slide 1 prenatal smoke exposure and psychiatric outcomes beth bailey, phd assistant professor,...

Prenatal Smoke Exposure Prenatal Smoke Exposure and Psychiatric Outcomesand Psychiatric Outcomes

Beth Bailey, PhDBeth Bailey, PhDAssistant Professor, Department of Family MedicineAssistant Professor, Department of Family Medicine

East Tennessee State UniversityEast Tennessee State UniversityDirector, Tennessee Intervention for Pregnant SmokersDirector, Tennessee Intervention for Pregnant Smokers

BackgroundBackground Mental health problems in children are Mental health problems in children are

recognized as a serious source of health recognized as a serious source of health morbidity, with negative consequences for morbidity, with negative consequences for the children themselves, their families, and the children themselves, their families, and their communitiestheir communities

Social and genetic factors are typically Social and genetic factors are typically recognized as impacting mental health in recognized as impacting mental health in childrenchildren

Environmental factors may also play a Environmental factors may also play a significant role, but are often overlooked for significant role, but are often overlooked for their role in impacting child mental healththeir role in impacting child mental health

BackgroundBackground While environmental influences can While environmental influences can

influence child health and development at influence child health and development at any time, those that occur during the any time, those that occur during the prenatal period have the potential for the prenatal period have the potential for the most significant impactmost significant impact

Many prenatal environmental influences Many prenatal environmental influences have been examined, including infection, have been examined, including infection, trauma, and hormonal variationstrauma, and hormonal variations

Prenatal toxin exposure has received the Prenatal toxin exposure has received the most attention in terms of the impact it may most attention in terms of the impact it may have on subsequent child developmenthave on subsequent child development

BackgroundBackground Many toxins have been examined, including Many toxins have been examined, including

lead, mercury, and PCBslead, mercury, and PCBs Effects includeEffects include

– Lead: decreased IQ, decreased executive function, Lead: decreased IQ, decreased executive function, working memory problems, behaviour problems working memory problems, behaviour problems (conduct)(conduct)

– Mercury: findings are mixed and highly confounded Mercury: findings are mixed and highly confounded with SES; specific IQ decreases have been notedwith SES; specific IQ decreases have been noted

– PCBs: decreased IQ, problems with sustained PCBs: decreased IQ, problems with sustained attention, flexibility and working memory; also attention, flexibility and working memory; also increased impulsivity and generalized behaviour increased impulsivity and generalized behaviour problemsproblems

BackgroundBackground Exposure to illicit drugs prenatally has also Exposure to illicit drugs prenatally has also

been implicated in influencing child been implicated in influencing child outcomes, as has prenatal alcohol exposureoutcomes, as has prenatal alcohol exposure– Illicit drugs: marijuana linked with cognitive Illicit drugs: marijuana linked with cognitive

deficits, attention problems, hearing perception, deficits, attention problems, hearing perception, depression, and delinquency; cocaine linked depression, and delinquency; cocaine linked with attention problems, language deficits, with attention problems, language deficits, conduct problems, achievement delaysconduct problems, achievement delays

– Alcohol: high levels of exposure lead to FAS Alcohol: high levels of exposure lead to FAS (physical, cognitive, and behavioural deficits); (physical, cognitive, and behavioural deficits); even lower levels – FASD – attention, working even lower levels – FASD – attention, working memory, and behavior problemsmemory, and behavior problems

BackgroundBackground Exposure to prescription drugs Exposure to prescription drugs

prenatally has also been implicated in prenatally has also been implicated in influencing child outcomes influencing child outcomes – Antidepressants: few large scale controlled Antidepressants: few large scale controlled

studies; some evidence of link between SRIs studies; some evidence of link between SRIs and autistic spectrum disorderand autistic spectrum disorder

– Anti-epileptics: sodium valproate linked with Anti-epileptics: sodium valproate linked with autism (rate 8 times higher)autism (rate 8 times higher)

– Steroids: link with behaviour problems, Steroids: link with behaviour problems, including aggression and distractibilityincluding aggression and distractibility

BackgroundBackground The most common prenatal exposure, The most common prenatal exposure,

tobaccotobacco, has been found to , has been found to significantly impact immediate and long significantly impact immediate and long term child outcomes, including mental term child outcomes, including mental healthhealth

Smoking PrevalenceSmoking Prevalence

Nationally, Nationally, 12.6%12.6% of women smoke of women smoke during pregnancyduring pregnancy

In Tennessee, In Tennessee, 17.1%17.1% of women smoke of women smoke during pregnancyduring pregnancy

And in Northeast Tennessee, the And in Northeast Tennessee, the pregnancy smoking rate is pregnancy smoking rate is 49.0%49.0%

Effects of Smoking on PregnancyEffects of Smoking on Pregnancy

Ectopic pregnancyEctopic pregnancy

IUGRIUGR

Placental previa and abruptionPlacental previa and abruption

PROMPROM

MiscarriageMiscarriage

Preterm deliveryPreterm delivery

Effects of Pregnancy Smoking on Effects of Pregnancy Smoking on Child HealthChild Health

Low birth weightLow birth weight

Growth restrictionGrowth restriction

Ear infectionsEar infections

Respiratory infectionsRespiratory infections

Asthma and allergiesAsthma and allergies

Elevated blood pressureElevated blood pressure

Elevated total cholesterolElevated total cholesterol

Effects of Pregnancy Smoking on Effects of Pregnancy Smoking on Child Cognitive OutcomesChild Cognitive Outcomes

Decreased global IQ and general Decreased global IQ and general cognitive functioningcognitive functioning

Problems with visuoperceptual Problems with visuoperceptual performanceperformance

Deficits in math performanceDeficits in math performance

Deficits in spelling performanceDeficits in spelling performance

Effects of Pregnancy Smoking on Effects of Pregnancy Smoking on Child Psychiatric OutcomesChild Psychiatric Outcomes

Multiple mental health outcomes have been Multiple mental health outcomes have been studied in relation to prenatal cigarette studied in relation to prenatal cigarette exposure:exposure:

• ADHDADHD• Conduct disorders (child)Conduct disorders (child)• Criminal behavior (adult)Criminal behavior (adult)• Depression/anxiety disordersDepression/anxiety disorders• Substance use/abuse/dependenceSubstance use/abuse/dependence• AutismAutism

Effects of Pregnancy Smoking on Effects of Pregnancy Smoking on Child Psychiatric OutcomesChild Psychiatric Outcomes

Important methodologic considerations:Important methodologic considerations:

• Sample size (and # of exposed)Sample size (and # of exposed)

• Assessment of prenatal cigarette exposure Assessment of prenatal cigarette exposure (retrospective vs prospective; amount, timing)(retrospective vs prospective; amount, timing)

• Assessment of psychiatric outcomes (checklists, Assessment of psychiatric outcomes (checklists, diagnostic interviews; sources of information)diagnostic interviews; sources of information)

• Control for confounding (demographic factors, Control for confounding (demographic factors, family/environmental factors, other prenatal family/environmental factors, other prenatal exposures; co-morbid disorders); issue of exposures; co-morbid disorders); issue of causalitycausality

Attention ProblemsAttention Problems

• Most frequently reported outcome Most frequently reported outcome associated with prenatal cigarette associated with prenatal cigarette exposureexposure

• Findings have been consistent across Findings have been consistent across diverse samples and both gendersdiverse samples and both genders

• Effects have been described for ADHD Effects have been described for ADHD diagnosis as well as differing levels of diagnosis as well as differing levels of attentional problemsattentional problems


Button et al (2005)Button et al (2005) • British sampleBritish sample

• N=1896 twin pairs, ages 5-18N=1896 twin pairs, ages 5-18

• Retrospective report of pregnancy smoking with Retrospective report of pregnancy smoking with amount smoked per day collapsed into 4 amount smoked per day collapsed into 4 categoriescategories

• DuPaul ADHD Rating ScaleDuPaul ADHD Rating Scale

• Significant association between amount of Significant association between amount of prenatal smoke exposure and ADHD scale prenatal smoke exposure and ADHD scale scoresscores


Nigg & Breslau (2007)Nigg & Breslau (2007) • U.S. sample (southeastern Michigan)U.S. sample (southeastern Michigan)

• N=713; assessments at ages 6, 11, and 17N=713; assessments at ages 6, 11, and 17

• Retrospective report of pregnancy smoking (never, not Retrospective report of pregnancy smoking (never, not during pregnancy, during pregnancy)during pregnancy, during pregnancy)

• DISC 2 interview with mother, DIS interview with kids at DISC 2 interview with mother, DIS interview with kids at age 17, and Achenbach TRF combined for ADHD age 17, and Achenbach TRF combined for ADHD diagnosisdiagnosis

• Prenatal smoke exposure significantly associated with Prenatal smoke exposure significantly associated with ADHD diagnosisADHD diagnosis

• Relationship persisted after control for LBW, but not Relationship persisted after control for LBW, but not after control for maternal substance use and education after control for maternal substance use and education levellevel


Thapar et al (2003)Thapar et al (2003) • British sampleBritish sample

• N=1452 twin pairs; ages 5-16N=1452 twin pairs; ages 5-16

• Retrospective report of amount of pregnancy Retrospective report of amount of pregnancy smoking (collapsed into 4 groups)smoking (collapsed into 4 groups)

• Teacher report rating scale of DSM-IV symptoms of Teacher report rating scale of DSM-IV symptoms of ADHD – total symptom severity scoreADHD – total symptom severity score

• Prenatal smoke exposure significantly associated Prenatal smoke exposure significantly associated with ADHD scoreswith ADHD scores

• Relationship persisted after control for potential Relationship persisted after control for potential demographic and environmental confounders, demographic and environmental confounders, including birth weightincluding birth weight


Mick et al (2003)Mick et al (2003) • U.S. sample (Boston area)U.S. sample (Boston area)

• N=522; ages 6-17N=522; ages 6-17

• Retrospective report of amount of pregnancy smoking Retrospective report of amount of pregnancy smoking (collapsed into pack/day+ vs rest)(collapsed into pack/day+ vs rest)

• K-SADS-E interview for ADHD diagnosisK-SADS-E interview for ADHD diagnosis

• Exposure to pack/day+ prenatally more than doubled Exposure to pack/day+ prenatally more than doubled the risk for ADHD; only variables more predictive were the risk for ADHD; only variables more predictive were parental ADHD diagnosis and prenatal alcohol exposureparental ADHD diagnosis and prenatal alcohol exposure

• Relationship persisted after control for potential Relationship persisted after control for potential confounders, including family environment, CD and confounders, including family environment, CD and other prenatal exposures; no differential effects by other prenatal exposures; no differential effects by gendergender


Milberger et al (1998)Milberger et al (1998) • U.S. sample (Boston area)U.S. sample (Boston area)

• N=300; ages 6-17N=300; ages 6-17

• Retrospective report of amount of pregnancy Retrospective report of amount of pregnancy smoking (collapsed into pack/day+ vs rest)smoking (collapsed into pack/day+ vs rest)

• K-SADS-E interview for ADHD diagnosisK-SADS-E interview for ADHD diagnosis

• Of those with ADHD, 47% were exposed to ppd+ Of those with ADHD, 47% were exposed to ppd+ during gestation; of those without ADHD, only 24% during gestation; of those without ADHD, only 24% were exposedwere exposed

• Relationship persisted after control for potential Relationship persisted after control for potential confounders, including maternal ADHD and birth confounders, including maternal ADHD and birth weight; no differential effects by genderweight; no differential effects by gender


Fergusson et al (1993)Fergusson et al (1993) • New Zealand sampleNew Zealand sample

• N=1000 (approx); assessed at ages 8, 10, & 12N=1000 (approx); assessed at ages 8, 10, & 12

• Amount of pregnancy smoking assessed at birth (avg Amount of pregnancy smoking assessed at birth (avg # cig/day across pregnancy collapsed into 3 groups)# cig/day across pregnancy collapsed into 3 groups)

• Modified Rutter & Conners completed by parent and Modified Rutter & Conners completed by parent and teacher – total score for attention deficitteacher – total score for attention deficit

• Amount of smoke exposure significantly related to Amount of smoke exposure significantly related to attention deficit at all 3 time periods – pack/day+ attention deficit at all 3 time periods – pack/day+ associated with highest scoresassociated with highest scores

• Relationship persisted after control for potential Relationship persisted after control for potential confounders, including postnatal smoke exposureconfounders, including postnatal smoke exposure

Attention ProblemsAttention ProblemsIndredavik et al (2007)Indredavik et al (2007)

• Norwegian sampleNorwegian sample

• N=84 (32 smoke exposed); aged 14N=84 (32 smoke exposed); aged 14

• Amount of pregnancy smoking assessed during Amount of pregnancy smoking assessed during pregnancy (collapsed into y/n)pregnancy (collapsed into y/n)

• Multiple sources of data on ADHD including Achenbach Multiple sources of data on ADHD including Achenbach CBCL, TRF, YSR; also ADHD Rating Scale IVCBCL, TRF, YSR; also ADHD Rating Scale IV

• Prenatal smoke exposure significantly related to Prenatal smoke exposure significantly related to attention problems across all methods of assessmentattention problems across all methods of assessment

• Relationships persisted after control for potential Relationships persisted after control for potential confounders, including birth weight, and maternal confounders, including birth weight, and maternal mental health and current substance use; no differential mental health and current substance use; no differential gender effectsgender effects

Attention ProblemsAttention ProblemsWakschlag et al (2006)Wakschlag et al (2006)

• U.S sample (Pittsburgh area)U.S sample (Pittsburgh area)

• N=448; ages 7-19 (males only)N=448; ages 7-19 (males only)

• Amount of pregnancy smoking assessed retrospectively Amount of pregnancy smoking assessed retrospectively at age 7 as exposed (daily pregnancy smokers) and on-at age 7 as exposed (daily pregnancy smokers) and on-exposed (never or occasional smoking)exposed (never or occasional smoking)

• DISC-R interview with parents for ADHD diagnosisDISC-R interview with parents for ADHD diagnosis

• Prenatal smoke exposure NOT significantly related to Prenatal smoke exposure NOT significantly related to ADHD after control for confoundingADHD after control for confounding

• Controlled for ODD which overlapped significantly with Controlled for ODD which overlapped significantly with ADHD –little variance left; also sample all boys, ADHD –little variance left; also sample all boys, retrospective assessment of smoking which was retrospective assessment of smoking which was crudely assessedcrudely assessed


ConclusionsConclusions• Significant evidence that prenatal smoke Significant evidence that prenatal smoke

exposure is associated with attention problemsexposure is associated with attention problems

• Association appears to be dose dependent Association appears to be dose dependent (those exposed at highest levels up to three (those exposed at highest levels up to three times as likely to have attentional deficits)times as likely to have attentional deficits)

• Association does not appear to be gender Association does not appear to be gender specificspecific

• Association does not appear to be due to Association does not appear to be due to potentially confounding factors, including potentially confounding factors, including maternal co-morbidity, family environment, LBW, maternal co-morbidity, family environment, LBW, or post-natal smoke exposureor post-natal smoke exposure

Conduct DisordersConduct DisordersIncluded here – CD, aggressive behavior, delinquency

Brook et al (2006)Brook et al (2006) • U.S. sample (NY City)U.S. sample (NY City)

• N=203; ages 8-12 N=203; ages 8-12

• Amount of pregnancy smoking assessed retrospectively Amount of pregnancy smoking assessed retrospectively at age 8+; collapsed into 5 categoriesat age 8+; collapsed into 5 categories

• Aggressive behavior scores from maternal report Aggressive behavior scores from maternal report (unpublished rating scale with 6 items) (unpublished rating scale with 6 items)

• Level of prenatal smoke exposure significantly related to Level of prenatal smoke exposure significantly related to aggressive behavior scores (r=.28)aggressive behavior scores (r=.28)

• Effect remained after control for confounding Effect remained after control for confounding demographics and current maternal smoking; no demographics and current maternal smoking; no differential gender effectdifferential gender effect

Conduct DisordersConduct Disorders

Williams et al (1998)Williams et al (1998) • Australian sampleAustralian sample

• N=5342; aged 5 N=5342; aged 5

• Amount of pregnancy smoking assessed during Amount of pregnancy smoking assessed during pregnancy (avg # cig/day)pregnancy (avg # cig/day)

• Externalizing behavior scores from maternal report Externalizing behavior scores from maternal report (CBCL) – dichotomized at 90(CBCL) – dichotomized at 90thth %ile %ile

• Level of prenatal smoke exposure significantly Level of prenatal smoke exposure significantly related to externalizing behavior scores; 20+ cig/day related to externalizing behavior scores; 20+ cig/day at first prenatal visit associated with RR=2.6at first prenatal visit associated with RR=2.6

• Effect remained after control for confounding Effect remained after control for confounding demographics and postnatal smoke exposuredemographics and postnatal smoke exposure

Conduct DisordersConduct DisordersFergusson et al (1993)Fergusson et al (1993)

• New Zealand sampleNew Zealand sample

• N=1000 (approx); assessed at ages 8, 10 & 12 N=1000 (approx); assessed at ages 8, 10 & 12

• Amount of pregnancy smoking assessed at birth (avg # Amount of pregnancy smoking assessed at birth (avg # cig/day collapsed into 3 groups)cig/day collapsed into 3 groups)

• Conduct disorder scores from maternal & report Conduct disorder scores from maternal & report (modified Rutter and Conners) (modified Rutter and Conners)

• Level of prenatal smoke exposure significantly related Level of prenatal smoke exposure significantly related to conduct disorder scores at all 3 time periods; 20+ to conduct disorder scores at all 3 time periods; 20+ cig/day at first prenatal visit associated with highest cig/day at first prenatal visit associated with highest scoresscores

• Effect remained after control for confounding Effect remained after control for confounding demographics and postnatal smoke exposuredemographics and postnatal smoke exposure

Conduct DisordersConduct DisordersFergusson et al (1998)Fergusson et al (1998)


• N=1000 (approx); assessed at age 18 N=1000 (approx); assessed at age 18

• Amount of pregnancy smoking assessed at birth (avg # Amount of pregnancy smoking assessed at birth (avg # cig/day collapsed into 4 groups)cig/day collapsed into 4 groups)

• Conduct disorder diagnosis and symptom rates from Conduct disorder diagnosis and symptom rates from Composite International Diagnostic Inventory Composite International Diagnostic Inventory

• Level of prenatal smoke exposure significantly related to Level of prenatal smoke exposure significantly related to conduct disorder scores; 20+ cig/day associated 2.5 conduct disorder scores; 20+ cig/day associated 2.5 times higher symptom ratestimes higher symptom rates

• Effect remained after control for confounding Effect remained after control for confounding demographics and environmental factors; effects were demographics and environmental factors; effects were stronger for malesstronger for males

Conduct DisordersConduct DisordersNigg & Breslau (2007)Nigg & Breslau (2007)

• U. S. sample (MI)U. S. sample (MI)

• N=713; assessed at ages 6, 11 & 17 N=713; assessed at ages 6, 11 & 17

• Amount of pregnancy smoking assessed at age 6 (3 Amount of pregnancy smoking assessed at age 6 (3 groups)groups)

• CD and ODD diagnoses from DISC maternal interview CD and ODD diagnoses from DISC maternal interview (ages 6 & 11), and DIS with 17 year olds(ages 6 & 11), and DIS with 17 year olds

• Prenatal smoke exposure significantly related to lifetime Prenatal smoke exposure significantly related to lifetime ODD (2+xs higher risk); effect remained after control for ODD (2+xs higher risk); effect remained after control for LBW and other factorsLBW and other factors

• Prenatal smoke exposure significantly related to lifetime Prenatal smoke exposure significantly related to lifetime CD, but not after control for ODD (consistent with known CD, but not after control for ODD (consistent with known dvptl pathway)dvptl pathway)

Conduct DisordersConduct DisordersWakschlag et al (2006)Wakschlag et al (2006)

• U. S. sample (Pittsburgh area)U. S. sample (Pittsburgh area)

• N=448; all boys; ages 7-19 N=448; all boys; ages 7-19

• Amount of pregnancy smoking assessed at age 7 (daily Amount of pregnancy smoking assessed at age 7 (daily vs never/occasional)vs never/occasional)

• ODD diagnosis from DISC parental interview; Self-ODD diagnosis from DISC parental interview; Self-Reported Antisocial Behavior and Delinquency Scales to Reported Antisocial Behavior and Delinquency Scales to assess onset of delinquency and level of severity assess onset of delinquency and level of severity

• Prenatal smoke exposure increased risk of ODD 3xs Prenatal smoke exposure increased risk of ODD 3xs (11.4% vs 3.9%) (11.4% vs 3.9%)

• The age at onset of significant delinquency was The age at onset of significant delinquency was significantly earlier for exposed boys (2 year difference significantly earlier for exposed boys (2 year difference – age 13 vs age 15)– age 13 vs age 15)

Conduct DisordersConduct DisordersMaughan et al (2001)Maughan et al (2001)

• British sampleBritish sample

• N=5770; assessed at ages 5, 10 & 16 N=5770; assessed at ages 5, 10 & 16

• Amount of pregnancy smoking assessed at birth (5 categories)Amount of pregnancy smoking assessed at birth (5 categories)

• Rutter A 2 behavior rating scales completed by parents, scores Rutter A 2 behavior rating scales completed by parents, scores on conduct problems scale dichotimized at 90on conduct problems scale dichotimized at 90thth %ile; %ile; adolescent report also used at age 16, dichotomized at 88%ile adolescent report also used at age 16, dichotomized at 88%ile

• Prenatal smoke exposure associated with conduct problems at Prenatal smoke exposure associated with conduct problems at ages 5 and 10, but not at age 16 (effects for child but not adol ages 5 and 10, but not at age 16 (effects for child but not adol onset)onset)

• Effects remained after control for confounders and postnatal Effects remained after control for confounders and postnatal smoke exposure; however, effects were much stronger if smoke exposure; however, effects were much stronger if smoke exposure continued into childhoodsmoke exposure continued into childhood

Conduct DisordersConduct DisordersMonuteaux et al (2006)Monuteaux et al (2006)

• U.S. sample (Providence, RI area)U.S. sample (Providence, RI area)

• N=682; assessed at age 22 (reporting on symptoms prior to N=682; assessed at age 22 (reporting on symptoms prior to age 18) age 18)

• Amount of pregnancy smoking assessed during pregnancy Amount of pregnancy smoking assessed during pregnancy (# cig/day collapsed into 3 categories)(# cig/day collapsed into 3 categories)

• DIS-III self-report of symptoms in childhood – symptom DIS-III self-report of symptoms in childhood – symptom counts for overt and covert conduct disorder symptoms counts for overt and covert conduct disorder symptoms

• Prenatal smoke exposure NOT significantly related to overt Prenatal smoke exposure NOT significantly related to overt or covert symptoms after control for confounders; no or covert symptoms after control for confounders; no differential gender effectdifferential gender effect

• However, among the lowest SES, both moderate and heavy However, among the lowest SES, both moderate and heavy prenatal cigarette exposure predicted overt, but not covert, prenatal cigarette exposure predicted overt, but not covert, CD symptoms (RR=2.1)CD symptoms (RR=2.1)

Conduct DisordersConduct DisordersConclusionsConclusions

• Significant evidence that prenatal smoke exposure is Significant evidence that prenatal smoke exposure is associated with externalizing problems, including levels of associated with externalizing problems, including levels of aggression, delinquency, and diagnosis of ODD and CDaggression, delinquency, and diagnosis of ODD and CD

• There is also significant evidence that the association is dose There is also significant evidence that the association is dose dependent (3Xs the risk)dependent (3Xs the risk)

• Moderate evidence that the effect may be more pronounced Moderate evidence that the effect may be more pronounced for boys, or at least that boys and girls may be differentially for boys, or at least that boys and girls may be differentially affectedaffected

• Some evidence that in addition to higher levels of Some evidence that in addition to higher levels of externalizing problems, prenatal cigarette exposure is externalizing problems, prenatal cigarette exposure is associated with earlier onset of problemsassociated with earlier onset of problems

• Some evidence that the symptoms of conduct problems Some evidence that the symptoms of conduct problems associated with prenatal smoke exposure may be more likely associated with prenatal smoke exposure may be more likely to be overt rather than covertto be overt rather than covert

Criminal BehaviorCriminal BehaviorBrennan et al (1999)Brennan et al (1999)

• Danish sampleDanish sample

• N=4169; birth cohort at age 33-35 (all male)N=4169; birth cohort at age 33-35 (all male)

• Amount of pregnancy smoking assessed prenatally and at birth Amount of pregnancy smoking assessed prenatally and at birth (# cig/day collapsed into 5 categories)(# cig/day collapsed into 5 categories)

• Danish National Criminal Register provided dichotomous data Danish National Criminal Register provided dichotomous data on nonviolent crime, violent crime, persistent crime, and on nonviolent crime, violent crime, persistent crime, and adolescent limited offending adolescent limited offending

• Prenatal smoke exposure not associated with adolescent Prenatal smoke exposure not associated with adolescent limited offending, but significantly associated with all 3 types limited offending, but significantly associated with all 3 types of adult offending (exposure to pack+/day – two-fold increased of adult offending (exposure to pack+/day – two-fold increased risk)risk)

• Effects remained after control for confounding (delivery Effects remained after control for confounding (delivery complications reduced effect – no other significant complications reduced effect – no other significant confounders)confounders)

Criminal BehaviorCriminal BehaviorRasanen et al (1999)Rasanen et al (1999)

• Finnish sampleFinnish sample

• N=5514; birth cohort at age 28 (all male) N=5514; birth cohort at age 28 (all male)

• Amount of pregnancy smoking assessed prenatallyAmount of pregnancy smoking assessed prenatally

• Ministry of Justice database of all crimes committed in Ministry of Justice database of all crimes committed in Finland – classified as nonviolent and violentFinland – classified as nonviolent and violent

• Non-offenders: 14.1% had prenatal smoke exposure non-Non-offenders: 14.1% had prenatal smoke exposure non-violent offenders: 21.1% violent violent offenders: 21.1% violent offenders: 33.1%offenders: 33.1%

• Those with any prenatal smoke exposure were twice as Those with any prenatal smoke exposure were twice as likely to have committed at least 1 violent crime and to likely to have committed at least 1 violent crime and to have committed more than 1 offensehave committed more than 1 offense

• Effects remained after control for confoundingEffects remained after control for confounding

Criminal BehaviorCriminal Behavior

Brennan et al (2002)Brennan et al (2002)


• N=8112; birth cohort at age 40 (male & female) N=8112; birth cohort at age 40 (male & female)

• Amount of pregnancy smoking assessed prenatally Amount of pregnancy smoking assessed prenatally and at birth (# cig/day collapsed into 4 groups)and at birth (# cig/day collapsed into 4 groups)

• Danish National Criminal Register provided data on Danish National Criminal Register provided data on criminal arrestscriminal arrests

• Prenatal cigarette exposure was significantly Prenatal cigarette exposure was significantly associated with history of criminal arrest – 10+ associated with history of criminal arrest – 10+ cig/day associated with a 1.6xs increase for males, cig/day associated with a 1.6xs increase for males, and a 1.4xs increase for females after control for and a 1.4xs increase for females after control for confoundersconfounders

Criminal BehaviorCriminal BehaviorConclusionsConclusions

• Moderate evidence that prenatal smoke exposure is Moderate evidence that prenatal smoke exposure is associated with criminal behavior into adulthoodassociated with criminal behavior into adulthood

• Moderate evidence that the association is dose Moderate evidence that the association is dose dependent dependent

• Preliminary evidence that effect occurs for both Preliminary evidence that effect occurs for both males and females; however, effect may be more males and females; however, effect may be more pronounced for males (aggression may take different pronounced for males (aggression may take different form for females?)form for females?)

• Effect does not appear to be a result of confounding Effect does not appear to be a result of confounding environmental factorsenvironmental factors

• Additional studies with more diverse populations Additional studies with more diverse populations neededneeded

Depression/Anxiety DisordersDepression/Anxiety DisordersWilliams et al (1998)Williams et al (1998)

• Australian sampleAustralian sample

• N=5342; age 5 N=5342; age 5

• Amount of pregnancy smoking assessed prenatally (# Amount of pregnancy smoking assessed prenatally (# cig/day)cig/day)

• Achenbach CBCL provided data on internalizing problems Achenbach CBCL provided data on internalizing problems (anxiety/depression, anxiety - dichotomized at 90(anxiety/depression, anxiety - dichotomized at 90thth %ile) %ile)

• Rates of internalizing behaviors were significantly higher Rates of internalizing behaviors were significantly higher in children who were exposed to ppd+ prenatallyin children who were exposed to ppd+ prenatally

• Results persisted after control for confoundingResults persisted after control for confounding

• Association with internalizing behaviors weaker than Association with internalizing behaviors weaker than association with externalizing behaviorsassociation with externalizing behaviors

Depression/Anxiety DisordersDepression/Anxiety DisordersIndredavik et al (2007)Indredavik et al (2007)

• Norwegian sampleNorwegian sample

• N=84; age 14 N=84; age 14

• Amount of pregnancy smoking assessed prenatally (# Amount of pregnancy smoking assessed prenatally (# cig/day collapsed into y/n)cig/day collapsed into y/n)

• Achenbach CBCL, TRF, YSR provided data on Achenbach CBCL, TRF, YSR provided data on internalizing problems internalizing problems

• Rates of internalizing behaviors were significantly higher Rates of internalizing behaviors were significantly higher in children who had any prenatal smoke exposurein children who had any prenatal smoke exposure

• However, effects no longer significant after control for However, effects no longer significant after control for confounding (LBW, maternal mental health, current confounding (LBW, maternal mental health, current maternal substance use)maternal substance use)

• No differential gender effectsNo differential gender effects

Depression/Anxiety DisordersDepression/Anxiety DisordersFergusson et al (1998)Fergusson et al (1998)


• N=1022; longitudinal cohort at age 18 N=1022; longitudinal cohort at age 18

• Amount of pregnancy smoking assessed at birth (# cig/day Amount of pregnancy smoking assessed at birth (# cig/day collapsed into 4 groups)collapsed into 4 groups)

• Composite International Diagnostic Interview & Seld-Report Composite International Diagnostic Interview & Seld-Report Delinquency Inventory – used DSM-IV criteria to construct Delinquency Inventory – used DSM-IV criteria to construct diagnoses of generalized anxiety disorder and major diagnoses of generalized anxiety disorder and major depression; also scales with # of symptoms reported depression; also scales with # of symptoms reported

• Depression, but not anxiety disorder significantly associated Depression, but not anxiety disorder significantly associated with ppd+ prenatal exposurewith ppd+ prenatal exposure

• Effects not significant after control for confounding (SES, Effects not significant after control for confounding (SES, poor child rearing, parental/family problems)poor child rearing, parental/family problems)

• Effects stronger for boysEffects stronger for boys

Depression/Anxiety DisordersDepression/Anxiety Disorders

Weissman et al (1999)Weissman et al (1999) • U.S. sample (NY)U.S. sample (NY)

• N=147; longitudinal cohort at ages 17-36 N=147; longitudinal cohort at ages 17-36

• Pregnancy smoking assessed retrospectively at Pregnancy smoking assessed retrospectively at first assessment (10+ cig/day vs rest)first assessment (10+ cig/day vs rest)

• SADS-LA interview for major depressive disorder SADS-LA interview for major depressive disorder and anxiety disorder and anxiety disorder

• Neither depression no anxiety associated with Neither depression no anxiety associated with prenatal cigarette exposure after control for prenatal cigarette exposure after control for confoundingconfounding

• Rates of depression and anxiety low in the sampleRates of depression and anxiety low in the sample

Depression/Anxiety DisordersDepression/Anxiety DisordersConclusionsConclusions

• Inconclusive evidence that prenatal smoke exposure Inconclusive evidence that prenatal smoke exposure is associated with internalizing problems, including is associated with internalizing problems, including depression and anxietydepression and anxiety

• If effects are present, they appear to be weaker than If effects are present, they appear to be weaker than those for externalizing problems those for externalizing problems

• Effects may be due to mediating factors, including Effects may be due to mediating factors, including parental psychopathology and child rearing parental psychopathology and child rearing environmentenvironment

• It is unclear if boys and girls are differentially affectedIt is unclear if boys and girls are differentially affected

• Additional studies with larger and more diverse Additional studies with larger and more diverse populations neededpopulations needed

Substance UseSubstance UseBrennan et al (2002)Brennan et al (2002)


• N=8112; birth cohort at age 40 (male & female) N=8112; birth cohort at age 40 (male & female)

• Amount of pregnancy smoking assessed prenatally and Amount of pregnancy smoking assessed prenatally and at birth (# cig/day collapsed into 4 groups)at birth (# cig/day collapsed into 4 groups)

• Psychiatric hospitalizations for substance abuse and Psychiatric hospitalizations for substance abuse and other factors were determinedother factors were determined

• Prenatal cigarette exposure was significantly associated Prenatal cigarette exposure was significantly associated with substance abuse hospitalization – 10+ cig/day with substance abuse hospitalization – 10+ cig/day associated with a 2.2xs increase for males, and a 2.7xs associated with a 2.2xs increase for males, and a 2.7xs increase for females after control for confoundersincrease for females after control for confounders

• No association with other types of psychiatric No association with other types of psychiatric hospitalizationhospitalization

Substance UseSubstance Use

Weissman et al (1999)Weissman et al (1999) • U.S. sample (NY)U.S. sample (NY)

• N=147; longitudinal cohort at ages 17-36 N=147; longitudinal cohort at ages 17-36

• Pregnancy smoking assessed retrospectively at first Pregnancy smoking assessed retrospectively at first assessment (10+ cig/day vs rest)assessment (10+ cig/day vs rest)

• SADS-LA interview for drug dependence/abuse SADS-LA interview for drug dependence/abuse

• Drug abuse/dependence associated with prenatal Drug abuse/dependence associated with prenatal cigarette exposure after control for confounding, but cigarette exposure after control for confounding, but only for females; relative risk of diagnosis associated only for females; relative risk of diagnosis associated with 10+cig/day was 5.4with 10+cig/day was 5.4

• Substance abuse/dependence associated with Substance abuse/dependence associated with prenatal exposure emerged between ages of 13 and 17prenatal exposure emerged between ages of 13 and 17

Substance UseSubstance UseFergusson et al (1998)Fergusson et al (1998)


• N=1022; longitudinal cohort at age 18 N=1022; longitudinal cohort at age 18

• Amount of pregnancy smoking assessed at birth (# cig/day Amount of pregnancy smoking assessed at birth (# cig/day collapsed into 4 groups)collapsed into 4 groups)

• Composite International Diagnostic Interview & Seld-Report Composite International Diagnostic Interview & Seld-Report Delinquency Inventory – used DSM-IV criteria to construct Delinquency Inventory – used DSM-IV criteria to construct diagnoses of alcohol abuse/dependence and illicit diagnoses of alcohol abuse/dependence and illicit substance use/dependence; also scales with # of substance use/dependence; also scales with # of symptoms reported symptoms reported

• Both alcohol and illicit substance use/dependence Both alcohol and illicit substance use/dependence significantly associated with ppd+ prenatal exposuresignificantly associated with ppd+ prenatal exposure

• Effects not significant after control for confounding (SES, Effects not significant after control for confounding (SES, poor child rearing, parental/family problems)poor child rearing, parental/family problems)

Substance UseSubstance Use

ConclusionsConclusions

• Preliminary evidence that prenatal smoke Preliminary evidence that prenatal smoke exposure is associated with substance use, exposure is associated with substance use, including abuse/dependence of alcohol, and including abuse/dependence of alcohol, and use/dependence of illicit substancesuse/dependence of illicit substances

• Preliminary evidence suggests effects may be Preliminary evidence suggests effects may be more likely to occur among females more likely to occur among females

• Effects may be due, at least in part, to mediating Effects may be due, at least in part, to mediating factors, including parental psychopathology factors, including parental psychopathology and child rearing environmentand child rearing environment


Tobacco Use/DependenceTobacco Use/DependenceBuka et al (2003)Buka et al (2003)

• U.S. sample (RI)U.S. sample (RI)

• N=1248; longitudinal cohort at avg age 29 N=1248; longitudinal cohort at avg age 29

• Amount of pregnancy smoking assessed prenatally (3 Amount of pregnancy smoking assessed prenatally (3 grps)grps)

• NIMH DIS-III assessed nicotine and marijuana dependence NIMH DIS-III assessed nicotine and marijuana dependence

• Exposure to ppd+ prenatally significantly associated with Exposure to ppd+ prenatally significantly associated with nicotine dependence after control for confounding (risk nicotine dependence after control for confounding (risk inc two-fold) inc two-fold)

• No effects for ever smoking or regular smoking for the full No effects for ever smoking or regular smoking for the full sample; Effects much stronger for males, and even signif sample; Effects much stronger for males, and even signif for ever smoked and regular smokingfor ever smoked and regular smoking

• No effects for marijuana use or dependenceNo effects for marijuana use or dependence

Tobacco Use/DependenceTobacco Use/DependenceMamun et al (2006)Mamun et al (2006)

• Australian sample Australian sample


• Amount of pregnancy smoking assessed prenatally and at birth Amount of pregnancy smoking assessed prenatally and at birth (3 grps)(3 grps)

• Standardized questions of smoking history Standardized questions of smoking history

• Any prenatal smoke exposure was significantly associated with Any prenatal smoke exposure was significantly associated with later smoking – those who were exposed were 2.7 times more later smoking – those who were exposed were 2.7 times more likely to start smoking by age 14 and to smoke regularly; 2.1 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 times more likely to start smoking at age 15+ than those with no exposureno exposure

• Exposure to postnatal smoking was associated with smoking Exposure to postnatal smoking was associated with smoking history, but not as strongly as prenatal exposurehistory, but not as strongly as prenatal exposure

• Effects remained after control for confoundersEffects remained after control for confounders

Tobacco Use/DependenceTobacco Use/DependenceCornelius et al (2005)Cornelius et al (2005)

• U.S. sample (Pittsburgh area) U.S. sample (Pittsburgh area)


• Amount of pregnancy smoking assessed prenatally (# cig/day)Amount of pregnancy smoking assessed prenatally (# cig/day)

• Questions on smoking history, adapted from the Health Questions on smoking history, adapted from the Health Behavior Questionnaire; also urine cotinineBehavior Questionnaire; also urine cotinine

• Prenatal smoke exposure significantly predicted any later Prenatal smoke exposure significantly predicted any later smoking after control for confounding, including postnatal smoking after control for confounding, including postnatal exposure; level of smoking and age at onset of smoking not exposure; level of smoking and age at onset of smoking not significant after control for confounding (14 yrs old, though)significant after control for confounding (14 yrs old, though)

• Dose response relationship – exposure throughout pregnancy Dose response relationship – exposure throughout pregnancy associated with highest rates of adolescent smokingassociated with highest rates of adolescent smoking

• No differential gender effectsNo differential gender effects

Tobacco Use/DependenceTobacco Use/DependenceCornelius et al (2000)Cornelius et al (2000)

• U.S. sample (Pittsburgh area) U.S. sample (Pittsburgh area)


• Amount of pregnancy smoking assessed prenatally Amount of pregnancy smoking assessed prenatally (# cig/day)(# cig/day)

• Standardized smoking history questions used Standardized smoking history questions used (collapsed into ever smoked vs never smoked)(collapsed into ever smoked vs never smoked)

• Prenatal smoke exposure significantly predicted Prenatal smoke exposure significantly predicted early tobacco experimentation after control for early tobacco experimentation after control for confounding, including postnatal exposure RR=5.5)confounding, including postnatal exposure RR=5.5)

• Postnatal exposure did NOT independently predict Postnatal exposure did NOT independently predict smokingsmoking

Tobacco Use/DependenceTobacco Use/DependenceConclusionsConclusions

• Significant evidence that prenatal smoke exposure is Significant evidence that prenatal smoke exposure is associated with later smoking initiation and associated with later smoking initiation and continuationcontinuation

• Effects are particularly pronounced for early initiation, Effects are particularly pronounced for early initiation, and development of dependence once begin smokingand development of dependence once begin smoking

• Moderate evidence that association is dose-dependentModerate evidence that association is dose-dependent

• Preliminary evidence suggests effects may be more Preliminary evidence suggests effects may be more pronounced in males pronounced in males

• Effects do not appear to be due to confounding factors, Effects do not appear to be due to confounding factors, including postnatal exposureincluding postnatal exposure


AutismAutism• Only one published study that has examined the Only one published study that has examined the

association between prenatal cigarette exposure association between prenatal cigarette exposure and autismand autism

• Indredavik (2007) – using prospectively collected Indredavik (2007) – using prospectively collected prenatal smoking data and the Autism Spectrum prenatal smoking data and the Autism Spectrum Screening Questionnaire – found significantly Screening Questionnaire – found significantly higher autism scores for those exposed to any higher autism scores for those exposed to any level of smoke prenatally; effects remained after level of smoke prenatally; effects remained after control for confounding; no differential gender control for confounding; no differential gender effectseffects

• While no published studies report no effect, While no published studies report no effect, additional study is clearly needed with larger additional study is clearly needed with larger samples and more thorough assessment of samples and more thorough assessment of Autism to verify the possible linkAutism to verify the possible link

MechanismsMechanisms• Why might prenatal smoke exposure impact mental Why might prenatal smoke exposure impact mental

health outcomes?health outcomes?

• Several possible explanations have been proposed, Several possible explanations have been proposed, and are based on two potential primary and are based on two potential primary mechanisms:mechanisms:• Hypoxic effects on the placenta and fetusHypoxic effects on the placenta and fetus

• Teratologic effects on the developing nervous systemTeratologic effects on the developing nervous system

• Reduction in blood flow – implicated in cell death, Reduction in blood flow – implicated in cell death, delayed development, and missed critical periods delayed development, and missed critical periods for nervous system developmentfor nervous system development

• Neurobehavioral teratogens – most evidence Neurobehavioral teratogens – most evidence suggests carbon monoxide and nicotine are key suggests carbon monoxide and nicotine are key (both cross placental barrier)(both cross placental barrier)

MechanismsMechanisms• Effects may be structural, neuroregulatory, Effects may be structural, neuroregulatory,

neurobehavioral, or involve all threeneurobehavioral, or involve all three

• Human studies have shown prenatal cigarette Human studies have shown prenatal cigarette exposure to be associated with reduced fetal head exposure to be associated with reduced fetal head growth involving:growth involving:• head circumferencehead circumference

• biparietal diameter biparietal diameter

• smaller atrial width of lateral ventriclesmaller atrial width of lateral ventricle

• smaller transcerebellar diametersmaller transcerebellar diameter

• Animal studies have shown increased incidence of Animal studies have shown increased incidence of apoptotic cells in all brain areas, especially the apoptotic cells in all brain areas, especially the cortex and cerebellum, and damage to the cortex and cerebellum, and damage to the developing epitheliumdeveloping epithelium

MechanismsMechanisms• Noted structural alterations associated with prenatal Noted structural alterations associated with prenatal

cigarette exposure have been associated with many cigarette exposure have been associated with many of the outcomes linked to prenatal cigarette exposureof the outcomes linked to prenatal cigarette exposure

• Cell death and smaller relative brain area size have Cell death and smaller relative brain area size have been associated withbeen associated with• deficits in cognitive functiondeficits in cognitive function

• delays in neupsychological abilities delays in neupsychological abilities

• schizophreniaschizophrenia

• autismautism

• Thus, structural alteratins may be one pathway Thus, structural alteratins may be one pathway through which prenatal smoke exposure influences through which prenatal smoke exposure influences child outcomeschild outcomes

MechanismsMechanisms• Xx- neurochemical effectsXx- neurochemical effects

Clinical ImplicationsClinical Implications• XXXX

Prevention Efforts in NE TNPrevention Efforts in NE TN• XXXX

slide 1 prenatal smoke exposure and psychiatric outcomes beth bailey, phd assistant professor,...

Documents

child health

attention problems

background exposure

memory problems

prenatal smoke exposure

behavior problems

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prenatal period