{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T19:57:00Z","timestamp":1792353420667,"version":"4.4.0"},"reference-count":31,"publisher":"S. Karger AG","issue":"6","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neonatology"],"published-print":{"date-parts":[[2021]]},"abstract":"<b><i>Background:<\/i><\/b> Total serum bilirubin (TSB) is used in managing neonates with jaundice, but clear evidence on its association with major outcomes is lacking. <b><i>Objectives:<\/i><\/b> We evaluated the association between TSB and kernicterus spectrum disorder (KSD). <b><i>Methods:<\/i><\/b> We searched PubMed, EMBASE, and CENTRAL till July 2021. Two authors independently selected relevant cohort studies, extracted data (CHARMS checklist), assessed risk of bias (RoB) (QUIPS tool), and rated certainty-of-evidence (Grades of Recommendation, Assessment, Development, and Evaluation). We pooled adjusted odds ratio (aOR) (random-effect) via generic inverse variance methods. <b><i>Results:<\/i><\/b> From 2,826 records retrieved, we included 37 studies (<i>n<\/i> = 648,979). Fifteen studies had low, 16 moderate, and 6 high RoB, with majority having concerns on confounder adjustment and statistical analysis. Twenty-two studies contributed meta-analysis data, and 15 were summarized narratively. TSB appears associated with KSD in infants with certain risk factors (aOR 1.10, 95% CI: 1.07\u20131.13; 5 studies [<i>n<\/i> = 4,484]). However, TSB (aOR 1.10, 95% CI: 0.98\u20131.23; 1 study [<i>n<\/i> = 34,533]) or hyperbilirubinemia (aOR 1.00, 95% CI: 0.51\u20131.95; 2 studies [<i>n<\/i> = 56,578]) have no clear association with kernicterus or neurological diagnosis in overall neonatal population (moderate-certainty-evidence). One study shows that infants with hyperbilirubinemia appear likelier to develop attention-deficit disorder (aOR 1.90, 95% CI: 1.10\u20133.28) and autistic spectrum disorder (aOR 1.60, 95% CI: 1.03\u20132.49, <i>n<\/i> = 56,019) (low-certainty-evidence). Certain clinical factors appear associated with KSD, although very few studies contributed to the analyses. <b><i>Conclusions:<\/i><\/b> Despite the importance of this question, there is insufficient high-quality evidence on the independent prognostic value of TSB for adverse neurodevelopmental outcomes in most neonatal populations. Future studies should incorporate all known risk factors alongside TSB in a multivariable analysis to improve certainty-of-evidence. <\/jats:p>","DOI":"10.1159\/000519497","type":"journal-article","created":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T22:00:36Z","timestamp":1635976836000},"page":"654-664","source":"Crossref","is-referenced-by-count":12,"title":["The Association between Serum Bilirubin and Kernicterus Spectrum Disorder: A Systematic Review and Meta-Analysis"],"prefix":"10.1159","volume":"118","author":[{"given":"Nai Ming","family":"Lai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna Priya","family":"Gerard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin Fang","family":"Ngim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azanna Ahmad","family":"Kamar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9772-482X","authenticated-orcid":false,"given":"Kee-Hsin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2021,11,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.12968\/hmed.2017.78.12.699"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.c2409"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2013.208"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1136\/bmjpo-2017-000105"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.2174\/1573396313666170123151408"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0b013e328336eb28"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.4103\/2249-4847.116402"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jp.7211157"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.2174\/1573396313666170815100214"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-019-0603-5"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-018-0216-4"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1754.2011.02217.x"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1159\/000445708"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1542\/peds.114.1.297"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2016-311556"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2005-0590"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2014.08.007"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2011.02.005"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1542\/peds.114.1.e130"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2008.121269"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.15.2008"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/s0095-5108(18)30573-6"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2008.02045.x"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.ED000129"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001744"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-158-4-201302190-00009"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1186\/s41512-019-0050-0"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i6460"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2019.12.023"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2008-3545"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1274506"}],"container-title":["Neonatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/519497","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/519497","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:26:07Z","timestamp":1745421967000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000519497"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021]]},"references-count":31,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,12,14]]},"published-print":{"date-parts":[[2021,12,27]]}},"URL":"https:\/\/doi.org\/10.1159\/000519497","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.16922938","asserted-by":"subject"}]},"ISSN":["1661-7800","1661-7819"],"issn-type":[{"value":"1661-7800","type":"print"},{"value":"1661-7819","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021]]}}}