Abstract Studies across different species have shown that moderate dietary restriction is associated with a longer life span. Surprisingly, however, when diet is restricted in prenatal life, the effect is completely the opposite. Animal studies and human epidemiologic data have shown that undernutrition in utero negatively affects health in later life and reduces life span considerably. In this issue of the Journal, Schoeps et al. (Am J Epidemiol. 2018;187(10):2085–2092) provide new evidence that variations in nutritional conditions during pregnancy relate to the future health of the unborn child. In a detailed analysis of data from Muslim and non-Muslim pregnant women in Burkina Faso, they showed that the occurrence of Ramadan in early life was strongly associated with mortality rates among children under 5 years of age. Mortality rates were highest when Ramadan had occurred in the preconception period or during the first trimester. That nutritional conditions in early life can have such profound consequences for child mortality is both astonishing and extremely relevant from a public health perspective. child mortality, famine, fasting, nutrition, prenatal exposure delayed effects, pregnancy The “developmental origins of health and disease” paradigm is currently gaining widespread momentum. The importance of a healthy early environment that sets the stage for a healthy life is increasingly being recognized. Since the beginning of this research field, with the work of Barker et al. (1) demonstrating clear associations between small size at birth and diabetes and heart disease (2), substantial attention has been given to the impact of nutrition in utero. Animal experimental work has provided a large body of evidence showing that manipulation of the prenatal and perinatal diet instigates clear effects on a wide range of health-related outcomes in the offspring, with decreased life span as a final outcome. An excellent example of such a study was performed by Ozanne and Hales (3), who demonstrated that mice that were undernourished prenatally had a 25% shorter life span than those that had not been undernourished before birth, and as such, the effects of dietary restriction in prenatal life were larger than those of postnatal diet. Studying the effects of poor nutrition in utero in humans, though, is obviously less straightforward. To overcome the limitation of being unable to experiment with nutritional conditions in humans and study its outcomes, researchers have used naturally occurring or manmade situations in which nutritional conditions varied. For example, the strong bimodal seasonality in the Gambia is associated with large differences in food availability in rural communities. Studies of the correlations between season of birth and mortality rates in young adulthood have shown that these are closely linked (4). People born during the rainy “hungry season” appeared to be up to 10 times more likely to die prematurely than those born during the dry season, which is characterized by relatively higher food abundance. Those born in the rainy season also had a 3-fold higher risk of mortality due to infectious disease (5). Over the last 100 years, famines have provided historical opportunities to study later-life health consequences of poor nutritional circumstances in early life. Different periods of famine during different periods of time across the world have been used to investigate consequences of undernutrition in early life. The most widely studied famines include the Dutch Hunger Winter, which struck the urban western part of the Netherlands at the end of World War II, and the Chinese famine, which coincided with the Great Leap Forward in 1959–1961 and was caused by the imposition of drastic changes in agriculture and economic mismanagement combined with natural disasters. Studies of the people who had been in utero during these famines have shown a range of health corollaries, especially for cardiometabolic health (6–9). Prenatal exposure to the Dutch famine has also been shown to be associated with increased mortality up to the age of 63 years (10, 11). Criticism of the famine studies has always been that the circumstances existing during these hunger periods were extremely severe and must also have caused severe stress and other physical discomfort, making it difficult to determine whether any results of prenatal famine exposure can be attributed to the state of undernutrition per se. Another point of critique that can be made is that nutritional circumstances in a war situation cannot be translated to nutritional conditions in nonwar circumstances. This is what makes the study reported by Schoeps et al. (12) in this issue of the Journal particularly interesting. The authors use the nutritional variation that accompanies the period of Ramadan, during which many Muslims participate in fasting, as a natural experiment to study the relationship between nutritional conditions in utero and child mortality. The study findings showed that, especially when Ramadan occurred during conception or the first trimester, mortality in children under age 5 years was higher by 33% and 29%, respectively, among children of Muslim mothers compared with children of non-Muslim mothers. When they looked at infant mortality only, up to the age of 1 year, exposure during the period of conception was even associated with 68% higher mortality. The results of this study largely converge with those from the Dutch famine studies in that nutritional deprivation during pregnancy, particularly the periods around conception and early pregnancy, seems to matter the most in shaping future health (6, 7, 10). Early gestation has also been demonstrated to be a critical time window for changes in the prenatal environment to affect DNA methylation levels, which are held to be responsible for the phenotypical consequences of being exposed to an adverse diet in utero (13). The finding that nutritional circumstances during the periconceptional period and early fetal life are so important in shaping future health conditions is of significant relevance from a public health point of view. The need to communicate the importance of a healthy diet, starting from the preconception period, is clearly present. The study by Schoeps et al. (12) provides important novel evidence that being in utero during the period of traditional fasting for Muslims is associated with increased child mortality. This adds to the evidence that nutrition at the very beginning of life, especially around conception and in early pregnancy, is highly important for the child’s health and may even be a matter of survival. ACKNOWLEDGMENTS Author affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands (Susanne R. de Rooij). Conflict of interest: none declared. REFERENCES 1 Barker DJ , Eriksson JG , Forsén T , et al. . Fetal origins of adult disease: strength of effects and biological basis . Int J Epidemiol . 2002 ; 31 ( 6 ): 1235 – 1239 . Google Scholar Crossref Search ADS PubMed 2 Harding JE . The nutritional basis of the fetal origins of adult disease . Int J Epidemiol . 2001 ; 30 ( 1 ): 15 – 23 . Google Scholar Crossref Search ADS PubMed 3 Ozanne SE , Hales CN . Lifespan: catch-up growth and obesity in male mice . Nature . 2004 ; 427 ( 6973 ): 411 – 412 . Google Scholar Crossref Search ADS PubMed 4 Moore SE , Cole TJ , Poskitt EM , et al. . Season of birth predicts mortality in rural Gambia . Nature . 1997 ; 388 ( 6641 ): 434 . Google Scholar Crossref Search ADS PubMed 5 Moore SE , Cole TJ , Collinson AC , et al. . Prenatal or early postnatal events predict infectious deaths in young adulthood in rural Africa . Int J Epidemiol . 1999 ; 28 ( 6 ): 1088 – 1095 . Google Scholar Crossref Search ADS PubMed 6 Roseboom TJ , Painter RC , van Abeelen AF , et al. . Hungry in the womb: what are the consequences? Lessons from the Dutch famine . Maturitas . 2011 ; 70 ( 2 ): 141 – 145 . Google Scholar Crossref Search ADS PubMed 7 Lumey LH , Stein AD , Susser E . Prenatal famine and adult health . Annu Rev Public Health . 2011 ; 32 : 237 – 262 . Google Scholar Crossref Search ADS PubMed 8 Li Y , He Y , Qi L , et al. . Exposure to the Chinese famine in early life and the risk of hyperglycemia and type 2 diabetes in adulthood . Diabetes . 2010 ; 59 ( 10 ): 2400 – 2406 . Google Scholar Crossref Search ADS PubMed 9 Li Y , Jaddoe VW , Qi L , et al. . Exposure to the Chinese famine in early life and the risk of hypertension in adulthood . J Hypertens . 2011 ; 29 ( 6 ): 1085 – 1092 . Google Scholar Crossref Search ADS PubMed 10 van Abeelen AF , Veenendaal MV , Painter RC , et al. . Survival effects of prenatal famine exposure . Am J Clin Nutr . 2012 ; 95 ( 1 ): 179 – 183 . Google Scholar Crossref Search ADS PubMed 11 Ekamper P , van Poppel F , Stein AD , et al. . Prenatal famine exposure and adult mortality from cancer, cardiovascular disease, and other causes through age 63 years . Am J Epidemiol . 2015 ; 181 ( 4 ): 271 – 279 . Google Scholar Crossref Search ADS PubMed 12 Schoeps A , van Ewijk R , Kynast-Wolf G , et al. . Ramadan exposure in utero and child mortality in Burkina Faso: analysis of a population-based cohort including 41,025 children . Am J Epidemiol . 2018 ; 187 ( 10 ): 2085 – 2092 . 13 Tobi EW , Slieker RC , Stein AD , et al. . Early gestation as the critical time-window for changes in the prenatal environment to affect the adult human blood methylome . Int J Epidemiol . 2015 ; 44 ( 4 ): 1211 – 1223 . Google Scholar Crossref Search ADS PubMed © The Author(s) 2018. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
American Journal of Epidemiology – Oxford University Press
Published: Oct 1, 2018
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