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Children With Restless Sleep May Have a Lower Threshold for Iron Supplementation Than Adults

MINNEAPOLIS—A serum ferritin threshold of 20 µg/L may be more appropriate for treatment decisions about children with restless sleep than the 50 µg/L threshold used for adults, according to research presented at the 28th Annual Meeting of the Associated Professional Sleep Societies. Using the adult treatment threshold to guide treatment in children may lead to inappropriate iron supplementation, said Alyson Connor.

Iron deficiency in adults and children has been linked to the presence and severity of restless legs syndrome (RLS) and periodic limb movements of sleep (PLMS). For adults, a serum ferritin level lower than 50 µg/L is the threshold commonly used to guide iron supplementation for patients with RLS or PLMS. A threshold of 40 to 50 µg/L has been used in pediatric studies.

A Retrospective Chart Review for Pediatric Patients
“Our findings raise a question about the best serum ferritin threshold to use when seeing a child with evidence of sleep restlessness, in particular with elevated periodic limb movement index [PLMI],” said Ms. Connor, a student in the biomedical research program at the University of Michigan, Ann Arbor. “While many children may benefit from iron supplementation for these disorders, this area is worthy of further study, as investigation in animals suggests that treatment of iron deficiency with high-dose iron supplementation in early development may differentially affect the development of the brain.”

Ms. Connor and her colleagues conducted a retrospective review of data for 537 children between the ages of 12 months and 18 years who were referred to the University of Michigan’s pediatric sleep clinic. In this cohort (mean age, 8.9 years; 62% male), a median serum ferritin level of 23.6 µg/L was associated with polysomnographic measures of PLMI of 5 or more per hour of total sleep time, while a median serum ferritin level of 30 µg/L was associated with PLMI of less than 5. Overall, about 26% of the subjects had a PLMI of 5 or more.

A Lower Serum Ferritin Threshold Improves Specificity
“There was a significant association between serum ferritin and PLMI, such that every 10 µg/L increase in serum ferritin decreased the odds of having an elevated PLMI by 11%,” said Ms. Connor. Boys, younger patients, those with lower serum ferritin levels, and those with a shorter time between hematology and polysomnography all had significantly increased odds of a PLMI of 5 or more. Approximately 19% of patients studied had a serum ferritin level above 50 µg/L, and 50% had a serum ferritin level below 30 µg/L.

“Essentially, the cutoff of 50 [µg/L] is very sensitive, giving few false negatives, but not very specific, whereas a lower cutoff improves specificity,” Ms. Connor said. Future studies are needed to assess the association between iron status and sleep measures in a general pediatric population and to determine the best iron dose, timing, and method of delivery for optimal developmental outcomes, she concluded.

Debra L. Beck

References

Suggested Reading
Bokkala S, Napalinga K, Pinninti N, et al. Correlates of periodic limb movements of sleep in the pediatric population. Pediatr Neurol. 2008;39(1):33-39.
Grim K, Lee B, Sung AY, Kotagal S. Treatment of childhood-onset restless legs syndrome and periodic limb movement disorder using intravenous iron sucrose. Sleep Med. 2013;14(11):1100-1104.
Simakajornboon N, Kheirandish-Gozal L, Gozal D. Diagnosis and management of restless legs syndrome in children. Sleep Med Rev. 2009;13(2):149-156.

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MINNEAPOLIS—A serum ferritin threshold of 20 µg/L may be more appropriate for treatment decisions about children with restless sleep than the 50 µg/L threshold used for adults, according to research presented at the 28th Annual Meeting of the Associated Professional Sleep Societies. Using the adult treatment threshold to guide treatment in children may lead to inappropriate iron supplementation, said Alyson Connor.

Iron deficiency in adults and children has been linked to the presence and severity of restless legs syndrome (RLS) and periodic limb movements of sleep (PLMS). For adults, a serum ferritin level lower than 50 µg/L is the threshold commonly used to guide iron supplementation for patients with RLS or PLMS. A threshold of 40 to 50 µg/L has been used in pediatric studies.

A Retrospective Chart Review for Pediatric Patients
“Our findings raise a question about the best serum ferritin threshold to use when seeing a child with evidence of sleep restlessness, in particular with elevated periodic limb movement index [PLMI],” said Ms. Connor, a student in the biomedical research program at the University of Michigan, Ann Arbor. “While many children may benefit from iron supplementation for these disorders, this area is worthy of further study, as investigation in animals suggests that treatment of iron deficiency with high-dose iron supplementation in early development may differentially affect the development of the brain.”

Ms. Connor and her colleagues conducted a retrospective review of data for 537 children between the ages of 12 months and 18 years who were referred to the University of Michigan’s pediatric sleep clinic. In this cohort (mean age, 8.9 years; 62% male), a median serum ferritin level of 23.6 µg/L was associated with polysomnographic measures of PLMI of 5 or more per hour of total sleep time, while a median serum ferritin level of 30 µg/L was associated with PLMI of less than 5. Overall, about 26% of the subjects had a PLMI of 5 or more.

A Lower Serum Ferritin Threshold Improves Specificity
“There was a significant association between serum ferritin and PLMI, such that every 10 µg/L increase in serum ferritin decreased the odds of having an elevated PLMI by 11%,” said Ms. Connor. Boys, younger patients, those with lower serum ferritin levels, and those with a shorter time between hematology and polysomnography all had significantly increased odds of a PLMI of 5 or more. Approximately 19% of patients studied had a serum ferritin level above 50 µg/L, and 50% had a serum ferritin level below 30 µg/L.

“Essentially, the cutoff of 50 [µg/L] is very sensitive, giving few false negatives, but not very specific, whereas a lower cutoff improves specificity,” Ms. Connor said. Future studies are needed to assess the association between iron status and sleep measures in a general pediatric population and to determine the best iron dose, timing, and method of delivery for optimal developmental outcomes, she concluded.

Debra L. Beck

MINNEAPOLIS—A serum ferritin threshold of 20 µg/L may be more appropriate for treatment decisions about children with restless sleep than the 50 µg/L threshold used for adults, according to research presented at the 28th Annual Meeting of the Associated Professional Sleep Societies. Using the adult treatment threshold to guide treatment in children may lead to inappropriate iron supplementation, said Alyson Connor.

Iron deficiency in adults and children has been linked to the presence and severity of restless legs syndrome (RLS) and periodic limb movements of sleep (PLMS). For adults, a serum ferritin level lower than 50 µg/L is the threshold commonly used to guide iron supplementation for patients with RLS or PLMS. A threshold of 40 to 50 µg/L has been used in pediatric studies.

A Retrospective Chart Review for Pediatric Patients
“Our findings raise a question about the best serum ferritin threshold to use when seeing a child with evidence of sleep restlessness, in particular with elevated periodic limb movement index [PLMI],” said Ms. Connor, a student in the biomedical research program at the University of Michigan, Ann Arbor. “While many children may benefit from iron supplementation for these disorders, this area is worthy of further study, as investigation in animals suggests that treatment of iron deficiency with high-dose iron supplementation in early development may differentially affect the development of the brain.”

Ms. Connor and her colleagues conducted a retrospective review of data for 537 children between the ages of 12 months and 18 years who were referred to the University of Michigan’s pediatric sleep clinic. In this cohort (mean age, 8.9 years; 62% male), a median serum ferritin level of 23.6 µg/L was associated with polysomnographic measures of PLMI of 5 or more per hour of total sleep time, while a median serum ferritin level of 30 µg/L was associated with PLMI of less than 5. Overall, about 26% of the subjects had a PLMI of 5 or more.

A Lower Serum Ferritin Threshold Improves Specificity
“There was a significant association between serum ferritin and PLMI, such that every 10 µg/L increase in serum ferritin decreased the odds of having an elevated PLMI by 11%,” said Ms. Connor. Boys, younger patients, those with lower serum ferritin levels, and those with a shorter time between hematology and polysomnography all had significantly increased odds of a PLMI of 5 or more. Approximately 19% of patients studied had a serum ferritin level above 50 µg/L, and 50% had a serum ferritin level below 30 µg/L.

“Essentially, the cutoff of 50 [µg/L] is very sensitive, giving few false negatives, but not very specific, whereas a lower cutoff improves specificity,” Ms. Connor said. Future studies are needed to assess the association between iron status and sleep measures in a general pediatric population and to determine the best iron dose, timing, and method of delivery for optimal developmental outcomes, she concluded.

Debra L. Beck

References

Suggested Reading
Bokkala S, Napalinga K, Pinninti N, et al. Correlates of periodic limb movements of sleep in the pediatric population. Pediatr Neurol. 2008;39(1):33-39.
Grim K, Lee B, Sung AY, Kotagal S. Treatment of childhood-onset restless legs syndrome and periodic limb movement disorder using intravenous iron sucrose. Sleep Med. 2013;14(11):1100-1104.
Simakajornboon N, Kheirandish-Gozal L, Gozal D. Diagnosis and management of restless legs syndrome in children. Sleep Med Rev. 2009;13(2):149-156.

References

Suggested Reading
Bokkala S, Napalinga K, Pinninti N, et al. Correlates of periodic limb movements of sleep in the pediatric population. Pediatr Neurol. 2008;39(1):33-39.
Grim K, Lee B, Sung AY, Kotagal S. Treatment of childhood-onset restless legs syndrome and periodic limb movement disorder using intravenous iron sucrose. Sleep Med. 2013;14(11):1100-1104.
Simakajornboon N, Kheirandish-Gozal L, Gozal D. Diagnosis and management of restless legs syndrome in children. Sleep Med Rev. 2009;13(2):149-156.

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Children With Restless Sleep May Have a Lower Threshold for Iron Supplementation Than Adults
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