European Journal of Epidemiology 19(10): 755-764, 2010. (62 refs.)

Attention-deficit/hyperactivity disorder (ADHD) is frequently diagnosed in children with Tourette syndrome (TS). The basis for this co-occurrence is uncertain. This study aimed to determine if specific pre- and perinatal risk factors, including heavy maternal smoking and severe psychosocial stress during pregnancy, were associated with one or both disorders, or neither. We compared maternal report data on pre- and perinatal risk factors on 222 children between the ages of 7 and 18 years including 45 individuals with TS alone, 52 individuals with ADHD alone, 60 individuals with condition of comorbid TS + ADHD, and 65 unaffected control children. Pre- and perinatal histories as well as psychiatric assessments were performed using standardized questionnaires and semi-structured interviews with the mothers and children. Logistic regression was used to determine the odds ratio for each variable of interest. Compared to the mothers of unaffected control children, the mothers of children with ADHD alone reported higher rates of heavy smoking (> 10 cigarettes per day) during pregnancy and higher levels of severe psychosocial stress during pregnancy (OR = 13.5, p < 0.01 and OR = 6.8, p < 0.002, respectively). The TS + ADHD and the TS alone patients also had higher rates heavy maternal smoking and high levels of psychosocial stress compared to the control children, but these differences failed to reach statistical significance (heavy smoking: OR = 8.5, p < 0.052, OR = 4.6, p < 0.19, respectively; severe psychosocial stress: OR = 3.1, p < 0.07, OR = 2.6, p < 0.11, respectively). Heavy maternal smoking and severe levels psychosocial stress during pregnancy were independently associated with a diagnosis of ADHD. TS patients also had higher rates of these risk factors, but the ORs failed to reach statistical significance. Efforts are needed to reduce the frequency of these risk factors in high-risk populations. Future studies, using genetically sensitive designs, are also needed to sort out the causal pathways.

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

Nomura Y; Marks DJ; Halperin JM. Prenatal exposure to maternal and paternal smoking on attention deficit hyperactivity disorders symptoms and diagnosis in offspring. Journal of Nervous and Mental Disease (9): 672-678, 2010. (52 refs.)

The study examined the effect of maternal and paternal smoking during pregnancy on the child's inattention and hyperactivity/impulsivity symptoms, and the risk for attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). Generalized estimating equations, incorporating data from multiple informants (parents and teachers), was used to evaluate levels of ADHD as a function of parental smoking. The risk for ADHD, ODD, and comorbid ADHD and ODD was evaluated using polytomous logistic regression. We found that maternal, but not paternal, smoking was significantly associated with elevated inattention, hyperactivity/impulsivity, and total ADHD symptoms in children. Children of smoking, relative to nonsmoking, mothers had a significant increased risk for comorbid ADHD and ODD and ADHD, but not ODD. Although father's smoking was not associated with an increased risk, as it strongly influenced mothers' smoking, intervention for both parents may be most effective in preventing the pathway to ADHD-related problems in the children.

O'Callaghan FV; Al Mamun A; O'Callaghan M; Alati R; Williams GM; Najman JM. Is smoking in pregnancy an independent predictor of academic difficulties at 14 years of age? A birth cohort study. Early Human Development 86(2): 71-76, 2010. (35 refs.)

Background. Studies of the effects of maternal smoking during pregnancy have reported inconsistent findings in relation to measures of offspring cognitive functioning Few studies, however, have examined learning outcomes in adolescents, as opposed to IQ Aim To examine the association between maternal smoking during pregnancy and academic performance among adolescent offspring Study design: Population-based birth cohort study. Subjects: 7223 mothers and children were enrolled in the Mater-University of Queensland Study of Pregnancy in Brisbane (Australia) from 1981 to 1984. Analyses were restricted to the 4294 mothers and children for whom all information was reported at 14-year follow-up Outcome measures Reports of academic performance of 14-year-old offspring in English. Science and Mathematics with different patterns of maternal smoking (never smoked, smoked before and/or after pregnancy but not during pregnancy, or smoked during pregnancy) Results. Low academic achievement was more common only in those whose mothers had smoked during pregnancy. Effect sizes were, however, small. The adjusted mean difference in total learning score for smoking before and/or after pregnancy but not during pregnancy, and for smoking during pregnancy were -0.18 (-0 58, 0 22) and -0 40 (-0 69, -0 12). Similarly, the adjusted odds ratios were 0.9 (0.65, 1.24) and 1.35(1 07, 1 70) Conclusion: Maternal smoking during pregnancy is a preventable prenatal risk factor associated with small decrements in offspring academic performance that continue into adolescence.

O'Leary CM; Nassar N; Zubrick SR; Kurinczuk JJ; Stanley F; Bower C. Evidence of a complex association between dose, pattern and timing of prenatal alcohol exposure and child behaviour problems. Addiction 105(1): 74-86, 2010. (59 refs.)

Background: There is a lack of evidence regarding the effect of dose, pattern and timing of prenatal alcohol exposure and behaviour problems in children aged 2 years and older. Methods: A 10% random sample of women delivering a live infant in Western Australia (1995-96) were invited to participate in an 8-year longitudinal survey (78% response rate n = 2224); 85% were followed-up at 2 years, 73% at 5 years and 61% at 8 years. Alcohol consumption was classified by combining the overall dose, dose per occasion and frequency to reflect realistic drinking patterns. Longitudinal analysis was conducted using generalized estimating equations (GEE) to investigate the association between child behaviour as measured by the Child Behaviour Checklist at 2, 5 and 8 years of age and prenatal alcohol exposure collected 3 months postpartum for each trimester separately, adjusting for a wide range of confounding factors. Results: Low levels of prenatal alcohol were not associated with child behaviour problems. There were increased odds of internalizing behaviour problems following heavy alcohol exposure in the first trimester; anxiety/depression [adjusted odds ratio (aOR) 2.82; 95% confidence interval (CI) 1.07-7.43] and somatic complaints (aOR 2.74; 95% CI 1.47-5.12) and moderate levels of alcohol exposure increased the odds of anxiety/depression (aOR 2.24; 95% CI 1.16-4.34). Conclusions: Prenatal alcohol exposure at moderate and higher levels increased the odds of child behaviour problems with the dose, pattern and timing of exposure affecting the type of behaviour problems expressed. Larger studies with more power are needed to confirm these findings.

Rahu K; Rahu M; Pullmann H; Allik J. Effect of birth weight, maternal education and prenatal smoking on offspring intelligence at school age. Early Human Development 86(8): 493-497, 2010. (53 refs.)

To examine the combined effect of birth weight, mothers' education and prenatal smoking on psychometrically measured intelligence at school age 1,822 children born in 1992-1999 and attending the first six grades from 45 schools representing all of the fifteen Estonian counties with information on birth weight, gestational age and mother's age, marital status, education, parity and smoking in pregnancy, and intelligence tests were studied. The scores of Raven's Standard Progressive Matrices were related to the birth weight: in the normal range of birth weight (>= 2500 g) every 500 g increase in birth weight was accompanied by around 0.7-point increase in IQ scores. A strong association between birth weight and IQ remained even if gestational age and mother's age, marital status, education, place of residence, parity and smoking during pregnancy have been taken into account. Maternal prenatal smoking was accompanied by a 3.3-point deficit in children's intellectual abilities. Marriage and mother's education had an independent positive correlation with offspring intelligence. We concluded that the statistical effect of birth weight, maternal education and smoking in pregnancy on offspring's IQ scores was remarkable and remained even if other factors have been taken into account.

Robinson M; McLean NJ; Oddy WH; Mattes E; Bulsara M; Li JH et al. Smoking cessation in pregnancy and the risk of child behavioural problems: A longitudinal prospective cohort study. Journal of Epidemiology and Community Health 64(7): 622-629, 2010. (51 refs.)

Background: The aim of this study was to examine the influence of smoking in pregnancy on child and adolescent behavioural development, in comparison with mothers who ceased smoking in the first 18 weeks of pregnancy and with those who never smoked, in a large prospective pregnancy cohort. Methods: The Western Australian Pregnancy Cohort (Raine) Study provided comprehensive data from 2900 pregnancies. Smoking was assessed at 18 weeks gestation, and children were followed up at ages 1, 2, 3, 5, 8, 10 and 14 years. The Child Behaviour Checklist (CBCL) was used to measure problem child behaviour with continuous z-scores and clinical cut points at ages 2, 5, 8, 10 and 14 years. Potential confounders included maternal and family sociodemographic characteristics and alcohol exposure. Results: After adjusting for confounders, children of light smokers who quit smoking by 18 weeks gestation had significantly lower CBCL total z-scores, indicative of better behaviour, than children of women who never smoked, children of heavy smokers who quit and continuing smokers. Maternal smoking during pregnancy resulted in higher CBCL total, internalising and externalising scores and a higher risk of clinically meaningful behaviour problems in children from ages 2 to 14. Conclusion: The maternal decision not to quit smoking, or the inability to quit smoking, during pregnancy appears to be a particularly strong marker for poor behavioural outcomes in children. There is a need for a greater understanding of the psychosocial characteristics associated with the decision and ability to quit smoking in pregnancy.

Robinson M; Oddy WH; McLean NJ; Jacoby P; Pennell CE; de Klerk NH et al. Low-moderate prenatal alcohol exposure and risk to child behavioral development: A prospective cohort study. (editorial). Obstetrical & Gynecological Survey 65(12): 759-760, 2010. (0 refs.)

The detrimental effects of fetal exposure to extreme levels of alcohol during pregnancy, such as the subsequent occurrence of childhood physical, cognitive, and behavioral deficits, are well known. Some investigators have suggested that there is a dose-response effect, with light drinking during pregnancy primarily affecting behavioral and adaptive functions and heavy drinking causing more serious developmental defects and problems. Accordingly, mild to moderate social drinking during pregnancy could be associated with long-term infant morbidity. The relatively few studies examining the long-term risk of fetal exposure to light-moderate levels of alcohol have failed to reach consensus, possibly due to deficiencies in study design. This prospective longitudinal cohort study investigated the effect of different levels of fetal alcohol exposure during pregnancy on child and adolescent behavioral development. The Western Australian Pregnancy Cohort (Raine) Study enrolled 2900 pregnancies between 1989 and 1991, with a 14-year follow-up. Maternal self-reported data for 5 levels of weekly alcohol intake were obtained at 18 and 34 weeks' gestation: no drinking, occasional drinking (up to one standard drink per week), light drinking (2-6 standard drinks per week), moderate drinking (7-10 standard drinks per week), and heavy drinking (11 or more standard drinks per week). A linear regression model was used to determine whether prenatal alcohol exposure could produce changes in Child Behavior Checklist scores over 14 years that reflected clinically meaningful differences in child behavioral development, after adjustment for maternal and sociodemographic confounders. Detailed clinical assessments of study children were conducted at birth, with follow-up conducted at 2, 5, 8, 10, and 14 years. The adjusted data showed that light and moderate drinking during the first 3 months of pregnancy resulted in Child Behavior Checklist z-scores indicative of positive behavior over 14 years. The z-scores reflected a clinically meaningful reduction in total, internalizing, and externalizing behavioral problems across the 14 years of follow-up. These findings suggest that low-moderate alcohol intake early in pregnancy is not associated with poor behavioral outcomes in offspring.

Rodriguez A; Olsen J; Kotimaa AJ; Kaakinen M; Moilanen I; Henriksen TB et al. Is prenatal alcohol exposure related to inattention and hyperactivity symptoms in children? Disentangling the effects of social adversity. Journal of Child Psychology and Psychiatry and Allied Disciplines 50(9): 1073-1083, 2009. (42 refs.)

Background: Studies concerning whether exposure to low levels of maternal alcohol consumption during fetal development is related to child inattention and hyperactivity symptoms have shown conflicting results. We examine the contribution of covariates related to social adversity to resolve some inconsistencies in the extant research by conducting parallel analyses of three cohorts with varying alcohol consumption and attitudes towards alcohol use. Methods: We compare three population-based pregnancy-offspring cohorts within the Nordic Network on ADHD from Denmark and Finland. Prenatal data were gathered via self-report during pregnancy and birth outcomes were abstracted from medical charts. A total of 21,678 reports concerning inattention and hyperactivity symptoms in children were available from the Strengths and Difficulties Questionnaire or the Rutter Scale completed by parents and/or teachers. Results: Drinking patterns differed cross-nationally. Women who had at least some social adversity (young, low education, or being single) were more likely to drink than those better off in the Finnish cohort, but the opposite was true for the Danish cohorts. Prenatal alcohol exposure was not related to risk for a high inattention-hyperactivity symptom score in children across cohorts after adjustment for covariates. In contrast, maternal smoking and social adversity during pregnancy were independently and consistently associated with an increase in risk of child symptoms. Conclusions: Low doses of alcohol consumption during pregnancy were not related to child inattention/hyperactivity symptoms once social adversity and smoking were taken into account.

Rose-Jacobs R; Soenksen S; Appugliese DP; Cabral HJ; Richardson MA; Beeghly M et al. Early adolescent executive functioning, intrauterine exposures and own drug use. Neurotoxicology and Teratology 33(3): 379-392, 2011. (116 refs.)

Individual differences in adolescents' executive functioning are often attributed either to intrauterine substance exposure or to adolescents' own substance use, but both predictors typically have not been evaluated simultaneously in the same study. This prospective study evaluated whether intrauterine drug exposures, the adolescents' own substance use, and/or their potential interactions are related to poorer executive functioning after controlling for important contextual variables. Analyses were based on data collected on a sample of 137 predominantly African-American/African Caribbean adolescents from low-income urban backgrounds who were followed since their term birth. Intrauterine substance exposures (cocaine, marijuana, alcohol, and cigarettes) and adolescents' substance use were documented using a combination of biological assays and maternal and adolescent self-report. At 12-14 years of age, examiners masked to intrauterine exposures and current substance use assessed the adolescents using the Delis Kaplan Executive Function System (D-KEFS), an age-referenced instrument evaluating multiple dimensions of executive functioning (EF). Results. of covariate-controlled analyses in this study suggest that when intrauterine substance exposures and young adolescents' substance use variables were in the same analysis models, subtle differences in specific EF outcomes were identifiable in this non-referred sample. While further study with larger samples is indicated, these findings suggest that 1) research on adolescent substance use and intrauterine exposure research should evaluate both predictors simultaneously, 2) subtle neurocognitive effects associated with specific intrauterine drug exposures can be identified during early adolescence, and 3) intrauterine substance exposure effects may differ from those associated with adolescents' own drug use.

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.

Ruckinger S; Beyerlein A; Jacobsen G; von Kries R; Vik T. Growth in utero and body mass index at age 5 years in children of smoking and non-smoking mothers. Early Human Development 86(12): 773-777, 2010. (35 refs.)

Background: High birth weight is associated with overweight later in life, while tobacco exposure in utero is associated with low birth weight, but with later risk of overweight. Aims: To examine whether body mass index (BMI) z-scores of children at age 5 are associated with measurements of mid-abdominal diameter (MAD) in utero comparing smoking and non-smoking mothers. Study Design: Growth in utero was recorded as MAD in mm per days of gestational age (MAD for gestational age) at 17, 25, 33 and 37 weeks of gestation in 561 infants whose mothers participated in a population-based study in Scandinavia (1986-1988). Outcome Measures: The offspring's BMI z-score at 5 years was used as a dependent variable, and MAD for gestational age as well as birth weight divided by gestational age in days were included as explanatory variables in separate linear regression models. Maternal BMI was considered as a potential confounder. Results: At 17 and 25 weeks gestation there were no relevant differences in MAD for gestational age between smokers and non-smokers. At 33 and 37 weeks gestation, children of smoking mothers had less increase in MAD than children of non-smoking mothers. In adjusted models, MAD for gestational age in week 33 and 37 was positively associated with BMI z-score at 5 years of age among children of both smoking and nonsmoking mothers. Conclusions: In this study overweight in children exposed to tobacco smoking in utero was apparently not mediated through foetal growth retardation, followed by enhanced fat accretion after birth.

Ruckinger S; Rzehak P; Chen CM; Sausenthaler S; Koletzko S; Bauer CP; y Group. Prenatal and postnatal tobacco exposure and behavioral problems in 10-year-old children: Results from the GINI-plus prospective birth cohort atudy. Environmental Health Perspectives 118(1): 150-154, 2010. (34 refs.)

BACKGROUND: Prenatal and postnatal tobacco exposure have been reported to be associated with behavioral problems. However, the magnitude of the association with tobacco exposure at specific periods of exposure is unclear. OBJECTIVE: We assessed the relative risk of behavioral problems in children who had been exposed to tobacco smoke in utero and postnatally. METHODS: We analyzed data from a prospective birth cohort study in two cities in Germany: the German Infant Nutrition Intervention. Our sample included 5,991 children born between 1995 and 1998 as well as their parents. We measured behavioral problems using the Strength and Difficulties Questionnaire (SDQ) at follow-up 10 years after birth. According to prespecified SDQ cutoff values, children were classified as "normal," "borderline," or "abnormal" according to the subscales "emotional symptoms," "conduct problems," "hyperactivity/inattention," "peer-relationship problems," and a total difficulties score. Smoke exposure and further covariates were assessed using parent questionnaires. RESULTS: Compared with children not exposed to tobacco smoke, children exposed both pre- and postnatally to tobacco smoke had twice the estimated risk [95% confidence interval (CI), 1.4-3.1] of being classified as abnormal according to the total difficulties score of the SDQ at 10 years of age. Children who were only prenatally exposed had a 90% higher relative risk (95% CI, 0.9-4.0), whereas children who were only postnatally exposed had a 30% higher relative risk (95% CI, 0.9-1.9). These results could not be explained by confounding by parental education, father's employment, child's time spent in front of computer or television screen, being a single father or mother, or mother's age. CONCLUSIONS: Prenatal exposure to tobacco smoke is associated with behavioral problems in school-age children. Although our findings do not preclude the influence of postnatal exposure, prenatal exposure seems to be more important.

Salo S; Kivisto K; Korja R; Biringen Z; Tupola S; Kahila H et al. Emotional availability, parental self-efficacy beliefs, and child development in caregiver-child relationships with buprenorphine-exposed 3-year-olds. Parenting. Science and Practice 9(3-4): 244-259, 2009. (50 refs.)

Objective. The purpose was to compare emotional availability, maternal self-efficacy beliefs, and child developmental status in caregiver-child relationships with prenatally buprenorphine-exposed and nonexposed 3-year-old children. Design. We compared prenatally buprenorphine-exposed children living either with the biological mother (n = 7) or in foster care (n = 14) to nonexposed participants (n = 13). Emotional availability was coded from videotaped parent-child free-play interactions. Results. After controlling for covariates, buprenorphine-exposed children scored lower on maternal Sensitivity and Nonhostility and child Responsiveness and Involvement as well as lower on the Bayley Cognitive and Language scales than did nonexposed children. As compared to foster mothers, biological mothers scored lower on Sensitivity and Nonhostility and self-efficacy beliefs, and their children scored lower on Responsiveness and the Bayley Cognitive Scale. Regardless of group status, the parenting variables were meaningfully related to child socioemotional variables. Conclusions. Buprenorphine-exposed children experienced more environmental risks in emotional availability and parental self-efficacy and performed worse on the Bayley as compared to nonexposed children.

Salvo EPD; Liu YH; Brenner S; Weitzman M. Adult household smoking is associated with increased child emotional and behavioral problems. Journal of Developmental and Behavioral Pediatrics 31(2): 107-115, 2010. (67 refs.)

Context: Although maternal smoking has been associated with child emotional and behavioral problems, to our knowledge, no study has evaluated the association between overall household smoking and such problems. Objectives: To investigate whether children who live with smokers are more likely than children who do not live with smokers to have emotional or behavioral problems and to explore this association in households with nonsmoking mothers. Design, Setting, and Participants: Nationally representative data from the 2000 to 2004 medical expenditure panel surveys, involving 30,668 children aged 5 to 17 years, were used. Associations between child emotional or behavioral problems and household smoking, and child, maternal, and family characteristics were examined. SUDAAN software was used to adjust for complex sampling design. Main Outcome Measures: Overall score on the Columbia Impairment Scale, a 13-item parent-report measure of child emotional or behavioral functioning (range, 0-52, >= 16 indicates a child with such problems). Results: Children in smoking versus nonsmoking households were significantly more likely to have behavioral problems (17.39% vs 9.29%, p < .001). After adjusting for all covariates, male sex, older age of child, younger age of mother, unmarried mother, maternal depression, and below average maternal physical and mental health, each were independently associated with increased likelihood of emotional and behavioral problems, as was the presence of one or more adult smokers in the household (adjusted odds ratio 1.42; 95% confidence interval: 1.26-1.60). The odds of Columbia Impairment Scale score >= 16 increased with increasing number of smokers in the household, even among children whose mothers did not smoke. Conclusion: Children living with smokers are at increased risk for emotional or behavioral problems, and rates of such problems increase with increasing numbers of smokers in the household, even in the absence of maternal smoking.

Santhanam P; Li ZH; Hu XP; Lynch ME; Coles CD. Effects of prenatal alcohol exposure on brain activation during an arithmetic task: An FMRI study. Alcoholism: Clinical and Experimental Research 33(11): 1901-1908, 2009. (41 refs.)

Background: While behavioral studies have established that prenatal alcohol exposure (PAE) can result in diminished arithmetic processing capability, the underlying neural correlates of this deficit are still unclear. The aim of the present study was to use functional magnetic resonance imaging to determine the effect of PAE on neuronal activation during a subtraction task. Methods: Participants were young adults from a low socio-economic status population who were identified prenatally; the sample consisted of healthy unexposed controls (n = 17) and PAE who were subdivided based on the presence (n = 19) or absence of physical dysmorphic signs (n = 18). Multiple regression analysis was used to determine extent of activation and percent signal change during arithmetic processing, using a letter-matching task as the baseline. Region of interest analysis of activation was performed in the native space and normalized for each individual to compensate for the considerable variability in head size observed in the alcohol-exposed population. Results: An exposure-dependent response was observed in task performance and neuronal activation. Dysmorphic PAE individuals showed significantly lower task-related performance and activation in regions known to be associated with arithmetic processing, including left superior and right inferior parietal regions and medial frontal gyrus, while the nondysmorphic PAE group was generally intermediate but not significantly different from the control group in task performance and activation. Conclusions: Results indicate that there is a range of effects of PAE on arithmetic processing and that the severity of this deficit may be dependent on degree of impairment demonstrated by the exposed individual. Evidence of physical dysmorphia may be indicative of functional damage to regions associated with arithmetic calculation, resulting in markedly impaired neuronal recruitment.

Schlotz W; Phillips DIW. Fetal origins of mental health: Evidence and mechanisms. (review). Brain, Behavior and Immunity 23(7): 905-916, 2009. (231 refs.)

The concept of fetal programming states that changes in the fetal environment during sensitive periods of organ development may cause long-lasting changes in the structure and functioning of these organs later in life and influence the risk for chronic diseases such as coronary heart disease and type 2 diabetes. Fetal growth is a summary marker of the fetal environment and is reflected by relatively easy-to-obtain measures of size at birth such as birth weight. In the last two decades, a body of evidence emerged linking fetal growth with behavioural and mental health outcomes later in life. Cognitive functioning and behavioural problems in childhood, in particular inattention/hyperactivity, have been shown to be inversely related to fetal growth. Although results are mixed, risk for personality disorders and schizophrenia seems to be linked with fetal growth and adversity, while the evidence for mood disorders is weak. Vulnerability for psychopathology may also be influenced by prenatal adversity. There is evidence for associations of fetal growth with temperament in childhood as well as stress reactivity and distress. The associations of fetal growth with mental health later in life are potentially caused by specific prenatal factors such as maternal smoking, alcohol, toxins/drugs, nutrition, psychosocial stress and infection during pregnancy. The mechanisms likely involve changes in neurodevelopment and in the set point of neuroendocrine systems, and there is evidence that prenatal adversity interacts with genetic and postnatal environmental factors. Future studies should examine the effects of specific prenatal factors and attempt to disentangle genetic and prenatal environmental effects.

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.

Simmons RW; Madra NJ; Levy SS; Riley EP; Mattson SN. Co-regulation of movement speed and accuracy by children with heavy prenatal alcohol exposure. Perceptual and Motor Skills 112(1): 172-182, 2011. (37 refs.)

The study investigated how children with heavy prenatal alcohol exposure regulate movement speed and accuracy during goal-directed movements. 16 children ages 7 to 17 years with confirmed histories of heavy in utero alcohol exposure, and 21 nonalcohol-exposed control children completed a series of reciprocal tapping movements between two spatial targets. 5 different targets sets were presented, representing a range of task difficulty between 2 and 6 bits of information. Estimates of percent error rate, movement time, slope, and linear fit of the resulting curve confirmed that for goal-directed, reciprocal tapping responses, performance of the group with prenatal alcohol exposure was described by a linear function, as predicted by Fitts' law, by sacrificing movement accuracy. The index of performance was the same for the two groups: it initially increased, then leveled off for more difficult movements.

Simmons RW; Thomas JD; Levy SS; Riley EP. Motor response programming and movement time in children with heavy prenatal alcohol exposure. Alcohol 44(4): 371-378, 2010. (49 refs.)

The present experiment assessed motor response programming and movement time in children with histories of heavy prenatal alcohol exposure (PEA). Alcohol-exposed children between the ages of 7 and 17 years were classified into two groups: Fetal Alcohol Syndrome (FAS: n = 9) and children with PEA (PEA: n = 19) but who did not have the defining characteristics of FAS. The FAS and PEA children were compared with non alcohol-exposed children (NC: n = 23) when completing two tasks: a simple reaction time task (RT alone condition) and a reaction plus movement task (RT + Move condition). The movement involved responding to an imperative stimulus signal and depressing three target buttons in a set sequence. Participants completed 24 trials each for the RT alone and RT Move response conditions. Results indicated no significant differences in performance among FAS, PEA, and NC groups during the RT alone condition. However, during the RT Move condition, the FAS group produced significantly longer and more variable RTs than the PEA and NC groups, which produced comparable RTs. The FAS group also produced significantly slower movement times when moving to all three targets, whereas movement time variability did not significantly differ as a function of group. The observed results indicate children with FAS experience deficits in response programming and movement time production.

Stavrou EP; Baker DF; Bishop JF. Maternal smoking during pregnancy and childhood cancer in New South Wales: A record linkage investigation. Cancer Causes and Control 20(9): 1551-1558, 2009. (78 refs.)

Following linkage between the NSW Central Cancer Registry (CCR) and the NSW Midwives Data Collection, an investigation of the association between maternal smoking during pregnancy and the risk of childhood cancer in their offspring was undertaken. Children born in NSW between 1994 and 2005, inclusive of 1,045,966 babies, were matched to 948 cancer cases in the CCR. After adjustment for maternal age, gestational age, baby's gender, birth weight, remoteness index, socioeconomic disadvantage and maternal health factors, no association (OR = 0.96, 95% CI 0.81-1.15, p = 0.68) was found with childhood cancer between mothers who smoked (81/100,000) and those who did not smoke during pregnancy (99/100, 000). Maternal smoking was, however, significantly associated with retinoblastoma (OR = 2.20, 95% CI 1.19-4.09, p = 0.01). Association between maternal smoking and preterm birth and low birth weight was significant. Maternal smoking during pregnancy is significantly associated with retinoblastoma and adverse birth outcomes. These results should be highlighted to expectant mothers through antitobacco-smoking campaigns.

Stone KC; High PC; Miller-Loncar CL; LaGasse LL; Lester BM. Longitudinal study of maternal report of sleep problems in children with prenatal exposure to cocaine and other drugs. Behavioral Sleep Medicine 7(4): 196-207, 2009. (47 refs.)

Sleep data were collected by maternal report in a prospective longitudinal follow up of cocaine-exposed and unexposed children. There were 139 participants: 23 with no prenatal drug exposure, 55 exposed to cocaine alone or in combination with other drugs, and 61 exposed to drugs other than cocaine. Characteristics differed between exposure groups including birth size, caretaker changes, maternal socioeconomic status, and postnatal drug use. Compared to those with no drug exposure, children with prenatal drug exposure other than cocaine experienced greater sleep problems (p = .026). Prenatal nicotine exposure was a unique predictor of sleep problems (p = .048). Early sleep problems predicted later sleep problems (all ps < .01). Together, these preliminary findings suggest possible neurotoxic sleep effects that persist over time. Larger studies, however, need to be conducted that better control for potential postnatal confounding factors.

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.

Whitaker TM; Bada HS; Bann CM; Shankaran S; LaGasse L; Lester BM et al. Serial pediatric symptom checklist screening in children with prenatal drug exposure. Journal of Developmental and Behavioral Pediatrics 32(3): 206-215, 2011. (38 refs.)

Objective: To examine screening results obtained by serial annual behavioral assessment of children with prenatal drug exposure. Method: The Maternal Lifestyle Study enrolled children with prenatal cocaine exposure (PCE) at birth for longitudinal assessments of developmental, behavioral, and health outcomes. At 8, 9, 10, 11, and 12 years of age, caregivers rated participants on the Pediatric Symptom Checklist (PSC). Serial PSC results were compared with an established broad-based behavioral measure at 9, 11, and 13 years. PSC results were analyzed for 1081 children who had at least 2 annual screens during the 5-year time span. Most subjects (87%) had 4 or more annual screens rated by the same caregiver (80%). PSC scores (and Positive screens) over time were compared at different time points for those with and without PCE. Covariates, including demographic factors and exposures to certain other substances, were controlled. Results: Children with PCE had significantly higher scores overall, with more Positive screens for behavior problems than children without PCE. Children with PCE had more externalizing behavior problems. Children exposed to tobacco prenatally and postnatally also showed higher PSC scores. Over time, PSC scores differed slightly from the 8-year scores, without clear directional trend. Earlier PSC results predicted later behavioral outcomes. Conclusion: Findings of increased total PSC scores and Positive PSC screens for behavioral concerns in this group of children with prenatal substance exposure support the growing body of evidence that additional attention to identification of mental health problems may be warranted in this high-risk group.

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.

Willford JA; Chandler LS; Goldschmidt L; Day NL. Effects of prenatal tobacco, alcohol and marijuana exposure on processing speed, visual-motor coordination, and interhemispheric transfer. Neurotoxicology and Teratology 32(6): 580-588, 2010. (120 refs.)

Deficits in motor control are often reported in children with prenatal alcohol exposure (PAE). Less is known about the effects of prenatal tobacco exposure (PTE) and prenatal marijuana exposure (PME) on motor coordination, and previous studies have not considered whether PTE, PAE, and PME interact to affect motor control. This study investigated the effects of PTE, PAE, and PME as well as current drug use on speed of processing, visual-motor coordination, and interhemispheric transfer in 16-year-old adolescents. Data were collected as part of the Maternal Health Practices and Child Development Project. Adolescents (age 16, n = 320) participating in a longitudinal study of the effects of prenatal substance exposure on developmental outcomes were evaluated in this study. The computerized Bimanual Coordination Test (BCT) was used to assess each domain of function. Other important variables, such as demographics, home environment, and psychological characteristics of the mother and adolescent were also considered in the analyses. There were significant and independent effects of PTE, PAE, and PME on processing speed and interhemispheric transfer of information. PTE and PME were associated with deficits in visual-motor coordination. There were no interactions between PAE. PTE, and PME. Current tobacco use predicted deficits in speed of processing. Current alcohol and marijuana use by the offspring were not associated with any measures of performance on the BCT.

Wouldes TA; Woodward LJ. Maternal methadone dose during pregnancy and infant clinical outcome. Neurotoxicology and Teratology 32(3): 406-413, 2010. (71 refs.)

In recent decades there has been an increase in the methadone dosages prescribed for opioid dependent women during pregnancy. Using prospective longitudinal data from a cohort of 32 methadone exposed and 42 non-methadone exposed infants, this study examined the relationship between maternal methadone dose during pregnancy and a range of infant clinical outcomes. Of particular interest was the extent to which any observed associations might reflect the direct causal effects of maternal methadone dose and/or the confounding effects of adverse maternal lifestyle factors correlated with methadone use during pregnancy. Findings revealed the presence of clear linear relationships between the mean methadone dose prescribed for mothers during pregnancy and a range of adverse infant clinical outcomes. With increasing maternal methadone dose there was a corresponding increase in infants' risk of being born preterm, being symmetrically smaller, spending longer periods in hospital and the need for treatment for Neonatal Abstinence Syndrome. After due allowance for potentially confounding maternal health and lifestyle factors, maternal methadone dose during pregnancy remained a significant predictor of preterm birth, growth, and the duration of infant hospitalization post delivery. These findings suggest a need to examine more closely the potential impacts of recent trends towards the use of higher methadone dose levels during pregnancy.

Xu XH; Cook RL; Ilacqua VA; Kan HD; Talbott EO. Racial differences in the effects of postnatal environmental tobacco smoke on neurodevelopment. Pediatrics 126(4): 705-711, 2010. (38 refs.)

OBJECTIVES: We used the 2001-2004 National Health and Nutrition Examination Survey to examine the association between postnatal environmental tobacco smoke exposure, measured as serum cotinine levels, and attention-deficit/hyperactivity disorder (ADHD) among children 4 to 15 years of age. We further investigated the interactions of race and serum cotinine levels with ADHD. METHODS: Logistic regression models were used to evaluate associations. RESULTS: This study found that the prevalence of ADHD increased as blood cotinine levels increased. The effects of blood cotinine levels on ADHD differed according to race. Compared with children of the same racial group with the lowest blood cotinine levels, the odds ratios were 2.72 (95% confidence interval: 1.25-5.93) for Mexican American children and 5.32 (95% confidence interval: 1.55-18.3) for children in other racial groups with the highest blood cotinine levels, with controlling for the effect of maternal smoking during pregnancy. However, no significant associations between blood cotinine levels and ADHD were observed among non-Hispanic white or non-Hispanic black children. CONCLUSIONS: The findings of this study underscore the possibility of racial disparities in the effects of environmental tobacco smoke on behavioral problems in children. These findings warrant further investigation.

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.

Zammit S; Thomas K; Thompson A; Horwood J; Menezes P; Gunnell D et al. Maternal tobacco, cannabis and alcohol use during pregnancy and risk of adolescent psychotic symptoms in offspring. British Journal of Psychiatry 195(4): 294-300, 2009. (52 refs.)

Background: Adverse effects of maternal substance use during pregnancy on fetal development may increase risk of psychopathology. Aims To examine whether maternal use of tobacco, cannabis or alcohol during pregnancy increases risk of offspring psychotic symptoms. Method A longitudinal study of 6356 adolescents, age 12, who completed a semi-structured interview for psychotic symptoms in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Results Frequency of maternal tobacco use during pregnancy was associated with increased risk of suspected or definite psychotic symptoms (adjusted odds ratio 1.20, 95% CI 1.05-1.37, P=0.007). Maternal alcohol use showed a non-linear association with psychotic symptoms, with this effect almost exclusively in the offspring of women drinking >21 units weekly. Maternal cannabis use was not associated with psychotic Symptoms. Results for paternal smoking during pregnancy and maternal smoking post-pregnancy lend some support for a causal effect of tobacco exposure in utero on development of psychotic experiences. Conclusions: These findings indicate that risk factors for development of non-clinical psychotic experiences may operate during early development. Future studies of how in utero exposure to tobacco affects cerebral development and function may lead to increased understanding of the pathogenesis of psychotic phenomena.