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Research Christmas 2019: Let it Be

Birth month, birth season, and overall and cardiovascular disease mortality in US women: prospective cohort study

BMJ 2019; 367 doi: (Published 18 December 2019) Cite this as: BMJ 2019;367:l6058

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Re: Birth month, birth season, and overall and cardiovascular disease mortality in US women: prospective cohort study

Dear Editor:

We appreciate the suggestion by Erren and colleagues to examine photoperiod (hours of daylight) in our recently published paper [1].

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 [5]. 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 [8]. More recently, Barker et al.’s early observation that birth weight predicts future ischemic heart disease risk [9] 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 [20], or the recent study of [21]). 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 [22]. 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 [1], we have applied a definition of photoperiod which we have described in greater detail elsewhere [7]. 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 [23]. 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]
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Competing interests: No competing interests

13 February 2020
Eva Schernhammer
Professor of Epidemiology
Yin Zhang, Elizabeth Devore, Susanne Strohmaier, Fran Grodstein
Medical University of Vienna, Austria, and Channing Division of Network Medicine, Harvard Medical School, Boston, MA
181 Longwood Ave, Boston, MA