Association of Sleep Problems and Melatonin Use in School-aged Children

Sleep problems are reported in 25% of children and adolescents.¹ Melatonin is available in many countries without a prescription and is often considered a pharmacologic strategy to treat sleep problems. However, no clinical guidelines are available, and effectiveness and long-term effects of melatonin use in children are largely unknown.¹ Melatonin use has been estimated to be 1% in healthy children. Little is known about the association of objectively measured sleep with melatonin use in this population. We investigated melatonin use in school-aged children and its association with subjective sleep and objectively estimated sleep parameters.

This cross-sectional study included children from the Generation R Study, a birth cohort representative of the general population in the Netherlands.² The Medical Ethics Committee of the Erasmus University Medical Center approved all study procedures, and all parents provided written informed consent. Primary caregivers indicated children’s use of sleep medication (type and frequency throughout 6 months) when children were aged 11 years. Sleep problems were reported by the primary caregiver using the Child Behavior Checklist for Ages 6-18 (5 items) and by the child using the Sleep Disturbance Scale for Children (6 items) when children were aged 10 years.³ At age 11 years, total sleep time, sleep onset latency, and wake after sleep onset were estimated with a sleep diary and triaxial wrist accelerometer (GENEActiv; Activinsights; R-package GGIR⁴). The study procedure has been described previously.⁵ Briefly, the prevalence of caregiver-reported melatonin use was determined first. Second, associations of sleep with melatonin use were assessed with logistic regression analyses, adjusted for appropriate confounders. Missing data for confounders were imputed. As melatonin use has been proposed particularly for children diagnosed as having attention-deficit/hyperactivity disorder and autism spectrum disorder, we repeated analyses excluding children with these diagnoses. A threshold of 2-sided P = .005 was used to correct for multiple testing. Analyses were conducted in SPSS version 24 (IBM Corporation).

A total of 871 children (mean [SD] age, 11.7 [0.2] years; 457 girls [52.2%]; 774 individuals [88.8%] were ethnically Dutch or of other Western European ethnicities; Table 1) were included in this study. Of 871 children, 53 (6.1%) used melatonin at least once a week in the previous 6 months. Caregiver- and child-reported sleep problems were associated with more melatonin use (Table 2). No other associations were observed after multiple testing correction (P = .005; Table 2). Results did not differ between week and weekend sleep and remained largely unchanged when excluding children with attention-deficit/hyperactivity disorder or autism spectrum disorder (n = 15), except that sleep diary–estimated total sleep time was now associated with melatonin use.

This study estimated a prevalence of 6% of melatonin use in school-aged children, indicating that 1 in 17 children is likely to take melatonin at least once a week. This is despite the unknown effects of the use of melatonin in children.¹

We found that caregiver- and child-reported sleep problems and sleep diary–reported shorter total sleep time were associated with melatonin use. The most likely explanation for our findings is that perceived poor sleep is an indication for melatonin use. Indeed, a previous study indicates that parents administer over-the-counter melatonin in 12-year-old children to improve sleep problems.¹ However, melatonin is often taken without prescription or good advice on dosage and timing of administration. If melatonin is taken wrongly, for example by administering it shortly before bedtime, it can actually worsen sleep.⁶ However, the current study is cross sectional, precluding any inference about temporality.

The use of melatonin in school-aged children is common, although potentially harmful effects of melatonin use in children are unknown. Longitudinal and well-controlled studies are urgently needed to identify the effectiveness and potential negative consequences of melatonin use in children. This would provide the evidence to formulate clinical guidelines for the indication and dosage of melatonin in children, which is pressing issue as melatonin is currently freely available.

Corresponding Author: Henning Tiemeier, MD, PhD, Department of Social and Behavioral Science, Harvard T. H. Chan School of Public Health, 677 Huntington Ave, Kresge Bldg, Room 619, Boston, MA 02115 (tiemeier@hsph.harvard.edu).

Accepted for Publication: March 23, 2019.

Published Online: July 22, 2019. doi:10.1001/jamapediatrics.2019.2084

Author Contributions: Drs Koopman-Verhoeff and Luik had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Koopman-Verhoeff, van den Dries, van Seters, Luijk, Luik.

Acquisition, analysis, or interpretation of data: Koopman-Verhoeff, van den Dries, van Seters, Tiemeier, Luik.

Drafting of the manuscript: Koopman-Verhoeff, van den Dries, van Seters, Luik.

Critical revision of the manuscript for important intellectual content: Koopman-Verhoeff, van den Dries, Luijk, Tiemeier, Luik.

Statistical analysis: Koopman-Verhoeff, van den Dries, van Seters.

Obtained funding: Luijk, Tiemeier.

Administrative, technical, or material support: Koopman-Verhoeff, van Seters.

Supervision: Koopman-Verhoeff, van den Dries, Luijk, Tiemeier, Luik.

Conflict of Interest Disclosures: Dr Luik reported nonfinancial and other support from Big Health outside the submitted work. No other disclosures were reported.

Funding/Support: The general design of Generation R Study is made possible by financial support from the Erasmus Medical Center in Rotterdam, the Netherlands; ZonMw; the Netherlands Organization for Scientific Research; and the Ministry of Health, Welfare and Sport and is conducted by the Erasmus Medical Center. This study received support from the Erasmus Medical Center Efficiency Grant (Mrace 2013; Dr Luijk). Dr Tiemeier was supported by a grant from Netherlands Organization for Scientific Research (VICI grant 016.VICI.170.200).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We gratefully acknowledge the contribution of children and parents, general practitioners, hospitals, midwives, and pharmacies in Rotterdam.