{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:59:53Z","timestamp":1785214793557,"version":"3.55.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T00:00:00Z","timestamp":1668038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004699","name":"Chung Shan Medical University Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004699","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The diagnosis of neonatal hypocalcemic seizures (HS) in newborns is made based on clinical signs and serum calcium level. Their etiology is broad and diverse, and timely detection and initiation of treatment is essential.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively reviewed 1029 patients admitted to the neonatal intensive care unit. Neonatal HS were diagnosed in 16 patients, and we compared etiologies and clinical outcomes, including clinical seizures and neurodevelopment at least over 1 year old.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The etiologies can be broadly categorized into 5 syndromic and 11 non-syndromic neonatal HS. Syndromic neonatal HS included 3 Digeorge syndrome, 1 Kleefstra syndrome and 1 Alstr\u00f6m syndrome. Non-syndromic neonatal HS included 8 vitamin D deficiency, 1 hypoparathyroidism, and 2 hypoxic-ischemic encephalopathy. Patients with syndromic neonatal HS were found to have worse clinical outcomes than those with nonsyndromic HS. In eight patients with vitamin D deficiency, neurodevelopment was normal. Five of five patients (100%) with syndromic HS used two or more antiseizure drugs. However, among patients with non-syndromic neonatal HS, only one of 11 (9.1%) used more than one drug (<jats:italic>p =<\/jats:italic> 0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This finding highlighted that syndromic hypocalcemic seizures in newborns have worse neurodevelopmental outcomes and are more often difficult to manage, and would benefit from a genetic diagnostic approach.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.998675","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T08:08:31Z","timestamp":1668067711000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Syndromic and non-syndromic etiologies causing neonatal hypocalcemic seizures"],"prefix":"10.3389","volume":"13","author":[{"given":"Yi-Chieh","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin-Chi","family":"Chao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inn-Chi","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1097\/00003246-197701000-00010","article-title":"Neonatal hypocalcemia mechanism of occurrence and management","volume":"5","author":"Tsang","year":"1977","journal-title":"Crit Care Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1979.03630470074022","article-title":"Hypocalcemia. differential diagnosis and mechanisms","volume":"139","author":"Juan","year":"1979","journal-title":"Arch Intern Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/0887-8994(94)90085-X","article-title":"Natural history and outcome of neonatal hypocalcemic and hypomagnesemic seizures","volume":"11","author":"Lynch","year":"1994","journal-title":"Pediatr Neurol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000004180","article-title":"Seizure detection algorithms in critically ill children: A comparative evaluation","volume":"48","author":"Din","year":"2020","journal-title":"A comparative evaluation. Crit Care Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s12098-010-0176-0","article-title":"Hypocalcemia in the newborn","volume":"77","author":"Jain","year":"2010","journal-title":"Indian J Pediatr"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2011-2659","article-title":"Transient neonatal hypocalcemia: presentation and outcomes","volume":"129","author":"Thomas","year":"2012","journal-title":"Pediatrics"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-2773","article-title":"Incidence of hypocalcemic seizures due to vitamin d deficiency in children in the united kingdom and Ireland","volume":"100","author":"Basatemur","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.20945\/2359-3997000000281","article-title":"Prevalence of vitamin d deficiency in exclusively breastfed infants at a tertiary healthcare facility in Nairobi, Kenya","volume":"64","author":"Said","year":"2021","journal-title":"Arch Endocrinol Metab"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114520001105","article-title":"The role of parathyroid hormone during pregnancy on the relationship between maternal vitamin d deficiency and fetal growth restriction: a prospective birth cohort study","volume":"124","author":"Meng","year":"2020","journal-title":"Br J Nutr"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2011.12.010","article-title":"Clinical review of genetic epileptic encephalopathies","volume":"55","author":"Noh","year":"2012","journal-title":"Eur J Med Genet"},{"key":"B11","doi-asserted-by":"publisher","first-page":"100770","DOI":"10.1016\/j.spen.2019.08.006","article-title":"Neonatal developmental and epileptic encephalopathies","volume":"32","author":"El Kosseifi","year":"2019","journal-title":"Semin Pediatr Neurol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/BF02723667","article-title":"Neonatal endocrinology","volume":"67","author":"Oden","year":"2000","journal-title":"Indian J Pediatr"},{"key":"B13","doi-asserted-by":"publisher","first-page":"86","DOI":"10.6065\/apem.2015.20.2.86","article-title":"Clinical and laboratory characteristics of neonatal hypocalcemia","volume":"20","author":"Cho","year":"2015","journal-title":"Ann Pediatr Endocrinol Metab"},{"key":"B14","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1001\/archneur.1976.00500100030012","article-title":"Neonatal encephalopathy following fetal distress. a clinical and electroencephalographic study","volume":"33","author":"Sarnat","year":"1976","journal-title":"Arch Neurol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0900854","article-title":"Moderate hypothermia to treat perinatal asphyxial encephalopathy","volume":"361","author":"Azzopardi","year":"2009","journal-title":"N Engl J Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"c363","DOI":"10.1136\/bmj.c363","article-title":"Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data","volume":"340","author":"Edwards","year":"2010","journal-title":"Bmj"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2014.10","article-title":"Using the bayley-III to assess neurodevelopmental delay: which cut-off should be used","volume":"75","author":"Johnson","year":"2014","journal-title":"Pediatr Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.5535\/arm.2018.42.2.313","article-title":"Comparison of second and third editions of the bayley scales in children with suspected developmental delay","volume":"42","author":"Yi","year":"2018","journal-title":"Ann Rehabil Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-100918","article-title":"wANNOVAR: annotating genetic variants for personal genomes via the web","volume":"49","author":"Chang","year":"2012","journal-title":"J Med Genet"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2015.105","article-title":"Genomic variant annotation and prioritization with ANNOVAR and wANNOVAR","volume":"10","author":"Yang","year":"2015","journal-title":"Nat Protoc"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/1750-1172-2-49","article-title":"Alstrom syndrome (OMIM 203800): A case report and literature review","volume":"2","author":"Joy","year":"2007","journal-title":"Orphanet J Rare Dis"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/tropej\/fmp063","article-title":"Nineteen cases of symptomatic neonatal hypocalcemia secondary to vitamin d deficiency: A 2-year study","volume":"56","author":"Teaema","year":"2010","journal-title":"J Trop Pediatr"},{"key":"B24","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1097\/PEC.0000000000000380","article-title":"The many etiologies of neonatal hypocalcemic seizures","volume":"31","author":"Levy-Shraga","year":"2015","journal-title":"Pediatr Emerg Care"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1136\/adc.66.2.193","article-title":"A new syndrome of congenital hypoparathyroidism, severe growth failure, and dysmorphic features","volume":"66","author":"Sanjad","year":"1991","journal-title":"Arch Dis Child"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.771100","article-title":"Endocrine and growth disorders in Taiwanese children with 22q11.2 deletion syndrome","volume":"13","author":"Lin","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(89)80837-6","article-title":"Prediction of persistent immunodeficiency in the DiGeorge anomaly","volume":"115","author":"Bastian","year":"1989","journal-title":"J Pediatr"},{"key":"B28","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1007\/BF00441974","article-title":"Clinical evaluation and course of partial and complete forms of the syndrome","volume":"147","author":"M\u00fcller","year":"1988","journal-title":"Eur J Pediatr"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2017.09.003","article-title":"Diagnostic yield from 339 epilepsy patients screened on a clinical gene panel","volume":"77","author":"Butler","year":"2017","journal-title":"Pediatr Neurol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14618","article-title":"Diagnostic exome sequencing in 100 consecutive patients with both epilepsy and intellectual disability","volume":"60","author":"Snoeijen-Schouwenaars","year":"2019","journal-title":"Epilepsia"},{"key":"B31","doi-asserted-by":"publisher","first-page":"14589","DOI":"10.1038\/s41598-022-14161-6","article-title":"Whole-exome analysis of 177 pediatric patients with undiagnosed diseases","volume":"12","author":"Narita","year":"2022","journal-title":"Sci Rep"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.50989","article-title":"Prognostic value of amplitude-integrated EEG in neonates with high risk of neurological sequelae","volume":"7","author":"Yuan","year":"2020","journal-title":"Ann Clin Transl Neurol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.691764","article-title":"Amplitude integrated electroencephalography and continuous electroencephalography monitoring is crucial in high-risk infants and their findings correlate with neurodevelopmental outcomes","volume":"9","author":"Lee","year":"2021","journal-title":"Front Pediatr"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2020.08.014","article-title":"Ictal and interictal electroencephalographic findings can contribute to early diagnosis and prompt treatment in KCNQ2-associated epileptic encephalopathy","volume":"120","author":"Lee","year":"2021","journal-title":"J Formos Med Assoc"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2022.08.017","article-title":"Real-time detection of neonatal seizures improves with on demand EEG interpretation","volume":"143","author":"Mendelsohn","year":"2022","journal-title":"Clin Neurophysiol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"bvac042","DOI":"10.1210\/jendso\/bvac042","article-title":"Autosomal dominant hypocalcemia type 1 (ADH1) associated with myoclonus and intracerebral calcifications","volume":"6","author":"Elston","year":"2022","journal-title":"J Endocr Soc"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2005.11.018","article-title":"Might calcium disorders cause or contribute to myoclonic seizures in epileptics","volume":"66","author":"Thiel","year":"2006","journal-title":"Med Hypotheses"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2018.01.001","article-title":"Electroencephalographic monitoring for seizure identification and prognosis in term neonates","volume":"23","author":"Massey","year":"2018","journal-title":"Semin Fetal Neonatal Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1159\/000478651","article-title":"A distinctive ictal amplitude-integrated electroencephalography pattern in newborns with neonatal epilepsy associated with KCNQ2 mutations","volume":"112","author":"Vilan","year":"2017","journal-title":"Neonatology"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.998675\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T08:08:33Z","timestamp":1668067713000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.998675\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,10]]},"references-count":39,"alternative-id":["10.3389\/fendo.2022.998675"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.998675","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,10]]},"article-number":"998675"}}