Transgenerational effects of prenatal exposure to the Dutch famine.

OBJECTIVE Maternal undernutrition during gestation is associated with increased metabolic and cardiovascular disease in the offspring. We investigated whether these effects may persist in subsequent generations. DESIGN Historical cohort study. SETTING Interview during a clinic or home visit or by telephone. POPULATION Men and women born in the Wilhelmina Gasthuis in Amsterdam between November 1943 and February 1947. METHODS We interviewed cohort members (F1) born around the time of the 1944-45 Dutch famine, who were exposed or unexposed to famine in utero, about their offspring (F2). MAIN OUTCOME MEASURES Birthweight, birth length, ponderal index and health in later life (as reported by F1) of the offspring (F2) of 855 participating cohort members, according to F1 famine exposure in utero. RESULTS F1 famine exposure in utero did not affect F2 (n = 1496) birthweight, but, among the offspring of famine-exposed F1 women, F2 birth length was decreased (-0.6 cm, P adjusted for F2 gender and birth order = 0.01) and F2 ponderal index was increased (+1.2 kg/m(3), P adjusted for F2 gender and birth order = 0.001). The association remained unaltered after adjusting for possible confounders. The offspring of F1 women who were exposed to famine in utero also had poor health 1.8 (95% CI 1.1-2.7) times more frequently in later life (due to miscellaneous causes) than that of F1 unexposed women. CONCLUSIONS We did not find transgenerational effects of prenatal exposure to famine on birthweight nor on cardiovascular and metabolic disease rates. F1 famine exposure in utero was, however, associated with increased F2 neonatal adiposity and poor health in later life. Our findings may imply that the increase in chronic disease after famine exposure in utero is not limited to the F1 generation but persists in the F2 generation.