Melatonin production in healthy infants: Evidence for seasonal variations

The objective of this study was to determine the normal range of nocturnal urinary excretion of the major melatonin metabolite, 6-sulfatoxymelatonin ( 6SMT) in a large sample of healthy fullterm infants (8 and 16 wk old) and a ssess whether the endogenous production of melatonin changes with season. 6 SMT was assessed in urine samples extracted from disposable diapers removed from full-term, 8- (n = 317) and 16-wk-old (n = 93) infants over the noctu rnal period (19:00-08:00 h). In addition, 6SMT was assessed in 8-wk-old (n = 35) healthy infants over the entire 24-h period. 6SMT was determined by a n ELISA assay. 6SMT excretion at 8 wk of age exhibited diurnal variations w ith (mean +/- SD) 61 +/- 18% of the daily production excreted during the no cturnal period regardless of season. The nocturnal 6SMT values in the entir e cohort (at 8 as well as 16 wk of age) were found to significantly depart from normal distribution (Kolmogorov-Smirnov lest). A normal distribution w as obtained using a natural base logarithmic (ln) transformation of the dat a. The normal range (2.5-97.5 percentile of the In 6SMT excretion per night ) was thus defined as 4.66-8.64 (106-5646 ng/night) for 8-wk-old and 5.19-9 .67 (180-15,820 ng/night) for 16-wk-old infants. A significant effect of th e month of birth on 6SMT production at the age of 8 wk was found (ANOVA, p < 0.002) with maximal levels produced by infants born in June (summer solst ice) and minimal excretion in infants born in December (winter solstice). S hort-photoperiod-born infants excreted on average about threefold less 6SMT compared with long-photoperiod-born infants (t test, p = 0.01). The season al variations were no longer present at 16 wk of age. No effect of breast-f eeding at the time of sampling on seasonality of 6SMT was found. Normal ran ges for the nocturnal urinary excretion of 6SMT in full-term infants at 8 a nd 16 wk of age are defined. This enables the evaluation of nocturnal 6SMT excretion as a prognostic and diagnostic factor for child development. The strong effect of season on the normal excretion of nocturnal 6SMT at 8 but not 16 wk of age suggests prenatal influence of the photoperiod on the onto geny of melatonin.