Prenatal Nutrition and Adult Disease

BACKGROUND:

A variety of studies have reported associations between birth weight and other proxy measures of fetal nutrition and chronic disease risk in adulthood, particularly "metabolic diseases" such as type 2 diabetes and cardiovascular disease (CVD). These findings have led to the theory of "fetal programming" of adult chronic disease. This theory is highly provocative because it suggests that the prevention of many chronic diseases should start with the improvement of materno-fetal nutrition. A mechanism for fetal programming of adult chronic disease risk, however, has not been identified. In addition, most epidemiological studies have been ecological and retrospective, with poor identification of exposure dose and timing, and control of confounders.

DESIGN NARRATIVE:

The cohort study determines whether famine exposure during the first, second, or third trimesters of gestation is associated with differences between sibs for CVD risk factors in adulthood, specifically centralized obesity, insulin resistance, increased blood pressures, dyslipidemia, and diagnosed type 2 diabetes. Using the data collected, the investigators propose to: (1) evaluate the key assumption that maternal undernutrition during pregnancy results in fetal programming of CVD risk factors; (2) better identify the critical period during gestation in which this may occur; and, (3) determine the strength of the associations with chronic disease risk factors in adulthood.

The study will utilize an innovative sib-pair design in which cases, or "probands," exposed to fetal undernutrition during the Dutch Famine during 1944-45, will be matched to same-sex full siblings who were born in different years and not exposed. The timing of births within the famine period will allow the investigators to classify proband exposure approximately by trimester of gestation. Thus, compared to most previous studies, they will be better able to identify the "critical period" - early, mid, or late gestation - during which fetal programming effects are most likely to occur. In addition, the investigators will randomly select a sample of unexposed probands with birth dates in 1943 or 1947, immediately before and after the famine, and matched siblings. All exposed and unexposed probands will be ascertained from the prenatal and delivery records of three hospitals in the Western Netherlands where the famine was most intense. These records include information on maternal and family medical history, socioeconomic status, pregnancy characteristics (blood pressure, weight gain, etc.), and birth outcomes, including anthropometry and gestational age. Siblings will be identified using national Population Registers (Bevolkings registers), and hospital prenatal and delivery records will be obtained.