{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:18:13Z","timestamp":1792030693870,"version":"4.4.0"},"reference-count":47,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T00:00:00Z","timestamp":1694822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,15]]},"abstract":"Abstract<\/jats:title>\n \n Context<\/jats:title>\n Due to ethical considerations, antenatal dose finding for prednisolone and dexamethasone in pregnant women is limited, leading to a knowledge gap.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n In order to guide the clinician in weighing benefits vs risks, the aim is to systematically review the current literature on the side effects of antenatal predniso(lo)ne and dexamethasone use on the fetus, newborn, and (pre)pubertal child.<\/jats:p>\n <\/jats:sec>\n \n Evidence Acquisition<\/jats:title>\n The search was performed in PubMed\/MEDLINE and Embase using prespecified keywords and Medical Subject Headings. This systematic review investigated studies published until August 2022, with the following inclusion criteria: studies were conducted in humans and assessed side effects of long-term antenatal predniso(lo)ne and dexamethasone use during at least one of the trimesters on the child during the fetal period, neonatal phase, and during childhood.<\/jats:p>\n <\/jats:sec>\n \n Evidence Synthesis<\/jats:title>\n In total, 328 papers in PubMed and 193 in Embase were identified. Fifteen studies were eligible for inclusion. Seven records were added through references. Antenatal predniso(lo)ne use may be associated with lower gestational age, but was not associated with miscarriages and stillbirths, congenital abnormalities, differences in blood pressure or low blood glucose levels at birth, or with low bone mass, long-term elevated cortisol and cortisone, or high blood pressure at prepubertal age. Increased risks of antenatal dexamethasone use include association with miscarriages and stillbirths, and from age 16 years, associations with disturbed insulin secretion and higher glucose and cholesterol levels.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Based on the limited evidence found, predniso(lo)ne may have less side effects compared with dexamethasone in short- and long-term outcomes. Current literature shows minimal risk of side effects in the newborn from administration of a prenatal predniso(lo)ne dose of up to 10 mg per day.<\/jats:p>\n <\/jats:sec>","DOI":"10.1210\/clinem\/dgad547","type":"journal-article","created":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:33:28Z","timestamp":1694738008000},"page":"e1328-e1335","source":"Crossref","is-referenced-by-count":8,"title":["Safety of Antenatal Predniso(lo)ne and Dexamethasone on Fetal, Neonatal and Childhood Outcomes: A Systematic Review"],"prefix":"10.1210","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8411-7825","authenticated-orcid":false,"given":"Elise M A","family":"Slob","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center , P.O. Box 9600, 2300 RC Leiden , The Netherlands"},{"name":"Department of Clinical Pharmacy, Haaglanden Medical Center , P.O. Box 432, 2501 CK The Hague , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline U M","family":"Termote","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Woman and Baby Division, Wilhelmina Children's Hospital-University Medical Center , P.O. Box 85090, 3508 AB Utrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janna W","family":"Nijkamp","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Women and Baby Division, Birth Centre Wilhelmina Children\u2019s Hospital, University Medical Center Utrecht , P.O. Box 85090, 3508 AB Utrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hetty J","family":"van der Kamp","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Wilhelmina Children's Hospital, University Medical Center Utrecht , P.O. Box 85090, 3508 AB Utrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5352-9328","authenticated-orcid":false,"given":"Erica L T","family":"van den Akker","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Endocrinology, Erasmus MC-Sophia Children's Hospital, University Medical Center Rotterdam , P.O. Box 2040, 3000 CA Rotterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2023,9,16]]},"reference":[{"issue":"3","key":"2024031503433035100_dgad547-B1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.biopsych.2005.03.032","article-title":"Prenatal anxiety predicts individual differences in cortisol in pre-adolescent children","volume":"58","author":"O\u2019Connor","year":"2005","journal-title":"Biol Psychiatry"},{"issue":"1","key":"2024031503433035100_dgad547-B2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.psyneuen.2012.08.012","article-title":"Glucocorticoid excess and the developmental origins of disease: two decades of testing the hypothesis\u20132012 curt richter award winner","volume":"38","author":"Reynolds","year":"2013","journal-title":"Psychoneuroendocrinology"},{"key":"2024031503433035100_dgad547-B3","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/neuro.08.019.2009","article-title":"Prenatal stress, glucocorticoids and the programming of adult disease","volume":"3","author":"Cottrell","year":"2009","journal-title":"Front Behav Neurosci"},{"issue":"Suppl 3","key":"2024031503433035100_dgad547-B4","doi-asserted-by":"crossref","first-page":"U49","DOI":"10.1530\/eje.0.151u049","article-title":"Prenatal glucocorticoids and long-term programming","volume":"151","author":"Seckl","year":"2004","journal-title":"Eur J Endocrinol"},{"issue":"9","key":"2024031503433035100_dgad547-B5","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.biopsych.2013.03.009","article-title":"Fetal glucocorticoid exposure is associated with preadolescent brain development","volume":"74","author":"Davis","year":"2013","journal-title":"Biol Psychiatry"},{"issue":"10","key":"2024031503433035100_dgad547-B6","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.placenta.2004.12.008","article-title":"The transplacental passage of prednisolone in pregnancies complicated by early-onset HELLP syndrome","volume":"26","author":"van Runnard Heimel","year":"2005","journal-title":"Placenta"},{"issue":"25","key":"2024031503433035100_dgad547-B7","doi-asserted-by":"crossref","first-page":"6948","DOI":"10.1182\/blood-2011-02-339234","article-title":"First-trimester low-dose prednisolone in refractory antiphospholipid antibody-related pregnancy loss","volume":"117","author":"Bramham","year":"2011","journal-title":"Blood"},{"issue":"3","key":"2024031503433035100_dgad547-B8","doi-asserted-by":"crossref","first-page":"e191","DOI":"10.1210\/clinem\/dgz145","article-title":"Exposure to glucocorticoids in the first part of fetal life is associated with insulin secretory defect in adult humans","volume":"105","author":"Riveline","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2024031503433035100_dgad547-B9","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1159\/000348515","article-title":"Acute encephalopathy with unilateral cortical-subcortical lesions in two unrelated kindreds treated with glucocorticoids prenatally for congenital adrenal hyperplasia due to 21-hydroxylase deficiency: established facts and novel insight","volume":"80","author":"Grunt","year":"2013","journal-title":"Horm Res Paediatr"},{"key":"2024031503433035100_dgad547-B10","volume-title":"Perinatale Zorg in Nederland Anno 2020: Duiding Door Landelijke Perinatale Audit en Registratie","author":"PeriNed","year":"2021"},{"issue":"9938","key":"2024031503433035100_dgad547-B11","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/S0140-6736(14)60458-X","article-title":"Who has been caring for the baby?","volume":"384","author":"Darmstadt","year":"2014","journal-title":"Lancet"},{"key":"2024031503433035100_dgad547-B12","volume-title":"JBI Mannual for Evidence Synthesis","author":"Moola","year":"2020"},{"issue":"10","key":"2024031503433035100_dgad547-B13","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1136\/ard.62.10.1010","article-title":"Questions about dexamethasone use for the prevention of anti-SSA related congenital heart block","volume":"62","author":"Costedoat-Chalumeau","year":"2003","journal-title":"Ann Rheum Dis"},{"issue":"5","key":"2024031503433035100_dgad547-B14","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s11882-013-0372-x","article-title":"Pharmacogenetics and the development of personalized approaches for combination therapy in asthma","volume":"13","author":"Miller","year":"2013","journal-title":"Curr Allergy Asthma Rep"},{"key":"2024031503433035100_dgad547-B15","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1546-0096-12-47","article-title":"Bone status of children born from mothers with autoimmune diseases treated during pregnancy with prednisone and\/or low molecular weight heparin","volume":"12","author":"Pagnini","year":"2014","journal-title":"Pediatr Rheumatol Online J"},{"issue":"7","key":"2024031503433035100_dgad547-B16","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1002\/art.38519","article-title":"Rheumatoid arthritis during pregnancy and postnatal catch-up growth in the offspring","volume":"66","author":"de Steenwinkel","year":"2014","journal-title":"Arthritis Rheumatol"},{"issue":"6","key":"2024031503433035100_dgad547-B17","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1111\/cen.12388","article-title":"The influence of foetal prednisone exposure on the cortisol levels in the offspring","volume":"80","author":"de Steenwinkel","year":"2014","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2024031503433035100_dgad547-B18","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.reprotox.2017.05.002","article-title":"Does prednisone use or disease activity in pregnant women with rheumatoid arthritis influence the body composition of their offspring?","volume":"71","author":"de Steenwinkel","year":"2017","journal-title":"Reprod Toxicol"},{"issue":"4","key":"2024031503433035100_dgad547-B19","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1002\/pds.4410","article-title":"Patterns of prednisone use during pregnancy in women with rheumatoid arthritis: daily and cumulative dose","volume":"27","author":"Palmsten","year":"2018","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"1","key":"2024031503433035100_dgad547-B20","doi-asserted-by":"crossref","first-page":"e000852","DOI":"10.1136\/rmdopen-2018-000852","article-title":"Associations between antenatal prednisone exposure and long-term cortisol and cortisone concentrations in children born to women with rheumatoid arthritis: results from a nationwide prospective cohort study","volume":"5","author":"Ince-Askan","year":"2019","journal-title":"RMD Open"},{"issue":"3","key":"2024031503433035100_dgad547-B21","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1530\/EJE-08-0280","article-title":"Long-term follow-up of prenatally treated children at risk for congenital adrenal hyperplasia: does dexamethasone cause behavioural problems?","volume":"159","author":"Hirvikoski","year":"2008","journal-title":"Eur J Endocrinol"},{"issue":"1","key":"2024031503433035100_dgad547-B22","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1080\/09297049.2012.745495","article-title":"Cognitive and social function in girls with congenital adrenal hyperplasia\u2014influence of prenatally administered dexamethasone","volume":"20","author":"Maryniak","year":"2014","journal-title":"Child Neuropsychol"},{"issue":"10","key":"2024031503433035100_dgad547-B23","doi-asserted-by":"crossref","first-page":"3838","DOI":"10.1210\/jc.2016-1543","article-title":"Sex-Dimorphic effects of prenatal treatment with dexamethasone","volume":"101","author":"Wallensteen","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"2024031503433035100_dgad547-B24","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.psyneuen.2018.02.033","article-title":"Prenatal dexamethasone treatment in the context of at risk CAH pregnancies: long-term behavioral and cognitive outcome","volume":"91","author":"Karlsson","year":"2018","journal-title":"Psychoneuroendocrinology"},{"key":"2024031503433035100_dgad547-B25","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.yhbeh.2017.11.004","article-title":"Evaluation of behavioral problems after prenatal dexamethasone treatment in Swedish children and adolescents at risk of congenital adrenal hyperplasia","volume":"98","author":"Wallensteen","year":"2018","journal-title":"Horm Behav"},{"issue":"11","key":"2024031503433035100_dgad547-B26","doi-asserted-by":"crossref","first-page":"e4074","DOI":"10.1210\/clinem\/dgaa611","article-title":"First trimester DEX treatment is not associated with altered brain activity during working memory performance in adults","volume":"105","author":"Van't Westeinde","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"issue":"7","key":"2024031503433035100_dgad547-B27","doi-asserted-by":"crossref","first-page":"e2439","DOI":"10.1210\/clinem\/dgaa280","article-title":"Perturbed Beta-cell function and lipid profile after early prenatal dexamethasone exposure in individuals without CAH","volume":"105","author":"Wallensteen","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2024031503433035100_dgad547-B28","doi-asserted-by":"crossref","first-page":"e2481","DOI":"10.1210\/clinem\/dgac081","article-title":"Ambulatory blood pressure monitoring in children and adults prenatally exposed to dexamethasone treatment","volume":"107","author":"Karlsson","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"2024031503433035100_dgad547-B29","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jns.2017.03.051","article-title":"Effectiveness and safety of immunosuppressive therapy in neuromyelitis optica spectrum disorder during pregnancy","volume":"377","author":"Shi","year":"2017","journal-title":"J Neurol Sci"},{"issue":"8","key":"2024031503433035100_dgad547-B30","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1007\/s00431-017-2949-1","article-title":"Maternal use of prednisolone is unlikely to be associated with neonatal adrenal suppression-a single-center study of 16 cases","volume":"176","author":"de Vetten","year":"2017","journal-title":"Eur J Pediatr"},{"issue":"4","key":"2024031503433035100_dgad547-B31","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1159\/000151652","article-title":"High-dose methylprednisolone in a pregnant woman with Crohn's Disease and adrenal suppression in her newborn","volume":"94","author":"Homar","year":"2008","journal-title":"Neonatology"},{"issue":"4","key":"2024031503433035100_dgad547-B32","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1111\/j.1365-2265.2010.03826.x","article-title":"Prenatal dexamethasone use for the prevention of virilization in pregnancies at risk for classical congenital adrenal hyperplasia because of 21-hydroxylase (CYP21A2) deficiency: a systematic review and meta-analyses","volume":"73","author":"Fern\u00e1ndez-Balsells","year":"2010","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2024031503433035100_dgad547-B33","author":"Slob"},{"issue":"12","key":"2024031503433035100_dgad547-B34","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1111\/j.1471-0528.2004.00288.x","article-title":"Infant cortisol response after prolonged antenatal prednisolone treatment","volume":"111","author":"Miller","year":"2004","journal-title":"BJOG"},{"issue":"8","key":"2024031503433035100_dgad547-B35","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1016\/j.psyneuen.2012.11.015","article-title":"Hair cortisol, stress exposure, and mental health in humans: a systematic review","volume":"38","author":"Staufenbiel","year":"2013","journal-title":"Psychoneuroendocrinology"},{"issue":"1","key":"2024031503433035100_dgad547-B36","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1210\/jc.2013-2924","article-title":"Increased scalp hair cortisol concentrations in obese children","volume":"99","author":"Veldhorst","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2024031503433035100_dgad547-B37","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1210\/endrev\/bnab016","article-title":"Congenital adrenal hyperplasia-current insights in pathophysiology diagnostics management","volume":"43","author":"Claahsen-van der Grinten","year":"2022","journal-title":"Endocr Rev"},{"issue":"9","key":"2024031503433035100_dgad547-B38","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1136\/gutjnl-2021-325317","article-title":"Enrollment PIftCsaCFCCRArpftrcfp. Exposure to corticosteroids in pregnancy is associated with adverse perinatal outcomes among infants of mothers with inflammatory bowel disease: results from the PIANO registry","volume":"71","author":"Odufalu","year":"2022","journal-title":"Gut"},{"issue":"12","key":"2024031503433035100_dgad547-B39","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1002\/bdra.10134","article-title":"First trimester exposure to corticosteroids and oral clefts","volume":"67","author":"Pradat","year":"2003","journal-title":"Birth Defects Res A Clin Mol Teratol"},{"issue":"1","key":"2024031503433035100_dgad547-B40","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/(SICI)1096-9926(199807)58:1<2::AID-TERA2>3.0.CO;2-4","article-title":"Corticosteroids during pregnancy and oral clefts: a case-control study","volume":"58","author":"Rodr\u00edguez-Pinilla","year":"1998","journal-title":"Teratology"},{"key":"2024031503433035100_dgad547-B41","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1186\/1471-2393-14-272","article-title":"Association between gestational age at birth, antenatal corticosteroids, and outcomes at 5 years: multiple courses of antenatal corticosteroids for preterm birth study at 5 years of age (MACS-5)","volume":"14","author":"Asztalos","year":"2014","journal-title":"BMC Pregnancy Childbirth"},{"issue":"6","key":"2024031503433035100_dgad547-B42","doi-asserted-by":"crossref","first-page":"e220483","DOI":"10.1001\/jamapediatrics.2022.0483","article-title":"Evaluation of long-term outcomes associated with preterm exposure to antenatal corticosteroids: A systematic review and meta-analysis","volume":"176","author":"Ninan","year":"2022","journal-title":"JAMA Pediatr"},{"issue":"11","key":"2024031503433035100_dgad547-B43","first-page":"3872","article-title":"Long-term somatic follow-up of prenatally treated children with congenital adrenal hyperplasia","volume":"83","author":"Lajic","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2024031503433035100_dgad547-B44","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/0306-4530(94)00070-0","article-title":"Effects of early prenatal dexamethasone on the cognitive and behavioral development of young children: results of a pilot study","volume":"20","author":"Trautman","year":"1995","journal-title":"Psychoneuroendocrinology"},{"key":"2024031503433035100_dgad547-B45","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"issue":"2","key":"2024031503433035100_dgad547-B46","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1097\/OGX.0000000000000405","article-title":"Risk factors for birth defects","volume":"72","author":"Harris","year":"2017","journal-title":"Obstet Gynecol Surv"},{"issue":"11","key":"2024031503433035100_dgad547-B47","doi-asserted-by":"crossref","first-page":"4043","DOI":"10.1210\/jc.2018-01865","article-title":"Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an endocrine society clinical practice guideline","volume":"103","author":"Speiser","year":"2018","journal-title":"J Clin Endocrinol Metab"}],"container-title":["The Journal of Clinical Endocrinology & Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgad547\/51788969\/dgad547.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/109\/4\/e1328\/56950119\/dgad547.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/109\/4\/e1328\/56950119\/dgad547.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T23:44:25Z","timestamp":1710459865000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/109\/4\/e1328\/7275659"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,16]]},"references-count":47,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,9,16]]},"published-print":{"date-parts":[[2024,3,15]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgad547","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,4]]},"published":{"date-parts":[[2023,9,16]]}}}