Prenatal Nutrition and Adult Disease
Condition: Cardiovascular Diseases; Heart Diseases; Diabetes Mellitus; Diabetes Mellitus, Non-insulin Dependent; Insulin Resistance; Obesity; Hypertension
MeSH terms: Cardiovascular Diseases; Heart Diseases; Diabetes Mellitus; Insulin Resistance; Diabetes Mellitus, Type 2
Study type: Observational

Summary: 
      To determine whether maternal undernutrition in pregnancy is associated with differences
      between siblings for cardiovascular risk factors in adulthood.
    

Detailed description: 
      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.

      In addition to collecting information from perinatal hospital and registry records, all
      subjects will undergo a home interview and clinical examination. The interview will collect
      information on sociodemographic characteristics, economic status, health history, including
      obstetric history, current health and medical treatment, and health behaviors, including
      physical activity. The clinical examine will include a fasting blood draw for lipid, glucose,
      and insulin concentrations, and a glucose tolerance test with additional blood draws at 30
      and 120 minutes post-glucose load. Blood will also be stored for future DNA isolation and
      assay of genetic polymorphisms that could influence associations among the study variables.
      Anthropometry will include height, weight, waist circumference, and abdominal sagital
      diameter. A food frequency questionnaire will also be administered during either the
      interview or examination phase.

      An innovative part of the study will be measurements of hand morphology: specifically,
      fingertip ridge-count differences and digit-lengths. These characteristics are established by
      the 19th week of gestation and are fixed thereafter throughout the lifetime. There is some
      evidence that the development of these characteristics prior to 19 weeks of gestation may be
      influenced by environmental factors, including materno-fetal nutrition. The investigators
      will test the hypothesis that these finger and hand characteristics are markers of
      undernutrition during the first half of pregnancy and predict other adult CVD risk factors.