Independent and additive association of prenatal famine exposure and intermediary life conditions with adult mortality between age 18–63 years

Abstract

Objectives To quantify the relation between prenatal famine exposure and adult mortality, taking into account mediating effects of intermediary life conditions. Design Historical follow-up study. Setting The Dutch famine (Hunger Winter) of 1944–1945 which occurred towards the end of WWII in occupied Netherlands. Study population From 408,015 Dutch male births born 1944–1947, examined for military service at age 18, we selected for follow-up all men born at the time of the famine in six affected cities in the Western Netherlands (n=25,283), and a sample of unexposed time (n=10,667) and place (n=9,087) controls. These men were traced and followed for mortality through the national population and death record systems. Outcome measure All-cause mortality between ages 18 and 63 years using Cox proportional hazards models adjusted for intermediary life conditions. Results An increase in mortality was seen after famine exposure in early gestation (HR 1.12; 95% confidence interval (CI): 1.01 to 1.24) but not late gestation (HR 1.04; 95% CI: 0.96 to 1.13). Among intermediary life conditions at age 18 years, educational level was inversely associated with mortality and mortality was elevated in men with fathers with a manual versus non-manual occupations (HR 1.08; CI: 1.02 to 1.16) and in men who were declared unfit for military service (HR 1.44; CI: 1.31 to 1.58). Associations of intermediate factors with mortality were independent of famine exposure in early life and associations between prenatal famine exposure and adult mortality were independent of social class and education at age 18. Conclusions Timing of exposure in relation to the stage of pregnancy may be of critical importance for later health outcomes independent of intermediary life conditions.

Mortality selection in the first three months of life and survival in the following thirty-three months in rural Veneto (North-East Italy) from 1816 to 1835

“…An increase of 12% in all causes of death between the ages of 18-63 was observed in the Western Netherlands among people born in 1944-1945 whose mothers were affected by the Great Famine during the first half of gestation, compared with those whose mothers were not so affected. This difference is considerable, and is greater compared to individuals whose fathers were employed in manual vs. nonmanual occupations (+8% for manual), and is independent of social class and education at age 18 (Ekamper et al 2013). A similar dynamic also holds true for the cohorts most severely affected by the Great Famine of the 1930s or by World War II in Ukraine (Shkolnikov 2012).…”

“…As children who died during the months 3-35 are censored, one way to assess this question is a semiparametric Cox regression, which provides the monthly risk of death as a response variable, controlling for the elimination process (see e.g., Bruckner, Catalano, and Smith 2013;Ekamper et al 2013). We model the risk of death between the 4 th and the 36 th months of life for individuals still surviving at the end of their 3 rd month, using the above-described covariates as explanatory variables.…”

A systematic review of the health effects of prenatal exposure to disaster

“…The remainder found no association (Roseboom et al 2001), or a slight increase in mortality after famine exposure in the first trimester (HR 1.12, 95 % CI 1.01, 1.24) (Ekamper et al 2014) and an increased risk of death from natural (HR 1.24, 95 % CI 1.03, 1.43) or external (HR 1.46, 95 % CI 1.09, 1.97) causes (Ekamper et al 2015).…”

An IPW estimator for mediation effects in hazard models: with an application to schooling, cognitive ability and mortality

“…4 We have information from the military examinations for 45,037 men. The data were described elsewhere, Ekamper et al (2014), here we provide the main characteristics. These data were linked to the Dutch death register through to the end of 2015 using unique personal identification numbers.…”