pediatrics 2011 sleep disordered breathing
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8/6/2019 Pediatrics 2011 Sleep Disordered Breathing
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Sleep Disordered Breathing in a Population-Based Cohort: Behavioral Effects at 4 and 7 Years
Karen Bonuck, PhD (corresponding author)Professor, Department of Family Medicine
Albert Einstein College of Medicine1300 Morris Park AvenueBronx, NY 10461Karen.bonuck@einstein.yu.edu phone 718 430 4085
Katherine Freeman, Dr.P.H.Professor, Department of Epidemiology and Population HealthMontefiore Medical Center/Albert Einstein College of Medicine111East 210 th StreetBronx, NY 10467
kfreeman@montefiore.org phone: 718 920 5223
Ronald D. Chervin, MD, MSProfessor, Department of Neurology and Director, Sleep Disorders CenterUniversity of MichiganC728 Med Inn Bldg1500 E. Medical Center Dr.Ann Arbor, MI 48109-5845chervin@umich.edu phone 734-647-9064
Linzhi Xu, PhDResearch Associate, Department of Family and Social MedicineAlbert Einstein College of Medicine1300 Morris Park AvenueBronx, NY 10461Linzhi.Xu@einstein.yu.edu
KeyWords: sleep-disordered breathing, behavior, longitudinal
This study was supported by grants from the National Heart Lung & Blood Institute- R21HL091241 and
R21HL091241-01A1.
Conflict of Interest: The authors have no conflicts of interest relevant to this article to disclose
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Contributor’s Statement Page
All authors meet the criteria for authorship. Dr. Bonuck conceptualized and designed the study, drafted theinitial manuscript, reviewed and modified the analyses in collaboration with Drs. Freeman and Xu, andincorporated co-author feedback into the final manuscript. Dr. Freeman worked to develop the methods, carriedout initial analyses, supervised final analyses of Dr. Xu, and reviewed and revised the final manuscript. Dr.Chervin advised on study design and analyses, and carefully reviewed and revised multiple versions of themanuscript. Dr. Xu collaborated on statistical design issues, completed final analyses, and reviewed and revised
the final version of the paper.
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Objectives: Examine statistical effects of sleep-disordered breathing (SDB) symptom trajectories from 6months to 7 years on subsequent behavior.
Patients and Methods: Parents in the Avon Longitudinal Study of Parents and Children (ALSPAC) reported onchildren’s snoring, mouth breathing, and witnessed apnea at >2 surveys at 6, 18, 30, 42, 57, and 69 months, andcompleted the Strengths and Difficulties Questionnaire (SDQ) at 4 (n=9,206) and 7 (n=8,342) years. Clusteranalysis produced 5 “Early” (6-42 months) and “Late” (6-69 months) symptom trajectories (“clusters”).Adverse behavioral outcomes were defined by top 10 th percentiles on SDQ total and subscales, at 4 and 7 years,
in multivariable logistic regression models.
Results: The SDB clusters predicted ≈ 20%-90% increased odds of subsequent problematic behavior,controlling for 16 potential confounders. Early clusters predicted problematic behavior at 7 years equally wellas at 4 years. The “Worst Case” cluster, with peak symptoms at 2.5 years that subsequently resolved,nonetheless at 7 years predicted hyperactivity (OR=1.96, 95% CI [1.52 to 2.53]), conduct (1.61, [1.39 to 2.19]),and peer difficulties (1.69, [1.39 to 2.06]), whereas a “Later Symptom” cluster predicted emotional difficulties(1.69, [1.39 to 2.06]). In two clusters, all SDB symptoms peaked before 1.5 years and abated by 2.5 years, butstill predicted 40%-50% increased odds of behavior problems at 7 years.
Conclusions: In this large, population-based, longitudinal study, early-life SDB symptoms had strong,
persistent statistical effects on subsequent behavior in childhood. Findings suggest that SDB symptoms mayrequire attention as early as the first year of life.
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What is Known on This Subject● Sleep disordered breathing (SDB) is associated with neurobehavioral morbidity in children.● Prior related research has generally been cross-sectional or short (i.e. 1-2 years) follow-up studies of a singlesymptom (i.e. snoring, obstructive sleep apnea, mouth-breathing), with limited control for confounders.
What This Study Adds● SDB was assessed as a trajectory of combined symptoms from 6 months to 6.75 years, in over 11,000
children.● SDB was associated with 40% and 60% more behavioral difficulties at 4 and 7 years, respectively.
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Introduction
Neurobehavioral morbidity is common in childhood sleep disordered breathing (SDB) that can range
from snoring to obstructive sleep apnea (OSA). Mouth-breathing is another frequent clinical finding. 1 2 SDB
causes abnormal gas exchange, interferes with normal restoration during sleep, and disrupts cellular and
chemical homeostasis. 3 The supposed resultant dysfunction of the prefrontal cortex impairs attention,
executive functioning, behavioral inhibition, self-regulation of affect and arousal, and other socio-emotional
behaviors. 4 Behavioral manifestations include both externalizing (e.g., hyperactivity, aggression, impulsivity)
and internalizing (e.g., somatic complaints, social withdrawal) behaviors. 5 SDB reportedly peaks from 2-6
years of age, 6 but also occurs in younger children. 7 It is unclear which of the core biological processes
associated with SDB best predict neurobehavioral morbidity; genetic, individual, and environmental variables
likely play a role in how this morbidity is expressed. 4 Regardless of etiology, SDB’s neurological effects may
be irreversible, 8 highlighting the saliency of under-detection.
Despite the breadth of studies on SDB’s neurobehavioral effects in children, methodological limitations
persist. Meta-analyses found existing work rife with poor sampling, insufficient consideration of confounders,
and imprecise use of statistical tools. 9 10 Nearly all studies have been cross-sectional, and most longitudinal
studies have focused on pre/post-adenotonsillectomy (T&A) assessments or have included no more than 2 years
of follow-up. A meta-analysis of SDB differences associated with attention-deficit/hyperactivity disorder
(ADHD) 11 relied upon just 2 small studies 12, 13 and excluded children with anxiety or depressive disorders.
This study describes the combined trajectory of 3 hallmark SDB symptoms—snoring, mouth-breathing,
and witnessed apnea—and their longitudinal statistical effects on behavior. Our research questions were: 1)
“What effect do early SDB patterns (i.e., “clusters”) from 6 through 42 months of life have upon social-
emotional behavior at 4 and 7 years?”; and 2) “What effect do SDB patterns from 6 months through nearly 6
years have on behavior at 7 years of age?” Data were collected over 7 time points during the critical period in
SDB development, from 6 months through nearly 7 years of age in a prospective, population-based cohort.
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Patients and Methods
Population
The Avon Longitudinal Study of Parents and Children (ALSPAC), a geographically based cohort study
of children, enrolled pregnant women residing in a defined part of the former county of Avon in southwest
England with an expected date of delivery between April 1991 and December 1992. A total of 14,541 pregnant
women were enrolled. The cohort , described in detail elsewhere, 14 is broadly representative of the UK
population in terms of socioeconomic status (SES), although with a slight under-representation of ethnic
minority families, and overrepresentation of wealthier families. Our analyses excluded: triplet and quadruplet
births, children who did not survive to 1 year and children with conditions such as major congenital disorders
that are likely to affect SDB or behavioral assessment. The resulting base sample, used to derive SDB clusters
and behavioral outcomes, was 13,810 infants.
ALSPAC’s internal law and ethics committee reviews all proposals for secondary analyses and approves
policies for data handling and analysis. Ethical approval for this study was obtained from the ALSPAC Law and
Ethics Committee and the Local Research Ethics Committee. All participants provided informed consent.
SDB Assessment
In ALSPAC’s mailed questionnaires, parents reported on their child’s snoring, apnea and mouth-
breathing when s/he was 6, 18, 30, 42, 57, 69 or 81 months of age. These items were: 1) Mouth-breathing:
“Does she breathe through her mouth rather than her nose?”. At 57 months and older, parents were asked to
report separately for mouth-breathing when awake vs. asleep, though only the latter was used in analyses; 2)
Snoring: “Does she snore for more than a few minutes at a time?”; and 3) Apnea: “When asleep, does she seem
to stop breathing or hold breath for several seconds at a time?”.
Responses were categorized along ordinal scales of 3, 4, or 5 levels. Given this inconsistency in
response categories, we extrapolated the values to a common scale (0-100) with the ‘Always’ responses
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anchored at one end and the ‘Never’ or ‘Rarely/Never’ responses anchored at the other, and proportionate
spacing in-between (i.e. 4 category scale was recoded as 0, 33, 66, 100). Variables were then transformed to z-
scores, with higher scores indicating greater symptom burden.
The ALSPAC parent-reported SDB measures are similar or identical to question-items previously
validated against polysomnographic (PSG) data from sleep laboratories. Some validated questionnaires have
included parent report of all three SDB symptoms, 15-19 -- whereas others have included only snoring and
apnea. 20, 21
Behavior Assessment
The Strengths & Difficulties Questionnaire (SDQ), 22 a widely used behavioral screen, was completed
by mothers when children were ≈ 4 and 7 years old. The 25 item SDQ has 5 scales: inattention/hyperactivity;
emotional symptoms (anxiety and depression); peer problems; conduct problems (aggressiveness and rule-
breaking); and a prosocial scale (sharing, helpfulness, etc.). A total difficulties (range= 0-40) score is generated
by summing all but the latter scale because the absence of prosocial behavior is conceptually different from the
presence of psychological difficulties. Higher scores denote more problems. Missing data were prorated
according to SDQ instructions.23
The SDQ scores were dichotomized at the upper 10% based on psychometric
testing, 24 ALSPAC, 25, 26 and other UK cohort studies. 27
Covariate Assessment
Initial covariate selection was guided by prior ALSPAC studies of SDQ outcomes 26, 28-34 , and non-
ALSPAC studies of sleep problem effects upon SDQ outcomes. 35, 36 Based upon this literature review, and
exploratory analyses, 16 potential confounders were incorporated into analyses.
Socioeconomic status was measured by paternal employment (manual vs. professional), maternal
education (higher vs. lower), and housing inadequacy (if either > 1 person/room or homeless). Family adversity
was measured by an 18 item index of stressors (e.g., maternal psychopathology, crime, financial insecurity)
used in other ALSPAC analyses; 37 higher values signify more adversity. Intrauterine exposures of maternal
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smoking or alcohol use in the first trimester (yes/no), and fish intake at 32 weeks gestation (servings/week)
were assessed, as was whether the child was ever breast-fed, and mother’s age at delivery. Household variables
included family size (0, 1, or >2 children in household at 6 months interview) and the HOME Inventory 38 to
assess the quality of parenting and home environment. Child demographics included race (white vs. other) and
gender, low birth weight (<2500 grams) and prematurity (< 37 weeks). BMI contributes to increased levels of
SDB, which, given causal mechanisms, 39 is more likely to affect neuro-behavioral outcomes than BMI.
Therefore, to decrease risk of over-adjustment in multivariate models, BMI was not included as a covariate.
Derivation of SDB Clusters
To predict behavior at 4 years, “Early” clusters were derived from n=11,309 participants in the base
sample with >2 of the first 4 SDB measures. To predict 7 year behavioral outcomes, we derived “Later” clusters
from n=11,510 participants in the base sample with >2 of the first 6 SDB measures. SDB Z scores (see above)
were partitioned into clusters using SAS FASTCLUS version 9.1 (Cary, NC) with k-means cluster solutions for
5, 6, 7 and 8 unique sets of clusters; within each solution, differences across time points were compared among
clusters to demonstrate their uniqueness. We validated the clusters’ clinical significance and uniqueness against
measures of a) wheezing and b) tonsils and/or adenoid removal. Wheezing history in ALSPAC is predictive of
physician-diagnosed asthma, 40 a known risk factor for SDB, 41, 42 while adenotonsillectomy is the first line
treatment for SDB. 7 Our methodology for selecting final cluster solutions was informed by prior analytic
work, 43-45 , This process produced e xposure variables that included n=5 conceptually and statistically distinct
“Early” clusters (6-42 months), and n=5 comparable “Later” clusters (6-69 months) that were extensions of
Early clusters. Briefly, these are: 1)symptoms “Peak @ 6” and then return to normal, 2) symptoms “Peak @ 18”
months and then return to normal, 3) symptoms peak at 30 months and then persist (“Worst case”), 4)
symptoms emerge at 42 months and then persist (“Late Symptom”) and 5) “Normals” who are asymptomatic
throughout.
Statistical Analysis
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For SDQ scores at 4 and 7 years, we calculated the mean (sd), and proportions above and below the 10%
cut-off for the base sample, and their associations with putative covariates. We describe the association between
SDQ mean (sd) total scores at 4 and 7 years and the Early and Later clusters, by analysis of variance
(ANOVA), Only participants with non-missing SDQ data are included in analyses of behavioral outcomes.
Multivariate logistic regression analyses examined adjusted and unadjusted relationships between
clusters and SDQ total and subscales at 4 and 7 years. Initial models included all putative covariates. Only
those variables that were significant (p<=0.05) variables were retained in multivariate models. Odds ratios (OR)
and 95% confidence intervals (95%CIs) represent the odds of being in the top 10% vs. the remaining 90% of
SDQ scores. To address multi-collinearity, variance inflation factors (VIF) were derived to assess the effects of
individual independent variables upon variance. A conservative VIF threshold of 10 was employed in model
testing. 46 Analyses were conducted using SAS v9.1. 47
Results:
Data completion and attrition.
SDB longitudinal data were relatively complete (not shown): Early cluster analyses (4 year SDQ
outcomes), based upon 9,206 participants, included n=7,701 (84%), n=1,107 (12%) and=398 (4%) with SDB
data for 4/4, 3/4, and 2/4 timepoints, respectively. Early cluster analyses of the n=8,167 participants with 81
month SDQ outcomes included n=7,875 (96%) with SDB data for >3/4 timepoints. Later cluster analyses (81
month SDQ data) for n=8,243 participants, included n=7,528 (91%) with SDB data for >5/6 timepoints.
Missing SDQ or SDB data were significantly associated with: non-white race, pre-maturity, low birth weight,
manual (vs. professional) paternal employment, lower (vs. higher) maternal educational status, housing
inadequacy, not being breastfed, and higher levels of wheezing (not shown).
Sample Characteristics and Association with Top 10% of SDQ Total Scores
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Characteristics of the base sample and associations with behavioral outcomes are shown in Table
1.Children in the upper 10% of SDQ scores had significantly more adverse characteristics (e.g.,higher maternal
smoking, lower maternal education, higher Family Adversity Index scores, and lower HOME scores) than the
remaining 90%, at 4 and 7 years, but no differences by race, maternal alcohol intake during pregnancy, or
adenoid removal.
Cluster Description and Association with Sample Characteristics
Five early clusters representing n=11,309 children are illustrated in Figures 1a-1e; their descriptive
characteristics are shown in Table 2. Four are symptomatic ( ≈ 55% of sample) and one (“Normals,” 45% of
sample) is asymptomatic. “Worst Case” has the greatest symptom burden, and most adverse risk profile,
followed by “Late Symptom”. The three symptoms’ patterns are essentially parallel in the other clusters, but in
these two, snoring levels are nearly double those of apnea or mouth-breathing. “Peak@ 18” and “Peak @ 6”
have moderate symptom levels which abate prior to 30 months. Whether assessed as a continuous or
dichotomous (10% v. 90%) variable, SDQ total scores differed significantly across the four symptomatic
clusters, and in combined symptomatic clusters vs. “Normals.”
Five comparable later clusters representing n=8,243 children are illustrated in Figures 2a-e (descriptive
characteristics not shown). Patterns are similar to the Early clusters, except that in this “Late Symptom” cluster
snoring and mouth-breathing peak together at lower levels at 57 months with no marked apnea, and; the “Peak
@ 6” apnea levels are nearly double those of the Early clusters.
SDQ Total Score
The SDB clusters significantly predict SDQ total scores at 4 and 7 years (Table 3). Unadjusted Early
cluster effects of ≈ 40%-140% attenuate to 20%-90% in multivariate analyses. The strongest and most persistent
Early cluster effects are for “Worst Case,” with outcomes essentially unchanged between 4 (OR=1.66, 95%
CI=1.29-2.13) and 7 years (OR=1.67, 95% CI= 1.27-2.18). Later clusters’ unadjusted effect sizes of ≈ 65%-
140% attenuate to 40%-90% in multivariate analyses. In these Later cluster models there is a ≈ 40% effect for
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“Peak@6” and ≈ 50% effect for “Peak@18.”Membership in any symptomatic cluster is associated with being in
the upper 10% of total SDQ scores (v. “Normals”), an effect that increases slightly from 4 (OR=1.40, 95%
CI=1.21 to 1.61) to 7 years (OR=1.57, 95% CI=1.34 to 1.84: Later clusters).
SDB effects were stronger than those of maternal smoking, alcohol use in pregnancy, maternal education
and paternal employment in multivariate analyses (Table 3). Neither race, pre-maturity, low- birthweight,
maternal fish intake, nor maternal age, were significant in any multivariate analyses—total or subscale (not
shown). Only male gender and not being the second or later-born child had greater adverse effects. Greater
family adversity was associated with poorer behavioral outcomes, while higher home environment scores were
associated with improved outcomes. Gender-cluster interactions were not significant for any total or sub-score
analyses.
SDQ Subscores
Unadjusted effects of Early and Later cluster models are shown in Table 4. For the Hyperactivity,
Emotional, Conduct, and Peer subscales, all but one cluster-subscale association was significant, with effects of
≈ 30%-130%. For the Pro-Social subscale, “Peak@6” was the only cluster to have consistent significant adverse
effects. In adjusted analyses, nearly every cluster-subscale association remained significant (Table 5), with
effects of 20%-100%.
Prosocial - “Peak@6” was associated with approximately 30% greater odds of being in the lowest decile across
outcomes at 4 and 7 years. All but one of the remaining associations was not significant.
Hyperactivity -with two exceptions, all effects were significant, and increased from 4 to 7 years. Furthermore,
Early cluster effects at 4 years for “Worst Case” (OR=1.55, 95% CI=1.23 to 1.96) and “Late Symptom”
(OR=1.51, 95% CI=1.21 to 1.88) clusters equaled or increased, respectively, at 7 years [(OR=1.95, 95%
CI=1.51 to 2.52) and (OR=1.59, 95% CI=1.23 to 2.04)].
Emotional - with one exception at 4 years, all effects were significant (range ≈ 20%-70%), and most increased
from 4 to 7 years. “Late Symptom” had the strongest effect at 4 (OR=1.49, 95% CI=1.18 to 1.89) and 7 years
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(OR=1.63, 95% CI=1.29 to 2.06) based upon Early cluster models, with effects persisting to 7 years (OR=1.69,
95% CI= 1.39 to 2.06) in Later cluster models.
Conduct - with two exceptions, all effects were significant (range ≈ 20%-70%). Both “Worst Case” and
“Peak@18” effects increased from 4 to 7 years, while “Late Symptom” and “Peak @6” effects attenuated over
that time.
Peer - While 8 of 12 cluster-subscale associations were significant, SDB effects were more modest (range ≈ 20%-
40%) and stable over time, compared to the other subscales. Effects were strongest for “Worst Case” in the
Later cluster models (OR=1.40, 95% CI=1.09 to 1.78).
Discussion
We examined the effects of snoring, apnea, and mouth-breathing patterns (clusters) upon behavior, from
infancy through 7 years in over 11,000 children. By 4 years, children in any symptomatic cluster were 40%
more likely to exhibit behavioral difficulties consistent with a clinical diagnosis; by 7 years, they were nearly
60% more likely. These effects, in a population-based cohort that controlled for 16 putative confounders,
exceeded those of any measured pre-natal (i.e., maternal age, smoking or alcohol use), gestational age, birth-
weight, breast-feeding, SES, family adversity, or home environment exposure. Furthermore, symptom clusters
observed through 3.5 years were as predictive of behavioral difficulties at 7 years, as they were at 4 years, for
nearly every SDQ total and subscale outcome. Regarding specific clusters, “Worst Case” had the greatest
overall effects-- 90% increased likelihood of behavioral problems based upon symptoms observed through 3.5
years—followed by the “Late Symptoms” cluster. In two clusters, all SDB symptoms peaked before 1.5 years
and abated by 2.5 years, but still predicted 40%-50% increased odds of behavior problems at 7 years. Regarding
specific behaviors, Hyperactivity, Emotional, Conduct, and Peer difficulties were significantly higher for
symptomatic children, with nearly every cluster-subscale association significant. As expected from prior
literature, effects were strongest for Hyperactivity, especially for “Worst Case-- nearly 60% at 4 years, and
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nearly 100% at 7 years. Peer relations, though generally linked to earlier SDB symptoms, appear to have
suffered the least among the behavior subscales.
Compared to prior parent-reported effects of SDB upon later behavior, our findings are conservative. In
a study of ≈ 1,000 third graders, snoring at baseline was associated with 2-10 fold increases in SDQ-assessed
hyperactivity, emotional, conduct and peer difficulties at one year follow-up in age- and gender-adjusted
analyses. 48 A pediatric clinic sample of 229 2-13 year olds found that baseline SDB symptoms predicted 4-fold
increases in hyperactive behaviors at 4 year follow-up, after adjustment for age, gender, and baseline
hyperactivity. 49 These studies differed from ours, with smaller, less representative samples, lack of data from
the earliest years, use of other (non-SDQ) behavioral measures, and limited control for confounders.
Alternatively, several cross-sectional studies that employed different operational definitions of SDB and SDQ
outcomes found no effects. One, a large nationally representative cross-sectional sample of ≈ 5000 Australian 4-
5 year olds, found that neither SDQ total, nor the Hyperactivity, Peer, or Emotional scale (actual) scores were
greater among children with ‘snoring and/or breathing difficulties’ during sleep > 4 times per week. 35 Likewise,
among n=635 6-8 year olds, snoring >1 time week in the past 6 months was not associated with high (upper
10 th%ile) SDQ scores. 36
This is the first study to assess SDB as a trajectory of combined symptoms, across a key period of
development from 6 months to 6.75 years, in a large sample. Previous studies had smaller samples that were
often cross-sectional, or longitudinal 2 years or less of follow-up. Many were not population-based, involved
school-age children only, or did not adjust for as wide a range of counfounders. 8, 50 The potential impact of
confounders is evidenced by the fact that aside from the SDB clusters, 10 of 16 putative covariates were not
significant in any multivariate analyses, and most unadjusted effects of SDB attenuated in controlled analyses.
The current study has several limitations. First, SDB data were derived from parent report, rather than objective
testing. However, the symptom-items used reflect widely accepted and well-validated SDB risk factors.
Further, use of objective measures such as polysomnography in large epidemiological studies is infeasible, and
may be less effective given their limited ability to predict SDB morbidity or response to treatment. 16 Second,
missing SDB and SDQ data were associated with identified SDB risk factors, e.g., maternal smoking, lower
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SES. Although biases that involve selective drop-out may alter prevalence estimates, other ALSPAC analyses
found only marginal effects on regression models predicting behavioral outcomes. 51 This is likely the case in
our study, in which such biases would render our findings more conservative.
These robust findings, from the largest ever cohort study of SDB exposure and future neurobehavioral
morbidity, provide importance evidence that early childhood SDB affects the developing brain to produce
phenotypes that may only become apparent years later. The most significant long-term effects occurred in
children who experienced the worst symptoms by 2.5 years of age. Furthermore, children whose symptoms
peaked by 1.5 years but then abated by 30 months continued to experience significant adverse behavioral
outcomes at 7 years. SDB is relatively common in childhood. In prior analyses of this cohort the prevalence of
habitual snoring ranged from 10%- 21% from 6 months to 6.75 years. 52 The potential clinical implications are
significant: in a large national survey of children’s health, those with ADHD in comparison to their peers had
increased adjusted risks of co-morbid learning disability (8-fold), anxiety (8-fold), and low social competence
(3-fold). 53
Conclusion
If ultimately confirmed by randomized controlled treatment trials, findings presented here could have
substantial implications for public health approaches to screening and treatment. A 2009 consensus statement
by U.K. pediatricians and pediatric specialists noted that “the natural history of SDB, where a child changes
from normality to abnormality, and where the risks of developing complications of the condition outweigh the
risks of the surgical intervention, has not been established.” 54 Although data from multicenter, randomized
controlled trials, such as the current NIH-funded Childhood Adenotonsillectomy (CHAT) study, will ultimately
be required to prove cause-and-effect relationships, the new data presented here provide important
epidemiologic evidence to support attention to SDB symptoms beginning as early as the first year of life.
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Acknowledgements:
We are extremely grateful to all the families who took part in this study, the midwives for their help in
recruiting them, and the whole ALSPAC team, which includes interviewers, computer and
laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and
nurses. In addition, the authors wish to thank the following members of the study’s advisory group:
Dr. Raanan Arens (Montefiore Medical Center/Albert Einstein College of Medicine), Dr. John Bent
(Montefiore Medical Center/Albert Einstein College of Medicine), Dr. Peter Blair (University of Bristol), Dr.
Pauline Emmett (University of Bristol), Dr. Peter Fleming (University of Bristol), Dr. Jon Heron (University of
Bristol), Dr. Carole Marcus (Children’s Hospital of Philadelphia), Dr. Kenneth Ong (Cambridge University), Dr.
Sanjay Parikh (Montefiore Medical Center/Albert Einstein College of Medicine), and Dr. Susan Redline (Case
Western Reserve University).
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References:
1. Li HY, LA. L. Sleep-disordered breathing in children. Chang Gung Med J. 2009;32(3):247-257.2. Sahin U, Ozturk O, Ozturk M, Songur N, Bircan A, A. A. Habitual snoring in primary school children:
prevalence and association with sleep-related disorders and school performance. Med Princ Pract. .2009;18(6):458-465.
3. Beebe DW, Gozal D. Obstructive sleep apnea and the prefrontal cortex: towards a comprehensive modellinking nocturnal upper airway obstruction to daytime cognitive and behavioral deficits. Journal of Sleep Research. Mar 2002;11(1):1-16.
4. Beebe DW. Neurobehavioral effects of obstructive sleep apnea: an overview and heuristic model.Current Opinion in Pulmonary Medicine. Nov 2005;11(6):494-500.
5. Owens JA. Neurocognitive and behavioral impact of sleep disordered breathing in children. Pediatr Pulmonol. May 2009;44(5):417-422.
6. Halbower AC, Marcus CL. Sleep disorders in children. Curr Opin Pulm Med. Nov 2003;9(6):471-476.7. American Academy of Pediatrics. Clinical practice guideline: diagnosis and management of childhood
obstructive sleep apnea syndrome. Pediatrics. Apr 2002;109(4):704-712.8. Simmons MS, Clark GT. The potentially harmful medical consequences of untreated sleep-disordered
breathing The evidence supporting brain damage. Journal of the American Dental Association. May2009;140(5):536-542.9. Ebert CS, Drake AF. The impact of sleep-disordered breathing on cognition and behavior in children: A
review and meta-synthesis of the literature. Otolaryngology-Head and Neck Surgery. Dec2004;131(6):814-826.
10. Mitchell RB, Kelly J. Behavior, neurocognition and quality-of-life in children with sleep-disorderedbreathing. International Journal of Pediatric Otorhinolaryngology. Mar 2006;70(3):395-406.
11. Cortese S, Faraone SV, Konofal E, Lecendreux M. Sleep in Children With Attention-Deficit/Hyperactivity Disorder: Meta-Analysis of Subjective and Objective Studies. Journal of the
American Academy of Child and Adolescent Psychiatry. Sep 2009;48(9):894-908.12. Gruber R, Xi T, Frenette S, Robert M, Vannasinh P, Carrier J. Sleep Disturbances in Prepubertal
Children with Attention Deficit Hyperactivity Disorder: A Home Polysomnography Study. Sleep. Mar2009;32(3):343-350.13. Owens JA, Maxim R, Nobile C, McGuinn M, Msall M. Parental and self-report of sleep in children with
attention-deficit/hyperactivity disorder. Arch. Pediatr. Adolesc. Med. Jun 2000;154(6):549-555.14. Golding J, Team AS. The Avon Longitudinal Study of Parents and Children (ALSPAC) - study design
and collaborative opportunities. European Journal of Endocrinology. Nov 2004;151:U119-U123.15. Chervin RD, Hedger K, Dillon JE, Pituch KJ. Pediatric Sleep Questionnaire: validity and reliability of
scales for sleep-disordered breathing, snoring, sleepiness, and behavioral problems. Sleep Medicine.2000;1:21-32.
16. Chervin RD, Weatherly RA, Garetz SL, et al. Pediatric sleep questionnaire: Prediction of sleep apneaand outcomes. Archives of Otolaryngology-Head & Neck Surgery. Mar 2007;133(3):216-222.
17. Franco RA Jr, Rosenfeld RM, M R. First place--resident clinical science award 1999. Quality of life forchildren with obstructive sleep apnea. Otolaryngol Head Neck Surg. 2000;123((1 Pt 1)):9-16.
18. Li AM, Cheung A, Chan D, et al. Validation of a questionnaire instrument for prediction of obstructivesleep apnea in Hong Kong Chinese children. Pediatr Pulmonol. 2006;41(12):1153-1160.
19. Brouillette RT, Fernbach SK, Hunt CE. Obstructive sleep apnea in infants and children. J Pediatr. Jan1982;100(1):31-40.
20. Bruni O, Ottaviano S, Guidetti V, et al. The sleep disturbance scale for children (SDSC) constructionand validation of an instrument to evaluate sleep disturbances in childhood and adolescence. Journal of Sleep Research. Dec 1996;5(4):251-261.
21. Ferreira VR, Carvalho LB, Ruotolo F, de Morais JF, Prado LB, GF P. Sleep disturbance scale forchildren: translation, cultural adaptation, and validation. Sleep Medicine. 2009;10(4):457-463.
Page 16
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8/6/2019 Pediatrics 2011 Sleep Disordered Breathing
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R e v i e w C
o p y
22. Goodman R. The strengths and difficulties questionnaire: A research note. Journal of Child Psychologyand Psychiatry and Allied Disciplines. Jul 1997;38(5):581-586.
23. www.sdqinfo.com/ScoreSheets/e1.pdf . Scoring the Informant Rated Strengths and DifficultiesQuestionnaire. Accessed 22 December 2010.
24. Goodman R. Psychometric properties of the strengths and difficulties questionnaire. J. Am. Acad. Child Adolesc. Psychiatr. Nov 2001;40(11):1337-1345.
25. Ramchandani P, Psychogiou L. Paternal psychiatric disorders and children's psychosocial development. Lancet. Aug 2009;374(9690):646-653.
26. Hibbeln JR, Davis JM, Steer C, et al. Maternal seafood consumption in pregnancy andneurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study. Lancet.Feb 2007;369(9561):578-585.
27. Kelly Y, Sacker A, Gray R, Kelly J, Wolke D, Quigley MA. Light drinking in pregnancy, a risk forbehavioural problems and cognitive deficits at 3 years of age? Int. J. Epidemiol. Feb 2009;38(1):129-140.
28. Wiles NJ, Northstone K, Emmett P, Lewis G, Team AS. "Junk food" diet and behavioural problems atage 7. American Journal of Epidemiology. Jun 2006;163(11):S18-S18.
29. Brion MJ, Victora C, Matijasevich A, et al. Maternal Smoking and Child Psychological Problems:Disentangling Causal and Noncausal Effects. Pediatrics. Jul 2010;126(1):E57-E65.
30. Enoch MA, Steer CD, Newman TK, Gibson N, Goldman D. Early life stress, MAOA, and gene-
environment interactions predict behavioral disinhibition in children. Genes Brain and Behavior. Feb2010;9(1):65-74.
31. Lawson DW, Mace R. Siblings and childhood mental health: Evidence for a later-born advantage. SocialScience & Medicine. Jun 2010;70(12):2061-2069.
32. Huisman M, Araya R, Lawlor DA, Ormel J, Verhulst FC, Oldehinkel AJ. Cognitive ability, parentalsocioeconomic position and internalising and externalising problems in adolescence: Findings from twoEuropean cohort studies. European Journal of Epidemiology. Aug 2010;25(8):569-580.
33. Wiles NJ, Peters TJ, Heron J, et al. Fetal growth and childhood behavioral problems: Results from theALSPAC cohort. American Journal of Epidemiology. May 2006;163(9):829-837.
34. Brion MJ, Zeegers M, Jaddoe V, et al. Intrauterine Effects of Maternal Prepregnancy Overweight onChild Cognition and Behavior in 2 Cohorts. Pediatrics. Jan 2011;127(1):E202-E211.
35. Hiscock H, Canterford L, Ukoumunne OC, Wake M. Adverse associations of sleep problems inAustralian preschoolers: national population study. Pediatrics. Jan 2007;119(1):86-93.
36. Smedje H, Broman JE, Hetta J. Associations between disturbed sleep and behavioural difficulties in 635children aged six to eight years: a study based on parents' perceptions. European Child & Adolescent Psychiatry. Mar 2001;10(1):1-9.
37. Bowen E, Heron J, Waylen A, Wolke D, Team AS. Domestic violence risk during and after pregnancy:findings from a British longitudinal study. Bjog-an International Journal of Obstetrics and Gynaecology. Aug 2005;112(8):1083-1089.
38. Mundfrom DJ, Bradley RH, Whiteside L. A factor-analytic study of the infant-toddler and early-childhood versions of the home inventory. . Educational and Psychological Measurement. Sum1993;53(2):479-489.
39. Jan JE, Reiter RJ, Bax MCO, Ribary U, Freeman RD, Wasdell MB. Long-term sleep disturbances inchildren: A cause of neuronal loss. European Journal of Paediatric Neurology. Sep 2010;14(5):380-390.40. Henderson J, Granell R, Heron J, et al. Associations of wheezing phenotypes in the first 6 years of life
with atopy, lung function and airway responsiveness in mid-childhood. Thorax. Nov 2008;63(11):974-980.
41. Kaditis AG, Kalampouka E, Hatzinikolaou S, et al. Associations of Tonsillar Hypertrophy and SnoringWith History of Wheezing in Childhood. Pediatric Pulmonology. Mar 2010;45(3):275-280.
42. Desager KN, Nelen V, Weyler JJJ, De Backer WA. Sleep disturbance and daytime symptoms inwheezing school-aged children. Journal of Sleep Research. Mar 2005;14(1):77-82.
43. Boone-Heinonen J, Gordon-Larsen P, Adair L. Obesogenic Clusters: Multidimensional AdolescentObesity-related Behaviors in the US. Annals of Behavioral Medicine. Dec 2008;36(3):217-230.
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44. Ercoli LM, Siddarth P, Kepe V, et al. Differential FDDNP PET Patterns in Nondemented Middle-Agedand Older Adults. American Journal of Geriatric Psychiatry. May 2009;17(5):397-406.
45. Lambert M, Schimmelmann BG, Schacht A, et al. Long-term patterns of subjective wellbeing inschizophrenia: Cluster, predictors of cluster affiliation, and their relation to recovery criteria in 2842patients followed over 3 years. Schizophrenia Research. Feb 2009;107(2-3):165-172.
46. O'Brien RM. A caution regarding rules of thumb for variance inflation factors. Qual. Quant. Oct2007;41(5):673-690.
47. SAS Institute Inc. Cary, N.C. ;Version 9.1.
48. Urschitz MS, Eitner S, Guenther A, et al. Habitual snoring, intermittent hypoxia, and impaired behaviorin primary school children. Pediatrics. Oct 2004;114(4):1041-1048.
49. Chervin RD, Ruzicka DL, Archbold KH, Dillon JE. Snoring predicts hyperactivity four years later.Sleep. Jul 1 2005;28(7):885-890.
50. Kuehni CE, Strippoli MPF, Chauliac ES, Silverman M. Snoring in preschool children: prevalence,severity and risk factors. European Respiratory Journal. Feb 2008;31(2):326-333.
51. Wolke D, Waylen A, Samara M, et al. Selective drop-out in longitudinal studies and non-biasedprediction of behaviour disorders. British Journal of Psychiatry. Sep 2009;195(3):249-256.
52. Bonuck KA, Chervin RD, Cole T, et al. Prevalence and persistence of sleep disordered breathingsymptoms in young children:
A 6 year population-based cohort study. Sleep. 2011;XXXX.
53. Larson K, Russ SA, Kahn RS, Halfon N. Patterns of Comorbidity, Functioning, and Service Use for USChildren With ADHD, 2007. Pediatrics. 2011.
54. Robb PJ, Bew S, Kubba H, et al. Tonsillectomy and adenoidectomy in children with sleep relatedbreathing disorders: consensus statement of a UK multidisciplinary working party. ClinicalOtolaryngology. Feb 2009;34(1):61-63.
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Table 1: Sample: Demographics for total sample and by SDQ Scores at 4 and 7 YearsSDQ total Score, 4 years SDQ Total Score, 7 Years
Total Sample * N=13,810
Top 10%N=1,250
Lower 90%N=8,102
Top10%N=908
Lower 90%N=7,208
Maternal
Smoked during pregnancy, any 25.1% 30.6%† 20.0% 30.9%† 18.7%
Alcohol during pregnancy, any 54.5% 55.7% 55.4% 58.4% 55.6%
Fish intake during pregnancy, mean(sd)
1.88(1.75) 1.94 (1.80) 1.87 (1.73) 1.80 (1.53) 1.89 (1.75)
Age at delivery, mean years (sd) 27.99(4.96) 27.52 (4.78)† 28.87 (4.64) 28.12 (4.74)† 29.03 (4.56)
Breastfed this child, ever 75.3% 72.6%† 78.51% 76.8% 79.2%
Child
Gender, male 51.6% 55.2%† 51.2% 60.0%† 50.6%
Race, white 97.4% 98.2% 98.3% 98.2% 98.3%
Premature, <37 weeks 5.9% 6.2% 5.2% 6.5%‡ 4.9%
Low birthweight, <2500 grams 5.2% 5.7% 4.5% 5.6%‡ 4.2%
Adenoids removed, ever 7.6% ----- ----- 4.9% 3.9%
Tonsils removed, ever 4.6% ----- ----- 9.2%† 6.3%
Socioeconomic and Family
Maternal Education, § Lower (%) 64.6% 70.9%† 59.0% 60.7%† 57.8%
Paternal Employment, Manual (%) 44.0% 51.9%† 2,328 (39.3%) 363 (47.5%)† 39.1%
Housing, Inadequate, (%) 12.4% 18.7%† 11.8% 18.4%† 11.1%Family Adversity Index, Mean (range,
0-18) 1.78(1.98) 2.63 (2.26) † 1.74 (1.88) 2.85 (2.38) † 1.71 (1.85)
HOME Score, mean (range: 0-8) 5.75(1.66) 5.61 (1.76) † 5.81 (1.62) 5.48 (1.75) † 5.84 (1.61)
Parity, >=1 55.4% 52.0% 54.5% 50.7%‡ 54.5%
*These n=13,810 constitute the base sample used to derive the clusters and SDQ outcomes.†p<.01 for difference between top 10% vs. lower 90%‡p<.05 for difference between top 10% vs. lower 90%§“Lower” defined as “O” level education or less (equivalent to school leaving certificate at 16 in the UK), from 5 original groupings.
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Table 2: Association Between Early Clusters (n= 11,309) and Potential Confounders and SDQ outcomePeak @ 6
n=2270(21.1%)
(1)
Peak @ 18n=2009(17.8%)
(2)
Worst Casen=862(7.6%)
(3)
Late Symptomn=1063(9.4%)
(4)
Normalsn=5105(45.1%)
(5)
P *
Maternal Characteristics
Smoked during pregnancy,any 24.9% 25.4% 29.2% 28.3% 18.3% <0..001Alcohol during pregnancy,any 53.8% 53.8% 55.0% 53.9% 56.5% 0.119Fish intake duringpregnancy, mean 1.85 1.86 1.95 1.93 1.87 0.673Age at delivery, mean(years) 28.32 28.01 27.78 27.90 28.93 <0.001Breastfed this child, Ever 74.9% 75.2% 69.3% 74.5% 78.5% <0.001Child Characteristics
Gender, male 54.1% 52.8% 55.7% 52.0% 49.3% <0.001Race, white 98.1% 96.8% 97.9% 97.6% 98.2% 0.008Premature, <37 weeks 5.4% 5.5% 7.7% 7.1% 5.0% 0.005Low birth weight, <2500grams 4.3% 5.7% 5.8% 5.8% 4.3% 0.013Socioeconomic andFamily CharacteristicsMaternal Education,Lower (%) 65.5% 66.4% 67.7% 67.1% 58.4% <0.001Paternal Employment,Manual (%) 43.1% 46.5% 47.4% 43.7% 39.5% <0.001Housing, Inadequate (%) 15.1% 15.0% 17.3% 12.9% 10.1% <0.001Family Adversity Indexmean (range, 0-18) 2.14 2.14 2.48 2.12 1.62 <0.001
HOME Score, mean(range: 0-8) 5.72 5.73 5.72 5.71 5.81 0.081Parity, >=1 55.1% 53.3% 55.1% 53.8% 55.7% 0.437Outcome SDQSDQ top10% @ 4 year 13.5% 15.1% 18.6% 20.1% 10.1% <0.001SDQ top10% @ 7 year 11.8% 12.9% 16.7% 14.6% 8.6% <0.001SDQ continuous @4 year 14.58 14.65 15.32 15.36 13.90 <0.001SDQ continuous @7 year 8.12 7.90 8.74 8.27 6.77 <0.001
Combined Symptomatic (1,2,3,&4)SDQ top10% @4 year 15.77% 10.14% <0.001SDQ top10% @7 year 13.28% 8.61% <0.001SDQ continuous @4 year 14.83 13.90 <0.001
SDQ continuous @7 year 8.16 6.78 <0.001*P values are calculated from chi-square test or analysis of variance.
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Table 3: Cluster Effects Upon SDQ Total Scores at 4 and 7 Years
Early Cluster Models Later Cluster Models
Top 10% v. Lower 90% OR (95% CI) 4 Years 1 p 7 years 1.2 p 7 years 1,2 p
Unadjusted, SDB
“Peak @ 6”(1) 1.38(1.17,1.63) <0.001 1.43(1.18,1.72) <0.001 1.65(1.34,2.04) <0.001
“Peak @ 18 Mos.”(2) 1.57(1.33,1.86) <0.001 1.57(1.29,1.91) <0.001 1.69(1.39,2.05) <0.001
“Worst Case” (3) 2.02(1.62,2.51) <0.001 2.12(1.66,2.72) <0.001 2.42(1.90,3.09) <0.001
“Late Symptom”(4) 2.23(1.83,2.72) <0.001 1.82(1.43,2.31) <0.001 2.03(1.66,2.48) <0.001
Symptomatic(1,2,3,4) v.“Normals” (5) 1.66(1.46,1.88) <0.001 1.63(1.41,1.88) <0.001 1.86(1.61,2.16) <0.001
Adjusted , SDB
“Peak @ 6”(1) 1.20(1.00,1.45) 0.051 1.20(0.98,1.47) 0.082 1.39 (1.11,1.74) 0.004“Peak @ 18 Mos.”(2) 1.36(1.13,1.65) <0.001 1.29(1.05,1.60) 0.017 1.49 (1.29,1.84) <0.001
“Worst Case” (3) 1.66(1.29,2.13) <0.001 1.67(1.27,2.18) <0.001 1.89(1.45,2.47) <0.001
“Late Symptom”(4) 1.84(1.46,2.30) <0.001 1.50(1.16,1.94) 0.002 1.69 (1.35,2.10) <0.001
Clusters1,2,3 & 4 v.“Normals” (5)
1.40(1.21,1.61) <0.001 1.34(1.15,1.36) <0.001 1.57(1.34,1.84) <0.001
Covariates 3
Smoking duringpregnancy
---------- N.S. 1.24 (1.04,1.49) <0.017 1.24 (1.04,1.48) 0.019
Gender, male 1.22 (1.07,1.40) 0.004 1.54 (1.32,1.80) <0.001 1.55 (1.33,1.81) <0.001Maternal education,
lower1.38 (1.18,1.61) <0.001 1.29 (1.10,1.52) 0.002 1.29 (1.10,1.52) 0.002
Paternal employment,manual 1.33 (1.15,1.54) 0.001 ----------- N.S. ---------- N.S.
Family Adversity Index 1.21 (1.17,1.25) <.001 1.24 (1.20,1.29) <0.001 1.24 (1.20,1.28) <0.001Home Score ---------- N.S. 0.91 (0.87,0.95) <0.001 0.91 (0.87,0.95) <0.001
Parity 1 v. 02 v. 0
0.91 (0.78,1.05)0.63 (0.52,0.78)
0.088<0.001
0.73 (0.61,0.86)0.58 (0.46,0.72)
0.6180.001
0.73 (0.62,0.87)0.59 (0.47,0.73)
0.600<0.001
1Adjusted for fish intake, FAI, Mother and home score, smoke during pregnancy, alcohol during pregnancy, race, breast feeding ever,housing inadequency, parity, gestation age, paternal social, maternal education, birth weight, maternal age, gender.2 Additional adjusted for Tonsils or adenoids removed.3 Covariates shown are only those that were significant (p<.05) in reduced models with each of the four symptomatic modelsincorporated as a separate variable (vs. combined clusters 1,2,3, & 4).
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Table 4 Unadjusted Cluster Effects Upon SDQ Subscales at 4 and 7 Years
Early Cluster Models Later Cluster Models
Top 10% v. Lower 90%
OR (95% CI)
4 Years p 7 years p 7 years p
Pro-Social “Peak @ 6” 1.35(1.13,1.63) 0.001 1.41(1.16,1.70) <0.001 1.37(1.11,1.68) 0.003
“Peak @ 18 Mos.” 1.17(0.96,1.43) 0.121 1.33(1.08,1.63) 0.006 1.22(0.99,1.49) 0.055
“Worst Case” 1.29(0.98,1.69) 0.068 1.37(1.03,1.82) 0.030 1.11(0.83,1.48) 0.481
“Late Symptom” 1.01(0.77,1.33) 0.928 0.95(0.71,1.27) 0.731 0.88(0.69,1.11) 0.275
Hyperactivity “Peak @ 6” 1.34(1.15,1.57) <0.001 1.56(1.30,1.88) <0.001 1.69(1.37,2.08) <0.001
“Peak @ 18 Mos.” 1.31(1.11,1.55) 0.001 1.53(1.26,1.87) <0.001 1.58(1.29,1.92) <0.001
“Worst Case” 1.89(1.53,2.33) <0.001 2.23(1.74,2.85) <0.001 2.25(1.76,2.88) <0.001
“Late Symptom” 1.72(1.41,2.10) <0.001 1.74(1.36,2.22) <0.001 1.94(1.58,2.37) <0.001
Emotional “Peak @ 6” 1.27(1.06,1.52) 0.011 1.47(1.23,1.75) <0.001 1.65(1.36,2.00) <0.001
“Peak @ 18 Mos.” 1.32(1.10,1.60) 0.003 1.43(1.19,1.71) <0.001 1.53(1.28,1.84) <0.001
“Worst Case” 1.58(1.23,2.02) <0.001 1.63(1.27,2.09) <0.001 1.76(1.38,2.24) <0.001
“Late Symptom” 1.54(1.23,1.95) <0.001 1.66(1.32,2.08) <0.001 1.90(1.58,2.29) <0.001
Conduct “Peak @ 6” 1.60(1.36,1.88) <0.001 1.51(1.25,1.82) <0.001 1.43(1.16,1.77) 0.001
“Peak @ 18 Mos.” 1.45(1.22,1.72) <0.001 1.55(1.27,1.88) <0.001 1.61(1.33,1.96) <0.001
“Worst Case” 1.71(1.37,2.15) <0.001 1.95(1.51,2.52) <0.001 1.98(1.54,2.55) <0.001
“Late Symptom” 1.95(1.59,2.39) <0.001 1.46(1.13,1.89) 0.004 1.55(1.26,1.91) <0.001
Peer “Peak @ 6” 1.29(1.07,1.54) 0.006 1.31(1.11,1.56) 0.002 1.37(1.14,1.66) 0.001
“Peak @ 18 Mos.” 1.29(1.07,1.56) 0.008 1.41(1.18,1.68) <0.001 1.42(1.19,1.70) <0.001
“Worst Case” 1.43(1.11,1.83) 0.006 1.65(1.30,2.09) <0.001 1.64(1.30,2.08) <0.001
“Late Symptom” 1.25(0.98,1.59) 0.077 1.38(1.10,1.74) 0.006 1.40(1.16,1.69) <0.001
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Table 5 Adjusted Clusters Effects Upon SDQ Subscales at 4 and 7 Years
Early Cluster Models Later Cluster Models
Top 10% v. Lower 90% OR (95% CI)
4 Years 1
p 7 years 2
p 7 years 2
p Pro,Social
“Peak @ 6” 1.25(1.03,1.51) 0.025 1.32(1.09,1.60) 0.005 1.27(1.03,1.56) 0.029
“Peak @ 18 Mos.” 1.16(0.94,1.43) 0.164 1.27(1.03,1.56) 0.024 1.16(0.95,1.42) 0.150“Worst Case” 1.16(0.87,1.54) 0.317 1.23(092,1.64) 0.162 0.99(0.74,1.33) 0.942
“Late Symptom” 0.99(0.74,1.31) 0.936 0.91(0.68,1.23) 0.538 0.87(0.68,1.10) 0.243Hyperactivity
“Peak @ 6” 1.13 (0.95,1.34) 0.166 1.42 (1.17,1.72) <0.001 1.50 (1.21,1.86) <0.001“Peak @ 18 Mos.” 1.07 (0.89,1.28) 0.500 1.36 (1.11,1.67) 0.004 1.42(1.16,1.75) <0.001
“Worst Case” 1.55 (1.23,1.96) <0.001 1.95 (1.51,2.52) <0.001 1.96(1.52,2.53) <0.001“Late Symptom” 1.51 (1.21,1.88) <0.001 1.59 (1.23,2.04) <0.001 1.78(1.44,2.20) <0.001
Emotional “Peak @ 6” 1.17(0.97,1.41) 0.105 1.39(1.16,1.67) <0.001 1.48(1.21,1.81) <0.001
“Peak @ 18 Mos.” 1.23(1.01,1.49) 0.037 1.33(1.09,1.61) 0.004 1.47(1.21,1.77) <0.001
“Worst Case” 1.44(1.12,1.86) 0.005 1.37(1.05,1.80) 0.022 1.51(1.15,1.97) 0.003“Late Symptom” 1.49(1.18,1.89) <0.001 1.63(1.29,2.06) <0.001 1.69(1.39,2.06) <0.001
Conduct “Peak @ 6” 1.41(1.20,1.66) <0.001 1.30(1.07,1.58) 0.009 1.21(0.97,1.51) 0.085
“Peak @ 18 Mos.” 1.26(1.05,1.50) 0.011 1.34(1.09,1.64) 0.005 1.41(1.15,1.72) 0.009“Worst Case” 1.40(1.11,1.77) 0.005 1.64(1.26,2.13) <0.001 1.61(1.39,2.19) <0.001
“Late Symptom” 1.68(1.36,2.08) <0.001 1.26(0.97,1.64) 0.088 1.36(1.09,1.68) 0.006Peer
“Peak @ 6” 1.22(1.02,1.47) 0.033 1.16(0.98,1.39) 0.093 1.19(0.98,1.45) 0.083“Peak @ 18 Mos.” 1.25(1.03,1.52) 0.022 1.27 (1.06,1.53) 0.010 1.28(1.07,1.54) 0.008
“Worst Case” 1.31(1.02,1.70) 0.038 1.36(1.06,1.75) 0.014 1.40(1.09,1.78) 0.008“Late Symptom” 1.15(0.90,1.48) 0.267 1.22(0.96,1.55) 0.099 1.25(1.03,1.52) 0.027
1Adjusted for fish intake, FAI, Mother and home score, smoke during pregnancy, alcohol during pregnancy, race, breastfeeding ever, housing inadequacy, parity, gestation age, paternal social, maternal education, birth weight, maternal age,gender.2Additional adjusted for Tonsils or adenoids removed ever.
e 23 of 33
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R e v i e w C
o p y
1a. Early Cluster
Peak @ 6 Month
-3
-2
-1
0
1
2
3
6 18 30 42
Month
S D B Z S c o r e
AP
SN
MB
Page 24
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R e v i e w C
o p y
1b Early Cluster
Peak @ 18 Month
-3
-2
-1
0
1
2
3
6 18 30 42
Month
S D B Z S c o r e
AP
SN
MB
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R e v i e w C
o p y
1c. Early Cluster
Worst Case
-3
-2
-1
0
1
2
3
6 18 30 42
Month
S D B Z S c o r e
AP
SN
MB
Page 26
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R e v i e w C
o p y
1e. Early Cluster
Normal Case
-3
-2
-1
0
1
2
3
6 18 30 42
Month
S D B Z S c o r e
AP
SN
MB
Page 28
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R e v i e w C
o p y
2a. Later Cluster
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R e v i e w C
o p y
2b. Later Cluster
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R e v i e w C
o p y
2c. Later Cluster
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R e v i e w C
o p y
2d. Later Cluster
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