Development of 24-hour rhythms in cortisol secretion across infancy: a systematic review and meta-analysis of individual participant dataMedical Library, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Department of Developmental Psychology, Behavioural Science Institute, Radboud University, 6500 HB, Nijmegen, The Netherlands; Department of Clinical Psychology, Institute of Psychology, Leiden University, 2333 AK, Leiden, The Netherlands.
Department of Environmental Health Sciences, Columbia Center for Children's Environmental Health, Columbia University Mailman School of Public Health, New York, USA.
Department of Psychological and Brain Sciences, Colgate University, 13 Oak Drive, Hamilton, NY 13346, USA; Department of Human Development and Family Studies, The Pennsylvania State University, University Park, PA 16801, USA.
Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Emma Children's Hospital, Amsterdam UMC location Vrije Universiteit Amsterdam, Pediatric Endocrinology, De Boelelaan 1117, Amsterdam, The Netherlands.
Department of Psychology and the Social Science Research Institute, The Pennsylvania State University, University Park, Pennsylvania, 16801, USA.
Psychobiology of Stress & Health Lab, Psychology Department, Mount Allison University, New Brunswick, Canada.
Departments of Psychiatry and Pediatrics, University of California, San Francisco (UCSF), USA.
Department of Molecular Sciences, "Iuliu Hațieganu" University of Medicine and Pharmacy, 6 Louis Pasteur St., 400349 Cluj-Napoca, Romania; Cognitive Neuroscience Laboratory, Babes-Bolyai University, 30 Fântânele St., 400294, Cluj-Napoca, Romania.
Faculty of Psychology, University of Warsaw, Stawki 5/7, 00-183 Warsaw, Poland; Institute of Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland.
Department of Psychology, Whitman College, WA, USA.
Department of Developmental Psychology, Behavioral Science Institute, Radboud University, 6500 HB Nijmegen, The Netherlands; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands.
Celerion Switzerland AG, Switzerland.
Paediatric Endocrinology & Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, D-95392 Giessen, Germany.
Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, Amsterdam, The Netherlands; Netherlands Institute for Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands; Amsterdam UMC, University of Amsterdam, Laboratory of Endocrinology, Department of Laboratory Medicine, Amsterdam, The Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Endocrinology, Metabolism and Nutrition, Amsterdam, The Netherlands; Amsterdam Neuroscience, Cellular and Molecular Mechanisms, Amsterdam, The Netherlands.
Department of Health, Medicine and Caring Sciences, Linköping University, 58185 Linköping, Sweden; School of Nursing and Midwifery, Edith Cowan University, Joondalup, WA 6027, Australia.
Emma Children's Hospital, Amsterdam UMC location Vrije Universiteit Amsterdam, Pediatric Endocrinology, De Boelelaan 1117, Amsterdam, The Netherlands; Amsterdam Reproduction & Development research institute, Amsterdam, The Netherlands.
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2025 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 110, no 2, p. e515-e524Article, review/survey (Refereed) Published
Abstract [en]
BACKGROUND: In adults, cortisol levels show a pronounced 24-hour rhythm with a peak in the early morning. It is unknown at what age this early-morning peak in cortisol emerges during infancy, hampering the establishment of optimal dosing regimens for hydrocortisone replacement therapy in infants with an inborn form of adrenal insufficiency. Therefore, we aimed to characterize daily variation in salivary cortisol concentration across the first year of life.
METHODS: We conducted a systematic review followed by an individual participant data meta-analysis of studies reporting on spontaneous (i.e., not stress induced) salivary cortisol concentrations in healthy infants aged 0-1 year. A one-stage approach using linear mixed-effects modelling was used to determine the interaction between age and time of day on cortisol concentrations.
FINDINGS: Through the systematic review, 54 eligible publications were identified, reporting on 29,177 cortisol observations. Individual participant data were obtained from 15 study cohorts, combining 17,079 cortisol measurements from 1,904 infants. The morning/evening cortisol ratio increased significantly from 1.7 (95% CI: 1.3-2.1) at birth to 3.7 (95% CI: 3.0-4.5) at 6-9 months (p < 0.0001). Cosinor analysis using all available data revealed the gradual emergence of a 24-hour rhythm during infancy.
INTERPRETATION: The early-morning peak in cortisol secretion gradually emerges from birth onwards to form a stable morning/evening ratio from age 6-9 months. This might have implications for hydrocortisone replacement therapy in infants with an inborn form of adrenal insufficiency.
Place, publisher, year, edition, pages
Oxford University Press, 2025. Vol. 110, no 2, p. e515-e524
Keywords [en]
Adrenal cortex hormones, adrenal insufficiency, biological clocks, circadian rhythm, cortisol, endocrinology, hydrocortisone, infant, pediatrics
National Category
Pediatrics
Identifiers
URN: urn:nbn:se:oru:diva-115717DOI: 10.1210/clinem/dgae590ISI: 001310220700001PubMedID: 39207206Scopus ID: 2-s2.0-85216569389OAI: oai:DiVA.org:oru-115717DiVA, id: diva2:1894078
Note
This study was supported by the International Fund Congenital Adrenal Hyperplasia (to MJJF). LK was partly supported by a VENI grant (2020-09150161910128 to LK) from the Netherlands Organization for Health Research and Development (ZonMw) and the BioClock Consortium (project number 1292.19.0777to LK and AK) funded by the research programme NWA-ORC of the Dutch Research Council (NWO).
Protocol
2024-09-022024-09-022026-01-23Bibliographically approved