Windows of Vulnerability: Consequences of Exposure Timing during the Dutch Hunger Winter

Abstract

Prior research on early-life exposures to famine has established in utero development as a critical period of vulnerability to malnutrition. Yet, previous research tends to focus narrowly on this stage, at the expense of a more comprehensive examination of childhood. As a result, the literature has yet to compare the severity of the consequences of exposure to malnutrition across developmentally salient periods. Such comparison is crucial not only in the magnitude of effects but also in the nature of outcomes. Using a restricted population registry-linked health survey, this study examines the Dutch Hunger Winter to provide a comprehensive examination of the long-term consequences of in utero, infant, childhood, and adolescent exposure to famine. The results show malnutrition leads to heterogeneous effects depending on when the exposure occurs. In utero exposure to malnutrition leads to deleterious conditions in physical health and lower socioeconomic attainment. For older cohorts, results suggest a resilience to the effects of malnutrition on physical health in late life, but a higher vulnerability to socioeconomic stunting. Furthermore, the results suggest important gender differences in the long-term impact of malnutrition. Males consistently show stronger negative consequences across a wider array of conditions.

Childhood obesity from the genes to the epigenome

“…However, in environments abundant with nutrition, this adaptive trait can increase the risk of obesity and associated metabolic syndromes. Supporting evidence for this hypothesis comes from studies of the Dutch hunger winter, which found that individuals born during the famine were more prone to developing obesity, diabetes, and other metabolic diseases compared to those born before the famine, with a more pronounced risk observed in males ( 116 ). Furthermore, infants exposed to famine during their mother’s first trimester faced a higher risk of metabolic diseases, underscoring the heightened susceptibility of the early developmental stage to environmental influences.…”

Sex differences in innate and adaptive immunity impact fetal, placental, and maternal health

“…Additional nutritional information has been gleaned from studies assessing children and adults born during periods of famine. In multiple studies, female offspring born to mothers affected by famine during gestation were found to exhibit higher rates of obesity than their male counterparts [36, 37]. The diversity in long-term outcomes of maternal nutrition on offspring development appears to result predominantly from a combination of the nature of the insult (caloric restriction, nutrient restriction, high-fat diet, etc.)…”

Nutrigenomics and redox regulation: Concepts relating to the Special Issue on nutrigenomics

“…Human fetuses can of course not be studied, but there are so-called natural experiments, where the exposure to severe environmental conditions was not under experimental control. For example, in the Dutch Hunger Winter occurring in the Netherlands during the winter of 1944/45 fetuses of their starving mothers were exposed to extreme undernutrition in utero [ 56 , 57 ]. This malnutrition led to impaired growth of the fetuses.…”