Re: Birth month, birth season, and overall and cardiovascular disease mortality in US women: prospective cohort study
We appreciate the suggestion by Erren and colleagues to examine photoperiod (hours of daylight) in our recently published paper .
Indeed, a fundamental question in health remains whether environmental signals during fetal development may have long-term effects on disease risk in humans. The Developmental origins of health and disease (DOHaD) concept [2-4] suggests that fetal adaptations in response to adverse intrauterine conditions may escalate the risk for childhood and adulthood disease. It is increasingly appreciated that, in addition to genetic programs underlying development, external and maternal influences act through gene x environment interactions or epigenetic programs to shape the developing brain and body, as well as disease vulnerability . In the context of human neurobehavioral disorders, altered development may contribute to heightened risks of mental health disorders later in life [6, 7]. Among findings that have highlighted the importance of developmental programming of brain circuits and behavior are those of Seckl and colleagues, who documented the fetal-maternal programming of anxiety behaviors through maternal-fetal glucocorticoid signaling . More recently, Barker et al.’s early observation that birth weight predicts future ischemic heart disease risk  has received renewed attention through the potential impact of early life environments such as nutritional status and microbiota on target organs including the cardiovascular system and the infant’s immune development [10, 11].
In animal models, melatonin signals perinatal light cycles from mother to fetus [12, 13], with effects on stability of the biologic clock and development of depression and anxiety behaviors that persist in adulthood [14-17] and are dependent on the melatonin 1 (MT1) receptor [18, 19], establishing that light is an environmental signal with enduring epigenetic effects on brain circuits and behavior. However, while animal models comprehensively illustrate the influence of perinatal light cycle exposure on development of abnormal behaviors during adulthood, work in humans is only beginning to emerge regarding the risk of e.g., affective disorders later in life (as reviewed in , or the recent study of ). Moreover, much less is known about the effect of environmental signals during the fetal period on markers of the cardiovascular system or the immune system . It is therefore a sensible question to explore whether light cycles during fetal development have lasting impact on human health through their programming of neural and endocrine circuits or affecting the development of the immune system.
In the context of our publication on birth month and birth season in relation to overall mortality and CVD mortality , we have applied a definition of photoperiod which we have described in greater detail elsewhere . Briefly, based on participants’ date and state of birth, we estimated the day length (i.e., photoperiod) during the presumed maternal pregnancy period (i.e., beginning 280 days prior to the participant’s birth date, as this represents the average length of human pregnancy) using mathematical equations published by the National Oceanic and Atmospheric Administration . We used the longitudinal coordinates of the center of population density for a participant’s birth state to represent the location of the participant during gestation. With these assumptions, we created two main exposures of interest: total photoperiod during maternal pregnancy (a proxy for total duration of light exposure, in hours, of the participant’s mother during pregnancy), which was calculated by summing the lengths of all 280 days across the pregnancy; and extreme differences in photoperiod during maternal pregnancy (a proxy for variation in light exposure during pregnancy), which was calculated by subtracting the longest and shortest day lengths during gestation.
Applying this definition of perinatal light exposure (i.e., day length) metrics during maternal pregnancy, we find no compelling evidence for photoperiod in relation to overall or CVD-specific mortality. These findings likely suffer from bias towards the null because information on behavioral factors (e.g., time spent outdoors) that influence maternal light exposure during pregnancy was lacking. Our definition of photoperiod assumed exposure to sun from sunrise to sunset, increasing the probability of non-differential exposure misclassification. Thus, additional more detailed investigations should not be discouraged by these negative findings. To more comprehensively explore the photoperiodic imprinting hypothesis in humans, studies are needed with more accurate information regarding actual exposure to outdoor light during fetal development.
1. Zhang Y, Devore EE, Strohmaier S, Grodstein F, Schernhammer ES. Birth month, birth season, and overall and cardiovascular disease mortality in US women: prospective cohort study. Bmj 2019;367:l6058. doi: 10.1136/bmj.l6058 [published Online First: 2019/12/20]
2. Barker DJP. Fetal Programming: Influences on Development and Disease in Later Life. In: Series NM, ed. New York: Dekker, M., 2000.
3. Bateson P, Barker D, Clutton-Brock T, Deb D, D'Udine B, Foley RA, et al. Developmental plasticity and human health. Nature 2004;430(6998):419-21. doi: 10.1038/nature02725 [published Online First: 2004/07/23]
4. Van den Bergh BR. Developmental programming of early brain and behaviour development and mental health: a conceptual framework. Developmental medicine and child neurology 2011;53 Suppl 4:19-23. doi: 10.1111/j.1469-8749.2011.04057.x [published Online First: 2011/10/05]
5. Thornburg KL, Shannon J, Thuillier P, Turker MS. In utero life and epigenetic predisposition for disease. Epigenetics and Cancer, Part B 2010;71:57-78. doi: 10.1016/B978-0-12-380864-6.00003-1
6. Gutman DA, Nemeroff CB. Persistent central nervous system effects of an adverse early environment: clinical and preclinical studies. Physiology & behavior 2003;79(3):471-8. [published Online First: 2003/09/05]
7. Devore EE, Chang SC, Okereke OI, McMahon DG, Schernhammer ES. Photoperiod during maternal pregnancy and lifetime depression in offspring. J Psychiatr Res 2018;104:169-75. doi: 10.1016/j.jpsychires.2018.08.004 [published Online First: 2018/08/10]
8. Seckl JR, Holmes MC. Mechanisms of disease: glucocorticoids, their placental metabolism and fetal 'programming' of adult pathophysiology. Nature clinical practice Endocrinology & metabolism 2007;3(6):479-88. doi: 10.1038/ncpendmet0515 [published Online First: 2007/05/23]
9. Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ. Weight in infancy and death from ischaemic heart disease. Lancet 1989;2(8663):577-80. doi: 10.1016/s0140-6736(89)90710-1 [published Online First: 1989/09/09]
10. Suzuki K. The developing world of DOHaD. J Dev Orig Health Dis 2018;9(3):266-69. doi: 10.1017/S2040174417000691 [published Online First: 2017/09/06]
11. Stiemsma LT, Michels KB. The Role of the Microbiome in the Developmental Origins of Health and Disease. Pediatrics 2018;141(4) doi: 10.1542/peds.2017-2437 [published Online First: 2018/03/10]
12. Goldman BD. Pattern of melatonin secretion mediates transfer of photoperiod information from mother to fetus in mammals. Science's STKE 2003;2003(192):PE29. doi: 10.1126/stke.2003.192.pe29
13. Torres-Farfan C, Richter HG, Germain AM, Valenzuela GJ, Campino C, Rojas-García P, et al. Maternal melatonin selectively inhibits cortisol production in the primate fetal adrenal gland. The Journal of Physiology 2004;554(Pt 3):841-56. doi: 10.1113/jphysiol.2003.056465
14. Shaw D, Goldman BD. Gender differences in influence of prenatal photoperiods on postnatal pineal melatonin rhythms and serum prolactin and follicle-stimulating hormone in the Siberian hamster (Phodopus sungorus). Endocrinology 1995;136(10):4237-46.
15. Ciarleglio CM, Axley JC, Strauss BR, Gamble KL, McMahon DG. Perinatal photoperiod imprints the circadian clock. Nat Neurosci 2011;14(1):25-7. doi: 10.1038/nn.2699
16. Ciarleglio CM, Resuehr HES, McMahon DG. Interactions of the serotonin and circadian systems: nature and nurture in rhythms and blues. NSC 2011:1-9. doi: 10.1016/j.neuroscience.2011.09.036
17. Pyter LM, Nelson RJ. Enduring effects of photoperiod on affective behaviors in Siberian hamsters (Phodopus sungorus). Behavioral Neuroscience 2006;120(1):125-34. doi: 10.1037/0735-7044.120.1.125
18. Ciarleglio CM, Resuehr HE, McMahon DG. Interactions of the serotonin and circadian systems: nature and nurture in rhythms and blues. Neuroscience 2011;197:8-16. doi: 10.1016/j.neuroscience.2011.09.036
19. Green NH, Jackson CR, Iwamoto H, Tackenberg MC, McMahon DG. Photoperiod programs dorsal raphe serotonergic neurons and affective behaviors. Curr Biol 2015;25(10):1389-94. doi: 10.1016/j.cub.2015.03.050
20. Foster RG, Roenneberg T. Human responses to the geophysical daily, annual and lunar cycles. Current biology : CB 2008;18(17):R784-R94. doi: S0960-9822(08)00865-8 [pii]
10.1016/j.cub.2008.07.003 [published Online First: 2008/09/13]
21. Disanto G, Morahan JM, Lacey MV, Deluca GC, Giovannoni G, Ebers GC, et al. Seasonal Distribution of Psychiatric Births in England. PLoS ONE 2012;7(4):e34866. doi: 10.1371/journal.pone.0034866.t001
22. Blom JM, Gerber JM, Nelson RJ. Day length affects immune cell numbers in deer mice: interactions with age, sex, and prenatal photoperiod. The American journal of physiology 1994;267(2 Pt 2):R596-601. doi: 10.1152/ajpregu.1994.267.2.R596 [published Online First: 1994/08/01]
23. Earth System Research Laboratory NOAA. Solar Calculation Details [Available from: www.esrl.noaa.gov/gmd/grad/solcalc/calcdetails.html accessed April 11 2016.
Competing interests: No competing interests