Seasonal variation in growth has been reported for normally growing children by several authors, most reporting peak growth during the summer months in the Northern Hemisphere [1–3]. Ikeda and Watanabe did not identify seasonal variation in growth of 1000 Japanese school children ages 6–11 years studied between 1983 and 1984 . They attributed this to the use of modern home-heating systems. Lee studied 27 boys and girls in Oakland, California, and observed persistent seasonal variability despite living in a climate that had little variation in temperature and humidity throughout the year, suggesting that temperature was not an important factor .
Number of daylight hours is thought to play a role in variation of seasonal growth rates, although the mechanism is not understood. Blind children have been reported to have limited variation in growth rate throughout the year . Rudolf et al. performed GH stimulation testing and integrated 24-hour GH profiles in 84 normally growing children in 2 consecutive seasons and identified no differences in GH or insulin-like growth factor 1 (IGF-1) levels to account for the observed variation in growth rate . These authors also evaluated growth in 52 GH-deficient children and identified seasonal variabitity in growth even on GH therapy. Growth rate generally peaked in summer, and was lowest in the Israeli autumn. They concluded that the effect of daylight hours appears to not be mediated through GH secretion.
In an early NCGS summary report, Tiwary noted seasonal variation in GH-treated patients with idiopathic short stature, IGHD, and Turner syndrome . In our study, 3-month HV data have been analyzed in a large number children diagnosed with IGHD children who were initially naive to GH therapy. Seasonal variability in HV during rhGH therapy was associated with number of daylight hours and was most apparent at latitudes farthest from the equator. The effect of daylight hours appears greatest in the first year but persists throughout subsequent years of therapy. The effect is modest and is likely to affect clinical assessment of short-term growth rate (3 to 4 months) only in latitudes far from the equator, particularly if there are additional contributing factors, such as intercurrent illness or intermittent compliance. Effect of daylight hours is slightly greater in children with peak stimulated GH response ≤ 3 ng/mL, however, the significance of this obervation is unclear due to small sample size.
Interestingly, annual HV, or total growth over the year, does not differ according to latitude, consistent with an equal total annual daylight hour exposure. Growth appears to speed up during times of greatest daylight exposure and slow down during periods of darkness, but overall has a consistent yearly “program,” possibly at the level of the growth plate. In a recent summary paper regarding evolution of the eye, Lamb describes the primitive eye, from which the current mammalian eye evolved 600 million years ago, as a light-sensitive organ whose function was that of maintaining circadian and seasonal rhythms . The modern retina communicates via neural tracts with the pineal gland and regulates melatonin secretion affecting circadian and seasonal rhythms [9, 10]. Pinealectomy eliminates daylight-entrained circadian patterns . Melatonin has been implicated in gonadotropin regulation and more recently glucose metabolism/insulin sensitivity [12–15]. Recently, GH response to GH-releasing hormone and spontaneous GH secretion in sheep were demonstrated to be greater during a long versus short photoperiod, and GH amplitude was reduced by melatonin administration . Effects of daylight hours on energy metabolism, other signaling at the level of the growth plate, or even GH secretion that were not identified in previous studies due to small numbers of patients evaluated may play a role. In plants, DNA methylation is involved in the photoregulation of flowering . Melatonin may also induce epigenetic changes in DNA expression . The observation that seasonal variation persists with continuous exogenous GH therapy, suggests that GH, if involved, is one of several factors.
In our analysis, BMI SDS at the start of each interval was associated with the HV of that interval. It is possible that weight gain during less active winter months in northern climates facilitates increased growth rate in summer. In the southern US, children’s activity level and weight gain are more similar year-round, and could account for less seasonal variability. This hypothesis was not supported by the finding that BMI SDS at the start of the HV interval was unrelated to the number of daylight hours (P = 0.28).
Our study was limited by the number of patients in the NCGS database who were measured at every 3 monthly intervals. Patients measured at 6 monthly intervals or longer were not included. Also, we do not have IGF-1 levels to correlate with 3 monthly HV intervals. 25-hydroxyvitamin D levels, a reflection of nutrition and ultraviolet light exposure, were also not assessed.