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Development of cortisol circadian rhythm in infancy
Abstract
Background and aims Cortisol is the final product of the hypothalamus-pituitary-adrenal (HPA) axis. It is secreted in a pulsatile fashion that displays a circadian rhythm. Infants are born without a circadian rhythm in cortisol and they acquire it during their first year of life. Studies do not agree on the age of appearance of the circadian rhythm (varying between 2 weeks till the age of 9 months) nor on whether it is related to the appearance of the sleep-wake circadian rhythm. The object of the present study was to find evidence of the age of appearance of the diurnal rhythm of cortisol and to compare the results obtained by several different analysis methods on a new data set. Design and measures Cortisol was determined in salival samples of 14 normally developing infants who were followed monthly between the ages of 2 and 5 months. The data were analyzed with several previously published analysis methods as well as with Multilevel Analysis (Hierarchical Linear Modeling). Results The previously published analysis methods each produced different results when applied to the current data set. Moreover, our results indicate striking differences between young infants in both age of appearance and stability of the diurnal cortisol rhythm. Also, a link was found between the appearance of the sleep-wake circadian rhythm and the cortisol circadian rhythm. An important intraindividual variability in cortisol levels was found even after correcting for the different variables that af…
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“prenatal exposure to maternal stress hormones is linked to temperamental reactivity and stress physiology, likely through epigenetic regulation of gene expression”
From The Adaptive Calibration Model of stress responsivity (2011) · cites this paper as de Weerth et al., 2003
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“In contrast, studies in saliva have demonstrated a discernible circadian rhythm in full-term neonates at 1 month of age,(142) albeit with significant intra and interindividual variability in terms of how early the rhythm appears and how persistent it is once it has appeared.(141,142,144) Further study is now needed to…”
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“First, several studies report a link between the establishment of a diurnal pattern in cortisol and sleeping through the night in infancy(44).”
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“For instance, napping (e.g., Watamura et al., 2004), respiratory illness, and feeding (De Weerth et al., 2003) have been found to influence the HPA axis.”
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“Although a normal pattern of diurnal cortisol production is typically established within the first year of life (de Weerth et al., 2003), the HPA axis continues to develop into early childhood and may continue to be sensitive to external influences during the formative early years.”
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“Infants are born without a circadian rhythm in cortisol and they normally acquire it within the first six months (de Weerth et al., 2003; Lupien et al., 2009).”
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“, diurnal rhythm, coritsol awakening response (CAR)] (95,101).”
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“, whether basal hpa function in newborns was assessed under fasting conditions, the stage of perinatal remodeling of the adrenocortex, diurnal variability of hpa activity (203)].”
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“Researchers generally agree that there is significant individual variability in when diurnal patterns emerge and studies vary considerably on when a reliable diurnal rhythm can be detected, generally suggesting between 2 and 9 months of age (de Weerth et al., 2003; Kiess et al., 1995).”
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“Intraindividual variability in cortisol levels was noted by de Weerth, Zijl, and Buitelaar (2003), who studied the early maturation of the cortisol circadian rhythm and highlighted its links with sleep.”
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“While several studies have examined the development of circadian rhythms (see [3]) or reactivity to mild stressors (see [4,5]), a full understanding of the normative development of basal cortisol levels has not yet been achieved.”
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“Also, cortisol varies throughout the day, with peak levels being reached upon awakening, and lowest levels found after sleep onset (deWeerth et al., 2003; Gunnar and Talge, 2008).”
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“…phase, when the mothers were The diurnal rhythm of the HPA-axis seems to be established during the first months of life even though a delay of up to nine months of age has been reported and individual differences may be prominent as to time and stability (for a review, see de Weerth et al., 2003).”
Seizure occurrence and the circadian rhythm of cortisol: a systematic review
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Olivera-Figueroa, L. A., Juster, R., Morin-Major, J.-K., Marin, M., & LUPIEN, S. J. (2015) · Biological Psychology · doi:10.1016/j.biopsycho.2015.09.002 · Cited by 58
Shiftwork Duration and the Awakening Cortisol Response Among Police Officers
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“The cortisol awakening response (CAR) is characterized by a 40–75% increase of salivary cortisol levels, with maximum values occurring about 30 min after awakening (de Weerth et al., 2003; Fries et al., 2009; Kudielka et al., 2006).”
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“Cortisol was determined with an in house competitive RIA (see below), which is insensitive to breast milk and formula contamination (de Weerth et al., 2003a).”
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Correlation between maternal and infant cortisol varies by breastfeeding status
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Is physiological glucocorticoid replacement important in children?
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“Although the blood samples were collected at varying times of day, preterm infants of this postnatal age, unlike adults, do not exhibit diurnal variation in cortisol production (26).”
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“Here, most evidence suggests that the development of a stable circadian pattern of cortisol secretion tends to fall into the first half year of life (Price et al., 1983; Spangler, 1991; Antonini et al., 2000), even though with considerable individual differences (De Weerth et al., 2003).”
Sheikh, H. I., Kryski, K. R., Smith, H. J., Hayden, E. P., & Singh, S. M. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.10.056 · Cited by 48
“All visits began between 12:00 pm and 3:30 pm to minimize the effects of diurnal variation on cortisol samples (de Weerth et al., 2003; Donzella et al., 2008).”
Iwata, O., Okamura, H., Saitsu, H., Saikusa, M., Kanda, H., Eshima, N., Iwata, S., Maeno, Y. V., & Matsuishi, T. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2750 · Cited by 43
Do infants show a cortisol awakening response?
Bright, M. A., Granger, D. A., & Frick, J. E. (2011) · Developmental Psychobiology · doi:10.1002/dev.20617 · Cited by 40
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The use of cortisol for the objective assessment of stress in animals: Pros and cons
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Shared Dysregulation of Homeostatic Brain-Body Pathways in Depression and Type 2 Diabetes
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Approaches to Salivary Cortisol Collection and Analysis in Infants
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“…attributed to a number of factors that have impacted studies on the topic such as differing working definitions of circadian rhythm, inconsistent sampling times, infant exposure to antenatal steroids, and variation in data collection procedures and methods of data analysis (de Weerth et al., 2003).”
BackgroundTollenaar, M. S., Beijers, R., Jansen, J., Riksen‐Walraven, J. M., & de Weerth, C. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.03.017 · Cited by 36
Maternal depression and infant daytime cortisol
Azak, S., Murison, R. C. C., Wentzel‐Larsen, T., Smith, L., & Gunnar, M. R. (2012) · Developmental Psychobiology · doi:10.1002/dev.21033 · Cited by 34
Influence of acoustic stimulation on the circadian and ultradian rhythm of premature infants
Dorn, F., Wirth, L., Gorbey, S., Wege, M., Zemlin, M., Maier, R. F., & Lemmer, B. (2014) · Chronobiology International · doi:10.3109/07420528.2014.948183 · Cited by 34
“…shown that the wide variance of the age of appearance of the circadian rhythm is due to different analytical working definitions and low sample Chronobiology International frequencies (Antonini et al., 2000; Krieger et al., 1971; Price et al., 1983; Santiago et al., 1996; de Weerth et al., 2003).”
BackgroundIntervention Effects on Morning and Stimulated Cortisol Responses among Toddlers in Foster Care
Nelson, E. M. M., & Spieker, S. J. (2013) · Infant Mental Health Journal · doi:10.1002/imhj.21382 · Cited by 37
Colombo, J. A., Carlson, S. E., Algarín, C. R., Reyes, S., Chichlowski, M., Harris, C. L., Wampler, J. L., Peirano, P. D., & Berseth, C. L. (2020) · Pediatric Research · doi:10.1038/s41390-020-1044-x · Cited by 34
Transforming growth factor beta (TGF-B) stimulation of angiogenesis: an electron microscopic study.
Phillips, G. D., Whitehead, R. A., Stone, A. M., Ruebel, M. W., Goodkin, M. L., & Knighton, D. R. (1993) · PubMed · Cited by 34
Albers, E. M., Beijers, R., Riksen-Walraven, J., Sweep, F. C., & de Weerth, C. (2016) · Stress · doi:10.3109/10253890.2015.1089230 · Cited by 33
“Infants acquire the cortisol circadian rhythm during their first year of life (Custodio et al., 2007; de Weerth & van Geert, 2002; de Weerth et al., 2003).”
BackgroundZhang, B. (2017) · PubMed Central · doi:10.13918/j.issn.2095-8137.2017.002 · Cited by 32
Hibel, L. C., Trumbell, J. M., & Mercado, E. (2013) · Early Human Development · doi:10.1016/j.earlhumdev.2013.11.007 · Cited by 34
“Infants develop a diurnal rhythm that consists of relatively high morning and low evening cortisol levels by three months of age [14,15].”
BackgroundMaternal emotional availability at bedtime and infant cortisol at 1 and 3months
Philbrook, L. E., Hozella, A. C., Kim, B. R., Jian, N., Shimizu, M., & Teti, D. M. (2014) · Early Human Development · doi:10.1016/j.earlhumdev.2014.05.014 · Cited by 31
“Many infants did not yet show a circadian pattern at both ages, however, supporting de Weerth and colleagues’ (8) finding that there is substantial interindividual variability in the emergence of a diurnal rhythm in cortisol.”
BackgroundMethodInfluentialPerinatal Programming of Circadian Clock-Stress Crosstalk
Astiz, M., & Oster, H. (2018) · Neural Plasticity · doi:10.1155/2018/5689165 · Cited by 31
Childbirth complications affect young infants’ behavior
de Weerth, C., & Buitelaar, J. K. (2007) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-007-0610-7 · Cited by 28
“This did not affect cortisol levels, as at this age the circadian rhythm is not present [5].”
BackgroundResultSelf-citationHalal, C. S. E., Bassani, D. G., Santos, I. S., Tovo‐Rodrigues, L., Del‐Ponte, B., da Silveira, M. F., Bertoldi, A. D., Barros, F. C., & Nunes, M. L. (2020) · Journal of Sleep Research · doi:10.1111/jsr.13047 · Cited by 27
Circle(s) of Life: The Circadian Clock from Birth to Death
Olejniczak, I., Pilorz, V., & Oster, H. (2023) · Biology · doi:10.3390/biology12030383 · Cited by 29
Isaksson, J., Lindblad, F., Valladares, E., & Högberg, U. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2015.09.016 · Cited by 27
Neonatal Hypopituitarism: Approaches to Diagnosis and Treatment
Kurtoğlu, S., Özdemi̇r, A., & Hatipoğlu, N. (2019) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.galenos.2018.2018.0036 · Cited by 26
“Thus, cortisol should be measured every hour of the day instead of only in the morning (34).”
BackgroundAssociations between bedtime and nighttime parenting and infant cortisol in the first year
Philbrook, L. E., & Teti, D. M. (2016) · Developmental Psychobiology · doi:10.1002/dev.21442 · Cited by 26
Gao, J., Xiao, H., Li, J., Guo, X., Cai, W., & Li, D. (2019) · Nutrients · doi:10.3390/nu11071699 · Cited by 26
“Cortisolcan affect insulin production and glucose metabolism and it can cause insulin resistance [45,46].”
BackgroundGlucocorticoid treatment and adrenal suppression in children: current view and open issues
Improda, N., Chioma, L., Capalbo, D., Bizzarri, C., & Salerno, M. (2024) · Journal of Endocrinological Investigation · doi:10.1007/s40618-024-02461-9 · Cited by 28
Tamayo‐Ortiz, M., Téllez‐Rojo, M. M., Wright, R. J., Coull, B. A., & Wright, R. O. (2016) · Environmental Health · doi:10.1186/s12940-016-0124-1 · Cited by 25
Neuroendocrine and immune pathways from pre- and perinatal stress to substance abuse
Horn, S. R. G.-V., Roos, L. E., Berkman, E. T., & Fisher, P. A. (2018) · Neurobiology of Stress · doi:10.1016/j.ynstr.2018.09.004 · Cited by 24
Shiftwork and Diurnal Salivary Cortisol Patterns Among Police Officers
Charles, L. E., Fekedulegn, D. B., Burchfiel, C. M., Hartley, T. A., Andrew, M. E., Violanti, J. M., & Miller, D. B. (2016) · Journal of Occupational and Environmental Medicine · doi:10.1097/jom.0000000000000729 · Cited by 25
Effects of Fatigue and Sleep Deprivation on Microvascular Anastomoses
Başaran, K., Mercan, E. S., & Aygıt, A. (2015) · The Journal of craniofacial surgery (Print) · doi:10.1097/scs.0000000000001719 · Cited by 23
“it is responsible for activating the metabolism and inducing glucose and protein release.(23) The maximum sympathomimetic effect of cortisol during the morning surgery (group III, 09.”
BackgroundMehler, K., Ulbrich, L., Börner, S., Joachim, A., Becker, I., Roth, B., & Hünseler, C. (2015) · Early Human Development · doi:10.1016/j.earlhumdev.2015.01.011 · Cited by 22
“infants admitted into the hospital [33], immunizations of late preterm infants and control infants were scheduled at parents' discretion and performed between 8:00 a.”
Thomas, K. A., Burr, R. L., & Spieker, S. J. (2016) · Sleep and Biological Rhythms · doi:10.1007/s41105-015-0046-2 · Cited by 22
Holochwost, S. J., Winebrake, D., Brown, E. D., Happaney, K. R., Wagner, N. J., & Mills-Koonce, R. (2022) · Journal of Cognition and Development · doi:10.1080/15248372.2022.2160721 · Cited by 30
Metadata
- Authors
- de Weerth, C., Zijl, R. H., & Buitelaar, J. K.
- Affiliations
- University Medical Center Utrecht (NL)
- Radboud University Nijmegen (NL)
- ORCID
- Buitelaar, Jan K
- Venue
- Early Human Development
- Publisher
- Elsevier BV
- Published
- 2003-08
- Volume
- 73
- Issue
- 1-2
- Pages
- 39-52
- ISSN
- 0378-3782 (ISSN-L)
- OpenAlex
- W2112583133
- Cited by
- 248
- References
- 40
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 12 · 2023: 13 · 2022: 12 · 2021: 9 · 2020: 15 · 2019: 12 · 2018: 8 · 2017: 15 · 2016: 18 · 2015: 22 · 2014: 17 · 2013: 14 · 2012: 10
- FWCI
- 1.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Early Human Development (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- cortisol, circadian rhythm, diurnal cycle, infancy, hypothalamic-pituitary-adrenal axis, salivary cortisol, sleep-wake cycle, age of onset, within-person variability, multilevel analysis
- MeSH terms
- Adult, Biological Clocks, Circadian Rhythm, Female, Humans, Hydrocortisone, Infant, Male, Pregnancy, Saliva, Sleep, Models, Statistical
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