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Prenatal Smoke Exposure and Psychiatric Outcomes. Beth Bailey, PhD Assistant Professor, Department of Family Medicine East Tennessee State University Director, Tennessee Intervention for Pregnant Smokers. Background.
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Prenatal Smoke Exposure and Psychiatric Outcomes Beth Bailey, PhD Assistant Professor, Department of Family Medicine East Tennessee State University Director, Tennessee Intervention for Pregnant Smokers
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 • Social and genetic factors are typically recognized as impacting mental health in children • Environmental factors may also play a significant role, but are often overlooked for their role in impacting child mental health
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 • Many prenatal environmental influences have been examined, including infection, trauma, and hormonal variations • Prenatal toxin exposure has received the most attention in terms of the impact it may have on subsequent child development
Background • Many toxins have been examined, including lead, mercury, and PCBs • Effects include • 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
Background • 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
Background • 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
Background • The most common prenatal exposure, tobacco, has been found to significantly impact immediate and long term child outcomes, including mental health
Smoking Prevalence • Nationally, 12.6% of women smoke during pregnancy • In Tennessee, 17.1% of women smoke during pregnancy • And in Northeast Tennessee, the pregnancy smoking rate is 49.0%
Effects of Smoking on Pregnancy • Ectopic pregnancy • IUGR • Placental previa and abruption • PROM • Miscarriage • Preterm delivery
Effects of Pregnancy Smoking on Child Health • Low birth weight • Growth restriction • Ear infections • Respiratory infections • Asthma and allergies • Elevated blood pressure • Elevated total cholesterol
Effects of Pregnancy Smoking on Child Cognitive Outcomes • Decreased global IQ and general cognitive functioning • Problems with visuoperceptual performance • Deficits in math performance • Deficits in spelling performance
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
Effects of Pregnancy Smoking on Child Psychiatric Outcomes Important methodologic considerations: • Sample size (and # of exposed) • Assessment of prenatal cigarette exposure (retrospective vs prospective; amount, timing) • 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
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
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 • DuPaul ADHD Rating Scale • Significant association between amount of prenatal smoke exposure and ADHD scale scores
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
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
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
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
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
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
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
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
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
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 90th %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
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
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
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)
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 3xs (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)
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 90th %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
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)
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 (3Xs 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
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, violent 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)
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
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 1.6xs increase for males, and a 1.4xs increase for females after control for confounders
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
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 90th %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
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
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
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
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
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 2.2xs increase for males, and a 2.7xs increase for females after control for confounders • No association with other types of psychiatric hospitalization
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
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)
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
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
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
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
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
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 dose-dependent • 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