{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T19:10:31Z","timestamp":1788808231871,"version":"build-2803163510"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Total calcium concentration (tCa) poorly reflects ionized hypocalcemia across species, and multiple factors influence ionized calcium concentration (iCa2+). These relationships have not been evaluated in Assaf ewes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis\/Objectives<\/jats:title>\n                    <jats:p>Assess the diagnostic accuracy of tCa for detecting hypocalcemia and identify factors associated with iCa2+ during pre- and post-lambing periods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>A total of 105 clinically healthy multiparous Assaf ewes from a commercial flock.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Prospective observational study. Venous blood samples were collected during pre- and post-lambing periods. Blood gas-electrolytes (pH, pCO\u2082, pO\u2082, HCO\u2083\u2212, TCO\u2082, Na+, K+, iCa2+) and biochemical analyses (total protein, albumin, tCa, magnesium, phosphorus, \u03b2-hydroxybutyrate [BHB], glucose, alkaline phosphatase) were performed. Discriminatory performance of tCa was evaluated using area under the receiver operating characteristic curve (AUC) analysis. Variables associated with iCa2+ were assessed using multiple linear regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During the pre-lambing period, tCa showed moderate diagnostic performance (AUC, 0.73; 95% CI, 0.57-0.87; sensitivity, 67%; specificity, 80%) at a cutoff of \u2264\u20092.42\u00a0mmol\/L, whereas performance was poor for the post-lambing period (AUC, 0.59; 95% CI, 0.47-0.70; sensitivity, 97%; specificity, 31%) at \u2264\u20092.77\u00a0mmol\/L. In multiple regression, tCa, BHB, pCO\u2082, and pO\u2082 were associated with iCa2+ during pre-lambing (adjusted R2\u00a0=\u00a00.27, P\u00a0&amp;lt;\u00a0.001), whereas tCa, BHB, phosphorus, albumin, and Na+ were associated with the post-lambing period (adjusted R2\u00a0=\u00a00.25, P\u00a0&amp;lt;\u00a0.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and clinical importance<\/jats:title>\n                    <jats:p>iCa2+ varied by production stage and was influenced by several physiologic variables. Direct measurement of iCa2+ should be prioritized to improve the accuracy of hypocalcemia assessment in Assaf ewes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jvimsj\/aalag202","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T19:06:46Z","timestamp":1788808006000},"source":"Crossref","is-referenced-by-count":0,"title":["Discriminatory performance of total calcium for ionized hypocalcemia and factors affecting ionized calcium in Assaf ewes during the pre- and post-lambing periods"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2861-0236","authenticated-orcid":false,"given":"Kenan \u00c7","family":"T\u00fcmer","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Faculty of Veterinary Medicine, Kastamonu University , 37150 Kastamonu ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8460-4885","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Buczinski","sequence":"additional","affiliation":[{"name":"D\u00e9partement des Sciences Cliniques, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al , St-Hyacinthe, J2S 2M2, \u00a0","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6239-1567","authenticated-orcid":false,"given":"Serkan","family":"Bozaci","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Veterinary Medicine, Kastamonu University , 37150 Kastamonu ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2981-2032","authenticated-orcid":false,"given":"\u00d6mer","family":"Deniz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Veterinary Medicine, Kastamonu University , 37150 Kastamonu ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6178-4641","authenticated-orcid":false,"given":"Tarik","family":"\u015eafak","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Veterinary Medicine, Kastamonu University , 37150 Kastamonu ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6204-1674","authenticated-orcid":false,"given":"Berrak I","family":"Deniz","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Veterinary Medicine, Kastamonu University , 37150 Kastamonu ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4077-3222","authenticated-orcid":false,"given":"Abdullah","family":"\u015eim\u015fek","sequence":"additional","affiliation":[{"name":"Ihsangazi Vocational School, Kastamonu University , 37150 Kastamonu ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6113-8458","authenticated-orcid":false,"given":"Thomas","family":"Wittek","sequence":"additional","affiliation":[{"name":"Clinical Centre for Ruminant and Camelid Medicine, Clinical Department for Farm Animals and Food System Science, University of Veterinary Medicine Vienna , 1210 Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"2026090715042320600_ref1","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1079\/BJN19700067","article-title":"Calcium metabolism in pregnant ewes","volume":"24","author":"Braithwaite","year":"1970","journal-title":"Br J Nutr"},{"key":"2026090715042320600_ref2","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1071\/AN17588","article-title":"Do calcium and magnesium deficiencies in reproducing ewes contribute to high lamb mortality?","volume":"60","author":"Friend","year":"2020","journal-title":"Anim Prod Sci"},{"key":"2026090715042320600_ref3","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1111\/avj.13321","article-title":"The effects of maternal calcium status during late gestation on lamb growth and survival in twin-bearing Merino ewes grazing pasture","volume":"102","author":"Munn","year":"2024","journal-title":"Aust Vet J"},{"key":"2026090715042320600_ref4","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1111\/rda.13855","article-title":"Factors associated with ewe and lamb survival, and subsequent reproductive performance of sheep undergoing emergency caesarean section","volume":"56","author":"Voigt","year":"2021","journal-title":"Reprod Domest Anim"},{"key":"2026090715042320600_ref5","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.3168\/jds.S0022-0302(03)73783-7","article-title":"Hypocalcemia reduces endogenous glucose production in hyperketonemic sheep","volume":"86","author":"Schlumbohm","year":"2003","journal-title":"J Dairy Sci"},{"key":"2026090715042320600_ref6","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.cvsm.2008.01.010","article-title":"Calcium: Total or ionized?","volume":"38","author":"Schenck","year":"2008","journal-title":"Vet Clin N Am Small Anim Pract"},{"key":"2026090715042320600_ref7","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.cvfa.2014.04.003","article-title":"Calcium and magnesium disorders","volume":"30","author":"Goff","year":"2014","journal-title":"Vet Clin North Am Food Anim Pract"},{"key":"2026090715042320600_ref8","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1177\/0004563213482892","article-title":"It is time to start ordering ionized calcium more frequently: preanalytical factors can be controlled and postanalytical data justify measurement","volume":"50","author":"Glendenning","year":"2013","journal-title":"Ann Clin Biochem"},{"key":"2026090715042320600_ref9","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.3390\/ani11041036","article-title":"Changes in the relationship between ionized and total calcium in clinically healthy dairy cows in the period around calving","volume":"11","author":"Ott","year":"2021","journal-title":"Animals."},{"key":"2026090715042320600_ref10","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1111\/jvim.16938","article-title":"Predictors of blood ionized calcium concentration in sick adult cattle","volume":"38","author":"Karapinar","year":"2024","journal-title":"J Vet Intern Med"},{"key":"2026090715042320600_ref11","doi-asserted-by":"publisher","first-page":"2592","DOI":"10.1111\/jvim.16879","article-title":"Evaluation of the relationship between ionized and total calcium concentrations in blood during the first week of lactation in dairy cows","volume":"37","author":"Cohrs","year":"2023","journal-title":"J Vet Intern Med"},{"key":"2026090715042320600_ref12","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1079\/BJN19690093","article-title":"Calcium metabolism in lactating ewes","volume":"23","author":"Braithwaite","year":"1969","journal-title":"Br J Nutr"},{"key":"2026090715042320600_ref13","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1017\/S002202991400020X","article-title":"Differences in peripartal plasma parameters related to calcium homeostasis of dairy sheep and goats in comparison with cows","volume":"81","author":"Wilkens","year":"2014","journal-title":"J Dairy Res"},{"key":"2026090715042320600_ref14","doi-asserted-by":"publisher","first-page":"515","DOI":"10.2460\/ajvr.71.5.515","article-title":"Evaluation of a portable clinical analyzer for the determination of blood gas partial pressures, electrolyte concentrations, and hematocrit in venous blood samples collected from cattle, horses, and sheep","volume":"71","author":"Peir\u00f3","year":"2010","journal-title":"Am J Vet Res"},{"key":"2026090715042320600_ref15","doi-asserted-by":"publisher","first-page":"e70107","DOI":"10.1111\/asj.70107","article-title":"Evaluating amino acid profiles and blood gas concentrations between single and twin merino newborn lambs","volume":"96","author":"Dunstan","year":"2025","journal-title":"Anim Sci J"},{"key":"2026090715042320600_ref16","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1111\/vec.70048","article-title":"Evaluation of the analytical and diagnostic performances of a point-of-care device for hematocrit measurement in calves","volume":"35","author":"T\u00fcmer","year":"2025","journal-title":"J Vet Emerg Crit Care (San Antonio)"},{"key":"2026090715042320600_ref17","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v098.i11","article-title":"Cutpointr: improved estimation and validation of optimal cutpoints in R","volume":"98","author":"Thiele","year":"2021","journal-title":"J Stat Softw"},{"key":"2026090715042320600_ref18","first-page":"3325","volume-title":"The Merck Veterinary Manual","author":"Aiello","year":"2016"},{"key":"2026090715042320600_ref19","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.cvfa.2010.10.004","article-title":"Treatment and control of peri-parturient metabolic diseases: pregnancy toxemia, hypocalcemia, hypomagnesemia","volume":"27","author":"Brozos","year":"2011","journal-title":"Vet Clin North Am Food Anim Pract"},{"key":"2026090715042320600_ref20","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s11250-022-03068-z","article-title":"Effect of physiological status and parity on metabolic and trace element profile of crossbred Rambouillet sheep of Himalayan region","volume":"54","author":"Singh","year":"2022","journal-title":"Tropl Anim Health Prod"},{"key":"2026090715042320600_ref21","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.domaniend.2009.10.003","article-title":"Effects of 1,25-dihydroxyvitamin D3 on calcium and phosphorus homeostasis in sheep fed diets either adequate or restricted in calcium content","volume":"38","author":"Wilkens","year":"2010","journal-title":"Domest Anim Endocrinol"},{"key":"2026090715042320600_ref22","doi-asserted-by":"publisher","first-page":"10073","DOI":"10.3390\/app142110073","article-title":"Metabolic periparturient diseases in small ruminants: an update","volume":"14","author":"Sim\u00f5es","year":"2024","journal-title":"Appl Sci"},{"key":"2026090715042320600_ref23","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1111\/j.1439-0442.2006.00832.x","article-title":"Effects of age and reproductive stage on certain serum biochemical parameters of Chios sheep under Greek rearing conditions","volume":"53","author":"Roubies","year":"2006","journal-title":"J Vet Med A Physiol Pathol Clin Med"},{"key":"2026090715042320600_ref24","doi-asserted-by":"publisher","first-page":"957","DOI":"10.9775\/kvfd.2009.858","article-title":"\u0130vesi koyunlar\u0131nda gebelik s\u00fcrecinde ve postpartum d\u00f6neminde baz\u0131 biyokimyasal parametreler ile mineral maddelerin ara\u015ft\u0131r\u0131lmas\u0131","volume":"15","author":"G\u00fcrg\u00f6ze","year":"2009","journal-title":"Kafkas Univ Vet Fak Derg"},{"key":"2026090715042320600_ref25","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1007\/s11250-023-03531-5","article-title":"Metabolic profile of transition period in ewes and its influence on passive immunity transference in lambs","volume":"55","author":"Chagas","year":"2023","journal-title":"Tropl Anim Health Prod"},{"key":"2026090715042320600_ref26","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.rvsc.2020.11.016","article-title":"Serum parameters related to mineral homeostasis and energy metabolism in ewes kept on different dietary magnesium supply during the transition period","volume":"134","author":"Ahmed","year":"2021","journal-title":"Res Vet Sci"},{"key":"2026090715042320600_ref27","first-page":"375","article-title":"Serum ionized calcium in the sheep: relation to total plasma calcium, blood pH, total plasma proteins and plasma magnesium","volume":"44","author":"Belonje","year":"1973","journal-title":"Afr Vet Ass"},{"key":"2026090715042320600_ref28","doi-asserted-by":"publisher","first-page":"475","DOI":"10.30466\/vrf.2021.139252.3096","article-title":"Prediction of ionized calcium concentration based on total calcium and protein levels in cattle and sheep","volume":"13","author":"Katsoulos","year":"2022","journal-title":"Vet Res Forum"},{"key":"2026090715042320600_ref29","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1016\/j.cca.2011.01.004","article-title":"Ionized calcium","volume":"412","author":"Baird","year":"2011","journal-title":"Clin Chim Acta"},{"key":"2026090715042320600_ref30","doi-asserted-by":"publisher","first-page":"669","DOI":"10.3168\/jds.S0022-0302(06)72130-0","article-title":"Hypocalcemia in dairy cows: meta-analysis and dietary cation anion difference theory revisited","volume":"89","author":"Lean","year":"2006","journal-title":"J Dairy Sci"},{"key":"2026090715042320600_ref31","doi-asserted-by":"publisher","first-page":"2134","DOI":"10.3168\/jds.2018-14628","article-title":"Meta-analysis of the effects of prepartum dietary cation-anion difference on performance and health of dairy cows","volume":"102","author":"Santos","year":"2019","journal-title":"J Dairy Sci"},{"key":"2026090715042320600_ref32","doi-asserted-by":"publisher","first-page":"skae205","DOI":"10.1093\/jas\/skae205","article-title":"Negative dietary cation and anion difference supplementation of twin-bearing merino ewes grazing pasture in late gestation did not affect lamb growth or survival","volume":"102","author":"Munn","year":"2024","journal-title":"J Anim Sci"},{"key":"2026090715042320600_ref33","doi-asserted-by":"publisher","first-page":"skae266","DOI":"10.1093\/jas\/skae266","article-title":"Effects of feeding a negative dietary cation and anion difference diet to twin-bearing Merino ewes in late gestation on parturition outcomes","volume":"102","author":"Munn","year":"2024","journal-title":"J Anim Sci"},{"key":"2026090715042320600_ref34","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.3168\/jds.S0022-0302(98)75732-7","article-title":"Effects of dietary cation-anion difference on the acid-base status of dry cows","volume":"81","author":"Vagnoni","year":"1998","journal-title":"J Dairy Sci"},{"key":"2026090715042320600_ref35","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1016\/j.clinbiochem.2012.04.025","article-title":"Investigation of hypercalcemia","volume":"45","author":"Endres","year":"2012","journal-title":"Clin Biochem"},{"key":"2026090715042320600_ref36","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1590\/1678-5150-pvb-6400","article-title":"Biochemical, endocrine, and histopathological profile of liver and kidneys of sheep with pregnancy toxemia","volume":"39","author":"Souto","year":"2019","journal-title":"Pesqui Vet Bras"},{"key":"2026090715042320600_ref37","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.2460\/javma.2000.217.1536","article-title":"Pregnancy toxemia in a flock of sheep","volume":"217","author":"Van Saun","year":"2000","journal-title":"J Am Vet Med Assoc"},{"key":"2026090715042320600_ref38","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1111\/j.1439-0442.1982.tb01832.x","article-title":"Plasma inorganic phosphorus and calcium concentrations in sheep with experimental phosphorus deficiency","volume":"29","author":"Breves","year":"2010","journal-title":"Zentralbl Veterinarmed A"},{"key":"2026090715042320600_ref39","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1017\/S0021859600059530","article-title":"Dietary phosphorus depletion in sheep: effects on plasma inorganic phosphorus, calcium, 1,25-(OH) 2-vit.D3 and alkaline phosphatase and on gastrointestinal P and Ca balances","volume":"105","author":"Breves","year":"1985","journal-title":"J Agric Sci"},{"key":"2026090715042320600_ref40","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1001\/archpedi.1989.02150230098031","article-title":"Serum phosphate concentration","volume":"143","author":"Lehmann","year":"1989","journal-title":"Am J Dis Child"},{"key":"2026090715042320600_ref41","doi-asserted-by":"publisher","first-page":"202A","DOI":"10.1203\/00006450-198704010-00216","article-title":"Effect of phosphate (P) concentration on ionized calcium (iCa) concentration in vitro","volume":"21","author":"Lehmann","year":"1987","journal-title":"Pediatr Res"},{"key":"2026090715042320600_ref42","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1017\/S0007114575000359","article-title":"Studies on the absorption and retention of calcium and phosphorus by young and mature Ca-deficient sheep","volume":"34","author":"Braithwaite","year":"1975","journal-title":"Br J Nutr"},{"key":"2026090715042320600_ref43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1113\/expphysiol.1969.sp001994","article-title":"Augmented renal excretion of calcium and magnesium in sheep after feeding","volume":"54","author":"Stacy","year":"1969","journal-title":"Q J Exp Physiol Cogn Med Sci"},{"key":"2026090715042320600_ref44","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1002\/recl.19570760504","article-title":"The interaction of sodium, potassium, calcium, and magnesium with human serum albumin, studied by means of conductivity measurements","volume":"76","author":"Os","year":"1957","journal-title":"Recl Trav Chim Pays-Bas"},{"key":"2026090715042320600_ref45","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1093\/clinchem\/30.2.304","article-title":"Effect of pH and NaCl on measurements of ionized calcium in matrices of serum and human albumin with a new calcium-selective electrode","volume":"30","author":"Rehfeld","year":"1984","journal-title":"Clin Chem"},{"key":"2026090715042320600_ref46","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S0167-5877(00)00115-X","article-title":"Principles and practical application of the receiver-operating characteristic analysis for diagnostic tests","volume":"45","author":"Greiner","year":"2000","journal-title":"Prev Vet Med"},{"key":"2026090715042320600_ref47","doi-asserted-by":"publisher","first-page":"113390","DOI":"10.1016\/j.buildenv.2025.113390","article-title":"The untapped potential of Bayesian region of practical equivalence for assessing null effects in multi-domain research","volume":"283","author":"Pan","year":"2025","journal-title":"Build Environ"}],"container-title":["Journal of Veterinary Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jvim\/article-pdf\/40\/5\/aalag202\/70985276\/aalag202.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jvim\/article-pdf\/40\/5\/aalag202\/70985276\/aalag202.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T19:06:47Z","timestamp":1788808007000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jvim\/article\/doi\/10.1093\/jvimsj\/aalag202\/8787476"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":47,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jvimsj\/aalag202","relation":{},"ISSN":["1939-1676"],"issn-type":[{"value":"1939-1676","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,9]]},"published":{"date-parts":[[2026,9,1]]},"article-number":"aalag202"}}