{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:27Z","timestamp":1787027847634,"version":"build-2736575974"},"reference-count":55,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: Iron plays a crucial role in neurotransmitter synthesis, myelination, and neuronal metabolism. Iron deficiency has been associated with a variety of neurodevelopmental disorders, particularly attention-deficit\/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). However, the prevalence, clinical impact, and treatment implications differ between these conditions. Objective: To synthesize current evidence on the prevalence, neurobehavioral consequences, and therapeutic implications of iron deficiency in ADHD and ASD, highlighting convergences and disorder-specific findings. Results: In ADHD, studies using serum ferritin and related peripheral markers show inconsistent associations with core symptom severity, with reported ferritin thresholds for deficiency ranging widely. While some studies suggest links between low ferritin and hyperactivity, inattention, or stimulant response, others report null findings. In contrast, emerging neuroimaging evidence consistently demonstrates reduced brain iron in dopaminergic regions in children. In ASD, the strongest link is between low ferritin and sleep-related motor disturbances, and iron supplementation may improve sleep and motor symptoms. Conclusions: Screening for iron status and targeted supplementation may improve sleep and behavioral outcomes in ADHD and ASD, meriting integration into clinical practice and further randomized controlled trials.<\/jats:p>","DOI":"10.3390\/children13020180","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T15:04:46Z","timestamp":1769612686000},"page":"180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["IronDeficiency Across Neurodevelopmental Disorders: Comparative Insights from ADHD and Autism Spectrum Disorder"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3349-8426","authenticated-orcid":false,"given":"Lourdes M.","family":"DelRosso","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California, San Francisco\u2013Fresno, Fresno, CA 93701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilliana","family":"Estrada Chaverri","sequence":"additional","affiliation":[{"name":"SleepMed, Medical Center for Diagnosis and Treatment of Sleep Disorders, San Jos\u00e9 10201, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Alberto","family":"Ceballos Fuentes","sequence":"additional","affiliation":[{"name":"Neurology & Sleep Center, Guatemala City 01010, Guatemala"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"740S","DOI":"10.3945\/jn.110.131169","article-title":"Early iron deficiency has brain and behavior effects consistent with dopaminergic dysfunction","volume":"141","author":"Lozoff","year":"2011","journal-title":"J. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1148\/radiology.176.2.2164237","article-title":"Age-dependent changes in localized proton and phosphorus MR spectroscopy of the brain","volume":"176","author":"Faber","year":"1990","journal-title":"Radiology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8433","DOI":"10.1523\/JNEUROSCI.4375-14.2015","article-title":"Subcortical glutamate mediates the reduction of short-range functional connectivity with age in a developmental cohort","volume":"35","author":"Ghisleni","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.neuroimage.2007.03.053","article-title":"Sexual dimorphism of brain developmental trajectories during childhood and adolescence","volume":"36","author":"Lenroot","year":"2007","journal-title":"Neuroimage"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e12896","DOI":"10.1111\/jsr.12896","article-title":"Peculiar lifespan changes of periodic leg movements during sleep in restless legs syndrome","volume":"29","author":"Ferri","year":"2020","journal-title":"J. Sleep. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0006-8993(79)90349-4","article-title":"Synaptic density in human frontal cortex\u2014Developmental changes and effects of aging","volume":"163","author":"Huttenlocher","year":"1979","journal-title":"Brain Res."},{"key":"ref_7","first-page":"917","article-title":"Developmental changes of cerebral blood flow and oxygen metabolism in children","volume":"20","author":"Takahashi","year":"1999","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S560","DOI":"10.1177\/15648265070284S409","article-title":"Iron deficiency and child development","volume":"28","author":"Lozoff","year":"2007","journal-title":"Food Nutr. Bull."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1468S","DOI":"10.1093\/jn\/133.5.1468S","article-title":"Iron deficiency alters brain development and functioning","volume":"133","author":"Beard","year":"2003","journal-title":"J. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1080\/87565640802646767","article-title":"The role of iron in neurocognitive development","volume":"34","author":"Thomas","year":"2009","journal-title":"Dev. Neuropsychol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101566","DOI":"10.1016\/j.dcn.2025.101566","article-title":"Neural, cognitive and psychopathological signatures of a prosocial or delinquent peer environment during early adolescence","volume":"73","author":"Liu","year":"2025","journal-title":"Dev. Cogn. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/s41583-020-00379-8","article-title":"Myelin plasticity: Sculpting circuits in learning and memory","volume":"21","author":"Xin","year":"2020","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s00360-023-01531-3","article-title":"The intersection of sleep and synaptic translation in synaptic plasticity deficits in neurodevelopmental disorders","volume":"194","author":"Coulson","year":"2024","journal-title":"J. Comp. Physiol. B"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1097\/00062752-200407000-00004","article-title":"Hepcidin in iron metabolism","volume":"11","author":"Ganz","year":"2004","journal-title":"Curr. Opin. Hematol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S491","DOI":"10.1177\/15648265070284S402","article-title":"Iron metabolism in infants and children","volume":"28","author":"Lonnerdal","year":"2007","journal-title":"Food Nutr. Bull."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Alhammad, R., Abu-Farha, M., Rahman, A., Thanaraj, T.A., Shaban, L., Alsabah, R., Hamad, S., Hammad, M.M., Channanath, A., and Al-Mulla, F. (2023). LRG1 Associates with Iron Deficiency Anemia Markers in Adolescents. Nutrients, 15.","DOI":"10.3390\/nu15143100"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.bpa.2023.11.001","article-title":"Diagnosing iron deficiency: Controversies and novel metrics","volume":"37","author":"Rusch","year":"2023","journal-title":"Best. Pract. Res. Clin. Anaesthesiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"106372","DOI":"10.1016\/j.neubiorev.2025.106372","article-title":"Psychiatric and cognitive outcomes of iron supplementation in non-anemic children, adolescents, and menstruating adults: A meta-analysis and systematic review","volume":"178","author":"Fiani","year":"2025","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_19","first-page":"284","article-title":"Iron deficiency in infants and children\u2014The current research challenges","volume":"28","author":"Chmielewska","year":"2025","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1089\/cap.2010.0053","article-title":"Serum ferritin and amphetamine response in youth with attention-deficit\/hyperactivity disorder","volume":"20","author":"Calarge","year":"2010","journal-title":"J. Child. Adolesc. Psychopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.jpeds.2005.06.037","article-title":"Iron and zinc supplementation does not improve parent or teacher ratings of behavior in first grade Mexican children exposed to lead","volume":"147","author":"Kordas","year":"2005","journal-title":"J. Pediatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1017\/S0007114514003493","article-title":"Long-chain n-3 PUFA supplementation decreases physical activity during class time in iron-deficient South African school children","volume":"113","author":"Smuts","year":"2015","journal-title":"Br. J. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1097\/DBP.0000000000000993","article-title":"Effect of Iron Supplementation in Children with Attention-Deficit\/Hyperactivity Disorder and Iron Deficiency: A Randomized Controlled Trial","volume":"43","author":"Pongpitakdamrong","year":"2022","journal-title":"J. Dev. Behav. Pediatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.jpeds.2017.12.008","article-title":"Infant Iron Deficiency and Iron Supplementation Predict Adolescent Internalizing, Externalizing, and Social Problems","volume":"195","author":"Doom","year":"2018","journal-title":"J. Pediatr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.pediatrneurol.2007.08.014","article-title":"Effects of iron supplementation on attention deficit hyperactivity disorder in children","volume":"38","author":"Konofal","year":"2008","journal-title":"Pediatr. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s12402-013-0108-8","article-title":"No cross-sectional and longitudinal association of ferritin and symptoms of attention-deficit-\/hyperactivity disorder in a large population-based sample of children: Results from the GINIplus and LISAplus studies","volume":"5","author":"Romanos","year":"2013","journal-title":"Atten. Defic. Hyperact. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1111\/j.1442-200X.2012.03664.x","article-title":"Ferritin and hyperactivity ratings in attention deficit hyperactivity disorder","volume":"54","author":"Oner","year":"2012","journal-title":"Pediatr. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/ejcn.2011.80","article-title":"Effects of essential fatty acids in iron deficient and sleep-disturbed attention deficit hyperactivity disorder (ADHD) children","volume":"65","author":"Yehuda","year":"2011","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.pediatrneurol.2006.11.004","article-title":"Children with autism: Effect of iron supplementation on sleep and ferritin","volume":"36","author":"Dosman","year":"2007","journal-title":"Pediatr. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1148\/radiol.14140047","article-title":"Multimodal MR imaging of brain iron in attention deficit hyperactivity disorder: A noninvasive biomarker that responds to psychostimulant treatment?","volume":"272","author":"Adisetiyo","year":"2014","journal-title":"Radiology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"101274","DOI":"10.1016\/j.dcn.2023.101274","article-title":"Brain tissue iron neurophysiology and its relationship with the cognitive effects of dopaminergic modulation in children with and without ADHD","volume":"63","author":"Cascone","year":"2023","journal-title":"Dev. Cogn. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.jpsychires.2024.03.035","article-title":"Brain iron concentration in childhood ADHD: A systematic review of neuroimaging studies","volume":"173","author":"Morandini","year":"2024","journal-title":"J. Psychiatr. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3726","DOI":"10.1007\/s00330-021-08516-2","article-title":"Quantitative susceptibility mapping reveals brain iron deficiency in children with attention-deficit\/hyperactivity disorder: A whole-brain analysis","volume":"32","author":"Chen","year":"2022","journal-title":"Eur. Radiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s10578-015-0562-y","article-title":"Iron Deficiency Parameters in Children and Adolescents with Attention-Deficit\/Hyperactivity Disorder","volume":"47","author":"Percinel","year":"2016","journal-title":"Child. Psychiatry Hum. Dev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.pediatrneurol.2005.09.001","article-title":"Serum ferritin in children with attention-deficit hyperactivity disorder","volume":"34","author":"Millichap","year":"2006","journal-title":"Pediatr. Neurol."},{"key":"ref_36","first-page":"530","article-title":"Iron deficiency in children with attention deficit hyperactivity disorder","volume":"13","author":"Lahat","year":"2011","journal-title":"Isr. Med. Assoc. J."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Giambersio, D., Marzulli, L., Margari, L., Matera, E., Nobili, L., De Grandis, E., Cordani, R., Barbieri, A., Peschechera, A., and Margari, A. (2023). Correlations between Sleep Features and Iron Status in Children with Neurodevelopmental Disorders: A Cross-Sectional Study. J. Clin. Med., 12.","DOI":"10.3390\/jcm12154949"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.sleep.2007.04.022","article-title":"Impact of restless legs syndrome and iron deficiency on attention-deficit\/hyperactivity disorder in children","volume":"8","author":"Konofal","year":"2007","journal-title":"Sleep. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1089\/cap.2015.0194","article-title":"Serum Ferritin, Weight Gain, Disruptive Behavior, and Extrapyramidal Symptoms in Risperidone-Treated Youth","volume":"26","author":"Calarge","year":"2016","journal-title":"J. Child. Adolesc. Psychopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jpsychires.2022.06.014","article-title":"Withdrawing methylphenidate in relation to serum levels of ferritin and zinc in children and adolescents with attention-deficit\/hyperactivity disorder","volume":"152","author":"Rosenau","year":"2022","journal-title":"J. Psychiatr. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"186","DOI":"10.4103\/aam.aam_17_17","article-title":"Iron and vitamin D levels among autism spectrum disorders children","volume":"16","author":"Bener","year":"2017","journal-title":"Ann. Afr. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1177\/1362361302006001008","article-title":"Iron deficiency in autism and Asperger syndrome","volume":"6","author":"Latif","year":"2002","journal-title":"Autism"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s13052-017-0407-3","article-title":"Iron deficiency parameters in autism spectrum disorder: Clinical correlates and associated factors","volume":"43","author":"Gunes","year":"2017","journal-title":"Ital. J. Pediatr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.sleep.2022.09.021","article-title":"Clinical efficacy and safety of intravenous ferric carboxymaltose treatment for restless legs symptoms and low serum ferritin in children with autism spectrum disorder","volume":"100","author":"DelRosso","year":"2022","journal-title":"Sleep. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.5664\/jcsm.8756","article-title":"Rethinking bedtime resistance in children with autism: Is restless legs syndrome to blame?","volume":"16","author":"Kanney","year":"2020","journal-title":"J. Clin. Sleep. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s00431-011-1506-6","article-title":"Ferritin and iron levels in children with autistic disorder","volume":"171","author":"Herguner","year":"2012","journal-title":"Eur. J. Pediatr."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Koh, M.Y., Lee, A.J.W., Wong, H.C., and Aishworiya, R. (2025). Occurrence and Correlates of Vitamin D and Iron Deficiency in Children with Autism Spectrum Disorder. Nutrients, 17.","DOI":"10.3390\/nu17172738"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1111\/jpc.12483","article-title":"Iron deficiency in children with global developmental delay and autism spectrum disorder","volume":"50","author":"Sidrak","year":"2014","journal-title":"J. Paediatr. Child Health"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Chamova, R., Nikolova, S., Toneva, A., Braykova, R., Hadzhieva, S., Bocheva, Y., and Pancheva, R. (2025). Iron Deficiency Prevalence in Bulgarian Children with Cerebral Palsy and Autism: A Call for Nutritional Interventions to Support Development. Nutrients, 17.","DOI":"10.3390\/nu17121969"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.pediatrneurol.2013.06.012","article-title":"Relationship of serum ferritin levels to sleep fragmentation and periodic limb movements of sleep on polysomnography in autism spectrum disorders","volume":"49","author":"Youssef","year":"2013","journal-title":"Pediatr. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"153","DOI":"10.5664\/jcsm.11392","article-title":"Treatment of restless legs syndrome and periodic limb movement disorder: An American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment","volume":"21","author":"Winkelman","year":"2025","journal-title":"J. Clin. Sleep. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1590\/S1516-44462009005000008","article-title":"Food intake and serum levels of iron in children and adolescents with attention-deficit\/hyperactivity disorder","volume":"32","author":"Menegassi","year":"2010","journal-title":"Braz. J. Psychiatry"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"137","DOI":"10.5664\/jcsm.11390","article-title":"Treatment of restless legs syndrome and periodic limb movement disorder: An American Academy of Sleep Medicine clinical practice guideline","volume":"21","author":"Winkelman","year":"2025","journal-title":"J. Clin. Sleep. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0140-6736(20)32594-0","article-title":"Iron deficiency","volume":"397","author":"Pasricha","year":"2021","journal-title":"Lancet"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e2433126","DOI":"10.1001\/jamanetworkopen.2024.33126","article-title":"Absolute and Functional Iron Deficiency in the US, 2017-2020","volume":"7","author":"Tawfik","year":"2024","journal-title":"JAMA Netw. Open"}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/2\/180\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T15:36:18Z","timestamp":1769614578000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/2\/180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":55,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["children13020180"],"URL":"https:\/\/doi.org\/10.3390\/children13020180","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]}}}