<!-- image -->

Research Article                                                                                                                                        Open Access

## Secondhand Smoke Exposure and Severity of AttentionDeficit/Hyperactivity Disorder in Preschoolers: A Pilot Investigation

Mini Tandon 1 , Christina N. Lessov-Schlaggar 1 , Rebecca Tillman 1 , Melbourne F. Hovell 2 , Joan Luby 1

1 Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA 2 Center for Behavioral Epidemiology and Community Health, San Diego State University, San Diego, CA, USA

*Corresponding author: tandonm@psychiatry.wustl.edu

## Abstract

Background: Less  is  known  about  the  effects  of  secondhand  smoke  (SHS)  on  mental  health  as  compared  with  other medical disorders.

Objective: The  aims  of  this  study  were  to  examine  the  following:  1)  the  association  of  SHS  exposure  with  childhood attention-deficit/hyperactivity (ADHD) and disruptive disorders; and 2) the association of maternal recall of a child's SHS exposure and that child's exposure as measured by bioassay.

Method: Sixty children had their saliva collected and assayed for cotinine when they were 4 years old and again when they were 6 years old. Phone interview data were collected to assess maternal recall of the children's exposure to SHS at these ages. The children were assessed annually for ADHD and disruptive disorders. Repeated measures analysis of exposure level by child characteristics was performed.

Results: Greater ADHD and conduct disorder severity scores were associated with greater child smoke exposure (ADHD severity, P = .043; conduct disorder severity, P = .035). A large proportion of mothers reported that their children had no exposure to SHS, despite high levels of measured cotinine in the children's saliva.

Conclusions: An association between SHS exposure and ADHD and conduct disorder symptoms was found. Children and parents may benefit from parent education regarding the deleterious effects of SHS.

Keywords: secondhand smoke, attention-deficit/hyperactivity disorder, disruptive, preschool, parenting

## Introduction

Approximately 60% of children between the ages of 4  and  11  years  old  are  exposed  to  secondhand smoke (SHS) in the United States (1). Children are exposed to SHS in multiple locations, most notably at home and in the car (2). In a review of maternal smoking and child behavioral problems, Weitzman and  colleagues  (3)  suggested  that,  despite  study discrepancies,  a  majority  of  studies  that  controlled for  confounding  factors  (e.g.,  prenatal  smoking, maternal  education,  late  prenatal  care)  found  an increased risk for behavior problems among children  who  had  been  exposed  to  SHS.  SHS  has been associated with an increased risk for conduct disorder and hyperactivity in children (4;5). Limitations of existing SHS studies include the use of parental or self-report of SHS without biomarker confirmation,  which  is  the  most  valid  measure  of exposure  (6). In addition, studies often fail to account for parental psychiatric diagnoses that may affect child diagnoses.

Although human studies have been wrought with such challenges, animal studies support the idea that SHS alters normal neurodevelopment in perinatally and postnatally exposed groups of rhesus monkeys (7). Slotkin and colleagues (7) have implicated changes in neurite formation, cell hypertrophy, and cell  loss.  How  such  animal  findings  translate  to human neurodevelopment remains unclear. However,  such  converging  evidence  from  human and animal studies gives rise to the need for further investigation  into  mental  health  outcomes  among young  children  who  are  exposed  to  SHS.  We considered  the  following  hypotheses:  1)  increased SHS is associated with increased severity of attention-deficit/hyperactivity disorder (ADHD), conduct  disorder  (CD),  and  oppositional  defiant disorder (ODD) after controlling for parental ADHD  and  CD  (lifetime);  and  2)  parents  are unaware  of  and  unable  to  accurately  estimate  the quantity of SHS exposure that their children received during early childhood. ADHD  is a diagnosis  ascribed  to  those  who  have  significant problems  with  attention  and  impulsivity  in  several settings and that is often first diagnosed during early childhood. ODD  and  CD  together are often referred to as disruptive disorders. The following study specifically  makes  use  of  the  definitions  found  in the Diagnostic and Statistical Manual of Mental Disorders, Fourth  Edition (DSM-IV),  which  was  published  by the American Psychiatric Association in 1994.

## Methods

Study Sample

Study  participants  were  recruited  from  community primary care sites for a study that focused on early childhood  depression.  Participants  in  this  ongoing study had received annual comprehensive diagnostic assessments  since  they  were  3  years  old.  Maternal reports  of  child  diagnoses  of  ADHD,  CD,  and ODD  were  collected  with  the  use  of  valid  and reliable  age-appropriate  psychiatric  assessments  for children between the ages of 3 and 13 years; these included the Preschool Age Psychiatric Assessment (8) and the Child and Adolescent Psychiatric Assessment  (9).  Mothers  reported  diagnoses of ADHD and CD (lifetime)  for  themselves  and  for the  children's  fathers  via  the  Family  Interview  for Genetic Studies (10). The mothers reported on the fathers  given  the  fathers'  low  participation  rates. Parental  ODD  was  not  addressed.  The  original sample was not ascertained for parents with ADHD, for parents with depression, or for parents who  smoked.  All  child  participants  were  asked  to provide  saliva  as  part  of  the  original  parent  study. During the last several years of the study, additional detailed  phone  interview  data  were  collected  to address  pregnancy  and  post-pregnancy  smoking  as well as maternal recall of the children's exposure to SHS  at  the  ages  of  4  and  6  years,  when  saliva samples were obtained and frozen  (November 2003/May  2005  and  October  2005/April  2007, respectively). These children were an average age of 11  years  and  2  months  old  (standard  deviation,  5 months)  when  their  mothers  were  contacted  by telephone. Saliva samples were assayed for cotinine, which is a valid and reliable biochemical marker of nicotine  exposure  that  has  excellent  stability  when frozen (half life, ≈17 hours) (11).

## Statistical Analysis

Repeated measures analysis of SHS exposure (according to cotinine levels at the ages of 4 and 6 years) and child characteristics was performed with the use of SAS statistical software version 9.2 (12). Separate univariate repeated measures mixed models with unstructured covariance structures were used to model the effects of potential predictors on SHS exposure levels. Initially, models were  run  without  covariates.  Follow-up  analyses included  maternal  reports  of  paternal  ADHD  and paternal  CD  as  covariates.  The  results  of  these models are presented in the following Results section. Maternal ADHD  and CD were not included because no mothers had CD and only one mother  had  ADHD.  The  dependent  variable  was the participant's SHS exposure, which was measured via the cotinine level (continuous). Independent variables in the separate mixed models were the participant's age and gender; SHS exposure (mother's  recall  [yes/no]  of  child's  exposure  to SHS); DSM-IV ADHD diagnosis; DSM-IV ADHD severity  score  (according  to  a  summary  of  all  18 DSM-IV symptoms, of 9 inattentive symptoms, or of  9  hyperactive/impulsive  symptoms);  DSM-IV CD, ODD, and CD/ODD severity scores (according  to  a  summary  of  all  15  DSM-IV  CD symptoms, of 8 DSM-IV ODD symptoms, or of 23 DSM-IV CD and ODD symptoms); family poverty (family  income  of  ≤$20,000/year);  and  mother's self-report of prenatal smoking status (yes/no).

## Results

Cotinine  levels  were  measured  in  60  participants. There  were  50  participants  with  saliva  available  at the  age  of  4  years  and  49  participants  with  saliva available at the age of 6 years. The mothers of the participants  included  13  women  who  had  ever smoked  and  11  women  who  were  smokers  at  the time of the interview.  Descriptive  statistics  for  the independent  variables  in  the  mixed  models  are presented in Table 1.

Results of the univariate repeated measures mixed models  of  cotinine  levels  are  shown  in  Table  2. These models included only 59 participants, because paternal ADHD and CD data were not available for one participant. Prenatal smoke exposure was associated  with  early  childhood  smoke  exposure, which was measured as SHS (cotinine level) in this sample (estimate [Est] = 1.62; standard error [SE] = 0.62; F-distribution [F] = 6.89; degrees of freedom [df] = 1, 55; P = .011). Child diagnoses of ADHD, CD,  and  ODD  were  not  associated  with  SHS. However,  higher  ADHD  and  CD  severity  scores were associated with increased levels of child  SHS exposure ( ADHD severity: Est = 0.11; SE = 0.05; F

= 4.29; df = 1, 57; P = .043; CD severity: Est = 0.36; SE = 0.17; F = 4.66; df = 1, 57; P =  .035).  There was  also  an  association  between  higher  levels  of SHS exposure and higher levels of poverty (Est = 1.29; SE = 0.63; F = 4.15; df = 1, 53; P = .047).

TABLE 1. Characteristics of study participants (N=60) at 4 and 6 years of age*

|                                           | Age 4 (N=50)   | Age 4 (N=50)   | Age 6 (N=49)   | Age 6 (N=49)   |
|-------------------------------------------|----------------|----------------|----------------|----------------|
| Characteristic                            | %              | N              | %              | N              |
| At or below poverty (≤$20,000/year)       | 18.4           | 9              | 23.4           | 11             |
| Male gender                               | 60.0           | 30             | 53.1           | 26             |
| Reported no child SHS exposure            | 83.3           | 40             | 77.1           | 37             |
| Child ADHD                                | 8.0            | 4              | 22.4           | 11             |
| Child CD and/or ODD                       | 24.0           | 12             | 26.5           | 13             |
| Mother reported prenatal smoking          | 16.7           | 8              | 16.7           | 8              |
|                                           | Mean           | SD             | Mean           | SD             |
| Child ADHD severity                       | 3.12           | 3.54           | 4.00           | 4.14           |
| Child ADHD inattentive severity           | 1.48           | 1.94           | 2.94           | 2.70           |
| Child ADHD hyperactive/impulsive severity | 1.64           | 1.89           | 1.31           | 2.32           |
| Child CD severity                         | 0.84           | 1.15           | 0.92           | 1.17           |
| Child ODD severity                        | 2.22           | 2.00           | 2.14           | 1.91           |
| Child CD/ODD severity                     | 3.06           | 2.87           | 3.00           | 2.75           |

Note: *There were 60 children with cotinine levels at age 4, age 6, or both age 4 and age 6.

ADHD, Attention-deficit/hyperactivity  disorder; CD, conduct  disorder; ODD, oppositional defiant disorder; SD, standard deviation; SHS, secondhand smoke

A  mother's  recall  of  her  child's  exposure  to  SHS was associated with greater child SHS exposure (Est = 1.69; SE = 0.35; F = 23.84; df = 1, 55; P < .001). However,  even  at  high  levels  of  child  SHS,  as indicated by child saliva cotinine levels of more than 0.70  ng/ml,  a  large  proportion  of  mothers  still reported that their children had no exposure to SHS (54.6% at the age of 4 years and 38.5% at the age of 6 years).

TABLE 2.  Univariate  repeated  measures  mixed  models  of  salivary  cotinine levels in 59 children*

| Characteristic                            |   Est. |   SE |     F | df    | P value   |
|-------------------------------------------|--------|------|-------|-------|-----------|
| Age 4 vs. age 6                           |   0.73 | 0.39 |  3.49 | 1, 57 | .067      |
| At or below poverty (≤$20,000/year)       |   1.29 | 0.63 |  4.15 | 1, 53 | .047      |
| Male vs. female                           |  -1.03 | 0.47 |  4.83 | 1, 56 | .032      |
| Reported child SHS exposure               |   1.69 | 0.35 | 23.84 | 1, 55 | <.001     |
| Child ADHD                                |   0.82 | 0.48 |  3.01 | 1, 57 | .088      |
| Child ADHD severity                       |   0.11 | 0.05 |  4.29 | 1, 57 | .043      |
| Child ADHD inattentive severity           |   0.12 | 0.08 |  2.29 | 1, 57 | .136      |
| Child ADHD hyperactive/impulsive severity |   0.14 | 0.09 |  2.47 | 1, 57 | .121      |
| Child CD and/or ODD                       |   0.69 | 0.44 |  2.44 | 1, 57 | .124      |
| Child CD severity                         |   0.36 | 0.17 |  4.66 | 1, 57 | .035      |
| Child ODD severity                        |   0.14 | 0.10 |  2.05 | 1, 57 | .158      |
| Child CD/ODD severity                     |   0.14 | 0.07 |  3.72 | 1, 57 | .059      |
| Mother reported prenatal smoking          |   1.62 | 0.62 |  6.89 | 1, 55 | .011      |

Note: *Paternal ADHD and CD diagnoses were used as covariants

ADHD, Attention-deficit/hyperactivity  disorder; CD, conduct  disorder; ODD, oppositional  defiant  disorder; SHS, secondhand  smoke; Est., estimate; SE, standard error; df, degrees of freedom

## Discussion

Categorical diagnoses of ADHD, CD, and ODD in children were not associated with SHS in this study. However, the severity of child ADHD and CD was associated  with  SHS,  thereby  warranting  further investigation in larger samples.

These study findings also shed light on a lack of maternal  recall  of  nicotine  exposure  in  children despite biomarker evidence. Whether parents underreported child SHS exposure or were blind to other sources of potential exposure (e.g., a smoker driving the child to school, the presence of contaminated surfaces or clothing) warrants study.

This pilot study faced important limitations, including  the  small  sample  size;  the  inability  to assess parents' personalities, parenting practices, and executive  function  skills;  and  the  lack  of  genetic analyses  with  respect  to  ADHD  and  smoking. Despite  these  limitations,  the  study  results  inform the underinvestigated role of  SHS  exposure  in children as it relates to ADHD. If SHS is confirmed as  playing  a  role  in  ADHD,  an  additional  impetus may be justified for  the  prevention  and  control  of SHS  exposure  to  prevent  ADHD  or  its  exacerbations.

Parental  education  may  be one  avenue  to  use  to reduce harm to families, especially to children who are  in  sensitive  developmental  stages,  such  as  early childhood. In accordance with Hovell and Hughes' ecologic model (13), future studies should emphasize the importance of smoking only outside of  the  home  and  car  and  of  caretakers  protecting their children from SHS  even from incidental sources in the community (e.g., visiting a friend who smokes).  Larger  study  samples  that  control  for maternal  smoking  during  pregnancy  and  maternal education are warranted. These study findings highlight the potential role of SHS in the development of ADHD and disruptive behavior as well as the need for pertinent education.

## Clinical Significance

The  present  study  investigated  the  effects  of  SHS on ADHD and disruptive disorders with the use of both  maternal  reports  and  bioassay  data  (cotinine) for  preschool-aged  children.  The  severity  of  SHS exposure was associated with the severity of ADHD and  CD  symptomatology  after  controlling  for  key covariates. Furthermore, these findings suggest that mothers  were  either  unaware  of  their  children's exposure  to  SHS  or  unable  to  recall  it.  In  either case, understanding the mechanisms by which SHS influences  the  severity  of  psychopathology  during childhood seems worthy of investigation. Until such findings  can  be  clarified  in  larger  investigations,  it may be helpful to teach parents that no amount of SHS is considered safe. Such findings, despite study size limitations, have significant public health implications.  Larger  investigations  that  detail  the associations  between  SHS  exposure  during  early childhood  and  neurocognition  and  behavior  are now warranted.

## References

1. Schober S, Zhang C, Brody D, Marano C. Disparities in secondhand smoke exposure-United States, 1988-1994 and 19992004. Morb Mortal Wkly Rep 2008;57(27):744-7.
2. Klerman  L.  Protecting  children:  reducing  their  environmental tobacco smoke exposure. Nicotine Tob Res 2004;6 Suppl 2:S23953.
3. Weitzman M, Byrd RS, Aligne CA, Moss M. The effects of tobacco exposure on children's behavioral and cognitive functioning: implications for clinical and public health policy and future research. Neurotoxicol Teratol 2002;24(3):397-406.
4. Braun  JM,  Froehlich  TE,  Daniels  JL,  Dietrich  KN,  Hornung  R, Auinger  P,  et  al.  Association  of  environmental  toxicants  and conduct disorder in U.S. children: NHANES 2001-2004. Environ Health Perspect 2008;116(7):956-62.
5. Hamer M, Ford T, Stamatakis E, Dockray S, Batty  GD. Objectively  measured  secondhand  smoke  exposure  and  mental health in children: evidence from the Scottish Health Survey. Arch Pediatr Adolesc Med 2011;165(4):326-31.
6. Hovell MF, Zakarian JM, Wahlgren DR, Matt GE, Emmons KM. Reported  measures  of  environmental  tobacco  smoke  exposure: trials and tribulations. Tob Control 2000;9 Suppl 3:III22-8.
7. Slotkin  TA,  Pinkerton  KE,  Auman  JT,  Qiao  D,  Seidler  FJ. Perinatal  exposure  to  environmental  tobacco  smoke  upregulates nicotinic  cholinergic  receptors  in  monkey  brain.  Dev  Brain  Res 2002;133(2):175-9.
8. Egger  H,  Ascher  B,  Angold  A.  The  Preschool  Age  Psychiatric Assessment: Version 1.4. Durham, NC: Duke University Medical Center; 1999, 2003.
9. Angold  A,  Costello  E.  The  Child  and  Adolescent  Psychiatric Assessment (CAPA). J Am  Acad Child Adolesc Psychiatry 2000;39(1):39-48.
10.  Maxwell ME. Manual for the Family Interview for Genetic Studies (FIGS). Bethesda, MD: Clinical Neurogenetics Branch, Intramural Research Program, National Insititute of Mental Health; 1992.
11.  Benowitz  N.  Cotinine  as  a  biomarker  of  environmental  tobacco smoke exposure. Epidemiol Rev 1996;18(2):188-204.
12.  Littell  R,  Milliken  G,  Stroup  W,  Wolfinger  R.  SAS  system  for mixed models. Cary, North Carolina: SAS Institute. Inc; 1996.
13.  Hovell  MF,  Hughes  SC.  The  behavioral  ecology  of  secondhand smoke exposure: A pathway to complete tobacco control. Nicotine Tob Res 2009;11(11):1254-64.

## Acknowledgments

Data collection for this investigation was supported by  the  National  Institutes  of  Health  {(and  the American Academy of Child and Adolescent Psychiatry, Prenatal Cigarette Exposure and Course of Childhood Attention-Deficit/Hyperactivity Disorder K12 DA000357 to Mini Tandon); Reward and Control Processing in Cigarette Smoking Using fMRI  K01  DA027046  to  Christina  N.  LessovSchlaggar; Clinician Promotion of Healthy Diet and Activity  to  Reduce  Obesity  Among  Adolescents (Healthy Smiles) R01 CA138192-01A1 and Innovation for Smoke-Free Homes: Real-Time Feedback (Project Fresh Air) R01 HL103684-01A1 to Melbourne F. Hovell; Preschool Mood Disorders:  Developmental  Continuity  and  School Age Outcomes R01 MH64769 to Joan Luby}.