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Slide 1 Prenatal Smoke Exposure and Psychiatric Outcomes Beth Bailey, Ph. D Assistant Professor, Slide 1 Prenatal Smoke Exposure and Psychiatric Outcomes Beth Bailey, Ph. D Assistant Professor, Department of Family Medicine East Tennessee State University Director, Tennessee Intervention for Pregnant Smokers

Slide 2 Background Mental health problems in children are recognized as a serious source Slide 2 Background Mental health problems in children are recognized as a serious source of health morbidity, with negative consequences for the children themselves, their families, and their communities l Social and genetic factors are typically recognized as impacting mental health in children l Environmental factors may also play a significant role, but are often overlooked for their role in impacting child mental health l

Slide 3 Background While environmental influences can influence child health and development at any Slide 3 Background While environmental influences can influence child health and development at any time, those that occur during the prenatal period have the potential for the most significant impact l Many prenatal environmental influences have been examined, including infection, trauma, and hormonal variations l Prenatal toxin exposure has received the most attention in terms of the impact it may have on subsequent child development l

Slide 4 Background Many toxins have been examined, including lead, mercury, and PCBs l Slide 4 Background Many toxins have been examined, including lead, mercury, and PCBs l Effects include l – Lead: decreased IQ, decreased executive function, working memory problems, behaviour problems (conduct) – Mercury: findings are mixed and highly confounded with SES; specific IQ decreases have been noted – PCBs: decreased IQ, problems with sustained attention, flexibility and working memory; also increased impulsivity and generalized behaviour problems

Slide 5 Background l Exposure to illicit drugs prenatally has also been implicated in Slide 5 Background l Exposure to illicit drugs prenatally has also been implicated in influencing child outcomes, as has prenatal alcohol exposure – Illicit drugs: marijuana linked with cognitive deficits, attention problems, hearing perception, depression, and delinquency; cocaine linked with attention problems, language deficits, conduct problems, achievement delays – Alcohol: high levels of exposure lead to FAS (physical, cognitive, and behavioural deficits); even lower levels – FASD – attention, working memory, and behavior problems

Slide 6 Background l Exposure to prescription drugs prenatally has also been implicated in Slide 6 Background l Exposure to prescription drugs prenatally has also been implicated in influencing child outcomes – Antidepressants: few large scale controlled studies; some evidence of link between SRIs and autistic spectrum disorder – Anti-epileptics: sodium valproate linked with autism (rate 8 times higher) – Steroids: link with behaviour problems, including aggression and distractibility

Slide 7 Background l The most common prenatal exposure, tobacco, has been found to Slide 7 Background l The most common prenatal exposure, tobacco, has been found to significantly impact immediate and long term child outcomes, including mental health

Slide 8 Smoking Prevalence l Nationally, 12. 6% of women smoke during pregnancy l Slide 8 Smoking Prevalence l Nationally, 12. 6% of women smoke during pregnancy l In Tennessee, 17. 1% of women smoke during pregnancy l And in Northeast Tennessee, the pregnancy smoking rate is 49. 0%

Slide 9 Effects of Smoking on Pregnancy l Ectopic pregnancy l IUGR l Placental Slide 9 Effects of Smoking on Pregnancy l Ectopic pregnancy l IUGR l Placental previa and abruption l PROM l Miscarriage l Preterm delivery

Slide 10 Effects of Pregnancy Smoking on Child Health l Low birth weight l Slide 10 Effects of Pregnancy Smoking on Child Health l Low birth weight l Growth restriction l Ear infections l Respiratory infections l Asthma and allergies l Elevated blood pressure l Elevated total cholesterol

Slide 11 Effects of Pregnancy Smoking on Child Cognitive Outcomes l Decreased global IQ Slide 11 Effects of Pregnancy Smoking on Child Cognitive Outcomes l Decreased global IQ and general cognitive functioning l Problems with visuoperceptual performance l Deficits in math performance l Deficits in spelling performance

Slide 12 Effects of Pregnancy Smoking on Child Psychiatric Outcomes Multiple mental health outcomes Slide 12 Effects of Pregnancy Smoking on Child Psychiatric Outcomes Multiple mental health outcomes have been studied in relation to prenatal cigarette exposure: • • • ADHD Conduct disorders (child) Criminal behavior (adult) Depression/anxiety disorders Substance use/abuse/dependence Autism

Slide 13 Effects of Pregnancy Smoking on Child Psychiatric Outcomes Important methodologic considerations: • Slide 13 Effects of Pregnancy Smoking on Child Psychiatric Outcomes Important methodologic considerations: • • Sample size (and # of exposed) • Assessment of psychiatric outcomes (checklists, diagnostic interviews; sources of information) • Control for confounding (demographic factors, family/environmental factors, other prenatal exposures; co-morbid disorders); issue of causality Assessment of prenatal cigarette exposure (retrospective vs prospective; amount, timing)

Slide 14 Attention Problems • Most frequently reported outcome associated with prenatal cigarette exposure Slide 14 Attention Problems • Most frequently reported outcome associated with prenatal cigarette exposure • Findings have been consistent across diverse samples and both genders • Effects have been described for ADHD diagnosis as well as differing levels of attentional problems

Slide 15 Attention Problems Button et al (2005) • British sample • N=1896 twin Slide 15 Attention Problems Button et al (2005) • British sample • N=1896 twin pairs, ages 5 -18 • Retrospective report of pregnancy smoking with amount smoked per day collapsed into 4 categories • Du. Paul ADHD Rating Scale • Significant association between amount of prenatal smoke exposure and ADHD scale scores

Slide 16 Attention Problems Nigg & Breslau (2007) • U. S. sample (southeastern Michigan) Slide 16 Attention Problems Nigg & Breslau (2007) • U. S. sample (southeastern Michigan) • N=713; assessments at ages 6, 11, and 17 • Retrospective report of pregnancy smoking • • • (never, not during pregnancy, during pregnancy) DISC 2 interview with mother, DIS interview with kids at age 17, and Achenbach TRF combined for ADHD diagnosis Prenatal smoke exposure significantly associated with ADHD diagnosis Relationship persisted after control for LBW, but not after control for maternal substance use and education level

Slide 17 Attention Problems Thapar et al (2003) • British sample • N=1452 twin Slide 17 Attention Problems Thapar et al (2003) • British sample • N=1452 twin pairs; ages 5 -16 • Retrospective report of amount of pregnancy • • • smoking (collapsed into 4 groups) Teacher report rating scale of DSM-IV symptoms of ADHD – total symptom severity score Prenatal smoke exposure significantly associated with ADHD scores Relationship persisted after control for potential demographic and environmental confounders, including birth weight

Slide 18 Attention Problems Mick et al (2003) • U. S. sample (Boston area) Slide 18 Attention Problems Mick et al (2003) • U. S. sample (Boston area) • N=522; ages 6 -17 • Retrospective report of amount of pregnancy • • • smoking (collapsed into pack/day+ vs rest) K-SADS-E interview for ADHD diagnosis Exposure to pack/day+ prenatally more than doubled the risk for ADHD; only variables more predictive were parental ADHD diagnosis and prenatal alcohol exposure Relationship persisted after control for potential confounders, including family environment, CD and other prenatal exposures; no differential effects by gender

Slide 19 Attention Problems Milberger et al (1998) • U. S. sample (Boston area) Slide 19 Attention Problems Milberger et al (1998) • U. S. sample (Boston area) • N=300; ages 6 -17 • Retrospective report of amount of pregnancy • • • smoking (collapsed into pack/day+ vs rest) K-SADS-E interview for ADHD diagnosis Of those with ADHD, 47% were exposed to ppd+ during gestation; of those without ADHD, only 24% were exposed Relationship persisted after control for potential confounders, including maternal ADHD and birth weight; no differential effects by gender

Slide 20 Attention Problems Fergusson et al (1993) • New Zealand sample • N=1000 Slide 20 Attention Problems Fergusson et al (1993) • New Zealand sample • N=1000 (approx); assessed at ages 8, 10, & 12 • Amount of pregnancy smoking assessed at birth • • • (avg # cig/day across pregnancy collapsed into 3 groups) Modified Rutter & Conners completed by parent and teacher – total score for attention deficit Amount of smoke exposure significantly related to attention deficit at all 3 time periods – pack/day+ associated with highest scores Relationship persisted after control for potential confounders, including postnatal smoke exposure

Slide 21 Attention Problems Indredavik et al (2007) • Norwegian sample • N=84 (32 Slide 21 Attention Problems Indredavik et al (2007) • Norwegian sample • N=84 (32 smoke exposed); aged 14 • Amount of pregnancy smoking assessed during • • • pregnancy (collapsed into y/n) Multiple sources of data on ADHD including Achenbach CBCL, TRF, YSR; also ADHD Rating Scale IV Prenatal smoke exposure significantly related to attention problems across all methods of assessment Relationships persisted after control for potential confounders, including birth weight, and maternal mental health and current substance use; no differential gender effects

Slide 22 Attention Problems Wakschlag et al (2006) • U. S sample (Pittsburgh area) Slide 22 Attention Problems Wakschlag et al (2006) • U. S sample (Pittsburgh area) • N=448; ages 7 -19 (males only) • Amount of pregnancy smoking assessed • • • retrospectively at age 7 as exposed (daily pregnancy smokers) and on-exposed (never or occasional smoking) DISC-R interview with parents for ADHD diagnosis Prenatal smoke exposure NOT significantly related to ADHD after control for confounding Controlled for ODD which overlapped significantly with ADHD –little variance left; also sample all boys, retrospective assessment of smoking which was crudely assessed

Slide 23 Attention Problems Conclusions • Significant evidence that prenatal smoke • • • Slide 23 Attention Problems Conclusions • Significant evidence that prenatal smoke • • • exposure is associated with attention problems Association appears to be dose dependent (those exposed at highest levels up to three times as likely to have attentional deficits) Association does not appear to be gender specific Association does not appear to be due to potentially confounding factors, including maternal co-morbidity, family environment, LBW, or post-natal smoke exposure

Slide 24 Conduct Disorders Included here – CD, aggressive behavior, delinquency Brook et al Slide 24 Conduct Disorders Included here – CD, aggressive behavior, delinquency Brook et al (2006) • U. S. sample (NY City) • N=203; ages 8 -12 • Amount of pregnancy smoking assessed • • • retrospectively at age 8+; collapsed into 5 categories Aggressive behavior scores from maternal report (unpublished rating scale with 6 items) Level of prenatal smoke exposure significantly related to aggressive behavior scores (r=. 28) Effect remained after control for confounding demographics and current maternal smoking; no differential gender effect

Slide 25 Conduct Disorders Williams et al (1998) • Australian sample • N=5342; aged Slide 25 Conduct Disorders Williams et al (1998) • Australian sample • N=5342; aged 5 • Amount of pregnancy smoking assessed during • • • pregnancy (avg # cig/day) Externalizing behavior scores from maternal report (CBCL) – dichotomized at 90 th %ile Level of prenatal smoke exposure significantly related to externalizing behavior scores; 20+ cig/day at first prenatal visit associated with RR=2. 6 Effect remained after control for confounding demographics and postnatal smoke exposure

Slide 26 Conduct Disorders Fergusson et al (1993) • New Zealand sample • N=1000 Slide 26 Conduct Disorders Fergusson et al (1993) • New Zealand sample • N=1000 (approx); assessed at ages 8, 10 & 12 • Amount of pregnancy smoking assessed at birth • • • (avg # cig/day collapsed into 3 groups) Conduct disorder scores from maternal & report (modified Rutter and Conners) Level of prenatal smoke exposure significantly related to conduct disorder scores at all 3 time periods; 20+ cig/day at first prenatal visit associated with highest scores Effect remained after control for confounding demographics and postnatal smoke exposure

Slide 27 Conduct Disorders Fergusson et al (1998) • New Zealand sample • N=1000 Slide 27 Conduct Disorders Fergusson et al (1998) • New Zealand sample • N=1000 (approx); assessed at age 18 • Amount of pregnancy smoking assessed at birth • • • (avg # cig/day collapsed into 4 groups) Conduct disorder diagnosis and symptom rates from Composite International Diagnostic Inventory Level of prenatal smoke exposure significantly related to conduct disorder scores; 20+ cig/day associated 2. 5 times higher symptom rates Effect remained after control for confounding demographics and environmental factors; effects were stronger for males

Slide 28 Conduct Disorders Nigg & Breslau (2007) • U. S. sample (MI) • Slide 28 Conduct Disorders Nigg & Breslau (2007) • U. S. sample (MI) • N=713; assessed at ages 6, 11 & 17 • Amount of pregnancy smoking assessed at age • • • 6 (3 groups) CD and ODD diagnoses from DISC maternal interview (ages 6 & 11), and DIS with 17 year olds Prenatal smoke exposure significantly related to lifetime ODD (2+xs higher risk); effect remained after control for LBW and other factors Prenatal smoke exposure significantly related to lifetime CD, but not after control for ODD (consistent with known dvptl pathway)

Slide 29 Conduct Disorders Wakschlag et al (2006) • U. S. sample (Pittsburgh area) Slide 29 Conduct Disorders Wakschlag et al (2006) • U. S. sample (Pittsburgh area) • N=448; all boys; ages 7 -19 • Amount of pregnancy smoking assessed at age • • • 7 (daily vs never/occasional) ODD diagnosis from DISC parental interview; Self-Reported Antisocial Behavior and Delinquency Scales to assess onset of delinquency and level of severity Prenatal smoke exposure increased risk of ODD 3 xs (11. 4% vs 3. 9%) The age at onset of significant delinquency was significantly earlier for exposed boys (2 year difference – age 13 vs age 15)

Slide 30 Conduct Disorders Maughan et al (2001) • British sample • N=5770; assessed Slide 30 Conduct Disorders Maughan et al (2001) • British sample • N=5770; assessed at ages 5, 10 & 16 • Amount of pregnancy smoking assessed at birth (5 • • • categories) Rutter A 2 behavior rating scales completed by parents, scores on conduct problems scale dichotimized at 90 th %ile; adolescent report also used at age 16, dichotomized at 88%ile Prenatal smoke exposure associated with conduct problems at ages 5 and 10, but not at age 16 (effects for child but not adol onset) Effects remained after control for confounders and postnatal smoke exposure; however, effects were much stronger if smoke exposure continued into childhood

Slide 31 Conduct Disorders Monuteaux et al (2006) • U. S. sample (Providence, RI Slide 31 Conduct Disorders Monuteaux et al (2006) • U. S. sample (Providence, RI area) • N=682; assessed at age 22 (reporting on symptoms • • prior to age 18) Amount of pregnancy smoking assessed during pregnancy (# cig/day collapsed into 3 categories) DIS-III self-report of symptoms in childhood – symptom counts for overt and covert conduct disorder symptoms Prenatal smoke exposure NOT significantly related to overt or covert symptoms after control for confounders; no differential gender effect However, among the lowest SES, both moderate and heavy prenatal cigarette exposure predicted overt, but not covert, CD symptoms (RR=2. 1)

Slide 32 Conduct Disorders Conclusions • Significant evidence that prenatal smoke exposure • • Slide 32 Conduct Disorders Conclusions • Significant evidence that prenatal smoke exposure • • is associated with externalizing problems, including levels of aggression, delinquency, and diagnosis of ODD and CD There is also significant evidence that the association is dose dependent (3 Xs the risk) Moderate evidence that the effect may be more pronounced for boys, or at least that boys and girls may be differentially affected Some evidence that in addition to higher levels of externalizing problems, prenatal cigarette exposure is associated with earlier onset of problems Some evidence that the symptoms of conduct problems associated with prenatal smoke exposure may be more likely to be overt rather than covert

Slide 33 Criminal Behavior Brennan et al (1999) • Danish sample • N=4169; birth Slide 33 Criminal Behavior Brennan et al (1999) • Danish sample • N=4169; birth cohort at age 33 -35 (all male) • Amount of pregnancy smoking assessed prenatally • • • and at birth (# cig/day collapsed into 5 categories) Danish National Criminal Register provided dichotomous data on nonviolent crime, persistent crime, and adolescent limited offending Prenatal smoke exposure not associated with adolescent limited offending, but significantly associated with all 3 types of adult offending (exposure to pack+/day – two-fold increased risk) Effects remained after control for confounding (delivery complications reduced effect – no other significant confounders)

Slide 34 Criminal Behavior Rasanen et al (1999) • Finnish sample • N=5514; birth Slide 34 Criminal Behavior Rasanen et al (1999) • Finnish sample • N=5514; birth cohort at age 28 (all male) • Amount of pregnancy smoking assessed prenatally • Ministry of Justice database of all crimes committed • • • in Finland – classified as nonviolent and violent Non-offenders: 14. 1% had prenatal smoke exposure non-violent offenders: 21. 1% violent offenders: 33. 1% Those with any prenatal smoke exposure were twice as likely to have committed at least 1 violent crime and to have committed more than 1 offense Effects remained after control for confounding

Slide 35 Criminal Behavior Brennan et al (2002) • Danish sample • N=8112; birth Slide 35 Criminal Behavior Brennan et al (2002) • Danish sample • N=8112; birth cohort at age 40 (male & female) • Amount of pregnancy smoking assessed • • prenatally and at birth (# cig/day collapsed into 4 groups) Danish National Criminal Register provided data on criminal arrests Prenatal cigarette exposure was significantly associated with history of criminal arrest – 10+ cig/day associated with a 1. 6 xs increase for males, and a 1. 4 xs increase for females after control for confounders

Slide 36 Criminal Behavior Conclusions • Moderate evidence that prenatal smoke • • exposure Slide 36 Criminal Behavior Conclusions • Moderate evidence that prenatal smoke • • exposure is associated with criminal behavior into adulthood Moderate evidence that the association is dose dependent Preliminary evidence that effect occurs for both males and females; however, effect may be more pronounced for males (aggression may take different form for females? ) Effect does not appear to be a result of confounding environmental factors Additional studies with more diverse populations needed

Slide 37 Depression/Anxiety Disorders Williams et al (1998) • Australian sample • N=5342; age Slide 37 Depression/Anxiety Disorders Williams et al (1998) • Australian sample • N=5342; age 5 • Amount of pregnancy smoking assessed prenatally • • (# cig/day) Achenbach CBCL provided data on internalizing problems (anxiety/depression, anxiety dichotomized at 90 th %ile) Rates of internalizing behaviors were significantly higher in children who were exposed to ppd+ prenatally Results persisted after control for confounding Association with internalizing behaviors weaker than association with externalizing behaviors

Slide 38 Depression/Anxiety Disorders Indredavik et al (2007) • Norwegian sample • N=84; age Slide 38 Depression/Anxiety Disorders Indredavik et al (2007) • Norwegian sample • N=84; age 14 • Amount of pregnancy smoking assessed prenatally • • (# cig/day collapsed into y/n) Achenbach CBCL, TRF, YSR provided data on internalizing problems Rates of internalizing behaviors were significantly higher in children who had any prenatal smoke exposure However, effects no longer significant after control for confounding (LBW, maternal mental health, current maternal substance use) No differential gender effects

Slide 39 Depression/Anxiety Disorders Fergusson et al (1998) • New Zealand sample • N=1022; Slide 39 Depression/Anxiety Disorders Fergusson et al (1998) • New Zealand sample • N=1022; longitudinal cohort at age 18 • Amount of pregnancy smoking assessed at birth (# • • cig/day collapsed into 4 groups) Composite International Diagnostic Interview & Seld. Report Delinquency Inventory – used DSM-IV criteria to construct diagnoses of generalized anxiety disorder and major depression; also scales with # of symptoms reported Depression, but not anxiety disorder significantly associated with ppd+ prenatal exposure Effects not significant after control for confounding (SES, poor child rearing, parental/family problems) Effects stronger for boys

Slide 40 Depression/Anxiety Disorders Weissman et al (1999) • U. S. sample (NY) • Slide 40 Depression/Anxiety Disorders Weissman et al (1999) • U. S. sample (NY) • N=147; longitudinal cohort at ages 17 -36 • Pregnancy smoking assessed retrospectively at • • • first assessment (10+ cig/day vs rest) SADS-LA interview for major depressive disorder and anxiety disorder Neither depression no anxiety associated with prenatal cigarette exposure after control for confounding Rates of depression and anxiety low in the sample

Slide 41 Depression/Anxiety Disorders Conclusions • Inconclusive evidence that prenatal smoke • • exposure Slide 41 Depression/Anxiety Disorders Conclusions • Inconclusive evidence that prenatal smoke • • exposure is associated with internalizing problems, including depression and anxiety If effects are present, they appear to be weaker than those for externalizing problems Effects may be due to mediating factors, including parental psychopathology and child rearing environment It is unclear if boys and girls are differentially affected Additional studies with larger and more diverse populations needed

Slide 42 Substance Use Brennan et al (2002) • Danish sample • N=8112; birth Slide 42 Substance Use Brennan et al (2002) • Danish sample • N=8112; birth cohort at age 40 (male & female) • Amount of pregnancy smoking assessed • • • prenatally and at birth (# cig/day collapsed into 4 groups) Psychiatric hospitalizations for substance abuse and other factors were determined Prenatal cigarette exposure was significantly associated with substance abuse hospitalization – 10+ cig/day associated with a 2. 2 xs increase for males, and a 2. 7 xs increase for females after control for confounders No association with other types of psychiatric hospitalization

Slide 43 Substance Use Weissman et al (1999) • U. S. sample (NY) • Slide 43 Substance Use Weissman et al (1999) • U. S. sample (NY) • N=147; longitudinal cohort at ages 17 -36 • Pregnancy smoking assessed retrospectively at • • • first assessment (10+ cig/day vs rest) SADS-LA interview for drug dependence/abuse Drug abuse/dependence associated with prenatal cigarette exposure after control for confounding, but only for females; relative risk of diagnosis associated with 10+cig/day was 5. 4 Substance abuse/dependence associated with prenatal exposure emerged between ages of 13 and 17

Slide 44 Substance Use Fergusson et al (1998) • New Zealand sample • N=1022; Slide 44 Substance Use Fergusson et al (1998) • New Zealand sample • N=1022; longitudinal cohort at age 18 • Amount of pregnancy smoking assessed at birth (# • • • cig/day collapsed into 4 groups) Composite International Diagnostic Interview & Seld. Report Delinquency Inventory – used DSM-IV criteria to construct diagnoses of alcohol abuse/dependence and illicit substance use/dependence; also scales with # of symptoms reported Both alcohol and illicit substance use/dependence significantly associated with ppd+ prenatal exposure Effects not significant after control for confounding (SES, poor child rearing, parental/family problems)

Slide 45 Substance Use Conclusions • Preliminary evidence that prenatal smoke • • • Slide 45 Substance Use Conclusions • Preliminary evidence that prenatal smoke • • • exposure is associated with substance use, including abuse/dependence of alcohol, and use/dependence of illicit substances Preliminary evidence suggests effects may be more likely to occur among females Effects may be due, at least in part, to mediating factors, including parental psychopathology and child rearing environment Additional studies with larger and more diverse populations needed

Slide 46 Tobacco Use/Dependence Buka et al (2003) • U. S. sample (RI) • Slide 46 Tobacco Use/Dependence Buka et al (2003) • U. S. sample (RI) • N=1248; longitudinal cohort at avg age 29 • Amount of pregnancy smoking assessed prenatally • • (3 grps) NIMH DIS-III assessed nicotine and marijuana dependence Exposure to ppd+ prenatally significantly associated with nicotine dependence after control for confounding (risk inc two-fold) No effects for ever smoking or regular smoking for the full sample; Effects much stronger for males, and even signif for ever smoked and regular smoking No effects for marijuana use or dependence

Slide 47 Tobacco Use/Dependence Mamun et al (2006) • Australian sample • N=3058; longitudinal Slide 47 Tobacco Use/Dependence Mamun et al (2006) • Australian sample • N=3058; longitudinal cohort at avg age 21 • Amount of pregnancy smoking assessed prenatally • • and at birth (3 grps) Standardized questions of smoking history Any prenatal smoke exposure was significantly associated with later smoking – those who were exposed were 2. 7 times more likely to start smoking by age 14 and to smoke regularly; 2. 1 times more likely to start smoking at age 15+ than those with no exposure Exposure to postnatal smoking was associated with smoking history, but not as strongly as prenatal exposure Effects remained after control for confounders

Slide 48 Tobacco Use/Dependence Cornelius et al (2005) • U. S. sample (Pittsburgh area) Slide 48 Tobacco Use/Dependence Cornelius et al (2005) • U. S. sample (Pittsburgh area) • N=567; longitudinal cohort at avg age 14 • Amount of pregnancy smoking assessed prenatally • • (# cig/day) Questions on smoking history, adapted from the Health Behavior Questionnaire; also urine cotinine Prenatal smoke exposure significantly predicted any later smoking after control for confounding, including postnatal exposure; level of smoking and age at onset of smoking not significant after control for confounding (14 yrs old, though) Dose response relationship – exposure throughout pregnancy associated with highest rates of adolescent smoking No differential gender effects

Slide 49 Tobacco Use/Dependence Cornelius et al (2000) • U. S. sample (Pittsburgh area) Slide 49 Tobacco Use/Dependence Cornelius et al (2000) • U. S. sample (Pittsburgh area) • N=589; longitudinal cohort at avg age 10 • Amount of pregnancy smoking assessed prenatally • • • (# cig/day) Standardized smoking history questions used (collapsed into ever smoked vs never smoked) Prenatal smoke exposure significantly predicted early tobacco experimentation after control for confounding, including postnatal exposure RR=5. 5) Postnatal exposure did NOT independently predict smoking

Slide 50 Tobacco Use/Dependence Conclusions • Significant evidence that prenatal smoke • • • Slide 50 Tobacco Use/Dependence Conclusions • Significant evidence that prenatal smoke • • • exposure is associated with later smoking initiation and continuation Effects are particularly pronounced for early initiation, and development of dependence once begin smoking Moderate evidence that association is dosedependent Preliminary evidence suggests effects may be more pronounced in males Effects do not appear to be due to confounding factors, including postnatal exposure Additional studies with larger and more diverse populations needed

Slide 51 Autism • Only one published study that has examined • • the Slide 51 Autism • Only one published study that has examined • • the association between prenatal cigarette exposure and autism Indredavik (2007) – using prospectively collected prenatal smoking data and the Autism Spectrum Screening Questionnaire – found significantly higher autism scores for those exposed to any level of smoke prenatally; effects remained after control for confounding; no differential gender effects While no published studies report no effect, additional study is clearly needed with larger samples and more thorough assessment of Autism to verify the possible link

Slide 52 Mechanisms • Why might prenatal smoke exposure impact • mental health outcomes? Slide 52 Mechanisms • Why might prenatal smoke exposure impact • mental health outcomes? Several possible explanations have been proposed, and are based on two potential primary mechanisms: • Hypoxic effects on the placenta and fetus • Teratologic effects on the developing nervous system • Reduction in blood flow – implicated in cell • death, delayed development, and missed critical periods for nervous system development Neurobehavioral teratogens – most evidence suggests carbon monoxide and nicotine are key (both cross placental barrier)

Slide 53 Mechanisms • Effects may be structural, neuroregulatory, • neurobehavioral, or involve all Slide 53 Mechanisms • Effects may be structural, neuroregulatory, • neurobehavioral, or involve all three Human studies have shown prenatal cigarette exposure to be associated with reduced fetal head growth involving: • head circumference • biparietal diameter • smaller atrial width of lateral ventricle • smaller transcerebellar diameter • Animal studies have shown increased incidence of apoptotic cells in all brain areas, especially the cortex and cerebellum, and damage to the developing epithelium

Slide 54 Mechanisms • Noted structural alterations associated with • prenatal cigarette exposure have Slide 54 Mechanisms • Noted structural alterations associated with • prenatal cigarette exposure have been associated with many of the outcomes linked to prenatal cigarette exposure Cell death and smaller relative brain area size have been associated with • deficits in cognitive function • delays in neupsychological abilities • schizophrenia • autism • Thus, structural alteratins may be one pathway through which prenatal smoke exposure influences child outcomes

Slide 55 Mechanisms • Xx- neurochemical effects Slide 55 Mechanisms • Xx- neurochemical effects

Slide 56 Clinical Implications • XX Slide 56 Clinical Implications • XX

Slide 57 Prevention Efforts in NE TN • XX Slide 57 Prevention Efforts in NE TN • XX