Prenatal famine exposure and adult mortality from cancer, cardiovascular disease, and other causes through age 63 years

Abstract

Nutritional conditions in early life may affect adult health, but prior studies of mortality have been limited to small samples. We evaluated the relationship between pre-/perinatal famine exposure during the Dutch Hunger Winter of 1944-1945 and mortality through age 63 years among 41,096 men born in 1944-1947 and examined at age 18 years for universal military service in the Netherlands. Of these men, 22,952 had been born around the time of the Dutch famine in 6 affected cities; the remainder served as unexposed controls. Cox proportional hazards models were used to estimate hazard ratios for death from cancer, heart disease, other natural causes, and external causes. After 1,853,023 person-years of follow-up, we recorded 1,938 deaths from cancer, 1,040 from heart disease, 1,418 from other natural causes, and 523 from external causes. We found no increase in mortality from cancer or cardiovascular disease after prenatal famine exposure. However, there were increases in mortality from other natural causes (hazard ratio = 1.24, 95% confidence interval: 1.03, 1.49) and external causes (hazard ratio = 1.46, 95% confidence interval: 1.09, 1.97) after famine exposure in the first trimester of gestation. Further follow-up of the cohort is needed to provide more accurate risk estimates of mortality from specific causes of death after nutritional disturbances during gestation and very early life.

Keywords: Dutch Hunger Winter; cohort studies; famine; fetal origins; prenatal exposure delayed effects; undernutrition.

Figure 1.

Food rations in the western Netherlands (daily average from weekly rations (26)) during the Dutch Hunger Winter, September 1944–October 1945.

Figure 2.

Famine exposure categories for 5 pregnancy cohorts among births taking place in the western Netherlands during the Dutch Hunger Winter, January 1944–April 1946. Famine exposure was defined as an average distributed food ration of 900 kcal/day or less during the exposure period of interest. PN, postnatal (exposed in the immediate postnatal period); T3, third trimester (exposed during the third trimester of pregnancy); T2, second trimester (exposed during the second trimester of pregnancy); T1, first trimester (exposed during the first trimester of pregnancy); PC, periconception (exposed just before the estimated date of conception).