Objective: To assess the age at which the circadian rhythm of melatonin begins. Methods: 55 children, divided into groups from the neonatal period to 24 months of life, were studied. Urine samples were taken from 28 newborn babies to measure 6-sulfatoxymelatonin (aMT6s). Salivary samples were collected from infants (27 cases), to measure melatonin (aMT). aMT was measured by RIA and aMT6s by ELISA using commercial kits. Changes in the levels of aMT6s and aMT were evaluated using the Friedman test and Wilcoxon matched pair test. Results: The group aged 27–41 days showed statistically significant differences in daily aMT6s and aMT concentrations. The highest values were always found between 24.00 and 8.00 h. This day/night difference persisted from 2–3 to 13–24 months of age. Conclusion: The data indicate that the circadian melatonin rhythm appears at the end of the neonatal period and persists thereafter.

1.
Cavallo A: The pineal gland in human beings: Relevance to pediatrics. J Pediatr 1993;123:843–851.
2.
Reitner RJ: The melatonin rhythm: Both a clock and a calendar. Experientia 1993;49:654–664.
3.
Yu HS, Reiter RJ: Melatonin: Biosynthesis, Physiological Effects and Clinical Applications. Boca Raton, CRC Press, 1993.
4.
Okatani Y, Okamoto K, Hayashi K, Wakatsuki A, Tamura S, Sagara Y: Maternal-fetal transfer of melatonin in pregnant women near term. J Pineal Res 1998;25:129–134.
5.
Kovacs J, Brodner W, Kirchlechner V, Arif T, Waldhauser F: Measurement of urinary melatonin: A useful tool for monitoring serum melatonin after its oral administration. J Clin Endocrinol Metab 2000;85:666–670.
6.
Salti R, Galluzzi F, Bindi G, Perfetto F, Tarquini R, Halberg F, Cornelissen G: Nocturnal melatonin patterns in children. J Clin Endocrinol Metab 2000;85:2137–2144.
7.
Hartmann L, Roger M, Lemaitre BJ, Massias JF, Chaussain JL: Plasma and urinary melatonin in male infants during the first 12 months of life. Clin Chim Acta 1982;121:37–42.
8.
Attanasio A, Rager K, Gupta D: Ontogeny of circadian rhythmicity for melatonin, serotonin, and N-acetylserotonin in humans. J Pineal Res 1986;3:251–256.
9.
Bojkowski CJ, Arendt J, Shih MC, Markey SP: Melatonin secretion in human assessed by measuring its metabolite, 6-sulfatoxymelatonin. Clin Chem 1987;33:1343–1348.
10.
Brown GM, Bar-Or A, Grossi D, Kashur S, Johannson E, Yie SM: Urinary 6-sulphatoxymelatonin, an index of pineal function in the rat. J Pineal Res 1991;10:141–147.
11.
Miles A, Philbrick D, Tidmarsh SF, Shaw DM: Direct radioimmunoassay of melatonin in saliva. Clin Chem 1985;31:1412–1413.
12.
Vakkuri O: Diurnal rhythm of melatonin in human saliva. Acta Physiol Scand 1985;124:409–412.
13.
Graham C, Cook MR, Kavet R, Sastre A, Smith DK: Prediction of nocturnal plasma melatonin from morning urinary measures. J Pineal Res 1998;24:230–238.
14.
Kennaway DJ, Stamp GE, Goble FC: Development of melatonin production in infants and the impact of prematurity. J Clin Endocrinol Metab 1992;75:367–369.
15.
McGraw K, Hoffmann RF, Harker C, Herman JH: The development of circadian rhythms in a human infant. Sleep 1999;22:303–310.
16.
Wetterberg L, Bratlid T, von Knorring L, Eberhard G, Yuwiler A: A multinational study of the relationships between nighttime urinary melatonin production, age, gender, body size, and latitude. Eur Arch Psychiatry Clin Neurosci 1999;249:256–262.
17.
Vaughan GM: New sensitive serum melatonin radioimmunoassay employing the Kennaway G-280 antibody: Syrian hamster morning adrenergic response. J Pineal Res 1993;15:88–103.
18.
Ardura J, Andres J, Revilla MA, Cornelissen G, Halberg F: Computer analysis of environmental temperature, light and noise in intensive care: Chaos or chronome nurseries? Med Hypotheses 1997;49:191–202.
19.
Altman DG: Practical Statistics for Medical Research. London, Chapman Hall, 1999.
20.
Nelson W, Tong YL, Lee JK, Halberg F: Methods for cosinor-rhythmometry: Chronobiologia 1979;6:305–323.
21.
Reiter RJ: Pineal melatonin: Cell biology of its synthesis and of its physiological interactions. Endocr Rev 1991;12:151–180.
22.
Reiter RJ: Antioxidant actions of melatonin. Adv Pharmacol 1997;38:103–117.
23.
Terzolo M, Piovesan A, Pia A, Arvat E, Bellone J, Valente F, Paccotti P, Ghigo E, Angeli A: Similarity of the nocturnal profile of serum melatonin at early puberty and early adulthood. Chronobiologia 1992;19:81–87.
24.
Luboshitzky R, Yanai D, Shen-Orr Z, Israeli E, Here P, Lavie P: Daily and seasonal variations in the concentration of melatonin in the human pineal gland. Brain Res Bull 1998;47:271–276.
25.
Kennaway DJ, Lushington K, Dawson D, Lack L, van den Heuvel C, Rogers N: Urinary 6-sulfatoxymelatonin excretion and aging: New results and a critical review of the literature. J Pineal Res 1999;27:210–220.
26.
Hellbrügge T, Lange JE, Rutenfranz J, Stehr K: Circadian periodicity of physiological functions in different stages of infancy and childhood. Ann NY Acad Sci 1964;177:361–373.
27.
Mills JN: Development of circadian rhythms in infancy. Chronobiologia 1975;2:363–371.
28.
Ardura J, Andres J, Aldana J, Revilla MA, Aragon MP: Heart rate biorhythm changes during the first three months of life. Biol Neonate 1997;72:94–101.
29.
Munoz-Hoyos A, Jaldo-Alba F, Molina-Carballo A, Rodriguez-Cabezas T, Molina-Font JA, Acuna-Castroviejo D: Absence of plasma melatonin circadian rhythm during the first 72 hours of life in human infants. J Clin Endocrinol Metab 1993:77:699–703.
30.
Kivela A, Kauppila A, Leppaluoto J, Vakkuri O: Melatonin in infants and mothers at delivery and in infants during the first week of life. Clin Endocrinol (Oxf) 1990;32:593–598.
31.
Mantagos S, Moustogiannis A, Makri M, Vagenakis A: The effect of light on plasma melatonin levels in premature infants. J Pediatr Endocrinol Metab 1996;9:387–392.
32.
Miyamoto A, Oki J, Takahashi S, Okuno A: Serum melatonin kinetics and long-term melatonin treatment for sleep disorders in Rett syndrome. Brain Dev 1999;21:59–62.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.