{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:51:04Z","timestamp":1783486264766,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005977","name":"Kaiser Permanente","doi-asserted-by":"publisher","award":["KP-RRC-20190501"],"award-info":[{"award-number":["KP-RRC-20190501"]}],"id":[{"id":"10.13039\/100005977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJNS"],"abstract":"<jats:p>Secondary screening for missed congenital hypothyroidism (CH) has been introduced sporadically, but its necessity and optimal strategy have not been recognized. We hypothesized that a simple clinical protocol (performed by a medical group without a governmental mandate) targeting infants at high risk for missed CH can identify cases. We performed a 9-year retrospective review of 338,478 neonates within a California health plan following the introduction of thyrotropin (TSH) secondary screening for neonates at high risk for missed CH due to very-low-birthweight (VLBW), hospitalized congenital heart disease (CHD), and same-sex multiples (SSM). Screening performance by day 60 of life was 95% successful for VLBW and &gt;50% for CHD and SSM, leading to an additional 35% CH treated cases despite re-testing only 1.7% of the cohort. Infants with VLBW or CHD were 33 times more likely (190 times more likely for CHD with Down Syndrome) to receive treatment for CH than random infants diagnosed by primary screening (p &lt; 0.001), and 92% of these infants were not found by primary newborn screening. Currently, permanent disease has been documented in 84% of CH by primary screening compared to 27% by secondary screening (p &lt; 0.001). This targeted secondary screening program identifies and treats additional CH cases after TSH-only newborn screening.<\/jats:p>","DOI":"10.3390\/ijns7040081","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T02:56:14Z","timestamp":1638413774000},"page":"81","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeted Secondary Screening for Congenital Hypothyroidism in High-Risk Neonates: A 9 Year Review in a Large California Health Care System"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7267-8054","authenticated-orcid":false,"given":"Alan B.","family":"Cortez","sequence":"first","affiliation":[{"name":"Southern California Permanente Medical Group, Department of Pediatrics, Pediatric Endocrinology, Tustin, CA 92780, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Lin","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Department of Research, Pasadena, CA 91188, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3378-2355","authenticated-orcid":false,"given":"Joshua A.","family":"May","sequence":"additional","affiliation":[{"name":"Southern California Permanente Medical Group, Department of Pediatrics, Pediatric Endocrinology, Los Angeles, CA 90027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S225","DOI":"10.1007\/s10545-010-9062-1","article-title":"Newborn screening strategies for congenital hypothyroidism: An update","volume":"33","author":"LaFranchi","year":"2010","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"American Academy of Pediatrics, Rose, S.R., Section on Endocrinology and Committee on Genetics, American Thyroid Association, Brown, R.S., Public Health Committee, and Lawson Wilkins Pediatric Endocrine Society (2006). Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics, 117, 2290\u20132303.","DOI":"10.1542\/peds.2006-0915"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1210\/jc.2013-1891","article-title":"European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism","volume":"99","author":"Olivieri","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1089\/10507250050137770","article-title":"Atypical hypothyroidism and the very low birthweight infant","volume":"10","author":"Mandel","year":"2000","journal-title":"Thyroid"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1067\/S0022-3476(03)00332-9","article-title":"Risk factors associated with delayed thyrotropin elevations in congenital hypothyroidism","volume":"143","author":"Larson","year":"2003","journal-title":"J. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1258\/096914105775220697","article-title":"Screening for congenital hypothyroidism: The value of retesting after four weeks in neonates with low and very low birth weight","volume":"12","author":"Starzyk","year":"2005","journal-title":"J. Med. Screen."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.1542\/peds.2009-1975D","article-title":"Trends in incidence rates of congenital hypothyroidism related to select demographic factors: Data from the United States, California, Massachusetts, New York, and Texas","volume":"125","author":"Hinton","year":"2010","journal-title":"Pediatrics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1515\/JPEM.2010.23.1-2.45","article-title":"Screening for congenital hypothyroidism in extreme premature and\/or very low birth weight newborns: The importance of a specific protocol","volume":"23","author":"Silva","year":"2010","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1007\/s10545-011-9286-8","article-title":"Newborn screening for congenital hypothyroidism in very-low-birth-weight babies: The need for a second test","volume":"34","author":"Bijarnia","year":"2011","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.jpeds.2010.10.018","article-title":"Congenital hypothyroidism with a delayed thyroid-stimulating hormone (TSH) elevation in very premature infants: Incidence and growth and developmental outcomes","volume":"158","author":"Woo","year":"2011","journal-title":"J. Pediatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"224","DOI":"10.3345\/kjp.2015.58.6.224","article-title":"Thyroid dysfunction in very low birth weight preterm infants","volume":"58","author":"Lee","year":"2015","journal-title":"Korean J. Pediatr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.pedneo.2017.04.006","article-title":"Screening of congenital hypothyroidism in preterm, low birth weight and very low birth weight neonates: A systematic review","volume":"59","author":"Hashemipour","year":"2018","journal-title":"Pediatr. Neonatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"E1115","DOI":"10.1210\/jc.2011-0057","article-title":"Increased Risk for Non-Autoimmune Hypothyroidism in Young Patients with Congenital Heart Defects","volume":"96","author":"Passeri","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_14","first-page":"557","article-title":"A population-based study on the frequency of additional congenital malformations in infants with congenital hypothyroidism: Data from the Italian Registry for Congenital Hypothyroidism, 1991\u20131998","volume":"87","author":"Olivieri","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1111\/j.1651-2227.2001.tb01601.x","article-title":"Thyroid dysfunction in children with Down syndrome","volume":"90","author":"Tuysuz","year":"2001","journal-title":"Acta Paediatr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/jp.2014.116","article-title":"Revisiting early hypothyroidism screening in infants with Down syndrome","volume":"34","author":"Purdy","year":"2014","journal-title":"J. Perinatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1210\/jc.2002-021303","article-title":"Lower Neonatal Screening Thyroxine Concentrations in Down Syndrome Newborns","volume":"88","author":"Vulsma","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4072","DOI":"10.1210\/jc.2001-011995","article-title":"Discordance of monozygotic twins for thyroid dysgenesis: Implications for screening and for molecular pathophysiology","volume":"87","author":"Bourdoux","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cca.2019.12.018","article-title":"Same-sex twins have a high incidence of congenital hypothyroidism and a high probability to be missed at newborn screening","volume":"502","author":"Jiang","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/S0022-3476(86)80276-1","article-title":"Detection of congenital hypopituitary hypothyroidism: Ten-year experience in the Northwest Regional Screening Program","volume":"109","author":"Hanna","year":"1986","journal-title":"J. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1159\/000480293","article-title":"Pilot Neonatal Screening Program for Central Congenital Hypothyroidism: Evidence of Significant Detection","volume":"88","author":"Braslavsky","year":"2017","journal-title":"Horm. Res. Paediatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1097\/01.PCC.0000216680.22950.D9","article-title":"Dopamine infusion: A possible cause of undiagnosed congenital hypothyroidism in preterm infants","volume":"7","author":"Filippi","year":"2006","journal-title":"Pediatr. Crit. Care Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.jpeds.2010.11.030","article-title":"Congenital hypothyroidism: Delayed detection after birth and monitoring treatment in the first year of life","volume":"158","author":"LaFranchi","year":"2011","journal-title":"J. Pediatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1111\/j.1651-2227.2009.01412.x","article-title":"Hypothyroidism in neonates post-iodinated contrast media: A systematic review","volume":"98","author":"Ahmet","year":"2009","journal-title":"Acta Paediatrica"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1210\/jc.2014-1956","article-title":"Iodine induced.hypothyroidism in full-term infants with congenital heart disease: More common than currently appreciated?","volume":"99","author":"Thaker","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_26","first-page":"875","article-title":"Evaluation of thyroid status of infants in the intensive care setting","volume":"50","author":"Hemmati","year":"2009","journal-title":"Singap. Med. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1136\/adc.2008.147884","article-title":"Difficulties in selecting an appropriate neonatal thyroid stimulating hormone (TSH) screening threshold","volume":"95","author":"Korada","year":"2010","journal-title":"Arch. Dis. Child."},{"key":"ref_28","first-page":"180","article-title":"Screening for congenital hypothyroidism: Comparison of borderline screening cut-off points and the effect on the number of children treated with levothyroxine","volume":"2","author":"Langham","year":"2013","journal-title":"Eur. Thyroid. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/jp.2016.213","article-title":"Congenital hypothyroidism with delayed thyroid-stimulating hormone elevation in premature infants born at less than.30 weeks gestation","volume":"37","author":"Kaluarachchi","year":"2017","journal-title":"J. Perinatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ymgme.2015.08.003","article-title":"Single newborn screen or routine second screening for primary congenital hypothyroidism","volume":"116","author":"Shapira","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/j.jpeds.2014.02.031","article-title":"Screening preterm infants for congenital hypothyroidism: Better the second time around","volume":"164","author":"LaFranchi","year":"2014","journal-title":"J. Pediatr."},{"key":"ref_32","unstructured":"(2020, August 01). United States Census Data (Estimates Last Updated July 1, 2019 Prior to Submission), Available online: www.census.gov\/quickfacts\/fact\/table\/CA."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1038\/gim.2012.76","article-title":"Birth prevalence of disorders detectable through newborn screening by race\/ethnicity","volume":"14","author":"Feuchtbaum","year":"2012","journal-title":"Genet. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"349","DOI":"10.21037\/tp.2017.09.07","article-title":"Transient hypothyroidism in the newborn: To treat or not to treat","volume":"6","author":"Kanike","year":"2017","journal-title":"Transl. Pediatr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1067\/mpd.2002.120268","article-title":"Very low birth weight newborns do not need repeat screening for congenital hypothyroidism","volume":"140","author":"Vincent","year":"2002","journal-title":"J. Pediatr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3141","DOI":"10.1210\/jc.2007-0238","article-title":"High Risk of Congenital Hypothyroidism in Multiple Pregnancies","volume":"92","author":"Olivieri","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1530\/EJE-13-0907","article-title":"Transient neonatal hyperthyrotropinemia is a risk factor for developing persistent hyperthyrotropinemia in childhood with repercussion on developmental status","volume":"172","author":"Cuestas","year":"2015","journal-title":"Eur. J. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S0022-3476(84)80544-2","article-title":"Abnormalities of thyroid function in infants with Down syndrome","volume":"104","author":"Fort","year":"1984","journal-title":"J. Pediatr."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"American Academy of Pediatrics (2011). Health Supervision for Children with Down Syndrome. Pediatrics, 128, 393\u2013406.","DOI":"10.1542\/peds.2011-1605"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3304","DOI":"10.1210\/jc.2005-0130","article-title":"The effect of thyroxine treatment started in the neonatal period on development and growth of two-year-old Down syndrome children: A randomized clinical trial","volume":"90","author":"Vulsma","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["International Journal of Neonatal Screening"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2409-515X\/7\/4\/81\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:38:28Z","timestamp":1760168308000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2409-515X\/7\/4\/81"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,1]]},"references-count":40,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["ijns7040081"],"URL":"https:\/\/doi.org\/10.3390\/ijns7040081","relation":{},"ISSN":["2409-515X"],"issn-type":[{"value":"2409-515X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,1]]}}}