Table 2.
Characteristics of the included observational studies.
| Reference, country/region | Study design | Population and diagnosis | Age of assessment, sex (% female), Ethnicity | Outcomes/Assessment method | Dosage, type | Length of treatment | Comparator | Comments |
|---|---|---|---|---|---|---|---|---|
| Carr et al., 2007, The Netherlands | Follow-up study of Wasdell 2008 (RCT) | 41 participants with neurodevelopmental disability (NDD). Included mental retardation, cerebral palsy, epilepsy, visual impairment (none completely blind) and autistic spectrum disorders. | Median age 8.6 years (range 4.8–19.3 years), Sex: 31.7, Ethnicity: not reported | Pubertal development. Assessment method not stated. | Mean dose 10.4 mg (SD 5.2) (range 5–15 mg), beaded sustained-release (1 mg fast and 4 mg controlled release) and later melatonin supplier replaced controlled-release melatonin (5 mg) with fast release (5 mg) formulation | Mean 4.3 years (range 2–12 years) | Not reported | The median age of the onset of puberty was 11.5 years (range 2—15 years). Precocious puberty developed in five children who had severe NDD, all prior to the MT therapy, at ages 2, 3, 4, 6 and 7 years. In the others with signs of puberty the onset was age appropriate (mean (±S.D.) age: 13.4 (±1.4) years). |
| Malow et al., 2021, United States and Europe | Follow-up study of Gringas (2017) (RCT) | 31 participants with Autism Spectrum Disorder (96%) and Smith-Magenis syndrome | Mean age 9 years (SD 4.2). Range 2–17 years. Sex: 25, Ethnicity: Not Hispanic or Latino (66.7%), Hispanic or Latino (20.0%), Other (13.3%) | Pubertal development. Assessed by a Physician in children≥8 years using Tanner pubertal staging score. | Range 2–10 mg, PedPRM | Mean 1.4 years (Range 3 days∗ to 2 years) | Control population matched on age and sex (Nilsson et al., 2001) | The study shows no delay in sexual maturation after 2 yr of continuous use of prolonged release melatonin. |
| vanGeijlswijk et al., 2011, The Netherlands | Follow-up study of vanGeijlswik 2010 (RCT) | 19 participants with Chronic idiopathic childhood sleep onset insomnia | Mean age 12.0 years (range 8.6–15.7 years), Sex: Group 1: 44, Group 2: 74, Group 3: 44, Group 4: 65 Ethnicity: not reported | Pubertal development. Written interview sent to the participants including three Tanner score questions. Self-reported | Mean dose 2.7 mg (range 0.3–10 mg), type not reported | Mean 3.1 years (range 1.0–4.6 years) | Control population matched on age and sex (Mul et al., 2001) | Puberty onset, as assessed by Tanner scores, seems to be undisturbed after 3.1 yr of exogenous melatonin usage. |
| Zwart et al., 2017, The Netherlands | Follow-up study of vanGeijlswik 2010 and 2011 (RCT) | 33 participants with Chronic idiopathic childhood sleep onset insomnia | Mean age 19.6 years (range 16.7–23.2 years), Sex: 57.6, Ethnicity: not reported | Pubertal development. Online questionnaire. Participants asked to indicate whether they felt their timing of pubertal development was any earlier or later than their peers. | Range 0.5–5 mg, type not reported | Mean duration of treatment 10.8 years. Overall average duration of treatment was 7.1 years. | Control population (Bratberg et al., 2007) | The perceived timing of pubertal development suggested a tendency towards delayed puberty. 31.3% of the participants experienced their pubertal timing as late. |
RCT: Randomised controlled trial: yr: Year; SD: Standard deviation; mg: Milligram; MT: Melatonin; NDD: Neurodevelopmental disorder.