{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:56:51Z","timestamp":1789772211329,"version":"4.0.1"},"reference-count":26,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Neonatal hypoglycemia is a common metabolic disorder that may cause long-term neurodevelopmental impairment. Reliable early biomarkers to estimate hypoglycemia risk are lacking.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate whether umbilical cord blood glucose (UCBG) values and derived parameters are associated with transitional neonatal hypoglycemia (TNH) and to establish percentile-based UCBG reference values.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This prospective cohort study was performed at a tertiary perinatal center in D\u00fcsseldorf, Germany. Data were collected from May 27, 2020, to September 1, 2022. The final dataset included neonates (gestational age, \u226535 weeks\u20090 days) with paired arterial and venous umbilical cord blood samples who were exposed or unexposed to hypoglycemia risk factors. Exclusion criteria consisted of incomplete or invalid cord blood samples, missing glucose measurements within the first 4 hours of life, and transient or persistent hyperinsulinism. Maternal and neonatal clinical data were systematically recorded. Data were analyzed from March 18 to July 15, 2025.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Paired arterial and venous cord blood samples collected at birth; standardized postnatal glucose screening and management.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary end point was hypoglycemia, defined as a glucose level of 45 mg\/dL or less during postnatal screening; severe hypoglycemia was defined as a glucose level of less than 30 mg\/dL. UCBG parameters included arterial and venous glucose values, venous-arterial difference, and glucose extraction rate. Prospective association of UCBG parameters with postnatal hypoglycemia was assessed using receiver operating characteristic (ROC) analyses.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Of 598 neonates included in the analysis, the median gestational age was 39\u2009weeks 0 days (IQR, 37 weeks\u20096 days to 40 weeks\u20090 days), and 332 (55.5%) were male. Hypoglycemia occurred in 188 neonates (31.4%) and severe hypoglycemia occurred in 22 neonates (3.7%). The median arterial UCBG level was 67 (IQR, 58-84) mg\/dL; venous UCBG level, 85 (IQR, 72-102) mg\/dL; venous-arterial level difference, 16 (IQR, 10-23) mg\/dL; and extraction rate, 19.0% (IQR, 12.2%-25.5%). Arterial UCBG values of 45 mg\/dL or less occurred in 22 neonates (3.7%). Compared with neonates with levels greater than 45 mg\/dL, those with levels of 45 mg\/dL or less had significantly higher median venous-arterial UCBG level differences (15 [IQR, 10-23] mg\/dL vs 24 [IQR, 17-38] mg\/dL), UCBG extraction rates (18.7% [IQR, 11.9%-25.0%] vs 35.3% [IQR, 27.5%-56.1%]), and higher incidence of severe TNH (3.3% [19\/576] vs 13.6% [3\/22]). ROC analyses demonstrated poor discriminative performance for all UCBG parameters (maximum area under the ROC curve, 0.64 [95% CI, 0.45-0.81]), and no percentile-based cutoff achieved clinically useful sensitivity or specificity. Percentiles for UCBG values are provided.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n The findings of this prospective cohort study suggest that UCBG parameters were not associated with subsequent TNH. However, this study provides a large, single-center, percentile-based UCBG dataset that can support future research and clinical interpretation. Very low UCBG values may help identify neonates with higher likelihood of pathologic hypoglycemia, but this requires further validation.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.6170","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T15:30:25Z","timestamp":1776699025000},"page":"e266170","source":"Crossref","is-referenced-by-count":3,"title":["Umbilical Cord Blood Glucose Concentrations and Transitional Neonatal Hypoglycemia"],"prefix":"10.1001","volume":"9","author":[{"given":"Marcia","family":"Roeper","sequence":"first","affiliation":[{"name":"Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital D\u00fcsseldorf, Heinrich-Heine-University, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Meissner","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital D\u00fcsseldorf, Heinrich-Heine-University, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Friesl","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital D\u00fcsseldorf, Heinrich-Heine-University, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin","family":"Kurz","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital D\u00fcsseldorf, Heinrich-Heine-University, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Dzietko","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital D\u00fcsseldorf, Heinrich-Heine-University, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ertan","family":"Mayatepek","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital D\u00fcsseldorf, Heinrich-Heine-University, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrike","family":"Hoermann","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital D\u00fcsseldorf, Heinrich-Heine-University, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Kummer","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital D\u00fcsseldorf, Heinrich-Heine-University, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"issue":"5","key":"zoi260217r1","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1016\/j.jpeds.2009.06.044","article-title":"Knowledge gaps and research needs for understanding and treating neonatal hypoglycemia: workshop report from Eunice Kennedy Shriver National Institute of Child Health and Human Development.","volume":"155","author":"Hay","year":"2009","journal-title":"J Pediatr"},{"issue":"5","key":"zoi260217r2","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1016\/j.jpeds.2012.05.022","article-title":"Incidence of neonatal hypoglycemia in babies identified as at risk.","volume":"161","author":"Harris","year":"2012","journal-title":"J Pediatr"},{"key":"zoi260217r3","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.jpeds.2020.02.079","article-title":"Glucose profiles in healthy term infants in the first 5 days: the Glucose in Well Babies (GLOW) study.","volume":"223","author":"Harris","year":"2020","journal-title":"J Pediatr"},{"issue":"6","key":"zoi260217r4","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.1016\/j.jpeds.2015.02.045","article-title":"Re-evaluating \u201ctransitional neonatal hypoglycemia\u201d: mechanism and implications for management.","volume":"166","author":"Stanley","year":"2015","journal-title":"J Pediatr"},{"issue":"5","key":"zoi260217r5","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1159\/000514711","article-title":"Neonatal hypoglycaemia: a never-ending story?","volume":"118","author":"Vain","year":"2021","journal-title":"Neonatology"},{"issue":"3","key":"zoi260217r6","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.3683","article-title":"Transitional neonatal hypoglycemia and adverse neurodevelopment in midchildhood.","volume":"7","author":"Roeper","year":"2024","journal-title":"JAMA Netw Open"},{"key":"zoi260217r7","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.580642","article-title":"Risk factors for adverse neurodevelopment in transient or persistent congenital hyperinsulinism.","volume":"11","author":"Roeper","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"key":"zoi260217r8","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.jpeds.2022.02.045","article-title":"Reliability and observer dependence of signs of neonatal hypoglycemia.","volume":"245","author":"Hoermann","year":"2022","journal-title":"J Pediatr"},{"key":"zoi260217r9","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1179102","article-title":"Neonatal hypoglycemia: lack of evidence for a safe management.","volume":"14","author":"Roeper","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"zoi260217r10","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1530\/eje.0.1490043","article-title":"Long-term follow-up of 114 patients with congenital hyperinsulinism.","volume":"149","author":"Meissner","year":"2003","journal-title":"Eur J Endocrinol"},{"issue":"1","key":"zoi260217r11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000481774","article-title":"Formal neurocognitive testing in 60 patients with congenital hyperinsulinism.","volume":"89","author":"Ludwig","year":"2018","journal-title":"Horm Res Paediatr"},{"key":"zoi260217r12","doi-asserted-by":"publisher","first-page":"156","DOI":"10.3389\/fendo.2017.00156","article-title":"Both low blood glucose and insufficient treatment confer risk of neurodevelopmental impairment in congenital hyperinsulinism: a multinational cohort study.","volume":"8","author":"Helleskov","year":"2017","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"4","key":"zoi260217r13","doi-asserted-by":"publisher","first-page":"e1542","DOI":"10.1210\/clinem\/dgab024","article-title":"Long-term outcome and treatment in persistent and transient congenital hyperinsulinism: a Finnish population-based study.","volume":"106","author":"M\u00e4nnist\u00f6","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"zoi260217r14","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1549310","article-title":"Developing a congenital hyperinsulinism prioritized research agenda: a patient-driven international collaborative research network.","volume":"16","author":"Pasquini","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"zoi260217r15","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s13023-022-02214-y","article-title":"Congenital hyperinsulinism in infancy and childhood: challenges, unmet needs and the perspective of patients and families.","volume":"17","author":"Banerjee","year":"2022","journal-title":"Orphanet J Rare Dis"},{"issue":"12","key":"zoi260217r16","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1111\/jpc.14473","article-title":"Does umbilical cord blood glucose extraction discriminate the risk of early neonatal hypoglycaemia in at-risk newborns?","volume":"55","author":"Kennedy","year":"2019","journal-title":"J Paediatr Child Health"},{"issue":"1","key":"zoi260217r17","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1186\/s12902-023-01532-x","article-title":"Umbilical artery cord blood glucose predicted hypoglycemia in gestational diabetes mellitus and other at-risk newborns.","volume":"23","author":"Wang","year":"2023","journal-title":"BMC Endocr Disord"},{"issue":"20","key":"zoi260217r18","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.","volume":"310","author":"World Medical Association","year":"2013","journal-title":"JAMA"},{"issue":"8","key":"zoi260217r19","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2022-063009","article-title":"Protecting against brain damage by improving treatment in neonates with hypoglycaemia: ProBrain-D\u2014a study protocol of a prospective longitudinal study.","volume":"12","author":"Hoermann","year":"2022","journal-title":"BMJ Open"},{"issue":"6","key":"zoi260217r20","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1001\/jamapediatrics.2024.0304","article-title":"Association of fetal catecholamines with neonatal hypoglycemia.","volume":"178","author":"Hoermann","year":"2024","journal-title":"JAMA Pediatr"},{"issue":"2","key":"zoi260217r21","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1111\/aogs.13471","article-title":"Arterio-venous blood gas ?values for validation of umbilical cord blood samples at birth are not only biased by sample mix ups but also affected by clinical factors.","volume":"98","author":"Mokarami","year":"2019","journal-title":"Acta Obstet Gynecol Scand"},{"issue":"7","key":"zoi260217r22","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1111\/j.1471-0528.2012.03308.x","article-title":"Evaluation of selection criteria for validating paired umbilical cord blood gas samples: an observational study.","volume":"119","author":"White","year":"2012","journal-title":"BJOG"},{"issue":"9","key":"zoi260217r23","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1016\/j.clinbiochem.2014.01.004","article-title":"Evaluation of the Nova StatStrip glucometer in a pediatric hospital setting.","volume":"47","author":"Lockyer","year":"2014","journal-title":"Clin Biochem"},{"issue":"10","key":"zoi260217r24","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1055\/s-2006-924458","article-title":"Analysis of the neonatal collective in the Federal Republic of Germany 12th report: presentation of detailed percentiles for the body measurement of newborns.","volume":"66","author":"Voigt","year":"2006","journal-title":"Geburtshilfe Frauenheilkd"},{"issue":"6","key":"zoi260217r25","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/0029-7844(96)00048-8","article-title":"The impact of gestational age and fetal growth on the maternal-fetal glucose concentration difference.","volume":"87","author":"Marconi","year":"1996","journal-title":"Obstet Gynecol"},{"key":"zoi260217r26","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2023.1071206","article-title":"New approaches to screening and management of neonatal hypoglycemia based on improved understanding of the molecular mechanism of hypoglycemia.","volume":"11","author":"Stanley","year":"2023","journal-title":"Front Pediatr"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2847957\/roeper_2026_oi_260217_1776101092.71925.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T15:30:26Z","timestamp":1776699026000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2847957"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2026.6170","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,20]]}}}