Ann M Reynolds1, Heidi V Connolly2, Terry Katz3, Suzanne E Goldman4, Shelly K Weiss5, Ann C Halbower3, Amy M Shui6, Eric A Macklin7, Susan L Hyman2, Beth A Malow4. 1. Department of Pediatrics, University of Colorado Denver, Aurora, Colorado. Electronic address: ann.reynolds@childrenscolorado.org. 2. Department of Pediatrics, University of Rochester, Rochester, New York. 3. Department of Pediatrics, University of Colorado Denver, Aurora, Colorado. 4. Sleep Disorders Division, Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee. 5. Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada. 6. Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts. 7. Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Abstract
BACKGROUND:Insomnia and low iron stores are common in children with autism spectrum disorders, and low iron stores have been associated with sleep disturbance. METHODS: We performed a randomized placebo-controlled trial of oral ferrous sulfate to treat insomnia in children with autism spectrum disorders and low normal ferritin levels. Twenty participants who met inclusion criteria and whose insomnia did not respond to sleep education were randomized to 3 mg/kg/day of ferrous sulfate (n = 9) or placebo (n = 11) for three months. RESULTS:Iron supplementation was well tolerated, and no serious adverse events were reported. Iron supplementation improved iron status (+18.4 ng/mL active versus -1.6 ng/mL placebo, P = 0.044) but did not significantly improve the primary outcome measures of sleep onset latency (-11.0 minutes versus placebo, 95% confidence interval -28.4 to 6.4 minutes, P = 0.22) and wake time after sleep onset (-7.7 minutes versus placebo, 95% confidence interval -22.1 to 6.6 min, P = 0.29) as measured by actigraphy. Iron supplementation was associated with improvement in the overall severity score from the Sleep Clinical Global Impression Scale (-1.5 points versus placebo, P = 0.047). Changes in measures of daytime behavior did not differ between groups. CONCLUSION: This trial demonstrated no improvement in primary outcome measures of insomnia in subjects treated with ferrous sulfate compared with placebo. Interpretation was limited by low enrollment.
RCT Entities:
BACKGROUND:Insomnia and low iron stores are common in children with autism spectrum disorders, and low iron stores have been associated with sleep disturbance. METHODS: We performed a randomized placebo-controlled trial of oral ferrous sulfate to treat insomnia in children with autism spectrum disorders and low normal ferritin levels. Twenty participants who met inclusion criteria and whose insomnia did not respond to sleep education were randomized to 3 mg/kg/day of ferrous sulfate (n = 9) or placebo (n = 11) for three months. RESULTS:Iron supplementation was well tolerated, and no serious adverse events were reported. Iron supplementation improved iron status (+18.4 ng/mL active versus -1.6 ng/mL placebo, P = 0.044) but did not significantly improve the primary outcome measures of sleep onset latency (-11.0 minutes versus placebo, 95% confidence interval -28.4 to 6.4 minutes, P = 0.22) and wake time after sleep onset (-7.7 minutes versus placebo, 95% confidence interval -22.1 to 6.6 min, P = 0.29) as measured by actigraphy. Iron supplementation was associated with improvement in the overall severity score from the Sleep Clinical Global Impression Scale (-1.5 points versus placebo, P = 0.047). Changes in measures of daytime behavior did not differ between groups. CONCLUSION: This trial demonstrated no improvement in primary outcome measures of insomnia in subjects treated with ferrous sulfate compared with placebo. Interpretation was limited by low enrollment.
Authors: Inge van der Wurff; Anke Oenema; Dennis de Ruijter; Claudia Vingerhoets; Thérèse van Amelsvoort; Bart Rutten; Sandra Mulkens; Sebastian Köhler; Annemie Schols; Renate de Groot Journal: Nutrients Date: 2022-03-26 Impact factor: 5.717