Elsevier

Sleep Medicine

Volume 48, August 2018, Pages 93-100
Sleep Medicine

Original Article
Phenotypes of sleep-disordered breathing symptoms to two years of age based on age of onset and duration of symptoms

https://doi.org/10.1016/j.sleep.2018.04.008Get rights and content

Highlights

  • We identified four SDB phenotypes to two years of age: no SDB (65.7%), early-onset SDB (15.7%) with peak symptoms at nine months, late-onset SDB (14.2%) with peak symptoms at 18 months, and persistent SDB (5.3%) with symptoms from 3 to 24 months.

  • Rhinitis was associated with all three SDB symptom trajectories.

  • Several unique risk factors for each SDB trajectory.

    • Children prescribed GERD medication were more likely to present with early or late SDB symptoms.

    • Children with a maternal history of OSAS were more likely to present with late or persistent SDB symptoms.

    • Atopic children were more likely to present with persistent SDB symptoms

    • Late premature infants were more likely to present with late SDB.

Abstract

Objective

Childhood sleep-disordered breathing (SDB) symptoms may comprise multiple phenotypes depending on craniofacial anatomy, tonsil and adenoid growth, body habitus, and rhinitis symptoms. The primary objective of this study is to identify and characterize the different SDB phenotypes to two years of age.

Methods

Data from 770 infants in the Edmonton sub-cohort of the Canadian Healthy Infant Longitudinal Study (CHILD) were analyzed to identify SDB phenotypes based on age of onset and duration of symptoms. Parents completed the 22-item sleep-related breathing disorder (SRBD) scale. Children with a SRBD ratio greater than 0.33 were considered positive for SDB at each quarterly assessment between three months and two years. The STATA Proc trajectory extension identified SDB phenotypes based on their age of onset and duration of symptoms and attributed the percentage chance of a participant being assigned to each phenotype. Multivariate linear regression identified factors associated with increased risk of being assigned to each SDB phenotype.

Results

Trajectory analysis identified four phenotypes: no SDB (65.7%), early-onset SDB (15.7%) with peak symptoms at nine months, late-onset SDB (14.2%) with peak symptoms at 18 months, and persistent SDB (5.3%) with symptoms from 3 to 24 months. Rhinitis was associated with all three SDB symptom trajectories (p < 0.05). Children with gastroesophageal reflux disease presented with early (p = 0.03) and late SDB (p < 0.001). Maternal obstructive sleep apnea syndrome (OSAS) was associated with persistent (p = 0.01) and late SDB (p < 0.001). Atopy (positive skin prick test at one year) was associated with persistent SDB (p = 0.04). Infants born prior to 36.5 weeks gestational age were more likely to present with late SDB (p = 0.03).

Conclusion

Childhood SDB symptoms, rather than being a homogenous disorder, may comprise multiple overlapping phenotypes each with unique risk factors.

Introduction

Sleep disordered breathing (SDB), which may range from habitual snoring to obstructive sleep apnea, affects up to 10% of children, with a peak prevalence between two and eight years of age [1], [2], [3]. An increased risk of snoring has been observed among first-born children [4] and children of mothers who smoked during pregnancy [5], while children who were breastfed for more than two months were less likely to develop SDB [6]. Several studies have shown that SDB is more common among atopic children [7], [8] although one study has reported that inner-city snoring children referred for a laboratory sleep study (polysomnography; PSG) were less likely to have asthma [9]. Self-reported proximity to road traffic was associated with self-reported habitual snoring in preschool children although the strength of the association was reduced when controlling for single-parent families and socioeconomic deprivation [8].

We present findings from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study where we sought to determine patterns of SDB symptoms (SDB phenotypes) based on age of onset and duration of symptoms. Childhood SDB may comprise multiple overlapping phenotypes depending on a child’s craniofacial anatomy, tonsil and adenoid growth, body habitus, and presence of rhinitis symptoms [10]. We hypothesized that the different symptom phenotypes may be distinguished by age of onset and duration of symptoms.

Each phenotype may be associated with different genetics (eg, parental history of SDB) and environmental exposures. Increased lymph-adenoid tissue can be triggered by respiratory syncytial virus [11], environmental tobacco smoke [12], [13], and environmental pollutants [14]. We have identified individual factors (eg, atopy, body mass index [BMI], gestational age [GA]) and environmental exposures (eg, breast-feeding, socioeconomic status (SES), daycare attendance) associated with the development of each SDB symptom.

Section snippets

Study participants

CHILD is a longitudinal birth cohort study designed to assess the influence of gene–environment interactions on the development of allergy and asthma. CHILD Edmonton families (N = 822) participated in an add-on study examining the longitudinal relationship between sleep and neurodevelopment. The sleep-related breathing disorder (SRBD) scale, the Brief Infant Sleep questionnaire (BISQ), parental history of obstructive sleep apnea syndrome (OSAS) based on the global sleep assessment questionnaire

Results

Of those with SDB data, three children had severe developmental delay and were excluded from the subsequent trajectory analysis. Over 93% (770/822) of CHILD Edmonton participants had a response to the SRBD for at least one quarterly questionnaire. Among children with SDB data, 68.5% (510/745) of children were Caucasian compared with 55.9% (19/34) of children without data (p > 0.05; Table 1). Mothers of children with SDB data had a mean age of 31.3 years [95% confidence interval (CI): 31.0,

Discussion

We identified four different parent-reported SDB symptom trajectories using data from a population-based birth cohort study; no SDB, early SDB, late SDB, and persistent SDB. Rhinitis and prior daycare attendance were associated with all SDB trajectories. We identified several unique risk factors for each SDB trajectory. Children prescribed GERD medication were more likely to present with early or late SDB symptoms. Children with a maternal history of OSAS were more likely to present with late

Conclusion

Our results suggest that childhood SDB may not be a homogenous disorder. Rather, childhood parent-reported SDB may represent multiple overlapping phenotypes. We identified three parent-reported SDB symptom trajectories to two years using data from the CHILD Edmonton birth cohort. The SDB trajectories were associated with common and unique risk factors in multivariate analyses. Rhinitis was associated with all SDB trajectories while BMI through the first two years was not associated with any of

Acknowledgments

We are grateful to all the families who took part in this study, and the whole CHILD team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The Canadian Institutes of Health Research (CIHR) and the Allergy, Genes and Environment (AllerGen) Network of Centres of Excellence provided core support for CHILD. This research was specifically funded by CIHR and the Women and Children’s Health

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  • Cited by (0)

    1

    These authors contributed equally to this manuscript.

    2

    A complete list of active investigators in the CHILD study is provided in the Supplementary Material.

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