Melatonin Use and Polysomnographic Sleep Architecture in Children.

Importance: Melatonin is the most widely used sleep aid in children, yet no large study has examined its association with objective sleep architecture measured by polysomnography (PSG). Objective: To assess whether outpatient melatonin use is associated with differences in PSG-derived sleep architecture in a pediatric sleep clinic population. Design, Setting, and Participants: This cross-sectional, propensity score-matched study used the Nationwide Children's Hospital Sleep DataBank, a deidentified dataset of PSG recordings and linked electronic health record data from children evaluated at a single academic pediatric sleep laboratory between 2017 and 2019. Children with at least 1 technically adequate PSG and complete electronic health record data were included; children older than 18 years were excluded. Data were analyzed from January to March 2026. Exposures: Outpatient melatonin prescription documented in the medication list. Main Outcomes and Measures: The prespecified primary outcome was percentage of rapid eye movement (REM) sleep. Fourteen additional PSG parameters (sleep stages, respiratory indices, arousal index, periodic limb movements, oxygen desaturation index) were exploratory. Propensity score matching (1:1 nearest-neighbor, caliper 0.2 SD of the logit propensity score) on age, sex, body mass index percentile, comorbidity burden, obstructive sleep apnea, and epilepsy yielded 342 matched pairs (684 children). Outcomes were compared with 2-sided Wilcoxon signed-rank tests at α = .05; Benjamini-Hochberg false discovery rate (FDR) correction was applied across the 15 outcomes. Results: The analytic cohort constituted 3392 children (mean [SD] age, 8.0 [5.0] years; 1924 male [56.7%]), including 346 melatonin users and 3046 nonusers. The matched cohort constituted 684 children (342 users and 342 nonusers). After matching, all 6 covariates achieved standardized mean differences below 0.10. Melatonin users had a lower median percentage of REM sleep than matched nonusers (16.7% [IQR, 11.6%-22.0%] vs 19.0% [IQR, 14.6%-23.2%]; Hedges g = -0.22 [95% CI, -0.32 to -0.11]; FDR-corrected P = .003). Total sleep time, sleep efficiency, non-REM sleep stages, respiratory indices, arousal index, periodic limb movements, and oxygen desaturation index did not differ (FDR-corrected P > .05 for all 14 exploratory outcomes). The REM association was robust to 1:k matching (each melatonin user matched to 2 or 3 nonusers) and to averaging across repeated PSG nights. After adjusting for 3 psychiatric diagnoses (attention-deficit/hyperactivity disorder, anxiety, depression), REM reduction was preserved with attenuated magnitude (16.6% [IQR, 11.6%-22.0%] vs 18.4% [IQR, 13.4%-22.8%]; Hedges g = -0.17 [95% CI, -0.27 to -0.06]; P = .01). Conclusions and Relevance: In this cross-sectional study of 684 propensity score-matched children, outpatient melatonin use was associated with a small reduction in REM sleep percentage and was not associated with differences in total sleep time, non-REM sleep stages, respiratory parameters, arousal architecture, or periodic limb movements. The REM association was attenuated when psychiatric diagnoses were added to the propensity model. Residual confounding cannot be excluded, and prospective studies with documented dose, timing, and adherence are needed to clarify the directionality of this association.